Claims for Patent: 9,682,968

Summary for Patent: 9,682,968

Title:	Piperidinyl-indole derivatives complement factor B inhibitors and uses thereof
Abstract:	The present invention provides a compound of formula I: (I) a method for manufacturing the compounds of the invention, and its therapeutic uses as inhibitors of the complement alternative pathway, in particular of Factor B. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
Inventor(s):	Adams Christopher Michael, Capparelli Michael Paul, Ehara Takeru, Karki Rajeshri Ganesh, Mainolfi Nello, Zhang Chun
Assignee:	Novartis AG
Application Number:	US14904694
Patent Claims:	2. A compound of claim 1 , or salt or tautomer thereof claim 1 , wherein n is 1.3. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein W is CHRor C(CH)R.4. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris C-Calkyl claim 1 , C-Calkoxy claim 1 , or cyclopropyl.5. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris methyl.6. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris hydrogen claim 1 , halogen or C-Calkyl.7. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris hydrogen.10. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris pyridin-3-yl which is substituted para to the piperidine ring with R.11. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris phenyl substituted para to the piperidine ring with Rand optionally substituted with fluoro claim 1 , methoxy claim 1 , hydroxymethyl or hydroxy.12. The compound of claim 11 , or a salt or tautomer thereof claim 11 , wherein Ris phenyl substituted para to the piperidine ring with R.14. The compound of claim 1 , or a salt or tautomer thereof claim 1 , wherein Ris COH claim 1 , CONH claim 1 , SONHor tetrazolyl.15. The compound of claim 1 , or a salt or tautomer thereof claim 1 , which compound is selected from the group consisting of1-((5,7-dimethyl-1H-indol-4-yl)methyl)-2-phenylpiperidin-4-ol;4-((4-methoxy-2-phenylpiperidin-1-yl)methyl)-5,7-dimethyl-1H-indole;5,7-dimethyl-4-((2-phenylpiperidin-1-yl)methyl)-1H-indole;1-((5,7-dimethyl-1H-indol-4-yl)methyl)-2-phenyl-piperidin-4-yl)methanol;4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzenesulfonamide;3-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzenesulfonamide;4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)-N-methylbenzenesulfonamide;3-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)-N-methylbenzenesulfonamide;4-((2-(4-fluorophenyl)-4-methoxypiperidin-1-yl)methyl)-5,7-dimethyl-1H-indole;(1-((5,7-dimethyl-1H-indol-4-yl)methyl)-2-phenylpiperidin-2-yl)methanol;(4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)methanol;5,7-dimethyl-4-((2-(4-(methylsulfonyl)phenyl)piperidin-1-yl)methyl)-1H-indole;4-((2-(4-(2H-tetrazol-5-yl)phenyl)piperidin-1-yl)methyl)-5,7-dimethyl-1H-indole;1-((5,7-dimethyl-1H-indol-4-yl)methyl)-2-phenylpiperidin-4-amine;4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzamide;4-(1-((5-chloro-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzamide;4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)-4-methoxypiperidin-2-yl)benzamide;4-(4-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-methylpiperidin-2-yl)benzamide;4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)-4-hydroxypiperidin-2-yl)benzoic acid;4-(1-((5-chloro-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;methyl 4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)-4-methoxypiperidin-2-yl)benzoate;4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-2-fluorobenzoic acid;4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)pyrrolidin-2-yl)benzoic acid;5-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)picolinic acid;4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-3-methoxybenzoic acid;4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;5-methoxy-7-methyl-4-((2-(pyridin-4-yl)piperidin-1-yl)methyl)-1H-indole;5-methoxy-7-methyl-4-((2-(pyridin-3-yl)piperidin-1-yl)methyl)-1H-indole;3-fluoro-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;4-(4-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)morpholin-3-yl)benzoic acid;6-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)nicotinic acid;4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-propoxypiperidin-2-yl)benzoic acid;4-(4-hydroxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-3-methylbenzoic acid;4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-5-methylpiperidin-2-yl)benzoic acid;4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-ethylpiperidin-2-yl)benzoic acid;2-(4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)acetic acid;2-(3-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)acetic acid;5-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-methoxypiperidin-2-yl)picolinic acid;2-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)thiazole-4-carboxylic acid;2-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-4-methylthiazole-5-carboxylic acid;3-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)azepan-2-yl)benzoic acid;4-((2-(4-(1H-pyrazol-4-yl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole;4-((2-(4-(1H-pyrazol-3-yl)phenyl)piperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole;4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-1-naphthoic acid;1-(2,2,2-trifluoro-1-(5-methoxy-7-methyl-1H-indol-4-yl)ethyl)piperidin-2-yl)benzoic acid;2-methoxy-4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;2-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)-2-phenylpiperidin-4-yl)acetonitrile;4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-methylpiperidin-2-yl)benzoic acid;4-(4-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;5-(4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)picolinic acid;4-(1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4,4-dimethylpiperidin-2-yl)benzoic acid;4-(4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzonitrile;4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;4-((4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)-4-methoxypiperidin-2-yl)benzoic acid;4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid;4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid;4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-methoxypiperidin-2-yl)benzoic acid;4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid;4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)-4-ethoxypiperidin-2-yl)benzoic acid;4-(5-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;4-(5-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzamide;4-(5-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;4-(5-hydroxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;1((5,7-dimethyl-1H-indol-4-yl)methyl)-N-methyl-2-phenylpiperidin-4-amine;(4-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)methanamine;(4-(4-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)methanol;4-((2-(3-(2H-tetrazol-5-yl)phenyl)piperidin-1-yl)methyl)-5,7-dimethyl-1H-indole;3-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzamide;(3-(1-((5,7-dimethyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)methanol;(4-((2-(4-(1H-tetrazol-5-yl)phenyl)-4-ethoxypiperidin-1-yl)methyl)-5-methoxy-7-methyl-1H-indole;4-(4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-N-(methylsulfonyl)benzamide;4-(4-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-N-methylbenzamide;4-(4-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-N,N-dimethylbenzamide;(4-(4-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)(morpholino)methanone;N-(2-hydroxyethyl)-4-(4-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzamide;4-(4-methoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)-N-(2-methoxyethyl)benzamide;N-((4-(1-((5-cyclopropyl-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)phenyl)sulfonyl)acetamide; 4-(6-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-6-azaspiro[2.5]octan-5-yl)benzoic acid;4-ethyl-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid;ethyl 4-((2S,4R)-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)-4-methylpiperidin-2-yl)benzoate; ethyl 4-((2S,4S)-4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoate and salts, stereoisomers and tautomers thereof.16. A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and a therapeutically effective amount of a compound of .17. A compound of which is 4-((2S claim 1 ,4S)-4-ethoxy-1-((5-methoxy-7-methyl-1H-indol-4-yl)methyl)piperidin-2-yl)benzoic acid or a pharmaceutically acceptable salt thereof.