IP Library › Granted Patent US 9,212,190

Granted Patent B2

US 9,212,190 · App. 13/738,410 · Granted Dec 15, 2015

IRAK inhibitors and uses thereof

Inventors: Geraldine C. Harriman (Charlestown, RI); Ronald T. Wester (Ledyard, CT); Donna L. Romero (Chesterfield, MO); Shaughnessy Robinson (Westerly, RI); Mee Shelley (Tigard, OR); Matthew David Wessel (Sisters, OR); Jeremy Robert Greenwood (Brooklyn, NY); Craig E. Masse (Cambridge, MA); Rosana Kapeller-Libermann (Chestnut Hill, MA)

Assignee: Nimbus Iris, Inc.

C07D495/04 A61K31/4365 A61K31/519 C07D495/14

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Quick Facts

Patent No.: US 9,212,190
App. No.: 13/738,410
Granted: Dec 15, 2015
Kind: B2

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Abstract

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

Claims (66)

1. A compound of formula XIV:

or a pharmaceutically acceptable salt thereof, wherein:

n is 1-2;

each R 1 is independently an optionally substituted group selected from C 1-6 aliphatic, phenyl, 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or halogen, —CN, —NO 2 , —OR, —CH 2 OR, —SR, —N(R) 2 , —S(O) 2 R, —S(O) 2 N(R) 2 , —S(O)R, —C(O)R, —C(O)OR, —C(O)N(R) 2 , —C(O)N(R)—OR, —N(R)C(O)OR, —N(R)C(O)N(R) 2 , Cy, or —N(R)S(O) 2 R; or R 1 is selected from one of the following formulas:

two R 1 groups are taken together with their intervening atoms to form an optionally substituted 4-7 membered fused, spiro-fused, or bridged bicyclic ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each Cy is an optionally substituted ring selected from a 3-7 membered saturated or partially unsaturated carbocyclic ring or a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

each R is independently hydrogen, or an optionally substituted group selected from C 1-6 aliphatic, phenyl, 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:

two R groups on the same nitrogen are taken together with their intervening atoms to form a 4-7 membered saturated, partially unsaturated, or heteroaryl ring having 0-3 heteroatoms, in addition to the nitrogen, independently selected from nitrogen, oxygen, or sulfur;

p is 0-2;

L 1 is a covalent bond or a C 1-6 bivalent hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by —N(R)—, —N(R)C(O)—, —C(O)N(R)—, —N(R)S(O) 2 —, —S(O) 2 N(R)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)— or —S(O) 2 —; and

each R 4 is independently halogen, —CN, —NO 2 , —OR, —SR, —N(R) 2 , —S(O) 2 R, —S(O) 2 N(R) 2 , —S(O)R, —C(O)R, —C(O)OR, —C(O)N(R) 2 , —N(R)C(O)R, —N(R)C(O)N(R) 2 , —C(O)N(R)OR, —N(R)C(O)OR, —N(R)S(O) 2 N(R) 2 , —N(R)S(O) 2 R, or an optionally substituted group selected from C 1-6 aliphatic, phenyl, 4-7 membered saturated or partially unsaturated heterocyclic having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

2. The compound of claim 1 , wherein R 4 is —OH or F, or pharmaceutically acceptable salt thereof.

3. A compound of formula XIX:

or a pharmaceutically acceptable salt thereof, wherein:

n is 1-2;

p is 0-2;

4. A compound of formula XXV:

or a pharmaceutically acceptable salt thereof, wherein:

Ring A is a 3-7 membered saturated or partially unsaturated carbocyclic ring or a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

n is 1-4;

p is 0-2;

R z is —R, —CN, —NO 2 , halogen, —C(O)N(R) 2 , —C(O)OR, —C(O)R, —N(R)C(O)OR, —N(R)C(O)N(R) 2 , —OR, or —S(O) 2 N(R) 2 ;

L 2 is a covalent bond or a C 1-6 bivalent hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by —N(R)—, —N(R)C(O)—, —C(O)N(R)—, —N(R)S(O) 2 —, —S(O) 2 N(R)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)— or —S(O) 2 —; and

wherein said compound is not:

5. The compound of claim 4 of formula XXVI:

6. The compound of claim 4 wherein n is 1, and R 1 is —N(R) 2 or Cy, or pharmaceutically acceptable salt thereof.

7. The compound of claim 4 , wherein n is 1 and R 1 is morpholino, or pharmaceutically acceptable salt thereof.

8. The compound of claim 4 , wherein n is 1 and R 1 is —N(CH 3 ) 2 , or pharmaceutically acceptable salt thereof.

9. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

n is 1;

Ring A is a 1,4-trans-substituted cyclohexyl ring;

Ring B is a cyclopento- or cyclohexo-fused ring;

m is 1-2;

p is 0-2;

W is N;

R z is —R, —CN, —NO 2 , halogen, —C(O)N(R) 2 , —C(O)OR, —C(O)R, —N(R)C(O)OR, —N(R)C(O)N(R) 2 , —OR, or —S(O) 2 N(R) 2 ;

L 1 is —O—;

each L 2 is independently a covalent bond or a C 1-6 bivalent hydrocarbon chain wherein one or two methylene units of the chain are optionally and independently replaced by —N(R)—, —N(R)C(O)—, —C(O)N(R)—, —N(R)S(O) 2 —, —S(O) 2 N(R)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —S(O)— or —S(O) 2 —;

two -L 2 (R 4 ) p —R 4 groups are taken together with their intervening atoms to form an optionally substituted 4-7 membered fused, spiro-fused, or bridged bicyclic ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

wherein said compound is not selected from the group consisting of:

10. A compound selected from the following:

11. A pharmaceutical composition comprising a compound according to claim 10 , and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 7, 2013

From: HARRIMAN, GERALDINE C.; WESTER, RONALD T.; ROMERO, DONNA L.; ROBINSON, SHAUGHNESSY; SHELLEY, MEE; WESSEL, MATTHEW DAVID; GREENWOOD, JEREMY ROBERT; MASSE, CRAIG E.; KAPELLER-LIBERMANN, ROSANA

To: NIMBUS IRIS, INC.

Reel/Frame 029942/0352 →

Continuity (6)

Provisional Application 61585194 · Jan 10, 2012

Provisional Application 61663227 · Jun 22, 2012

Provisional Application 61682637 · Aug 13, 2012

Provisional Application 61724695 · Nov 9, 2012

Provisional Application 61734133 · Dec 6, 2012

Related Publication 20130231328A1 · Sep 5, 2013