Patent ID: 6605618
Filing Date: 2003-08-12
Classification: A61P,C07D

Abstract:
A method of treating type II diabetes in a mammal in need thereof which comprises providing to said mammal, an effective amount of a compound of Formula I having the structure wherein, (a) a 5-6 membered heterocyclic ring having 1-4 heteroatoms selected from O, N, and S, substituted with (R1)m; (b) a phenyl ring substituted with (R1)m; (c) a naphthyl ring substituted with (R1)m; or (d) a phenyl fused heterocycle selected from the group consisting of U is â€”OCH2â€” or a bond; V is O or a bond; W is O, S(O)a; NR2, or NCOR2; X is SO2, CO, â€”(CH2)bâ€”, a bond, or Ar; Y is â€”NR3R4, Het, Ar, alkyl of 1-8 carbon atoms, or â€”O(CH2)dR5; R1 is alkyl of 1-8 carbon atoms, alkenyl of 2-7 carbon atoms, â€”OR6, halogen, cyano, trifluoromethyl, â€”CO2R6, â€”CONR6R7, â€”NHCOR6, or NHSO2R8; R2 is hydrogen, alkyl of 1-8 carbon atoms, or arylalkyl having 1-8 carbon atoms in the alkyl moiety; R3 and R4 are each, independently, hydrogen, alkyl of 1-8 carbon atoms, cycloalkyl of 3-8 carbon atoms, arylalkyl having 1-8 carbon atoms in the alkyl group, â€”(CH2)gR9, â€”(CH2)hCOR9, â€”(CH2)jCR10R11(CH2)jR9, or â€”(CH2)kCONR12R13; or R3 and R4 may be taken together together with the nitrogen to which they are attached to form a 3-7 membered saturated heterocycle, which may optionally contain 1-2 additional heteroatoms selected from O and S, and said heterocycle may optionally be substituted with R14; R5 is hydrogen; alkyl of 1-8 carbon atoms optionally substituted by 1-3 substituents selected from hydroxy, halogen, and aryl; cycloalkyl of 1-8 carbon atoms; Ar or Het; R6, R7, and R8 are each, independently, hydrogen, or alkyl of 1-8 carbon atoms, or aryl of 6-10 carbon atoms; R9 is hydrogen; alkyl optionally substituted with 1-3 substitutents selected from hydroxy, halogen, and aryl; cycloalkyl of 3-8 carbon atoms; Ar, or Het; R10 and R11 are each, independently, hydrogen, alkyl, or aryl optionally substituted with alkyl of 1-8 carbon atoms or halogen; or R10 and R11 are taken together to form a spiro fused cycloalkyl ring of 3-8 carbon atoms; R12 and R13 are each, independently, hydrogen, alkyl of 1-8 carbon atoms, aryl optionally substituted with alkyl of 1-8 carbon atoms or halogen; or R12 and R13 are taken together with the nitrogen to which they are attached to form a 3-7 membered saturated heterocycle, which may optionally contain 1-2 additional heteroatoms selected from O and S, and said heterocycle may optionally be substituted with R14; R14 is CO2R15 or aryl optionally substituted with a 1-3 substituents selected from â€”OR15 and cycloalkyloxy of 3-8 carbon atoms; R15 is alkyl of 1-8 carbon atoms or arylalkyl having 1-8 carbon atoms in the alkyl moiety; Ar is an aromatic ring system containing 1-2 carbocyclic aromatic rings having 6-10 carbon atoms optionally mono-, di-, or tri-substituted with R16; Het is (a) a 5-6 membered heterocyclic ring having 1-4 heteroatoms selected from O, S, and N which may be optionally mono- or di-substituted with R16; or (b) a heterocyclic ring system optionally mono- or di-substituted by R16 containing a 5-6 membered heterocyclic ring fused to one or two carbocyclic or heterocyclic rings such that the heterocyclic ring system contains 1-4 heteroatoms selected from O, S, and N; R16 is halogen, alkyl of 1-8 carbon atoms, â€”OR17, cycloalkyl of 3-8 carbon atoms, trifluoromethyl, cyano, â€”CO2R17, â€”CONR17R18, â€”SO2NR17R18, â€”NR19CONR17R18, â€”NR17R18, â€”NR17COR18, â€”NO2, â€”O(CH2)pCO2R17, â€”OCONR17R18, â€”O(CH2)qOR17, or a 5-6 membered heterocyclic ring containing 1-4 heteroatoms selected from O, S, and N; R17, R18, and R19 are each, independently, hydrogen, alkyl of 1-8 carbon atoms, arylalkyl having 1-8 carbon atoms in the alkyl moiety, or aryl optionally mono-, di-, or tri-substituted with halogen, cyano, nitro, hydroxy, alkyl of 1-8 carbon atoms, or alkoxy of 1-8 carbon atoms; or when R17 and R18 are contained on a common nitrogen, R17 and R18 may be taken together with the nitrogen to which they are attached to form a 3-7 membered saturated heterocycle, which may optionally contain 1-2 additional heteroatoms selected from O and S; a=0-2; b=1-6; d=0-3; g=0-6; h=0-6; j=0-6; k=0-6; m=0-2; p=1-6; q=1-6; or a pharmaceutically acceptable salt thereof.