COMPOUNDS FOR TREATMENT OF DRUG RESISTANT AND PERSISTENT TUBERCULOSIS

1 .- 8 . (canceled)

9 . A compound of Formula (Ia), a pharmaceutically acceptable salt, solvate, polymorph, prodrug, metabolite, N-oxide, stereoisomer, or isomer thereof:

wherein:

Y 1 is S or O or NR 2 ;

Y 3 is CR 5 or N;

R 1 is —O-(optionally substituted alkyl), —O-(alkenyl), —O-(alkynyl), —O-(cycloalkyl), —O-(heterocyclyl), —O-(optionally substituted aralkyl), —O-(optionally substituted heteroaralkyl), —O-(alkyl)-(alkoxy), —O-(alkyl)-(aralkoxy), —O-(alkyl)-(heterocyclyl), —O-(alkyl)-(COOR a ), —O-(alkyl)-(NR 6 R 7 ), —NR 6 R 7 or R 8 ;

R 2 and R 3 are each independently selected from H, optionally substituted alkyl, and optionally substituted aryl; or R 1 and R 2 taken together form a heterocycle;

R 4 is H, halogen, —CN, alkyl, aryl, —R b COOR a or —R b CH(COOR a ) 2 ;

R 5 is H, halogen, optionally substituted alkyl, or cycloalkyl; or R 4 and R 5 taken together form a carbocycle or an optionally substituted heterocycle;

R 6 and R 7 are each independently selected from H and optionally substituted alkyl;

wherein the optional substituent is halogen; or R 6 and R 7 taken together form an optionally substituted heterocycle with the nitrogen to which they are attached;

wherein the optional substituent is halogen;

R 8 is optionally substituted alkyl;

each R a is independently selected from H and alkyl;

R b is a bond or alkylenyl;

R c is a bond or alkenylenyl; and

A is optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted carbocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl or —R c -(optionally substituted heteroaryl).

10 .- 16 . (canceled)

17 . The compound of claim 9 , wherein Y 3 is CR 5 .

18 . The compound of claim 9 , wherein Y 1 is S.

19 . The compound of claim 9 , wherein Y 1 is S and Y3 is CH.

20 . The compound of claim 9 , wherein R 4 is H.

21 . The compound of claim 9 , wherein R 1 is —O-(optionally substituted alkyl); and R2 and R3 are both H.

22 . The compound of claim 9 , wherein A is optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted carbocyclyl, optionally substituted aralkyl, optionally substituted heteroaralkyl or —Rc-(optionally substituted heteroaryl); and the optionally substituted aryl, the optionally substituted heterocyclyl, the optionally substituted heteroaryl, the optionally substituted carbocyclyl, the optionally substituted aralkyl and the optionally substituted heteroaralkyl are substituted with 1-6 R10; wherein

each R 10 is independently selected from H, halogen, —CN, —NO 2 , —CF 3 , alkyl, —SR 6 , —OR 6 ,

—NR 6 R 7 , —NR 6 C(═O)(alkyl), —NR 6 C(═O)(cycloalkyl), —NR 6 C(═O)(heterocyclyl),

—NR 6 C(═O)(aryl), —NR 6 C(═O)(heteroaryl), —C(═O)NR 6 R 7 ,

—C(═O)NR 6 (cycloalkyl),

—C(═O)NR 6 (heterocycloalkyl), —C(═O)NR 6 (aryl), —C(═O)NR 6 (heteroaryl),

—NR 6 C(═O)NR 6 R 7 , —NR 6 C(═O)NR 7 (cycloalkyl),

—NR 6 C(═O)NR 7 (heterocycloalkyl),

—NR 6 C(═O)NR 7 (aryl), —NR 6 C(═O)NR 7 (heteroaryl), —NR 6 C(═O)O(alkyl),

—NR 6 C(═O)O(cycloalkyl), —NR 6 C(═O)O(heterocycloalkyl), —NR 6 C(═O)O(aryl),

—NR 6 C(═O)O(heteroaryl), —NR 6 SO 2 (alkyl), —NR 6 SO 2 (cycloalkyl),

—NR 6 SO 2 (heterocycloalkyl), —NR 6 SO 2 (aryl), —NR 6 SO 2 (heteroaryl), —SO 2 NR 6 R 7 ,

—SO 2 NR 6 (cycloalkyl), —SO 2 NR 6 (heterocycloalkyl), —SR 6 , —SO 2 R 6 , —SO 2 NR 6 (aryl),

—SO 2 NR 6 (heteroaryl), haloalkyl, aryl, heteroaryl, heterocyclyl and tetrazoyl.

23 . (canceled)

24 . The compound of claim 22 , wherein A is optionally substituted heteroaryl.

25 . The compound of claim 24 , wherein A is selected from:

26 . (canceled)

27 . The compound of claim 24 , wherein A is selected from:

wherein:

X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , and X 7 are independently selected from N and CR 10 ; and at least one of X 1 -X 7 is N.

28 . The compound of claim 27 wherein A is selected from:

29 . The compound of claim 24 , wherein A is selected from:

wherein:

X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , and X 7 are independently selected from N and CR 10 ; and

X is O, S, or NR 2 .

30 . The compound of claim 29 , wherein A is selected from:

31 . The compound of claim 30 , wherein A is selected from:

32 .- 35 . (canceled)

36 . The compound of claim 24 , wherein A is selected from:

wherein:

X is O, S, or NR 2 ; and

R 11 is H, alkyl, aryl, heteroaryl, —SO 2 -(alkyl), —SO 2 -(cycloalkyl), —SO 2 -(aryl),

—SO 2 -(heteroaryl), —SO 2 -(heterocycloalkyl), —C(═O)O(alkyl), —C(═O)O(cycloalkyl),

—C(═O)O(heterocycloalkyl), —C(═O)O(aryl), —C(═O)O(heteroaryl), —C(═O)NR 6 R 7 ,

—C(═O)NR 6 (cycloalkyl), —C(═O)NR 6 (heterocycloalkyl), —C(═O)NR 6 (aryl),

—C(═O)NR 6 (heteroaryl), —C(═O)(alkyl), —C(═O)(cycloalkyl),

—C(═O)(heterocycloalkyl),

—C(═O)(aryl), or —C(═O)(heteroaryl).

37 . The compound of claim 24 , wherein A is selected from:

38 .- 52 . (canceled)

53 . A compound selected from:

or pharmaceutically acceptable salt, solvate, polymorph, prodrug, metabolite, N-oxide, stereoisomer, or isomer thereof.

54 . A compound selected from:

or pharmaceutically acceptable salt, solvate, polymorph, prodrug, metabolite, N-oxide, stereoisomer, or isomer thereof.

55 .- 64 . (canceled)

65 . A pharmaceutical composition comprising a compound of claim 9 , or a pharmaceutically acceptable salt, solvate, polymorph, prodrug, metabolite, N-oxide, stereoisomer, or isomer thereof, and a pharmaceutically acceptable excipient.

66 . A method to treat drug resistant and persistent tuberculosis in a mammal, the method comprising administering a composition comprising a therapeutically effective amount of a compound of claim 9 .