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(12) United States Patent (10) Patent No.: US 8,633,210 B2 Us M USOO863321 OB2 (12) United States Patent (10) Patent No.: US 8,633,210 B2 Charrier et al. (45) Date of Patent: *Jan. 21, 2014 (54) TRIAZOLE COMPOUNDS USEFUL AS 5,710, 158 A 1/1998 Myers et al. PROTEINKNASE INHIBITORS (Continued) (75) Inventors: Jean-Damien Charrier, Wantage (GB); FOREIGN PATENT DOCUMENTS Pan Li, Lexington, MA (US); Ronald Knegtel, Abingdon (GB); Julian DE 2458965 6, 1976 Marian Charles Golec, Faringdon E. 09: k l 3. (GB); David Bebbington, Newbury EP O3O2312 2, 1989 (GB); Hayley Marie Binch, Encinitas, GB 205.2487 1, 1981 CA (US) JP 10-130 150 5, 1998 JP 2000-026421 1, 2000 (73) Assignee: Vertex Pharmaceuticals Incorporated, wo E. gig. Cambridge, MA (US) WO 9322681 11, 1993 (*) 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. OTHER PUBLICATIONS This patent is Subject to a terminal dis- Wolff et, al., “Burger's Medicinal Chemistry and Drug Discovery.” claimer. 5th Ed. Part 1, pp.975-977 (1995).* Banker, et. al., (1996), Modern Pharmaceuticals, p. 596.* (21) Appl. No.: 13/094, 183 (1980),Ivashchenko, (12), 1673-7.*et al. Khimiya Geterotsiklicheskikh Soedinenii (22) Filed: Apr. 26, 2011 (Continued) (65) Prior Publication Data Primary Examiner — Jeffrey Murray US 2012/OO71657 A1 Mar. 22, 2012 (74) Attorney, Agent, or Firm — Rory C. Stewart Related U.S. Application Data (57) ABSTRACT (62) Division of application No. 1 1/492.450, filed on Jul. This invention describes novel triazole compounds of for 25, 2006, now Pat. No. 7,951,820, which is a division mula IX: of application No. 09/953,471, filed on Sep. 14, 2001, now Pat. No. 7,115,739. (60) Provisional application No. 60/232,795, filed on Sep. R2 IX 15, 2000, provisional application No. 60/257.887, filed on Dec. 21, 2000, provisional application No. Na 60/286,949, filed on Apr. 27, 2001. us M NH (51) Int. Cl. HN N AOIN 43/54 (2006.01) R. A 6LX3/57 (2006.01) N72 CO7D 40/00 (2006.01) A CO7D 403/00 (2006.01) y 2 CO7D 413/00 (2006.01) R Z CO7D 417/00 (2006.01) CO7D 49/00 (2006.01) (52) U.S. Cl. wherein-- Z'71 is: - -nitrogen or CR 9 and Z,2 is: - -nitrogen or CH, 58 fo - - - - - ificati- - - - - -s - - - - - - - h 514/266.23:544/284 provided that at least one of Z' and Z is nitrogen; G is Ring (58) es OSSO Sea C or Ring D; Ring C is selected from a phenyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or 1,2,4-triazinyl ring, See application file for complete search history. wherein said Ring C has one or two ortho substituents inde (56) References Cited p endentlyy selected from —R'; Ring9. D is a 5-7 membered monocyclic ring or 8-10 membered bicyclic ring selected U.S. PATENT DOCUMENTS from aryl, heteroaryl, heterocyclyl or carbocyclyl; R and R' 3,133,081 A 5/1964 Lafferty are independently selected from T-R, or R and Rare taken 3,755,322 A 8, 1973 Winter et al. together with their intervening atoms to form a fused ring; R', 3,935,183 A 1/1976 Baron et al. R, and T are as described in the specification. The com 3,998,951 A 12/1976 Harnish et al. pounds are useful as protein kinase inhibitors, especially as 4,051.252 A 9/1977 Mayer et al. 4,493.726 A 1, 1985 Burdeska et al. inhibitors of GSK-3 and Aurora, for treating diseases such as 4,540,698 A 9, 1985 Ishikawa et al. diabetes, cancer, and Alzheimer's disease. 4,711,951 A 12/1987 Axen et al. 5,124,441 A 6, 1992 Carlsson et al. 22 Claims, No Drawings US 8,633,210 B2 Page 2 (56) References Cited 2003/0069248 A1 4/2003 Chakravarty et al. 2003/OO73687 A1 4/2003 Bebbington et al. 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