IP Library Granted Patent US 10,336,735
Granted Patent B2
US 10,336,735 · App. 15/534,225 · Granted Jul 2, 2019

Small molecule inhibitors of fibrosis

Inventors: Luke Lairson (San Diego, CA); Arnab K. Chatterjee (San Diego, CA); Michael Bollong (San Diego, CA); Baiyuan Yang (San Diego, CA); Peter G. Schultz (La Jolla, CA)
Assignee: THE SCRIPPS RESEARCH INSTITUTE
C07D405/14C07D403/10C07D405/12C07D495/04A01N57/00
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Quick Facts
Patent No.
US 10,336,735
App. No.
15/534,225
Granted
Jul 2, 2019
Kind
B2
Abstract

Described herein are compounds and compositions for the treatment of a fibrotic disease.

Claims (23)

1. A compound of Formula (I) or Formula (Ia):

wherein:

R 1 is —CH(CH 3 )CH 2 CH 2 CH 3 or —CH(CH 2 CH 3 ) 2 ;

R 5 is H, —CN, halogen, haloalkyl, alkyl, —NR 13 R 14 , -alkylene(NR 13 R 14 ), and —SO 2 R 13 ;

each R 8 is independently selected from halogen, —OH, —NO 2 , —N 3 , —CN, alkyl, alkoxy, haloalkoxy, haloalkyl, hydroxyalkyl, alkoxyalkyl, -alkylene(NR 13 R 14 ), -alkylene(cycloalkyl), -alkylene(heterocyclyl), cycloalkyl, heterocyclyl, aryl, heteroaryl, —SR 13 , —SOR 13 , —SO 2 R 13 , —SO 2 NR 13 R 14 , —NR 13 R 14 , —NR 13 SO 2 R 14 , —NR 13 C(O)R 14, —NR 13 C(O)OR 14 , —NR 13 C(O)NR 13 R 14 , —C(O)R 14 , —C(O)OR 14 , and —C(O)NR 13 R 14 ; or two adjacent R 8 form a heterocyclyl ring;

each R 13 and each R 14 is each independently selected from H, alkyl, cycloalkyl, heterocyclylalkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, arylalkyl, heteroarylalkyl, aryl, and heteroaryl; or R 13 and R 14 taken together form a heterocycle with the atoms to which they are attached; and

n is selected from 0, 1, 2, 3, and 4;

or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.

2. The compound of claim 1 , wherein R 1 is —CH(CH 2 CH 3 ) 2 .

3. The compound of claim 1 , wherein R 1 is —CH(CH 3 ) 2 —.

4. The compound of claim 1 , wherein n is 0.

5. The compound of claim 1 , wherein n is 1 or 2.

6. The compound of claim 5 , wherein each R 8 is independently selected from halogen, —CN, alkyl, alkoxy, haloalkoxy, and haloalkyl.

7. The compound of claim 6 , wherein each R 8 is halogen.

8. The compound of claim 7 , wherein each R 8 is Cl.

9. The compound of claim 1 , wherein R 5 is H.

10. The compound of claim 1 , wherein R 5 is halogen.

11. The compound of claim 10 , wherein R 5 is F.

12. The compound of claim 1 having the structure:

or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.

13. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof, and a pharmaceutically acceptable excipient.

14. A method of treating fibrosis in a subject comprising administering to the subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.

15. The method of claim 14 wherein the fibrosis is liver fibrosis, idiopathic pulmonary fibrosis, kidney fibrosis, or cardiac fibrosis.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 20, 2017
From: LAIRSON, LUKE; CHATTERJEE, ARNAB K.; YANG, BAIYUAN; SCHULTZ, PETER G.
To: THE CALIFORNIA INSTITUTE FOR BIOMEDICAL RESEARCH
Reel/Frame 043915/0945 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 20, 2017
From: LAIRSON, LUKE; BOLLONG, MICHAEL; SCHULTZ, PETER G.
To: THE SCRIPPS RESEARCH INSTITUTE
Reel/Frame 043917/0704 →
Continuity (3)
Provisional Application 62090267 · Dec 10, 2014
Provisional Application 62117846 · Feb 18, 2015
Related Publication 20170362211A1 · Dec 21, 2017