FUMAGILLOL DERIVATIVES

摘要

Disclosed are compounds of Formula 1,;;stereoisomers thereof and pharmaceutically acceptable salts of the compounds and stereoisomers, wherein R1 and R2 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, a stereoisomer thereof or a pharmaceutically acceptable salt of the compound or stereoisomer, wherein: R1 and R2 are each independently selected from phenyl, C3-5 heteroaryl, —OR4, and —N(R4)R5, wherein each phenyl and C3-5 heteroaryl is independently substituted with from 0 to 3 Ra, and each C3-5 heteroaryl has 5 or 6 ring atoms of which 1 or 2 are heteroatoms independently selected from N, O, and S; each Ra is independently selected from halo, —CN, R3, and R4; each R3 is independently selected from —OR4, —N(R4)R5, —NR4C(O)R6, —NR4C(O)OR5, —C(O)OR4, —C(O)N(R4)R5, —C(O)N(R4)OR5, —C(O)N(R4)S(O)2R6, —N(R4)S(O)2R6, —SR4, —S(O)R6, —S(O)2R6, and —S(O)2N(R4)R5; each R4 and R5 is independently selected from
(a) C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each substituted with from 0 to 3 Rb, and(b) C3-8 cycloalkyl-(CH2)m—, C2-6 heterocyclyl-(CH2)m—, C6-14 aryl-(CH2)m—, and C1-9 heteroaryl-(CH2)m—, each substituted with from 0 to 3 Rc; each R6 is independently selected from
(a) C1-6 alkyl, which is substituted with from 0 to 3 Rb, and(b) C3-8 cycloalkyl-(CH2)m—, C2-6 heterocyclyl-(CH2)m—, C6-14 aryl-(CH2)m—, and C1-9 heteroaryl-(CH2)m—, each substituted with from 0 to 3 Rd; each Rb is independently selected from halo, —CN, and R7; each Rc is independently selected from
(a) halo, —CN, and R7, and(b) C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, each substituted with from 0 to 3 Rb; each Rd is independently selected from
(a) halo, —CN, and R7, and(b) C1-6 alkyl, which is substituted with from 0 to 3 Rb; each R7 is independently selected from —OR8, —N(R8)R9, —NR8C(O)R9, —NR8C(O)OR9, —C(O)OR8, —C(O)N(R8)R9, —C(O)N(R8)OR9, —C(O)N(R8)S(O)2R9, —N(R8)S(O)2R9, —SR8, —S(O)R8, —S(O)2R8, and —S(O)2N(R8)R9; each R8 and R9 is independently selected from C1-6 alkyl, C3-8 cycloalkyl-(CH2)m—, and C2-6 heterocyclyl-(CH2)m—, each substituted with from 0 to 3 substituents independently selected from halo and —CN; and each m is independently selected from 0, 1, 2, 3, and 4; wherein each heteroaryl moiety listed in R4, R5, and R6 independently has from 1 to 4 heteroatoms independently selected from N, O, and S, and each heterocyclyl moiety listed in R4, R5, R6, and R8 independently has from 1 to 4 heteroatoms independently selected from N, O, and S.