Nitrogen-containing heterocyclyl ketones and methods of use

• US 8,314,087 B2
• Filed: 02/15/2008
• Issued: 11/20/2012
• Est. Priority Date: 02/16/2007
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Albrecht, Brian K., Bellon, Steven, Booker, Shon, Cheng, Alan C., D'Amico, Derin, D'Angelo, Noel, Harmange, Jean-Christophe, Kim, Tae-Seong, Liu, Longbin, Norman, Mark H., Siegmund, Aaron C., Stec, Markian, Xi, Ning, Yang, Kevin
• Primary Examiner(s): Wilson, James O
• Assistant Examiner(s): Jaisle, Cecilia M
• Application Number:
  US12/070,309
• Publication Number:
  US 20080280917A1
• Time in Patent Office: 1,740 Days
• Field of Search: 544/128, 544/238, 544/405.318, 546/122, 546/153, 546/162, 514/314, 514/210.02, 514/312, 514/235.2, 514/252.04, 514/255.05, 514/274
• US Class Current: 514/210.02
• 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 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• 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 237/16 Two oxygen atoms
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon 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 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems

Abstract

Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Claims

1. A compound of the following Formula I

2. A compound of claim 1 wherein R¹ is

(1) —

NR⁸R⁹, —

NR⁶CONR⁸R⁹, —

NR⁶COOR⁷, —

CN, or —

CONR⁸R⁹;

or

(2) aryl, heteroaryl, heterocyclyl, alkenyl or alkynyl any of which may be optionally independently substituted as allowed by valence with one or more R¹⁰ .

3. A compound of claim 2 wherein R¹ is aryl, heteroaryl or heterocyclyl any of which may be optionally independently substituted as allowed by valence with one or more R¹⁰ .

5. A pharmaceutical composition comprising a compound of any of claims 1 or 4 and a pharmaceutically-acceptable carrier.

6. A compound of claim 3 or a pharmaceutically acceptable salt thereof wherein

R¹ is phenyl, naphthyl, naphthyridinyl, thienyl, benzothienyl, furanyl, benzofuranyl, pyridyl, pyrazinyl, pyrimidinyl, imidazolyl, triazolyl, quinoxalinyl, benzodioxolyl, benzodioxinyl dihydrobenzodioxinyl, indolinyl, indolyl, benzoimidazolyl, benzisoxazolyl, benzoisothiazolyl, benzoxazolyl, benzothiazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, morpholinyl, pyrrolidinyl, pyrazolyl, indazolyl, piperazinyl, piperadinyl, azetidinyl, pyranyl, pyridazinyl, dihydropyranyl, tetrahydropyranyl, quinolinyl, quinazolinyl, cinnolinyl, phthalazinyl, dihydroquinolinyl or isoquinolinyl any of which may be optionally independently substituted as allowed by valence with one or more R¹⁰ .

4. A compound or a pharmaceutically acceptable salt thereof selected from: