IP Library › Granted Patent US 9,415,049

Granted Patent B2

US 9,415,049 · App. 14/137,700 · Granted Aug 16, 2016

Heteroaryl compounds and uses thereof

Inventors: Richland Tester (Marlborough, MA); Prasoon Chaturvedi (Shrewsbury, MA); Zhendong Zhu (Westborough, MA); Sekhar S. Surapaneni (Warren, NJ); Lisa Beebe (Acton, MA)

Assignee: Celgene Avilomics Research, Inc.

A61K31/505 A61K31/4035 A61K31/454 A61K31/4985 A61K31/506 A61K31/5377

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Quick Facts

Patent No.: US 9,415,049
App. No.: 14/137,700
Granted: Aug 16, 2016
Kind: B2

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Abstract

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Claims (323)

1. A combination comprising a compound of Formula I-a:

or a pharmaceutically acceptable salt thereof, wherein:

X and X′ are each independently O;

p and q are each independently 0 or 1, wherein p and q are not both 1;

R 1 is —OCH 2 CO 2 H, —OH, —OCH 3 , —OSO 3 H, —OGlu, —OCH 2 CH 2 OCH 3 , —OCH 2 CH 2 OSO 3 H, or —OCH 2 CH 2 OGlu;

each Glu is a glucuronyl moiety;

R 4 is —H, —OH, —OSO 3 H or —OGlu;

R x and R y are each independently —OH, —OSO 3 H, or —OGlu;

R z , R z′ and R z″ are each independently —H, —CH 3 , —OH, —OSO 3 H, or —OGlu; and

m and n are each independently 0, 1, 2, 3 or 4,

provided that at least one of the following is true:

(a) R 1 is —OH, —OSO 3 H, —OGlu, —OCH 2 CO 2 H, —OCH 2 CH 2 OSO 3 H or —OCH 2 CH 2 OGlu;

(b) at least one of R 4 , R z , R z′ and R z″ is —OH, —OSO 3 H or —OGlu;

(d) one of p or q is 1;

and an additional therapeutic agent selected from:

(i) a compound of formula A:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is an optionally substituted group selected from straight or branched C 1-8 aliphatic, aryl, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl or heterocyclylalkyl;

R 2 is hydrogen or an optionally substituted group selected from straight or branched C 1-8 aliphatic, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl, heterocyclylalkyl, aralkyl, or cycloalkylalkyl; and

R 3 is hydrogen or an optionally substituted straight or branched C 1-8 aliphatic group;

wherein when an aliphatic group is substituted with one or more substituents, such substituents are independently selected from halogen; aliphatic; hydroxyl; alkoxy; alkoxyaliphatic; amino; alkylamino; carboxy; nitro; cyano; thiol; thioether; imine; imide; amidine; guanidine; enamine; aminocarbonyl; acylamino; phosphonato; phosphine; thiocarbonyl; sulfonyl; sulfone; sulfonamide; ketone; aldehyde; ester; urea; urethane; oxime; hydroxylamine; alkoxyamine; aralkoxyamine; N-oxide; hydrazine; hydrazide; hydrazone; azide; isocyanate; isothiocyanate; cyanate; thiocyanate; oxo (═O); B(OH) 2 , or —O(aliphatic)aminocarbonyl; or

(ii) a compound selected from a compound of formulae C, D, F or G or a compound selected from B and E:

or a pharmaceutically acceptable salt thereof.

2. The combination according to claim 1 , wherein in the compound of Formula I-a:

R 4 is —H or —OH;

R x and R y are each independently —OH; and

R z , R z′ and R z″ are each independently —H, —CH 3 or —OH;

provided that at least one of the following is true:

(a) R 1 is —OH or —OCH 2 CO 2 H;

(b) at least one of R 4 , R z , R z′ and R z″ is —OH;

(d) one of p or q is 1.

3. The combination according to claim 1 , wherein in the compound of Formula I-a R 1 is —OCH 2 CH 2 OCH 3 .

4. The combination according to claim 1 , wherein the compound of Formula I-a has the structure:

or a pharmaceutically acceptable salt thereof.

5. The combination according to claim 4 , wherein in the compound of Formula IV R 1 is —OCH 2 CH 2 OCH 3 .

6. The combination according to claim 4 , wherein in the compound of Formula IV R 1 is —OH.

7. The combination according to claim 4 , wherein in the compound of Formula IV R 1 is —OCH 2 CO 2 H.

8. The combination according to claim 4 , wherein in the compound of Formula IV R 4 is —OH.

9. The combination according to claim 4 , wherein in the compound of Formula IV m is 1 and R x is —OH.

10. The combination according to claim 4 , wherein in the compound of Formula IV:

R 4 is —H or —OH; and

R x and R y are each independently —OH;

provided that at least one of the following is true:

(a) R 1 is —OH or —OCH 2 CO 2 H; or

(b) R 4 is —OH; or

11. A combination comprising a compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof wherein:

R 1 is —OR′, —OCH 2 CH 2 OR′ or —OCH 2 CO 2 H;

R′ is —H, —CH 3 , —SO 3 H or -Glu;

each Glu is a glucuronyl moiety;

R 4 is —H, —OH, —OSO 3 H or —OGlu;

R y is —OH, —OSO 3 H, or —OGlu; and

n is 0, 1, 2, 3 or 4;

and an additional therapeutic agent selected from:

(i) a compound of formula A:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is an optionally substituted group selected from straight or branched C 1-8 aliphatic, aryl, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl or heterocyclylalkyl;

R 3 is hydrogen or an optionally substituted straight or branched C 1-8 aliphatic group;

(ii) a compound selected from a compound of formulae C, D, F or G or a compound selected from B and E:

or a pharmaceutically acceptable salt thereof.

12. A combination comprising a compound of Formula I-a:

or a pharmaceutically acceptable salt thereof, wherein:

X and X′ are each independently O;

p is 1 and q is 0;

R 1 is —OR′, —OCH 2 CH 2 OR′ or —OCH 2 CO 2 H;

R′ is —H, —CH 3 , —SO 3 H or -Glu;

each Glu is a glucuronyl moiety;

R 4 is —H, —OH, —OSO 3 H or —OGlu;

R x and R y are each independently —OH, —OSO 3 H, or —OGlu;

R z , R z′ and R z″ are each independently —H, —CH 3 , —OH, —OSO 3 H, or —OGlu; and

m and n are each independently 0, 1, 2, 3 or 4;

and an additional therapeutic agent selected from:

(i) a compound of formula A:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is an optionally substituted group selected from straight or branched C 1-8 aliphatic, aryl, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl or heterocyclylalkyl;

R 3 is hydrogen or an optionally substituted straight or branched C 1-8 aliphatic group;

(ii) a compound selected from a compound of formulae C, D, F or G or a compound selected from B and E:

or a pharmaceutically acceptable salt thereof.

13. A combination comprising a compound of Formula I-a:

or a pharmaceutically acceptable salt thereof, wherein:

X and X′ are each independently O;

p is 0 and q is 1;

R 1 is —OR′, —OCH 2 CH 2 OR′ or —OCH 2 CO 2 H;

R′ is —H, —CH 3 , —SO 3 H or -Glu;

each Glu is a glucuronyl moiety;

R 4 is —H, —OH, —OSO 3 H or —OGlu;

R x and R y are each independently —OH, —OSO 3 H, or —OGlu;

R z , R z′ and R z″ are each independently —H, —CH 3 , —OH, —OSO 3 H, or —OGlu; and

m and n are each independently 0, 1, 2, 3 or 4;

and an additional therapeutic agent selected from:

(i) a compound of formula A:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is an optionally substituted group selected from straight or branched C 1-8 aliphatic, aryl, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl or heterocyclylalkyl;

R 3 is hydrogen or an optionally substituted straight or branched C 1-8 aliphatic group;

(ii) a compound selected from a compound of formulae C, D, F or G or a compound selected from B and E:

or a pharmaceutically acceptable salt thereof.

14. A combination comprising a compound of Formula I-a:

or a pharmaceutically acceptable salt thereof, wherein:

R z is selected from —CH 3 , —OH, —OSO 3 H, and —OGlu;

R z′ and R z″ are each independently —H, —CH 3 , —OH, —OSO 3 H, or —OGlu;

X and X′ are each independently O;

p and q are each independently 0 or 1, wherein p and q are not both 1;

R 1 is —OR′, —OCH 2 CH 2 OR′ or —OCH 2 CO 2 H;

R′ is —H, —CH 3 , —SO 3 H or -Glu;

each Glu is a glucuronyl moiety;

R 4 is —H, —OH, —OSO 3 H or —OGlu;

R x and R y are each independently —OH, —OSO 3 H, or —OGlu; and

m and n are each independently 0, 1, 2, 3 or 4; and an additional therapeutic agent selected from:

(i) a compound of formula A:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is an optionally substituted group selected from strai ht or branched C 1-8 aliphatic, aryl, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl or heterocyclylalkyl;

R 3 is hydrogen or an optionally substituted straight or branched C 1-8 aliphatic group;

(ii) a compound selected from a compound of formulae C, D, F or G or a compound selected from B and E:

or a pharmaceutically acceptable salt thereof.

15. The combination according to claim 14 , wherein in the compound of Formula I-a R z is —OH.

16. The combination according to claim 14 , wherein in the compound of Formula I-a R z is —CH 3 .

17. A combination comprising a compound of Formula I-a:

or a pharmaceutically acceptable salt thereof, wherein:

R z′ is selected from —CH 3 , —OH, —OSO 3 H, and —OGlu;

R z and R z″ are each independently —H, —CH 3 , —OH, —OSO 3 H, or —OGlu;

X and X′ are each independently O;

p and q are each independently 0 or 1, wherein p and q are not both 1;

R 1 is —OR′, —OCH 2 CH 2 OR′ or —OCH 2 CO 2 H;

R′ is —H, —CH 3 , —SO 3 H or -Glu;

each Glu is a glucuronyl moiety;

R 4 is —H, —OH, —OSO 3 H or —OGlu;

R x and R y are each independently —OH, —OSO 3 H, or —OGlu; and

m and n are each independently 0, 1, 2, 3 or 4;

and an additional therapeutic agent selected from:

(i) a compound of formula A:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is an optionally substituted group selected from straight or branched C 1-8 aliphatic, aryl, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl or heterocyclylalkyl;

R 3 is hydrogen or an optionally substituted straight or branched C 1-8 aliphatic group;

(ii) a compound selected from a compound of formulae C, D, F or G or a compound selected from B and E:

or a pharmaceutically acceptable salt thereof.

18. The combination according to claim 17 , wherein in the compound of Formula I-a R z′ is —OH.

19. The combination according to claim 17 , wherein in the compound of Formula I-a R z′ is —CH 3 .

20. A combination comprising a compound of Formula I-a:

or a pharmaceutically acceptable salt thereof, wherein:

R z″ is selected from —CH 3 , —OH, —OSO 3 H, and —OGlu;

R z and R z′ are each independently —H, —CH 3 , —OH, —OSO 3 H, or —OGlu;

X and X′ are each independently O;

p and q are each independently 0 or 1, wherein p and q are not both 1;

R 1 is —OR′, —OCH 2 CH 2 OR′ or —OCH 2 CO 2 H;

R′ is —H, —CH 3 , —SO 3 H or -Glu;

each Glu is a glucuronyl moiety;

R 4 is —H, —OH, —OSO 3 H or —OGlu;

R x and R y are each independently —OH, —OSO 3 H, or —OGlu; and

m and n are each independently 0, 1, 2, 3 or 4;

and an additional therapeutic agent selected from:

(i) a compound of formula A:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is an optionally substituted group selected from straight or branched C 1-8 aliphatic, aryl, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl or heterocyclylalkyl;

R 3 is hydrogen or an optionally substituted straight or branched C 1-8 aliphatic group;

(ii) a compound selected from a compound of formulae C, D, F or G or a compound selected from B and E:

or a pharmaceutically acceptable salt thereof.

21. The combination according to claim 20 , wherein in the compound of Formula I-a R z″ is —OH.

22. The combination according to claim 20 , wherein in the compound of Formula I-a R z″ is —CH 3 .

23. A combination comprising a compound of Formula IV:

or a pharmaceutically acceptable salt thereof wherein:

R 1 is —OR′, —OCH 2 CH 2 OR′ or —OCH 2 CO 2 H; or R 1 is —OCH 2 CH 2 OR′ wherein R′ is —CH 3 , —SO 3 H or -Glu;

R′ is —H, —CH 3 , —SO 3 H or -Glu;

each Glu is a glucuronyl moiety;

R 4 is —H, —OH, —OSO 3 H or —OGlu;

R x is —OH, —OSO 3 H, or —OGlu;

R y is —OH;

m is 0, 1, 2, 3 or 4; and

n is 1;

and an additional therapeutic agent selected from:

(i) a compound of formula A:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is an optionally substituted group selected from straight or branched C 1-8 aliphatic, aryl, cycloalkyl, heteroaryl, heterocyclyl, heteroaralkyl or heterocyclylalkyl;

R 3 is hydrogen or an optionally substituted straight or branched C 1-8 aliphatic group;

(ii) a compound selected from a compound of formulae C, D, F or G or a compound selected from B and E:

or a pharmaceutically acceptable salt thereof.

24. The combination according to claim 1 , wherein the compound of formula A is selected from:

7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-((trans-4-methoxycyclohexyl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(cis-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-((cis-4-methoxycyclohexyl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-ethyl-7-(1H-pyrrolo[3,2-b]pyridin-5-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-((cis-4-methoxycyclohexyl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-benzo[d]imidazol-4-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-((trans-4-methoxycyclohexyl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-((trans-4-hydroxycyclohexyl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(cis-4-hydroxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-(cis-4-hydroxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-ethyl-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-((cis-4-hydroxycyclohexyl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-(tetrahydro-2H-pyran-4-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-indol-4-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-((trans-4-hydroxycyclohexyl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-((cis-4-hydroxycyclohexyl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(trans-4-hydroxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(trans-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-isopropyl-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-(trans-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-(trans-4-hydroxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-isopropyl-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-ethyl-7-(5-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-hydroxypyridin-4-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-isopropyl-7-(4-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

5-(8-isopropyl-7-oxo-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)-4-methylpicolinamide

7-(1H-indazol-4-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-aminopyrimidin-5-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-aminopyridin-4-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(methylamino)pyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-hydroxypyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(4-(1H-pyrazol-3-yl)phenyl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(pyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-indazol-4-yl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-indazol-6-yl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(pyrimidin-5-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-methoxypyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(2-methoxyethyl)-7-(1H-pyrrolo[2,3-b]pyridin-5-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-ethyl-7-(1H-pyrrolo[2,3-b]pyridin-5-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-ethyl-7-(1H-indazol-4-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one 7-(pyridin-4-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-aminopyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-methyl-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

2-(2-hydroxypropan-2-yl)-5-(8-(trans-4-methoxycyclohexyl)-7-oxo-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)pyridine 1-oxide

4-methyl-5-(7-oxo-8-((tetrahydro-2H-pyran-4-yl)methyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)picolinamide

5-(8-((cis-4-methoxycyclohexyl)methyl)-7-oxo-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)-4-methylpicolinamide

7-(1H-pyrazol-4-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(trans-4-methoxycyclohexyl)-7-(4-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

3-((7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-2-oxo-3,4-dihydropyrazino[2,3-b]pyrazin-1 (2H)-yl)methyl)benzonitrile

1-((trans-4-methoxycyclohexyl)methyl)-7-(4-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

3-(7-oxo-8-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)benzamide

5-(8-((trans-4-methoxycyclohexyl)methyl)-7-oxo-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)-4-methylpicolinamide

3-((7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-2-oxo-3,4-dihydropyrazino[2,3-b]pyrazin-1 (2H)-yl)methyl)benzonitrile

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((1R,3R)-3-methoxycyclopentyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((1S,3R)-3-methoxycyclopentyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((1S,3S)-3-methoxycyclopentyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((1R,3S)-3-methoxycyclopentyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-indazol-6-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(2-morpholinoethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(trans-4-hydroxycyclohexyl)-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(cis-4-hydroxycyclohexyl)-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-(2-morpholinoethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-isopropyl-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-imidazo[4,5-b]pyridin-6-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-((cis-4-methoxycyclohexyl)methyl)-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(trans-4-hydroxycyclohexyl)-7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(cis-4-hydroxycyclohexyl)-7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

4-(7-oxo-8-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-5,6,7,8-tetrahydropyrazino[2,3-b]pyrazin-2-yl)benzamide

7-(1H-indazol-5-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-((1S,3R)-3-methoxycyclopentyl)-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-((1R,3R)-3-methoxycyclopentyl)-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-((1R,3S)-3-methoxycyclopentyl)-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-((1S,3S)-3-methoxycyclopentyl)-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-indol-5-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(1H-indol-6-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(4-(2-hydroxypropan-2-yl)phenyl)-1-(trans-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-((trans-4-methoxycyclohexyl)methyl)-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((cis-4-methoxycyclohexyl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(2-methoxyethyl)-7-(4-methyl-2-(methylamino)-1H-benzo[d]imidazol-6-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(7-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-methyl-4-(4H-1,2,4-triazol-3-yl)phenyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(2-methoxyethyl)-7-(4-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-benzyl-7-(2-methyl-4-(4H-1,2,4-triazol-3-yl)phenyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(3-fluoro-4-(4H-1,2,4-triazol-3-yl)phenyl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(3-fluoro-4-(4H-1,2,4-triazol-3-yl)phenyl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(3-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(trans-4-methoxycyclohexyl)-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-(trans-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(5-fluoro-2-methyl-4-(4H-1,2,4-triazol-3-yl)phenyl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(3-fluoro-2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(2-methoxyethyl)-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans-4-methoxycyclohexyl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(cyclopentylmethyl)-7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(4-(2-hydroxypropan-2-yl)phenyl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

(S)-7-(6-(1-hydroxyethyl)pyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

(R)-7-(6-(1-hydroxyethyl)pyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(4-(2-hydroxypropan-2-yl)phenyl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-(4-(trifluoromethyl)benzyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-(3-(trifluoromethyl)benzyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-(3-methoxypropyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(4-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(4-methyl-2-(methylamino)-1H-benzo[d]imidazol-6-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-amino-4-methyl-1H-benzo[d]imidazol-6-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

(R)-7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-3-methyl-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

(S)-7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-3-methyl-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-3,3-dimethyl-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-amino-4-methyl-1H-benzo[d]imidazol-6-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(2-methyl-4-(1H-1,2,4-triazol-3-yl)phenyl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

7-(4-(1H-1,2,4-triazol-5-yl)phenyl)-1-(2-(tetrahydro-2H-pyran-4-yl)ethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(1-hydroxypropan-2-yl)-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

1-(2-hydroxyethyl)-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one.

25. The combination according to claim 1 , wherein the compound of formula C is selected from:

or a pharmaceutically acceptable salt thereof.

26. The combination according to claim 1 , wherein the compound of formula F is selected from:

or a pharmaceutically acceptable salt thereof.

27. The combination according to claim 1 , wherein the compound of formula G is selected from:

or a pharmaceutically acceptable salt thereof.

Assignments (2)

MERGER AND CHANGE OF NAME Recorded Feb 16, 2017

From: CELGENE AVILOMICS RESEARCH, INC.; CELGENE CAR LLC

To: CELGENE CAR LLC

Reel/Frame 041738/0041 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 28, 2014

From: TESTER, RICHLAND; ZHU, ZHENDONG; SURAPANENI, SEKHAR; BEEBE, LISA; CHATURVEDI, PRASOON

To: CELGENE AVILOMICS RESEARCH, INC.

Reel/Frame 032547/0866 →

Continuity (1)

Related Publication 20150174128A1 · Jun 25, 2015