Note: Claims are shown in the official language in which they were submitted.
105
What is claimed is:
1. A protein tyrosine phosphatase activity-modulating compound with the
structure depicted in Formula (B):
X-C(R')=C(R")COOR"'
(B)
wherein
(i) R' and R'' are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11alkyl, optionally
substituted
arylC1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, vitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11alkyl,
arylC1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-11alkyl, C0-
11alkylthioC0-
11alkyl, arylC0-11,alkylthioC0-11alkyl, C0-11alkylaminoC0-11alkyl, arylC0-
11alkylaminoC0-
11alkyl, di(arylC1-11alkyl)aminoC0-11alkyl, C1-11alkylcarbonylC0-11alkyl,
arylC1-
11alkylcarbonylC0-11alkyl, C1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarboxyC0-
11alkyl, C1-11alkylcarbonylaminoC0-11alkyl, arylC1-11alkylcarbonylaminoC0-
11alkyl,-
C0-11alkylCOOR1, -C0-11alkylCONR2R3 wherein R1, R2 and R3 are independently
selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or R2 and R3 are taken
together
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11 alkyl, arylC0-C11 alkyl substituent.
(ii) R''' is selected from the group consisting of
(a) hydrogen,
(b) C1-11alkyl, substituted C1-11alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11alkyloxy, arylC0-11alkyloxy, C0-11alkylthio, arylC0-11alkylthio, C0-
11alkylamino,
arylC0-11alkylamino, di(arylC0-11alkyl)amino, C1 -11alkylcarbonyl, arylC1-
11alkylcarbonyl, C1-11alkylcarboxy, arylC1-11alkylcarboxy, C1-
11alkylcarbonylamino,
aryl C1-11alkylcarbonylamino, -C0-11alkylCOOR4, -C0-11alkylCONR5R6 wherein R4,
R5 and R6 are independently selected from hydrogen, C1-C11alkyl, arylC0-
C11alkyl, or
106
R5 and R6 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent,
(c) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R'', and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
2. A compound as defined in claim 1 wherein aryl is selected from phenyl,
biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl,
azulenyl,
anthryl, phenanthryl, fluorenyl, pyrenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
3. A compound as defined in claim 1 wherein aryl is selected from thienyl,
benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl,
benzofuranyl,
isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl,
indolizinyl,
indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl,
pyrimidinyl,
triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl,
107
quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl,
acridinyl,
phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl,
purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl,
isothiazolyl,
benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, thiadiazolyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
4. A compound as defined in claim 1 wherein aryl is selected from thienyl,
benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, phenothiazinyl,
thiazolyl,
isothiazolyl, benzthiazolyl, thiadiazolyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
5. A compound as defined in claim 1 wherein aryl is selected from furyl,
pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, phenoxazinyl,
chromanyl, benzodioxolyl, hydroxypyronyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
6. A compound as defined in claim 1 wherein aryl is selected from pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, purinyl,
pyrazolyl,
triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl,
isoxazolyl,
benzoxazolyl, oxadiazolyl, thiadiazolyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
7. A compound as defined in claim 1 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, benzothienyl, isobenzothienyl, furyl,
benzofuranyl,
isobenzofuranyl, pyrrolyl, indolyl, isoindolyl, imidazolyl, benzimidazolyl,
pyridyl,
108
pyrazinyl, pyradazinyl, pyrimidinyl, quinolyl, isoquinolyl, phthalazinyl,
quinazolinyl,
quinoxalinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl,
isothiazolyl,
benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, thiadiazolyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
8. A compound as defined in claim 1 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, benzothienyl, furyl, benzofuranyl, pyrrolyl,
indolyl,
imidazolyl, benzimidazolyl, pyridyl, quinolyl, thiazolyl, benzthiazolyl,
oxazolyl,
benzoxazolyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
9. A compound as defined in claim 1 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, fiuyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
10. A compound as defined in claim 1 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
11. A compound as defined in claim 1 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
12. A compound as defined in claim 1 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
13. A compound as defined in claim 1 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
14. A compound as defined in claim 1 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
109
15. A compound as defined in claim 1 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
16. A compound with the structure depicted in Formula (A2):
Image
wherein at least one of R1, R2 and R3 substituents has the general structure
depicted in
Formula (B)
X-C(R')=C(R")COOR'''
(B)
wherein
(i) R' and R'' are independently selected from the group consisting of
hydrogen, halo, cyano, vitro, trihalomethyl, C1-11alkyl, optionally
substituted
arylC1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11alkyl,
arylC1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-11alkyl, C0-
11alkylthioC0-
11alkyl, arylC0-11alkylthio C0-11alkyl, C0-11alkylaminoC0-11alkyl, arylC0-
11alky laminoC0-
11alkyl, di(arylC1-11alkyl)aminoC0-11alkyl, C1-11alkylcarbonylC0-11alkyl,
arylC1-
11alkylcarbonylC0-11alkyl, C1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarboxyC0-
11alkyl, C1-11alkylcarbonylaminoC0-11alkyl, arylC1-11alkylcarbonylaminoC0-
11alkyl, -
C0-11alkylCOOR4, -C0-11alkylCONR5R6 wherein R4, R5 and R6 are independently
selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or R5 and R6 are taken
together
110
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11alkyl, arylC0-C11alkyl substituent.
(ii) R''' is selected from the group consisting of
(a) hydrogen,
(b) C1-11alkyl, substituted C1-11alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11alkyloxy, arylC0-11alkyloxy, C0-11alkylthio, arylC0-11alkylthio, C0-
11alkylamino,
arylC0-11alkylamino, di(arylC0-11alkyl)amino, C1-11alkylcarbonyl,
arylC1-11alkylcarbonyl, C1-11alkylcarboxy, aryl C1-11alkylcarboxy, C1-
11alkylcarbonylamino,
aryl C1-11alkylcarbonylamino, -C0-11alkylCOOR7, -C0-11alkylCONR8R9 wherein R7,
R8 and R9 are independently selected from hydrogen, C1-C11alkyl, arylC0-
C11alkyl, or
R8 and R9 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent,
(c) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R'', and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazoiyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazoiyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
111
and wherein the remaining of R1, R2 and R3 are independently selected from the
group
consisting of:
(i) hydrogen;
(ii) C1-11 alkyl, substituted C1-11 alkyl wherein the alkyl substituents are
defined
as above,
(iii) aryl C0-11 alkyl,
(iv) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
17. A compound as defined in claim 16 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
18. A compound as defined in claim 16 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
19. A compound as defined in claim 16 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
20. A compound as defined in claim 16 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
21. A compound as defined in claim 16 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
22. A compound as defined in claim 16 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
112
23. A compound as defined in claim 16 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
24. A compound with the structure depicted in Formula (A3):
Image
wherein at least one of R1, R2 and R3 substituents has the general structure
depicted in
Formula (B)
X-C(R')=C(R")COOR"'
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11 alkyl, optionally
substituted
aryl C1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11 alkyl,
aryl C1-11 alkyl, C0-11 alkyloxy C0-11 alkyl, aryl C0-11 alkyloxy C0-11 alkyl,
C0-11 alkylthio
C0-11 alkyl, aryl C0-11 alkylthio C0-11 alkyl, C1-11 alkylamino C0-11 alkyl,
aryl C0-11 alkylamino
C0-11 alkyl, di(aryl C1-11 alkyl)amino C0-11 alkyl, C1-11 alkylcarbonyl C0-11
alkyl, aryl
C1-11 alkylcarbonyl C0-11 alkyl, C1-11 alkylcarboxy C0-11 alkyl, aryl C1-11
alkylcarboxy
C0-11 alkyl, C1-11 alkylcarbonylamino C0-11 alkyl, aryl C0-11
alkylcarbonylamino C0-11, alkyl,
-C0-11 alkyl COOR4, -C0-11 alkyl CONR5R6 wherein R4, R5 and R6 are
independently
selected from hydrogen, C1-11 alkyl, aryl C0-C11 alkyl, or R5 and R6 are taken
together
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11 alkyl, aryl C0-C11 alkyl substituent.
(ii) R"' is selected from the group consisting of
(a) hydrogen,
113
(b) C1-11 alkyl, substituted C1-11 alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11 alkyloxy, aryl C0-11 alkyloxy, C0-11 alkylthio, aryl C0-11 alkylthio, C0-
11 alkylamino,
aryl C0-11 alkylamino, di(aryl C0-11 alkyl)amino, C1-11 alkylcarbonyl, aryl
C1-11 alkylcarbonyl, C1-11 alkylcarboxy, aryl C1-11 alkylcarboxy, C1-11
alkylcarbonylamino,
aryl C1-11 alkylcarbonylamino, -C0-11 alkyl COOR7, -C0-11 alkyl CONR8R9
wherein R7,
R8 and R9 are independently selected from hydrogen, C1-C11 alkyl, aryl C0-C11
alkyl, or
R8 and R9 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11 alkyl,
aryl
C0-C11 alkyl substituent,
(c) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein the remaining of R1, R2 and R3 are independently selected from the
group
consisting of:
(i) hydrogen;
114
(ii) C1-11 alkyl, substituted C1-11 alkyl, C1-11 alkylcarbonyl, substituted
C1-11 alkylcarbonyl wherein the alkyl substituents are defined as above,
(iii) aryl C0-11 alkyl, aryl C0-11 alkylcarbonyl,
(iv) mono-, di- and tri-substituted aryl C0-C11 alkyl, mono-, di- and
tri-substituted aryl C0-C11 alkylcarbonyl wherein the aryl substituents are
defined as
above,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
25. A compound as defined in claim 24 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
26. A compound as defined in claim 24 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
27. A compound as defined in claim 24 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
28. A compound as defined in claim 24 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
29. A compound as defined in claim 24 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
30. A compound as defined in claim 24 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
31. A compound with the structure depicted in Formula (A4):
115
Image
wherein at least one of R1, R2 substituents has the general structure depicted
in
Formula (B)
X-C(R')=C(R")COOR"'
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11 alkyl, optionally
substituted
aryl C1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11alkyl,
aryl C1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-11alkyl, C0-
11alkylthio
C0-11alkyl, arylC0-11alkylthioC0-11alkyl, C0-11alkylaminoC0-11alkyl, arylC0-
11alkylamino
C0-11alkyl, di(arylC1-11alkyl)aminoC0-11alkyl, C1-11alkylcarbonylC0-11alkyl,
aryl
C1-11alkylcarbonylC0-11alkyl, C1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarboxy
C0-11alkyl, C1-11alkylcarbonylaminoC0-11alkyl, arylC1-11alkylcarbonylaminoC0-
11 alkyl,
-C0-11alkylCOOR3, -C0-11alkylCONR4R5 wherein R3, R4 and R5 are independently
selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or R4 and R5 are taken
together
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11alkyl, arylC0-C11alkyl substituent.
(ii) R"' is selected from the group consisting of
(a) hydrogen,
(b) C1-11alkyl, substituted C1-11alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11alkyloxy, arylC0-11alkyloxy, C0-11alkylthio, arylC0-11alkylthio, C0-
11alkylamino,
arylC0-11alkylamino, di(aryl C0-11alkyl)amino, C1-11alkylcarbonyl, aryl
116
C1-11 alkylcarbonyl, C1-11 alkylcarboxy, aryl C1-11 alkylcarboxy, C1-11
alkylcarbonylamino,
aryl C1-11 alkylcarbonylamino, -C0-11 alkyl COOR6, -C0-11 alkyl CONR7R8
wherein R6,
R7 and R8 are independently selected from hydrogen, C1-C11 alkyl, aryl C0-C11
alkyl, or
R7 and R8 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11 alkyl,
aryl
C0-C11 alkyl substituent,
(c) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazoiyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein the remaining of R1, R2 is selected from the group consisting of:
(i) hydrogen;
(ii) C1-11 alkyl, substituted C1-11 alkyl wherein the alkyl substituents are
defined
as above,
(iii) aryl C-11 alkyl,
(iv) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
117
32. A compound as defined in claim 31 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
33. A compound as defined in claim 31 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
34. A compound as defined in claim 31 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
35. A compound as defined in claim 31 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
36. A compound as defined in claim 31 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
37. A compound as defined in claim 31 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
38. A compound as defined in claim 31 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
39. A compound with the structure depicted in Formula (A5):
Image
wherein at least one of R1, R2 substituents has the general structure depicted
in
Formula (B)
118
X-C(R')=C(R")COOR"'
(B)
wherein
(i) R' and R' are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11 alkyl, optionally
substituted
aryl C1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11 alkyl,
aryl C1-11 alkyl, C0-11 alkyloxy C0-11 alkyl, aryl C0-11 alkyloxy C0-11 alkyl,
C0-11 alkylthio
C0-11 alkyl, aryl C0-11 alkylthio C0-11 alkyl, C0-11 alkylamino C0-11 alkyl,
aryl C0-11 alkylamino
C0-11 alkyl, di(aryl C1-11 alkyl)amino C0-11 alkyl, C1-11 alkylcarbonyl C0-11
alkyl, aryl
C1-11 alkylcarbonyl C0-11 alkyl, C1-11 alkylcarboxy C0-11 alkyl, aryl C1-11
alkylcarboxy
C0-11 alkyl, C1-11 alkylcarbonylamino C0-11 alkyl, aryl C1-11
alkylcarbonylamino C0-11 alkyl,
-C0-11 alkyl COOR3, -C0-11 alkyl CONR4R5 wherein R3, R4 and R5 are
independently
selected from hydrogen, C1-C11 alkyl, aryl C0-C11 alkyl, or R4 and R5 are
taken together
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11 alkyl, aryl C0-C11 alkyl substituent.
(ii) R"' is selected from the group consisting of
(a) hydrogen,
(b) C1-11 alkyl, substituted C1-11 alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11 alkyloxy, aryl C0-11 alkyloxy, C0-11 alkylthio, aryl C0-11 alkylthio, C0-
11 alkylamino,
aryl C0-11 alkylamino, di(aryl C0-11 alkyl)amino, C1-11 alkylcarbonyl, aryl
C1-11 alkylcarbonyl, C1-11 alkylcarboxy, aryl C1-11 alkylcarboxy, C1-11
alkylcarbonylamino,
aryl C1-11 alkylcarbonylamino, -C0-11 alkyl COOR6, -C0-11 alkyl CONR7R8
wherein R6,
R7 and R8 are independently selected from hydrogen, C1-C11 alkyl, aryl C0-C11
alkyl, or
R7 and R8 are taken together with the nitrogen to which they are attached
forming a
119
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent,
(c) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein the remaining of R1, R2 is selected from the group consisting of:
(i) hydrogen;
(ii) C1-11alkyl, substituted C1-11alkyl wherein the alkyl substituents are
defined
as above,
(iii) arylC0-11alkyl,
(iv) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
40. A compound as defined in claim 39 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
120
41. A compound as defined in claim 39 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
42. A compound as defined in claim 39 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
43. A compound as defined in claim 39 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
44. A compound as defined in claim 39 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
45. A compound as defined in claim 39 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
46. A compound as defined in claim 39 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
47. A compound with the structure depicted in Formula (A6):
Image
wherein at least one of R1, R2, R3 and R4 substituents has the general
structure
depicted in Formula (B)
X-C(R')=C(R")COOR"'
121
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11 alkyl, optionally
substituted
aryl C1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11 alkyl,
aryl C1-11 alkyl, C0-11 alkyloxy C0-11 alkyl, aryl C0-11 alkyloxy C0-11 alkyl,
C0-11 alkylthio
C0-11 alkyl, aryl C0-11 alkylthio C0-11 alkyl, C0-11 alkylamino C0-11 alkyl,
aryl C0-11 alkylamino
C0-11 alkyl, di(aryl C1-11 alkyl)amino C0-11 alkyl, C1-11 alkylcarbonyl C0-11
alkyl, aryl
C1-11 alkylcarbonyl C0-11 alkyl, C1-11 alkylcarboxy C0-11 alkyl, aryl C1-11
alkylcarboxy
C0-11 alkyl, C1-11 alkylcarbonylamino C0-11 alkyl, aryl C1-11
alkylcarbonylamino C0-11 alkyl,
-C0-11 alkyl COOR5, -C0-11 alkyl CONR6R7 wherein R5, R6 and R7 are
independently
selected from hydrogen, C1-C11 alkyl, aryl C0-C11 alkyl, or R6 and R7 are
taken together
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11 alkyl, aryl C0-C11 alkyl substituent.
(ii) R"' is selected from the group consisting of
(a) hydrogen,
(b) C1-11 alkyl, substituted C1-11 alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11 alkyloxy, aryl C0-11 alkyloxy, C0-11 alkylthio, aryl C0-11 alkylthio, C0-
11 alkylamino,
aryl C0-11 alkylamino, di(aryl C0-11 alkyl)amino, C1-11 alkylcarbonyl, aryl
C1-11 alkylcarbonyl, C1-11 alkylcarboxy, aryl C1-11 alkylcarboxy, C1-11
alkylcarbonylamino,
aryl C1-11 alkylcarbonylamino, -C0-11 alkyl COOR8, -C0-11 alkyl CONR9R10
wherein R8,
R9 and R10 are independently selected from hydrogen, C1-C11 alkyl, aryl C0-C11
alkyl, or
R9 and R10 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11 alkyl,
aryl
C0-C11 alkyl substituent,
122
(c) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein the remaining of R1, R2, R3 and R4 are independently selected from
the
group consisting of:
(i) hydrogen;
(ii) C1-11 alkyl, substituted C1-11 alkyl wherein the alkyl substituents are
defined
as above,
(iii) aryl C0-11 alkyl,
(iv) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above, with the proviso that when R3 and R4 are
selected
from substituted phenyl or substituted furyl then the phenyl and furyl
substituents
exclude hydroxy, halo, trifluoromethyl, C1-6 alkyl, C1-6 alkyloxy, C1-6
alkylthio, amino,
C1-6 alkylamino, di(C1-6 alkyl)amino, phenyl C1-6 alkylamino and di(phenyl
C1-6 alkyl)amino,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
123
48. A compound as defined in claim 47 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
49. A compound as defined in claim 47 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
50. A compound as defined in claim 47 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
51. A compound as defined in claim 47 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
52. A compound as defined in claim 47 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
53. A compound as defined in claim 47 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
54. A compound as defined in claim 47 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
55. A compound with the structure depicted in Formula (A6):
Image
124
wherein R4 is selected from -COR5, -COOR6, -CONR7R8 wherein R5 thru R8 are
independently selected from hydrogen, C1-C11 alkyl, substituted C1-11 alkyl
where the
alkyl substituents are as defined below, optionally substituted aryl C0-C11
alkyl where
the aryl substituents are as defined below, or R7 and R8 are taken together
with the
nitrogen to which they are attached forming a cyclic system containing 3 to 8
carbon
atoms with at least one C1-C11 alkyl, aryl C0-C11 alkyl substituent, and
wherein at least
one of R1, R2, and R3 substituents has the general structure depicted in
Formula (B)
X-C(R')=C(R")COOR"'
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11 alkyl, optionally
substituted
aryl C1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11 alkyl,
aryl C1-11 alkyl, C0-11 alkyloxy C0-11 alkyl, aryl C0-11 alkyloxy C0-11 alkyl,
C0-11 alkylthio
C0-11 alkyl, aryl C0-11 alkylthio C0-11 alkyl, C0-11 alkylamino C0-11 alkyl,
aryl C0-11 alkylamino
C0-11 alkyl, di(aryl C1_11 alkyl)amino C0-11 alkyl, C1-11 alkylcarbonyl C0-11
alkyl, aryl
C1-11 alkylcarbonyl C0-11 alkyl, C1-11 alkylcarboxy C0-11 alkyl, aryl C1-11
alkylcarboxy
C0-11 alkyl, C1-11 alkylcarbonylamino C0-11 alkyl, aryl C1-11
alkylcarbonylamino C0-11 alkyl,
-C0-11 alkyl COOR9, -C0-11 alkyl CONR10R11 wherein R9, R10 and R11 are
independently
selected from hydrogen, C1-C11 alkyl, aryl C0-C11, alkyl, or R10 and R11 are
taken
together with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8 carbon atoms with at least one C1-C11 alkyl, aryl C0-C11
alkyl
substituent.
(ii) R"' is selected from the group consisting of
(a) hydrogen,
(b) C1-11 alkyl, substituted C1-11 alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
125
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11 alkyloxy, aryl C0-11 alkyloxy, C0-11 alkylthio, aryl C0-11 alkylthio, C0-
11 alkylamino,
aryl C0-11 alkylamino, di(aryl C0-11 alkyl)amino, C1-11 alkylcarbonyl, aryl
C1-11 alkylcarbonyl, C1-11 alkylcarboxy, aryl C1-11 alkylcarboxy, C1-11
alkylcarbonylamino,
aryl C1-11 alkylcarbonylamino, -C0-11 alkyl COOR12, -C0-11 alkyl CONR13R14
wherein
R12, R13 and R14 are independently selected from hydrogen, C1-C11 alkyl, aryl
C0-C11 alkyl, or R13 and R14 are taken together with the nitrogen to which
they are
attached forming a cyclic system containing 3 to 8 carbon atoms with at least
one
C1-C11 alkyl, aryl C0-C11 alkyl substituent,
(c) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, iridolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein the remaining of R1, R2 and R3 are independently selected from the
group
consisting of:
(i) hydrogen;
(ii) C1-11 alkyl, substituted C1-11 alkyl wherein the alkyl substituents are
defined
as above,
(iii) aryl C0-11 alkyl,
126
(iv) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
56. A compound as defined in claim 55 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
57. A compound as defined in claim 55 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
58. A compound as defined in claim 55 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
59. A compound as defined in claim 55 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
60. A compound as defined in claim 55 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
61. A compound as defined in claim 55 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
62. A compound as defined in claim 55 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
63. A compound with the structure depicted in Formula (A6):
127
Image
wherein R3 is selected from -COR5, -COOR6, -CONR7R8 wherein R5 thru R8 are
independently selected from hydrogen, C1-C11 alkyl, substituted C1-11 alkyl
where the
alkyl substituents are as defined below, optionally substituted aryl C0-C11
alkyl where
the aryl substituents are as defined below, or R7 and R8 are taken together
with the
nitrogen to which they are attached forming a cyclic system containing 3 to 8
carbon
atoms with at least one C1-C11 alkyl, aryl C0-C11 alkyl substituent, and
wherein at least
one of R1, R2, and R4 substituents has the general structure depicted in
Formula (B)
X-C(R')=C(R")COOR"'
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11 alkyl, optionally
substituted
aryl C1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11 alkyl,
aryl C1-11 alkyl, C0-11 alkyloxy C0-11 alkyl, aryl C0-11 alkyloxy C0-11 alkyl,
C0-11 alkylthio
C0-11 alkyl, aryl C0-11 alkylthio C0-11 alkyl, C0-11 alkylamino C0-11 alkyl,
aryl C0-11 alkylamino
C0-11 alkyl, di(aryl C1-11 alkyl)amino C0-11 alkyl, C1-11 alkylcarbonyl C0-11
alkyl, aryl
C1-11 alkylcarbonyl C0-11 alkyl, C1-11 alkylcarboxy C0-11 alkyl, aryl C1-11
alkylcarboxy
C0-11 alkyl, C1-11 alkylcarbonylamino C0-11 alkyl, aryl C1-11
alkylcarbonylamino C0-11 alkyl,
-C0-11 alkyl COOR9, -C0-11 alkyl CONR10R11 wherein R9, R10 and R11 are
independently
selected from hydrogen, C1-C11 alkyl, aryl C0-C11 alkyl, or R10 and R11 are
taken
together with the nitrogen to which they are attached forming a cyclic system
128
containing 3 to 8 carbon atoms with at least one C1-C11 alkyl, aryl C0-C11
alkyl
substituent.
(ii) R"' is selected from the group consisting of
(a) hydrogen,
(b) C1-11 alkyl, substituted C1-11 alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11 alkyloxy, aryl C0-11 alkyloxy, C0-11 alkylthio, aryl C0-11 alkylthio, C0-
11 alkylamino,
aryl C0-11 alkylamino, di(aryl C0-11 alkyl)amino, C1-11 alkylcarbonyl, aryl
C1-11 alkylcarbonyl, C1-11 alkylcarboxy, aryl C1-11 alkylcarboxy, C1-11
alkylcarbonylamino,
aryl C1-11 alkylcarbonylamino, -C0-11 alkyl COOR12, -C0-11 alkyl CONR13R14
wherein
R12, R13 and R14 are independently selected from hydrogen, C1-C11 alkyl, aryl
C0-C11 alkyl, or R13 and R14 are taken together with the nitrogen to which
they are
attached forming a cyclic system containing 3 to 8 carbon atoms with at least
one
C1-C11 alkyl, aryl C0-C11 alkyl substituent,
(c) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
129
and wherein the remaining of R1, R2 and R4 are independently selected from the
group
consisting of:
(i) hydrogen;
(ii) C1-11 alkyl, substituted C1-11 alkyl wherein the alkyl substituents are
defined
as above,
(iii) aryl C0-11 alkyl,
(iv) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
64. A compound as defined in claim 63 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
65. A compound as defined in claim 63 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
66. A compound as defined in claim 63 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
67. A compound as defined in claim 63 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
68. A compound as defined in claim 63 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
69. A compound as defined in claim 63 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
130
70. A compound as defined in claim 63 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
71. A compound with the structure depicted in Formula (A7):
Image
wherein R2 is selected from -COR5, -COOR6, -CONR7R8 wherein R5 thru R8 are
independently selected from hydrogen, C1-C11 alkyl, substituted C1-11 alkyl
where the
alkyl substituents are as defined below, optionally substituted aryl C0-C11
alkyl where
the aryl substituents are as defined below, or R7 and R8 are taken together
with the
nitrogen to which they are attached forming a cyclic system containing 3 to 8
carbon
atoms with at least one C1-C11 alkyl, aryl C0-C11 alkyl substituent, and
wherein at least
one of R1 and R3 substituents has the general structure depicted in Formula
(B)
X-C(R')=C(R")COOR"'
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11 alkyl, optionally
substituted
aryl C1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11 alkyl,
aryl C1-11 alkyl, C0-11 alkyloxy C0-11 alkyl, aryl C0-11 alkyloxy C0-11 alkyl,
C0-11 alkylthio
C0-11 alkyl, aryl C0-11 alkylthio C0-11 alkyl, C0-11 alkylamino C0-11 alkyl,
aryl C0-11 alkylamino
C0-11 alkyl, di(aryl C1-11 alkyl)amino C0-11 alkyl, C1-11 alkylcarbonyl C0-11
alkyl, aryl
C1-11 alkylcarbonyl C0-11 alkyl, C1-11 alkylcarboxy C0-11 alkyl, aryl C1-11
alkylcarboxy
131
C0-11 alkyl, C1-11 alkylcarbonylamino C0-11 alkyl, aryl C1-11
alkylcarbonylamino C0-11 alkyl,
-C0-11 alkyl COOR9, -C0-11 alkyl CONR10R11 wherein R9, R10 and R11 are
independently
selected from hydrogen, C1-C11 alkyl, aryl C0-C11 alkyl, or R10 and R11 are
taken
together with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8 carbon atoms with at least one C1-C11 alkyl, aryl C0-C11
alkyl
substituent.
(ii) R"' is selected from the group consisting of
(a) hydrogen,
(b) C1-11 alkyl, substituted C1-11 alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11 alkyloxy, aryl C0-11 alkyloxy, C0-11 alkylthio, aryl C0-11 alkylthio, C0-
11 alkylamino,
aryl C0-11 alkylamino, di(aryl C0-11 alkyl)amino, C1-11 alkylcarbonyl, aryl
C1-11 alkylcarbonyl, C1-11 alkylcarboxy, aryl C1-11 alkylcarboxy, C1-11
alkylcarbonylamino,
aryl C1-11 alkylcarbonylamino, -C0-11 alkyl COOR12, -C0-11 alkyl CONR13R14
wherein
R12, R13 and R14 are independently selected from hydrogen, C1-C11 alkyl, aryl
C0-C11 alkyl, or R13 and R14 are taken together with the nitrogen to which
they are
attached forming a cyclic system containing 3 to 8 carbon atoms with at least
one
C1-C11 alkyl, aryl C0-C11 alkyl substituent,
(c) mono-, di- and tri-substituted aryl C0-C11 alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
132
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein the remaining of R1 and R3 are independently selected from the
group
consisting of:
(i) hydrogen;
(ii) C1-11alkyl, substituted C1-11alkyl wherein the alkyl substituents are
defined
as above,
(iii) aryl C0-11alkyl,
(iv) mono-, di- and tri-substituted arylC0-C11 alkyl wherein the aryl
substituents are defined as above,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
72. A compound as defined in claim 71 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
73. A compound as defined in claim 71 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
74. A compound as defined in claim 71 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
75. A compound as defined in claim 71 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
76. A compound as defined in claim 71 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
133
77. A compound as defined in claim 71 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
78. A compound as defined in claim 71 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
79. A compound with the structure depicted in Formula (A8):
Image
wherein at least one of R1 and R2 substituents has the general structure
depicted in
Formula (B)
X-C(R')=C(R")COOR"'
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11 alkyl, optionally
substituted
aryl C1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11 alkyl,
aryl C1-11 alkyl, C0-11 alkyloxy C0-11 alkyl, aryl C0-11 alkyloxy C0-11 alkyl,
C0-11 alkylthio
C0-11 alkyl, aryl C0-11 alkylthio C0-11 alkyl, C0-11 alkylamino C0-11 alkyl,
aryl C0-11 alkylamino
C0-11 alkyl, di(aryl C1-11 alkyl)amino C0-11 alkyl, C1-11 alkylcarbonyl C0-11
alkyl, aryl
C1-11 alkylcarbonyl C0-11 alkyl, C1-11 alkylcarboxy C0-11 alkyl, aryl C1-11
alkylcarboxy
134
11alkyl, C1-11alkylcarbonylaminoC0-11alkyl, arylC1-11alkylcarbonylaminoC0-
11alkyl,
-C0-11alkylCOOR4, -C0-11alkylCONR5R6 wherein R4, R5 and R6 are independently
selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or R5 and R6 are taken
together
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11alkyl, arylC0-C11alkyl substituent.
(ii) R''' is selected from the group consisting of
(a) hydrogen,
(b) C1-11alkyl, substituted C1-11alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11alkyloxy, arylC0-11alkyloxy, C0-11alkylthio, arylC0-11alkylthio, C0-
11alkylamino,
arylC0-11alkylamino, di(arylCo-11alkyl)amino, C1 -11alkylcarbonyl,
arylC1-11alkylcarbonyl, C1-11alkylcarboxy, arylC1-11alkylcarboxy, C1-
11alkylcarbonylamino,
aryl C1-11alkylcarbonylamino, -C0-11alkylCOOR7, -C0-11alkylCONR8R9 wherein R7,
R8 and R9 are independently selected from hydrogen, C1-C11alkyl, arylC0-
C11alkyl, or
R8 and R9 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent,
(c) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
135
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein the remaining of R1 and R2 is independently selected from the
group
consisting of:
(i) hydrogen;
(ii) C1-11alkyl, substituted C1-11alkyl wherein the alkyl substituents are
defined
as above,
(iii) arylC0-11alkyl,
(iv) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above,
and wherein m is an integer between 0 and 4 and each R3 is independently
selected
from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl,
hydroxypyronyl, C1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-
11alkyl,
C0-11alkylthioC0-11alkyl, arylC0-11alkylthioC0-11alkyl, C0-11alkylaminoC0-
11alkyl,
arylC0-11alkylaminoC0-11alkyl, di(arylC1-11alkyl)aminoC0-11alkyl, C1-
11alkylcarbonylC0-11alkyl,
C1-11alkylcarboxyC0-11alkyl, C1-11alkylcarbonylaminoC0-11alkyl,
arylC1-11alkylcarbonylC0-11alkyl, arylC1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarbonyl-
aminoC0-11alkyl, -CH=CHCOOR10,
-CH=CHCONR11R12, -C0-11alkylCOOR13, -C0-11alkylCONR14R15 wherein R10 thru
R15 are independently selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or
R11
and R12 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent, or R14 and R15 are taken together with the
nitrogen to which they
are attached forming a cyclic system containing 3 to 8 carbon atoms with at
least one
C1-C22alkyl, arylC0-C11alkyl substituent,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
136
80. A compound as defined in claim 79 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
81. A compound as defined in claim 79 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
82. A compound as defined in claim 79 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
83. A compound as defined in claim 79 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
84. A compound as defined in claim 79 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
85. A compound as defined in claim 79 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
86. A compound as defined in claim 79 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
87. A compound with the structure depicted in Formula (A8):
Image
137
wherein R1 is selected from -COR16, -COOR17, -CONR18R19 wherein R16 thru R19
are
independently selected from hydrogen, C1-C11alkyl, substituted C1-11alkyl
where the
alkyl substituents are as defined below, optionally substituted arylC0-
C11alkyl where
the aryl substituents are as defined below, or R18 and R19 are taken together
with the
nitrogen to which they are attached forming a cyclic system containing 3 to 8
carbon
atoms with at least one C1-C11alkyl, arylC0-C11alkyl substituent, and wherein
R2 has
the general structure depicted in Formula (B)
X-C(R')=C(R")COOR'''
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11alkyl, optionally
substituted
arylC1-11alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11alkyl,
arylC1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-11alkyl, C0-
11alkylthioC0-11alkyl,
arylC0-11alkylthioC0-11alkyl, C0-11alkylaminoC0-11alkyl, arylC0-11alkylaminoC0-
11alkyl,
di(arylC1-11alkyl)aminoC0-11alkyl, C1-11alkylcarbonylC0-11alkyl,
arylC1-11alkylcarbonylC0-11alkyl, C1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarboxyC0-11alkyl,
C1-11alkylcarbonylaminoC0-11alkyl, arylC1-11alkylcarbonylaminoC0-11alkyl,
-C0-11alkylCOOR4, -C0-11alkylCONR5R6 wherein R4, R5 and R6 are independently
selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or R5 and R6 are taken
together
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11alkyl, aryl C0-C11alkyl substituent.
(ii) R''' is selected from the group consisting of
(a) hydrogen,
(b) C1-11alkyl, substituted C1-11alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-1alkyloxy, arylC0-11alkyloxy, C0-11alkylthio, arylC0-11alkylthio, C0-
11alkylamino,
138
arylC0-11alkylamino, di(arylC0-11alkyl)amino, C1 -11alkylcarbonyl,
arylC1-11alkylcarbonyl, C1-11alkylcarboxy, arylC1-11alkylcarboxy, C1-
11alkylcarbonylamino,
aryl C1-11alkylcarbonylamino, -C0-11alkylCOOR7, -C0-11alkylCONR8R9 wherein R7,
R8 and R9 are independently selected from hydrogen, C1-C11alkyl, arylC0-
C11alkyl, or
R8 and R9 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent,
(c) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein R2 is selected from the group consisting of:
(i) hydrogen;
(ii) C1-11alkyl, substituted C1-11alkyl wherein the alkyl substituents are
defined
as above,
(iii) arylC0-11alkyl,
(iv) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above,
139
and wherein m is an integer between 0 and 4 and each R3 is independently
selected
from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl,
hydroxypyronyl, C1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-
11alkyl,
C0-11alkylthioC0-11alkyl, arylC0-11alkylthioC0-11alkyl, C0-11alkylaminoC0-
11alkyl,
arylC0-11alkylaminoC0-11alkyl, di(aryl C1-11alkyl)aminoC0-11alkyl, C1-
11alkylcarbonylC0-11alkyl,
C1-11alkylcarboxyC0-11alkyl, C1-11alkylcarbonylaminoC0-11alkyl,
arylC1-11alkylcarbonylC0-11alkyl, arylC1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarbonyl-
aminoC0-11alkyl, -CH=CHCOOR10,
-CH=CHCONR11R12, -C0-11alkylCOOR13, -C0-11alkylCONR14R15 wherein R10 thru
R15 are independently selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or
R11
and R12 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl
substituent, or R14 and R15 are taken together with the nitrogen to which they
are attached forming a cyclic system containing 3 to 8 carbon atoms with at
least one
C1-C11alkyl, arylC0-C11alkyl substituent,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
88. A compound as defined in claim 87 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
89. A compound as defined in claim 87 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
90. A compound as defined in claim 87 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
91. A compound as defined in claim 87 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
140
92. A compound as defined in claim 87 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
93. A compound as defined in claim 87 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
94. A compound as defined in claim 87 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
95. A compound with the structure depicted in Formula (A9):
Image
wherein at least one of R1 and R2 substituents has the general structure
depicted in
Formula (B)
X-C(R')=C(R")COOR'''
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11alkyl, optionally
substituted
arylC1-11alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11alkyl,
arylC1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-11alkyl, C0-
11alkylthioC0-11alkyl,
141
arylC0-11alkylthioC0-11alkyl, C0-11a1kylaminoC0-11alkyl, arylC0-11alkylaminoC0-
11alkyl,
di(arylC1-11alkyl)aminoC0-11alkyl, C1-11alkylcarbonylC0-11alkyl,
arylC1-11alkylcarbonylC0-11alkyl, C1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarboxyC0-11alkyl,
C1-11alkylcarbonylaminoC0-11alkyl, arylC1-11alkylcarbonylaminoC0-11 alkyl,
C0-11alkylCOOR4, -C0-11alkylCONR5R6 wherein R4, R5 and R6 are independently
selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or R5 and R6 are taken
together
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11alkyl, arylC0-C11alkyl substituent.
{ii) R'''is selected from the group consisting of
{a) hydrogen,
(b) C1-11alkyl, substituted C1-11alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11alkyloxy, arylC0-11alkyloxy, C0-11alkylthio, arylC0-11alkylthio, C0-
11alkylamino,
arylC0-11alkylamino, di(arylC0-11alkyl)amino, C1-11alkylcarbonyl,
arylC1-11alkylcarbonyl, C0-11alkylcarboxy, arylC1-11alkylcarboxy, C1-
11alkylcarbonylamino,
aryl C1-11alkylcarbonylamino, -C0-11alkylCOOR7, -C0-11alkylCONR8R9 wherein R7,
R8 and R9 are independently selected from hydrogen, C1-C11alkyl, arylC0-
C11alkyl, or
R8 and R9 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent,
(c) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
142
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein the remaining of R1 and R2 is independently selected from the
group
consisting of:
(i) hydrogen;
(ii) C1-11alkyl, substituted C1-11alkyl wherein the alkyl substituents are
defined
as above,
(iii) arylC0-11alkyl,
(iv) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above,
and wherein m is an integer between 0 and 3 and each R3 is independently
selected
from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl,
hydroxypyronyl, C1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-
11alkyl,
C0-11alkylthioC0-11alkyl, arylC0-11alkylthioC0-11alkyl, C0-11alkylaminoC0-
11alkyl,
arylC0-lkylaminoC0-11alkyl, di(arylC1-11alkyl)aminoC0-11alky, C1-
11alkylcarbonylC0-11alkyl,
C1-11alkylcarboxyC0-11alkyl, C1-11alkylcarbonylaminoC0-11alkyl,
arylC1-11alkylcarbonylC0-11alkyl, arylC1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarbonyl-
aminoC0-11alkyl, -CH=CHCOOR10,
-CH=CHCONR11R12, -C0-11alkylCOOR13, -C0-11alkylCONR14R15 wherein R10 thru
R15 are independently selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or
R11
and R12 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent, or R14 and R15 are taken together with the
nitrogen to which they
are attached forming a cyclic system containing 3 to 8 carbon atoms with at
least one
C1-C11alkyl, arylC0-C11alkyl substituent,
143
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
96. A compound as defined in claim 95 wherein aryl is selected from phenyl,
naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
97. A compound as defined in claim 95 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
98. A compound as defined in claim 95 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
99. A compound as defined in claim 95 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
100. A compound as defined in claim 95 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
101. A compound as defined in claim 95 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
102. A compound as defined in claim 95 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
103. A compound having the structure depicted in Formula (A9):
144
Image
wherein R1 or R2 is selected from -COR16, -COOR17, -CONR18R19 wherein R16 thru
R19 are independently selected from hydrogen, C1-C11alkyl, substituted C1-
11alkyl
where the alkyl substituents are as defined below, optionally substituted
arylC0-C11alkyl
where the aryl substituents are as defined below, or R18 and R19 are taken
together with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8 carbon atoms with at least one C1-C11alkyl, arylC0-C11alkyl
substituent, and wherein the remainder of R1 or R2 has the general structure
depicted
in Formula (B)
X-C(R')=C(R")COOR'''
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11alkyl, optionally
substituted
aryl C1-11alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11alkyl,
arylC1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-11alkyl, C0-
11alkylthioC0-11alkyl,
arylC0-11alkylthioC0-11alkyl, C0-11alkylaminoC0-11alkyl, arylC0-11alkylaminoC0-
11alkyl,
di(arylC1-11alkyl)aminoC0-11alkyl, C1-11alkylcarbonylC0-11alkyl,
arylC1-11alkylcarbonylC0-11alkyl, C1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarboxyC0-11alkyl,
C1-11alkylcarbonylaminoC0-11alkyl, arylC1-11alkylcarbonylaminoC0-11alkyl,
-C0-11alkylCOOR4, -C0-11alkylCONR5R6 wherein R4, R5 and R6 are independently
selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or R5 and R6 are taken
together
145
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11alkyl, arylC0-C11alkyl substituent.
(ii) R''' is selected from the group consisting of
(a) hydrogen,
(b) C1-11alkyl, substituted C1-11alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11alkyloxy, arylC0-11alkyloxy, C0-11alkylthio, arylC0-11alkylthio, C0-
11alkylamino,
arylC0-11alkylamino, di(arylC0-11alkyl)amino, C1 -11alkylcarbonyl,
arylC1-11alkylcarbonyl, C1-11alkylcarboxy, arylC1-11alkylcarboxy, C1-
11alkylcarbonylamino,
aryl C1-11alkylcarbonylamino, -C0-11alkylCOOR7, -C0-11alkylCONR8R9 wherein R7,
R8 and R9 are independently selected from hydrogen, C1-C11alkyl, arylC0-
C11alkyl, or
R8 and R9 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent,
(c) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
146
and wherein R2 is selected from the group consisting of:
(i) hydrogen;
(ii) C1-11alkyl, substituted C1-11alkyl wherein the alkyl substituents are
defined
as above,
(iii) arylC0-11alkyl,
(iv) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above,
and wherein m is an integer between 0 and 3 and each R3 is independently
selected
from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl,
hydroxypyronyl, C1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-
11alkyl,
C0-11alkylthioC0-11alkyl, arylC0-11alkylthioC0-11alkyl, C0-11alkylaminoC0-
11alkyl,
arylC0-11alkylaminoC0-11alkyl, di(arylC1-11alkyl)aminoC0-11alkyl, C1-
11alkylcarbonylC0-11alkyl,
C1-11alkylcarboxyC0-11alkyl, C1-11alkylcarbonylaminoC0-11alkyl,
arylC1-11alkylcarbonylC0-11alkyl, arylC1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarbonyl-
aminoC0-11alkyl, -CH=CHCOOR10,
-CH=CHCONR11R12, -C0-11alkylCOOR13, -C0-11alkylCONR14R15 wherein R10 thru
R15 are independently selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or
R11
and R12 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent, or R14 and R15 are taken together with the
nitrogen to which they
are attached forming a cyclic system containing 3 to 8 carbon atoms with at
least one
C1-C11alkyl, arylC0-C11alkyl substituent,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
104. A compound as defined in claim 103 wherein aryl is selected from
phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
105. A compound as defined in claim 103 wherein aryl is phenyl,
147
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
106. A compound as defined in claim 103 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
107. A compound as defined in claim 103 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
108. A compound as defined in claim 103 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
109. A compound as defined in claim 103 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
110. A compound as defined in claim 103 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
111. A compound with the structure depicted in Formula (A10):
Image
wherein Z1 and Z2 are independently selected from the group consisting of OR3,
SR4,
NR5R6, wherein R3, R4, R5, R6 are independently selected from:
(i) hydrogen;
(ii) C1-11alkyl, substituted C1-11alkyl, C1-11alkylcarbonyl, substituted
C1-11alkylcarbonyl wherein the alkyl substituents are defined as below,
(iii) arylC0-11alkyl, arylC0-11alkylcarbonyl;
148
(iv) mono-, di- and tri-substituted arylC0-C11alkyl; mono-, di- and
tri-substituted arylC0-C11alkylcarbonyl wherein the aryl substituents are
defned as in
below,
and wherein at least one of R1 and R2 substituents has the general structure
depicted in
Formula (B)
X-C(R')=C(R")COOR'''
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11alkyl, optionally
substituted
arylC1-11 alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11alkyl,
arylC1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-11alkyl, C0-
11alkylthioC0-11alkyl,
arylC0-11alkylthioC0-11alkyl, C0-11alkylaminoC0-11alkyl, 11alkyl, arylC0-
11alkylaminoC0-11alkyl,
di(arylC1-11alkyl)aminoC0-11alkyl, C1-11alkylcarbonylC0-11alkyl,
arylC1-11alkylcarbonylC0-11alkyl, C1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarboxyC0-11alkyl,
C1-11alkylcarbonylaminoC0-11alkyl, arylC1-11alkylcarbonylaminoC0-11alkyl,
C0-11alkylCOOR7, -C0-11alkylCONR8R9 wherein R7, R8 and R9 are independently
selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or R8 and R9 are taken
together
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11alkyl, arylC0-C11alkyl substituent.
(ii) R''' is selected from the group consisting of
(a) hydrogen,
(b) C1-11alkyl, substituted C1-11alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11alkyloxy, arylC0-11alkyloxy, C0-11alkylthio, arylC0-11alkylthio, C0-
11alkylamino,
ary1C0-11alkylamino, di(arylC0-11alkyl)amino, C1-11alkylcarbonyl,
arylC1-11alkylcarbonyl, C1-11alkylcarboxy, arylC1-11alkylcarboxy, C1-
11alkylcarbonylamino,
149
aryl C1-11alkylcarbonylamino, -C0-11alkylCOOR10, -C0-11alkylCONR11R12 wherein
R10, R11 and R12 are independently selected from hydrogen, C1-C11alkyl,
arylC0-C11alkyl, or R11 and R12 are taken together with the nitrogen to which
they are
attached forming a cyclic system containing 3 to 8 carbon atoms with at least
one
C1-C11alkyl, arylC0-C11alkyl substituent,
(c) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein the remaining of R1, and R2 is independently selected from the
group
consisting of:
(i) hydrogen;
(ii) C1-11alkyl, substituted C1-11alkyl wherein the alkyl substituents are
defined
as above,
(iii) arylC0-11alkyl,
(iv) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
150
112. A compound as defined in claim 111 wherein aryl is selected from
phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
113. A compound as defined in claim 111 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
114. A compound as defined in claim 111 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
115. A compound as defined in claim 111 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
116. A compound as defined in claim 111 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
117. A compound as defined in claim 111 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
118. A compound as defined in claim 111 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
119. A compound with the structure depicted in Formula (A11):
Image
151
wherein at least one of R1, R2 and R3 substituents has the general structure
depicted in
Formula (B)
X-C(R')=C(R")COOR'''
(B)
wherein
(i) R' and R" are independently selected from the group consisting of
hydrogen, halo, cyano, nitro, trihalomethyl, C1-11alkyl, optionally
substituted
arylC1-11alkyl wherein the aryl substituents are independently selected from
the group
consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C1-
11alkyl,
arylC1-11alkyl, C0-11alkyloxyC0-11alkyl, arylC0-11alkyloxyC0-11alkyl, C0-
11alkylthioC0-11alkyl,
arylC0-11alkylthioC0-11alkyl, C0-11alkylaminoC0-11alkyl, arylC0-11alkylaminoC0-
11alkyl,
di(arylC1-11alkyl)aminoC0-11alkyl, C1-11alkylcarbonylC0-11alkyl,
arylC1-11alkylcarbonylC0-11alkyl, C1-11alkylcarboxyC0-11alkyl, arylC1-
11alkylcarboxyC0-11alkyl,
C1-11alkylcarbonylaminoC0-11alkyl, arylC1-11alkylcarbonylaminoC0-11alkyl,
-C0-11alkylCOOR5, -C0-11alkylCONR6R7 wherein R5, R6 and R7 are independently
selected from hydrogen, C1-C11alkyl, arylC0-C11alkyl, or R6 and R7 are taken
together
with the nitrogen to which they are attached forming a cyclic system
containing 3 to 8
carbon atoms with at least one C1-C11alkyl, arylC0-C11alkyl substituent.
(ii) R''' is selected from the group consisting of
(a) hydrogen,
(b) C1-11alkyl, substituted C1-11alkyl wherein the substituents are
independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl,
tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,
hydroxypyronyl,
C0-11alkyloxy, arylC0-11alkyloxy, C0-11alkylthio, arylC0-11alkylthio, C0-
11alkylamino,
arylC0-11alkylamino, di(arylC0-11alkyl)amino, C1-11alkylcarbonyl,
arylC1-11alkylcarbonyl, C1-11alkylcarboxy, arylC1-11alkylcarboxy, C1-
11alkylcarbonylamino,
aryl C1-11alkylcarbonylamino, -C0-11alkylCOOR8, -C0-11alkylCONR9R10 wherein
R8,
R9 and R10 are independently selected from hydrogen, C1-C11alkyl, arylC0-
C11alkyl, or
152
R9 and R10 are taken together with the nitrogen to which they are attached
forming a
cyclic system containing 3 to 8 carbon atoms with at least one C1-C11alkyl,
arylC0-C11alkyl substituent,
(c) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above for R' and R",
(iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents
are
defined as above for R' and R", and aryl is selected from phenyl, biphenyl,
naphthyl,
dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl,
phenanthryl,
fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-
dihydrobenzothienyl,
furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrcbenzofuranyl,
pyrrolyl,
indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl,
pyridyl,
pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-
quinolizinyl,
cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl,
pteridinyl,
carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl,
benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl,
tetrazolyl,
thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl,
oxadiazolyl,
or thiadiazolyl,
and wherein the remaining of R1, R2 and R3 are independently selected from the
group
consisting of:
(i) hydrogen;
(ii) C1-11alkyl, substituted C1-11alkyl wherein the alkyl substituents are
defined
as above,
(iii) arylC0-11alkyl,
(iv) mono-, di- and tri-substituted arylC0-C11alkyl wherein the aryl
substituents are defined as above,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
120. A compound as defined in claim 119 wherein aryl is selected from
phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,
153
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
121. A compound as defined in claim 119 wherein aryl is phenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
122. A compound as defined in claim 119 wherein aryl is naphthyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
123. A compound as defined in claim 119 wherein aryl is biphenyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
124. A compound as defined in claim 119 wherein aryl is thienyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
125. A compound as defined in claim 119 wherein aryl is furyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
126. A compound as defined in claim 119 wherein aryl is pyridyl,
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
127. A compound as defined in claim 1 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
128. A compound as defined in claim 1 with the structure as depicted below
154
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
129. A compound as defined in claim 63 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
130. A compound as defined in claim 63 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
131. A compound as defined in claim 47 with the structure as depicted below
155
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
132. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
133. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
134. A compound as defined in claim 47 with the structure as depicted below
156
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
135. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
136. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
137. A compound as defined in claim 47 with the structure as depicted below
157
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
138. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
139. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
140. A compound as defined in claim 47 with the structure as depicted below
158
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
141. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
142. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
143. A compound as defined in claim 47 with the structure as depicted below
159
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
144. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
145. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
146. A compound as defined in claim 47 with the structure as depicted below
160
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
147. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
148. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
149. A compound as defined in claim 47 with the structure as depicted below
161
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
150. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
151. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
152. A compound as defined in claim 47 with the structure as depicted below
162
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
153. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
154. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
154. A compound as defined in claim 47 with the structure as depicted below
or its pharmaceutically acceptable salts, prodrugs, ester, or solvates
thereof.
155. A compound as defined in claim 47 with the structure as depicted below
163
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
156. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
157. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
158. A compound as defined in claim 47 with the structure as depicted below
164
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
159. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
160. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
161. A compound as defined in claim 47 with the structure as depicted below
165
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
162. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
163. A compound with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
164. A compound as defined in claim 47 with the structure as depicted below
166
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
165. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
166. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
167. A compound as defined in claim 47 with the structure as depicted below
167
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
168. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
169. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
170. A compound as defined in claim 47 with the structure as depicted below
168
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
171. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
172. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
173. A compound as defined in claim 47 with the structure as depicted below
169
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
174. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
175. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
176. A compound as defined in claim 47 with the structure as depicted below
170
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
177. A compound with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
I78. A compound as defined in claim 39 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
179. A compound as defined in claim 39 with the structure as depicted below
Image
171
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
180. A compound as defined in claim 39 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
181. A compound as defined in claim 39 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
182. A compound as defined in claim 39 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
183. A compound as defined in claim 39 with the structure as depicted below
172
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
184. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
185. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
186. A compound as defined in claim 47 with the structure as depicted below
173
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
187. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
189. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
174
190. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
191. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
192. A compound as defined in claim 47 with the structure as depicted below
Image
175
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
193. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
194. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
195. A compound as defined in claim 47 with the structure as depicted below
176
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof
196. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
197. A compound as defined in claim 47 with the structure as depicted below
Image
177
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
198. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
199. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
200. A compound as defined in claim 47 with the structure as depicted below
178
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
201. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
202. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
179
203. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
204. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
205. A compound as defined in claim 47 with the structure as depicted below
Image
180
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
206. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
207. A compound as defined in claim 47 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
208. A compound as defined in claim 47 with the structure as depicted below
181
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
209. A compound as defined in claim 63 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
210. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
182
211. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
212. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
213. A compound as defined in claim 24 with the structure as depicted below
Image
183
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
214. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
2I5. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
216. A compound as defined in claim 24 with the structure as depicted below
Image
184
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
217. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
218. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
219. A compound as defined in claim 24 with the structure as depicted below
185
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
220. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
221. A compound as defined in claim 24 with the structure as depicted below
Image
186
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
222. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
223. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
224. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
187
225. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
226. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
227. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
188
228. A compound as defined in claim 24 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof
229. A compound as defined in claim 55 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
230. A compound as defined in claim 71 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
231. A compound as defined in claim 79 with the structure as depicted below
189
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
232. A compound as defined in claim 79 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
233. A compound as defined in claim 79 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
234. A compound as defined in claim 79 with the structure as depicted below
190
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
235. A compound as defined in claim 79 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
236. A compound as defined in claim 79 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
237. A compound as defined in claim 87 with the structure as depicted below
191
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
238. A compound as defined in claim 87 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
239. A compound as defined in claim 95 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
240. A compound as defined in claim 103 with the structure as depicted below
192
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
241. A compound as defined in claim 103 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
242. A compound as defined in claim 111 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
243. A compound as defined in claim 111 with the structure as depicted below
Image
193
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
244. A compound as defined in claim 111 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
245. A compound as defined in claim 111 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
246. A compound as defined in claim 111 with the structure as depicted below
194
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
247. A compound as defined in claim 119 with the structure as depicted below
Image
or its pharmaceutically acceptable salts, prodrugs, esters, or solvates
thereof.
248. A pharmaceutical composition comprising as active component a
compound according to any one of the preceding compound claims together with a
pharmaceutically acceptable carrier or diluent.
249. A pharmaceutical composition suitable for modulating the activity of
PTPases or other molecules with tyrosine phosphate recognition unit(s)
comprising an
effective amount of a compound according to any one of the preceding compound
claims together with a pharmaceutically acceptable carrier or diluent.
250. The pharmaceutical composition according to any one of the claims 248
or 249 suitable for treating or preventing type I diabetes, type II diabetes,
impaired
195
glucose tolerance, insuline resistance, obesity, immune dysfunctions including
autoimmunity and AIDS, diseases with dysfunctions of the coagulation system,
allergic diseases, osteoperosis, proliferative disorders including cancer and
psoriosis,
diseases with decreased or increased synthesis or effects of growth hormone,
diseases
with decreased or increased synthesis of hormones or cytokines that regulate
the
release of/or response to growth hormone, diseases of the brain including
Alzheimer's
disease and schizophrnia, and infectious diseases.
251. The pharmaceutical composition according to any one of the claims 248,
249 or 250 comprising between 0.5mg and 1000mg of a compound according to any
one of the preceding compound claims per unit dose.
252. A method of modulating the activity of PTPases or other molecules with
phosphotyrosine recognition unit(s) in a subject in need of such treatment
comprising
administering to said subject an effective amount of a compound or composition
according to any one of the preceding compound or composition claims.
253. The use of a compound according to any one of the preceding compound
claims for preparing a medicament.
254. The use of a compound according to any one of the preceding compound
claims for preparing a medicament for modulating the activity of PTPases or
other
molecules with phosphotyrosine recognition unit(s).
255. The use of a compound according to any one of the preceding compound
claims for preparing a medicament for treating or preventing type I diabetes,
type II
diabetes, impaired glucose tolerance, insuline resistance, obesity, immune
dysfunctions including autoimmunity and AIDS, diseases with dysfunctions of
the
coagulation system, allergic diseases, osteoperosis, proliferative disorders
including
196
cancer and psoriosis, diseases with decreased or increased synthesis or
effects of
growth hormone, diseases with decreased or increased synthesis of hormones or
cytokines that regulate the release of/or response to growth hormone, diseases
of the
brain including Alzheimer's disease and schizophrnia, and infectious diseases.
256. The use of a compound according to any one of the preceding compound
claims for preparing a medicament for treating a subject in need of such
treatment.
257. The use of a compound according to any one of the preceding compound
claims for preparing a medicament for use as an immunosuppressant.
258. An immobilized compound comprising a suitable solid-phase coupled
with a compound according to any one of the preceding compound claim.
259. A method for coupling a compound according to any one of the
preceding compound claims to a suitable solid-phase matrix.
260. A method for isolating a protein or a glycoprotein with affinity for a
compound according to any one of the preceding compound claims from a
biological
sample, comprising
- contacting an immobilized compound according to claim 258 with said
biological sample in order for said immobilized compound to form a complex by
binding said protein or glycoprotein
- removing unbound material from said biological sample and isolating said
complex
- extracting said protein or glycoprotein from said complex.
197
261. A method for isolating a protein-tyrosine phosphatase with amity for a
compound according to any one of the preceding compound claims from a
biological
sample, comprising
- contacting an immobilized compound according to claim 258 with said
biological sample in order for said immobilized compound to form a complex by
binding said protein-tyrosine phosphatase
- removing unbound material from said biological sample and isolating said
complex
- extracting said protein-tyrosine phosphatase from said complex.
262. A method for isolating a Src-homology 2 domain containing protein or a
phosphotyrosine binding domain containg protein with affinity for a compound
according to any one of the preceding compound claims from a biological
sample,
comprising
- contacting an immobilized compound according to claim 258 with said
biological sample in order for said immobilized compound to form a complex by
binding said Src-homology 2 domain containing protein or a phosphotyrosine
binding
domain containg protein
- removing unbound material from said biological sample and isolating said
complex
- extracting said Src-homology 2 domain containing protein or a
phosphotyrosine binding domain containg protein from said complex.
263. A compound according to any one of the preceding compound claims
coupled to a fluorescent or radioactive molecule.
264. A method for coupling a fluorescent or radioactive molecule to a
compound according to any one of the preceding compound claims comprising
198
- contacting said compound with said fluorescent or radioactive molecule in a
reaction mixture to produce a complex
- removing uncomplexed material and isolating said complex from said
reaction mixture.
265. A method for detecting a protein-tyrosine phosphatase or other molecules
with phosphotyrosine recognition unit(s) in a cell or in a subject using a
compound
according to claim 263 comprising
- contacting said cell or an extract thereof or a biological sample from said
subject or by injecting said compound into said subject in order for said
compound to
produce a complex with said protein-tyrosine phosphatase or said other
molecules
with phosphotyrosine recognition unit(s)
- detecting said complex, thereby detecting the presence of said
protein-tyrosine phosphatase or said other molecules with phosphotyrosine
recognition
unit(s).
266. A method for quantifying the amount of protein-tyrosine phosphatase or
other molecules with phosphotyrosine recognition unit(s) in a cell or in a
subject
using a compound according to claim 263 comprising
- contacting said cell or an extract thereof or a biological sample from said
subject or by injecting said compound into said subject in order for said
compound to
produce a complex with said protein-tyrosine phosphatase or said other
molecules
with phosphotyrosine recognition unit(s)
- measuring the amount of said complex, thereby detecting the presence of
said protein-tyrosine phosphatase or said other molecules with phosphotyrosine
recognition unit(s).
267. A method for determining the function of a given protein-tyrosine
phosphatase or group of protein-tyrosine phosphatases or said molecules with
199
phosphotyrosine recognition unit(s) in a cell or in a subject using a compound
according to claim 263 comprising
- contacting said cell or an extract thereof or a biological sample from said
subject or by injecting said compound into said subject in order for said
compound to
produce a complex with said protein-tyrosine phosphatase or said other
molecules
with phosphotyrosine recognition unit(s)
- measuring the biological effects induced by said complex.
