Benzotriazine Oxides as Drugs Targeting Mycobacterium Tuberculosis

1 . A compound having the structure of formula I:

wherein:

each X is independently H, halogen, alkyl, OR, SR, NR′R, or BR′R, wherein each R and each R′ is independently H, halogen, or alkyl;

W is N;

each A and B is optionally substituted alkyl, or A and B are joined in an optionally substituted heterocycloalkyl; and

Z is an optionally present, optionally substituted 5 or 6-membered ring, saturated or unsaturated, fused to the bezotriazine ring at the 6,7 position,

or a pharmaceutically acceptable salt or stereoisomer thereof.

2 . The compound of claim 1 wherein:

each X is H;

W is N;

A and B are joined in an optionally substituted piperidinyl or pyrrolidinyl; and

Z is present as a 5-membered ring, fused to the bezotriazine ring at the 6,7 position,

or a pharmaceutically acceptable salt or stereoisomer thereof.

3 . The compound of claim 1 selected from:

3-(diethylamino)benzo[e][1,2,4]triazine 1,4-dioxide (17o);

3-morpholinobenzo[e][1,2,4]triazine 1,4-dioxide (17p);

3-(pyrrolidin-1-yl)benzo[e][1,2,4]triazine 1,4-dioxide (17q);

3-(pyrrolidin-1-yl)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (20q);

3-(piperidin-1-yl)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (20r);

3-(dimethylamino)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (20s);

3-(benzyl(methyl)amino)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (20t);

3-(methyl(phenethyl)amino)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (20u);

3-(thiomorpholinosulfone-1-yl)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (20v);

3-(2-methylpiperidin-1-yl)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (20w); and

3-(4-(methylsulfonyl)piperazin-1-yl)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (20x),

or a pharmaceutically acceptable salt or stereoisomer thereof.

4 . The compound of claim 1 that is:

3-(pyrrolidin-1-yl)-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazine 1,4-dioxide (20q),

or a pharmaceutically acceptable salt or stereoisomer thereof.

5 . A pharmaceutical composition or kit comprising a compound of claim 1 and a second, different anti- mycobacterium tuberculosis (Mtb) drug.

6 . A pharmaceutical composition or kit comprising a compound of claim 2 and a second, different anti- mycobacterium tuberculosis (Mtb) drug.

7 . A method of making a compound of claim 1 according to the following scheme:

(a) HOF.ACN, DCM; b) HNR 2 R 3 , Et 3 N, DCM; wherein X is R 1 , W is N, A is R 3 and B is R 2 .

8 . A method of making a compound of claim 2 according to the following scheme:

(a) HOF.ACN, DCM; b) HNR 2 R 3 , Et 3 N, DCM; wherein X is R 1 , W is N, A is R 3 and B is R 2 .

9 . A method of treating a mycobacterium tuberculosis (Mtb) infection, comprising: contacting a person in need thereof with an effective amount of compound of claim 1 .

10 . A method of treating a mycobacterium tuberculosis (Mtb) infection, comprising: contacting a person in need thereof with an effective amount of compound of claim 2 .