US 2004/0006058 A1 · DIAMINOTHIAZOLES

Abstract

The present invention is directed to novel diaminothiazoles of formula 1 These compounds inhibit cyclin-dependent kinase 4 (Cdk4) and are selective against Cdk2 and Cdk1. These compounds and their pharmaceutically acceptable salts and esters have antiproliferative activity and are useful in the treatment or control of cancer, in particular solid tumors. This invention is also directed to pharmaceutical compositions containing such compounds and to methods of treating or controlling cancer, most particularly the treatment 6r control of breast, lung and colon and prostate tumors.

Claims63

Dependent claims

A compound of formula

334
wherein,
O—R1 represents a group selected from
335
R2 and R3 are independently selected from the group consisting of
H,
lower alkyl, and
halogen;
R4 is selected from the group consisting of
lower alkyl,
lower alkyl-cycloalkyl,
cycloalkyl,
O-lower alkyl,
halogen,
NO2,
S-lower alkyl
CF3, and
CN;
R5 is selected from the group consisting of
H,
O-lower alkyl,
lower alkyl,
halogen, and
OH,
or alternatively, R4 and R5 together with the two carbon atoms and bond between them from the benzene ring (C) to which R4 and R5 are attached can form a ring having 5-7 atoms, said 5-7 atom ring optionally including one or two heteroatoms and being optionally substituted by C1-C4-alkyl;
R6 and R7 are each independently selected from the group consisting of
H,
lower alkyl,
lower alkyl substituted by OH, and
COOR12,
or, alternatively, the group —NR6R7 can be a ring having 5-7 atoms, said ring optionally including one or two additional heteroatoms and being optionally substituted by lower alkyl;
R8 and R9 are each independently selected from the group consisting of
H, and
lower alkyl;
R10 is selected from the group consisting of
H,
lower alkyl,
lower alkyl substituted by OH, and
COOR 12;
R11 is selected from the group consisting of
H,
lower alkyl, and
lower alkyl substituted by OH;
and
COOR12,
R12 is lower alkyl;
m is 1 or 2;
n is 0, 1 or 2;
provided that when m is 2 and R4 is F, R5 is not H, and provided further that when m is 2 and R4 is lower alkyl, R5 is not OH;
or a pharmaceutically acceptable salt or ester thereof.

47 more elements

Dependencies are inferred from the claim text.

Diaminothiazoles

Life of this patent

Diaminothiazoles

Life of this patent

Abstract

Claims63