发明名称 Dihydropyridophthalazinone inhibitors of poly(ADP-ribose)polymerase (PARP)
摘要 A compound having the structure set forth in Formula (I) and Formula (II):; wherein the substituents Y, Z, A, B, R1, R2, R3, R4 and R5 are as defined herein. Provided herein are inhibitors of poly(ADP-ribose)polymerase activity. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat diseases, disorders and conditions that are ameliorated by the inhibition of PARP activity.
申请公布号 US8999987(B2) 申请公布日期 2015.04.07
申请号 US201313787496 申请日期 2013.03.06
申请人 BioMarin Pharmaceutical Inc. 发明人 Wang Bing;Chu Daniel
分类号 A01N43/58;A61K31/495;C07D237/36;A61K31/5025;A61K31/5377;C07D471/06 主分类号 A01N43/58
代理机构 Jones Day 代理人 Jones Day
主权项 1. A compound of Formula (I):wherein: Y is selected from the group consisting of: a) an aryl group optionally substituted with 1, 2, or 3 R6; andb) a substituent independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkylene, oxo, heterocycloalkyl, heterocycloalkylalkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, (NRARB)alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene;Z is selected from the group consisting of:a) an aryl group optionally substituted with 1, 2, or 3 R6;b) a heteroaryl group optionally substituted with 1, 2, or 3 R6; andc) a substituent independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkynyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, hydroxyalkylene, oxo, heterocycloalkyl, heterocycloalkylalkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, (NRARB)alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene;R1, R2, and R3 are each independently selected from the group consisting of hydrogen, halogen, alkenyl, alkoxy, alkoxycarbonyl, alkyl, cycloalkyl, alkynyl, cyano, haloalkoxy, haloalkyl, hydroxyl, hydroxyalkylene, nitro, NRARB, NRARBalkylene, and (NRARB)carbonyl; A and B are each independently selected from the group consisting of hydrogen, Br, Cl, F, I, OH, C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl, wherein C1-C6alkyl, C3-C8cycloalkyl, alkoxy, and alkoxyalkyl are optionally substituted with at least one substituent selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, and C3-C8cycloalkyl, wherein B is not OH; RA, and RB are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, and alkylcarbonyl; or RA and RB taken together with the atom to which they are attached form a 3-10 membered heterocycle ring optionally having one to three heteroatoms or hetero functionalities selected from the group consisting of —O—, —NH, —N(C1-C6-alkyl)-, —NCO(C1-C6-alkyl)-, —N(aryl)-, —N(aryl-C1-C6-alkyl-)-, —N(substituted-aryl-C1-C6-alkyl-)-, —N(heteroaryl)-, —N(heteroaryl-C1-C6-alkyl-)-, —N(substituted-heteroaryl-C1-C6-alkyl-, —S—, and S(O)q—, wherein q is 1 or 2 and the 3-10 membered heterocycle ring is optionally substituted with 0, 1, 2, 3, or 4 substituents independently selected from C2-C10-alkenyl, C1-C10-alkoxy, C1-C10-alkoxy-C1-C10-alkyl, C1-C10-alkoxycarbonyl, C1-C10-alkyl, C1-C10-alkylcarbonyl, C1-C10-alkylcarbonyloxy, C1-C10-alkylthio, C1-C10-alkylthio-C1-C10-alkyl, C2-C10-alkynyl, carboxy, cyano, formyl, C1-C10-haloalkoxy, C1-C10-haloalkyl, halogen, hydroxyl, C1-C10-hydroxyalkylene, mercapto, nitro, —NRARB, and (NRARB)carbonyl; R4 and R5 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkoxyalkyl, haloalkyl, hydroxyalkylene, and (NRARB)alkylene; and each R6 is selected from the group consisting of OH, NO2, CN, Br, Cl, F, I, C1-C6alkyl, C3-C8cycloalkyl, 3-8 membered heterocycloalkyl, C2-C6alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, C2-C6alkynyl, aryl, arylalkyl, (C3-C8cycloalkyl)alkyl, haloalkoxy, haloalkyl, hydroxyalkylene, oxo, heteroaryl, heteroarylalkoxy, heteroaryloxy, heteroarylthio, heteroarylalkylthio, heterocycloalkoxy, (3-8 membered heterocycloalkyl)thio, heterocyclooxy, NRARB, (NRARB)C1-C6alkylene, (NRARB)carbonyl, (NRARB)carbonylalkylene, (NRARB)sulfonyl, and (NRARB)sulfonylalkylene; or a single isomer, stereoisomer, or enantiomer, or mixture thereof, optionally as a salt thereof.
地址 Novato CA US