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(12) United States Patent (10) Patent No.: US 8,841,323 B2 Imogai Et Al

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(12) United States Patent (10) Patent No.: US 8,841,323 B2 Imogai Et Al USOO8841.323B2 (12) United States Patent (10) Patent No.: US 8,841,323 B2 Imogai et al. (45) Date of Patent: Sep. 23, 2014 (54) 1,4-DISUBSTITUTED 3-CYANO-PYRIDONE (56) References Cited DERVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF U.S. PATENT DOCUMENTS MGLUR2-RECEPTORS 4,051,244. A 9, 1977 Mattioda et al. 4,066,651 A 1/1978 Brittain et al. 4,146,716 A 3, 1979 Cox et al. (75) Inventors: Hassan Julien Imogai, Geneva (CH): 4,196,207 A 4, 1980 Webber Vincent Mutel, legal representative, 4,256,738 A 3, 1981 Woitun et al. Geneva (CH); Jose Maria Cid-Nunez, 4,358,453 A 11/1982 Bristol et al. Toledo (ES); Jose Ignacio Andres-Gil. 4.550,166 A 10, 1985 Moran et al. Toledo (ES); Andres Avelino 4.866,074 A 9/1989 Spada et al. 4,898,654 A 2f1990 Toda et al. Trabanco-Suarez, Toledo (ES); Julen 4,978,663 A 12/1990 Effland et al. Oyarzabal Santamarina, Toledo (ES); 5,032,602 A 7/1991 Fey et al. 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No.: 12/282,663 (74) Attorney, Agent, or Firm — Baker & Hostetler LLP (57) ABSTRACT (22) PCT Filed: Mar. 15, 2007 The present invention relates to novel compounds, in particu lar novel pyridinone derivatives according to Formula (I) (86). PCT No.: PCT/EP2007/052442 S371 (c)(1), (I) (2), (4) Date: Dec. 9, 2009 (87) PCT Pub. No.: WO2007/104783 PCT Pub. Date: Sep. 20, 2007 (65) Prior Publication Data US 2010/O166655A1 Jul. 1, 2010 (R) wherein all radicals are defined in the application and claims. (30) Foreign Application Priority Data The compounds according to the invention are positive allos teric modulators of metabotropic receptors-Subtype 2 Mar. 15, 2006 (EP). ... O6111215 (“mCluR2’) which are useful for the treatment or prevention Mar. 7, 2007 (EP) ..................................... O7103.654 of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 Subtype of metabotropic receptors is involved. In particular, (51) Int. Cl. Such diseases are central nervous system disorders selected A6 IK3I/4439 (2006.01) from the group of anxiety, Schizophrenia, migraine, depres CO7D 23/85 (2006.01) Sion, and epilepsy. The invention is also directed to pharma ceutical compositions and processes to prepare such com (52) U.S. Cl. pounds and compositions, as well as to the use of Such USPC ........................................... 514/316:546/193 compounds for the prevention and treatment of such diseases (58) Field of Classification Search in which mGluR2 is involved. USPC ........................................... 514/316:546/193 See application file for complete search history. 7 Claims, No Drawings US 8,841,323 B2 Page 2 (56) References Cited 7,579,360 B2 8, 2009 Li 7,700,593 B2 4/2010 Chakrabarti et al. U.S. PATENT DOCUMENTS 7,879.837 B2 2/2011 Hayashi et al. 7,960,563 B2 6/2011 Johnson et al. 5,332,750 A 7, 1994 Mederski et al. 7,977,325 B2 7/2011 Schwede et al. .............. 514, 183 5,356,911. 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