# US 6,720,346 B2 · Thiazole benzamide derivatives and pharmaceutical compositions for inhibiting cell proliferation

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- Number: US 6,720,346 B2
- Document ID: US6720346B2
- Status: Granted
- Kind: B2
- Application number: 10/190,219
- Filed: 2002-07-05
- Published: 2003-12-04
- Granted: 2004-04-13
- Earliest claimed: 2001-07-06
- Assignees: Agouron Pharmaceuticals, Inc.
- Inventors: Shao Song Chu; Larry Andrew Alegria; Ted Michael Bleckman; Wesley Kwan Mung Chong; Rohit K. Duvadie; Lin Li; Siegfried Heinz Reich; William Henry Romines, III; Michael B. Wallace; Yi Yang
- Web page: https://patentgrep.com/patent/US6720346B2

## CPC

- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/06: Antianaemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/06: Antiarrhythmics
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/08: of the prostate
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/10: for osteoporosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 27/16: Otologicals
- A61P 29/02: without antiinflammatory effect
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 31/18: for HIV
- A61P 31/20: for DNA viruses
- A61P 31/22: for herpes viruses
- A61P 33/00: Antiparasitic agents
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/04: Immunostimulants
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 233/56: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D 277/42: Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D 491/10: Spiro-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Aminothiazole compounds with mono-/di-substituted benzamide are represented by the Formula (I), and their pharmaceutically acceptable salts, pharmaceutically acceptable prodrugs, pharmaceutically active metabolites, and pharmaceutically acceptable salts of said metabolites are described. These agents modulate and/or inhibit the cell proliferation and activity of protein kinases and are useful as pharmaceuticals for treating malignancies and other disorders.

## Claims

### Claim 1

A compound represented by Formula (I):
wherein:
R1 and R2 are each independently hydrogen, or —CH2—R10, a C2-C11 alkyl, alkenyl, alkynyl, heteroalkyl, alkoxy, amino alkyl, aryl, or cycloalkyl group unsubstituted or substituted with one or more R10 substituents selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—RaO—, —ORb, —CO—Rc, O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—ORc, ═O, ═S, SO2—Rc, —SO—Rc, —NRdRc, —CO—NRdRe, —O—CO—NRdRe, —NRc—CO—NRdRe, —NRc—CO—Re, NRc—CO—ORe, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO2—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, O—CSO2—Rc, —SO2—NRdRe, —SO—NRdRe, —S—NRdRc, —NRd—CSO2—Rd, —NRc—CSO—Rd, NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, and Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRc, —CO—NRdRe, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are defined above, where R1 and R2 are not both hydrogen; or
R1 or R2, together with the
and two adjacent carbon atoms of the phenyl ring of Formula (I), forms a 5- or 6-membered ring structure fused to the phenyl ring of Formula (I) and unsubstituted or substituted with one or more substituents independently selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRe, —O—CO—NRdRe, —NRc—CO—NRdRe, —NRc—CO—Rc, —NRc—CO—ORc, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO2—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—CSO2—Rc, —SO2—NRdRc, —SO—NRdRc, —S—NRdRc, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, and Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRe, —CO—NRdRc, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are as defined above; or
R1 and R2, taken together with the nitrogen atom to which they are bonded, form a monocyclic or fused or non-fused polycyclic structure which may contain one to three additional heteroatoms, the structure being unsubstituted or substituted with one or more substituents selected from the group consisting alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRc, —O—CO—NRdRc, —NRc—CO—NRdRc, —NRc—CO—Rc, —NRc—CO—ORe, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—O—Rc, —SO2—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRcCS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—CSO2—Rc, —SO2—NRdRe, —SO—NRdRe, —S—NRdRe, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRc, —CO—NRdRe, —CO—ORc, —CO—Rc, —NRcCO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, and unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are defined above;
R3 is an aryl, alkyl, or cycloalkyl group, unsubstituted or substituted with one or more substituents independently selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRc, —O—CO—NRdRe, —NRc—CO—NRdRe, —NRc—CO—Rc, —NRc—CO—ORe, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO2—CO—Rc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—CSO2—Rc, —SO2—NRdRe, —SO—NRdRc, —S—NRdRc, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRe, —CO—NRdRe, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, and unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are defined above; and
Y is hydrogen, alkyl, heteroalkyl, haloalkyl, halocycloalkyl, cycloalkyl, NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, ═O, ═S, —NRdRe, —CO—NRdRe, —O—CO—NRdRc, —NRc—CO—Re, —NRc—CO—ORe, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc-CS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—SO2—Rc, —SO2—NRdRe, —SO—NRdRe, —S—NRdRe, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, and cycloalkyl, Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl alkenyl, alkynyl, —CORf, —COORf, —O—CO—Rf, —O—CO—Rf, —OH, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl;
or a pharmaceutically acceptable salt of said compound, or a pharmaceutically acceptable prodrug of said compound.

### Claim 2 (depends on 1)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 1, wherein Y is hydrogen, OH, a halogen or an alkoxy group.

### Claim 3 (depends on 1)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 1, wherein R3 is an aryl group substituted with one or more substituents selected from the group consisting of halogen, alkoxy, alkyl, nitro, —OH, amide, and —SO2-alkyl.

### Claim 4 (depends on 1)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 1, wherein the —C(O)NR1R2 moiety is meta or para to the amine linking the phenyl and thiazole rings.

### Claim 5 (depends on 1)

A compound or pharmaceutically acceptable salt of said compound according to claim 1, wherein the —C(O)NR1R2 moiety is para to the amine linking the phenyl and thiazole rings.

### Claim 6 (depends on 5)

A compound or pharmaceutically acceptable salt of said compound according to claim 5, wherein Y is hydrogen, or an alkyl, alkoxy, or halogen group; and
R3 is a monocyclic aryl group substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, —OH, amide, and —SO2-alkyl.

### Claim 7 (depends on 5)

A compound or pharmaceutically acceptable salt of said compound according to claim 5, wherein Y is hydrogen; and
R3 is a monocyclic aryl group substituted with one or more substituents selected from the group consisting of halogen and alkyl.

### Claim 8 (depends on 1)

A compound or pharmaceutically acceptable salt of said compound according to claim 1, wherein the —C(O)NR1R2 moiety is para and Y is meta to the amine linking the phenyl and thiazole rings.

### Claim 9 (depends on 8)

A compound or pharmaceutically acceptable salt of said compound according to claim 8, wherein Y is hydrogen, or an alkyl alkoxy, or halogen group; and
R3 is a monocyclic aryl group substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, —OH, amide, and —SO2-alkyl.

### Claim 10 (depends on 8)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 8, wherein Y is hydrogen; and
R3 is a monocyclic aryl group substituted with one or more substituents selected from the group consisting of halogen and alkyl.

### Claim 11 (depends on 1)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug, of said compound according to claim 1, wherein the —C(O)NR1R2 moiety is para to the NH moiety;
R1 and R2 are each independently hydrogen, or an —CH2—R10, alkyl, alkenyl, alkynyl, aryl, or cycloalkyl group unsubstituted or substituted with one or more R10 substituents independently selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRe, —O—CO—NRdRc, —NRc—CO—NRdRe, —NRc—CO—Rc, —NRc—CO—ORc, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO2—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—CSO2—Rc, —SO2—NRdRc, —SO—NRdRe, —S—NRdRc, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, and Rc, Rd and Re are each independently selected from the group consisting of hydrogen halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRe, —CO—NRdRc, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are defined above; where R1 and R2 are not both hydrogen.

### Claim 12 (depends on 11)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound, according to claim 11, wherein Y is hydrogen, or an alkyl, alkoxy, or halogen group; and
R3 is a monocyclic aryl group substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, —OH, amide, and —SO2-alkyl.

### Claim 13 (depends on 11)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 11, wherein Y is hydrogen; and
R3 is a monocyclic aryl group substituted with one or more substituents selected from the group consisting of halogen and alkyl.

### Claim 14 (depends on 1)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 1, wherein the —C(O)NR1R2 moiety is para to the NH moiety;
R1 is hydrogen; and
R2 is an alkyl, alkenyl, alkynyl, aryl, or cycloalkyl, group unsubstituted or substituted with one or more substituents independently selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRe, —O—CO—NRdRc, —NRc—CO—NRdRe, —NRc—CO—Re, —NRc—CO—ORc, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO2—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, —NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rd, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—CSO2—Rc, —SO2—NRdRc, —SO—NRdRc, —S—NRdRc, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, and Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, —N—ORc, —NRdRc, —CO—NRdRe, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—Rc, O—CO—NRdRc, —SH, —O—Rb, —O—Ra—O—, —S—Rb, and unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are as defined above.

### Claim 15 (depends on 14)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound-according to claim 14, wherein Y is selected from the group consisting of hydrogen or a hydroxy, halogen, alkyl or alkoxy group;
R3 is a monocyclic aryl group substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkoxy, —OH, amide, and —SO2-alkyl.

### Claim 16 (depends on 14)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound, according to claim 14, wherein Y is hydrogen; and
R3 is a monocyclic aryl group substituted with one or more substituents selected from the group consisting of halogen and alkyl.

### Claim 17

A compound represented by Formula II:
wherein:
R1 is selected from the group consisting of a C2-C11 alkyl, —CH2—R10, alkenyl, alkynyl, heteroalkyl, alkoxy, amino-alkyl, aryl, cycloalkyl, or group unsubstituted or substituted with one or more R10 substituents selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRe, —O—CO—NRdRc, —NRc—CO—NRdRe, —NRc—CO—Rc, —NRc—CO—ORc, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO2—CO—ORc, —SO—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—CSO2—Rc, —SO2—NRdRe, —SO—NRdRc, —S—NRdRe, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, and Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRe, —CO—NRdRe, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, —O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, and unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re as are defined above;
R4, R5, and R6 are each independently selected from the group consisting of hydrogen, alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, O—ORc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRe, —O—CO—NRdRe, —NRc—CO—NRdRe, —NRc—CO—Re, —NRd—CO—ORc, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO2—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, —O—CSO2—Rc, —SO2—NRdRe, —SO—NRdRe, —S—NRdRe, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2—ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRc, —OH, aryl, and cycloalkyl, and Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRe, —CO—NRdRc, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, —O—CO—NRdRc, —SH, —O—Rb, —O—Ra—O—, —S—Rb, unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd and Rc are as defined above; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable prodrug thereof.

### Claim 18 (depends on 17)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 17, wherein R1 is —CH2—R10 or C2-C11 alkyl unsubstituted or substituted with one or more R10 substituents selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl; NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRe, —O—CO—NRdRe, NRc—CO—NRdRe, —NRc—CO—Rc, —NR—CO—ORc, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, S—CO—Rc, —SO—CO—ORc, —SO2—CO—ORc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, O—CSO2—Rc, —SO2—NRdRe, —SO—NRdRe, —S—NRdRe, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, SH, —S—Rb, and —PO2ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRc, —OH, aryl, and cycloalkyl, and Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, and Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl, or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRc, —CO—NRdRe, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, —O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, unsubstituted alkyl, unsubstituted aryl, and unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd and Re are as defined above.

### Claim 19 (depends on 18)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 18, wherein R4, R5 and R6 are each independently selected from hydrogen and halogen.

### Claim 20 (depends on 18)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 18, wherein said R1 is —CH2— or C2-C11 alkyl.

### Claim 21 (depends on 20)

A compound, pharmaceutically acceptable salt, or, pharmaceutically acceptable prodrug of said compound, according to claim 20, wherein R4, R5 and R6 are each independently selected from hydrogen and halogen.

### Claim 22 (depends on 17)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 17, wherein R1 is aryl, unsubstituted or substituted with one or more R10 substituents selected from the group consisting of alkyl, heteroalkyl, haloalkyl, haloaryl, halocycloalkyl, aryl, cycloalkyl, —NO2, —NH2, —N—OH, N—ORc, —CN, —(CH2)z—CN where z is 0-4, halogen, —OH, —O—Ra—O—, —ORb, —CO—Rc, —O—CO—Rc, —CO—ORc, —O—CO—ORc, —O—CO—O—CO—Rc, ═O, ═S, —SO2—Rc, —SO—Rc, —NRdRe, —CO—NRdRc, —O—CO—NRdRc, —NRc—CO—NRdRc, —NRc—CO—Rc, —NRc—CO—ORc, —CO—NRc—CO—Rd, —O—SO2—Rc, —O—SO—Rc, —O—S—Rc, —S—CO—Rc, —SO—CO—ORc, —SO2—CO—Rc, —O—SO3, —NRc—SRd, —NRc—SO—Rd, NRc—SO2—Rd, —CO—SRc, —CO—SO—Rc, —CO—SO2—Rc, —CS—Rc, —CSO—Rc, —CSO2—Rc, —NRc—CS—Rd, —O—CS—Rc, —O—CSO—Rc, O—CSO2—Rc, —SO2—NRdRe, —SO—NRdRe, —S—NRdRc, —NRd—CSO2—Rd, —NRc—CSO—Rd, —NRc—CS—Rd, —SH, —S—Rb, and —PO2ORc, where Ra is selected from the group consisting of alkyl, heteroalkyl, alkenyl, and alkynyl, Rb is selected from the group consisting of alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, halogen, —CO—Rc, —CO—ORc, —O—CO—O—Rc, —O—CO—Rc, —NRc—CO—Rd, —CO—NRdRe, —OH, aryl, and cycloalkyl, and Rc, Rd and Re are each independently selected from the group consisting of hydrogen, halogen, alkyl, heteroalkyl, haloalkyl, alkenyl, alkynyl, —CORf, —COORf, —O—CO—O—Rf, —O—CO—Rf, —OH, aryl, and cycloalkyl, Rf is selected from the group consisting of hydrogen, alkyl, and heteroalkyl, and where any of the alkyl, heteroalkyl, alkylene, aryl or cycloalkyl, moieties present in the above substituents may be further substituted with one or more substituents independently selected from the group consisting of NO2, —NH2, —CN, —(CH2)z—CN where z is 0-4, halogen, haloalkyl, haloaryl, —OH, ═O, —N—OH, N—ORc, —NRdRe, —CO—NRdRe, —CO—ORc, —CO—Rc, —NRc—CO—NRdRe, —C—CO—ORc, —NRc—CO—Rd, —O—CO—O—Rc, O—CO—NRdRe, —SH, —O—Rb, —O—Ra—O—, —S—Rb, unsubstituted alkyl, and unsubstituted aryl, unsubstituted cycloalkyl, where Ra, Rb, Rc, Rd, and Re are as defined above.

### Claim 23 (depends on 20)

A compound, pharmaceutically acceptable salt, or pharmaceutically acceptable prodrug of said compound according to claim 20, wherein R4, R5 and R6 are each independently selected from hydrogen and halogen.

### Claim 24 (depends on 1)

A pharmaceutical composition comprising an amount of an agent effective to modulate cellular proliferation and a pharmaceutically acceptable carrier, said agent being selected from the group consisting of compounds, pharmaceutically acceptable salts, and pharmaceutically acceptable prodrugs as defined in claim 1.

### Claim 25 (depends on 1)

A pharmaceutical composition comprising an amount of an agent effective to inhibit a protein kinase and a pharmaceutically acceptable carrier, said agent being selected from the group consisting of compounds, pharmaceutically acceptable salts and pharmaceutically acceptable prodrugs; as defined in claim 1.

### Claim 26 (depends on 25)

A pharmaceutical composition according to claim 25, wherein said protein kinase is a CDK1, CDK1/cyclin complex, CDK2, CDK2/cyclin complex, CDK4, CDK4/cyclin complex, CDK6, CDK6/cyclin complex, FGF, or LCK.

### Claim 27 (depends on 17)

A pharmaceutical composition comprising an amount of an agent effective to modulate cellular proliferation and a pharmaceutically acceptable carrier, said agent being selected from the group consisting of compounds, pharmaceutically acceptable salts, and pharmaceutically acceptable prodrugs as defined in claim 17.

### Claim 28 (depends on 17)

A pharmaceutical composition comprising an amount of an agent effective to inhibit a protein kinase and a pharmaceutically acceptable carrier, said agent being selected from the group consisting of a compound, pharmaceutically acceptable salts, and pharmaceutically acceptable prodrugs as defined in claim 17.

### Claim 29 (depends on 25)

A pharmaceutical composition according to claim 25, wherein said protein kinase is a CDK1, CDK1/cyclin complex, CDK2, CDK2/cyclin complex, CDK4, CDK4/cyclin complex, CDK6, CDK6/cyclin complex, VGEF, FGF, or LCK.

### Claim 30

A compound selected from the group consisting of:
or a pharmaceutically acceptable salt of said compound.