Thiol mediated/activated prodrugs of sulfur dioxide (SO₂) having anti-bacterial activity

摘要

Disclosed herein are thiol mediated/activated prodrugs of SO2, particularly 2,4-dinitrophenylsulfonamide analogs, having Formula-I or pharmaceutically acceptable salts thereof exhibiting tunable release profiles of SO2 with significant therapeutic efficacy against bacterial infections. Further, the present invention provides pharmaceutical compositions comprising compound of Formula I or pharmaceutically acceptable salts thereof, along with pharmaceutically acceptable carriers/excipients.

主权项

1. A pharmaceutical composition for the treatment of an infection by at least one pathogen of the genus Staphylococcus, Enterococcus or Mycobacterium, comprising an effective amount of a thiol activated prodrug of SO2 having general Formula I or a pharmaceutically acceptable salt thereof, exhibiting tunable release profiles of SO2 with therapeutic efficacy against said infection, wherein either:
a) R1 is independently selected from the group consisting of H, (C1-C8) alkyl, alkylaryl, allyl, (C2-C8) alkynyl, a group of Formula II and a group of Formula III; and R2 is selected from the group consisting of allyl, a group of Formula IV and a group of Formula V; wherein n is either 0 or 1; R3 is independently selected from the group consisting of H, halogen, —CF3, (C1-C6) alkoxy, and —CN; and R4 and R4′ are independently selected from the group consisting of and substituted or unsubstituted (C1-C6) alkyl; orb) R1 and R2, together with the nitrogen atom to which R1 and R2 are attached, form a 5 or 6 membered heterocyclic ring, optionally containing an additional substituted or unsubstituted heteroatom selected from the group consisting of O and N, said 5 or 6 membered heterocyclic ring being optionally substituted with a substituent selected from the group consisting of H, (C1-C6) alkyl, and —COO(R5);
wherein R5 is H or (C1-C6) alkyl;further comprising an active ingredient selected from the group consisting of anti-tuberculosis drugs selected from the group consisting of rifampin, isoniazide, ethambutol, and pyrazinamide; Fluoroquinolones; Cephalosporins; Penicillins; Carbepenems; Aminoglycosides; Tetracyclines; and mixtures thereof.