US 12,435,040 B2
1,3-substituted cyclobutyl derivatives and uses thereof
Donglei Liu, Dover, MA (US); Julien Papillon, Somerville, MA (US); Stefan Peukert, Arlington, MA (US); and James J. Powers, Waltham, MA (US)
Assigned to Bausch + Lomb Ireland Limited, Dublin (IE)
Filed by Bausch + Lomb Ireland Limited, Dublin (IE)
Filed on Oct. 24, 2023, as Appl. No. 18/493,441.
Application 18/493,441 is a continuation of application No. 17/656,313, filed on Mar. 24, 2022, granted, now 11,845,730.
Claims priority of provisional application 63/166,289, filed on Mar. 26, 2021.
Prior Publication US 2024/0308965 A1, Sep. 19, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 217/02 (2006.01); C07D 401/12 (2006.01); C07D 405/12 (2006.01); C07D 417/12 (2006.01)
CPC C07D 217/02 (2013.01) [C07D 401/12 (2013.01); C07D 405/12 (2013.01); C07D 417/12 (2013.01)] 19 Claims
 
1. A method of treating pain or inflammation caused by TRPV1 activation in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein:
W is C(═O) or absent;
X is N or N oxide;
Y is N or CH;
Z is NH, O or S;
A is CH2 or absent;
L is selected from 5- to 10-membered heteroaryl having 1-3 heteroatoms independently selected from N, O, and S, C6-C10aryl, and 6- to 10-membered partially saturated heterocyclyl having 1-3 heteroatoms independently selected from N, O, and S;
RA is at each occurrence independently selected from halo, —CN, C1-C6haloalkyl, C1-C6alkyl, SF5, C3-C6cycloalkyl, C1-C6alkoxyl, C1-C6haloalkoxyl, 4- to 6-membered heterocyclyl having 1-2 heteroatoms independently selected from N, O, and S, —(CH2)p—NR3R4 and —C(═O)—O—(C1-C6alkyl),
wherein the C3-C6cycloalkyl and 4- to 6-membered heterocyclyl are each independently substituted with 0-4 RA1;
RA1 is at each occurrence independently selected from halo and C1-C6haloalkyl;
R1 is at each occurrence independently selected from hydroxyl, C1-C6alkyl, C1-C6alkoxyl, halo, C1-C6haloalkyl and NR3R4,
wherein the C1-C6alkyl and C1-C6haloalkyl are each independently substituted with 0-4 R1a;
R1a is at each occurrence independently selected from hydroxyl, NR3R4 and —C(═O)—OH;
R2 is selected from hydrogen and C1-C6alkyl;
R3 is at each occurrence independently selected from hydrogen and C1-C6alkyl;
R4 is at each occurrence independently selected from —SO2R5, hydrogen, —C(═O)—(C1-C6alkyl) and C1-C6alkyl;
R5 is at each occurrence independently selected from NH2 and C1-C6alkyl;
n is 0, 1, 2, 3 or 4;
m is 0, 1, 2, 3, 4 or 5;
p is 0, 1 or 2.