Tricyclic compounds as inhibitors of mutant IDH enzymes

1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:

wherein:

A is —CH(R 1 )— or —N(R 2 )—; R 1 is selected from the group consisting of hydrogen, —O—C 1-10 alkyl, and C 1-10 alkyl optionally substituted with one to four halogens; and R 2 is selected from the group consisting of hydrogen, —S(O) 2 —C 1-4 alkyl, and C 1-10 alkyl optionally substituted with one to four halogens;

B is —CH 2 — or —O—;

R is selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) —C 1-10 alkyl,

(4) —O—C 1-10 alkyl,

(5) —NR x R y , wherein each of R x and R y is independently selected from the group consisting of (a) hydrogen and (b) C 1-6 alkyl optionally substituted with one to four substituents independently selected from halogen and heterocyclyl; wherein the heterocyclyl is optionally substituted with one to four substituents independently selected from methyl, ethyl, propyl, butyl, —CH 2 —Cl, —CH 2 —F, —CH 2 CH 2 —Cl, —CH 2 CH 2 —F, and —CH 2 CF 3 ; and

(6) heterocyclyl, optionally substituted with one to four substituents independently selected from halogen, hydroxyl, —C 1-10 alkyl, and —O—C 1-10 alkyl;

R e is selected from the group consisting of:

(1) hydrogen,

(2) halogen, and

(3) C 1-6 alkyl; and

each of R f , R g , R h , R m , R n and R p is independently selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) C 1-6 alkyl, and

(4) —S(O) 2 —C 1-4 alkyl;

with the proviso that when R e is hydrogen, at least one of R f , R g , R h , R m , R n and R p is not hydrogen.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each occurrence of a heterocyclyl is independently selected from the group consisting of 2-azabicyclo[2.2.2]octanyl, 8-azabicyclo[3.2.1]octanyl, 2-azaspiro[3.3]heptanyl, azaindolyl, 1,6-diazaspiro[3.3]heptanyl, 2,3-dihydro-1,4-dioxinyl, 1,4-dioxanyl, hexahydro-3,6-epiminofuro[3,2-b]furanyl, hexahydro-1H-furo[3,4-c]pyrrolyl, imidazolyl, isoxazolyl, morpholinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 6-oxa-2-azaspiro[3.5]nonanyl, 2-oxa-5-azabicyclo[2.2.2]octanyl, 3-oxa-8-azabicyclo[3.2.1]octanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, 1-oxa-8-azaspiro[4.5]decanyl, 6-oxa-2-azaspiro[3.4]octanyl, 3-oxa-1,7-diazaspiro[4.4]nonanyl, 3,9-dioxa-7-azabicyclo[3.3.1]nonanyl, oxazolidinyl, piperazinyl, piperidinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolidinyl, pyrrolyl, tetrahydrofuranyl and tetrahydropyranyl.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

A is —CH(R 1 )— or —N(R 2 )—; R 1 is selected from the group consisting of hydrogen, —C 1-6 alkyl and —O—C 1-6 alkyl; R 2 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, —CH 2 CF 3 , and —S(O) 2 —C 1-4 alkyl; and

B is —CH 2 — or —O—.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R is selected from the group consisting of:

(1) hydrogen,

(2) halogen,

(3) —O—C 1-4 alkyl,

(4) —NH—C 1-2 alkyl, wherein the —C 1-2 alkyl is substituted with a heterocyclyl; wherein the heterocyclyl is optionally substituted with methyl, ethyl, propyl, —CH 2 Cl or —CH 2 CF 3 ; and

(5) heterocyclyl, optionally substituted with one to four substituents independently selected from halogen, C 1-4 alkyl, and —O—C 1-4 alkyl;

wherein each occurrence of a heterocyclyl of (4) and (5) is independently selected from the group consisting of 2-azabicyclo[2.2.2]octanyl, 8-azabicyclo[3.2.1]octanyl, 2-azaspiro[3.3]heptanyl, azaindolyl, 1,6-diazaspiro[3.3]heptanyl, 2,3-dihydro-1,4-dioxinyl, 1,4-dioxanyl, hexahydro-3,6-epiminofuro[3,2-b]furanyl, hexahydro-1H-furo[3,4-c]pyrrolyl, imidazolyl, isoxazolyl, morpholinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 6-oxa-3-azabicyclo[3.1.1]heptanyl, 6-oxa-2-azaspiro[3.5]nonanyl, 2-oxa-5-azabicyclo[2.2.2]octanyl, 3-oxa-8-azabicyclo[3.2.1]octanyl, 8-oxa-3-azabicyclo[3.2.1]octanyl, 1-oxa-8-azaspiro[4.5]decanyl, 6-oxa-2-azaspiro[3.4]octanyl, 3-oxa-1,7-diazaspiro[4.4]nonanyl, 3,9-dioxa-7-azabicyclo[3.3.1]nonanyl, oxazolidinyl, piperazinyl, piperidinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, tetrahydrofuranyl, and tetrahydropyranyl.

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R is selected from the group consisting of:

(1) hydrogen,

(2) —F,

(3) —Cl,

(4) —Br,

(5) —O-methyl,

(6) —O-ethyl,

(7) —NH—CH 2 -heterocyclyl, wherein the heterocyclyl is substituted with —CH 2 Cl, and

(8) heterocyclyl, optionally substituted with one to two substituents independently selected from —F, —Cl, methyl, ethyl, propyl, —O-methyl, —O-ethyl, —O-propyl and —O— isopropyl;

wherein each occurrence of a heterocyclyl of (7) and (8) is independently selected from the group consisting of 2-azabicyclo[2.2.2]octanyl, 8-azabicyclo[3.2.1]octanyl, 1,4-dioxanyl, hexahydro-3,6-epiminofuro[3,2-b]furanyl, morpholinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 6-oxa-2-azaspiro[3.5]nonanyl, 2-oxa-5-azabicyclo[2.2.2]octanyl, 3,9-dioxa-7-azabicyclo[3.3.1]nonanyl, oxazolidinyl, pyrazolyl, and tetrahydropyranyl.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R is selected from the group consisting of:

(1) hydrogen,

(2) —F,

(3) —Cl,

(4) —Br,

(5) —O-methyl,

(6) —O-ethyl,

(7) —NH—CH 2 -tetrahydropyranyl, wherein the tetrahydropyranyl is substituted with —CH 2 Cl, and

(8) heterocyclyl, optionally substituted with one to two substituents independently selected from —Cl, —F, methyl, ethyl, propyl, —O-methyl, —O-ethyl, —O-propyl and —O— isopropyl;

wherein the heterocyclyl is selected from the group consisting of 2-azabicyclo[2.2.2]octanyl, 8-azabicyclo[3.2.1]octanyl, 1,4-dioxanyl, hexahydro-3,6-epiminofuro[3,2-b]furanyl, morpholinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 6-oxa-2-azaspiro[3.5]nonanyl, 2-oxa-5-azabicyclo[2.2.2]octanyl, 3,9-dioxa-7-azabicyclo[3.3.1]nonanyl, oxazolidinyl and pyrazolyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R e is hydrogen, —F, —Cl, methyl or ethyl; and

each of R f , R g , R h , R m , R n and R p is independently selected from the group consisting of:

(1) hydrogen,

(2) —F,

(3) —Cl,

(4) —Br,

(5) methyl,

(6) ethyl,

(7) propyl, and

(8) —S(O) 2 —C 1-2 alkyl;

with the proviso that when R e is hydrogen, at least one of R f , R g , R h , R m , R n and R p is not hydrogen.

8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R e is —F, —Cl, methyl or ethyl; and

each of R f , R g , R h , R m , R n and R p is hydrogen.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

A is —CH(R 1 )— or —N(R 2 )—; R 1 is selected from the group consisting of hydrogen, methyl, —O— methyl, —O-ethyl, —O-propyl and —O-isopropyl; R 2 is selected from the group consisting of hydrogen, —CH 2 CF 3 , and —S(O) 2 -ethyl;

B is —CH 2 — or —O—;

R is selected from the group consisting of:

(1) hydrogen,

(2) —F,

(3) —Cl,

(4) —O-methyl,

(5) —O-ethyl,

(6) —NH—CH 2 -tetrahydropyranyl, wherein the tetrahydropyranyl is substituted with —CH 2 Cl, and

(7) heterocyclyl, optionally substituted with one to two substituents independently selected from —Cl, —F, methyl, ethyl, propyl, —O-methyl, —O-ethyl, and —O-propyl;

wherein the heterocyclyl is selected from the group consisting of 2-azabicyclo[2.2.2]octanyl, 8-azabicyclo[3.2.1]octanyl, 1,4-dioxanyl, hexahydro-3,6-epiminofuro[3,2-b]furanyl, morpholinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 6-oxa-2-azaspiro[3.5]nonanyl, 2-oxa-5-azabicyclo[2.2.2]octanyl, 3,9-dioxa-7-azabicyclo[3.3.1]nonanyl, oxazolidinyl and pyrazolyl;

R e is hydrogen, —Cl, —F, methyl or ethyl; and

each of R f , R g , R h , R m , R n and R p is independently selected from the group consisting of:

(1) hydrogen,

(2) —F,

(3) —Cl,

(4) —Br,

(5) methyl,

(6) ethyl,

(7) propyl, and

(8) —S(O) 2 -methyl;

with the proviso that when R e is hydrogen, at least one of R f , R g , R h , R m , R n and R p is not hydrogen.

10. The compound of claim 1 of formula (Ia), or a pharmaceutically acceptable salt thereof:

wherein

A is —CH(R 1 )— or —N(R 2 )—; R 1 is selected from the group consisting of hydrogen, methyl, —O— propyl and —O-isopropyl; R 2 is —CH 2 CF 3 or —S(O) 2 -ethyl;

R e is hydrogen, —Cl, —F, methyl or ethyl; and

each of R f , R g , R h , R m , R n and R p is independently selected from the group consisting of:

(1) hydrogen,

(2) —F,

(3) —Cl,

(4) —Br,

(5) methyl,

(6) ethyl,

(7) propyl, and

(8) —S(O) 2 -methyl;

with the proviso that when R e is hydrogen, at least one of R f , R g , R h , R m , R n and R p is not hydrogen.

11. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein:

R e is —F or methyl; and

each of R f , R g , R h , R m , R n and R p is hydrogen.

12. The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein:

R e is hydrogen;

each of R m and R n is hydrogen; and

each of R f , R g , R h , and R p is independently selected from the group consisting of:

(1) hydrogen,

(2) —F,

(3) —Cl,

(4) methyl, and

(5) —S(O) 2 -methyl;

with the proviso that at least one of R f , R g , R h and R p is not hydrogen.

13. The compound of claim 1 of formula (Ib), or a pharmaceutically acceptable salt thereof:

wherein

A is —CH(R 1 )—; and R 1 is —O-propyl or —O-isopropyl;

R e is hydrogen;

each of R f , R g , R m and R n is hydrogen;

each of R h and R p is independently selected from the group consisting of:

(1) hydrogen,

(2) —F, and

(3) —Cl;

with the proviso that at least one of R h and R p is not hydrogen; and

R is a heterocyclyl selected from the group consisting of 2-azabicyclo[2.2.2]octanyl, 8-azabicyclo[3.2.1]octanyl, 1,4-dioxanyl, hexahydro-3,6-epiminofuro[3,2-b]furanyl, morpholinyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 6-oxa-2-azaspiro[3.5]nonanyl, 2-oxa-5-azabicyclo[2.2.2]octanyl, 3,9-dioxa-7-azabicyclo[3.3.1]nonanyl, oxazolidinyl and pyrazolyl.

14. The compound of claim 1 selected from the group consisting of:

(8-Chloro-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-Chloro-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(trans-4-isopropoxycyclohexyl)methanone,

(8-Bromo-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(trans-4-isopropoxycyclohexyl)methanone,

(8-Chloro-3,9-difluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(trans-4-isopropoxycyclohexyl)methanone,

(8-Chloro-3,9-difluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(3-Fluoro-8-((3R,3aR,6R,6aR)-hexahydro-3,6-epiminofuro[3,2-b]furan-7-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-(2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-(2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(3-Fluoro-8-((1R,3r,5 S)-3-methoxy-8-azabicyclo[3.2.1]octan-8-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-((2S,5 S)-2,5-Dimethylmorpholino)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(3-Fluoro-8-(6-oxa-2-azaspiro[3.5]nonan-2-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

[3-Fluoro-8-(2-oxa-5-azabicyclo[2.2.2]oct-5-yl)-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl][trans-4-(propan-2-yloxy)cyclohexyl]methanone,

[3-Fluoro-8-(2-oxa-5-azabicyclo[2.2.2]oct-5-yl)-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl][trans-4-(propan-2-yloxy)cyclohexyl]methanone,

(8-((1R,5 S)-3,9-Dioxa-7-azabicyclo[3.3.1]nonan-7-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

[3-Fluoro-8-(6-oxa-2-azaspiro[3.5]non-2-yl)-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl][trans-4-(propan-2-yloxy)cyclohexyl]methanone,

(3-Fluoro-8-((3R,3aR,6R,6aR)-hexahydro-3,6-epiminofuro[3,2-b]furan-7-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(trans-4-isopropoxycyclohexyl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(trans-4-isopropoxycyclohexyl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(cis-4-isopropoxycyclohexyl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl)-3,9-difluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(3,9-Difluoro-8-(6-oxa-2-azaspiro[3.5]nonan-2-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(3,9-Difluoro-8-((3R,3 aR,6R,6aR)-hexahydro-3,6-epiminofuro[3,2-b]furan-7-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-((2S,5 S)-2,5-Dimethylmorpholino)-3,9-difluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

{3,9-Difluoro-8-[(1 S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl}[trans-4-(propan-2-yloxy)cyclohexyl]methanone,

[3,9-Difluoro-8-(6-oxa-2-azaspiro[3.5]non-2-yl)-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl][trans-4-(propan-2-yloxy)cyclohexyl]methanone,

[3,9-Difluoro-8-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl][trans-4-(propan-2-yloxy)cyclohexyl]methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl)-9-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(9-Fluoro-8-((3R,3 aR,6R,6aR)-hexahydro-3,6-epiminofuro[3,2-b]furan-7-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-(2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3,9-difluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(3,9-Difluoro-8-((1R,3r,5 S)-3-methoxy-8-azabicyclo[3.2.1]octan-8-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-((1R,4R)-2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3,9-difluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3,9-difluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-((S)-1,4-Dioxan-2-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-((R)-1,4-dioxan-2-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-(1,4-Dioxan-2-yl)-3,9-difluoro-5H-benzo[b]pyrido[2,3-e][1,4]diazepin-6(11H)-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-(1,4-Dioxan-2-yl)-9-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-(1,4-Dioxan-2-yl)-9-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(3-Fluoro-8-((1R,3 S,5 S)-3-methoxy-8-azabicyclo[3.2.1]octan-8-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(3-Fluoro-8-(6-oxa-2-azaspiro[3.5]nonan-2-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-((1R,5 S)-3,9-Dioxa-7-azabicyclo[3.3.1]nonan-7-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-(((3-(Chloromethyl)tetrahydro-2H-pyran-3-yl)methyl)amino)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-(2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(ethylsulfonyl)piperidin-4-yl)methanone,

(8-(2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3,9-difluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(3,9-Difluoro-8-(6-oxa-2-azaspiro[3.5]nonan-2-yl)-5H-benzo[b]pyrido[2,3-e][1,4]diazepin-6(11H)-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl)-3,9-difluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(3,9-Difluoro-8-((1R,3 S,5 S)-3-methoxy-8-azabicyclo[3.2.1]octan-8-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-((1R,4R)-2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(3,9-Difluoro-8-(1-methyl-1H-pyrazol-5-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(3,9-Difluoro-8-(1H-pyrazol-5-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(9-Fluoro-8-(1-methyl-1H-pyrazol-4-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(9-Fluoro-8-(1-methyl-1H-pyrazol-5-yl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(S)-(8-(1,4-Dioxan-2-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(R)-(8-(1,4-Dioxan-2-yl)-3-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(R)-(8-(1,4-Dioxan-2-yl)-9-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(S)-(8-(1,4-Dioxan-2-yl)-9-fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(Trans-4-isopropoxycyclohexyl){9-methyl-8-[(1S,4S)-2-oxa-5-azabicyclo[2.2.2]oct-5-yl]-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl}methanone,

(Trans-4-isopropoxycyclohexyl){7-methyl-8-[(1S,4S)-2-oxa-5-azabicyclo[2.2.2]oct-5-yl]-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl}methanone,

(Trans-4-isopropoxycyclohexyl){9-methyl-8-[(1R,4R)-2-oxa-5-azabicyclo[2.2.2]oct-5-yl]-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl}methanone,

(Trans-4-isopropoxycyclohexyl){7-methyl-8-[(1R,4R)-2-oxa-5-azabicyclo[2.2.2]oct-5-yl]-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl}methanone,

[9-Fluoro-8-(2-oxa-5-azabicyclo[2.2.2]oct-5-yl)-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl](trans-4-isopropoxycyclohexyl)methanone,

[7-Fluoro-8-(2-oxa-5-azabicyclo[2.2.2]oct-5-yl)-5,11-dihydro-6H-pyrido[2,3-b][1,5]benzodiazepin-6-yl](trans-4-isopropoxycyclohexyl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.1]heptan-5-yl)-9-fluoro-5H-benzo[b]pyrido[2,3-e][1,4]diazepin-6(11H)-yl)((2R,5 S)-5-isopropoxytetrahydro-2H-pyran-2-yl)methanone,

(8-Chloro-5-methyl-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(trans-4-isopropoxycyclohexyl)methanone,

(Trans-4-isopropoxycyclohexyl)(5-methyl-8-morpholino-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)methanone,

(8-Methoxy-5-methyl-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(Trans-4-isopropoxycyclohexyl)(8-methoxy-5-methyl-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3-methyl-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(trans-4-isopropoxycyclohexyl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3-(methylsulfonyl)-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(trans-4-isopropoxycyclohexyl)methanone,

(8-((1 S,4S)-2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3-chloro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(trans-4-isopropoxycyclohexyl)methanone,

(3,9-Difluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

(8-(2-Oxa-5-azabicyclo[2.2.2]octan-5-yl)-3,9-difluoro-5H-benzo[b]pyrido[2,3-e][1,4]diazepin-6(11H)-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone, and

(9-Fluoro-5,11-dihydro-6H-benzo[b]pyrido[2,3-e][1,4]diazepin-6-yl)(1-(2,2,2-trifluoroethyl)piperidin-4-yl)methanone,

or a pharmaceutically acceptable salt thereof.

15. A composition which comprises an inert carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

16. A method for treating a disease or disorder associated with mutant IDH enzyme activity in a mammalian subject in need thereof, which comprises administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

17. A method for treating a disease or disorder associated with mutant IDH enzyme activity in a mammalian subject which comprises B administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically B acceptable salt thereof n combination with another anti-cancer agent.

18. The method of claim 16 , wherein the disease or disorder associated with mutant IDH enzyme activity is a cancer selected from the group consisting of glioma, glioblastoma multiforme, paraganglioma, supratentorial primordial neuroectodermal tumors, acute myeloid leukemia (AML), breast cancer, prostate cancer, thyroid cancer, colon cancer, chondrosarcoma, cholangiocarcinoma, peripheral T-cell lymphoma, and melanoma.

19. The method of claim 18 , wherein the cancer is selected from glioma, glioblastoma multiforme, acute myeloid leukemia and breast cancer.