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COMPOUNDS AS MODULATORS OF ENDOPLASMIC RETICULUM AMINOPEPTIDASE 1 (ERAP1)

机译:作为内质网氨基肽酶1(ERAP1)调节剂的化合物

摘要

A compound of formula (I-1), or a pharmaceutically acceptable salt or hydrate thereof, formula (I-1) wherein: ring A is a monocyclic 5, 6, or 7-membered heterocycloalkyl ring optionally substituted by one or more substituents selected from alkyl, CN, cycloalkyl, OH, alkoxy, halo, haloalkyl and heteroaryl, wherein said heteroaryl group is in turn optionally further substituted with one or more groups selected from halo and alkyl, and wherein one or two carbons in the 5, 6, or 7-membered heterocycloalkyl ring are optionally replaced by a group selected from O, NH, S and CO; L is a linker group which is a 2 to 7-membered saturated or unsaturated aliphatic group, wherein one or two carbon atoms in said group, other than the carbon atom directly bonded to ring A, are optionally replaced by a heteroatom-containing group selected from O, NH and S, and wherein when two carbon atoms are replaced, the heteroatom-containing groups are separated by at least two carbon atoms and the linker group is at least a 5- membered group;; the group X-Y is -NR23SO2- or -SO2NR23-; R1 is H, CN or alkyl; R2 is selected from COOH, tetrazolyl and C(O)NHSO2R24; R3 is selected from H, halo and alkyl; R4 is selected from H and halo; R6 is H; R7 is selected from H, CN, haloalkyl, halo, SO2-alkyl, SO2NR18R19, CONR20R21, heteroaryl and alkyl, wherein said heteroaryl group is optionally substituted by one or more substituents selected from alkyl, halo, alkoxy, CN, haloalkyl and OH; R8 is selected from H, alkyl, haloalkyl and halo; R9 is H, alkyl or halo; R18- R21 and R23 are each independently selected from H and alkyl; R24 is selected from alkyl and cyclopropyl. Further aspects of the invention relate to such compounds for use in the field of immuno- oncology and related applications.
机译:式(I-1)的化合物或其医药上可接受的盐或水合物,式(I-1),其中:环A是任选地由一个或多个选自烷基、CN、环烷基、OH、烷氧基、卤代、卤代烷基和杂芳基的取代基取代的单环5、6或7元杂环烷基环,其中,所述杂芳基又任选地被一个或多个选自卤代和烷基的基团进一步取代,并且其中5、6或7元杂环烷基环中的一个或两个碳任选地被选自O、NH、S和CO的基团取代;L是一个连接基,它是一个2至7元饱和或不饱和脂肪族基团,其中所述基团中的一个或两个碳原子,而不是直接连接到环a的碳原子,可选地被一个含杂原子的基团取代,该杂原子基团选自O、NH和S,其中当两个碳原子被取代时,所述含杂原子的基团由至少两个碳原子隔开,并且所述连接基团为至少一个五元基团;;X-Y组为-NR23SO2-或-SO2NR23-;R1为H、CN或烷基;R2选自COOH、四氮唑基和C(O)NHSO2R24;R3选自H、卤和烷基;R4选自H和halo;R6是H;R7选自H、CN、卤代烷基、卤代、SO2烷基、SO2NR18R19、CONR20R21、杂芳基和烷基,其中所述杂芳基任选地被选自烷基、卤代、烷氧基、CN、卤代烷基和OH的一个或多个取代基取代;R8选自H、烷基、卤代烷基和卤代;R9为H、烷基或卤;R18-R21和R23分别独立地选自H和烷基;R24选自烷基和环丙基。本发明的其他方面涉及用于免疫肿瘤学和相关应用领域的此类化合物。

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