BENZYLGLYCOSYLAMIDES AS INHIBITORS OF SMOOTH MUSCLE CELL PROLIFERATION

BENZYLGLYCOSYLAMIDES UTILISES COMME INHIBITEURS DE LA PROLIFERATION CELLULAIRE DES MUSCLES LISSES

English Abstract

This invention provides smooth muscle cell proliferation inhibitors of formula
(I) having the structure (a) wherein Y is C or N; where n is 0 - 3; X is (II);
or a pharmaceutically acceptable salt thereof.

French Abstract

La présente invention concerne des inhibiteurs de la prolifération cellulaire des muscles lisses représentés par la formule (I), ayant la structure (a) dans laquelle Y représente C ou N; n étant compris entre 0 et 3; X représente (II); ou un sel de ceux-ci acceptable sur le plan pharmaceutique.

Claims

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WHAT IS CLAIMED IS:
1. A compound of formula I having the structure
Image
wherein
Y is C or N;
where n is 0 - 3;
X is
Image
R1, and R2 are each independently, hydrogen, alkyl of 1 to 6 carbon atoms,
halo,
acetyl, phenyl, CF3, CN, OH, NO2, NH2, alkoxy of 1 to 6 carbon atoms, or
cyanoalkoxy of 2 to 7 carbon atoms;
R3 is hydrogen, acylamide of 2 to 6 carbon atoms or alkoxy of 1 to 6 carbon
atoms;
R4, R5, R6, R7, and R8 are each, independently, hydrogen, acyl of 1 to 6
carbon
atoms, benzyl substituted with R1, and R2; or benzoyl substituted with R1
and R2;
R9 and R10 are each, independently, acyl of 1 to 6 carbon atoms, or the R9 and
R10 groups on the 4' and 6' positions of the maltose may be taken together
to form a cyclic acetal which may be substituted with alkyl of 1 to 6
carbon atoms, two alkyl groups each having 1 to 6 carbon atoms, pyridine
substituted with R1, phenyl substituted with R1, benzyl substituted with R1,
2-phenylethyl substituted with R1, or 3-phenylpropyl substituted with R1;
with the provisio that when R1 or R2 are cyanoalkoxy of 2-7 carbon atoms, R3
is not acylamide, and further provided that when R1, R2, or R3 are alkoxy of 1-
6
carbon atoms, at least one of R1, R2, R3, or R4 are not hydrogen;
or a pharmaceutically acceptable salt thereof.


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2. The compound according to claim 1, wherein
n is 0-1;
R1, and R2 are each independently, hydrogen, halogen, CF3, OH, NO2, NH2,
methoxy,
butoxy, or butoxynitrile;
R3 is hydrogen, acetamide, or methoxy;
R4, R5, R6, R7, and R8 are each, independently, hydrogen, an acyl of 1-6
carbon atoms,
or benzoyl;
R9 and R10 are each, independently, acyl of 1-6 carbon atoms, or the R9 and
R10 groups
on the 4' and 6' positions of the maltose are taken together form a
benzylidene ring;
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 2, wherein
n is 0;
R1, and R2 are each independently, hydrogen or halogen;
R3 is hydrogen;
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1, which is (R)-3-(acetylamino)-N-[6-O-
benzoyl-4-O-[4,6- O -(phenylmethylene)-.alpha.-D-glucopyranosyl]-~3-D-
glucopyranosyl]-
4-chlorobenzamide or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1, which is 4-chloro-N-[(2,2',3,3'-tetra-O-
acetyl- 6-benzoyl-4',6'- O benzylidene)-.beta.-D-maltosyl]-3-nitro-benzamide.
6. The compound of claim 1, which is (R)-N-[2-O-acetyl-4-O-[2-O-
acetyl-4,6-O -(phenylmethylene)-.alpha.-D-glucopyranosyl]-6-O-benzoyl-.beta.-D-

glucopyranosyl]-3-(acetylamino)-4-chlorobenzamide chlorobenzamide or a
pharmaceutically acceptable salt thereof.


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7. The compound of claim 1, which is N-(6-O-benzoyl-4',6'-O-
benzylidene-(3-D-maltosyl)-3-chloro-4-(4-nitrilo-butoxy)-phenylamide
chlorobenzamide or a pharmaceutically acceptable salt thereof.
8. The compound of claim 1, which is N-(6-O-benzoyl-4',6'-O-
benzylidene-.beta.-D-maltosyl}-4-chloro-3-methoxy-benzamide chlorobenzamide or
a
pharmaceutically acceptable salt thereof.
9. The compound of claim 1, which is N-(6-O-benzoyl-4', 6'-O-
benzylidene-.beta.-D-maltosyl)-4-(4-nitrilo-butoxy)-3-nitro-benzamide
chlorobenzamide
or a pharmaceutically acceptable salt thereof.
10. The compound of claim 1, which is 3-acetylamino-N-(6-O-benzoyl-4',
6'-O-benzylidene-.beta.-D-maltosyl)-4-(4-nitrilo-butoxy)-benzamide
chlorobenzamide or
a pharmaceutically acceptable salt thereof.
11. The compound of claim 1, which is N-(hepta-O-acetyl-.beta.-D-maltosyl)-
3-chloro-4-methoxy-benzamide.
12. The compound of claim 1, which is N-(6-O-benzoyl-4',6'-O-
benzylidene-.beta.-D-maltosyl)-2-(3,4-dimethoxy-phenyl)-acetamide
chlorobenzamide or
a pharmaceutically acceptable salt thereof.
13. The compound of claim 1, which is 2-[3-acetyl-amino)-4-chloro-
phenyl]-N-(6-O-benzoyl-4',6'-O-benzylidene-.beta.-D-maltosyl)-acetamide
chlorobenzamide or a pharmaceutically acceptable salt thereof.
14. The compound of claim 1, which is:
a) N-(hepta-O-acetyl-1-deoxy-.beta.-D-maltosyl)-4-chloro-3-nitro-benzamide;
b) 3-amino-4-chloro-N-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-.alpha.-
D
glucopyranosyl)-(3-D-glucopyranosyl)-benzamide;


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c) 3-(acetylamino)-4-chloro-N-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-
.alpha.-
D-glucopyranosyl)-.beta.-D-glucopyranosyl}-benzamide;
d) (R)-3-(acetylamino)-4-chloro-N-[4-O-[4,6- O -(phenylmethylene)-.alpha.-D-
glucopyranosyl]-.beta.-D-glucopyranosyl]-benzamide or a pharmaceutically
acceptable
salt thereof;
e) (R)-4-chloro-3-nitro-N-[4-O-[4,6- O -(phenylmethylene)-.alpha.-D-
glucopyranosyl]-.beta.-D-glucopyranosyl]-benzamide or a pharmaceutically
acceptable
salt thereof;
f) (R)-4-chloro-N-[(6-O-benzoyl-4',6'- O -benzylidene)--.beta.-D-maltosyl]-3-
nitro-
benzamide or a pharmaceutically acceptable salt thereof;
g) N-(Hepta-O-acetyl-.beta.-D-maltosyl)-4-chloro-benzamide;
h) N-(4', 6'-O-benzylidene-.beta.-D-maltosyl)-4-chloro-benzamide or a
pharmaceutically acceptable salt thereof;
i) N-(6-O-benzoyl-4',6'-O -benzylidene-.beta.-D-maltosyl)-4-chloro-benzamide
or a
pharmaceutically acceptable salt thereof;
j) N-[(2,2',3,3'4',6,6'-hepta-O-acetyl-.beta.-D-maltosyl]-3-chloro-4-
nitrilobutoxy-
benzoic acid amide;
k) N-[(2,2',3,3'4',6,6'-hepta-O-acetyl-.alpha.-D-maltosyl]-3-chloro-4-
nitrilobutoxy-
benzoic acid amide;
l) N-(4',6'-O-benzylidene-.beta.-D-maltosyl)-3-chloro-4-(4-nitrilo-butoxy)-
benzamide or a pharmaceutically acceptable salt thereof;
m) N-(2,2',3,3'-tetra-O-acetyl-6-O-benzoyl-4',6'-O-benzylidene-.beta.-D-
maltosyl)-
3-chloro-4-(4-nitrilo-butoxy)-benzamide;
n) 4-butoxy-3-chloro-N-[2,3,6-tri- O-acetyl-4-O-(2,3,4,6-tetra- O-acetyl-
.alpha.-D-
glucopyranosyl)-.beta.-D-glucopyranosyl] benzamide;
o) 4-butoxy-3-chloro-N-[(6-O-benzoyl-4', 6'-O-benzylidene)-.beta.-D-maltosyl]-
benzamide or a pharmaceutically acceptable salt thereof;
p) 4-butoxy-3-chloro-N-[(2,3,2',3'-tetra-O-acetyl-6-O-benzoyl-4',6'-O-
benzylidene)-(3-D-maltosyl]-benzamide;
q) 4-chloro-3-methoxy-N-[2,3,6-tri- O-acetyl-4-O-(2,3,4,6-tetra- O-acetyl-
.alpha.-D-
glucopyranosyl)-(3-D-glucopyranosyl] benzamide;


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r) N-(2,2',3,3',4,6,6'-hepta- O-acetyl- .beta.-D-maltosyl]-4-butoxy-5-chloro-3-

methoxy-benzamide;
s) N[(6-O-benzoyloxy-4', 6'-O-benzylidene)-.beta.-D-maltosyl]-4-butoxy-3-
chloro-
5-methoxy-benzamide or a pharmaceutically acceptable salt thereof;
t) N-[(2,2',3,3'4',6,b'-hepta-O-acetyl-.beta.-D-maltosyl]4-(4-nitrilo-butoxy)-
3-
nitro-benzamide;
u) N-(4',6'-O-benzylidene-.beta.-D-maltosyl)-4-(4-nitrilo-butoxy)-3-nitro-
benzamide or a pharmaceutically acceptable salt thereof;
v) N-(2,2',3,3'-tetra-O-acetyl-6-O-benzoyl-4',6'-O-benzylidene-.beta.-D-
maltosyl)-
4-(4-nitrilo-butoxy)-3-nitro-benzamide;
w) N-[(2,2',3,3'4',6,6'-hepta-O-acetyl-.beta.-D-maltosyl]-3-amino-4-(4-nitrilo-

butoxy)-benzamide;
x) N-[(2,2',3,3'4',6,6'-hepta-O-acetyl-.beta.-D-maltosyl]-6-chloropyridine-3-
carboxamide or a pharmaceutically acceptable salt thereof;
y) N-(hepta-O-acetyl-.beta.-D-maltosyl)-2,6-dimethoxy-pyridine-3-carboxamide
or a
pharmaceutically acceptable salt thereof;
z) N-(hepta-O-acetyl-.beta.-D-maltosyl)-5-bromopyridine-3-carboxamide or a
pharmaceutically acceptable salt thereof;
aa) N-(hepta-O-acetyl-(3-D-maltosyl)-3-(trifluoromethyl)-benzamide;
bb) N-(4',6'-O-benzylidene-(3-D-maltosyl)-3-(trifluoromethyl)-benzamide or a
pharmaceutically acceptable salt thereof;
cc) N-[{6-O-benzoyl-4',6'-O-benzylidene}-.beta.-D-maltosyl]-3-
(trifluoromethyl)-
benzamide or a pharmaceutically acceptable salt thereof;
dd) N-(hepta-O-acetyl-(3-D-maltosyl)-6-methylpyridine-3-carboxamide or a
pharmaceutically acceptable salt thereof;
ee) N-(2,2',3,3',4',6,6'-hepta-O-acetyl-.beta.-maltosyl)-4-butoxy-3,5-dichloro-

benzylamide;
ff) N-(4',6'-O-benzylidene-.beta.-D-maltosyl)-4-butoxy-3,5-dichloro-benzamide
or a
pharmaceutically acceptable salt thereof;
gg) N-(2,2',3,3',4',6,6'-hepta-O-acetyl-.beta.-D-maltosyl)-1-(3,4-dimethoxy)-
phenyl-
acetamide;


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hh) N-(hepta-O-acetyl-.beta.-D-maltosyl)-2-(4-hydroxy-3-nitro-phenyl)-
acetamide or
a pharmaceutically acceptable salt thereof; or
ii) N-(2,2',3,3',4',6,6'-hepta-O-acetyl-.beta.-D-maltosyl)-2-(4-chloro-3-nitro-

phenyl)-acetamide;
15. A method of treating or inhibiting hyperproliferative vascular
disorders in a mammal in need thereof, which comprises administering to said
mammal an effective amount of a compound of formula I having the structure
Image
wherein
Y is C or N;
where n is 0 - 3;
X is
Image
R1, and R2 are each independently, hydrogen, alkyl of 1 to 6 carbon atoms,
halo,
acetyl, phenyl, CF3, CN, OH, NO2, NH2, alkoxy of 1 to 6 carbon atoms, or
cyanoalkoxy of 2 to 7 carbon atoms;
R3 is hydrogen, acylamide of 2 to 6 carbon atoms or alkoxy of 1 to 6 carbon
atoms;
R4, R5, R6, R7, and R8 are each, independently, hydrogen, acyl of 1 to 6
carbon
atoms, benzyl substituted with R1, and R2; or benzoyl substituted with R1
and R2;
R9 and R10 are each, independently, acyl of 1 to 6 carbon atoms, or the R9 and
R10 groups on the 4' and 6' positions of the maltose may be taken together
to form a cyclic acetal which may be substituted with alkyl of 1 to 6
carbon atoms, two alkyl groups each having 1 to 6 carbon atoms, pyridine


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substituted with R1, phenyl substituted with R1, benzyl substituted with R1,
2-phenylethyl substituted with R1, or 3-phenylpropyl substituted with R1;
with the provisio that when R1 or R2 are cyanoalkoxy of 2-7 carbon atoms, R3
is not acylamide, and further provided that when R1, R2, or R3 are alkoxy of 1-
6
carbon atoms, at least one of R1, R2, R3, or R4 are not hydrogen;
or a pharmaceutically acceptable salt thereof.
16. A method of treating or inhibiting restenosis in a mammal in need
thereof, which comprises administering to said mammal an effective amount of a
compound of formula I having the structure
Image
wherein
Y is C or N;
where n is 0 - 3;
X is
Image
R1, and R2 are each independently, hydrogen, alkyl of 1 to 6 carbon atoms,
halo,
acetyl, phenyl, CF3, CN, OH, NO2, NH2, alkoxy of 1 to 6 carbon atoms, or
cyanoalkoxy of 2 to 7 carbon atoms;
R3 is hydrogen, acylamide of 2 to 6 carbon atoms or alkoxy of 1 to 6 carbon
atoms;
R4, R5, R6, R7, and R8 are each, independently, hydrogen, acyl of 1 to 6
carbon
atoms, benzyl substituted with R1, and R2; or benzoyl substituted with R1
and R2;
R9 and R10 are each, independently, acyl of 1 to 6 carbon atoms, or the R9 and
R10 groups on the 4' and 6' positions of the maltose may be taken together


-53-

to form a cyclic acetal which may be substituted with alkyl of 1 to 6
carbon atoms, two alkyl groups each having 1 to 6 carbon atoms, pyridine
substituted with R1, phenyl substituted with R1, benzyl substituted with R1,
2-phenylethyl substituted with R1, or 3-phenylpropyl substituted with R1;
with the provisio that when R1 or R2 are cyanoalkoxy of 2-7 carbon atoms, R3
is not acylamide, and further provided that when R1, R2, or R3 are alkoxy of 1-
6
carbon atoms, at least one of R1, R2, R3, or R4 are not hydrogen;
or a pharmaceutically acceptable salt thereof.
17. The method according to claim 16, wherein the restenosis results from
a vascular angioplasty procedure, vascular reconstructive surgery, or organ or
tissue
transplantation.
18. A method of inhibiting angiogenesis in a malignant tumor, sarcoma, or
neoplastic tissue in a mammal in need thereof, which comprises administering
to said
mammal an effective amount of a compound of formula I having the structure
Image
wherein
Y is C or N;
where n is 0 - 3;
X is
Image
R1, and R2 are each independently, hydrogen, alkyl of 1 to 6 carbon atoms,
halo,
acetyl, phenyl, CF3, CN, OH, NO2, NH2, alkoxy of 1 to 6 carbon atoms, or
cyanoalkoxy of 2 to 7 carbon atoms;


-54-

R3 is hydrogen, acylamide of 2 to 6 carbon atoms or alkoxy of 1 to 6 carbon
atoms;
R4, R5, R6, R7, and R8 are each, independently, hydrogen, acyl of 1 to 6
carbon
atoms, benzyl substituted with R1, and R2; or benzoyl substituted with R1
and R2;
R9 and R10 are each, independently, acyl of 1 to 6 carbon atoms, or the R9 and
R10 groups on the 4' and 6' positions of the maltose may be taken together
to form a cyclic acetal which may be substituted with alkyl of 1 to 6
carbon atoms, two alkyl groups each having 1 to 6 carbon atoms, pyridine
substituted with R1, phenyl substituted with R1, benzyl substituted with R1,
2-phenylethyl substituted with R1, or 3-phenylpropyl substituted with R1;
with the provisio that when R1 or R2 are cyanoalkoxy of 2-7 carbon atoms, R3
is not acylamide, and further provided that when R1, R2, or R3 are alkoxy of 1-
6
carbon atoms, at least one of R1, R2, R3, or R4 are not hydrogen;
or a pharmaceutically acceptable salt thereof.
19. A pharmaceutical composition which comprises a compound of
formula I having the structure
Image
wherein
Y is C or N;
where n is 0 - 3;
X is
Image


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R1, and R2 are each independently, hydrogen, alkyl of 1 to 6 carbon atoms,
halo,
acetyl, phenyl, CF3, CN, OH, NO2, NH2, alkoxy of 1 to 6 carbon atoms, or
cyanoalkoxy of 2 to 7 carbon atoms;
R3 is hydrogen, acylamide of 2 to 6 carbon atoms or alkoxy of 1 to 6 carbon
atoms;
R4, R5, R6, R7, and R8 are each, independently, hydrogen, acyl of 1 to 6
carbon
atoms, benzyl substituted with R1, and R2; or benzoyl substituted with R1
and R2;
R9 and R10 are each, independently, acyl of 1 to 6 carbon atoms, or the R9 and
R10 groups on the 4' and 6' positions of the maltose may be taken together
to form a cyclic acetal which may be substituted with alkyl of 1 to 6
carbon atoms, two alkyl groups each having 1 to 6 carbon atoms, pyridine
substituted with R1, phenyl substituted with R1, benzyl substituted with R1,
2-phenylethyl substituted with R1, or 3-phenylpropyl substituted with R1;
with the provisio that when R1 or R2 are cyanoalkoxy of 2-7 carbon atoms, R3
is not acylamide, and further provided that when R1, R2, or R3 are alkoxy of 1-
6
carbon atoms, at least one of R1, R2, R3, or R4 are not hydrogen;
or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier.

Description

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BENZYLGLYCOSYLAMIDES AS INHIBITORS OF SMOOTH
MUSCLE CELLPROLIFERATION
BACKGROUND OF THE INVENTION
S
This invention relates to the use of substituted benzylglycosylamides as
smooth muscle cell proliferation inhibitors and as therapeutic compositions
for
treating diseases and conditions which are characterized by excessive smooth
muscle
proliferation such as restenosis.
All forms of vascular reconstruction such as angioplasty and vein bypass
procedures effect a response to injury that ultimately leads to smooth muscle
cell
(SMC) proliferation and subsequently, deposition of profuse amounts of
extrtacellular matrix (Clowes, A. W.; Reidy, M. A. J. Vasc. Surg 1991, 13,
885).
These events are also central processes in the pathogenesis of atherosclerosis
(Raines
E.W.; Ross R. Br. Heart J. 1993, 69 (Supplement), S. 30) as well as transplant
arteriosclerosis (Isik, F.F.; McDonald, T. O.; Ferguson, M.; Yamanaka, E.;
Gordon
Am. J. Pathol. 1992, 141, 1139). In the case of restenosis following
angioplasty,
clinically relevant solutions for controlling SMC proliferation through
pharmacological intervention have remained elusive to date (Herrman, J. P. R.;
Hermans, W.R.M.; Vos, J.; Serruys P. W. Drugs 1993, 4, 18 and 249). Any
successful approach to selective SMC proliferation inhibition must not
interfere with
endothelial cell repair or the normal proliferation and function of other
cells
(Weissberg, P.L.; Grainger, D.J.; Shanahan C.M.; Metcalfe, J.C. Cardiovascular
Res. 1993, 27, 1191 ).
The glycosaminoglycans heparin and heparan sulfate are endogenous
inhibitors of SMC proliferation, yet are able to promote endothelial cell
growth
(Castellot, J.J. Jr.; Wright, T. C.; Karnovsky, M.J. Seminars in Thrombosis
and
Hemostasis 1987, 13, 489). However, the full clinical benefits of heparin,
heparin
fragments, chemically modified heparin, low molecular weight heparins, and
other
heparin mimicking anionic polysaccharides may be compromised due to other
pharmacological liabilities (excessive bleeding arising from anticoagulation
effects, in


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WO 00/31094 PCT/US99/27823
-2-
particular) coupled with heterogeneity of the various preparations (Borman, S.
Chemical. and Engineering News, 1993, June 28, 27).
WO 96/14325 discloses acylated benzylglycosides as smooth muscle cell
proliferation inhibitors. The compounds of the present invention differ in
that (a) the
carbohydrate posesses an anomeric amide, (b) the substituents on the
carbohydrate
backbone are substantually different and, (c) the activity against smooth
muscle cell
proliferation is greater.
Zehavi, U., in Carbohyd. Res. 1986, 151, 371, disclosed 4-carboxy-2-
nitrobenzyl 4-O-a-D-glucopyranosyl-~i-D-glucopyranoside which is attached to a
polymer for study as an acceptor in the glycogen synthase reaction. The
compounds
of the present invention differ in that (a) the carbohydrate posesses an
anomeric
amide, (b) the substituents on the benzyl groups are different and (c) the use
(smooth
muscle antiproliferation) is different.
Patent numbers US 5,498,775, W096/14324, and US 5,464,827 describe
polyanionic benzylglycosides or cyclodextrins as smooth muscle cell
proliferation
inhibitors for treating diseases and conditions which are characterized by
excessive
smooth muscle proliferation. ~i-cyclodextrin tetradecasulfate has been
described as a
smooth muscle cell proliferation inhibitor and as an effective inhibitor of
restenosis
(Reilly, C.F.; Fujita, T.; McFall, R. C.; Stabilito, I. L; Wai-se E.; Johnson,
R. G.
Drarg Development Research 1993, 29, 137). US 5019562 discloses anionic
derivatives of cyclodextrins for treating pathological conditions associated
with
undesirable cell or tissue growth. WO 93/09790 discloses antiproliferative
polyanionic derivatives of cyclodextrins bearing at least 2 anionic residues
per
carbohydrate residues. Meinetsberger (EP 312087 A2 and EP 312086 A2) describes
the antithrombotic and anticoagulant properties of sulfated bis-aldonic acid
amides.
US 4431637 discloses polysulfated phenolic glycosides as modulators of the
complement system. The compounds of the present invention differ from all of
the
prior art in that the compounds (a) are benzylglycosylamides which bear no
structural
resemblance to heparin, sulfated cyclodextrins, or to sulfated lactobionic
acid dimers,
(b) contain no more than two contiguous sugar residues (disaccharide), (c) are
of a
defined structure, (d) and are not sulfated.


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WO 00/31094 PCT/US99/27823
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DESCRIPTION OF THE INVENTION
This invention provides benzylglosylamides of formula I
H N n R'
O ~~:~R2
~Rs
I
wherein
YisCorN;
where n is 0 - 3;
X is
R s°O
R90
R80 Rs
RIO O
R 50
Ra
R', and RZ are each independently, hydrogen, alkyl of 1 to 6 carbon atoms,
halo,
acetyl, phenyl, CF3, CN, OH, NO2, NHZ, alkoxy of 1 to 6 carbon atoms, or
cyanoalkoxy of 2 to 7 carbon atoms;
R' is hydrogen, acylamide of 2 to 6 carbon atoms or alkoxy of 1 to 6 carbon
atoms;
R°, RS, R6, R', and R8 are each, independently, hydrogen, acyl of 1 to
6 carbon
atoms, benzyl substituted with R', and R2; or benzoyl substituted with R'
and R2;
R9 and R'° are each, independently, acyl of 1 to 6 carbon atoms, or the
R9 and
R'° groups on the 4' and 6' positions of the maltose may be taken
together
to form a cyclic acetal which may be substituted with alkyl of 1 to 6
carbon atoms, two alkyl groups each having 1 to 6 carbon atoms, pyridine
substituted with R', phenyl substituted with R', benzyl substituted with R',
2-phenylethyl substituted with R', or 3-phenylpropyl substituted with R';
with the proviso that when Rl or R2 are cyanoalkoxy of 2-7 carbon atoms, R3 is
not acylamide, and further provided that when R1, R2, or R3 are alkoxy of 1-6
carbon atoms, at least one of Rl, R2, R3, or Ra are not hydrogen;
or a pharmaceutically acceptable salt thereof.


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Alkyl includes both straight chain as well as branched moieties. Halogen
means bromine, chlorine, fluorine, and iodine. When Y is nitrogen, it is
preferred
that the pyridine carboxamide is pyridine 3-carboxamide.
S Pharmaceutically acceptable salts can be formed from organic and inorganic
acids, for example, acetic, propionic, lactic, citric, tartaric, succinic,
fumaric, malefic,
malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric,
nitric,
sulfuric, methanesulfonic, napthalenesulfonic, benzenesulfonic,
toluenesulfonic,
camphorsulfonic, and similarly known acceptable acids. Salts may also be
formed
from organic and inorganic bases, preferably alkali metal salts, for example,
sodium,
lithium, or potassium. Acid addition salts can be prepared when Y is nitrogen
or the
compound of formula I contains a basic nitrogen, and base addition salts can
typically
be prepared when the compound of formula I contains a hydroxyl group.
The compounds of this invention may contain an asymmetric carbon atom and
some of the compounds of this invention may contain one or more asymmetric
centers and may thus give rise to optical isomers and diastereomers. While
shown
without respect to stereochemistry in Formula I, the present invention
includes such
optical isomers and diastereomers; as well as the racemic and resolved,
enantiomerically pure R and S stereoisomers; as well as other mixtures of the
R and S
stereoisomers and pharmaceutically acceptable salts thereof.
Preferred compounds formula I of this invention are those in which
nis0-1;
R', and RZ are each independently, hydrogen, halogen, CF3, OH, NO2, NH2,
methoxy,
butoxy, or butoxynitrile;
R' is hydrogen, acetamide, or methoxy;
R", R5, R6, R', and R8 are each, independently, hydrogen, an acyl of 1-6
carbon atoms,
or benzoyl;
R' and R'° are each, independently, acyl of 1-6 carbon atoms, or the R9
and R'° groups
on the 4' and 6' positions of the maltose are taken together form a
benzylidene ring;
or a pharmaceutically acceptable salt thereof, with all other substituents as
defined
above.


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WO 00/31094 PCT/US99/27823
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More preferred compounds of formula I are those in which
n is 0;
R', and RZare each independently, hydrogen or halogen;
R3 is hydrogen;
R', R5, R6, R', and R$ are each, independently, hydrogen, acyl of 1 to 6
carbon atoms,
or benzoyl;
R9 and R'° are each, independently, acyl of 1-6 carbon atoms, or the R9
and R'° groups
on the 4' and 6' positions of the maltose are taken together form a
benzylidene ring;
or a pharmaceutically acceptable salt thereof, with all other substituents as
defined
above.
Specifically preferred compounds of this invention are:
N-(Hepta-O-acetyl-1-deoxy-(3-D-maltosyl)-4-chloro-3-nitro-benzamide;
3-Amino-4-chloro-N-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D-
glucopyranosyl)-[3-D-glucopyranosyl }-benzamide;
3-(Acetylamino)-4-chloro-N-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D-

glucopyranosyl)-[i-D-glucopyranosyl }-benzamide;
(R)-3-(Acetylamino)-4-chloro-N-[4-O-[4,6- O -(phenylmethylene)-a-D-
glucopyranosyl]-~-D-glucopyranosyl]-benzamide;
(R)-4-chloro-3-nitro-N-[4-O-[4,6- O -(phenylrnethylene)-a-D-glucopyranosyl]-(3-
D-
glucopyranosyl]-benzamide;
(R)-3-(Acetylamino)-N-[6-O-benzoyl-4-O-[4,6- O -(phenylmethylene)-a-D-
glucopyranosyl]-[3-D-glucopyranosyl]-4-chlorobenzamide;
(R)-N-[2-0-Acetyl-4-O-[2-O-acetyl-4,6-O -(phenylmethylene)-a-D-gluco-
pyranosyl]-6-O-benzoyl-~i-D-glucopyranosyl]-3-(acetylamino)-4-chlorobenzamide;
(R)-4-chloro-N-[(6-O-benzoyl-4',6'- O -benzylidene)--(3-D-maitosyl]-3-nitro-
benzamide;
4-Chloro-N-[(2.2',3,3'-tetra-O-acetyl- 6-benzoyl-4',6'- O benzylidene)-(3-D-
maltosyl]-3-nitro-benzamide;
N-(Hepta-O-acetyl-(3-D-maltosyl)-4-chloro-benzamide;


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-6-
N-(4', 6'-O-Benzylidene-(3-D-maltosyl)-4-chloro-benzamide;
N-(6-O-benzoyl-4',6'-O -benzylidene-(3-D-maltosyl)-4-chloro-benzamide;
N-[(2,2',3,3' 4',6,6'-hepta-O-acetyl-(3-D-maltosyl]-3-chloro-4-nitrilobutoxy-
benzoic
acid amide;
N-[(2,2',3,3'4',6,6'-hepta-O-acetyl-a-D-maltosyl]-3-chloro-4-nitrilobutoxy-
benzoic
acid amide;
N-(4', 6'-O-Benzylidene-(3-D-maltosyl)-3-chloro-4-(4-nitrilo-butoxy)-
benzamide;
N-(6-O-Benzoyl-4', 6'-D-benzylidene-(3-D-maltosyl)-3-chloro-4-(4-nitrilo-
butoxy)-
phenyl amide;
N-(2,2',3,3'-tetra-D-Acetyl-6-O-benzoyl-4', 6'-O-benzylidene-~i-D-maltosyl)-3-
chloro-4-(4-nitrilo-butoxy)-benzamide;
4-Butoxy-3-chloro-N-[2,3,6-tri- D-acetyl-4-O-(2,3,4,6-tetra- O-acetyl-a-D-
glucopyranosyl)-~3-D-glucopyranosyl] benzamide;
4-Butoxy-3-chloro-N-((6-O-benzoyl-4', 6'-O-benzylidene)-(3-D-maltosyl]-
benzamide;
4-Butoxy-3-chloro-N-[(2,3,2',3'-tetra-O-acetyl-6-O-benzoyl-4', 6'-O-
benzylidene)-
~3-D-maltosyl]-benzamide;
4-Chloro-3-methoxy-N-(2,3,6-tri- O-acetyl-4-O-(2,3,4,6-tetra- O-acetyl-a-D-
glucopyranosyl)-(3-D-glucopyranosyl] benzamide;
N-(6-O-Benzoyl-4',6'-O-benzylidene-(3-D-maltosyl)-4-chloro-3-methoxy-
benzamide;
N-(2,2',3,3',4,6,6'-hepta- O-acetyl- ~i-D-maltosyl]-4-butoxy-5-chloro-3-
methoxy-
benzamide;
N[(6-O-benzoyloxy-4', 6'-O-benzylidene)-~3-D-maltosyl]-4-butoxy-3-chloro-5-
methoxy-benzamide;
N-[(2,2',3,3'4',6.6'-hepta-O-acetyl-(3-D-maltosyl]4-(4-nitrilo-butoxy)-3-nitro-

benzamide;
N-(4', 6'-O-Benzylidene-~i-D-maltosyl)-4-(4-nitrilo-butoxy)-3-nitro-benzamide;
N-(6-O-Benzoyl-4', 6'-O-benzylidene-~i-D-maltosyl)-4-(4-nitrilo-butoxy)-3-
nitro-
benzamide;


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N-(2,2',3,3'-tetra-O-Acetyl-6-O-benzoyl-4', 6'-O-benzylidene-~i-D-maltosyl)-4-
(4-
nitrilo-butoxy)-3-nitro-benzamide;
N-[(2,2',3,3'4',6,6'-hepta-O-acetyl-~i-D-maltosyl]-3-amino-4-(4-nitrilo-
butoxy)-
benzamide;
3-Acetylamino-N-(6-O-benzoyl-4', 6'-O-benzylidene-~i-D-maltosyl)-4-(4-nitrilo-
butoxy)-benzamide;
N-[(2,2',3,3'4',6,6'-Hepta-O-acetyl-~i-D-maltosyl]-6-chloropyridine-3-
carboxamide;
N-(Hepta-D-acetyl-~3-D-maltosyl)-2,6-dimethoxy-pyridine-3-carboxamide;
N-(Hepta-O-acetyl-~i-D-maltosyl)-5-bromopyridine-3-carboxamide;
IS
N-(Hepta-O-acetyl-[i-D-maltosyl)-3-(trifluoromethyl)-benzamide;
N-(4',6'-O-Benzylidene-/3-D-maltosyl)-3-{trifluoromethyl)-Benzamide;
N-[{6-O-Benzoyl-4',6'-O-benzylidene}-/3-D-maltosyl]-3-(trifluoromethyl)-
benzamide;
N-(Hepta-O-acetyl-~i-D-maltosyl)-6-methylpyridine-3-carboxamide;
N-(2,2',3,3',4',6,6'-Hepta-O-acetyl-[i-maltosyl)-4-butoxy-3,5-dichloro-
benzylamide;
N-(4',6'-O-Benzylidene-[i-D-maltosyl)-4-butoxy-3,5-dichloro-benzamide;
N-(Hepta-O-acetyl-~i-D-maltosyl)-3-chloro-4-methoxy-benzamide;
N-(2,2',3,3',4',6,6'-hepta-O-acetyl-~i-D-maltosyl)-1-(3,4-dimethoxy)-phenyl-
acetamide;
N-(6-O-Benzoyl-4',6'-4-benzylidene-(3-D-maltosyl)-2-(3,4-dimethoxy-phenyl)-
acetamide;
N-(Hepta-O-acetyl-~i-D-maltosyl)-2-(4-hydroxy-3-nitro-phenyl)-acetamide;
N-(2,2',3,3',4',6,6'-hepta-O-acetyl-/3-D-maltosyl)-2-(4-chloro-3-nitro-phenyl)-

acetamide;
2-[3-Acetyl-amino)-4-chloro-phenyl]-N-(6-O-benzoyl-4',6'-O-benzylidene-(3-D-
maltosyl)-acetamide;
or pharmaceutically acceptable salts thereof.


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_g_
The compounds of this invention were be prepared according to the following
scheme from commercially available starting materials or starting materials
which
can be prepared using literature procedures. This scheme shows the preparation
of
representative compounds of this invention.
Scheme I
Ac
,ecp ~ n R'
I~C~S~NHz + CI,H z
Ac O , ..
3
2
glycosidation
when F~ = NO~
OAc
pK~~. H n R' Pc
~~I Yz reduction Pc0
O~ H n R'
3
HC AC ~~ 2
acetolysis q ~NHz
H acylation or
HO ~, sulfonylation
HO H
' OO--~~Q H n R' PcCC
H N~~~~z acetolysis
HO (7 ~l t", Ac OAc
hcOCC?~-~~H n R~
2
pc Ac
1. benrylidination
R, 2 benzoylation S
Re0 ORs
R RO
Rs0 R ~ z
O
3
acylatiw~
R'
Ra0
R RIO ORs
H n
R Re0 ~ z
J
3
In Scheme I, Y, n. R', RZ, R3, R', R5, R6, R', R8, R9, and R'° are as
defined above.


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Thus, the maltosyl amine 1 is coupled with a benzoic acid derivative 2 in the
presence of a coupling reagent such as EEDQ, DEC/HOBT, or DCC/HOBT in a
suitable solvent system such as benzene, ethanol, dichloromethane, triethyl
amine at
room temperatures to yield glycoside 3. The glycoside can also be prepared by
coupling the amine 1 to a substituted acid chloride 2 in the presense of
triethyl amine
in a suitable solvent system such as tetrahydofuran, dichloromethane,
acetonitrile, and
ethyl acetate to yield glycoside 3. When R' equals a nitro group reduction of
the nitro
group of 3 can be accomplished with a reducing agent such as stannous chloride
or
iron metal in a polar aprotic solvent such as ethyl acetate or a polar protic
solvent
such as ethanol or methanol at ambient temperature to reflux, or by catalytic
hydrogenation in the presence of a catalyst such as palladium on carbon gives
an
anilino compound 4. Coupling of 4 with an acid chloride or sulfonyl chloride
in the
presence of an amine base such as triethylamine or diisopropulethylamine in an
aprotic solvent such as dichloromethane or tetrahydrofuran at temperatures
ranging
from -20 °C to ambient temperature yields the target compounds 5.
The acetate groups of 3 or 5 can be removed by hydrolysis with a base such as
catalytic sodium methoxide in methanol or aqueous sodium hydroxide in methanol
at
ambient temperature to reflux to yield 6. After hydrolysis of the acetate
groups, the
4' and 6' hydroxy groups of maltose can be reacted with benzaldehyde diemthyl
acetal in the presence of an acid catalyst such as camphorsulfonic acid or
toluene
sulfonic acid in a polar aprotic solvent such as acetonitrile or dimethyl
formamide at
ambient temperature to 70 °C to yield a benzylidene derivative. The 6
hydroxyl
group can be selectively benzoylated in a collidine / tetrahydofuran mixture
at -78 °C
to ambient temperature to yield 7. Reacylation with an acyl anhydride in the
presence
of an amine base such as pyridine or triethyl amine at temperatures ranging
from 0 °C
to ambient temperature to yield 8.
The compounds of this invention are useful as antiproliferative agents. The
following procedures show the evaluation of representative compounds of this
invention in standard pharmacological test procedure which measured ability of
the
evaluated compound to inhibit smooth muscle cell proliferation


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Effects of Compounds on Cell Proliferation Using 3H Thvmidine Incorporation
Human and porcine smooth muscle cells were tested in early passage
(generally passage 3 - 7) at sub-confluent conditions. Cultures were grown in
16
S mm (24 well) multi-well culture dishes in medium 199 supplemented with 10%
fetal
bovine serum and 2% antibiotic / antimycotic. At sub-confluence, the cells
were
placed in a defined serum free medium (AIM-V; Gibco) for 24 - 48 h prior to
initiating the experimental protocol.
Although compounds were found to be more effective with longer pre
incubations, in general, the procedures were initiated with the addition of
compound,
'H thymidine and serum / growth factor to serum deprived synchronized cells
and
results are reported accordingly.
Compounds were added to each well at 50 fold dilution (20 uI. / well) and the
plates were incubated for 24 - 36 h at 37 °C in 5% CO2. Compounds were
initially
dissolved in 50% ethanol and serially diluted into media. Compounds were
routinely
evaluated at concentrations from 1 to 100 p.M. As a control, grade II porcine
intestinal mucosal heparin (sodium salt) was routinely evaluated in all cell
preparations at concentrations from 0.1 to 100 ~g/mL.
At the completion of the test procedure, plates were placed on ice, washed
three times with ice cold phosphate buffered saline (PBS} and incubated in ice
cold
10% trichloroacetic acid (TCA) got 30 min to remove acid soluble proteins.
Solution
was transferred to scintillation vials containing 0.4 N HCl (500 pL/ vial to
neutralize
NaOH) and each well was rinsed two times with water (500 pL) for a total
volume of
2 mL / vial.
Data was obtained, in triplicate, for both control and experimental samples.
Control (100%) data was obtained from maximally stimulated cells, as the
result of
growth factor or serum stimulation. Experimental data was obtained from cells
maximally stimulated with growth factor or serum and treated with compound.
Data
are expressed as an ICSp in Table I below.


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Table 1.
Porcine Smooth Muscle
Com ound of Exam Cell
le Anti roliferation IC50


1 21.2


2 11.13


3 54.3


4 3.2 M


5 37% at 50


6 0.45


7 0.55 M


8 0.26


9 1.253


10 36.6


11 15% at 50 M


12 49.2


13 32.8 M


14 51.3


15 30% at 50


16 0.27


17 33% at 50


18 3.5


19 35% at 50


20 3.14


21 9.8 M


22 18.5


23 2% at 50 M


24 2.0 M


25 2.7


26 32% at 50


27 45 % at 50 M


28 3% at 50 M


29 4% at 50


30 1.4


31 15% at 50


32 10% at 50


33 0% at 50 M


34 0.98 M


35 66.6


36 13.6 M


37 16.4 M


38 5.8


39 15 % at 50


40 7.15




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-12-
Table 1 (Continued)
41 65.77 _


42 28.9


43 44.5 M


44 5.4 M


45 16.6 M


46 0% at 50 M


47 8.0


48 37% at 50


49 12.6 M


50 4.23 M


51 0.916 M


The compounds of this invention are useful in treating or inhibiting diseases
which are characterized by excessive smooth muscle cell proliferation (smooth
muscle cell hyperproliferation). The compounds are particularly useful in
treating
hyperproliferative vascular diseases which are characterized by smooth muscle
cell
hyperproliferation, such as restenosis, which most frequently arises from
vascular
reconstrucdve surgery and transplantation, for example, balloon angioplasty,
vascular
graft surgery, coronary artery bypass surgery, and heart transplantation.
Other
disease states in which there is unwanted "cellular" vascular proliferation
include
hypertension, asthma, and congestive heart failure. The compounds of this
invention
are also useful as inhibitors of angiogenesis. Angiogenesis
(neovascularization), the
process by which new capillaries are formed, is of principal importance for a
number
of pathological events including chronic inflammation and malignant processes.
The
compounds of this invention are therefore useful as antineoplastic agents.
The compounds of this invention can be formulated neat or with a
pharmaceutical Garner for administration, the proportion of which is
determined by
the solubility and chemical nature of the compound, chosen route of
administration
and standard pharmacological practice. The pharmaceutical carrier may be solid
or
liquid.
A solid carrier can include one or more substances which may also act as
flavoring agents, lubricants, solubilizers, suspending agents, fillers,
glidants,
compression aids. binders or tablet-disintegrating agents; it can also be an


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encapsulating material. In powders, the carrier is a finely divided solid
which is in
admixture with the finely divided active ingredient. In tablets, the active
ingredient is
mixed with a carrier having the necessary compression properties in suitable
proportions and compacted in the shape and size desired. The powders and
tablets
preferably contain up to 99% of the active ingredient. Suitable solid carriers
include,
for example, calcium phosphate, magnesium stearate, talc, sugars, lactose,
dextrin,
starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose,
polyvinylpyrrolidine, low melting waxes and ion exchange resins.
Liquid carriers are used in preparing solutions, suspensions, emulsions,
syrups, elixirs and pressurized compositions. The active ingredient can be
dissolved
or suspended in a pharmaceutically acceptable liquid carrier such as water, an
organic
solvent, a mixture of both or pharmaceutically acceptable oils or fats. The
liquid
carrier can contain other suitable pharmaceutical additives such as
solubilizers,
emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending
agents,
thickening agents, colors, viscosity regulators, stabilizers or osmo-
regulators.
Suitable examples of liquid carriers for oral and parenteral administration
include
water (partially containing additives as above, e.g. cellulose derivatives,
preferably
sodium carboxymethyl cellulose solution), alcohols (including monohydric
alcohols
and polyhydric alcohols, e.g. glycols) and their derivatives, lethicins, and
oils (e.g.
fractionated coconut oil and arachis oil). For parenteral administration, the
carrier
can also be an oily ester such as ethyl oleate and isopropyl myristate.
Sterile liquid
carriers are useful in sterile liquid form compositions for parenteral
administration.
The liquid carrier for pressurized compositions can be halogenated hydrocarbon
or
other pharmaceutically acceptable propellant.
Liquid pharmaceutical compositions which are sterile solutions or suspensions
can be utilized by, for example, intramuscular, intraperitoneal or
subcutaneous
injection. Sterile solutions can also be administered intravenously. The
compounds
of this invention can also be administered orally either in liquid or solid
composition
form.
The compounds of this invention rnay be administered rectally or vaginally in
the form of a conventional suppository. For administration by intranasal or
intrabronchial inhalation or insufflation, the compounds of this invention may
be
formulated into an aqueous or partially aqueous solution, which can then be
utilized
in the form of an aerosol. The compounds of this invention may also be
administered
transdermally through the use of a transdermal patch containing the active
compound
and a carrier that is inert to the active compound, is non toxic to the skin,
and allows
delivery of the agent for systemic absorption into the blood stream via the
skin. The


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Garner may take any number of forms such as creams and ointments, pastes,
gels, and
occlusive devices. The creams and ointments may be viscous liquid or semisolid
emulsions of either the oil-in-water or water-in-oil type. Pastes comprised of
absorptive powders dispersed in petroleum or hydrophilic petroleum containing
the
active ingredient may also be suitable. A variety of occlusive devices may be
used to
release the active ingredient into the blood stream such as a semipermeable
membrane covering a reservoir containing the active ingredient with or without
a
carrier, or a matrix containing the active ingredient. Other occlusive devices
are
known in the literature.
The dosage requirements vary with the particular compositions employed, the
route of administration, the severity of the symptoms presented and the
particular
subject being treated. Based on the results obtained in the standard
pharmacological
test procedures, projected daily dosages of active compound would be 0.1 to 10
mg/kg administered parenterally (intravenous preferred), with projected daily
oral
dosage being approximately ten-fold higher. Anticipated intravenous
administration
would last for approximately 5-30 days following acute vascular injury (i.e.,
balloon
angioplasty or transplantation) and for a longer duration for the treatment of
chronic
disorders. Treatment will generally be initiated with small dosages less than
the
optimum dose of the compound. Thereafter the dosage is increased until the
optimum effect under the circumstances is reached; precise dosages for oral,
parenteral, nasal, or intrabronchial administration will be determined by the
administering physician based on experience with the individual subject
treated.
Preferably, the pharmaceutical composition is in unit dosage form, e.g. as
tablets or
capsules. In such form, the composition is sub-divided in unit dose containing
appropriate quantities of the active ingredient; the unit dosage forms can be
packaged
compositions, for example, packaged powders, vials, ampoules, pre filled
syringes or
sachets containing liquids. The unit dosage form can be, for example, a
capsule or
tablet itself, or it can be the appropriate number of any such compositions in
package
form.


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The following provides the preparation of representative compounds of this
invention.
EXAMPLE 1
N-lHe~ta-O-acetyl--1-deoxy-I3-D-maltosyl)-4-chloro-3-nitro-benzamide
Stepl
Hepta-O-acetyl-1-~i-maltosylamine
Hepta-O-acetyl-1-~3-maltosylamine was obtained by the platinum oxide
reduction of the azide prepared by the method of A. Bertho, Justus Liebigs
Ann.
Chem., 562, 229 ( 1949).
Step 2
N-(Hepta-O-acetyl-1-deoxy-~i-D-maltosyl)-4-chloro-3-vitro-benzamide
To a stirred solution of 4-chloro-3-nitrobenzoic acid (3.806 g, 0.0189 mol) in
benzene-ethanol (1:1, v/v, 140 ml) was added in one portion 2-ethoxy-N
carbonyl
1,2-dihydroquinoline (5.057 g, 0.0205 mol). After 0.5 h, Hepta-O-acetyl-1-(3
maltosylamine ( 10.0 g 0.0157 mol) was added and the mixture was stirred
overnight
at room temperature. The solvents were evaporated and the residue dissolved in
methylene chloride. The organic layer was washed successively with 1 N
hydrochloric acid, water, 1 % sodium hydrogencarbonate, and water, dried
(MgS04)
and concentrated. Purification by flash chromatography (40%-60%
EtOAc/petroleum ether gradient) afforded 10.785 g (84%) of the title compound
as a
white solid, mp 185 °C; 'H NMR (CDC13) b 2.011 (s, 3 H), 2.029 (s, 3
H), 2.032 (s, 3
H), 2.062 (s, 3 H), 2.081 (s, 3 H), 2.101 (s, 3 H), 2.133 (s, 3 H), 3.86 -
3.96 (m, 2 H),
4.02 - 4.07 (m, 2 H), 4.21 - 4.28 (m, 2 H), 4.47 (dd, J = 12.3, 2.2 Hz, 1 H),
4.83
4.89 (m, 2 H), 5.07 (apparent t, J = 10. l Hz, 1 H), 5.34 - 5.49 (m, 4 H),
7.04 (d, J = 9
Hz, 1 H), 7.65 (d, J = 8.3 Hz, 1H), 7.85 (dd, J = 8.6, 2.2, Hz, 1 H), 8.27 (d,
J = 2.2
Hz, 1H). IR (KBr) 2950, 1750, 1250 and 1050 cm~', mass spectrum (FAB), m/e 819
(M + H}, 841 (M + Na). Anal. Calcd. for C33H39C1N2OZO: C, 48.39; H, 4.80; N,
3.42.
Found: C, 48.33; H, 4.83; N, 3.30.


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EXAMPLE 2
3-Amino-4-chloro-N-f2,3.6-tri-O-acetyl-4-O-(2.3.4.6-tetra-O-acetyl-a-D-
gluco~vranosyl)- 3L-D-glucopyranosyl l-benzamide
A solution of N-(Hepta-O-acetyl-1-deoxy-~i-D-maltosyl)-4-chloro-3-nitro-
benzamide ( 1.355 g, 1.65 mmol) and tin (II) chloride dihydrate ( 1.87 g, 8.27
mmol)
in EtOAc (40 ml) was refluxed for 2 h. The reaction was cooled to room
temperature, carefully quenched with sat. aq. NaHCO, (until basic), diluted
with
EtOAc (250 ml), stirred overnight and filtered. The biphasic filtrate was
separated
and the aqueous phase extracted with EtOAc. The combined organic extracts were
20 dried (MgS04) and concentrated. Purification by flash chromatography (30%
EtOAc/methylene chloride) gave 0.953 g (76%) of 3-Amino-4-chloro-N-[2,3,6-tri-
O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl)-~i-D-glucopyranosyl }-
3-
nitro-benzamide as a white solid, mp 115 - 119 °C; 'H NMR (CDC13) 8
2.00 (s, 3 H),
2.01 (s, 3 H), 2.03 (s, 3 H), 2.05 (s, 3 H), 2.08 (s, 3 H), 2.10 (s. 3 H),
2.13 (s, 3 H),
3.85 - 3.89 (m, 1 H), 3.92 - 3.96 (m, 1 H), 3.99 - 4.07 (m, 2 H), 4.25 (dt, J
= 12.5, 4.2
Hz, 2 H), 4.45 (dd, J = 12.3, 2.6 Hz, 1 H), 4.84 - 4.89 (m, 2 H), 5.07 (t, J =
10.1 Hz,
1 H), 5.39 - 5.47 (m, 4 H), 6.83 (d, J = 9.2 Hz, 1 H), 6.95 (dd, J = 8.35, 2
Hz, 1H),
7.22 (d, J = 2 Hz, 1 H), 7.29 (d, J = 8.13 Hz, 1 H). IR (KBr) 3500, 2950,
1750, 1240
and 1050 cm', mass spectrum (FAB), m/e 789/791 (M + H), 811/813 {M + Na).
Anal. Calcd. for C33H;,C1NZO,8 ~ 0.5 HzO: C, 49.66; H, 5.30; N, 3.51. Found:
C,
49.62; H, 5.33; N, 3.30.
EXAMPLE 3
3-(Acetylamino)-4-chloro-N-f2 3 6-tri-O-acetyl-4-O-(2 3 4,6-tetra-O-acetyl-a-D-

~luconvranosyl)-~3-D-glucopvranos~l-benzamide
To a stirred solution of 3-Amino-4-chloro-N-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-
tetra-O-acetyl-a-D-glucopyranosyl)-~i-D-glucopyranosyl}-benzamide (0.883 g,
1.17
mmol) and triethylamine (0.326 ml, 2.34 mmol) in THF (8 ml) at 0°C was
added
dropwise acetyl chloride (0.1 ml, 1.4 mmol) and warmed to ambient temperature.
After 4 h, the reaction was diluted with methylene chloride (20 ml), quenched
with
sat. aq. NaHCO, ( 10 ml), diluted with brine ( 100 ml) and extracted with
methylene
chloride. The combined organic extracts were dried (MgSO,) and concentrated.


CA 02350755 2001-05-08
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Purification by flash chromatography (30 - 50% EtOAc/methylene chloride
gradient)
gave 0.836 g (86 %) of the title compound as a white solid, mp 122 - 124
°C; 'H
NMR (CDCI3) 8 2.00 (s, 3 H), 2.01 (s, 3 H), 2.03 (s, 3 H), 2.05 (s, 3 H), 2.08
(s, 3 H),
2.I0 (s. 3 H), 2.13 (s, 3 H), 3.85 - 3.89 (m, 1 H), 3.92 - 3.96 (m, 1 H), 3.99
- 4.06 (m,
2 H), 4.25 (dt, J =12.0, 3.7 Hz, 2 H), 4.45 (dd, J = 12.5, 2.2 Hz, 1 H), 4.86 -
4.93 (m,
2 H), 5.07 (apparent t, J = 10.1 Hz, 1 H), 5.35 - 5.46 (m, 4 H), 7.06 (d, J =
8.8 Hz, I
H), 7.45 (d, J = 8.3 Hz, 1H), 7.52 (dd, J = 8.3, 2.2 Hz, 1 H), 7.64 (s, 1 H),
8.71 (s, 1
H). IR (I~Br) 3400, 2950, 1750, 1245 and 1050 cm ', mass spectrum (FAB), m/e
831/833 (M + H), 853/855 (M + Na). Anal. Calcd. for C35H43C1N20,9 ~ 0.5 H20:
C,
50.04; H, 5.28; N, 3.33. Found: C, 49.87; H, 5.25; N, 3.13.
EXAMPLE 4
(R)-3-(Acetylamino)-4-chloro-N-f4-O-f4.6- O -lphenvlmethvlene)-a-D-
~lucopvranosyll-Q-D gluco~vranosyll-benzamide
Step 1
3-(Acetylamino)-4-chloro-N-[4-O-a-D-glucopyranosyl)-(3-D-glucopyranosyl}-
benzamide
To a solution of 3-(Acetylamino)-4-chloro-N-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-
tetra-O-acetyl-a-D-glucopyranosyl)-(3-D-glucopyranosyl }-benzamide (738 mg,
0.90
mmol) in methanol (5 ml) was added 0.075 ml of a 0.34 M solution of sodium
methoxide. The reaction was stirred overnight and quenched with Dowex H+
resin.
After 0.5 hr the solution filtered and concentrated in vacuo to give 461 mg
(97%) of
the title compound as a white solid, mp decomposed at 165; 'H NMR (DMSO-d6)
b 2.10 (s, 3 H), 3.06 (apparent t, J = 9.0 Hz, 1 H), 3.22 - 3.70 (m, 12 H),
4.96
(apparent t, J = 8.8 Hz, 1 H), 5.04 (d, J = 4.0 Hz, 1 H), 7.60 (d, J = 8.3 Hz
1 H), 7.72
(dd, J = 8.3 Hz, 2.2 Hz, I H), 8.17 (d, J = 2.0 Hz, 1 H) 8.98 (d, J = 8.8 Hz,
1 H), 9.67
(s, 1H). IR (KBr) 3375, 2900, 1660, 1550 and 1050 cm-', mass spectrum (FAB),
m/e
537/539 (M + H), 559/561 (M + Na). Anal. Calcd. for CZ,H~9C1N20,2 ~ H20 C,
45.05;
H, 5.63; N, 5.05. Found: C, 45.35; H, 5.75; N, 5.21.


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Step 2
(R)-3-(Acetylamino)-4-chloro-N-[4-O-[4,6-O -(phenylmethylene)-a-D-
glucopyranosyl]-~3-D-glucopyranosyl]-benzamide
A solution containing 3-(Acetylamino)-4-chloro-N-[4-O-a-D-gluco-
pyranosyl)-(3-D-glucopyranosyl }-benzamide (0.40 g, 0.7468 mmol), benzaldehyde
dimethyl acetal (0.17 ml, 1.12 mmol) and camphorsulfonic acid (10 mg, 0.043
mmol)
was heated at 70 °C. After 4h, the reaction was cooled to ambient
temperature and
quenched with 0.5 ml of a I N NaOH solution . The solution was concentrated
and
purified by flash chromatography (2, 5 - 10% MeOH/methylene chloride gradient)
IO gave 0.327 g (70 %) of the title compound as a white solid, mp 175
°C; 'H NMR
(DMSO-d6) 8 2.1 (s, 3 H), 3.35 - 3.40 (m, 5 H), 3.49 - 3.62 (m, 3 H), 3.64 -
3.77 (m,
3 H), 4.12 (dd, J = 9.2, 4.2 Hz, 1 H), 4.66 (bs, 1 H), 4.99 (apparent t, J =
8.8 Hz, 1
H), 5.07 (d, J = 5.9 Hz, 1 H), 5.16 (d, J = 4.0 Hz, 1 H), 5.32 (d, J = 4.6 Hz,
1 H), 5.57
(s, 1 H), 5.59 (d, J = 2.2 Hz, 1 H), 5.70 (d, J = 6.2 Hz, 1 H), 7.35 - 7.40
(m, 3 H),
7.43 - 7.46 (m, 2 H), 7.60 (d, J = 8.3 Hz, 1 H), 7.73 (dd, J = 8.3, 2.0 Hz, I
H), 8.17
(d, J = 1.5 Hz, I H), 8.99 (d, J = 8.8 Hz, I H), 9.68 (s, 1 H). IR (KBr) 3400,
2900,
1650 andI075 cm~', mass spectrum (+FAB), m/e 625/627 (M + H), 647/649 (M +
s Na). Anal. Calcd. for C~H33CIN2O,2 0.5 H,O: C, 53.04; H, 5.41; N, 4.42.
Found: C,
52.86; H, 5.45; N, 4.5.
EXAMPLE 5
(R)-4,-chloro-3-vitro-N-f4-O-f4.6- O - henylmethvlene)-a-D- lg_ucoRyranosvll-
j~ D-
glucopyranosyll-benzamide
Step 1
4-chloro-N-(4-O-a-D-glucopyranosyl-(3-D-glucopyranosyl)-3-vitro-benzamide
Hydrate
The title compound was prepared according to the procedure of Example 4 as
a white solid, mp decomposed at 150; 'H NMR (CD30D-d,) 8 3.44 - 3.57 (m, 3 H),
3.59 - 3.74 (m, 6 H), 3.83 - 3.85 (m, 3 H), 5.13 (d, J = 9.2 Hz, 1 H), 5.18
(d, J = 3.7
Hz, 1 H), 7.79 (d, J = 8.3 Hz 1 H), 8.12 (dd, J = 8.3 Hz, 2.2 Hz, 1 H), 8.47
(d, J = 2.2
Hz, 1 H). IR (KBr) 3400, 2900, 1670, 1550 and 1050 cm-', mass spectrum (ESI),
m/e


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523 (M - H). Anal. Calcd. for C,9HZSC1N~O,3 ~ H20 C, 42.04; H, 4.97; N, 5.16.
Found: C, 42.30; H, 5.12; N, 4.96.
Step 2
(R)-4-chloro-3-vitro-N-[4-O-[4,6- O -(phenylmethylene)-a-D-glucopyranosylJ-(3-
D-glucopyranosyl]-benzamide
The title compound was prepared according to the procedure of Example 4 as
a white solid, mp 235 °C; 'H NMR (DMSO-d6) 8 3.35 - 3.42 (m, 5 H), 3.50
- 3.63
(m, 3 H), 3.65 - 3.75 (m, 3 H), 4.12 (dd, J = 9.2, 4.4 Hz, 1 H), 4.64
(apparent t, J =
5.5 Hz, 1 H), 4.99 (apparent t, J = 9.0 Hz, 1 H), 5.16-5.19 (m, J = 5.9 Hz, 2
H), 5.32
(d, J = 5.3 Hz, 1 H), 5.57 (s, 1 H), 5.62 (d, J = 3.3 Hz, 1 H), 5.69 (d, J =
6.6 Hz, 1 H),
7.35 - 7.38 (m, 3 H), 7.43 - 7.46 (m, 2 H), 7.93 (d, J = 8.6 Hz, 1 H), 8.2
(dd, J = 8.6,
2.0 Hz, 1 H), 8.58 (d, J = 2.0 Hz, I H), 9.29 (d, J = 8.8 Hz, 1 H). IR (KBr)
3400,
2900, 1650 1550, and1075 cm ', mass spectrum (ESI), m/z 613.1/615.2 (M + H),
630.2/632.2 (M + NHa). Anal. Calcd. for Cz6H29C1N2O~3 ~ 0.5 H20: C, 50.21; H,
4.86;
N, 4.50. Found: C, 50.48; H, 4.67; N, 4.38.
EXAMPLE 6
(R)-3-(Acetylamino)-N-f6-O-benzoyl-4-O-X4.6- O -(phenvlmethylene~-a-D-
lg uco~,vranosvll-~i-D$lucoQ rv anOSVII-4-chlorobenzamide
A solution of (R)-3-(Acetylamino)-4-chloro-N-[4-O-[4,6-O-(phenyl-
methylene)-a-D-glucopyranosyl]-~i-D-glucopyranosyl]-benzamide (0.20 g, 0.32
mmol) in dry tetrahydrofuran (I.5 ml) and anhydrous 2,4,6 collidine (1.5 mI)
was
cooled to -40 °C for 0.5 h. Benzoyl chloride (0.047 ml, 0.384 mmol) was
added
slowly and the reaction allowed to warm to ambient temperature overnight. The
reaction was diluted with ethyl acetate (30 ml), and washed consecutively with
1 N
HCl ( 15 ml), satruated aqueous sodium bicarbonate ( 15 ml), and brine ( 15
ml). The
organic layer was dried (MgSO,) and filtered. Evaporation and flash
chromatography
(2, 5 - 10% MeOH/methylene chloride gradient) gave 0.327 g (70 %) of the title
compound as a white solid, mp 225 °C; 'H NMR (DMSO-db) 8 2.09 (s, 3 H),
3.29 -
3.36 (m, 1 H), 3.39 - 3.41 (m, 1 H), 3.49 - 3.66 (m, 5 H), 3.71 - 3.76 (m, I
H), 3.84
(bs, 1 H), 4.00 (dd. J = 9.7, 4.8 Hz, 1 H), 4.34 (dd, J = 12.5, 4.0 Hz, 1 H),
4.51 (d, J =


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11.2 Hz, 1 H), 5.08 (apparent t, J = 8.8 Hz, 1 H), 5.15 (d, J = 3.7 Hz, 1 H),
5.21 (bs, 1
H), 5.36 (bs, 1 H), 5.51 (s, 1H) 5.67 (s, 1 H), 5.86 (bs, 1 H), 7.35 - 7.37
(m, 3 H),
7.40 - 7.43 (m, 2 H), 7.52 (t, J = 7.9 Hz, 1 H), 7.59 (d, J = 8.3 Hz, 1 H),
7.63 - 7.67
(m, 1 H), 7.73 (dd, J = 8.6, 2.0 Hz, 1 H), 7.96 (dd, J = 8.6, 1.1 Hz, 1 H),
8.17 (d, J =
1.8 Hz, 1 H), 9.05 (d, J = 8.8 Hz, 1 H), 9.66 (s, 1H). IR (KBr) 3400, 2900,
1660,
1275 and 1075 cni', mass spectrum (+FAB), m/z 729/731 (M + H), 751/?53 (M +
Na). Anal. Calcd. for C33H3,C1NZO" ~ 1.0 HZO: C, 56.27; H, 5.26; N, 3.75.
Found: C,
56.34; H, 5.18; N, 3.68.
EXAMPLE 7
(R)-4-chloro-N-f~6-O-benzo~-4'.6'-O -benzvlidenel-J3-D-maltosvll-3-nitro-
benzamide
The title compound was prepared according to the procedure of Example 6 as
a white solid, mp I74 °C; 'H NMR (DMSO-d6) 8 3.34 - 3.66 (m, 7 H), 3.69
- 3.73
(m, 1 H), 3.87 (bd, J = 4.0 Hz, 1 H), 4.01 (dd, J = 10.1, 4.6 Hz, 1 H), 4.34
(dd, J =
12.0, 4.0 Hz, 1 H), 4.52 (d, J = 11.4 Hz, 1 H), 5.09 (apparent t, J = 9.0 Hz,
1 H), 5.18
(d, J = 3.7 Hz, 1 H), 5.30 (d, J = 5.3 Hz, 1 H), 5.35 (d, J = 5.1 Hz, 1 H),
5.51 (s, I H),
5.69 (s, 1 H), 5.83 (d, J = 6.2 Hz, 1 H), 7.34 - 7.37 (m, 3 H), 7.40 - 7.43
(m, 2 H),
7.52 (apparent t, 3 = 7.9 Hz, 1 H), 7.63 -7.67 (m, 1 H), 7.90 - 7.96 (m, 3 H),
8.20 (dd,
J = 8.6, 2.0 Hz, 1 H), 8.58 (d, J = 2.0 Hz, 1 H) 9.34 (d, J = 8.8 Hz, 1 H). IR
(KBr)
3400, 2900, 1725, 1550, and 1075 cni', mass spectrum (+FAB), m/z 717/719 (M +
H), 739/741 (M + Na). Anal. Calcd. for C33H33C1N2O,4 ~ 1.0 H20: C, 53.92; H,
4.80;
N, 3.8I. Found: C. 54.09; H, 4.77; N, 3.64.
EXAMPLE 8
4-Chloro-N-f(2 2' 3 3'-tetra-O-acet~- 6-benzovl-4' 6'- O benzvlidene)-~i-D-
maltosyll-3-vitro-benzamide
At 0°C, to a stirred solution containing (R)-4-chloro-N-[(6-O-benzoyl-
4',6'-
O -benzylidene)-(3-D-maltosyl]-3-vitro-benzamide (2.33 g, 3.2493 mmol),
triethylamine (3.62 ml, 25.98 mmol) and catalytic 4-dimethylaminopyridine in
anhydrous methylene chloride (60 ml) was added acetic anhydride (2.15 ml,
22.75
mmol). After 6 h. the reaction was diluted with methylene chloride (100 ml),
washed


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successively with sat. aq. NaHC03 (2x), and brine (2x), dried (MgSO,) and
concentrated. Purification by flash chromatography (40%-50% EtOAc/petroleum
ether gradient} gave 2.865 g (99%) of the title compound as a white solid, mp
230 °C;
'H NMR (CDC13) S 2.04 (s, 3 H), 2.05 (s, 3 H), 2.09 (s, 3 I-I), 2.11 (s, 3 H),
3.54 -
3.63 (m, 2 H), 3.82 - 3.85 (m, 1 H), 3.97 - 4.04 (m, 2 H), 4.23 (apparent t, J
= 1 H),
4.51 (dd, J = 12.3, 3.5 Hz, 1 H), 4.85 - 4.93 (m, 3 H), 5.41 - 5.56 (m, 5 H),
6.94 (d, J
= 9.0 Hz, 1 H), 7.32 - 7.34 (m, 3 H), 7.36 - 7.40 (m, 2 H), 7.45 (t, J = 8.0
Hz, 1 H),
7.55 - 7.60 (m, 2 H), 7.62 (d, J = 8.6 Hz, 1 H), 7.83 (dd, J = 8.4, 2.2 Hz, 1
H), 8.05
(dd, J = 7.7, 0.7 Hz, 1 H), 8.23 (d, J = 2.0 Hz, 1 H). IR (KBr) 3400, 2930,
1750,
1550, 1245 and1075 cm~', mass spectrum (+FAB), m/z 885/887 (M + H), 907/909 (M
+ Na). Anal. Calcd. for C"H4,C1NZO,8: C, 55.63; H, 4.67; N, 3.16. Found: C,
55.61;
H, 4.?7; N, 2.92.
EXAMPLE 9
(R)-N-f2-O-Acetyl-4-O-f2-O-aced-4.6-O -(phenvlmethvlene)-a-D-
yucopyranosyll-6-O-benzovl-~3-D-gluco~vranosyll-3-(acetylamino)-4-
chlorobenzamide
The title compound was prepared according to the procedure of Example 8 as
a white solid; 'H NMR (DMSO-d6) 8 1.94 (s, 3 H), 2.07 (s, 3 H), 2.08 (s, 3 H),
3.48
(apparent t, J = 9.4 Hz, 1 H), 3.54 (apparent t, J = 10.1 Hz, 1 H), 3.64 -
3.67 (m, 1 H},
3.77 - 3.87 (m, 4 H), 3.95 - 3.99 (m, 1 H), 4.36 (dd, J = 12.3, 3.3 Hz, 1 H),
4.52 -
4.59 (m, 2 H), 4.85 (apparent t, J = 9.2 Hz, 1 H), 5.33 - 5.39 (m, 2 H), 5.5 -
5.56 (m,
3 H), 7.33 - 7.40 (m, 5 H), 7.52 - 7.59 (m, 4 H), 7.65 - 7.69 (m, 1 H), 7.98 -
8.00 (m,
2 H), 8.09 (s, 1 H), 9.14 (d, J = 9.2 Hz, 1 H), 9.64 (s, 1H). IR (KBr) 3400,
2900,
1750, 1660, 1250 and 1075 cm~', mass spectrum (+FAB), m/z 813/815 (M + H),
835/837 (M + Na). Anal. Calcd. for C39H4,C1NZO,5 ~ 2.5 H20: C, 54.58; H, 5.40;
N,
3.26. Found: C, 54.81; H, 5.23; N, 3.28.
EXAMPLE 10
N-(Hepta-O-acetyl- .iL-D-maltosvl)-4-chloro-benzamide
To a stirred mixture of Hepta-O-acetyl-1-/J-maltosylamine, (0.90 g, 1.42
mmol) and triethyl amine (0.538 g, 3.54 mmol) in dichloromethane (8 ml), and


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tetrahydrofuran (4 ml) was added in one portion 4-chlorobenzoyl chloride
(0.322 g,
1.84 mmol). After 12 h, the reaction was diluted with dichloromethane (50 ml)
and
washed successively with water (20 ml), 10% sodium hydroxide (20 ml) and 0.1 N
hydrogen chloride (20 ml), dried (MgSO,) and concentrated. Purification by
flash
chromatography (20%-30% EtOAc/dichloromethane gradient) gave 0.70 g (74%) of
the title compound as a white solid, mp 113 - 115 °C; 'H NMR (CDCl3) 8
2.01 (s, 6
H), 2.03 (s, 3 H), 2.06 (s, 3 H), 2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3 H),
3.86 - 4.13
(m, 4 H ), 4.21 - 4.29 (m, 2 H), 4.45 (dd, J = 12.1, 2.42, Hz, 2 H), 4. 84 -
4.89 (m, 2
H), 5.07 (aparant t, J = 9.9, 1 H), 5.35 - 5.49 (m, 4 H), 6.86 (d, J = 9.2, 1
H), 7.42 (d,
J = 8.6, 2 H), 7.68 (d, J = 8.4, 2 H). IR (KBr) 3400, 2930, 1750, 1550, 1245
and
1075 cni', mass spectrum (+ESI), m/z 774 (M + H), 791 (M + NH~). Anal. Calcd.
for
C33H4oC1N0,8: C, 51.20; H, 5.21; N, 1.81. Found: C, 51.04; H, 5.24; N, 1.81.
EXAMPLE 11
N-l4', 6'-O-Benzylidene-(3-D-maltosvl)-4-chloro-benzamide
The title compound was prepared according to the procedure of Example 4 as
a white solid, mp decomposed at 225 - 230 °C; 'H NMR (DMSO-db) b 3.34 -
3.75 (m,
11 H), 4.12 (dd, J = 9.4, 4.4, Hz, 1 H), 4.63 (apparent t, J = 5.5 Hz, 1 H),
4.98
(apparent t, J = 9.0 Hz, 1 H), 5.09 (d, J = 5.7 Hz, 1 H), 5.16 (d, J = 4.0 Hz,
1 H), 5.31
(d, J = 5.1 Hz, 1 H), 5.57 (s, I H), 5.59 (d, J = 3.1 Hz, 1H), 5.69 (d, J =
6.6 Hz, 1H),
7.36 - 7.38 (m, 3 H) 7.43 - 7.46 (m, 2H), 7.55 (d, J = 8.6, Hz, 1 H), 7.93 (d,
J = 8.6
Hz, 1H), 8.98 (d, J = 8.8 Hz, 1H). IR (KBr) 3400, 2900, 2200, 1650, 1550 and
1050
cm-', mass spectrum (+ESI), m/z 568 (M + H). Anal. Calcd. for CZ6H3oC1N0" ~
0.5
H,O: C, 54.12; H, 5.42; N, 2.43. Found: C, 54.16; H, 5.24; N, 2.47.
EXAMPLE 12
N-(6-O-benzoyl-4',6'-O -benzXlidene-.iL-D-maltosyl)-4-chloro-benzamide
The title compound was prepared according to the procedure of Example 6 as
a white solid, mp 250 °C; 'H NMR (DMSO-d6) 8 3.34 - 3.76 (m, 8 H), 3.82
- 3.85
(m, 1 H), 3.99 - 4.03 (m, 1 H), 4.34 (dd, J = 12.3, 4.0 Hz, 1 H), 4.51 (d, J =
12.3 Hz,
1 H), 5.08 (apparent t, J = 9.0 Hz, 1 H), 5.17 (d, J = 3.7 Hz, 1 H), 5.22 (d,
J = 5.7 Hz,
1 H), 5.36 (d, J = 5.3 Hz, 1 H), 5.51 (s, 1 H), 5.67 (d, J = 2.4 Hz, 1 H),
5.85 (d, J =


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6.2 Hz, 1 H), 7.34 - 7.43 (m, 5 H), 7.50 - 7.56 (m, 4 H), 7.63 -7.67 (m, 1 H),
7.91 -
7.96 (m, 4 H), 9.05 (d, J = 8.8 Hz, 1 H). IR (KBr) 3400, 2900, 1725, 1600,
1550,
and 1075 cm'', mass spectrum (+FAB), m/z 672 (M + H), 694 (M + Na). Anal.
Calcd.
for C33H34C1NO,,: C, 58.98; H, 5.10; N, 2.08. Found: C, 58.54; H, 4.92; N,
2.00.
EXAMPLE 13 & 14
N-f!2 2'.3.3'4'.6.6'-he_pta-O-acetyl-Q-D-maltosyll-3-chloro-4-nitrilobutoxy-
benzoic
acid amide (13)
N-f 12.2' .3.3' 4' .6.6' -henta-O-acetyl-a-D-m altosvll-3-chloro-4-nitril
obutoxy-benzoic
i amide (14)
Step 1
3-Chloro-4-(4-nitrila-butoxy)-benzoic acid methyl ester
A mixture of methyl-3-chloro-4-hydroxy benzoate (5.0 g, 26.8 mmol), 4-
bromo butyronitrile (4.0 ml, 40.19 mmol), potassium carbonate (7.4 g, 53.6
mmol),
1 S and methyl sulfoxide (40 ml) in 2-butanone ( 100 ml) was refluxed for 24
h. The
reaction mixture was cooled and filtered. The mixture was concentrated in
vacuo,
diluted with ethyl ether, and washed twice with water and once with saturated
sodium
chloride solution. The organic layer was dried (MgS04), filtered and
concentrated to
give 6.75 g (99%) of a light brown solid. An analytical sample was obtained by
silica gel chromatography (10%-20% EtOAc/petroleum ether gradient) mp 90
°C; 'H
NMR (CDC13) b 2.20 - 2.26 (m, 2 H), 2.68 (t, J = 7.0 Hz, 2 H), 3.90 (s, 3 H),
4.21 (t,
J = 5.5 Hz, 2 H), 6.93 (d, J = 8.6 Hz, 1 H), 7.93 (dd, J = 8.6, 2.0 Hz, 1 H),
8.06 (d, J
= 2.0 Hz, 1 H). IR (KBr) 3400, 2280, 1700, 1600, 1500, 1245 and1050 cm'', mass
spectrum (EI), m/z 253/255. Anal. Calcd. for C,ZH,zC1N03: C, 56.82; H, 4.77;
N,
5.52. Found: C, 56.69; H. 4.69; N, 5.47.
Step 2
3-Chloro-4-(4-nitrilo-butoxy)-benzoic acid
A solution of 3-Chloro-4-(4-nitrilo-butoxy)-benzoic acid methyl ester (6.24 g,
24.6 mmol in THF (100 ml) and methanol (100 ml) was treated with 5 N sodium
hydroxide solution (35 ml) with stirring at room temperature for 1 h. The
reaction
mixture was concentrated in vacuo, diluted with water, and acidified to pH 1
with 5 N


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hydrochloric acid. The resulting suspension was extracted with ethyl acetate.
The
organic layer was dried (MgSO,), filtered, and concentrated in vacuo. The
resulting
off white solid was triturated with hot petroleum ether, cooled and filtered
to give
5.58 g (95 %) of the title compound as a white solid mp 150 °C; 'H NMR
(CDC13) S
2.22 - 2.28 (m, 2 H), 2.69 (t, J = 7.0 Hz, 2 H), 3.90 (s, 3 H), 4.23 (t, J =
5.5 Hz, 2 H),
6.97 (d, J = 8.6 Hz, 1 H), 8.01 (dd, J = 8.6, 2.2 Hz, 1 H), 8.14 (d, J = 2.0
Hz, 1 H).
IR (KBr) 3400, 2200, 1700, 1600, 1450, 1275 and1050 cm', mass spectrum (EI),
m/z
239/241. Anal. Calcd. for C"H,oC1N03: C, 55.13; H, 4.21; N, 5.85. Found: C,
54.84;
H, 4.01; N, 5.69.
Step 3
N-[(2,2',3,3'4',6,6'-hepta-O-acetyl-(3-D-maltosyl]-3-chloro-4-nitrilobutoxy-
benzoic acid amide
The title compounds were prepared according to the following procedure. To
a mixture of Hepta-O-acetyl-1-(3-maltosylamine (1.255 g, 1.97 mmol) and 3-
Chloro-
4-(4-nitrilo-butoxy)-benzoic acid (0.591 g, 2.47 mmol) was added triethyl
amine
(0.40g, 3.95 mmol), HOBT (0.480 g, 3.55 mmol) and DEC (0.567 g, 2.96 mmol).
After stirring at ambient temperature overnight the reaction was concentrated
and
partitioned between ethyl acetate (80 ml) and 1N sodium hydroxide (50 ml). The
aqueous layer was seperated and extracted with ethyl acetate (3 x 30 ml). The
organic layers were washed with 1N hydrogen chloride (50 ml) then water (50
ml)
and dried (MgSO,) and concentrated. Purification by flash chromatography (20%-
50% EtOAc/petroleum ether gradient) afforded 47 % ~i anomer and 7% a anomer as
white solids, ~i anomer mp 102 - 103 °C; 'H NMR (CDCl3) 8 2.011 (s, 3
H), 2.01 (s, 3
H), 2.03 (s, 3 H), 2.05 (s, 3 H), 2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3 H),
2.19 - 2.26
(m, 2 H), 2.67 (t, J = 7:0 Hz, 2 H), 3.85 - 4.06 (m, 4 H), 4.17 - 4.25 (m, 3
H), 4.45
(dd, J = 12.7, 2.6 Hz, 1 H), 4.84 - 4.89 (m, 2 H), 5.07 (apparent t, J = 10.1
Hz, 1 H),
5.35 - 5.48 (m, 4 H), 6.79 (d, J = 9.2 Hz, 1 H), 6.94 (d, J = 8.6 Hz, 1H),
7.59 (dd, J =
8.6, 2.4, Hz, 1 H), 7.82 (d, J = 2.2 Hz, 1H). IR (KBr) 3400, 2950, 2280, 1750,
1250
and 1050 crri', mass spectrum (+ESI), m/z 857.4/859.4 {M + H), 874.4/876.3 (M
+
NH,), 879.4/881.31 (M + Na). Anal. Calcd. for C3,H4sC1N2O,9 ~ 1.0 H20: C,
50.78; H,
5.41; N, 3.20. Found: C, 50.93; H, 5.17; N, 3.35.


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N-[(2,2',3,3'4',6,6'-hepta-O-acetyl-a-D-maltosylj-3-chloro-4-nitrilobutoxy-
benzoic acid amide
a anomer mp 105 - 106 °C; 'H NMR (CDC13} 8 1.98 (s, 3 H), 2.00 (s, 3
H), 2.03 (s, 3
H), 2.10 (s, 6 H), 2.14 (s, 3 H), 2.20 - 2.27 (m, 2 H), 2.67 (t, J = 7.0 Hz, 2
H), 3.94 -
3.98 (m, 2 H), 4.03 - 4.08 (m, 2 H), 4.21 - 4.40 (m, 4 H), 4.42 (d, J = 2.0
Hz, 1 H),
4.87 (dd, J = 10.5, 4.0, Hz, 1 H), 5.07 (apparent t, J = 10.1 Hz, 1 H), 5.18
(dd, J =
9.7, 5.3, Hz, 1 H), 5.33 - 5.44 (m, 3 H), 5.95 (apparent bt, J = 6.2 Hz, I H),
6.34 (d, J
= 8.0 Hz, 1 H), 6.97 (d, J = 8.8 Hz, 1H}, 7.84 (dd, J = 8.8, 1.8, Hz, 1 H),
7.97 (d, J =
1.1 Hz, IH). IR (KBr) 3400, 2950, 2280, 1750, 1250 and 1050 cni', mass
spectrum
(+ESI), mlz 857.4/859.4 (M + H}, 874.4/876.4 (M + NH,), 879.4/881.4 (M + Na).
EXAMPLE 15
N-l4' 6'-O-Benzvlidene- -D-maltosyl)-3-chloro-4-(4-nitrilo-butoxv)-benzamide
Step 1
3-chloro-4-(3-cyanopropoxy)-N-(4-O-a-D-glucopyranosyl-(3-D-glucopyranosyl)-
benzamide Hydrate
The title compound was prepared according to the procedure of Example 4,
Step 1 as a white solid, mp 203 °C; 'H NMR (CD30D-d,) 2.15 - 2.22 (m, 2
H), 2.70
(t, J = 7.2 Hz, 2 H), 3.26 (t, J = 9.4 Hz, 2 H), 3.43 - 3.53 (m, 3 H), 3.57 -
3.73 (m, 4
H), 3.78 - 3.84 (m, 3 H), 4.23 (apparent t, J = 5.7 Hz, 1 H), 5.08 - 5.13 (m,
1 H), 5.18
(d, J = 3.7 Hz, 1 H), 7.17 (d, J = 8.8 Hz, IH), 7.86 (dd, J = 8.6, 2.0, Hz, 1
H), 7.98 (d,
J = 2.2 Hz, 1H), 8.91 (d, J = 9.0 Hz, 1H). IR (KBr) 3375, 2900, 2200, 1600,
1550
and 1050 crri', mass spectrum (+FAB), m/z 563/565 (M + H), 585/587 (M + Na).
Anal. Calcd. for C23H31CIN2O,2 ~ 1.0 H20: C, 47.55; H, 5.73; N, 4.82. Found:
C,
47.26; H, 5.84; N, 4.75.
Step 2
N-(4', 6'-O-Benzylidene-(3-D-maltosyl)-3-chloro-4-(4-nitrilo-butoxy)-benzamide
The title compound was prepared according to the procedure of Example 4,
Step 2 as a white solid, mp decomposed at I90 °C; 'H NMR (DMSO-d6) 2.05
- 2.12
(m, 2 H), 2.67 (t, J = 7.5 Hz, 2 H), 3.34 - 3.42 (m, 4 H), 3.48 - 3.62 (m, 4
H), 3.64
3.78 (m, 3 H), 4.14 (dd, J = 9.4, 4.6, Hz, 1 H), 4.19 (apparent t, J = 5.9 Hz,
1 H), 4.62


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(apparent t, J = 5.5 Hz, 1 H), 4.97 (apparent t, J = 9.0 Hz, 1 H), 5.09 (d, J
= 5.7 Hz, 1
H), 5.16 (d, J = 3.7 Hz, 1 H), 5.32 (d, J = 5.1 Hz, 1 H), 5.57 (s, 1 H), 5.59
(d, J = 2.9
Hz, 1H), 5.70 (d, J = 6.6 Hz, 1H), 7.26 (d, J = 8.8 Hz, 1H), 7.34 - 7.40 (m,
3H) 7.42 -
7.46 (m, 2H), 7.90 (dd, J = 8.6, 2.2, Hz, 1 H), 8.04. (d, J = 2.2 Hz, 1H),
8.89 (d, J =
8.8 Hz, 1H). IR (KBr) 3400, 2900, 2200, 1650, 1550 and 1050 cm ', mass
spectrum
(+ESI), m/z 651 (M + H). Anal. Calcd. for C3oH35C1NZO,~: C, 55.34; H, 5.42; N,
4.30.
Found: C, 55.00; H, 5.30; N, 4.10.
N-(6-O-BenzQyl-4' . 6'-O-benzylidene-J3-D-maltosvl)-3-chloro-4-(4-nitrilo-
butox~
phenyl amide
The title compound was prepared according to the procedure of Example 6 as
a white solid, mp ; 'H NMR (DMSO-d6) 2.04 - 2.11 (m, 2 H), 2.66 (t, J = 7.2
Hz, 2
H), 3.33 - 3.75 (m, 8 H), 4.14 (bd, J = 4.6, Hz, 1 H), 4.00 (dd, J = 9.9, 4.4,
Hz, 1 H),
4.I8 (apparent t, J = 6.0 Hz, 1 H), ), 4.34 (dd, J = 12.3, 4.0, Hz, 1 H), ),
4.50 (bd, J =
11.2, Hz, 1 H), 5.06 (apparent t, J = 9.0 Hz, 1 H), 5.17 (d, J = 3.7 Hz, 1 H),
5.22 (d, J
= 5.7 Hz, I H), 5.36 (d, J = 5.3 Hz, 1 H), 5.51 (s, 1 H), 5.67 (d, J = 2.0 Hz,
1H), 5.85
(d, J = 6.2 Hz, 1H), 7.25 (d, J = 8.8 Hz, 1H), 7.34 - 7.40 (m, 3H) 7.41 - 7.43
(m, 2H),
7.52 (t, J = 7.7 Hz, 1 H), 7.89 (dd, J = 8.6, 2.2, Hz, 1 H), 7.94 - 7.96 (m,
2H), 8.04 (d,
J = 2.2 Hz, IH), 8.95 (d, J = 8.8 Hz, 1H). IR (KBr) 3400, 2900, 2200, 1650,
1550,
1225, and 1050 cm', mass spectrum (+FAB), m/z 755 (M + H), 777 (M + Na). Anal.
Calcd. for C3,H39C1NZO" ~ 0.5 HZO: C, 58.16; H, 5.28; N, 3.66. Found: C,
58.12; H,
5.32; N, 3.73.
EXAMPLE 17
N-12.2',3.3'-tetra-O-Acetvl-6-O-benzoyl-4'.6'-O-benzvlidene-J3-D-maltosvl)-3-
~hloro-4-l4-nitrilo-butoxy)-benzamide
The title compound was prepared according to the procedure of Example 8 as
a white solid, mp 230 - 232 °C; 'H NMR (CDC13) 2.02 (s, 3 H), 2.04 (s,
3 H), 2.07 (s,
3 H), 2.11 (s, 3 H), 2.20 - 2.24 (m, 2 H), 2.66 (t, J = 7.0 Hz, 2 H), 3.52 -
3.62 (m, 2
H), 3.81 - 3.87 (m, 1 H), 3.95 - 4.04 (m, 2 H), 4.17 (apparent t, J = 5.5 Hz,
2 H), 4.22
(apparent t, J = 9.5 Hz, 1 H), 4.51 (dd, J = 12.5, J = 3.0, Hz, 1 H), 4.84 -
4.93 (m, 3
H), 5.40 (s, 1 H), 5.43 - 5.54 (m, 4 H), 7.73 (d, J = 9.2 Hz, 1 H), 6.91 (d, J
= 8.8 Hz,


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1 H), 7.31 - 7.39 (m, 5 H) 7.43 - 7.47 (m, 2 H), 7.55 - 7.60 (m, 2 H), 7.78
(d, J = 2.2
Hz, 1 H), 8.04 - 8.07 (m, 2 H). IR (KBr) 3400, 2900, 2200, 1750, 1650, 1550,
1250,
and 1050 cm'', mass spectrum (+FAB), m/z 923 (M + H), 945 (M + Na).
EXAMPLE 18
4-butoxy-3-chloro-N-f2.3,6-tri-O-acetyl-4-O-(2.3.4.6-tetra- O-acetyl-a-D-
gluco~vranosyl)-a-D- lg ucopvranosyll benzamide
Step 1
3-Chloro-4-(4-nitrilo-butoxy)-benzoic acid methyl ester
The title compound was prepared according to the procedure of Example 13,
Step 1 affording 95 % as a clear oil; 'H NMR (CDC13) 8 1.0 (t, J = 7.2 Hz, 3),
1.49 -
1.58 (m, 2 H) 1.81 - 1.88 (m, 2 H), 3.89 (s, 3 H), 4.09 (t, J = 6.6 Hz, 2 H),
6.92 (d, J
= 8.8 Hz, 1 H), 7.91 (dd, J = 8.6, 2.2 Hz, 1 H), 8.05 (d, J = 2.2 Hz, 1 H). IR
(KBr)
2950, 1675, 1600, 1500, 1225 and 1050 cm'', mass spectrum (-ESI), m/z 227.3.
Anal. Calcd. for C"H,3C103: C, 57.78; H, 5.73. Found: C, 57.89; H, 5.62.
Step 2
3-Chloro-4-(4-nitrilo-butoxy)-benzoic acid methyl ester
The title compound was prepared according to the procedure of Example 13,
Step 2 affording 95 % as a white solid, mp 144 °C; 'H NMR (CDC13) 8 1.0
(t, J = 7.5
Hz, 3), 1.50 - 1.60 (m, 2 H) 1.83 - 1.90 (m, 2 H), 4.12 (t, J = 6.4 Hz, 2 H),
6.96 (d, J
= 8.8 Hz, 1 H), 7.98 (dd, J = 8.6, 2.2 Hz, 1 H), 8.12 (d, J = 2.2 Hz, i H). IR
(KBr)
2950, 1700, 1600, 1500, 1225 and1050 cm ', mass specwm (+EI), m/z 242/244.
Anal. Calcd. for C,=H,SC103: C, 59.39; H, 6.23. Found: C, 59.22; H, 6.25.
Step 3
4-butoxy-3-chloro-N-[2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra- O-acetyl-a-D-
glucopyranosyl)-~3-D-glucopyranosyl] benzamide
The title compound was prepared according to the procedure of Example 10,
Step 3 affording 92 % as a white solid, mp °C; 'H NMR (CDCl3) 8 0.99
(t, 7.5 Hz,
3H), 1.50 - 1.58 (m. 2 H), 1.80 - 1.87 (m, 2 H), 2.01 (s, 6 H), 2.03 (s, 3 H),
2.05 (s, 3
H), 2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3 H), 3.86 - 3.89 (m, 1 H), 3.92 -
3.96 (m, 1


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H), 3.99 - 4.09 (m, 4 H), 4.45 (dd, J = 12.3, 2.4 Hz, 1 H), 4.84 - 4.90 (m, 2
H), 5.07
(apparent t, J = 9.7 Hz, 1 H), 5.35 - 5.48 (m, 4 H), 6.76 (d, J = 9.2 Hz, 1
H), 6.92 (d,
J = 4.3 Hz, 1H), 7.57 (dd, J = 8.6, 2.2, Hz, 1 H), 7.80 (d, J = 2.4 Hz, 1H).
IR (KBr)
3400, 2950, 1750, 1250 and 1050 cm', mass spectrum (+ESI), m/z 846.1/848.1 (M
+
H), 863.1 (M + NH,). Anal. Calcd. for C37Ha8C1N20,9: C, 52.52; H, 5.72; N,
1.65.
Found: C, 52.31; H, 5.64; N, 1.61.
EXAMPLE 19
4-Butox~r-3-chloro-N-f(4',, 6'-O-benzylidene)-J3-D-maltosyll-benzamide hydrate
Stepl
4-Butoxy-3-chloro-N-((3-D-maltosyl)-benzamide Hydrate
The title compound was prepared according to the procedure of Example 4,
Step 1 as a white solid, mp decomposition at 180; 'H NMR (CD30D-d4) 0.94 (t,
7.2
Hz, 3H), 1.41 - 1.50 (m, 2 H), 1.70 - 1.77 (m, 2 H), 3.03 - 3.09 (m, 1 H),
3.17 (d, 4.8
Hz, 1H), 3.22 - 3.70 (m, 11 H), 4.12 (apparent t, J = 6.4 Hz, 1 H), 4.46 -
4.51 (m, 2
H), 4.90 (bd, J = 4.2 Hz, 2 H), 4.95 (t, J = 9.0 Hz, 1H), 5.05 (bd, 3.7 Hz,
1Hz), 5.06
(bs, 1Hz), 5.5 (bs, 1 Hz), 5.6 (bs, 1Hz), 7.23 (d, J = 8.8 Hz, 1H), 7.88 (dd,
J = 8.6,
2.2, Hz, 1 H), 8.02 (d, J = 2.2 Hz, 1H), 8.86 {d, 4.4 Hz, 1Hz). IR (KBr) 3375,
2900,
1600, 1550 and 1050 cm'', mass spectrum (-ESI), m/z 550.1 {M - H). Anal.
Calcd. for
C~H3,C1N0,z ~ 0.5 HZO: C, 49.25; H, 6.29; N, 2.50. Found: C, 49.28; H, 6.27;
N,
2.49.
Step 2
4-Butoxy-3-chloro-N-[(4', 6'-O-benzylidene)-(3-D-maltosyl]-benzamide Hydrate
The title compound was prepared according to the procedure of Example 4,
Step 2 as a white solid, mp decomposed at 215 - 220; 'H NMR (DMSO-d6) 0.94 (t,
7.2 Hz, 3H), 1.41 - 1.51 (m, 2 H), 1.70 - 1.77 (m, 2 H), 3.28 - 3.42 {m, 4 H),
3.48 -
3.65 (m, 4 H), 3.67 - 3.78 (m, 4 H), 4.12 (apparent t, J = 6.2 Hz, 3 H), 4.63
(apparent
t, J = 5.5 Hz, 1 H), 4.97 (apparent t, J = 8.8 Hz, 1 H), 5.15 (apparent t, J =
7.7 Hz, 1
H), 5.34 (d, J = 5.1 Hz, 1 H), 5.57 (s, 1H), 5.62 (d, J = 2.9 Hz, 1 H), 5.73
(d, J = 6.6
Hz, 1 H), 7.23 (d, J = 9.0 Hz, 1H), 7.34 - 7.40 (m, 3H), 7.43 - 7.46 (m, 2H),
7.88 (dd,
J = 8.8, 2.2, Hz, 1 H), 8.03 (d, J = 2.2 Hz, 1H), 8.90 (d, J = 8.8 Hz, 1H). IR
(KBr}


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3400, 2900, 1650, 1550 and 1050 cm-', mass spectrum (+FAB) m/z 640/642 (M +
H),
662/664 (M + Na). Anal. Calcd. for C3oH38C1NO,Z ~ 0.5 H20: C, 55.52; H, 6.06;
N,
2.16. Found: C, 55.72; H, 6.01; N, 2.07.
EXAMPLE 20
4-Butoxy-3-chloro-N-f l6-O-benzoyl-4'. 6'-O-benzylidene)-Q-D-maltosyll-
benzamide
The title compound was prepared according to the procedure of Example 6 as
a white solid, mp 224; 'H NMR (DMSO-db) 0.92 (t, 7.5 Hz, 3H), 1.42 - 1.47 (m,
2
H), 1.69 - 1.74 (m, 2 H), 3.33 - 3.65 (m, 7 H), 3.69 - 3.73 (m, 1 H), 3.81 -
3.83 (m, 1
H), 4.0 (dd, J = 9.9, 4.8, Hz, 1 H), 4.12 (apparent t, J = 6.4 Hz, 2 H), 4.33
(dd, J =
12.3, 3.7, Hz, 1 H), 4.50 (d, J = 11 Hz, 1 H), 5.06 (apparent t, J = 9.0 Hz, 1
H), 5.17
(d, J = 4.0 Hz, 1 H), 5.21 (d, J = 5.7 Hz, 1 H), 5.36 (d, J = 5.1 Hz, 1 H),
5.51 (s, 1 H),
5.67 (d, J = 2.0 Hz, 1 H), 5.85 (d, J = 6.2 Hz, 1 H), 7.22 (d, J = 8.8 Hz, 1
H), 7.35 -
7.37 (m, 3 H), 7.40 - 7.43 (m, 2 H), 7.52 (t, J = 8.0 Hz, 1 H), 7.63 - 7.67
(m, 1 H),
7.88 (dd, J = 8.6, 2.2, Hz, 1 H), 7.95 (d, J = 8.3 Hz, 1 H), 8.02 (d, J = 2.2
Hz, 1 H),
8.02 (d, J = 2.2 Hz, 1 H). 8.93 (d, J = 8.8 Hz, 1 H). IR (KBr) 3400, 2900,
1650,
1500, 1225 and 1050 cm', mass spectrum (+FAB) m/z 744/746 (M + H), 766/768 (M
+ Na}. Anal. Calcd. for C3,H4zC1NO,3: C, 59.72; H, 5.69; N, 1.88. Found: C,
59.61;
H, 5.84; N, 1.87.
EXAMPLE 21
4-Butoxy-3-chloro-N-f (2.3.2' .3' -tetra-O-acetyl-6-O-benzovl-4' . 6' -O-ben
zvlidene)-
~i-D-maltosyl~'-benzamide
The title compound was prepared according to the procedure of Example 8 as
a white solid, mp 260 - 261; 'H NMR (CDCl3) 0.98 (t, 7.5 Hz, 3H), 1.49 - 1.55
(m, 2
H), 1.79 - 1.84 (m, 2 H), 2.02 (s, 3 H), 2.04 (s, 3 H), 2.07 (s, 3 H), 2.11
(s, 3 H), 3.52
- 3.61 (m, 2 H), 3.82 - 3.85 (m, 1 H), 3.95 - 4.03 (m, 3 H), 4.06 (apparent t,
J = 6.4
Hz, 1 H), 4.22 (apparent t, J = 6.4 Hz, 1 H), 4.51 (dd, J = 12.5, 3.1, Hz, 1
H), 4.83
4.93 (m, 3 H), 5.40 (s, 1 H), 5.43 - 5.54 (m 4 H), 6.70 (d, J = 9.2 Hz, 1 H),
6.90 (d, J
= 8.8 Hz, 1 H), 7.31 - 7.34 (m, 3 H), 7.36 - 7.40 (m, 2 H), 7.43 - 7.47 (m, 2
H), 7.55 -
7.59 (m, 2 H), 7.76 (d, J = 2.2, Hz, 1 H), 8.05 (d, J = 1.3 Hz, 1H), 8.07 (d,
J = 1.3 Hz,
1H). IR (KBr) 3400, 2900, 1750, 1500, 1250 and 1050 cm-', mass spectrum (+
FAB)


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m/z 912/914 (M + H), 934/936 (M + Na). Anal. Calcd. for C~,HSOCINO": C, 59.24;
H, 5.52; N, 1.54. Found: C, 59.24; H, 5.59; N, 1.61.
EXAMPLE 22
4-Chloro-3-methoxv-N-f 2.3.6-tri- O-acetyl-4-O-(2.3.4.6-tetra- O-acetyl-a-D-
lg ucopyranosyl)-~i-D-glucopvranosyll benzamide
The title compound was prepared according to the procedure of Example 10
affording 83 % as a white solid, mp 106-110 °C; 'H NMR (DMSO-d6) 8 1.86
(s, 6 H),
1.95 (s, 3 H), 1.98 (s, 3 H), 2.00 (s, 3 H), 2.01 (s, 3 H), 2.04 (s, 3 H),
3.87 - 4.02 (m,
3 H), 3.90 (s, 3H), 4.11 - 4.17 (m, 3 H), 4.35 (bd, J = 9.9 Hz, 1 H), 4.87
(dd, J = 10.5,
3.7 Hz, 1 H), 4.98 (q, J = 10.1 Hz, 2 H), 5.23 (apparent t, J = 9.7 Hz, 1 H),
5.34 (d, J
= 3.7 Hz, 1 H), 5.44 (apparent t, J = 9.2 Hz, 1 H), 5.59 (apparent t, J = 9.2
Hz, 1 H),
7.40 (dd, J = 8.4, 1.8 Hz, 1 H), 7.50 (d, J = 1.8 Hz, IH), 7.54 (d, J = 8.4,
Hz, 1 H),
9.21 (d, J = 4.6 Hz, 1H). IR (KBr) 3400, 2950, 1750, 1250 and 1050 cm', mass
spectrum (+ESI), m/z (M + H), (M + NH4). Anal. Calcd. for C3,H42C1NO,9: C,
50.78;
H, 5.26; N, 1.74. Found: C, 50.2; H, 5.06; N, 1.59
EXAMPLE 23
N-(4'.6'-O-Benzvlidene-~i-D-maltosvl)-4-chloro-3-methoxv-benzamide
Step 1
N-((3-D-MattosyI)-4-chloro-3-methoxy-benzamide
The title compound was prepared according to the procedure of Example 4,
Step 1 affording a white solid, mp 165 - 168 °C; 'H NMR (CD30D-d4) 8
3.24 - 3.34
(m, 2 H), 3.44 - 3.89 (m, 10 H), 3.95 (s, 3 H), 5.12 - 5.29 (m, 2 H), 7.45 (d,
J = 1.3
Hz, 2 H), 7.58 (s, 1 H), 8.98 (d, J = 9.0, Hz, 1 H). IR (KBr) 3400, 2950,
1650, 1250
and 1045 cm ', mass spectrum (+FAB), m/z 510/512 (M + H), 532/534 (M + NH,).
Anal. Calcd. for C~oH.,$CINO,i 0.5 H20: C, 46.29; H, 5.63; N, 2.70. Found: C,
46.43;
H,5.81;N,2.67.


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Step 2
N-(4',6'-O-Benzylidene-(3-D-maltosyl)-4-chloro-3-methoxy-benzamide
The title compound was prepared according to the procedure of Example 4,
Step 2 affording a white solid; 'H NMR (DMSO-db) S 3.34 - 3.43 (m, 4 H), 3.49 -

3.75 (m, 6 H), 3.93 (s, 3 H), 4.08 - 4.14 (m, 2 H), 4.65 (apparent t, J = 5.3
Hz, 1 H),
5.01 (apparent t, J = 8.8 Hz, 1 H), 5.12 (d, J = 5.7 Hz, 1 H), 5.16 (d, J =
3.7 Hz, 1 H),
5.28 (d, J = 5.1 Hz, 1 H), 5.57 (s, 1 H), 5.61 (d, J = 3.1 Hz, 1 H), 5.71 (d,
J = 6.6 Hz,
1 H), 7.35 - 7.40 (m, 3 H), 7.43 - 7.46 (m, 2 H), 7.49 - 7.55 (m, 2 H), 7.61
(d, J = 1.3
Hz, 1H), 8.98 (d, J = 8.8, Hz, 1 H). IR (KBr) 3400, 2900, 1650, 1300 and 1075
cm',
mass spectrum (+ FAB), m/z 599 (M + H), 620/622 (M + Na). Anal. Calcd. for
CZ,H3zC1N0,2: C, 54.23; H, 5.39; N, 2.34. Found: C, 54.27; H, 5.50; N, 2.25.
EXAMPLE 24
N-f 6-O-Benzoyl-4' .6'-O-benzylidene-(3-D-maltosyl)-4-chloro-3-methoxv-
benzamide
The title compound was prepared according to the procedure of Example 6
affording a white solid, mp 245 °C; 'H NMR (DMSO-ds) 8 3.34 - 3.74 (m,
8 H), 3.84
- 3.87 (m, 1 H), 3.91 (s, 3 H), 4.00 (dd, J = 9.9, 4.8 Hz, 1 H), 4.35 (dd, J =
12.3, 4.2
Hz, 1 H), 4.51 (d, J = 11.0 Hz, 1H), 5.10 (apparent t, J = 9.0 Hz, 1 H), 5.17
(d, J =
3.7 Hz, 1 H), 5.26 (d, J = 5.7 Hz, 1 H), 5.37 (d, J = 5.1 Hz, 1 H), 5.51 (s, 1
H), 5.69
(d, J = 2.4 Hz, 1 H), 5.86 (d, J = 6.4 Hz, 1 H), 7.35 - 7.37 (m, 3 H), 7.38 -
7.43 (m, 2
H), 7.49 - 7.54 (m, 4 H), 7.61 - 7.67 (m, 2 H), 7.95 (dd, J = 8.6, 1.0 Hz,
1H), 9.04 (d,
J = 9.0, Hz, 1 H). IR (KBr) 3400, 2900, 1650, 1250 and 1055 cm', mass spectrum
(+
FAB), m/z 702 (M + H), 724 (M + Na). Anal. Calcd. for C3,H36C1NO,3 ~ 0.5 H20:
C,
57.43; H, 5.24; N, 1.97. Found: C, 57.34; H, 5.27; N, 1.96.
EXAMPLE 25
N-(2 2' 3 3' 4 6 6'-hepta- O-acetyl- ~i-D-maltosyll-4-butoxy-5-chloro-3-
methoxv-
b nzami a
The title compound was prepared according to the procedure of Example 10
affording 88 % as a white solid, 104-106 mp °C; 'H NMR (CDC13) 8 0.97
(t, 7.2 Hz,
3H), 1.49 - 1.56 (m, 2 H), 1.73 - 1.80 (m, 2 H), 2.01 (s, 3 H), 2.02 (s, 3 H),
2.03 (s, 3
H), 2.05 (s, 3 H), 2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3H), 3.85 - 3.96 (m,
2 H), 3.89


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(s, 3H), 3.99 - 4.08 (m, 4 H), 4.21 - 4.28 (m, 2H), 4.46 (dd, J = 12.3, 2.4
Hz, 1 H),
4.84 - 4.89 (m, 2 H), 5.07 (apparent t, J = 10.7 Hz, 1 H), 5.35 - 5.48 (m, 4
H), 6.79
(d, J = 9.0 Hz, 1 H), 7.26 (m, 2H). IR (KBr} 3400, 2950, 1750, 1250 and 1050
cm',
mass spectrum (+FAB), m/z 876/878 (M + H), 898/900 (M + Na). Anal. Calcd. for
C38HSOC1NO2o: C, 52.09; H, 5.75; N, 1.60. Found: C, 52.26; H, 5.76; N, 1.51.
EXAMPLE 26
4-butoxy-3-chloro-N-f l4',6'-O-benzylidene)-~i-D-maltosyll-5-methoxv-benzamide
H dra a
Step 1
4-butoxy-3-chloro-N-(a-D-maltosyl)-5-methoxy-benzamide Hydrate
The title compound was prepared according to the procedure of Example 4,
Step 1 affording 100 % as a white solid, mp decomposition at 210; 'H NMR (DMSO-

d6) 0.91 (t, 7.5 Hz, 3H), 1.41 - 1.50 (m, 2 H), 1.70 - 1.77 (m, 2 H), 3.06
(bt, 1H), 3.22
- 3.70 (m, 12 H), 3.87 (s, 3H), 4.00 (apparent t, J = 6.4 Hz, 3 H), 4.48 -
4.51 (m, 2H),
6.40 (bd, J = 3.5 Hz), 4.96 (apparent t, J = 8.8 Hz, 1 H), 5.04 (d, J = 3.7
Hz, 1 H),
5.11 (bs, 1H), 5.5 (bs, 1 Hz), 5.56 (bs, 1Hz), 7.51 (d, J = 2.0 Hz, 1H), 7.62
(d, J =
2.0, Hz, 1 H), 8.93 (d, J = 9.0 Hz, 1 H). IR (KBr) 3300, 2900, 1600, 1550 and
1050
cm ', mass spectrum (+FAB), m/z 582/584 (M + H), 604/606 (M + Na).. Anal.
Calcd.
for C~,H36C1N0,3 ~ 0.5 H20: C, 48.78; H, 6.26; N, 2.37. Found: C, 48.99; H,
6.13; N,
2.43.
Step 2
4-butoxy-3-chloro-N-[(4', 6'-4-benzylidene)-(3-D-maltosyl]-5-methoxy-
benzamide Hydrate
The title compounds were prepared according to the procedure of Example 4,
Step 2 as a white solid, mp 226 °C; 'H NMR (DMSO-db) 0.92 (t, 7.2 Hz,
3H), 1.43 -
1.49 (m, 2 H), 1.63 - 1.70 (m, 2 H), 3.34 - 3.75 (m, 5 H), 3.34 - 3.75 (m, 11
H), 3.88
(s, 3H), 4.00 (apparent t, J = 6.4 Hz, 3 H), 4.12 (dd, J = 9.5, 4.4 Hz, 1 H),
4.63 (bs,
1H), 4.98 (apparent t, J = 9.0 Hz, 1 H), 5.11 (d, J = 5.3 Hz, 1 H}, 5.16 (d, J
= 4.0 Hz,
1 H), 5.32 (d, J = 4.6 Hz, 1 H), 5.57 (s, 1H), 5.60 (d, J = 2.6 Hz, 1 H), 5.70
(d, J = 6.4


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Hz, 1H), 7.35 - 7.38 (m, 3H), 7.43 - 7.46 {m, 2H), 7.52 (d, J = 1.8, Hz, 1 H),
7.63 (d,
J = 2.0 Hz, 1H), 8.94 (d, J = 9.0 Hz, 1H). IR (KBr) 3400, 2900, 1650, 1550 and
1050
cm', mass spectrum (+ESI) mlz 670/672 (M + H). Anal. Calcd. for C3,H,oC1N0,3 '
1.0
H20: C, 54.11; H, 6.15; N, 2.03. Found: C, 54.30; H, 6.10; N, 2.06.
EXAMPLE 27
Nf (6-O-benzo~oxv-4' . 6'-O-benz~idene)-Q-D-maltosvll-4-butoxy-3-chloro-5-
methoxy-benzamide
The title compounds were prepared according to the procedure of Example 6
affording 64%, as a white solid, mp 217; 'H NMR (DMSO-d6) 0.91 (t, 7.5 Hz,
3H),
1.42 - 1.47 (m, 2 H), 1.63 - 1.67 (m, 2 H), 3.34 - 3.73 (m, 8 H), 3.83 - 3.86
(m, 4 H),
3.97 - 4.02 (m, 3 H), 4.34 (dd, J = 12.0, 3.3, Hz, 1 H), 4.51 (d, J = I 1.9
Hz, 1 H),
5.07 (apparent t, J = 8.8 Hz, 2 H), 5.17 (d, J =3.5 Hz, 1 H), 5.25 (d, J = 5.7
Hz, 1 H),
5.36 (d, J = 5.3 Hz, 1 H), 5.51 (s, 1H), 5.68 (s, 1 H), 5.85 (d, J = 6.4 Hz, 1
H), 7.35 -
7.36 (m, 3H), 7.40 - 7.42 (m, 2H), 7.50 - 7.54 (m, 3H), 7.63 - 7.67 (m, 2H),
7.95 (d, J
= 8.1 Hz, 2H), 8.99 (d, J = 8.8 Hz, 1H). IR (KBr) 3400, 2900, 1725, 1650,
1500,
1225 and 1050 cm', mass spectrum (-FAB) m/z 772/774 (M - H). Anal. Calcd. for
C38H"C1N0"' 0.5 HZO: C, 58.27; H, 5.79; N, 1.79. Found: C, 58.24; H, 5.92; N,
1.78.
EXAMPLE 28
N-((2.2'.3.3'4',6.6'-he~ta-O-acet ~~1-~3-D-maltosvll-4-(4-nitrilo-butoxy)-3-
nitro-
nzami a
Step 1
4-(4-Nitrilo-butoxy)-3-nitro-benzoic acid 4-nitrilo-butyl ester
The title compound was prepared according to the procedure of Example 13,
Step I as a yellow solid (74 %), mp 60 °C; 'H NMR (CDC13) 8 2.13 - 2.26
(m, 4 H),
2.55 (t, J = 7.2 Hz, 2 H), 2.70 (t, J = 6.8 Hz, 2 H), 4.32 (t, J = 5.7 Hz, 2
H), 4.47 (t, J
= 6.0 Hz, 2 H), 7.14 (d, J = 8.8 Hz, 1 H), 8.25 (dd, J = 8.8, 2.2 Hz, 1 H),
8.53 (d, J =
2.2 Hz, 1 H). IR (KBr) 3400, 2280, 1700, 1625, 1550, 1275 and1050 cni', mass
spectrum (EI), m/z 317. Anal. Calcd. for C,SH,SN305: C, 56.78; H, 4.77; N,
13.24.
Found: C, 56.53; H, 4.62; N, 13.06.


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Step 2
4-(4-Nitrilo-butoxy)-3-vitro-benzoic acid
The title compounds were prepared according to the procedure of Example
13, Step 2 as a light tan solid, mp 162 - 163 °C; 'H NMR (CDCl3) 8 2.04
- 2.11 (m, 2
H), 2.64 (t, J = 7.3 Hz, 2 H), 4.30 (t, J = 5.9 Hz, 2 H), 7.48 (d, J = 9.0 Hz,
1 H), 8.16
(dd, J = 8.8, 2.2 Hz, 1 H), 8.35 (d, J = 2.2 Hz, 1 H), 13.31 (bs, 1H). IR
(KBr) 3400,
3000, 2200, 1700, 1600, 1550, 1275 and1050 cm-', mass spectrum (EI), m/z 250.
Anal. Calcd. for C"H,oN205: C, 52.80; H, 4.03; N, 11.20. Found: C, 52.45; H,
3.88;
N, 11.03.
Step 3
N-[(2,2',3,3'4',6,6'-hepta-O-acetyl-(3-D-maltosyl]-4-(4-nitrilo-butoxy)-3-
nitro-
benzamide
The title compounds were prepared according to the procedure of Example 1,
Step 2 affording 66 % as a white solid, mp 110 °C; 'H NMR (CDC13) 8
2.01 (s, 3 H),
2.02 (s, 3 H), 2.03 (s, 3 H), 2.06 (s, 3 H), 2.08 (s, 3 H), 2.10 (s, 3 H),
2.13 (s, 3 H),
2.15 - 2.24 (m, 2 H), 2.69 (t, J = 7.0 Hz, 2 H), 3.89 - 4.13 (m, 4 H), 4.22 -
4.32 (m, 3
H), 4.47 (dd, J = 12.3, 2.4 Hz, 1 H), 4.85 - 4.89 (m, 2 H), 5.07 (apparent t,
J = 10.1
Hz, 1 H), 5.35 - 5.49 (m, 5 H), 6.96 (d, J = 9.2 Hz, 1 H), 7.14 (d, J = 8.8
Hz, 1H),
7.94 (dd, J = 8.8, 2.2, Hz, 1 H), 8.29 (d, J = 2.4 Hz, 1H). IR (KBr) 3400,
2950, 2200,
1750, 1250 and 1050 cm', mass spectrum (+FAB), m/z 868 (M + H), 890 (M + Na).
Anal. Calcd. for C"H,SN,O2,: C, 51.21; H, 5.23; N, 4.84. Found: C, 50.62; H,
5.15;
N, 4.66.
EXAMPLE 29
N-(4'. 6'-O-Benzvlidene-~fi-D-maltosyl)-4-(4-nitrilo-butoxy)-3-vitro-benzamide
Step 1
N-((3-D-maitosyl)-4-(4-nitrilo-butoxy)-3-vitro-benzamide
The title compound was prepared according to the procedure of Example 4,
Step 1 as a white solid, mp 144 - 145; 'H NMR (DMSO-d6) 2.03 - 2.09 (m, 2 H),
2.62
(t, J = 7.0 Hz, 2 H), 3.05 (t, J = 9.2 Hz, 2 H), 3.22 - 3.68 (m, 10 H), 4.28
(t, J = 5.7
Hz, 2 H), 4.95 (apparent t> J = 8.8 Hz, 1 H), 5.04 (d, J = 3.7 Hz, 1 H), 7.46
(d, J = 9.0


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Hz, 1 H), 8.17 (dd, J = 9.0, 2.0, Hz, 1 H}, 8.46 (d, J = 2.2 Hz, 1H), 9.10 (d,
J = 8.8
Hz, 1H). IR (KBr) 3400, 2900, 2200, 1650, 1545 and 1050 cm-', mass spectrum
(+FAB), m/z 574 (M + H), 596 (M + Na). Anal. Calcd. for C23H3,N3O'4 ~ 0.5 HZO:
C,
47.42; H, 5.54; N, 7.21. Found: C, 47.41; H, 5.61; N, 7.05.
Step 2
N-(4', 6'-O-Benzylidene-(3-D-maltosyl)-4-(4-nitrilo-butoxy)-3-vitro-benzamide
The title compound was prepared according to the procedure of Example 4,
Step 2 as a white solid (62 %), mp 165 - 170 °C; 'H NMR (CD30D-d,) 2.15
- 2.21
(m, 2 H), 2.69 (t, 7.0 Hz, 2 H), 3.44 - 3.62 (m, 5 H), 3.71 - 3.79 (m, 3 H),
3.82 - 3.92
(m, 3 H), 4.23 (dd, J = 10.1, 4.8 Hz, 1 H), 4.33 (apparent t, J = 5.7 Hz, 2
H), 5.13 -
5.18 (m, 1 H), 5.24 (d, J = 4.0 Hz, 1 H), 5.57 (s, 1H), 7.32 - 7.35 (m, 3H),
7.40 (d, J
= 9.0, Hz, 1 H), 7.47 - 7.51 (m, 2H), 8.17 (dd, J = 8.8, 2.2, Hz, 1 H), 8.45
(d, J = 2.4
Hz, IH), 9.09 (d, J = 8.8 Hz, 1H). IR (ICBr) 3400, 2900, 2250, 1650, 1525 and
1050
cm', mass spectrum (-FAB) m/z 660 (M - H). Anal. Calcd. for C3oH,sN3O" ~ 0.5
HZO:
C, 53.73; H, 5.41; N, 6.26. Found: C, 53.51; H, 5.46; N, 6.18.
EXAMPLE 30
N-(6-O-Benzoyl-4'. 6'-O-benzvlidene-(3-D-maltosvl)-4-l4-nitrilo-butoxy)-3-
nitro-
benzamide
The title compound was prepared according to the procedure of Example 6 as
a white solid, mp 174 - 176 °C; 'H NMR (DMSO-d6) 2.03 - 2.10 (m, 2 H),
2.64 (t, J =
7.2 Hz, 2 H), 3.28 - 3.76 (m, 8 H), 3.85 (bm, 1 H), 4.00 (dd, J = 9.9, 4.8,
Hz, 1 H),
4.29 (apparent t, J = 5.7 Hz, 1 H), 4.34 (dd, J = 12.3, 3.7, Hz, 1 H), 4.51
(d, J = 11.4,
Hz, 1 H), 5.09 (apparent t, J = 9.0 Hz, 1 H), 5.17 (d, J = 4.0 Hz, 1 H), 5.27
(d, J = 5.7
Hz, 1 H), 5.37 (d, J = 5.1 Hz, 1 H), 5.51 (s, 1 H), 5.69 (d, J = 2.0 Hz, 1 H),
5.85 (d, J
= 6.2 Hz, 1 H), 7.34 - 7.37 (m, 3 H) 7.39 - 7.43 (m, 2 H), 7.47 - 7.54 (m, 3
H), 7.63 -
7.67 (m, 1 H), 7.95 (d, J = 7.0 Hz, 1 H), 8.20 (dd, J = 8.8, 2.2, Hz, 1 H),
8.49 (d, J =
2.2 Hz, 1 H), 9.1 S (d, J = 8.8 Hz, 1 H}. IR (KBr) 3400, 2900, 2280, 1650,
1545,
1225, and 1070 cm ', mass spectrum (+FAB), m/z 788 (M + Na). Anal. Calcd. for
C3,H39CINZO,3 ~ 1.0 H20: C, 56.70; H, 5.27; N, 5.36. Found: C, 56.71; H, 5.06;
N,
5.34.


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EXAMPLE 31
N-(2.2'.3.3'-tetra-O-Acetyl-6-O-benzovl-4'. 6'-O-benz 1i~~3-D-maltosvl)-4-(4-
nitrilo-butoxy)-3-nitro-benzamide
The title compound was prepared according to the procedure of Example 8 as
a white solid (90 90), mp 222 - 224 °C; 'H NMR (CDCI,) 2.03 (s, 3H),
2.03 (s, 3H),
2.08 (s, 3H), 2.10 (s, 3H), 2.18 - 2.24 (m, 2 H), 2.68 (t, J = 6.8 Hz, 2 H),
3.53 - 3.62
(m, 2 H), 3.81 - 3.89 (m, 1 H), 3.96 - 4.04 (m, 2 H), 4.23 (apparent t, J =
9.7 Hz, 1
H), 4.28 (apparent t, J = 5.5 Hz, 1 H), 4.52 (dd, J = 12.5, 3.I, Hz, 1 H),
4.85 - 4.93
(m, 3 H), 5.40 (s, 1 H), 5.44 - 5.55 (m, 4 H), 6.87 (d, J = 9.0 Hz, 1 H), 7.11
(d, J =
8.8 Hz, 1 H), 7.31 - 7.34 (m, 3H) 7.37 - 7.40 (m, 2 H), 7.43 - 7.47 (m, 2 H},
7.55 -
7.59 (m, 1 H), 7.93 (dd, J = 8.8, 2.2, Hz, 1 H), 8.04 - 8.07 (m, 1 H), 8.24
(d, J = 2.4
Hz, 1 H). IR (KBr) 3400, 2900, 2230, 1750, 1650, 1545, 1250, and 1070 cm~',
mass
spectrum (+FAB), m/z 956 (M + Na).
EXAMPLE 32
N-f (2.2',3.3'4',6.6'-he~ta-O-acetyl-p-D-maltosvll-3-amino-4-f4-nitrilo-
butoxy)-
benzamide
The title compound was prepared according to the procedure of Example 2 as
a white solid (86 ~l~), mp 185 - 187 °C; 'H NMR (CDC13) S 2.00 (s, 3
H), 2.01 (s, 3
H), 2.03 (s, 3 H), 2.05 (s, 3 H), 2.08 (s, 3 H), 2.10 (s. 3 H), 2.13 (s, 3 H),
2.19 - 2.24
(m, 2 H), 2.59 (t, J = 7.0 Hz, 2 H), 3.84 - 4.07 (m, 4 H), 4.15 - 4.29 (m, 4
H), 4.44
(dd, J = 12.3, 2.4 Hz, 1 H), 4.85 - 4.90 (m, 2 H), 5.07 (t, J = 10.1 Hz, 1 H),
5.35 -
5.47 (m, 4 H), 6.73 - 6.77 (m, 2 H), 7.05 (dd, J = 8.35, 2.2 Hz, 1 H), 7.15
(d, J = 2.2
Hz, 1 H). IR (KBr) 3300, 2950, 2250, 1750, 1500, 1240 and 1050 cm', mass
spectrum (+FAB), m/z 838 (M + H), 860 (M + Na).
EXAMPLE 33
N-f l2, 2' .3.3' 4' .6.6' -hepta-O-acetyl-~3-D-maltosyll-3-acetvlamino-4-(4-
nitrilo-
butoxy)-benzamide
The title compound was prepared according to the procedure of Example 3 as
a White solid (98 9r ), mp 213 °C; 'H NMR (CDC13) 8 2.01 (s, 6 H), 2.03
(s, 3 H), 2.04
(s, 3 H), 2.08 (s, 3 H), 2.11 (s, 3 H), 2.15 (s. 3 H), 2.21 (s, 3 H), 2.25 -
2.28 (m, 2 H),


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2.58 - 2.62 (m, 2 H), 3.87 - 4.06 (m, 4 H), 4.21 - 4.27 (m, 4 H), 4.45 (dd, J
= 12.1,
2.2 Hz, 1 H), 4.86 - 4.94 (m, 2 H), 5.07 (apparent t, J = 10.1 Hz, 1 H), 5.35 -
5.49 (m,
4 H), 6.88 (d, J = 8.8 Hz, 1 H), 7.00 (d, J = 8.8 Hz, 1H), 7.60 (dd, J = 8.6,
2.2 Hz, 1
H), 8.08 (s, 1 H), 8.76 (d, J = 2.0 Hz, 1 H). IR (KBr) 3400, 2950, 2250, 1750,
1245
and 1050 cm', mass spectrum (+FAB), m/z 880 (M + H), 902 (M + Na). Anal.
Calcd.
for C39H49N3020 ~ C~ 53.24; H, 5.61; N, 4.78. Found: C, 52.83; H, 5.49; N,
4.67.
EXAMPLE 34
3-Acetvlamino-N-(6-O-benzoyl-4', 6'-O-benzvlidene-Q-D-maltosvl)-4-(4-nitrilo-
butoxyl-benzamide
The title compound was prepared according to the procedure of Example 6 as
a white solid (92 ~o), mp 238 °C; 'H NMR (DMSO-d6) 2.05 - 2.09 (m, 5
H), 2.75 (t, J
= 7.0 Hz, 2 H), 3.33 - 3.40 (m, 1 H), 3.50 - 3.66 (m, 7 H), 3.70 - 3.85 (bm, 1
H), 4.01
(dd, J = 9.9, 4.8, Hz, 1 H), 4.13 (apparent t, J = 5.1 Hz, 1 H), 4.34 (dd, J =
12.3, 3.7,
Hz, 1 H), 4.50 (d, J = 11.0, Hz, 1 H), 5.08 (apparent t, J = 8.8 Hz, 1 H),
5.13 - 5.16
(m, 2 H), 5.36 (d, J = 5.3 Hz, 1 H), 5.51 (s, 1 H), 5.65 (d, J = 1.8 Hz, 1 H),
5.85 (d, J
= 6.2 Hz, 1 H), 7.08 (d, J = 8.6 Hz, 1 H), 7.35 - 7.37 (m, 3 H) 7.40 - 7.43
(m, 2 H),
7.50 - 7.54 (m, 2 H), 7.63 - 7.70 (m, 2 H), 7.94 - 7.96 (m, 2 H), 8.41 (s, Hz,
1 H),
8.80 (d, J = 9.0 Hz, 1 H), 8.99 (s, 1 H). IR (KBr) 3400, 2900, 2280, 1650,
1545,
1225, and 1070 cm-', mass spectrum (+ESI), m/z 778 (M + H), (-ESI), m/z 776 (M
-
H). Anal. Calcd. for C39H43N3014 ~ 1.5 HzO: C, 58.21; H, 5.76; N, 5.22. Found:
C,
58.21; H, 5.64; N, 5.24.
EXAMPLE 35
N-(Hepta-O-acetyl-~i-D-maltosyl;i-6-chloropyridine-3-carboxamide
The title compound was prepared according to the procedure of Example l,
Step 2 affording a white solid, mp 190 °C; 'H NMR (CDCI3) b 2.01 (s, 3
H), 2.02 (s,
3 H), 2.03 (s, 3 H), 2.05 (s, 3 H), 2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3
H), 3.86 -
3.96 (m, 2 H), 4.00 - 4.07 (m, 2 H), 4.21 - 4.29 {m, 2 H), 4.47 (dd, J = 12.3,
2.4 Hz, 1
H), 4.84 - 4.89 (m, 2 H), 5.07 (apparent t, J = 10.1 Hz, 1 H), 5.34 - 5.49 (m,
4 H),
6.99 (d, J = 8.8 Hz, 1 H), 7.42 (dd, J = 8.3, 0.7 Hz, 1 H), 8.02 (dd, J = 8.3,
2.6, Hz, 1
H), 8.73 (dd, J = 2.6, 0.7 Hz, 1 H). IR (KBr) 3400, 2950, 1750, 1250 and 1050
cm',


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mass spectrum (+FAB), m/z 775 (M + H), 797 (M + Na). Anal. Calcd. for
C32H39N20(8 Cl ~ 1.0 HZO: C, 48.46; H, 5.21; N, 3.53. Found: C, 48.60; H,
4.95; N,
3.45.
EXAMPLE 36
N-lHepta-O-acetyl-Q-D-maltosvl)-2.6-dimethox~nvridine-3-carboxamide
The title compound was prepared according to the procedure of Example 1,
Step 2 affording a white solid, mp 125 -130 °C; 'H NMR (CDCl3) 8 1.98
(s, 3 H),
2.00 (s, 3 H), 2.03 (s, 6 H), 2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3 H),
3.86 - 3.99 (m,
2 H), 3.96 (s, 3 H), 4.01 - 4.06 (m, 2 H), 4.07 (s, 3 H), 4.22 - 4.30 (m, 2
H), 4.42 (dd,
J = 12.3, 2.6 Hz, 1 H), 4.87 (dd, J = 10.5, 4.0 Hz, 1 H), 4.99 (apparent t, J
= 9.4 Hz, 1
H), 5.06 (apparent t, J = 9.7 Hz, 1 H), 5.35 - 5.49 (m, 4 H), 6.45 (d, J = 8.3
Hz, 1 H),
8.35 (d, J = 8.4 Hz, 1 H), 8.37 (d, J = 8.8, Hz, 1 H). IR (KBr) 3400, 2950,
1750,
1400, 1250 and 1050 cni', mass spectrum (+FAB), m/z 801 (M + H), 823 (M + Na).
Anal. Calcd. for C~,H"NZO2o ~ 0.5 H20: C, 50.43; H, 5.60; N, 3.46. Found: -C,
50.64;
H, 5.52; N, 3.32.
EXAMPLE 37
N-lHepta-O-acet ELI-~3-D-maltosvl)-5-bromop5rridine-3-carboxamide
The title compound was prepared according to the procedure of Example l,
Step 2 affording a white solid, mp 167 - 170 °C; 'H NMR (CDC13) S 2.01
(s, 3 H),
2.03 (s, 6 H), 2.06 (s, 3 H), 2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3 H),
3.86 - 4.00 (m,
2 H), 4.02 - 4.07 (m, 2 H), 4.22 - 4.28 (m, 2 H), 4.47 (dd, J = 12.3, 2.4 Hz,
1 H), 4.85
- 4.90 (m, 2 H), 5.07 (apparent t, J = 9.7 Hz, 1 H), 5.35 - 5.49 (m, 4 H),
7.03 (d, J =
9.0 Hz, 1 H), 8.25 (t, J = 2.2 Hz, 1 H), 8.83 (s, 1 H). IR (KBr) 3300, 2950,
1750,
1250 and 1050 cm', mass spectrum (+FAB), m/z 819/821 (M + H), 841/843 (M +
Na). Anal. Calcd. for C32H39N2O,g BI: C, 46.90; H, 4.80; N, 3.42. Found: C,
46.77; H,
4.82; N, 3.14.


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EXAMPLE 38
N-(Hepta-O-acetyl-J3-D-maltosylr)-3-(trifluoromethvl)-benzamide
The title compound was prepared according to the procedure of Example 10
affording a white solid, mp 109-I 11 °C; 'H NMR (CDCl3) S 2.01 (s, 3
H), 2.02 (s, 3
H), 2.03 (s, 3 H), 2.06 (s, 3 H), 2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3 H),
3.88 - 3.96
(m, 2 H), 4.02 - 4.07 (m, 2 H), 4.21 - 4.29 (m, 2 H), 4.46 (dd, J = 12.3, 2.4
Hz, 1 H),
4.86 - 4.91 (m, 2 H), 5.07 (t, J = 10.1 Hz, 1 H), 5.35 - 5.50 (m, 4 H), 6.96
(d, J = 9.0
Hz, 1 H), 7.59 (t, J = 7.7 Hz, 1 H), 7.80 (d, J = 7.7 Hz, 1 H), 7.88 (d, J =
7.9 Hz, 1 H)
8.05 (s, 1 H). IR (ICBr) 3400, 2930, 1750, 1550, 1245 and 1050 crri ', mass
spectrum
(+FAB}, m/z 808 (M + H), 830 (M + Na). Anal. Calcd. for C~H4oF3N0,e: C, 50.56;
H,4.99; N, I .73. Found: C, 49.97; H,4.87; N, 1.68.
EXAMPLE 39
N-(4'.6'-O-Benzylidene- (~-D-maltosyl)-3-(trifluoromethvl l-Benzamide
I S Step 1
N-((3-D-Maltosyl)-3-(trifluoro-methyl)-6enzamide
The title compound was prepared according to the procedure of Example 4,
Step I affording a white solid, mp 158-159 °C; 'H NMR (DMSO-d6) 8 3.06
(apparent
t, J = 9.0 Hz, 2 H), 3.21- 3.71 (m, 17 H), 4.97 (d, J = 3.7 Hz, 1 H), 5.01 (d,
J = 8.8
Hz, 1 H), 7.63 (t , J = 7.7 Hz, 1 H), 7.79 (d, J = 7.7 Hz, 1 H), 8.19 (d, J =
7.9 Hz, 1
H), 8.26 (s, 1 H). IR (KBr) 3400, 2930, 1675, 1550, 1350 and1075 cm ', mass
spectrum (+FAB), m/z 514 (M + H), 536 (M + Na). Anal. Calcd. for CZOHz6F,NO" ~
2
H20: C,43.72; H, 5.50; N, 2.55. Found: C, 43.38; H, 5.06; N, 2.4.
Step 2
N-(4',6'-O-Benzylidene-~3-D-maltosyl)-3-(trifluoromethyl)-Benzamide
The title compound was prepared according to the procedure of Example 4
Step 2 affording a white solid, mp 230 °C decomposed; 'H NMR (DMSO-db)
3.32 -
3.48 (m, 4 H), 3.50 - 3.60 (m, 4 H), 3.61 - 3.78 (m, 3 H), 4.67 (bs, 1 H),
5.02 (t , J =
9.0 Hz, 1 H), 5.15 - 5.17 (m, 2 H), 5.32 (d, J = 0.6 Hz, 1 H), 5.58 (s, 1 H),
5.61 (d, J
= 2.2 Hz, I H), 5.71 (d, J = 6.4 Hz, 1 H), 7.32 - 7.40 (m, 3 H), 7.4I - 7.47
(m, 2 H),
7.74 (t, J = 7.9, 1 H), 7.92 (d, J = 7.7 Hz, 1 H), 8.21 (d, J = 7.7 Hz, l H),
8.28 (s, 1 H),


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9.2 (d, J = 8.8 Hz, 1 H). IR (ICBr) 3400, 2930, 1700, 1550, 1255, and 1075
cm'', mass
spectrum (+FAB), m/z 602 (M + H), 624 (M + Na). Anal. Calcd. for C27H3oF,N0"
0.5 H20: C, 53.12; H, 5.08; N, 2.29. Found: C, 52.82; H, 5.05; N, 2.41.
EXAMPLE 40
N-f ~~6-O-Benzo~l-4'.6'-O-benzvlidenel-~3-D-maltosyll-3-(trifluoromethyl?-
benzamide
The title compound was prepared according to the procedure of Step 6 affording
a
white solid, mp 190 °C decomposed; 'H NMR (DMSO-db) 8 3.28 - 3.76 (m, 8
H),
3.86 (bs, 1 H), 4.01 (dd, J = 9.9, 4.6 Hz, 1 H), 4.30 (dd, J = 12.3, 4.0 Hz, 1
H), 4.51
(d, J = 11.4 Hz, 1 H), 5.17 (aparant t, J = 3.7 Hz, 1 H), 5.29 (d, J = 5.5 Hz,
1 H), 5.37
(d, J = 5.1 Hz, 1 H), 5.51 (s, 1 H), 5.69 (d, J = 2.0 Hz, 1 H), 5.87 (d, J =
5.9 Hz, 1 H),
7.33 - 7.40 (m, 3 H), 7.41 - 7.43 (m, 2 H), 7.52 (t, J = 7.7 Hz, 2 H), 7.65
(t, J = 7.5
Hz, 1 H), 7.72 (t, J = 7.9, Hz, 1 H), 7.92 (d, J = 7.1 Hz, 1 H), 7.95 (d, J =
7.3 Hz, 1
H), 8.24 (d, J = 2.2 Hz, 1 H), 8.27 (s, 1 H), 9.26 (d, J = 8.8 Hz, 1 H).IR
(KBr) 3400,
2930, 1735, 1550, 1300, and 1075 cm-', mass spectrum (+FAB), m/z 706 (M + H},
728 (M + Na). Anal. Calcd. for C34H34F3N012 ~ 0.5 HZO: C, 57.14; H, 4.94; N,
1.96.
Found: C, 57.29; H. 4.88; N,1.99.
EXAMPLE 41
N-(Henta-O-acetyl-Q-D-maltosvl)-6-methvlnvridine-3-carboxamide
The title compound was prepared according to the procedure of Example 1
Step 2 affording a white solid, mp 115 °C; 'H NMR (CDCl3) S 2.01 (s, 6
H), 2.03 (s,
3 H), 2.U5 (s, 3 H), 2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3 H), 2.63 (s, 3
H), 3.86 -
4.00 (m, 2 H), 4.02 - 4.11 (m, 2 H), 4.21 - 4.29 (m, 2 H), 4.46 (dd, J = 12.1,
2.6 Hz, 1
H), 4.85 - 4.91 (m, 2 H), 5.07 (apparent t, J = 10.1 Hz, 1 H), 5.34 - 5.48 (m,
4 H),
7.03 (d, J = 8.6 Hz. 1 H), 7.30 (d, J = 7.9 Hz, 1 H}, 7.97 (dd, J = 8.1, 2.4
Hz, 1H),
8.86 (d, J = 2.0 Hz. 1 H). IR (ICBr) 3400. 2950, 1750, 1250 and 1050 cm-',
mass
spectrum (+FAB), m/z 755 (M + H), 777 (M + Na). Anal. Calcd. for C33H,,N20'8
0.5: C, 51.90; H, 5.68; N, 3.67. Found: C, 51.99; H, 5.63; N, 3.55.


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EXAMPLE 42
4-Butox,~r-3.5-dichloro-N-~f3-D-maltosyl-benzamide
The title compound was prepared according to the procedure of Example 4,
Step 1 affording a white solid, mp 210 °C decomposed; 'H NMR (DMSO
d6)
8 0.94 (t, J = 7.3 Hz, 4 H), 1.47 - 1.52 (m, 2 H), 1.72 - 1.79 (m, 2 H), 3.02 -
3.07 (m,
1 H), 3.22 -3.70 (m, 11 H), 4.04 (t, J = 6.4, 2 H), 4.46 -4.52 (m, 2 H), 4.88 -
4.95 (m,
3 H), 5.04 (d, J = 3.7 Hz, 1 H), 5.13 (d, J = 5.5 Hz, 1 H), 5.48 (d, J = 5.9
Hz, 1 H),
5.59 (d, J = 3.8 Hz, 1 H), 8.01 (s, 2 H ), 9.06 (d, J = 8.8 Hz, 1 H). IR (KBr)
3400,
2930, 1600, 1550, and 1075 cm'', mass spectrum (+FAB), m/z 586/588/590 (M +
H),
608/610/612 (M + Na). Anal. Calcd. for C23H33C12NO,2: C, 47.11; H, 5.67; N,
2.39.
Found: C, 46.78; H, 5.74; N, 2.39.
EXAMPLE 43
N-(4' .6'-O-Benzvlidene-(3-D-maltosvl)-4-butoxy-3.5-dichloro-benzamide
The title compound was prepared according to the procedure of Example 4,
Step 2 affording a white solid, mp 105-107 °C; 'H NMR (DMSO) 8 0.94 (t,
J = 7.5
Hz, 3 H), 1.47 -1.53 (m, 2 H), 1.72 - 1.77 (m, 2 H), 3.34 - 3.41 (m, 4 H},
3.48 - 361
(m, 9 H), 3.64 - 3.74 (m, 3 H), 4.04 (t, J = 6.4 Hz, 2 H), 4.12 (dd, J = 9.2,
4.2 Hz, 1
H), 4.95 (t, J = 8.8 Hz, 1 H), 5.16 (d, J = 3.7 Hz, 1 H), 5.57 (s, 1 H), 7.36 -
7.38 (m,
3 H), 7.43 - 7.46 (m, 2 H), 8.02 (s, 2 H), 9.09 (d, J = 8.8 Hz, 1 H}. IR (KBr)
3400,
2930, 1550, 1450, 1350, 1255 and 1075 cm', mass spectrum (+FAB), m/z 696/698
(M + Na). Anal. Calcd. for C3oH3,C12NO,2 ~ 1.5 HzO: C, 51.36; H, 5.75; N,
2.00.
Found: C, 51.25; H, 5.46; N, 2.12.
EXAMPLE 44
N-(Henta-O-acetyl_~i-D-maltosyl)-3-chloro-4-methoxy-benzamide
The title compound was prepared according to the procedure of Example 10
affording a white solid, mp 106 - 110 °C; 'H NMR (CDCl3) 8 2.01 (s, 6
H), 2.03 (s, 3
H), 2.05 (s, 3 H), 2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3 H), 3.86 - 4.07
(m, 4 H), 3.95
(s, 3 H), 4.21 - 4.29 (m, 2 H), 4.45 (dd, J = I2.3, 2.4 Hz, 1 H), 4.85 - 4.90
(m, 2 H),
5.07 (apparent t, J = 10.1 Hz, 1 H), 5.35 - 5.48 (m, 4 H), 6.78 (d, J = 9.2
Hz, 1 H),
6.86 (d, J = 8.6 Hz, 1 H), 7.61 (dd, J = 8.6, 2.2 Hz, 1 H), 7.81 (d, J = 2. 2
Hz, 1 H).


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IR (KBr) 3400, 2950, 1750, 1250 and 1050 cm-', mass spectrum (+ESI}, m/z 804
(M
+ H), 821.1 (M + NH4).
EXAMPLE 4S
N-(2.2'.3.3'.4'.6.6'-hepta-O-acet ~~1-~3-D-maltose)-1-f3,4-dimethoxy)-phenyl-
acetami
The title compound was prepared according to the procedure of Example 10
affording a white solid, mp 95 - 97°C; 'H NMR (CDCl3) 8 1.83 (s, 3 H),
1.98 (s, 3
H), 1.99 (s, 6 H), 2.02 (s, 3 H), 2.04 (s, 3 H), 2.09 (s, 3 H), 2.12 (s, 3 H),
3.47 (ABq,
J = 15.6, ~8 = 0.03, 2 H), 3.75 - 3.79 (m, 1 H), 3.87 - 3.94 (m, 7 H), 4.02
(dd, J =
12.3, 2.4 Hz, 1 H), 4.20 {t, J = 3.5 Hz, 1 H), 4.23 (t, J = 3.7 Hz, 1 H), 4.
41 (dd, J =
10.5, 3.9 Hz, 1 H), 5.04 (t, J = 9.7 Hz, 1 H), 5.21 (aparant t, J = 9.7 Hz, 1
H), 5.29 -
5.36 (m, 3 H), 6.06 (d, J = 9.2 Hz, 1 H), 6.71 - 6.75 (m, 2 H), 6.83 (d, J =
8.12 Hz, 1
H). IR (KBr) 3400, 2930, 1750, 1530, 1245 and 1050 cm ', mass spectrum (+FAB),
m/z 814 (M + H), 836 (M + Na).
EXAMPLE 46
N-l4'.6'-Benzvlidene-~3-D-maltosyl)-2-(3.4-dimethoxv-phenyl)-acetamide
Step 1
N-(~3-D-maltosyl)-2-(3,4-dimethoxy-phenyl)acetamide
The title compound was prepared according to the procedure of Example 4,
Step 1 affording a white solid, mp 210-213°C; 'H NMR (DMSO-db) 8 3.02 -
3.64 (m,
20 H), 4.72 (t, J = 9.0 Hz, 1 H), 5.01 (d, J = 3.7 Hz, 1 H), 6.75 (dd, J =
8.3, 1.7 Hz, 1
H), 6.83 - 6.88 (m, 2 H), 8.57 (d, J = 9.2 Hz, 1 H). IR (KBr) 3400, 2930,
1675, 1530,
1265 and 1050 cm-', mass spectrum (-FAB), m/z 518 (M - H). Anal. Calcd. for
C2zH33NO'3: C, 50.87; H, 6.40; N, 2.70. Found: C, 50.59; H, 6.44; N, 2.60.
Step 2
N-(4',6'-Benzylidene-/i-D-maltosyl)-2-(3,4-dimethoxy-phenyl)-acetamide
The title compound was prepared according to the procedure of Example 4,
Step 2 affording a white solid, mp 200 - 205 dec. °C; 'H NMR (DMSO-d6)
b 3.13 -
3.70 (m, 19 H), 4.10 (dd, J = 9.0, 4.0 Hz, 1 H), 4.60 (aparant t, J = 5.5 Hz,
1 H), 4.74


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(aparant t, J = 9.0 Hz, 1 H), 5.01 (d, J = 6.2 Hz, 1 H), 5.14 (d, J = 3.7 Hz,
1 H), 5.31
(d, J = 5.3 Hz, 1 H), 5.55 (d, J = 4.6 Hz, 2 H), 5.70 (d , J = 6.6 Hz, 1 H),
6.76 (dd, J =
8.1, 1.8 Hz, 1 H), 6.83 - 6.89 (m, 2 H), 7.34 - 7.36 (m, 3 H), 7.42 - 7.45 (m,
2 H),
8.58 (d, J = 9.2 Hz, I H). IR (KBr) 3400, 2930, 1750, 1550, 1245 and1075 cm~',
mass spectrum (-FAB), m/z 606 (M - H).
EXAMPLE 47
N-(6-O-Benzovl-4'.6'-O-benzylidene-~3-D-maltosyll-2-(3,4-dimethoxy-pheny~-
acetamide
The title compound was prepared according to the procedure of Example 6
affording a white solid, mp 205 - 207 °C; 'H NMR (DMSO-d6)
8 3.28 - 3.50 (m, 5 H), 3.52 - 3.68 (m, 5 H), 3.71- 3.97 (m, 1 H), 3.67 (s, 3
H), 3.69
(s, 3 H}, 3.99 (dd, J = 9.9, 4.8 Hz, 1 H), 4.30 (dd, J = 12.3, 4.20 Hz, 1 H),
4.46 (d, J
= 11 Hz, 1 H), 4.85 (aparant t, J = 9.0 Hz, 1 H), 5.14 (d, J = 4.6 Hz, 2 H),
5.34 (d, J =
5.1 Hz, 1 H), 5.50 (s, 1 H), 5.62 (d, J = 2.6 Hz, I H), 5.84 (d, J = 6.2 Hz, 1
H), 6.74
(dd, J = 8.3, 2.0 Hz, 1 H), 6.80 (d, J = 8.1 Hz, 1 H), 6.86 (d, J = 2.0 Hz, 1
H), 7.33 - 7
50 (m, 5 H), 7.52 (t, J = 7.9 Hz, 1 H), 7.63 - 7.67 (m, 2 H), 7.95 (dd, J =
7.0, 1.3 Hz,
2 H), 8.66 (d, J = 9.0 Hz, 1 H).
IR (KBr) 3400, 2930, 1750, 1550, 1245 and1075 cm~', mass spectrum (+ESI), m/z
712 (M + H), 734 (M + Na}. Anal. Calcd. for C36H"N0,4~ 1.5 H20: C, 58.53; H,
5.87;
N, 1.90. Found: C, 58.93; H,5.77; N, 1.78.
EXAMPLE 48
N-(Hepta-O-acetyl- 3~-D-maltosvl)-2-f4-h dv roxy-3-nitro-phenyl)-acetamide
The title compound was prepared according to the procedure of Example 13,
Step 3 affording a white solid, mp 106 °C; 'H NMR (CDCI3) 8 1.93 (s, 3
H), 2.00 (s,
3 H), 2.01 (s, 3 H), 2.02 (s, 3 H}, 2.05 (s, 3 H), 2.09 (s, 3 H), 2.13 (s, 3
H), 3.51
ABq, J = 15.8 Hz. D8 = 0.30, 2 H, 3.76 - 3.80 (m, 1 H), 3.89 - 3.96 (m, 2 H),
4.03
(dd, J = 12.5, 2.2 Hz, 1 H), 4.22 (dd, J = 12.5, 4.0 Hz, 1 H), 4.43 (dd, J =
12.3, 2.2
Hz, 1 H), 4.67 (apparent t, J = 9.7 Hz, 1 H), 5.05 (apparent t, J = 10.1 Hz, 1
H), 5.20
(apparent t, J = 9.2 Hz, 1 H), 5.32 - 5.38 (m, 3 H), 6.15 (d, J = 9.0 Hz, 1
H), 7.15 (d,
J = 8.6 Hz, 1 H), 7.46 (dd, J = 8.6, 2.0 Hz, 1 H), 7.95 (d, J = 2.0 Hz, 1 H),
10.5 (d, J


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= 0.4 Hz, 1 H). IR (KBr) 3400, 2950, 1750, 1250 and 1050 cm'', mass spectrum
(+FAB), m/z 815 (M + H), 837 (M + Na).
EXAMPLE 49
N-12.2'.3.3'.4'.6,6'-Hepta-O-acetvl-p-maltosyl?-4-butoxv-3.5-dichloro-
benzylamide
The title compound was prepared according to the procedure of Example 10
affording a white solid, mp 104-105 °C; 'H NMR (CDC13) 8 0.99 (t, J =
7.5 Hz, 3 H),
1.52 - 1.60 (m, 2 H), 1.81 - 1.87 (m, 2 H), 2.01 (s, 3 H), 2.03 {s, 6 H), 2.06
(s, 3 H),
2.08 (s, 3 H), 2.10 (s, 3 H), 2.13 (s, 3 H), 3.84 - 3.94 (m, 2 H), 3.95 - 4.08
(m, S H),
4.22 - 4.27 (m, 2 H), 4.46 (dd, J = 12.1, 2.4 Hz, 1 H), 4.83 - 4.89 (m, 2 H),
5.07
(apparent t, J = 9.4 Hz, 1 H), 5.34 - 5.47 (m, 3 H), 6.77 (d, J = 9.23 Hz, 1
H), 7.78 (s,
2 H}. IR (KBr) 3400, 2930, 1750, 1550, 1325, 1245 and 1075 cm', mass spectrum
(+FAB), m/z 880/882/884 (M + H), 902/904/906 (M + Na). Anal. Calcd. for
C3,H"C12NO~9: C, 50.46; H, 5.38; N, 1.59. Found: C, 50.01; H, 5.39; N, 1.58.
EXAMPLE 50
N-(2.2',3.3'.4'.6.6'-hepta-O-acet~rl-~i-D-maltosyl)-2-(4-chloro-3-nitro-
nhenvll-
acetamide
The title compound was prepared according to the procedure of Example 13,
Step 3 affording a white solid, mp 103 °C; 'H NMR (CDC13) b 1.93 (s, 3
H), 2.00 (s,
3 H), 2.01 (s, 3 H), 2.02 (s, 3 H), 2.06 (s, 3 H), 2.09 (s, 3 H), 2.13 (s, 3
H), 3.51 {q, J
= 15.2 Hz, 2 Hi. 3.76 - 3.80 (m, 1 H), 3.90 - 3.97 (m, 2 H), 4.04 (dd, J =
12.5, 2.2
Hz, 1 H), 4.20 - 4.24 (m, 2 H), 4.44 (dd, J = 12.1, 2.4 Hz, 1 H), 4.69
(apparent t, J =
9.4 Hz, 1 H}, 4.85 (dd, J = 10.5, 4.2 Hz, 1 H), 5.05 (apparent t, J = 10.1 Hz,
1 H),
5.20 (apparent t, J = 9.2 Hz, 1 H), 5.32 - 5.38 (m, 3 H), 6.23 (d, J = 9.0 Hz,
1 H),
7.41 (dd, J = 8.3, 2.2 Hz, 1 H), 7.53 (d, J = 8.1 Hz, 1 H), 7.75 (d, J = 2.0
Hz, 1 H).
IR (KBr) 3400, 2950, 1750, 1245 and 1050 cm-', mass spectrum (+FAB), m/z 833
(M
+ H), 855 (M + Na). Anal. Calcd. for C3,H4,C1NZOZO: C, 49.02; H, 4.96; N,
3.36.
Found: C, 48.67; H, 5.06; N, 3.19.


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EXAMPLE 51
2-f3-Acetyl-amino)-4-chloro-phenvll-N-f6-O-benzovl-4'.6'-O-benzvlidene- i-D-
maltosvl)-acetamide
The title compound was prepared according to the procedure of Example 6
affording
a white solid, 'H NMR (DMSO-d6) 8 2.05 (s, 3 H), 3.21 - 3.75 (m, 11 H), 3.99
(dd, J
= 9.9, 4.8 Hz, 1 H), 4.31 (dd, J = 12.3, 4.0 Hz, 1 H}, 4.45 (d, J = 10.8 Hz, 1
H), 4.84
(apparent t, J = 9.0 Hz, I H), 5.13 - 5.15 (m, 2 H), 5.34 (d, J = 5.3 Hz, 1
H), 5.50 (s,
1 H), 5.63 (d, J = 2.6 Hz, 1 H), 5.83 (d, J = 6.2 Hz, 1 H), 7.06 (dd, J = 8.3,
2.0 Hz, 1
H), 7.33 - 7 42 (m, 6 H), 7.49 - 7.56 (m, 3 H), 7.63 - 7.68 (m, 1 H), 7.95
(dd, J = 8.6,
1.1 Hz, 2 H), 8.74 (d, J = 9.0 Hz, 1 H), 9.45 (s, 1 H).
IR (KBr) 3400, 2930, 1750, 1550, 1245 and 1075 cm~', mass spectrum (+FAB), m/z
765/767 (M + Na).

Representative Drawing