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(12) United States Patent (10) Patent No.: US 9.403,799 B2 Schadt Et Al

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(12) United States Patent (10) Patent No.: US 9.403,799 B2 Schadt Et Al USOO9403799B2 (12) United States Patent (10) Patent No.: US 9.403,799 B2 Schadt et al. (45) Date of Patent: * Aug. 2, 2016 (54) PYRIMIDINYL-PYRIDAZINONE (52) U.S. Cl. DERVATIVES FOR TREATING ADISEASE CPC ............ C07D 403/10 (2013.01); A61 K9/0014 WHICH IS INFLUENCED BY INHIBITION OF (2013.01); A61 K9/0019 (2013.01); A61 K MET KINASE 9/0031 (2013.01); A61K 9/0048 (2013.01); A61 K9/02 (2013.01); A61 K9/06 (2013.01); (71) Applicant: Merck Patent GmbH, Darmstadt (DE) A61 K9/08 (2013.01); A61 K9/2018 (2013.01); A6 IK3I/501 (2013.01); A61 K3I/506 (72) Inventors: Oliver Schadt, Rodenbach (DE); Dieter (2013.01); A61 K3I/5355 (2013.01); A61 K Dorsch, Ober-Ramstadt (DE); Frank 31/5377 (2013.01); A61 K3I/55 (2013.01); Stieber, Heidelberg (DE); Andree A61K 45/06 (2013.01); A61K 47/02 (2013.01); Blaukat, Schriesheim (DE) C07D401/10 (2013.01); C07D401/14 (2013.01); C07D 403/14 (2013.01); C07D (73) Assignee: MERCK PATENT GMBH, Darmstadt 405/14 (2013.01); C07D 409/14 (2013.01); (DE) C07D 413/10 (2013.01); C07D 413/14 (2013.01); C07D 417/10 (2013.01); C07D (*) Notice: Subject to any disclaimer, the term of this 417/14 (2013.01); C07D 451/06 (2013.01); patent is extended or adjusted under 35 C07D 453/02 (2013.01); A61 K9/19 (2013.01); U.S.C. 154(b) by 0 days. A61 K9/2826 (2013.01) This patent is Subject to a terminal dis (58) Field of Classification Search claimer. CPC ....... A61K 47/02: A61 K9/08: A61 K9/2826; A61 K9/19; A61 K9/0014: A61 K9/0019; (21) Appl. No.: 14/602.921 A61K31/506; A61K31/5355; A61K 31/501; A61K 31/55; A61K31/5377; A61K45/06; (22) Filed: Jan. 22, 2015 C07D 417/10; C07D 417/14: CO7D 451/06; C07D 409/14: CO7D405/14: CO7D 453/02; (65) Prior Publication Data C07D 413/10; C07D 413/14: CO7D 403/14: US 2015/O1334.52 A1 May 14, 2015 CO7D401 (10 USPC ................... 514/236.5, 252.02:544/123, 298 See application file for complete search history. Related U.S. Application Data (62) Division of application No. 14/149.110, filed on Jan. 7, (56) References Cited 2014, now Pat. No. 9,062,029, which is a division of U.S. PATENT DOCUMENTS application No. 13/565,914, filed on Aug. 3, 2012, now Pat. No. 8,658,643, which is a division of application 6,242.461 Bl 6/2001 Goldstein No. 12/668,491, filed as application No. 6,403,586 B1 6/2002 Ohkuchi et al. PCT/EP2008/005508 on Jul. 4, 2008, now Pat. No. (Continued) 8,329,692. FOREIGN PATENT DOCUMENTS (30) Foreign Application Priority Data DE 19604388 8, 1997 Jul. 12, 2007 (DE) ......................... 10 2007 032 507 DE 102005057924 6, 2007 Apr. 29, 2008 (WO)................. PCT/EP2008/OO3473 (Continued) (51) Int. Cl. OTHER PUBLICATIONS A6 IK 47/02 (2006.01) A6 IK9/08 (2006.01) “Cancer MedLine Plus (2009). Accessed Mar 17, 2009. http:// A 6LX 9/19 (2006.01) www.nlm.nih.gov/medlineplus/cancer.html. CO7D 4 7/10 (2006.01) (Continued) CO7D 45/06 (2006.01) CO7D 409/4 (2006.01) CO7D 405/4 (2006.01) Primary Examiner — James O Wilson CO7D 453/02 (2006.01) Assistant Examiner — Ebenezer O Sackey CO7D 43/10 (2006.01) (74) Attorney, Agent, or Firm — Millen White Zelano and CO7D 403/4 (2006.01) Branigan, PC: Csaba Henter; Anthony Zelano CO7D 403/0 (2006.01) CO7D 40/0 (2006.01) (57) ABSTRACT CO7D 40/4 (2006.01) CO7D 413/4 (2006.01) Compounds selected from the group according to claim 1 are CO7D 417/4 (2006.01) inhibitors of tyrosine kinases, in particular of Metkinase, and A6 IK3I/50 (2006.01) can be employed, interalia, for the treatment of tumors. A6 IK3I/506 (2006.01) (Continued) 20 Claims, No Drawings US 9,403,799 B2 Page 2 (51) Int. Cl. WO 2009083076 T 2009 A 6LX3/5355 (2006.01) W. 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