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(12) United States Patent (10) Patent No.: US 8,916,564 B2 Pettersson Et Al

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(12) United States Patent (10) Patent No.: US 8,916,564 B2 Pettersson Et Al USOO891.6564B2 (12) United States Patent (10) Patent No.: US 8,916,564 B2 Pettersson et al. (45) Date of Patent: Dec. 23, 2014 (54) SUBSTITUTED PYRIDO 1.2-APYRAZINES 7,812,040 B2 10/2010 Wager FOR THE TREATMENT OF 7,897,632 B2 3/2011 Kimura et al. 7,902,195 B2 3/2011 Hughes et al. NEURODEGENERATIVE AND 7,923.450 B2 4/2011 Baumann et al. NEUROLOGICAL DISORDERS 8,097,621 B2 1/2012 Bell et al. 8,697,673 B2 4/2014 Pettersson et al. (71) Applicant: Pfizer Inc., Groton, CT (US) 2002/0132817 A1 9/2002 Natsugari et al. 2003. O195205 A1 10, 2003 DeNinno et al. (72) Inventors: Martin Youngjin Pettersson, Littleton, 2004/0220186 Al 11/2004 Bell et al. MA (US); Douglas Scott Johnson 2006/0106035 A1 5/2006 Hendrix et al. s g s 2006/011 1372 A1 5, 2006 Hendrix et al. Concord, MA (US); Chakrapani 2007/0031416 A1 2/2007 Shoji et al. Subramanyam, South Glastonbury, CT 2007/0117798 A1 5, 2007 Kimura et al. (US); Christopher John O'Donnell, 2007/01 17839 A1 5/2007 Kimura et al. O O 2007/O155731 A1 7/2007 Butora et al. NRE's reely. 2007. O197581 A1 8, 2007 Asberometal. am Ende, Mystic, CT (US); Michael 2008, OOO9490 A1 1/2008 Williams et al. Eric Green, Boston, MA (US); Nandini 2008/0076.738 A1 3, 2008 Cai et al. Chaturbhai Patel, Waltham, MA (US); 2008. O194591 A1 8, 2008 Entwistle et al. Cory Michael Stiff, New London, CT 2008/02O7900 A1 8/2008 Kimura et al. 2008/0280948 A1 11/2008 Baumann et al. (US); Tuan Phog Tra. Ledyard, CT 2009.0062529 A1 3/2009 Kimura et al. (US); Gregory Wayne Kauffman, East 2009/0163482 A1 6/2009 McHardy et al. Greenwich, RI (US); Antonia 2009, 0215759 A1 8/2009 Baumann et al. Friederike Stepan, Providence, RI (US); 2009,0306054 A1 12/2009 Cai et al. Patrick Robert Verhoest, Newton, MA 2010, OO16373 A1 1/2010 Khilevich et al. (US) s s 2010.0041680 A1 2/2010 Rivkin 2010/0093.731 A1 4/2010 Goetschi et al. 2010, O105904 A1 4/2010 Kimura et al. (73) Assignee: Pfizer Inc., New York, NY (US) 2010, 0120874 A1 5/2010 Baumann et al. (*) Notice: Subject to any disclaimer, the term of this (Continued) patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. FOREIGN PATENT DOCUMENTS EP 1145714 10, 2001 (21) Appl. No.: 14/031,163 GB 1419789 12, 1975 (22) Filed: Sep.19, 2013 (Continued) OTHER PUBLICATIONS (65) Prior Publication Data PCT Search Report and Written Opinion from International Search US 2014/0088.111A1 Mar. 27, 2014 ing Authority for PCT/IB2013/058347 dated Jan. 15, 2014. Related U.S. Application Data (Continued) (60)60) Provisionalya applicauonapplication No.No 61/703.969,909, filedIlled on Sep.Sep Primary Examiner — Douglas MWillis s (74) Attorney, Agent, or Firm — Richard V. Zanzalari (51) Int. Cl. A6 IK3I/4985 (2006.01) (57) ABSTRACT CO7D 47L/04 (2006.01) Compounds and pharmaceutically acceptable salts of the (52) U.S. Cl. compounds are disclosed, wherein the compounds have the CPC .................................... C07D 471/04 (2013.01) structure of Formula I USPC ......... 514/249; 544/349; 548/335.1; 549/429 (58) Field of Classification Search CPC .................................................. A61K 31f4985 I USPC ......... 514/249; 544/349; 548/335.1; 549/429 R7 Q R2a R2b See application file for complete search history. 24. R3 N1 N1 (56) References Cited R4b U.S. PATENT DOCUMENTS X 4 2 R 5,700,810 A 12/1997 Natsugari et al. O R5a R55 6,489,315 B1 12/2002 Natsugari et al. 7,238,721 B2 7/2007 Chen et al. 7,253,180 B2 8, 2007 Chen et al. as defined in the specification. Corresponding pharmaceuti 7,253,195 B2 8, 2007 Chen cal compositions, methods of treatment, methods of synthe 7,342,118 B2 3/2008 Brodney et al. 7,517,532 B2 4/2009 Wai et al. sis, and intermediates are also disclosed. 7,638,629 B2 12/2009 Hannam et al. 7,741,315 B2 6/2010 Vacca et al. 25 Claims, No Drawings US 8,916,564 B2 Page 2 (56) References Cited Gillman, K., et al., “Discovery and Evaluation of BMS-708 163, a Potent Selective and Orally Bioavailabley-Secretase Inhibitor'. ACS U.S. PATENT DOCUMENTS Medicinal Chemistry Letters, Mar. 22, 2010, pp. 120-124; 1(3). Goel, A., et al., “Amberlyst 15-Catalyzed Efficient synthesis of 2010/013 0495 A1 5, 2010 Forsblom et al. 5-Acetyl-4-hydroxy-coumarone and 5-Acetyl-6-hydroxy 2010.0137320 A1 6/2010 Huang et al. coumarone: Crucial Precursors for Several Naturally Occurring 2010/0204230 A1 8, 2010 Blurton et al. 2010/0222320 A1 9, 2010 Fischer et al. 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