CATIONIC PEPTIDOPOLYSACCHARIDES WITH EXCELLENT BROAD- SPECTRUM ANTIMICROBIAL ACTIVITIES AND HIGH SELECTIVITY

摘要

The disclosure provides cationic peptidopolysaccharides of Formula I:;;which has a bacterial peptidoglycan-mimetic structure, and shows outstanding broad spectrum activities against clinically significant bacteria and fungi. The structural affinity of these compounds with microbial cell wall constituents promotes its passage to the cytoplasmic membrane resulting in excellent antimicrobial activity and record high selectivity.

主权项

1. A compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein: each R is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, (CH2)jOR1, (CH2)jC(O)R1, (CH2)jC(O)OR1, (CH2)jOC(O)R1, (CH2)jNR2R3, (CH2)jC(O)NR2R3, (CH2)jOC(O)NR2R3, (CH2)jC(NR4)NR2R3, (CH2)jNR4C(O)R1, (CH2)jNR4C(O)OR1, (CH2)jNR4C(O)NR2R3, (CH2)jNR4C(O)NR2R3, (CH2)jNR4C(NH)NR2R3, (CH2)jSH, (CH2)jS(O)kCH3, (CH2)jNR4S(O)kCH3, (CH2)jS(O)kNR2R3 and (CH2)jNR4S(O)kNR2R3, wherein j is an integer independently selected from 0 to 6, k is an integer independently selected from 0 to 2, and wherein each R group is optionally independently substituted with 1-3 substituent groups, each substituent group is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, perfluoroalkyl, amino, cyano, halogen, hydroxyl, nitro, aryl, arylalkyl, heterocycle, heteroaryl, and heteroarylalkyl; R1, R2, R3 and R4 are each independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, wherein each R1, R2, R3 and R4 group is optionally independently substituted with 1-3 substituent groups, each substituent group is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, perfluoroalkyl, amino, cyano, halogen, hydroxyl, nitro, aryl, arylalkyl, heterocycle, heteroaryl, and heteroarylalkyl; m is an integer independently selected from 1 to 100,000; n is an integer independently selected from 1 to 100,000; and x is an integer independently selected from 1 to 5,000.