DIAZEPANONE-FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF

1 . A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

X is O or S;

R 1 is —(C(R 4 ) 2 ) n R 5 , wherein R 5 is substituted with 0, 1, or 2 R 5′ ;

n is 0, 1, 2, or 3;

each R 4 is independently hydrogen, alkyl, halo, haloalkyl, hydroxy, alkoxy, or heteroalkyl;

R 5 is cycloalkyl, heterocycloalkyl, aryl, heteroaryl;

each R 5′ is independently aryl, heteroaryl, alkyl, cycloalkyl, heterocycloalkyl, halo, heteroalkyl, haloalkyl, cyano, hydroxy, amino, —N(R 6 ) 2 , —S(═O) 2 alkyl, —S(═O) 2 aryl, —S(═O) 2 heteroaryl, or alkoxy;

each R 6 is independently alkyl, cycloalkyl, aryl, or heteroaryl;

R 2 is aryl, heteroaryl, cycloalkyl, or heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, or heterocycloalkyl is substituted with at least one R 7 and 0, 1, or 2 R 8 ;

each R 7 is independently

Y is —C(═O)—, —S(═O)—, or —S(═O) 2 —;

R 9 and R 9′ are independently hydrogen, halo, alkyl, haloalkyl, cycloalkyl, heteroalkyl, or (alkyl)heterocycloalkyl;

R 10 is hydrogen, alkyl, haloalkyl, or cycloalkyl;

each R 8 is independently aryl, heteroaryl, alkyl, cycloalkyl, heterocycloalkyl, halo, heteroalkyl, haloalkyl, cyano, hydroxy, amino, —N(R 11 ) 2 , —S(═O) 2 alkyl, —S(═O) 2 aryl, —S(═O) 2 heteroaryl, or alkoxy;

each R 11 is independently alkyl, cycloalkyl, aryl, or heteroaryl;

R 3 is alkyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl substituted with 0, 1, 2, or 3 R 12 ;

each R 12 is independently aryl, heteroaryl, alkyl, heteroalkyl, haloalkyl, halo, cyano, alkoxy, heterocycloalkyl, —N(R 13 ) 2 , —S(═O) 2 NH 2 , —S(═O) 2 NMe 2 , —S(═O) 2 alkyl, —S(═O) 2 aryl, —S(═O) 2 heteroaryl, or cycloalkyl, wherein the aryl, heteroaryl, heterocycloalkyl, or cycloalkyl are each independently substituted with 0, 1, or 2 R 14 ;

each R 13 is independently alkyl, cycloalkyl, aryl, or heteroaryl

each R 14 is independently aryl, heteroaryl, alkyl, cycloalkyl, heterocycloalkyl, halo, heteroalkyl, haloalkyl, cyano, hydroxy, amino, —N(R 15 ) 2 , —S(═O) 2 alkyl, —S(═O) 2 aryl, —S(═O) 2 heteroaryl, or alkoxy;

each R 15 is independently alkyl, cycloalkyl, aryl, or heteroaryl;

each R 16 is independently aryl, heteroaryl, alkyl, heteroalkyl, haloalkyl, halo, cyano, hydroxy, amino, alkoxy, heterocycloalkyl, —N(R 17 ) 2 , —S(═O) 2 NH 2 , —S(═O) 2 NMe 2 , —S(═O) 2 alkyl, —S(═O) 2 aryl, —S(═O) 2 heteroaryl, or cycloalkyl, wherein the aryl, heteroaryl, heterocycloalkyl, or cycloalkyl are each independently substituted with 0, 1, or 2 R 18 ;

each R 17 is independently alkyl, cycloalkyl, aryl, or heteroaryl

each R 18 is independently aryl, heteroaryl, alkyl, cycloalkyl, heterocycloalkyl, halo, heteroalkyl, haloalkyl, cyano, hydroxy, amino, —N(R 19 ) 2 , —S(═O) 2 alkyl, —S(═O) 2 aryl, —S(═O) 2 heteroaryl, or alkoxy;

each R 19 is independently alkyl, cycloalkyl, aryl, or heteroaryl; and

m is 0, 1, 2, 3, or 4.

2 . (canceled)

3 . The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 5 is cyclopropyl, phenyl, naphthyl, anthracenyl, phenanthrenyl, pyridyl, pyrimidinyl, pyrazolyl, or imidazolyl and wherein R 5 is unsubstituted or R 5 is substituted with 1 or 2 R 5′ .

4 . (canceled)

5 . (canceled)

6 . The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein each R 4 is independently hydrogen, alkyl, halo, haloalkyl, or alkoxy.

7 . (canceled)

8 . (canceled)

9 . (canceled)

10 . The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein each R 5′ is independently phenyl, pyrrolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, methyl, ethyl, tert-butyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, fluoro, chloro, cyano, hydroxy, —N(R 6 ) 2 , methoxy, ethoxy, or trifluoromethoxy.

11 . (canceled)

12 . The compound of claim 10 or a pharmaceutically acceptable salt thereof, wherein each R 6 is independently alkyl or aryl.

13 - 17 . (canceled)

18 . The compound of claim 12 or a pharmaceutically acceptable salt thereof, wherein R 2 is phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, or triazinyl, wherein R 2 is unsubstituted or substituted with 1 or 2 R 8 .

19 . (canceled)

20 . The compound of claim 18 or a pharmaceutically acceptable salt thereof, wherein R 7 is

and Y is —C(═O) or —S(═O) 2 .

21 - 23 . (canceled)

24 . The compound of claim 20 or a pharmaceutically acceptable salt thereof, wherein R 9 and R 9′ are independently hydrogen, halo, alkyl, heteroalkyl, haloalkyl, or (alkyl)heterocycloalkyl.

25 . (canceled)

26 . (canceled)

27 . The compound claim 24 or a pharmaceutically acceptable salt thereof, wherein R 10 is hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, trifluoromethyl, or cyclopropyl.

28 . (canceled)

29 . (canceled)

30 . The compound of claim 27 or a pharmaceutically acceptable salt thereof, wherein each R 8 is independently methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, fluoro, chloro, heteroalkyl, cyano, hydroxy, amino, —N(R 11 ) 2 , methoxy, ethoxy, or trifluoromethoxy.

31 - 32 . (canceled)

33 . The compound of claim 30 or a pharmaceutically acceptable salt thereof, wherein each R 11 is independently methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, phenyl, naphthyl, anthracenyl, or phenanthrenyl.

34 - 36 . (canceled)

37 . The compound of claim 33 or a pharmaceutically acceptable salt thereof, wherein R 3 is phenyl, cyclopentyl, tetrahydropyranyl, oxetanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, indolyl, indazolyl, benzimidazolyl, azaindolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, cinnolinyl, or naphthyridinyl and wherein R 3 is unsubstituted or substituted with at least 1 R 12 .

38 - 45 . (canceled)

46 . The compound of claim 37 or a pharmaceutically acceptable salt thereof, wherein each R 12 is independently methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, hydroxyethyl, methoxyethyl, trifluoromethyl, trifluoroethyl, pentafluoroethyl, fluoro, chloro, cyano, methoxy, azetidinyl, oxetanyl, pyrrolidinyl, imidazolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl, morpholinyl, —N(R 13 ) 2 , cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl, wherein R 12 is unsubstituted or substituted 1 or 2 R 14 .

47 - 49 . (canceled)

50 . The compound of claim 46 or a pharmaceutically acceptable salt thereof, wherein each R 13 is independently alkyl or cycloalkyl.

51 - 55 . (canceled)

56 . The compound of claim 51 or a pharmaceutically acceptable salt thereof, wherein each R 14 is independently alkyl, cycloalkyl, heterocycloalkyl, halo, cyano, —N(R 15 ) 2 , or alkoxy.

57 . (canceled)

58 . (canceled)

59 . The compound of claim 56 or a pharmaceutically acceptable salt thereof, wherein each R 15 is independently alkyl or cycloalkyl.

60 - 62 . (canceled)

63 . The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

64 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

65 - 87 . (canceled)

88 . A method of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

89 . The method of claim 88 , wherein the cancer is selected from bladder cancer, prostate cancer, breast cancer, cervical cancer, colorectal cancer, endometrial cancer, gastric cancer, glioblastoma, head and neck cancer, lung cancer, and non-small cell lung cancer.

90 - 105 . (canceled)