| 摘要 |
Disclosed are new substituted nitrogen-containing heterocyclic derivatives represented by formula (I) as AKT inhibitors, optical isomers, pharmaceutically acceptable salts or solvates thereof, wherein the definition of R1, R2, R3, R4, R5, R6, ring A, ring C, B, Q, Y, Z and m is shown in the description for details. In addition, medicaments comprising the derivatives as active components are also disclosed, which can be useful for treating proliferative diseases, such as cancer and inflammation, especially diseases relating to AKT kinase. |
| 主权项 |
1. A compound of general formula (I): and an optical isomer thereof, or a pharmaceutically acceptable salt or a solvate thereof, wherein: ring A is selected from the group consisting of unsubstituted or substituted 5- or 6-membered aryl, 5- or 6-membered heterocyclic aryl containing 1 to 4 heteroatoms selected from O, N and S; B is selected fromwherein B1 and B2 are the same or different; B1 and B2 are each independently selected from the group consisting of O, N(Ra), C(Rb)(Rc) or are absent, wherein Ra, Rb and Rc are each independently selected from the group consisting of H, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy;
ring C is selected from unsubstituted or substituted 5-8 membered saturated or unsaturated aliphatic nitrogen-containing heterocyclic ring; R1 is selected from the group consisting of H, C1-C4 alkyl, halogenated C1-C4 alkyl,wherein n is an integer from 0 to 4; Rd is selected from the group consisting of H, C1-C4 alkyl, halogenated C1-C4 alkyl; Re is selected from the group consisting of C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy;
R2 is selected from unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic aryl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted saturated heterocyclic alkyl, unsubstituted or substituted unsaturated heterocyclic alkyl, optionally fused aryl and heterocyclic aryl; m is an integer from 0 to 3; R3 is selected from the group consisting of amino, cyano, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, C1-C4 carboxyl, halogenated C1-C4 alkoxy,wherein n is an integer from 0 to 4; Rd is selected from the group consisting of H, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy; Re is selected from the group consisting of C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy; ring D is selected from unsubstituted or substituted 5-8 membered saturated or unsaturated aliphatic nitrogen-containing heterocyclic ring
R4, R5 are each independently selected from the group consisting of H, halogen, nitro, amino, cyano, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy, unsubstituted or substituted furanyl, thienyl, phenyl, pyridinyl; Q, Y are each independently selected from N and —C(Rf)—; Z is selected from N and —C(Rg)—, and at least one group of Q, Y and Z is N, and at most two groups are the same; wherein Rf is selected from H, halogen; Rg is selected from the group consisting of H, halogen, hydroxyl, carboxyl, hydroxymethyl, saturated or unsaturated C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclic aryl, saturated or partly saturated heterocyclic ring without substituting, substituted saturated or partly saturated heterocyclic ring, unsubstituted or substituted cycloalkyl; R6 is selected from the group consisting of H, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, halogenated C1-C4 alkoxy; the substituent is optionally selected from the group consisting of halogen, nitro, amino, cyano, hydroxyl, C1-C4 alkyl, halogenated C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkylamido, halogenated C1-C4 alkoxy, halogenated C1-C4 alkylamido. |
