METHODS OF USING [3.2.0] HETEROCYCLIC COMPOUNDS AND ANALOGS THEREOF FOR TREATING INFECTIOUS DISEASES
Disclosed are methods of treating infectious diseases comprising administering to an animal, a therapeutically effective amount of a heterocyclic compound. The animal is a mammal, preferably a human or a rodent.
1 . A method of preventing mycobacterium tuberculosis from becoming multi-drug resistant comprising administering to an animal infected with said mycobacterium tuberculosis Salinosporamide A:
2 . The method of claim 1 , further comprising co-administering one or more anti-infective agent(s).
3 . The method of the claim 2 , wherein the one or more anti-infective agent(s) is selected from the group consisting of isoniazid, rifampin, ethambutol, pyrazinamide, rifater, streptomycin, rifapentine and epoxomicin.
4 . A method of treating drug resistant Tuberculosis comprising administering to an animal in need thereof. Salinosporamide A:
5 . The method of claim 4 , wherein the bacteria causing Tuberculosis is Mycobacterium tuberculosis.
6 . The method of claim 5 , further comprising co-administering one or more anti-infective agent(s).
7 . The method of the claim 6 , wherein the anti-infective agent(s) is selected from the group consisting of isoniazid, rifampin, ethambutol, pyrazinamide, rifater, streptomycin, rifapentine and epoxomicin.
8 . The method of the claim 7 , wherein the anti-infective agent is isoniazid.
9 . The method of claim 8 , wherein the bacteria causing Tuberculosis is Mycobacterium tuberculosis.
10 . A method of treating an infectious disease comprising administering to an animal in need thereof a compound having the structure of any one of Formulas I and II, or a pharmaceutically acceptable salt thereof:
wherein:
the dashed lines represent a single or a double bond;
each R 1 is separately a hydrogen, a halogen, a cyano, a nitro, an azido, a hydroxy, or a thiocyano, or selected from the group consisting of optionally substituted: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarbonyloxy, phenyl, cycloalkylacyl, alkylthio, arylthio, oxysulfonyl, carboxy, thio, sulfoxide, sulfone, sulfonate esters, boronic acids and esters, and halogenated alkyl including polyhalogenated alkyl;
n is 1 or 2, where if n is 2, then each R 1 can be the same or different;
m is 1 or 2, where if m is 2, then each R 4 can be the same or different;
R 2 is a hydrogen, a halogen, a cyano, a nitro, an azido, a hydroxy, or a thiocyano, or selected from the group consisting of optionally substituted: C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarbonyloxy, phenyl, cycloalkylacyl, alkylthio, arylthio, oxysulfonyl, carboxy, thio, sulfoxide, sulfone, sulfonate esters, boronic acids and esters, and halogenated alkyl including polyhalogenated alkyl;
R 3 is a halogen or selected from the group consisting of optionally substituted C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, aminocarbonyl, aminocarbonyloxy, nitro, azido, phenyl, cycloalkylacyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl;
each of E 1 , E 3 , E 4 and E 5 is an optionally substituted heteroatom;
E 2 is an optionally substituted heteroatom or —CH 2 — group;
each R 4 is separately a halogen, a cyano, a nitro, an azido, or a thiocyano, or selected from the group consisting of optionally substituted C 1 -C 24 alkyl, C 2 -C 24 alkenyl, C 2 -C 24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxycarbonyl, alkoxycarbonylacyl, amino, hydroxy, aminocarbonyl, aminocarbonyloxy, phenyl, cycloalkylacyl, alkylthio, arylthio, oxysulfonyl, carboxy, thio, sulfoxide, sulfone, sulfonate esters, boronic acids and esters, and halogenated alkyl including polyhalogenated alkyl; and
wherein the infectious disease is Tuberculosis.
11 . The method of claim 10 , wherein the compound is Salinosporamide A:
12 . The method of claim 11 , wherein the bacteria causing Tuberculosis is selected from the group consisting of Mycobacterium bovis, Mycobacterium africanum and Mycobacterium microti.
13 . The method of claim 11 , wherein the bacteria causing Tuberculosis is Mycobacterium tuberculosis.
14 . The method of claim 13 , further comprising co-administering one or more anti-infective agent(s).
15 . The method of the claim 14 , wherein the anti-infective agent(s) is selected from the group consisting of isoniazid, rifampin, ethambutol, pyrazinamide, rifater, streptomycin, rifapentine and epoxomicin.
16 . The method of the claim 15 , wherein the anti-infective agent(s) is isoniazid.
17 . The method of claim 10 , wherein the animal is a human.
18 . The method of claim 17 , wherein the compound is Salinosporamide A:
19 . The method of claim 18 , further comprising co-administering one or more anti-infective agent(s).
20 . The method of the claim 19 , wherein the anti-infective agent(s) is selected from the group consisting of isoniazid, rifampin, ethambutol, pyrazinamide, rifater, streptomycin, rifapentine and epoxomicin.