Modulators of CFTR

• US 9,725,440 B2
• Filed: 02/27/2015
• Issued: 08/08/2017
• Est. Priority Date: 05/09/2007
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Hadida-Ruah, Sara, Bear, Brian, Grootenhuis, Peter, Miller, Mark, Zhou, Jinglan, McCartney, Jason
• Primary Examiner(s): Anderson, James D
• Application Number:
  US14/633,278
• Publication Number:
  US 20150166516A1
• Time in Patent Office: 893 Days
• Field of Search: None
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
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• CPC Class Codes: A61P 21/04 for myasthenia gravis
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• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/16 : for decreasing, blocking or antagonising the activity of the thyroid hormones
• CPC Class Codes: A61P 5/18 : of the parathyroid hormones
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: C07D 213/75 : Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: G01N 2333/705 : Assays involving receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: G01N 2500/04 : Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 2500/10 : involving cells
• CPC Class Codes: G01N 33/502 : for testing non-proliferative effects

Abstract

Compounds of the present invention, and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating CFTR mediated diseases using compounds of the present invention.

Claims

1. A compound of formula VI:

2. The compound according to claim 1, wherein said compound has formula VIA:

3. The compound according to claim 1, wherein said compound has formula VIB:

4. A pharmaceutical composition comprising:

(i) a compound or a pharmaceutically acceptable salt thereof according to claim 1; and

(ii) a pharmaceutically acceptable carrier.

5. A method of modulating CFTR activity comprising the step of contacting said CFTR with a compound or a pharmaceutically acceptable salt thereof according to claim 1.

6. A method of treating or lessening the severity of a disease in a patient, wherein said disease is cystic fibrosis, said method comprising the step of administering to said patient an effective amount of a compound or a pharmaceutically acceptable salt thereof according to claim 1.

7. A kit for use in measuring the activity of CFTR or a fragment thereof in a biological sample in vitro or in vivo, comprising:

(i) a composition comprising a compound or a pharmaceutically acceptable salt thereof according to claim 1; and

(ii) instructions for;

a) contacting the composition with the biological sample; and

b) measuring activity of said CFTR or a fragment thereof.