Fumagillol derivatives

A method for treating a disease, disorder or condition in a subject, the method comprising administering to the subject 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;
• and
• wherein the disease, disorder or condition is selected from hyperglycemia, diabetes, dyslipidaemia, obesity, insulin resistance, metabolic syndrome X, impaired glucose tolerance, polycystic ovary syndrome, cardiovascular disease, non-alcoholic liver steatosis, atherosclerosis, and Prader-Willi syndrome.