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(12) United States Patent (10) Patent No.: US 9,062,029 B2 Schadt Et Al

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(12) United States Patent (10) Patent No.: US 9,062,029 B2 Schadt Et Al USOO9062O29B2 (12) United States Patent (10) Patent No.: US 9,062,029 B2 Schadt et al. (45) Date of Patent: *Jun. 23, 2015 (54) PYRIMIDINYL PYRIDAZINONE 417/10 (2013.01); C07D 417/14 (2013.01); DERVATIVES C07D 451/06 (2013.01); C07D 453/02 (2013.01); A61 K3I/501 (2013.01); A61 K (71) Applicant: Merck Patent GmbH, Darmstadt (DE) 3 1/506 (2013.01); A61 K3I/5355 (2013.01): (72) Inventors: Oliver Schadt, Rodenbach (DE); Dieter A6IK3I/5377 (2013.01); A61K3I/55 Dorsch, Ober-Ramstadt (DE); Frank (2013.01); A61K 45/06 (2013.01) Stieber, Heidelberg (DE); Andree (58) Field of Classification Search Blaukat, Schriesheim (DE) CPC C07D 403/14: A61K31/506; A61K31/5377 USPC ................... 514/236.5, 252.02:544/123, 298 (73) Assignee: Merck Patent GmbH, Darmstadt (DE) See application file for complete search history. (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 (56) References Cited U.S.C. 154(b) by 0 days. This patent is Subject to a terminal dis U.S. PATENT DOCUMENTS claimer. 6,242.461 Bl 6/2001 Goldstein 6,403,586 B1 6/2002 Ohkuchi et al. (21) Appl. No.: 14/149,110 8,071,593 B2 12/2011 Schadt et al. 8,173,653 B2 5, 2012 Dorsch et al. (22) Filed: Jan. 7, 2014 8,329,692 B2 12/2012 Schadt et al. 8,580,781 B2 * 1 1/2013 Dorsch et al. ............ 514,217.06 (65) Prior Publication Data 8,658,643 B2 * 2/2014 Schadt et al. .............. 514,236.5 2004/O152739 A1 8, 2004 Hanau US 2014/O128396 A1 May 8, 2014 2004/0259863 A1 12/2004 Eggenweiler et al. 2005/0107391 A1 5/2005 Cui et al. 2007, OO15771 A1 1/2007 Matteucci et al. Related U.S. Application Data 2007/0043057 A1 2/2007 Matteucci et al. 2007/0203136 A1 8, 2007 Lu et al. (62) Division of application No. 13/565,914, filed on Aug. 2007/0265272 A1 1 1/2007 Cheng et al. 3, 2012, now Pat. No. 8,658,643, which is a division of 2008.O293719 A1 11/2008 Dorsch et al. application No. 12/668,491, filed as application No. 2009/00981.81 A1 4/2009 Lu et al. PCT/EP2008/005508 on Jul. 4, 2008, now Pat. No. 2009, O124612 A1 5/2009 Albrecht et al. 8,329,692. 2010/O197690 A1 8, 2010 Schadt et al. 2010, O234354 A1 9/2010 Dorsch et al. (30) Foreign Application Priority Data (Continued) Jul. 12, 2007 (DE) ......................... 10 2007 032 507 FOREIGN PATENT DOCUMENTS Apr. 29, 2008 (WO)................. PCT/EP2008/OO3473 DE 196 04388 8, 1997 (51) Int. Cl. DE 10 2005 057 924 6, 2007 A6 IK3I/506 (2006.01) (Continued) A 6LX3/5377 (2006.01) CO7D 403/4 (2006.01) OTHER PUBLICATIONS CO7D 403/0 (2006.01) CO7D 40/0 (2006.01) “Cancer MedLine Plus (2009). Accessed Mar 17, 2009. http:// CO7D 40/4 (2006.01) www.nlm.nih.gov/medlineplus/cancer.html. CO7D 405/4 (2006.01) CO7D 409/4 (2006.01) (Continued) CO7D 43/10 (2006.01) CO7D 413/4 (2006.01) CO7D 4 7/10 (2006.01) Primary Examiner — James O Wilson CO7D 417/4 (2006.01) Assistant Examiner — Ebenezer O Sackey CO7D 45/06 (2006.01) (74) Attorney, Agent, or Firm — Millen, White, Zelano & CO7D 453/02 (2006.01) Branigan, P.C. A6 IK3I/50 (2006.01) A 6LX3/5355 (2006.01) A6 IK3I/55 (2006.01) (57) ABSTRACT A6 IK 45/06 (2006.01) (52) U.S. Cl. Compounds selected from the group according to Claim 1 are CPC ............ C07D 403/10 (2013.01); C07D401/10 inhibitors of tyrosine kinases, in particular of Metkinase, and (2013.01); C07D401/14 (2013.01); C07D can be employed, interalia, for the treatment of tumours. 403/14 (2013.01); C07D405/14 (2013.01); C07D 409/14 (2013.01); C07D 413/10 (2013.01); C07D 413/14 (2013.01); C07D 4 Claims, No Drawings US 9,062,029 B2 Page 2 (56) References Cited Database CA (Online) Chemical Abstracts Service, Columbus, Ohio US; 1967. 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