发明名称 Piperidine derivatives and compositions for the inhibition of nicotinamide phosphoribosyltransferase (NAMPT)
摘要 The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below: Formula (I);
申请公布号 US9555039(B2) 申请公布日期 2017.01.31
申请号 US201114115849 申请日期 2011.09.02
申请人 Forma TM, LLC. 发明人 Bair Kenneth W.;Baumeister Timm R.;Buckmelter Alexandre J.;Clodfelter Karl H.;Han Bingsong;Kuntz Judith D.;Lin Jian;Reynolds Dominic J.;Smith Chase C.;Wang Zhongguo;Zheng Xiaozhang
分类号 A61K31/44;A01N43/42;A61K31/5377;C07D215/48;C07D471/04;C07D513/04;C07D519/00;A61K31/4545;A61K45/06 主分类号 A61K31/44
代理机构 Gearhart Law LLC 代理人 Gearhart Law LLC
主权项 1. A compound of Formula II: wherein W is —C(O)—, —S(O)—, or —S(O)2—; R is an aryl or bicyclic heteroaryl; wherein said heteroaryl contains 1, 2, or 3 heteroatoms independently selected from N, S, and O, with the proviso that no two adjacent ring heteroatoms are both S or both O; and each of said aryl or heteroaryl is optionally substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, amino, aminoalkyl, (amino)alkoxy, —CONH2, —C(O)NH(alkyl), —C(O)N(alkyl)2, —C(O)NH(aryl), —C(O)N(aryl)2, —CF3, —CHF2, —CH2F, -alkyl, alkoxy, hydroxyl, hydroxyalkyl, (alkoxyalkyl)amino, —N(R3)—C(O)-alkyl, —N(R3)—C(O)-aryl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, with the proviso that no two adjacent ring heteroatoms in said heteroaryl are both S or both O; G is aryl, heteroaryl, cycloalkyl, heterocycloalkyl or —NR1R2; wherein each of said aryl, heteroaryl, heterocycloalkyl, and cycloalkyl is either unsubstituted or substituted with 1, 2, 3, or 4 substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, amino, aminoalkyl, (amino)alkoxy-, —CONH2, —C(O)NH(alkyl), —C(O)N(alkyl)2, —C(O)NH(aryl), —C(O)N(aryl)2, —CF3, —CHF2, —CH2F, alkyl, alkenyl, alkynyl, alkoxy, hydroxyl, hydroxyalkyl, aryloxy, (alkoxyalkyl)amino, —N(R3)—C(O)-alkyl, —N(R3)—C(O)-aryl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; and R1 and R2 are the same or they are different, and are independently selected from H, C1 to C7 alkyl, C1 to C7 alkoxy, C1 to C4 hydroxyalkyl, aryl, heteroaryl, heterocycloalkyl, and cycloalkyl, and wherein heteroatoms of said heteroaryl and heterocycloalkyl are independently selected from N, O, and S, with the proviso that no two adjacent ring heteroatoms are both S or both O; and further wherein R1 and R2 are each unsubstituted or optionally substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, amino, aminoalkyl, (amino)alkoxy, —CONH2, —C(O)NH(alkyl), —C(O)N(alkyl)2, —C(O)NH(aryl), —C(O)N(aryl)2, —CF3, —CHF2, —CH2F, alkyl, hydroxyalkyl, -alkoxy, hydroxyl, hydroxyalkyl, carboxy, (alkoxyalkyl)amino, -alkylamine, aminocarbonyl, —CHO, —N(R3)—C(O)-alkyl, —N(R3)—C(O)-aryl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; R3 is H, alkyl or arylalkyl; and n is 4, 5 or 6; or a pharmaceutically acceptable salt thereof.
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