US 6,800,660 B2 · Taxol enhancer compounds

Abstract

Disclosed is a compound represented by the Structural Formula (I): Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C═Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R7R8)—. R1 and R2 are independently an aryl group or a substituted aryl group, R3 and R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R5-R6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R7 and R8 are each independently —H, an aliphatic or substituted aliphatic group, or R7 is —H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent. Also disclosed is a method of treating a subject with cancer by administering to the subject a compound of Structural Formula (I) in combination with taxol or an analog of taxol.

Claims117

Dependent claims

A compound represented by the following structural formula:

or a pharmaceutically acceptable salt thereof, wherein:
Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group, or, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group;
R1 and R2 are independently an aryl group or a substituted aryl group;
R3 and R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group;
R5-R6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group;
and
Z is ═O or ═S;
provided that when Y is —CH2—, R3 and R4 are both phenyl and R5-R6 are all —H, then R1 and R2 are not both phenyl.

5 more elements

A compound represented by the following structural formula:

or a physiologically acceptable salt thereof, wherein
a) R1 and R2 are both phenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
b) R1 and R2 are both phenyl;
R3 and R4 are both ethyl;
R7 and R8 are both —H;
c) R1 and R2 are both 4-cyanophenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
d) R1 and R2 are both 4-methoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
e) R1 and R2 are both phenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
f) R1 and R2 are both phenyl;
R3 and R4 are both ethyl;
R7 is methyl;
R8 is —H;
g) R1 and R2 are both 4-cyanophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
h) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
i) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is—H;
j) R1 and R2 are both 3-cyanophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
k) R1 and R2 are both 3-fluorophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
l) R1 and R2 are both 4-chlorophenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
m) R1 and R2 are both 2-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
n) R1 and R2 are both 3-methoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
o) R1 and R2 are both 2,3-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
p) R1 and R2 are both 2,3-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is—H;
q) R1 and R2 are both 2,5-difluorophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
r) R1 and R2 are both 2,5-difluorophenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
s) R1 and R2 are both 2,5-dichlorophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
t) R1 and R2 are both 2,5-dimethyLphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
u) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
v) R1 and R2 are both phenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
or
w) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H.

76 more elements

A pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula:

or physiologically acceptable salt thereof, wherein:
a) R1 and R2 are both phenyl;
R3 and R4 are both phenyl;
R7 and R8 are both —H;
b) R1 and R2 are both phenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
c) R1 and R2 are both phenyl;
R3 and R4 are both ethyl;
R7 and R8 are both —H;
d) R1 and R2 are both 4-cyanophenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
e) R1 and R2 are both 4-methoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
t) R1 and R2 are both phenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
g) R1 and R2 are both phenyl;
R3 and R4 are both ethyl;
R7 is methyl;
R8 is —H;
h) R1 and R2 are both 4-cyanophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
i) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
j) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8is —H;
k) R1 and R2 are both 3-cyanophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
l) R1 and R2 are both 3-fluorophenyl;
R3 and R3 are both methyl;
R7 and R8 are both —H;
m) R1 and R2 are both 4-chlorophenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
n) R1 and R2 are both 2-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
o) R1 and R2 are both 3-methoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
p) R1 and R2 are both 2,3-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
q) R1 and R2 are both 2,3-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
r) R1 and R2 are both 2,5-difluorophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
s) R1 and R2 are both 2,5-difluorophenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
t) R1 and R2 are both 2,5-dichlorophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
u) R1 and R2 are both 2,5-dimethylphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
v) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
w) R1 and R2 are both phenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
or
x) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H.

79 more elements

A method of treating a subject with cancer, said method comprising administering to the subject an effective amount of taxol or a taxol analog and an effective amount of a compound represented by the following structural formula:

or physiologically acceptable salt thereof, wherein:
a) R1 and R2 are both phenyl;
R3 and R4 are both phenyl;
R7 and R8 are both —H;
b) R1 and R2 are both phenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
c) R1 and R2 are both phenyl;
R3 and R4 are both ethyl;
R7 and R8 are both —H;
d) R1 and R2 are both 4-cyanophenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
e) R1 and R2 are both 4-methoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
f) R1 and R2 are both phenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
g) R1 and R2 are both phenyl;
R3 and R4 are both ethyl;
R7 is methyl;
R8 is —H;
h) R1 and R2 are both 4-cyanophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
i) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
j) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
k) R1 and R2 are both 3-cyanophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
l) R1 and R2 are both 3-fluorophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
m) R1 and R2 are both 4-chlorophenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
n) R1 and R2 are both 2-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
o) R1 and R2 are both 3-methoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
p) R1 and R2 are both 2,3-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
q) R1 and R2 are both 2,3-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
r) R1 and R2 are both 2,5-difluorophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
s) R1 and R2 are both 2,5-difluorophenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H;
t) R1 and R2 are both 2,5-dichlorophenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
u) R1 and R2 are both 2,5-dimethylphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
v) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
w) R1 and R2 are both phenyl;
R3 and R4 are both methyl;
R7 and R8 are both —H;
or
x) R1 and R2 are both 2,5-dimethoxyphenyl;
R3 and R4 are both methyl;
R7 is methyl;
R8 is —H.

79 more elements

Dependencies are inferred from the claim text.

Taxol enhancer compounds

Life of this patent

Taxol enhancer compounds

Life of this patent

Abstract

Claims117