Canadian Patents Database

Claims page

---

Patent Document Number: 2411778

(54) English Title: ORGANIC COMPOUNDS

(54) French Title: COMPOSES ORGANIQUES

---

Claims:

Note: Claims are shown in the official language in which they were submitted.




-42-
WHAT IS CLAIMED IS:
1. A compound of formula I:
Image
where Y is selected from the group consisting of:
a) a group of the formula Image, where R
is an unsubstituted pyridine or pyrimidine ring; a pyridine or pyrimidine ring
which is mono- or independently di-substituted by halo, trifluoromethyl,
cyano, nitro or C1-6alkyl; unsubstituted benzoyl; a benzoyl group which is
mono- or di-substituted by halo or C1-6alkyl; C1-6alkylcarbonyl; di-C1-
6alkylaminocarbonyl; unsubstituted phenylaminocarbonyl; or a
phenylaminocarbonyl group which is mono- or di-substituted on the phenyl
ring by halo or C1-6alkyl;
Image
b) a group of the formula , where R1
is an unsubstituted pyridine, pyrimidine or phenyl ring; a pyridine,
pyrimidine or phenyl ring which is mono- or independently di-substituted by
halo, trifluoromethyl, cyano, nitro or C1-6alkyl; an unsubstituted
phenylsulfonyl group; a phenylsulfonyl group which is mono- or di-
substituted on the phenyl ring by halo, trifluoromethyl, cyano, nitro or C1-
6alkyl; unsubstituted benzoyl; a benzoyl group which is mono- or di-
substituted by halo or C1-6alkyl; C1-6alkylcarbonyl; thienyl sulfonyl;





-43-
unsubstituted benzothiazole; or a benzothiazole group which is substituted
on the phenyl ring by halo or C1-6alkyl;
Image
c) a group of the formula Image, where R2
is an unsubstituted phenyl ring; or a phenyl ring which is mono- or di-
substituted by halo or C1-6alkyl;
d) a group of the formula Image, where R3
is an unsubstituted phenylsulfonyl group; a phenylsulfonyl group which is
mono- or di-substituted on the phenyl ring by halo, trifluoromethyl, cyano,
nitro or C1-6- alkyl; C1-6alkylcarbonyl; di-C1-6alkylaminocarbonyl;
unsubstituted benzoyl; a benzoyl group which is mono- or di-substituted by
halo or C1-6alkyl; unsubstituted phenylaminocarbonyl;
phenylaminocarbonyl which is mono- or di-substituted on the phenyl ring
by halo or C1-6alkyl; a phenyl-substituted thiazole ring; or a phenyl-
substituted thiazole ring wherein the phenyl ring is mono- or di-substituted
by halo or C1-6alkoxy;
e) a (4-pentylbicyclo[2.2.2]oct-l-yl)amine group;
Image
f) a group of the formula Image, where R4
is an unsubstituted phenyl ring; or a phenyl ring which is mono- or di-
substituted by halo, trifluoromethyl, cyano, nitro or C1-6alkyl; and
g)




-44-
Image
where R5 is C3-8cycloalkyl-carbonyl, if Z is N; or R5 is C3-8cycloalkyl-
carbonylamino, if Z is CH;
and wherein the bond containing the wavy line signifies the point of
attachment of the
"Y" group to the glycyl-2-cyanopyrrolidine moiety;
or an acid addition salt thereof.
2. A compound according to Claim 1 of formula Ia:
Image
where Y' is selected from the group consisting of:
Image
a) a group of the formula Image, where R'
is an unsubstituted pyridine or pyrimidine ring; a pyridine or pyrimidine ring
which is mono- or independently di-substituted by halo, trifluoromethyl or
cyano; unsubstituted benzoyl; a benzoyl group which is monosubstituted
by halo or C1-6 alkyl; C1-6alkylcarbonyl; di-C1-6alkylaminocarbonyl;
unsubstituted phenylaminocarbonyl; or a phenylaminocarbonyl group
which is monosubstituted on the phenyl ring by halo or C1-6alkyl;

b) a group of the formula Image, where R1
is an unsubstituted pyridine, pyrimidine or phenyl ring; a pyridine,
pyrimidine or phenyl ring which is monosubstituted by halo, trifluoromethyl,
cyano, nitro or C1-6-alkyl; an unsubstituted phenylsulfonyl group; a
phenylsulfonyl group which is monosubstituted on the phenyl ring by halo,





-45-
trifluoromethyl, cyano, nitro or C1-6-alkyl; unsubstituted benzoyl; a benzoyl
group which is monosubstituted by halo or C1-6alkyl; C1-6alkylcarbonyl;
thienyl sulfonyl; unsubstituted benzothiazole; or a benzothiazole group
which is substituted on the phenyl ring by halo or C1-6alkyl;
Image
c) a group of the formula Image, where R~
is an unsubstituted phenyl ring; or a phenyl ring which is monosubstituted
by halo or C1-6alkyl;
d) a group of the formula Image, where R~
is an unsubstituted phenylsulfonyl group; a phenylsulfonyl group which is
monosubstituted on the phenyl ring by halo, trifluoromethyl, cyano, nitro or
C1-
6alkyl; C1-6alkylcarbonyl; di-C1-6alkylaminocarbonyl; unsubstituted benzoyl; a
benzoyl group which is monosubstituted by halo or C1-6alkyl; unsubstituted
phenylaminocarbonyl; phenylaminocarbonyl which is monosubstituted on the
phenyl ring by halo or C1-6alkyl; a phenyl-substituted thiazole ring; or a
phenyl-
substituted thiazole ring wherein the phenyl ring is monosubstituted by halo
or
C1-6alkoxy;
e) a (4-pentylbicyclo[2.2.2]oct-l-yl)amine group; and
f) a group of the formula Image, where R~
is an unsubstituted phenyl ring; or a phenyl ring which is monosubstituted
by halo, trifluoromethyl, cyano, nitro or C1-6alkyl;
or an acid addition salt thereof.
3. A compound according to Claim 2 of formula Ic:




-46-
Image
where Y"' is:
Image
a) a group of the formula Image, where R"'
is an unsubstituted pyridine or pyrimidine ring; a pyridine or pyrimidine ring
which is monosubstituted by chloro, trifluoromethyl or cyano or
disubstituted by chloro; unsubstituted benzoyl; a benzoyl group which is
monosubstituted by chloro, methyl or ethyl; C1-6alkylcarbonyl; di-C1-
6alkylaminocarbonyl; unsubstituted phenylaminocarbonyl; or a
phenylaminocarbonyl group which is monosubstituted on the phenyl ring
by chloro;

b) a group of the formula Image, where R~
is an unsubstituted pyridine, pyrimidine or phenyl ring; a pyridine,
pyrimidine or phenyl ring which is monosubstituted by chloro,
trifluoromethyl or cyano; an unsubstituted phenylsulfonyl group; a
phenylsulfonyl group which is monosubstituted on the phenyl ring by
chloro or trifluoromethyl; unsubstituted benzoyl; a benzoyl group which is
monosubstituted by chloro; C1-6alkylcarbonyl; thienyl sulfonyl;
unsubstituted benzothiazole; or a benzothiazole group which is substituted
on the phenyl ring by chloro;
Image
c) a group of the formula Image, where R~




-47-
is an unsubstituted phenyl ring; or a phenyl ring which is monosubstituted
by fluoro;
Image
d) a group of the formula Image,
is an unsubstituted phenylsulfonyl group; a phenylsulfonyl group which is
monosubstituted on the phenyl ring by chloro or trifluoromethyl; C1-
6alkylcarbonyl; di-C1-6alkylaminocarbonyl; unsubstituted benzoyl; a benzoyl
group which is monosubstituted by chloro; unsubstituted
phenylaminocarbonyl; phenylaminocarbonyl which is monosubstituted on
the phenyl ring by chloro; a phenyl-substituted thiazole ring; or a phenyl-
substituted thiazole ring wherein the phenyl ring is monosubstituted by
chloro or methoxy;
e) a (4-pentylbicyclo[2.2.2)oct-l-yl)amine group; and

f) a group of the formula Image, where R~
is an unsubstituted phenyl ring; or a phenyl ring which is monosubstituted
by chloro or trifluoromethyl;
or an acid addition salt thereof.
4. The compound according to anyone of claims 1 to 3 of selected from formulae
Image




-48-
Image and Image
5. The compound according to any one of Claims 1 to 4 which is selected from
the
group consisting of
1-[[[4-(benzoylamino)cyclohexyl]amino]acetyl]-2-cyano-(S)-pyrrolidine,
1-[[[1-[(4-chlorophenyl)sulfonyl]-4-piperidinyl]amino]acetyl]-2-cyano-(S)-
pyrrolidine,
and
1-[[[4-[(4-fluorobenzoyl)amino]cyclohexyl]amino]acetyl]-2-cyano-(S)-
pyrrolidine,
or, in each case, an acid addition salt thereof.
6. The compound according to Claim 5 in free base form.
7. A pharmaceutical composition comprising a pharmaceutically acceptable
carrier or
diluent and a therapeutically effective amount of a compound according to any
one of
Claims 1 to 6, or a pharmaceutically acceptable acid addition salt thereof.
8. Use of a compound according to any one of Claims 1 to 6 or a
pharmaceutically
acceptable salt thereof for the manufacture of a medicament for inhibiting
dipeptidyl
pepidase-IV or for the prevention or treatment of diseases or conditions
associated
with elevated levels of DPP-IV.
9. Use according to claim 8 for the manufacture of a medicament for the
treatment of
non-insulin dependent diabetes mellitus, arthritis, obesity, osteoporosis and
further
conditions of impaired glucose tolerance.




-49-

10. A method of inhibiting dipeptidyl pepidase-IV or for preventing or
treating
diseases or conditions associated with elevated levels of DPP-IV comprising
administering to a mammal in need of such treatment a therapeutically
effective
amount of a compound according to any one of Claims 1 to 6, or a
pharmaceutically
acceptable acid addition salt thereof.