Claims for Patent: 9,296,724

Summary for Patent: 9,296,724

Title:	Substituted pyridazinecarboxamides as kinase inhibitors
Abstract:	Pyridazine derivatives (e.g., Formula I) have unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as cancer.
Inventor(s):	Congxin Liang, Zhigang Li
Assignee:	Tyrogenex Inc, Xcovery Holdings Inc
Application Number:	US14/249,245
Patent Claims:	1. A compound of formula I: or a salt thereof; wherein: R1 , is arylalkyl or heteroarylalkyl, each optionally substituted with 1-4 independent Z1; R3 is hydrogen, hydroxy, alkoxy, or alkylamino; R6 is aryl, wherein R6 is optionally substituted by 1-3 groups, independently selected from alkyl, cycloalkyl, heterocyclyl, alkoxy, hydroxyalkyl, —C(O)NR7R8, and Z1; R7 and R8 are each independently selected from H, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, heteroaryl, or R7 and R8 together with nitrogen form a heterocyclyl or heteroaryl; each Z1 is halogen, CN, NO2, OR15, SR15, S(O)2OR15, NR15R16, C1-C2 perfluoroalkyl, C1-C2 perfluoroalkoxy, 1,2-methylenedioxy, C(O)OR15, C(O)NR15R16, OC(O)NR15R16, NR15C(O)NR15R16, C(NR16)NR15R16, NR15C(NR16)NR15R16, S(O)2NR15R16, R17, C(O)R17, NR15C(O)R17, S(O)R17, S(O)2R17, R16, oxo, C(O)R16, C(O)(CH2)nOH, (CH2)nOR15, (CH2)nC(O)NR15R16, or NR15S(O)2R17, where n is independently 0, 1, 2, 3, 4, 5 or 6; each R15 is independently hydrogen, C1-C4 alkyl or C3-C6 cycloalkyl; each R16 is independently hydrogen, alkenyl, alkynyl, C3-C6 cycloalkyl, aryl, heterocyclyl, heteroaryl, C1-C4 alkyl or C1-C4 alkyl substituted with C3-C6 cycloalkyl, aryl, heterocyclyl or heteroaryl; and each R17 is independently C3-C6 cycloalkyl, aryl, heterocyclyl, heteroaryl, C1-C4 alkyl or C1-C4 alkyl substituted with C3-C6 cycloalkyl, aryl, heterocyclyl or heteroaryl. 2. The compound of claim 1, of formula II: or a salt thereof, wherein: R6 is aryl, wherein R6 is optionally substituted by alkyl, cycloalkyl, heterocyclyl, alkoxy, hydroxyalkyl, or —C(O)NR7R8; and R7 and R8 are each independently selected from H, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, heterocyclyl, heteroaryl, or R7 and R8 together with nitrogen form a heterocyclyl or heteroaryl. 3. The compound of claim 1, wherein R6 is aryl substituted by alkyl, alkoxy, or —C(O)NR7R8. 4. The compound of claim 3, wherein R6 is aryl substituted by —C(O)NR7R8. 5. The compound of claim 1, wherein R6 is substituted by Z1. 6. The compound of claim 1, wherein R1 is arylalkyl optionally substituted with 1-4 independent Z1. 7. The compound of claim 1, wherein R3 is hydrogen. 8. The compound of claim 1, wherein the compound is selected from the following: {6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-[4-(pyrrolidinylcarbonyl)phenyl]carboxamide (5); {6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-[4-(N-methylcarbamoyl)phenyl]carboxamide (6); {6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-(4-methoxyphenyl)carboxamide (15); {6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-(4-morpholin-4-ylphenyl)carboxamide (16); {(6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-benzamide (17); {6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-[4-(2-morpholin-4-ylethoxy)phenyl]carboxamide (18); {(6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-{4-[(4-methylpiperazinyl)carbonyl]phenyl}carboxamide (25); and {6-amino-5-[(2,6-dichloro-3-fluorophenyl)ethoxy]pyridazin-3-yl}-N-[4-(piperazinylcarbonyl)phenyl]carboxamide (26). 9. A method of treating a disease in a subject comprising administering to the subject a compound of claim 1; wherein the disease is non-small cell lung cancer; anaplastic large cell lymphoma; inflammatory myofibroblastic tumor: neuroblastoma; ovarian cancer; papillary renal carcinoma; glioma; or breast cancer. 10. The method of claim 9, wherein the disease is mediated by the c-met, pecepteur d'origine nantais, or anaplastic lymphoma kinase or fusion proteins. 11. The method of claim 10, wherein the fusion proteins are selected from echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase and nucleophosmin-anaplastic lymphoma kinase. 12. A method of treating a disease in a subject comprising administering to the subject a composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier; wherein the disease is non-small cell lung cancer; anaplastic large cell lymphoma; inflammatory myofibroblastic tumor; neuroblastoma; ovarian cancer; papillary renal carcinoma; glioma; or breast cancer.