MK2 inhibitors and uses thereof

Patent metadata

Field	Value
Publication number	US-9790235-B2
Application number	US-201615280157-A
Country	US
Kind code	B2
Filing date	Sep 29, 2016
Priority date	Sep 17, 2014
Publication date	Oct 17, 2017
Grant date	Oct 17, 2017

Abstract

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

First claim

We claim:

1. A compound of formula III:

or a pharmaceutically acceptable salt thereof, wherein:
T is —NH— or —O—;
each R is independently hydrogen or an optionally substituted C 1-6 aliphatic, or:
two R groups on the same nitrogen are taken together with the nitrogen to form a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms selected from nitrogen, oxygen, or sulfur;

R 1 is methyl;
R 2 is halogen, —CN, —SR y , —S(O)R y , —SO 2 R y , —OSO 2 R y , —OC(O)R y , or —OP(O) 2 OR y ;
each R y is independently selected from optionally substituted C 1-6 aliphatic or optionally substituted phenyl;
R 3 is hydrogen, optionally substituted C 1-6 aliphatic, —CN, —NO 2 , halogen, —OR, —N(R) 2 , —C(O)N(R) 2 , —C(O)OR, -Cy, —C(O)N(R)-Cy, —C(O)-Cy, —O-Cy, —O—(CH 2 ) n -Cy, —(CH 2 ) n —O-Cy, —N(R)-Cy, —N(R)—(CH 2 ) n -Cy, —(CH 2 ) n —N(R)-Cy, or —(CH 2 ) m -Cy;
each of m and n is independently 0-4; and
each Cy is independently an optionally substituted ring selected from a 3-9 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 3-9 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, phenyl, a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 7-12 membered saturated or partially unsaturated fused or bridged bicyclic carbocyclic ring, or a 7-12 membered saturated or partially unsaturated fused or bridged bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

2. The compound according to claim 1 , wherein -T- is —O—.

3. The compound according to claim 1 , wherein R 2 is halogen.

4. The compound according to claim 3 wherein R 2 is chloro.

5. The compound according to claim 1 , wherein R 3 is selected from —N(R) 2 , -Cy, —C(O)N(R)-Cy, —C(O)-Cy, —O-Cy, —O—(CH 2 ) n -Cy, —(CH 2 ) n —O-Cy, —N(R)-Cy, —N(R)—(CH 2 ) n -Cy, —(CH 2 ) n —N(R)-Cy, or —(CH 2 ) m -Cy.

6. The compound according to claim 5 , wherein each -Cy is independently an optionally substituted ring selected from a 3-7 membered saturated or partially unsaturated carbocyclic ring.

7. The compound according to claim 5 , wherein each -Cy is independently an optionally substituted ring selected from a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

8. The compound according to claim 5 , wherein each -Cy is independently an optionally substituted ring selected from oxetanyl, piperidinyl, pyrrolidinyl tetrahydrofuranyl, piperazinyl, and morpholinyl.

9. The compound according to claim 5 , wherein each -Cy is independently an optionally substituted ring selected from a 7-12 membered saturated or partially unsaturated fused or bridged bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

10. The compound according to claim 5 , wherein -Cy is substituted with a group selected from halogen, —(CH 2 ) 0-4 R ∘ , —(CH 2 ) 0-4 OR ∘ , or —(CH 2 ) 0-4 N(R ∘ ) 2 , wherein each R ∘ is independently hydrogen or C 1-6 aliphatic optionally substituted with halogen or —OR ● , wherein R ● is C 1-4 aliphatic.

11. The compound according to claim 1 , wherein R 3 is optionally substituted C 1-6 aliphatic.

12. The compound according to claim 11 , wherein R 3 is C 1-6 aliphatic optionally substituted with a group selected from —(CH 2 ) 0-4 OR ∘ , —(CH 2 ) 0-4 N(R ∘ ) 2 , or —(CH 2 ) 0-4 SO 2 R ∘ , wherein each R ∘ is independently hydrogen, a 5-6 membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or C 1-6 aliphatic optionally substituted with halogen, —CN, —(CH 2 ) 0-2 R ● , or —(CH 2 ) 0-2 OR ● , wherein R ● is C 1-4 aliphatic.

13. The compound according to claim 12 , wherein R 3 is C 1-6 aliphatic substituted with —(CH 2 ) 0-4 OR ∘ , wherein R ∘ is hydrogen or C 1-6 aliphatic optionally substituted with halogen, —CN, or —(CH 2 ) 0-2 OR ● , wherein R ● is C 1-4 aliphatic.

14. The compound according to claim 12 , wherein R 3 is C 1-6 aliphatic substituted with —(CH 2 ) 0-4 N(R ∘ ) 2 , wherein each R ∘ is independently hydrogen or C 1-6 aliphatic optionally substituted with —(CH 2 ) 0-2 OR ● , wherein R ● is C 1-4 aliphatic.

15. The compound according to claim 13 , wherein R 3 is C 1-6 aliphatic substituted with —(CH 2 ) 0-4 OR ∘ , wherein R ∘ is hydrogen or C 1-6 aliphatic optionally substituted with halogen.

16. The compound according to claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

17. The compound according to claim 1 selected from:

or a pharmaceutically acceptable salt thereof.

18. A pharmaceutically acceptable composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

Assignees

• Celgene Car Llc

Inventors

• Alexander Matthew David
• Chuaqui Claudio
• Malona John
• Mcdonald Joseph John
• Ni Yike
• Niu Deqiang
• Petter Russell C
• Singh Juswinder
• Pabba Chittari

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• C07D495/14 Primary

  Ortho-condensed systems · CPC title

• A61K31/551

  having two nitrogen atoms, e.g. dilazep · CPC title