INDAZOLE DERIVATIVES

摘要

Disclosed are compounds of Formula 1,;;and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, and R6 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating obesity and related diseases, disorders, and conditions associated with MetAP2.

主权项

1. A compound of Formula 1, or a pharmaceutically acceptable salt thereof, wherein: R1 is hydrogen; R2 is selected from hydrogen, —OH, chloro, fluoro, —CN, methyl, and hydroxymethyl; R3 is selected from C6-14 aryl, C1-9 heteroaryl, and C2-6 heterocyclyl, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, R7, and R8; R4 is hydrogen; R5 is C1-3 halo alkyl; R6 is selected from hydrogen, —OH, —NH2, chloro, fluoro, and methyl; each R7 is independently selected from—
OR9, —N(R9)R10, —NR9C(O)R10, —NHC(O)NR9R10, —NR9C(O)NHR10, —C(O)R9, —C(O)OR9, —C(O)N(R9)R10, —C(O)N(R9)OR10, —C(O)N(R9)S(O)2R8, —N(R9)S(O)2R8, —SR9, —S(O)R8, —S(O)2R8, and —S(O)2N(R9)R10; each R8 is independently selected from
(a) C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, and R11; and(b) C3-8 cycloalkyl-(CH2)m—, C2-6 heterocyclyl-(CH2)m—, C6-14 aryl-(CH2)m—, and C1-9 heteroaryl-(CH2)m—, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, R11, and C1-6 alkyl optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, and R11; each R9 and R10 is independently selected from
(a) hydrogen;(b) C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, and R11; and(c) C3-8 cycloalkyl-(CH2)m—, C2-6 heterocyclyl-(CH2)m—, C6-14 aryl-(CH2)m—, and C1-9 heteroaryl-(CH2)m—, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, R11, and C1-6 alkyl optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, and R11; each R11 is independently selected from—
OR12, —N(R12)R13, —N(R12)C(O)R13, —NHC(O)NR12R13, —NR12C(O)NHR13, —C(O)R12, —C(O)OR12, —C(O)N(R12)R13, —C(O)N(R12)OR13, —C(O)N(R12)S(O)2R14, —NR12S(O)2R14, —SR12, —S(O)R14, —S(O)2R14, and —S(O)2N(R12)R13; each R12 and R13 is independently selected from
(a) hydrogen; and(b) C1-6 alkyl and C3-8 cycloalkyl-(CH2)m—, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, —OH, and —NH2; each R14 is independently selected from C1-6 alkyl and C3-8 cycloalkyl-(CH2)m—, each optionally substituted with from one to five substituents independently selected from halo, oxo, —CN, —OH, and —NH2; and each m is independently selected from 0, 1, 2, 3, and 4; wherein each heteroaryl and heterocyclyl moiety has from one to four heteroatoms independently selected from N, O, and S.