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(12) United States Patent (10) Patent No.: US 9,085,577 B2 Cid-Nunez Et Al

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(12) United States Patent (10) Patent No.: US 9,085,577 B2 Cid-Nunez Et Al US009085577B2 (12) United States Patent (10) Patent No.: US 9,085,577 B2 Cid-Nunez et al. (45) Date of Patent: Jul. 21, 2015 (54) 7-ARYL-1,2,4-TRIAZOLO4,3-APYRIDINE (58) Field of Classification Search DERVATIVES AND THEIR USE AS POSITIVE CPC A61 K9/2018; A61 K9/0014: A61 K9/0019; ALLOSTERIC MODULATORS OF MIGLUR2 A61 K9/0095; A61 K9/06; A61 K9/2009: RECEPTORS A61 K9/2059; A61K 45/06; A61K 31/437; A61K 31/444; A61K 31/4545; A61 K31/5377: (71) Applicants:JANSSEN PHARMACEUTICALS, A61K 47/06; A61K 47/10; A61 K47/26: INC. Titusville, NJ (US); ADDEX A61K 47/38 PHARMA, S.A., Geneva (CH) USPC .......................................................... 514/303 See application file for complete search history. (72) Inventors: Jose Maria Cid-Nunez, Toledo (ES); Ana Isabel De Lucas Olivares, Toledo (ES); Andres Avelino Trabanco-Suarez, (56) References Cited Toledo (ES); Gregor James U.S. PATENT DOCUMENTS MacDonald, Beerse (BE) 4,051,244. A 9, 1977 Matiioda et al. (73) Assignees: Janssen Pharmaceuticals, Inc., 4,066,651 A 1/1978 Brittain et al. Titusville, NJ (US); Addex Pharma, (Continued) S.A., Geneva (CH) FOREIGN PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 BE 841390 11, 1976 U.S.C. 154(b) by 0 days. CA 1019323 1Of 1977 (Continued) (21) Appl. No.: 14/215,462 OTHER PUBLICATIONS (22) Filed: Mar 17, 2014 Dwyer, J Molecular Psychiatry, vol. 1 (15), 2013, p. 1-4.* (65) Prior Publication Data (Continued) US 2014/O2OO2O8 A1 Jul. 17, 2014 Primary Examiner — D M Seaman Related U.S. Application Data (74) Attorney, Agent, or Firm — Baker & Hostetler LLP (63) Continuation of application No. 13/319.568, filed as application No. PCT/EP2010/002909 on May 11, (57) ABSTRACT 2010, now Pat. No. 8,716,480. The present invention relates to novel triazolo 4,3-alpyridine derivatives of Formula (I) wherein all radicals are as defined (30) Foreign Application Priority Data in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate May 12, 2009 (EP) ..................................... O916OO64 receptor subtype 2 (“mCluR2), which are useful for the treatment or prevention of neurological and psychiatric dis (51) Int. Cl. orders associated with glutamate dysfunction and diseases in A6 IK 47/38 (2006.01) which the mGluR2 subtype of metabotropic receptors is CO7D 47L/04 (2006.01) involved. The invention is also directed to pharmaceutical A6 IK 45/06 (2006.01) compositions comprising Such compounds, to processes to A6 IK9/20 (2006.01) prepare such compounds and compositions, and to the use of A6 IK3I/437 (2006.01) Such compounds for the prevention or treatment of neurologi A6 IK3I/444 (2006.01) cal and psychiatric disorders and diseases in which mGluR2 A6 IK3 L/4545 (2006.01) is involved. A 6LX3/5377 (2006.01) A6 IK9/00 (2006.01) A6 IK 47/06 (2006.01) (I) (Continued) (52) U.S. Cl. CPC ............ C07D 471/04 (2013.01); A61 K9/0014 (2013.01); A61 K9/0019 (2013.01); A61 K 9/0095 (2013.01); A61 K9/06 (2013.01); A61 K 9/2009 (2013.01); A61 K9/2018 (2013.01); A61 K9/2059 (2013.01); A61 K3I/437 (2013.01); A61 K3I/444 (2013.01); A61 K 31/4545 (2013.01); A61K3I/5377 (2013.01); A61K 45/06 (2013.01); A61K 47/06 (2013.01); A61K47/10 (2013.01); A61K 47/26 (2013.01); A61K47/38 (2013.01) 15 Claims, No Drawings US 9,085,577 B2 Page 2 (51) Int. Cl. 6,333,428 B1 12/2001 Nakazato et al. A6 IK 47/10 (2006.01) 6,358,975 B1 29: s l 6,361,571 B1 3/2002 Goettel et al. A6 IK 47/26 (2006.01) 6,403,588 B1 6/2002 Hayakawa et al. A6 IK9/06 (2006.01) 6,407,094 B1 6/2002 Adam et al. 6.432,958 B1 8/2002 He 6,433,014 B1 8/2002 Acher et al. (56) References Cited 6,455,528 B1 9/2002 Adachi et al. 6,465,484 B1 10/2002 Bilodeau et al. U.S. PATENT DOCUMENTS 6,472,392 B1 10/2002 Starck et al. 6.479,436 B1 1 1/2002 Otten et al. 2:3: A 38. 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