AKT INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF

摘要

Disclosed are inhibitors of the serine/threonine kinase Akt, pharmaceutical compositions comprising such inhibitors, and a method of preventing or treating a disease or condition in an animal by the use of such inhibitors. The Akt inhibitors have the formula (I) wherein X and Y are independently selected from the group consisting of O, CF₂, CH₂, and CHF; wherein A is independently selected from the group consisting of P(O)OH, CH₂000H, and CH(COOH)₂; R₂ is selected from the group consisting of H, OH, isosteres of OH, C₁-C₂₅ alkyloxy, C₆-C₁₀ aryloxy, C₃-C₈ cycloalkyloxy, C₃-C₈ cycloalkyl C₁-C₆ alkoxy, C₂-C₂₂ alkenyloxy, C₃-C₈ cycloalkenyloxy, C₇-C₃₂ aralkyloxy, C₇-C₃₂ alkylaryloxy, C₉-C₃₂ aralkenyloxy, and C₉-C₃₂ alkenylaryloxy; R₃-R₆ are independently selected from the group consisting of H, OH, isosteres of OH; and R₁ and R₇ are independently selected from the group consisting of C₁-C₂₅ alkyl, C₆-C₁₀ aryl, C₃-C₈ cycloalkyl, C₂-C₂₂ alkenyl, C₃-C₈ cycloalkenyl, C₇-C₃₂ aralkyl, C₇-C₃₂ alkylaryl, C₉-C₃₂ aralkenyl, and C₉-C₃₂ alkenylaryl; with the provisos that (i) when X is O, Y is O or CH₂, and R₃ is H, at least one of R₂ and R₄-R₆ is not OH; (ii) when A is CH₂COOH or CH(COOH)₂, X and Y cannot be simultaneously O; and (iii) all of R₂-R₆ are not simultaneously H. The inhibitors can be in the form of a salt also