Modulator of cystic fibrosis transmembrane conductance regulator, pharmaceutical compositions, methods of treatment, and process for making the modulator

• US 10,570,115 B2
• Filed: 09/29/2017
• Issued: 02/25/2020
• Est. Priority Date: 09/30/2016
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Alcacio, Timothy, Baek, Minson, Grootenhuis, Peter, Hadida Ruah, Sara Sabina, Hughes, Robert M., Keshavarz-Shokri, Ali, McAuley-Aoki, Rachel, McCartney, Jason, Miller, Mark Thomas, Van Goor, Fredrick, Zhang, Beili, Anderson, Corey, Cleveland, Thomas, Frieman, Bryan A., Khatuya, Haripada, Joshi, Pramod Virupax, Krenitsky, Paul John, Melillo, Vito, Pierre, Fabrice Jean Denis, Termin, Andreas P., Uy, Johnny, Zhou, Jinglan, Abela, Alexander Russell, Busch, Brett Bradley, Paraselli, Prasuna, Siesel, David Andrew
• Primary Examiner(s): Coughlin, Matthew P
• Assistant Examiner(s): Patel, Sagar
• Application Number:
  US15/721,390
• Publication Number:
  US 20180093969A1
• Time in Patent Office: 879 Days
• Field of Search: 514341, 514343, 514407, 514422, 5462754, 5462794, 5483641, 548518
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/12 Mucolytics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/14 Ortho-condensed systems
• CPC Class Codes: C07D 498/14 Ortho-condensed systems

Abstract

Compounds of Formula I:

pharmaceutically acceptable salts thereof, deuterated derivatives of any of the foregoing, and metabolites of any of the foregoing are disclosed. Pharmaceutical compositions comprising the same, methods of treating cystic fibrosis using the same, and methods for making the same are also disclosed.

Claims

1. A compound having the following formula:

2. A pharmaceutical composition comprising the compound, pharmaceutically acceptable salt, or deuterated derivative of claim 1, a pharmaceutically acceptable carrier and optionally one or more of:

(a) Compound II;

3. A method of treating cystic fibrosis comprising administering to a patient in need thereof a pharmaceutical composition according to claim 2.

6. A pharmaceutical composition comprising the compound of claim 1.

11. A method of treating cystic fibrosis comprising administering to a patient in need thereof the compound according to claim 1.

14. A method of treating cystic fibrosis comprising administering to a patient in need thereof the pharmaceutical composition according to claim 6.

4. A compound of the formula:

7. A pharmaceutical composition comprising the compound of claim 4.

12. A method of treating cystic fibrosis comprising administering to a patient in need thereof the compound according to claim 4.

15. A method of treating cystic fibrosis comprising administering to a patient in need thereof the pharmaceutical composition according to claim 7.

5. A compound having the following formula:

8. A pharmaceutical composition comprising the compound of claim 5.

13. A method of treating cystic fibrosis comprising administering to a patient in need thereof the compound according to claim 5.

16. A method of treating cystic fibrosis comprising administering to a patient in need thereof the pharmaceutical composition according to claim 8.

9. A pharmaceutical composition comprising a compound having the following formula:

10. The pharmaceutical composition of claim 9, wherein the compound having the following formula:

17. A method of treating cystic fibrosis comprising administering to a patient in need thereof the pharmaceutical composition according to claim 9.

18. A method of treating cystic fibrosis comprising administering to a patient in need thereof the pharmaceutical composition according to claim 10.