Methods and compositions utilizing quinazolinones

• US 6,831,085 B1
• Filed: 11/28/2000
• Issued: 12/14/2004
• Est. Priority Date: 10/27/1999
• Status: Expired due to Term

• Current Assignee: Cytokinetics, Inc.
• Original Assignee: Cytokinetics, Inc.
• Inventors: Chabala, John C., Smith, Whitney W., Bergnes, Gustave
• Primary Examiner(s): Raymond, Richard L.
• Assistant Examiner(s): TRUONG, TAMTHOM NGO
• Application Number:
  US09/724,941
• Time in Patent Office: 1,477 Days
• Field of Search: 514/266.2, 514/266.3, 514/266.31, 544/287, 544/284
• US Class Current: 514/266.2
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 239/90 with acyclic radicals attached in position 2 or 3
• CPC Class Codes: C07D 239/91 with aryl or aralkyl radicals attached in position 2 or 3

Abstract

Quinazolinones of formulae 1a, 1b, 1c and 1d are disclosed. They are useful for treating cellular proliferative diseases and disorders associated with KSP kinesin activity.

Claims

1. A compound having the following structure:

wherein

R₁ is chosen from lower alkyl, benzyl, substituted benzyl and substituted phenyl;

R₂ is ethyl or propyl;

R₂′

is hydrogen;

R_3″

is chosen from said substituted phenyl, heterocyclyl and naphthyl;

R₄ is chosen from subtituted benzyl heterocyclyl substituted lower alkyl and R₁₆-alkylene-;

R₆ and R₇ are chosen from hydrogen and halogen;

R₅ and R₈ are hydrogen;

R₁₆ is chosen from di(lower alkylamino), (lower alkylamino, amino, pyrrolidino, piperidino, imidazolyl and morpholino.

3. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound or salt of claim 1, or 2.

4. A compound according to claim 1, wherein the carbon to which R₂ and R_2′

are attached is of the R configuration.

2. A compound having the following structure:

wherein

R₁ is benzyl;

R₂ is ethyl;

R₂′

is hydrogen;

R_3″

is chosen from halophenyl, polyhalophenyl, tolyl, dimethylphenyl, methoxyphenyl, dimethoxyphenyl, cyanophenyl, trifluoromethylphenyl, trifluoromethoxyphenyl, bis(trifluoromethyl)phenyl, carboxyphenyl, t-butylphenyl, methoxycarbonylphenyl, piperidinyl and naphthyl;

R₄ is chosen from substituted benzyl, piperidinyl, hydroxy(lower alkyl) and R₁₆-alkylene-;

R₆ and R₇ are chosen from hydrogen and halo;

R₅ and R₈ are hydrogen;

R₁₆ is chosen from dimethylamino, amino, pyrrolidinyl and piperidinyl.

5. A compound according to claim 2, wherein the carbon to which R₂ and R_2′

are attached is of the R configuration.