Synthesis and use of amine-containing flavonoids as potent anti-leishmanial agents

摘要

The present invention relates to novel series of amine-containing flavonoids and compositions containing the compounds, as well as the synthesis and the use of the same. The invention also relates to methods of treatment and prevention of diseases, in particular, parasitic infections including Leishmaniasis, comprising administration of the compounds.

主权项

1. An anti-leishmanial compound having the general formula of: wherein: the flavonoid is selected from the group consisting of flavone, flavonol, flavanone, and isoflavonoid; X is a linker, wherein each linker independently comprises one or more groups selected from the group consisting of alkylene, ethyleneoxy, propyleneoxy, butyleneoxy, alkylC(O)—, ethylene amine, propylene amine, butylene amine, alkylcyclic amine, alkylcyclic diamine, or a combination thereof; R1 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkenyl, alkoxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, heteroaryl, —(CH2)n-aryl, —(CH2)n-heteroaryl, —(CH2)n-cycloalkyl, (CH2)n-cycloalkenyl, —(CH2)n-heterocycloalkyl, —(CH2)n-heterocycloalkenyl, —C(O)-alkyl, —C(O)-aryl, —C(O)-heteroaryl, —C(O)-cycloalkyl, —C(O)-cycloalkenyl, —C(O)-heterocycloalkyl, —C(O)-heterocycloalkenyl, —C(O)O-alkyl, —C(O)O-aryl, —C(O)O-heteroaryl, —C(O)O-cycloalkyl, —C(O)O-cycloalkenyl, —C(O)O-heterocycloalkyl, —C(O)O-heterocycloalkenyl, —SO2alkyl, —SO2aryl, —SO2-heteroaryl, —SO2cycloalkyl, —SO2heterocycloalkyl any of which may be optionally substituted; R2 is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, hydroxyalkenyl, hydroxyalkynyl, alkoxyalkenyl, alkoxyalkynyl, aminoalkyl, aminoalkenyl, aminoalkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, aryl, heteroaryl, —(CH2)n-aryl, —(CH2)n-heteroaryl, —(CH2)n-cycloalkyl, (CH2)n-cycloalkenyl, —(CH2)n-heterocycloalkyl, —(CH2)n-heterocycloalkenyl, —C(O)-alkyl, —C(O)-aryl, —C(O)-heteroaryl, —C(O)-cycloalkyl, —C(O)-cycloalkenyl, —C(O)-heterocycloalkyl, —C(O)-heterocycloalkenyl, —C(O)O-alkyl, —C(O)O-aryl, —C(O)O-heteroaryl, —C(O)O-cycloalkyl, —C(O)O-cycloalkenyl, —C(O)O-heterocycloalkyl, —C(O)O-heterocycloalkenyl, —SO2alkyl, —SO2aryl, —SO2-heteroaryl, —SO2cycloalkyl, —SO2heterocycloalkyl any of which may be optionally substituted; alternatively, NR1R2 form a cyclic compound with a general structure of —(CH2)n-Y—(CH2)m- wherein Y is CH2, O, or NR1, any of which may be optionally substituted; wherein n and m are independently selected from an integer between 1 to 6, or is a pharmaceutically acceptable salt thereof.