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(12) United States Patent (10) Patent No.: US 9,365,579 B2 Wishart Et Al

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(12) United States Patent (10) Patent No.: US 9,365,579 B2 Wishart Et Al USOO9365579B2 (12) United States Patent (10) Patent No.: US 9,365,579 B2 Wishart et al. (45) Date of Patent: Jun. 14, 2016 (54) TRICYCLIC COMPOUNDS 4,053,474 A 10, 1977 Treuner et al. 5,212,310 A 5/1993 Thurkaufetal. 5,266,698 A 11/1993 Shaw et al. (71) Applicant: AbbVie Inc., North Chicago, IL (US) 5,521, 173 A 5/1996 Venkatesan et al. 5,605,690 A 2f1997 Jacobs et al. (72) Inventors: Neil Wishart, Jefferson, MA (US); 5,693,801 A 12/1997 Shaw et al. Maria A. Argiriadi, Wayland, MA (US); 5,733,905 A 3/1998 Albright et al. David J. Calderwood, Framingham, 5,736,540 A 4/1998 Albright et al. 5,753,648 A 5/1998 Albright et al. MA (US); Anna M. Ericsson, 5,763,137 A 6/1998 Deprez et al. Shrewsbury, MA (US); Bryan A. 5,840,888 A 11/1998 Shaw et al. Fiamengo, Worcester, MA (US); 5.990,109 A 11/1999 Chen et al. Kristine E. Frank, Grayslake, IL (US); 6,090,382 A 7/2000 Salfeld et al. Michael M. Friedman, Brookline, MA 6,262,241 B1 7/2001 Cook et al. 6,653,471 B2 11/2003 Yohannes et al. (US); Dawn M. George, Charlton, MA 6,949,562 B2 9, 2005 Yohannes et al. (US); Eric R. Goedken, Worcester, MA 7,169,926 B1 1/2007 Burgess et al. (US); Nathan S. Josephsohn, Boston, 7.593,820 B2 9, 2009 Wilks et al. MA (US); Biqin C. Li, Southborough, 7,772,231 B2 8/2010 Sheppard et al. MA (US); Michael J. Morytko, 8,426,411 B2 4/2013 Wishart et al. Framingham, MA (US); Kent D. 8,637,529 B2 1/2014 Woller et al. Stewart, Gurnee, IL (US); Jeffrey W. (Continued) Voss, Holden, MA (US); Grier A. Wallace, Sterling, MA (US); Lu Wang, FOREIGN PATENT DOCUMENTS Northborough, MA (US); Kevin R. CA 2675288 A1 T 2008 Woller, Antioch, IL (US) EA 007415 B1 10, 2006 (73) Assignee: AbbVie Inc., North Chicago, IL (US) (Continued) OTHER PUBLICATIONS (*) Notice: Subject to any disclaimer, the term of this Banker, et al., (1996), Modern Pharmaceuticals, p. 596. patent is extended or adjusted under 35 Dorwal, F. Z., Side Reactions in Organic Synthesis : A Guide to U.S.C. 154(b) by 0 days. Successful Sythesis Design, Weinheim: WILEY-VCH Verlag GmbH & Co. KGaA, 2005, Preface. (21) Appl. No.: 14/610,119 Epps, S.V. et al., “Design and Synthesis of Tricyclic Cores for Kinase Inhibition.” Bioorganic & Medicinal Chemistry Letters, 2013, vol. (22) Filed: Jan. 30, 2015 23, p. 693-698. Hauser, et al., Journal of Organic Chemistry (1961), 26, 451-5. (65) Prior Publication Data Hisham A. Abd El-Nabi. 1-Aryl-2-Chloro-5-Methoxy-1H-3-Pyr rolecarbaldehyde as Synthons for Fused Heterocycles: Synthesis of US 2015/0210708 A1 Jul. 30, 2015 Pyrazolo 3,4-D Pyridine Derivatives, Journal of Chemical Research, May 2004, pp. 325-327, vol. 5. Related U.S. Application Data (Continued) (63) Continuation of application No. 12/481,028, filed on Primary Examiner — Wu-Cheng Winston Shen Jun. 9, 2009, now Pat. No. 8,962,629. Assistant Examiner — Christopher R Stone (60) Provisional application No. 61/201,064, filed on Dec. (74) Attorney, Agent, or Firm — McCarter & English, LLP: 5, 2008, provisional application No. 61/190,159, filed Elizabeth A. Hanley: Yu Lu on Aug. 26, 2008, provisional application No. 61/131,599, filed on Jun. 10, 2008, provisional (57) ABSTRACT application No. 61/131,602, filed on Jun. 10, 2008. The invention provide a compound of Formula (I) (51) Int. Cl. CO7D 487/4 (2006.01) Formula (I) CO7D 498/4 (2006.01) UsX CO7D 51.3/4 (2006.01) (O / (52) U.S. Cl. CPC ............ C07D 487/14 (2013.01); C07D498/14 (2013.01); C07D 513/14 (2013.01) (58) Field of Classification Search CPC ... C07D 487/14: CO7D 498/14: CO7D 513/14 See application file for complete search history. pharmaceutically acceptable salts, pro-drugs, biologically (56) References Cited active metabolites, stereoisomer and isomer thereof wherein the variable are defined herein. The compound of the inven U.S. PATENT DOCUMENTS tion are useful for treating immunological and oncological conditions. 3,663,559 A 5/1972 Derijckere et al. 3,929,992 A 12/1975 Sehgal et al. 15 Claims, No Drawings US 9,365,579 B2 Page 2 (56) References Cited WO 2008/063287 A2 5, 2008 WO 2008/084861 A1 T 2008 U.S. PATENT DOCUMENTS WO 2008/094602 A2 8, 2008 WO 2008/112695 A2 9, 2008 8,785,639 B2 7/2014 Wishartet al. WO 2008121748 A2 10, 2008 2003/0078277 A1 4, 2003 Hibi et al. WO 2009/005.675 A1 1/2009 2004/0023992 A1 2, 2004 Das et al. WO 2009/108827 A1 9, 2009 2005/0176796 A1 8, 2005 D’Alessio et al. WO 2009,152133 A1 12/2009 2006, O183758 A1 8, 2006 Beard et al. WO 2010003133 A2 1/2010 2008/0070914 A1 3/2008 Freyne et al. WO 2011068899 A1 6, 2011 2009/0215724 A1 8, 2009 DuBois et al. 2009/0215750 A1 8/2009 Bamberg et al. OTHER PUBLICATIONS 38885 A. 858 Esty al. Jain, Sanjay et al., A Novel Synthesis of Di(I-Methylazacycloalkeno) 2009.0312338 A1 12, 2009 Wishart et al. 2,3-b:2',3'-dPyridines Through Annulation on Lactam 2011, 0021425 A1 1/2011 Billedeau Acetals;Tetrahedron Letters, 1990 , pp. 13 1-134, vol. 31 No. 1. 2011/O190489 A1 8, 2011 Wishart et al. Jordan, V. C. “Tamoxifen: A most Unlikely Pionering Medicine.” 2012/0034250 A1 2/2012 Shirakami et al. Nature Reviews: Drug Discovery, 2003, 2: 205-213. 2012/0330012 A1 12/2012 Frank et al. Kempson, J. et al., “Synthesis, initial SAR and biological evaluation 2013, OO72470 A1 3/2013 Wishart et al. of 1.6-dihydroimidazo[4, 5-dipyrrolo[2,3-bipyridin-4-amine 2013/0216497 A1 8, 2013 Wishart et all derived inhibtors of IkB kinase”, Bioorganic & Medicinal Chemistry Letters, 2009, vol. 19, pp. 2646-2649. Metabolite. Merriam-Webstercom. Merriam-Webster, n.d. Web. FOREIGN PATENT DOCUMENTS Dec. 4, 2013. <http://www.merriam-Webster.com/dictionary/me tabolite. E. 3: A: :38: Mikhaleva, et al., Khimiya Geterotsiklicheskikh Soedinenii GB T16327 A 10, 1954 (1972).(2), 1696-9, RU 2158127 C2 10/2000 Noble, M. et al., “Protein Kinase Inhibitors: Insights into Drug WO 91/10671 A1 7, 1991 Design from Structure.” Science, 2004, 303 (5665): p. 1800-1805. WO 92.16553 A1 10, 1992 Rochais et al., “Synthesis of New Dipyrrolo-and Furopyr WO 92/22552 A1 12, 1992 rolopyazinones related to Tripentones and their Biological Evalua WO 93.22314 A1 11, 1993 tion as Potential Kinases (CDKs 1-5. GSK3) Inhibitors.” Eur.J.Med. WO 94.05665 A1 3, 1994 Chem(2009)44:708–716. W. 2.93. A. SE: Schram et al. (Journal of Heterocyclic Chemistry (1975) 12:(5); pp. 1021-1023. W S. A. E. Shashi Nayana et al., COMFA and Docking Studies on WO 99/45009 A1 9, 1999 Triazolopyridine Oxazole Derivatives as P38 Map Kinase Inhibitors, WO O3OOO695 A1 1, 2003 European Journal of Medicinal Chemistry 43, pp. 1261-1269, 2008, WO 03/031606 A2 4, 2003 Abstract; p. 1263-p. 1268. WO 2004/065378 A1 8, 2004 Stella et al., “Prodrugs: Challenges and Rewards, Part 1 Biotechnol WO 2005/110410 A2 11/2005 ogy Pharmaceutical Aspects.” 2007, p. 24. WO 2006.002051 A1 1, 2006 The Merck Index. An Encyclopedia of Chemicals, Drugs, and WO 2006/010567 A1 2, 2006 Biologicals, Fourteenth Edition (2006) p. 863, Infliximab; p. 1422, WO 2006/074984 A1 T 2006 Rituximab, p. 81 15, Rapamycin; p. 637, Etanercept; and p. 26. WO 2006/074985 A1 T 2006 Adalimumab. W. 2.97. A. 1939: Wolff et al., “Burger's Medicinal Chemistry and Drug Discovery.” WO 2007/022268 A2 2/2007 5th Ed. Part 1, p.975-977 (1995). WO 2007/035935 A1 3, 2007 Zaragoza, Side Reactions in Organic Synthesis: A Guide to Success WO 2007/061764 A2 5/2007 ful Synthesis Design, Weinheim: WILEY-VCH Verlag GmbH & Co. WO 2007/077949 A1 7/2007 KGaA, 2005, Preface. WO 2007/079164 A2 7/2007 Wermuth, Camille G., “The Practice of Medicinal Chemistry.” Chap WO 2007,143434 A2 12/2007 ter 13: Molecular Variations Based on Isoteric Replacements. Aca WO 2008/021369 A2 2, 2008 demic Press, London, 1996, pp. 203-237. US 9,365,579 B2 1. 2 TRICYCLIC COMPOUNDS T is N, U is CR, X is CR and Y is N; or T is CR, U is CR, X is CR and Y is N; or CROSS REFERENCE TO RELATED T is CR, U is N, X is NR and Y is C; or APPLICATION T is O, U is N, X is CR and Y is C; or T is NR, U is N, X is CR and Y is C; or This application is a continuation of U.S. patent applica T is CR, U is CR, X is NR and Y is C; or tion Ser. No. 12/481,028 filed on Jun. 9, 2009, which claims T is S, U is N, X is CR and Y is C; priority to U.S. Provisional Application Ser. No. 61/131,599 R", R and R are each independently hydrogen, deute filed on Jun. 10, 2008, U.S. Provisional Application Ser. No. rium, N(R)(R), halogen, —OR", -SR", -S(O)R", 61/131,602 filed on Jun. 10, 2008, U.S. Provisional Applica 10 S(O),R, NO, C(O)OR, CN, C(O)N(R)(R), tion Ser.
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