Heteroaryls and uses thereof

• US 9,751,854 B2
• Filed: 11/09/2016
• Issued: 09/05/2017
• Est. Priority Date: 01/14/2014
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: Bharathan, Indu T., Blackburn, Chris, Ciavarri, Jeffrey P., Chouitar, Jouhara, Cullis, Courtney A., D'Amore, Natalie, Fleming, Paul E., Gigstad, Kenneth M., Gipson, Krista E., Girard, Mario, Hu, Yongbo, Lee, Janice, Li, Gang, Rezaei, Mansoureh, Sintchak, Michael D., Soucy, Francois, Stroud, Stephen G., Vos, Tricia J., Wong, Tzu-Tshin, Xu, He, Xu, Tianlin, Ye, Yingchun
• Primary Examiner(s): Pagano, Alexander R
• Application Number:
  US15/347,334
• Publication Number:
  US 20170073326A1
• Time in Patent Office: 300 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/497 containing further heterocyclic rings
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/549 having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 513/04 : Ortho-condensed systems

Abstract

The present invention provides a compound of formula I:

and pharmaceutically acceptable salts thereof, wherein X, R¹, R², R³, R⁴, R⁵, L¹, L², m, and n, are as described in the specification. Such compounds are inhibitors of VPS34 and thus useful for treating proliferative, inflammatory, or cardiovascular disorders.

Claims

1. A compound selected from the group consisting of:

2. The compound of claim 1, which is

3. The compound of claim 1, which is

4. The compound of claim 1, which is

5. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

6. The pharmaceutical composition of claim 5, wherein the compound is

7. The pharmaceutical composition of claim 5, wherein the compound is

8. The pharmaceutical composition of claim 5, wherein the compound is