US 6,440,959 B1 · Pyrazolobenzodiazepines

Abstract

Disclosed are novel pyrazolobenzodiazepines having the formula and the pharmaceutically acceptable salts thereof, wherein R1, R2, R3 and R4 are as defined herein. These compounds inhibit cyclin-dependent kinases (CDKs), in particular CDK2. These compounds and their pharmaceutically acceptable salts, and prodrugs of said compounds, are anti-proliferative agents useful in the treatment or control of cell proliferative disorders, in particular cancer, more particularly, the treatment or control of breast, colon, lung and prostate tumors. Also disclosed are pharmaceutical compositions containing the compounds of formula I as well as intermediates useful in the preparation of the compounds of formula I.

Claims45

Dependent claims

A compound having the formula:

and the pharmaceutically acceptable salts thereof, wherein:
R1 is selected from the group consisting of
—H,
—NO2,
—CN,
-halogen,
-lower alkyl which is straight-chained and which optionally may be substituted by the group consisting of —OH and halogen,
—OR5,
—R6OR7,
—COOR7,
—CONR8R9,
—NR10R11,
—NHCOR12, and
—NHSO2R13;
R2 and R4 are each independently selected from the group consisting of
—H,
-halogen,
—NO2,
—CF3, and
-straight chained lower alkyl;
R3 is selected from the group consisting of
—H,
-lower alkyl which optionally may be substituted by —OH,
—OR9, F, and aryl,
-cycloalkyl,
-aryl,
-heterocycle,
-heteroaryl,
—COOR7
—CN,
-alkenyl,
—CONR8R9, and
-alkynyl;
R5 is selected from lower alkyl which optionally may be substituted by halogen;
R6 is selected from lower alkylene;
R7 is selected from the group consisting of —H and lower alkyl;
R8 and R9 are each independently selected from the group consisting of —H and -lower alkyl which itself optionally may be substituted by —OH and —NH2;
alternatively, R8 and R9 may form a 5- or 6-membered heterocycle which optionally may be substituted by the group consisting of —OH, —NH2, and lower alkyl;
R10, R11 and R12 are each independently selected from the group consisting of —H and lower alkyl;
R13 is selected from the group consisting of lower alkyl which optionally may be substituted by the group consisting of halogen and —NR14R15;
and
R14 and R15 are each independently selected from the group consisting of —H and lower alkyl which optionally may be substituted halogen, or alternatively, —NR14R15 is a heterocycle.

39 more elements

Dependencies are inferred from the claim text.

Pyrazolobenzodiazepines

Life of this patent

Pyrazolobenzodiazepines

Life of this patent

Abstract

Claims45