BORONIC ACID BEARING LIPHAGANE COMPOUNDS AS INHIBITORS OF P13K- a AND/OR B

摘要

Compounds with unique liphagane meroterpenoid scaffold having boronic acid functionality in the skeleton are described (formula 1) together with pharmacological potential of these compounds as anticancer agents. A method of preparation and inhibiting the activity of phosphoinositide-3-kinase (PI3K-alpha and beta) has been presented. In particular, the invention describes a method of inhibiting PI3K isoforms, wherein the compounds are novel structures based on liphagane scaffold with unique boronic acid functionality. The methods and uses thereof are described herein this invention.

主权项

1. A compound of general formula 1, and pharmaceutically acceptable salts thereof, wherein, a) ‘Y’=O, S, NH or NR, wherein R=alkyl moiety, aryl moiety, heteroaryl moiety cyclic aliphatic ring or aromatic system; b) wherein n=0 or 1; ciii) wherein R1, R2 and R3 are independently selected from a group consisting of H, OH, OR, COR, CHO, CO2R, OCOR, NH2, NHR, NR, NRR′, NO2, F, Cl, Br, I, OSO3H, SO2R, CN, SiRR′R″, OCF3, CF3 and R, wherein, R, R′, R″ are independently selected from a group consisting of alkyl moiety, aryl moiety, heteroaryl moiety and cyclic aliphatic ring, wherein the cyclic aliphatic ring is selected from a group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl ring and wherein the cyclic aliphatic ring has different substitutions at different positions, wherein the alkyl moiety is selected from a group consisting of methyl, ethyl, propyl, isopropyl, butyl and isobutyl, and wherein aryl or heteroaryl moiety has substitutions selected from a group consisting of halo, alkyl with different chain length, nitro, amino, and sulphonyl substitutions; diii) wherein R4=H or OR or SR or SO2R or OSO3R or SiRR′R″ or NH2 or NHR or NRR′ or an alkyl substituent or one to ten carbon chain either linear or branched, saturated or unsaturated alkyl group optionally substituted with OH, H, ═O, ═S, OR, COR, CHO, CO2R, OCOR, NH2, NHR, NRR′, NO2, F, Cl, Br, I, OSO3H, SO2R′, CN, SiRR′R″ or R, wherein R, R′, R″ are independently selected from a group consisting of alkyl moiety, aryl moiety, heteroaryl moiety and cyclicaliphatic ring with different substitutions with varying chain length cyclicaliphatic ring with different substitutions and varying chain length, wherein the alkyl moiety is selected from a group consisting of methyl, ethyl, propyl, isopropyl, butyl isobutyl, and wherein aryl or heteroaryl moiety has substitutions selected from a group consisting of halo, alkyl with different chain length, nitro, amino, and sulphonyl substitutions; wherein the alkyl substituent is selected from a group consisting of methyl, ethyl, propyl and higher homologues, wherein the higher homologues are linear, branched or alicyclic substituents, wherein the alicyclic substituents are selected from a group consisting of cyclopentane, cyclohexane, higher membered rings, fused rings and aryl/heteroaryl substituted alkyl groups, wherein the aryl/heteroaryl substituted alkyl groups are benzylic or unsaturated alkyl groups further selected from a group consisting of cinnamul, crotyl and prenyl substituents; e) wherein R5, R6 and R7 are independently selected from a group consisting of H, one to ten carbon chain either linear or branched, saturated or unsaturated at any position, and alkyl group, wherein the alkyl group is optionally substituted with OH, H, ═O, ═S, OR, COR, CHO, CO2R, OCOR, NH2, NHR′, NRR′, NO2, F, Cl, Br, I, OSO3H, SO2R, CN, SiR′R′R″ and R, wherein R, R′, R″ independently selected from a group consisting of alkyl moiety, aryl moiety, heteroaryl moiety and cyclicaliphatic ring with different substitutions.