Heterocyclic compounds and uses thereof

1. A compound of formula (I):

or a pharmaceutically acceptable salt, a prodrug, a solvate, a hydrate, a tautomer, a stereosiomer or a deuterated analog thereof,

wherein

(i) Y 1 and Y 2 are N, Y 3 is CR 2 , Y 4 is CH or N and Y 5 is CH; or

(iii) Y 1 is N, Y 2 is CH, Y 3 is CR 2 , Y 4 is N and Y 5 is N; or

(iv) Y 1 is C, Y 2 is CH, Y 3 is NR 2 , Y 4 is N and Y 5 is N;

L is —CHR 5 , wherein R 5 is H, D, halogen, —OH, C 1-6 alkyl, deuterated C 1-6 alkyl, C 2-6 -alkenyl, C 2-6 alkynyl, aryl, aryl-C 1-4 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl, heterocycloalkyl heterocycloalkyl-C 1-4 alkyl, heteroaryl, heteroaryl-C 1-4 alkyl, C 1-6 haloalkyl or C 1-6 -haloalkoxy, wherein the aliphatic or aromatic portion of R 5 is further optionally substituted with from 1-3 R c members, wherein each R c member is independently halogen, CN, —OH, —NH 2 , —NO 2 , —C(O)OH, —CH═CH 2 , —C≡CH, —C(S)OH, —C(O)NH 2 , —C(S)NH 2 , —S(O) 2 NH 2 , —NHC(O)NH 2 , —NHC(S)NH 2 , —NHS(O) 2 NH 2 , —C(NH)NH 2 , —OR d , —SR d , —OC(O)R d , —OC(S)R d , —P(═O)HR d , —P(═O)R d R d , —PH(═O)OR d , —P(═O)(OR d ) 2 , —OP(═O)(OR d ) 2 , —C(O)R d , —C(S)R d , —C(O)OR d , —C(S)OR d , —S(O)R d , —S(O) 2 R d , —C(O)NHR d , —C(S)NHR d , —C(O)NR d R d , —C(S)NR d R d , —S(O) 2 NHR d , —S(O) 2 NR d R d , —C(NH)NHR d , —C(NH)NR d R d , —NHC(O)R d , —NHC(S)R d , —NR d C(O)R d , —NR d C(S)R d , —NHS(O) 2 R d , —NR d S(O) 2 R d , —NHC(O)NHR d , —NHC(S)NHR d , —NR d C(O)NH 2 , —NR d C(S)NH 2 , —NR d C(O)NHR d , —NR d C(S)NHR d , —NHC(O)NR d R d , —NHC(S)NR d R d , —NR d C(O)NR d R d , —NR d C(S)NR d R d , —NHS(O) 2 NHR d , —NR d S(O) 2 NH 2 , —NR d S(O) 2 NHR d , —NHS(O) 2 NR d R d , —NR d S(O) 2 NR d R d , —NHR d , —NR d R d or R d , wherein each R d is independently C 1-6 alkyl or aryl; or two R d groups when attached to the same nitrogen atom are taken together with the nitrogen atom to which they are attached form a 4- to 6-membered ring: wherein each R d is further optionally substituted with from 1-3 R e , wherein each R e is independently halogen, CN, —OH, —NH 2 , —NO 2 , —C(O)OH, —C(S)OH, —C(O)NH 2 , —C(S)NH 2 , —S(O) 2 NH 2 , —NHC(O)NH 2 , —NHC(S)NH 2 , —NHS(O) 2 NH 2 , —C(NH)NH 2 , —OR f , —SR f , —OC(O)R f , —OC(S)R f , —P(═O)HR f , —P(═O)R f R f , —PH(═O)OR f , —P(═O)(OR f ) 2 , —OP(═O)(OR f ) 2 , —C(O)R f , —C(S)R f , —C(O)OR f , —C(S)OR f , —S(O)R f , —S(O) 2 R f , —C(O)NHR f , —C(S)NHR f , —C(O)NR f R f , —C(S)NR f R f , —S(O) 2 NHR f , —S(O) 2 NR f R f , —C(NH)NHR f , —C(NH)NR f R f , —NHC(O)R f , —NHC(S)R f , —NR f C(O)R f , —NR f C(S)R f , —NHS(O) 2 R f , —NR f S(O) 2 R f , —NHC(O)NHR f , —NHC(S)NHR f , —NR f C(O)NH 2 , —NR f C(S)NH 2 , —NRC(O)NHR f , —NR f C(S)NHR f , —NHC(O)NR f R f , —NHC(S)NR f R f , —NR f C(O)NR f R f , —NR f C(S)NR f R f , —NHS(O) 2 NHR f , —NR f S(O) 2 NH 2 , —NR'S(O) 2 NHR f , —NHS(O) 2 NR f R f , —NR f S(O) 2 NR f R f , —NHR f , —NR f R f or R f , wherein each R f is independently C 1-6 alkyl; or two R f groups when attached to the same nitrogen atom are taken together with the nitrogen atom to which they are attached form a 4- to 6-membered ring;

R 1 is optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heteroaryl or optionally substituted heterocycloalkyl;

R 2 is optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aryl-C 1-2 alkyl or optionally substituted heteroaryl-C 1-2 alkyl;

R 3 is a 5-membered heteroaryl having from 1-4 heteroatoms as ring members that are each independently O, N or S and wherein the heteroaryl is substituted with from 1-2 C 1-2 alkyl, which is optionally substituted with from 1-3 members that are each independently halogen, OH or CN; and

the notation is a single bond or a double bond to maintain ring A being aromatic.

2. The compound of claim 1 , having:

formula (Ia):

or a pharmaceutically acceptable salt, a solvate, a hydrate, a tautomer, a stereosiomer or a deuterated analog thereof,

wherein Y 4 is CH or N;

formula (Ic):

or a pharmaceutically acceptable salt, a solvate, a hydrate, a tautomer, a stereosiomer or a deuterated analog thereof; or

formula (Ie):

or a pharmaceutically acceptable salt, a solvate, a hydrate, a tautomer, a stereosiomer or a deuterated analog thereof.

3. The compound of claim 2 , wherein R 5 is H, C 1-6 alkyl, aryl, C 3-6 cycloalkyl, heteroaryl or heterocycloalkyl, each of which is optionally substituted with from 1-3 independently selected R c substituents.

4. The compound of claim 2 , wherein L is —CH 2 —, -CD 2 -, —CH(CH 3 )—, —CH(CH 2 CH 3 )—,

each of which is optionally substituted with from 1-3 R c substituents, wherein each R c is independently halogen, CN, —OH, —NH 2 , —NO 2 , —C(O)OH, —CH═CH 2 , —C≡CH, —C(S)OH, —C(O)NH 2 , —C(S)NH 2 , —S(O) 2 NH 2 , —NHC(O)NH 2 , —NHC(S)NH 2 , —NHS(O) 2 NH 2 , —C(NH)NH 2 , —OR d , —SR d , —OC(O)R d , —OC(S)R d , —P(═O)HR d , —P(═O)R d R d , —PH(═O)OR d , —P(═O)(OR d ) 2 , —OP(═O)(OR d ) 2 , —C(O)R d , —C(S)R d , —C(O)OR d , —C(S)OR d , —S(O)R d , —S(O) 2 R d , —C(O)NHR d , —C(S)NHR d , —C(O)NR d R d , —C(S)NR d R d , —S(O) 2 NHR d , —S(O) 2 NR d R d , —C(NH)NHR d , —C(NH)NR d R d , —NHC(O)R d , —NHC(S)R d , —NR d C(O)R d , —NR d C(S)R d , —NHS(O) 2 R d , —NR d S(O) 2 R d , —NHC(O)NHR d , —NHC(S)NHR d , —NR d C(O)NH 2 , —NR d C(S)NH 2 , —NR d C(O)NHR d , —NR d C(S)NHR d , —NHC(O)NR d R d , —NHC(S)NR d R d , —NR d C(O)NR d R d , —NR d C(S)NR d R d , —NHS(O) 2 NHR d , —NR d S(O) 2 NH 2 , —NR d S(O) 2 NHR d , —NHS(O) 2 NR d R d , —NR d S(O) 2 NR d R d , —NHR d , —NR d R d , or R d , wherein each R d is independently C 1-6 alkyl or aryl; or two R d groups when attached to the same nitrogen atom are taken together with the nitrogen atom to which they are attached form a 4- to 6-membered ring, wherein the wavy line indicates the point of attachment to the rest of molecule.

5. The compound of claim 2 , wherein R 1 is cycloalkyl, aryl, heteroaryl or heterocycloalkyl, each of which is optionally substituted with from 1-3 independently selected R c substituents or 1-3 independently selected R e substituents.

6. The compound of claim 2 , wherein R 1 is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, or 2-pyridyl, each of which is optionally substituted with from 1-3 independently selected halogen.

7. The compound of claim 2 , wherein R 2 is aryl, heteroaryl, aryl-C 1-2 alkyl or heteroaryl-C 1-2 alkyl, each of which is optionally substituted with from 1-3 independently selected R c substituents or 1-3 independently selected R e substituents.

8. The compound of claim 2 , wherein R 2 is 4-pyrazolyl, phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyrimidinyl, benzyl or 2-pyridyl-methyl, each of which is substituted with from 1-3 R g groups, where each R g group is independently halogen, CN, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, phenyl, carboxy, —C 1-6 alkyl-C(O)OH, —C 1-6 alkyl-C(O)O—C 1-6 alkyl or —C(O)O—C 1-6 alkyl, wherein the R g group is further optionally substituted with from 1-3 members that are each independently halogen, —OH, C 1-6 alkyl, C 1-6 alkoxy, carboxy or —C(O)O—C 1-6 alkyl.

9. The compound of claim 2 , wherein R 2 is 4-pyrazolyl, phenyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyrimidinyl, benzyl or 2-pyridyl-methyl, each of which is substituted with from 1-3 R h groups, wherein each R h group is independently halogen, —OH, —CN, methyl, -CD 3 , —CH 2 OH, -CD 2 OH, phenyl, methoxy, —CHF 2 , —CF 3 , —CFH 2 , CF 3 CH 2 —, —COOH, —CH 2 COOH, —CH 2 COOCH 3 , —COOCH 3 , 1-carboxycyclopropyl, or C 3-6 cycloalkyl.

10. The compound of claim 2 , wherein R 3 is a 5-membered heteroaryl having from 1-3 heteroatoms as ring members that are each independently from O, N or S, wherein the heteroaryl is substituted with from 1-2 methyl groups, which are optionally substituted with from 1-2 members that are each independently halogen, OH or CN.

11. The compound of claim 2 , wherein R 3 is

each of which is substituted with from 1-2 methyl groups, which are optionally substituted with from 1-2 members that are each independently halogen, OH or CN, wherein the wavy line indicates the point of attachment to the rest of molecule.

12. The compound of claim 2 , wherein R 3 is

13. The compound of claim 2 , having formula (Ia):

wherein Y 4 is CH or N.

14. A compound of formula:

or a pharmaceutically acceptable salt or a stereoisomer thereof.

15. A pharmaceutical composition comprising a compound of claim 2 and a pharmaceutical acceptable excipient or carrier.

16. A pharmaceutical composition comprising a compound of claim 2 and another therapeutic agent.

17. A method for modulating bromodomain, said method comprising: administering to a subject in need thereof a compound of claim 2 .

18. A method for modulating bromodomain, said method comprising: contacting a cell with a compound of claim 2 .

19. A method for treating a subject having a disease or condition mediated by a bromodomain, said method comprising:

administering to the subject in need thereof an effective amount of a compound of claim 2 .

20. The method of claim 19 , wherein the disease or condition is selected from a cancer, an autoimmune condition, an inflammatory condition or a combination thereof.