HETEROCYCLIC COMPOUNDS USEFUL FOR KINASE INHIBITION

• US 20130123284A1
• Filed: 03/24/2011
• Published: 05/16/2013
• Est. Priority Date: 03/24/2010
• Status: Active Grant

• Current Assignee: Amitech Therapeutic Solutions, Inc.
• Original Assignee: Amitech Therapeutic Solutions, Inc.
• Inventors: Arnold, Lee Daniel, Murphy, Eric A.
• Granted Patent: US 8,957,216 B2
• Time in Patent Office: Days
• US Class Current: 514/265.1
• CPC Class Codes: A61K 31/4196 1,2,4-Triazoles
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4725 containing further heterocyclic rings
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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 249/14 Nitrogen atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/14 : containing three or more hetero rings
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/22 : in which the condensed system contains four or more hetero rings
• CPC Class Codes: C12N 2501/48 : Regulators of apoptosis
• CPC Class Codes: C12N 5/0693 : Tumour cells; Cancer cells

Abstract

Provided herein are compounds useful for kinase inhibition.

Claims

1-82. -82. (canceled)

83. A compound having the structure (1) or an N-oxide, N,N′

-dioxide, N,N′

,N″

-trioxide, or a

84. The compound of any one of claims 83, wherein W is C₆-C₁₂ aryl.

85. The compound of claim 84, wherein W is phenyl.

86. The compound of claim 83, wherein R₁ is an unsubstituted or a substituted C₃-C₁₂ heteroaryl having 1-3 heteroatoms.

87. The compound of claim 83, wherein R₁ is an unsubstituted or a substituted pyridine or pyrimidine.

88. The compound of claims 83, wherein R₄ is hydrogen.

89. The compound of claim 83, wherein each R₂ and R₃ are independently selected from a group consisting of a C₁-C₆ alkyl, —

CF₃, and halogen, wherein p is 0 or 1 or 2;

or, optionally, R₂ and R₃ are joined to form a five to seven membered carbocycle.

90. The compound of claim 83, wherein the compound having structure (I) is selected from the group consisting of:

91. The compound of claim 83, having the structure (II)

92. The compound of claim 91, wherein

each R₂ and R₃ are independently selected from a group consisting of a hydrogen, a C₁-C₆ alkoxy, an optionally substituted C₁-C₆ alkyl, —

CF₃, halogen, —

CN, and —

CO₂R′

wherein R is hydrogen or C₁-C₆ alkyl;

or, optionally, R₂ and R₃ are joined to form a five to seven membered carbocycle.

93. The compound of claim 92, wherein R₈ and R₉ are independently selected from the group consisting of optionally substituted C₁-C₆ alkoxy, —

NR₁₀R₁₁, and —

SO_mR₁₂, and m is 0-2.

94. The compound of claim 92, wherein each R₂ and R₃ are independently selected from a group consisting of a C₁-C₆ alkyl, —

CF₃, and halogen wherein p is 0 or 1 or 2;

or, optionally, R₂ and R₃ are joined to form a five to seven membered carbocycle.

95. The compound of claim 92, wherein the compound having structure (II) is selected from the group consisting of

96. The compound of claim 83, wherein the compound is selected from the group consisting of

101. A pharmaceutical composition comprising a compound of claim 83, in a pharmaceutically acceptable carrier.

102. A method for treating cancer, restenosis, intimal hyperplasia, fibrotic diseases or angiogenesis-dependent disorder in a human subject comprising administering a compound of claim 83 to a patient in need thereof.

97. A compound having the structure (IV) or an N-oxide, N,N′

-dioxide, N,N′

,N″

-trioxide, or a pharmaceutically acceptable salt thereof;

98. The compound of claim 97, wherein the compound having structure (IV) is selected from the group consisting of

99. A compound having the structure (V) or an N-oxide, N,N′

-dioxide, N,N′

,N″

-trioxide, or a pharmaceutically acceptable salt thereof;

100. The compound of claim 99, the compound having structure (V) is selected from the group consisting of