IP Library › Granted Patent US 8,703,941

Granted Patent B2

US 8,703,941 · App. 13/347,610 · Granted Apr 22, 2014

IRAK inhibitors and uses thereof

Inventors: Donna L. Romero (Chesterfield, MO); Matthew David Wessel (Sisters, OR); Shaughnessy Robinson (Westerly, RI); Jeremy Robert Greenwood (Brooklyn, NY); Karl Shawn Watts (Portland, OR); Leah Lynn Frye (Portland, OR); Geraldine C. Harriman (Charlestown, RI); Alan Franklin Corin (Sudbury, MA); Craig E. Masse (Cambridge, MA); Mee Shelley (Tigard, OR)

Assignee: Nimbus Iris, Inc.

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Quick Facts

Patent No.: US 8,703,941
App. No.: 13/347,610
Granted: Apr 22, 2014
Kind: B2

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Abstract

The present invention provides thienopyrimidine and thienopyridine compounds, compositions thereof, and methods of using the same for the treatment of diseases mediated by IRAK enzymes. Such diseases include inflammatory and proliferative diseases.

Claims (53)

1. A compound of formula IV-i:

or a pharmaceutically acceptable salt thereof, wherein:

each R is independently hydrogen or an optionally substituted group selected from C 1-6 aliphatic, aryl, 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; and

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

2. A compound of formula IV-h:

or a pharmaceutically acceptable salt thereof, wherein

n is 1, and R 1 is of one the following formulas:

3. A compound of formula IV-h:

or a pharmaceutically acceptable salt thereof, wherein

n is 1 and R 1 is —N(CH 3 ) 2 ;

4. A compound of formula IV-h:

or a pharmaceutically acceptable salt thereof, wherein

n is 1, and R 1 is Cy;

5. The compound of claim 4 having the formula IV-j:

or a pharmaceutically acceptable salt thereof.

6. A compound of formula II-f:

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;

each R 1 is independently —R, halogen, —CN, —NO 2 , —OR, —CH 2 OR, —SR, —N(R) 2 , —SO 2 R—SO 2 N(R) 2 —SOR, —C(O)R, —CO 2 R, —C(O)N(R) 2 , —C(O)N(R)—OR, —NRC(O)R, —NRC(O)N(R) 2 , Cy, or —NRSO 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;

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

Ring B is an unsubstituted 4-8 membered partially unsaturated carbocyclic fused ring; and L is —O—.

7. A compound of formula II-f:

or a pharmaceutically acceptable salt thereof, wherein:

n is 1-4;

each R 1 is independently —R, halogen, —CN, —NO 2 , —OR, —CH 2 OR, —SR, —N(R) 2 —SO 2 R, —SO 2 N(R) 2 —SOR, —C(O)R, —CO 2 R, —C(O)N(R) 2 , —C(O)N(R)—OR, —NRC(O)R, —NRC(O)N(R) 2 , Cy, or —NRSO 2 R; or R 1 is selected from one of the following formulas:

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

Ring B is an unsubstituted 4-8 membered partially unsaturated carbocyclic fused ring; and L is —S—.

8. A compound selected from:

or a pharmaceutically acceptable salt thereof.

9. The compound of claim 8 , wherein said compound is selected from:

or a pharmaceutically acceptable salt thereof.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 19, 2012

From: SHELLEY, MEE

To: NIMBUS IRIS, INC.

Reel/Frame 029321/0725 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 23, 2012

From: ROMERO, DONNA L.; WESSEL, MATTHEW DAVID; ROBINSON, SHAUGHNESSY; GREENWOOD, JEREMY ROBERT; WATTS, KARL SHAWN; FRYE, LEAH LYNN; HARRIMAN, GERALDINE C.; CORIN, ALAN FRANKLIN; MASSE, CRAIG E.

To: NIMBUS IRIS, INC.

Reel/Frame 028614/0306 →

Continuity (3)

Provisional Application 61545873 · Oct 11, 2011

Provisional Application 61431227 · Jan 10, 2011

Related Publication 20120283238A1 · Nov 8, 2012