Back to results
US 2014/0228279 A1Published application
Cationic peptidopolysaccharides with excellent broad- spectrum antimicrobial activities and high selectivity
AssigneeNanyang Technological University
InventorsBee Eng Mary Chan, Peng Li
Life of this patent
Estimating the term…
Abstract
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.
Claims21
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.
4 more elements
(canceled)
(canceled)
A method of preparing a compound of Formula I:
- or a pharmaceutically acceptable salt thereof, the method comprising the steps of:
- a) reacting a compound of Formula II with a compound of Formula III to provide a compound of Formula IV;
- and
- b) deprotecting the compound of Formula IV to provide the compound of Formula I:
- wherein:
- each PG is a protecting group;
- 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.
9 more elements
(canceled)
Dependencies are inferred from the claim text.