US 12,258,340 B2
Pyrazole MAGL inhibitors
Cheryl A. Grice, Redwood City, CA (US); John J. M. Wiener, La Jolla, CA (US); Olivia D. Weber, San Diego, CA (US); and Katharine K. Duncan, McLean, VA (US)
Assigned to H. LUNDBECK A/S, Valby (DK)
Filed by H. Lundbeck A/S, Valby (DK)
Filed on Mar. 16, 2023, as Appl. No. 18/185,227.
Application 18/185,227 is a continuation of application No. 16/615,747, granted, now 11,655,217, previously published as PCT/US2018/033959, filed on May 22, 2018.
Claims priority of provisional application 62/510,213, filed on May 23, 2017.
Prior Publication US 2023/0219897 A1, Jul. 13, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/499 (2006.01); A61K 31/496 (2006.01); A61K 31/5377 (2006.01); A61P 25/06 (2006.01); A61P 29/00 (2006.01); C07D 231/14 (2006.01); C07D 401/06 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/06 (2006.01); C07D 403/12 (2006.01); C07D 403/14 (2006.01); C07D 405/10 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 417/12 (2006.01); C07D 417/14 (2006.01); C07D 451/02 (2006.01); C07D 471/04 (2006.01); C07D 471/10 (2006.01); C07D 487/04 (2006.01); C07D 491/048 (2006.01); C07D 491/08 (2006.01); C07D 519/00 (2006.01)
CPC C07D 413/14 (2013.01) [A61K 31/496 (2013.01); A61K 31/499 (2013.01); A61K 31/5377 (2013.01); A61P 25/06 (2018.01); A61P 29/00 (2018.01); C07D 231/14 (2013.01); C07D 401/06 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/06 (2013.01); C07D 403/12 (2013.01); C07D 403/14 (2013.01); C07D 405/10 (2013.01); C07D 413/12 (2013.01); C07D 417/12 (2013.01); C07D 417/14 (2013.01); C07D 451/02 (2013.01); C07D 471/04 (2013.01); C07D 471/10 (2013.01); C07D 487/04 (2013.01); C07D 491/048 (2013.01); C07D 491/08 (2013.01); C07D 519/00 (2013.01)] 20 Claims
 
1. A method of treating inflammatory pain in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of a compound of Formula (I):

OG Complex Work Unit Chemistry
wherein:
R1 is —C(O)OR15 or —C(O)NR10R11;
R2 is H, halogen, C1-6 alkyl, or C1-6 haloalkyl;
R3 is

OG Complex Work Unit Chemistry
A is N or C(H);
Y is —CH2— or —C(O)—;
Z is —S—, —O—, or —N(R18)—;
R4 is H, halogen, —OR7, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, —C(O)NR8R9, C3-8cycloalkyl, C2-9 heterocycloalkyl, —C1-6 alkyl-C2-9 heterocycloalkyl, C6-10 aryl, or C1-9 heteroaryl, wherein C3-8 cycloalkyl, C2-9 heterocycloalkyl, —C1-6 alkyl-C2-9 heterocycloalkyl, C6-10 aryl, or C1-9 heteroaryl are optionally substituted with 1 or 2 R14;
R5 is H, halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, or phenyl;
R6 is H, halogen, or C1-6 alkyl;
R7 is H, C1-6 alkyl, C1-6 haloalkyl, —C1-6 alkyl-OH, C2-9 heterocycloalkyl, C6-10 aryl, or C1-9 heteroaryl, wherein C2-9 heterocycloalkyl, C6-10 aryl, or C1-9 heteroaryl are optionally substituted with 1 or 2 R14;
each R8 and each R9 are independently selected from H and C1-6alkyl; or R8 and R9 together with the nitrogen to which they are attached are combined to form a heterocycloalkyl ring;
R10 and R11 are each independently H or C1-6alkyl;
R12 is H, halogen, or C1-6alkyl;
R13 is H or C1-6alkyl;
each R14 is independently selected from halogen, —OH, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C1-6 alkyl-OH, C3-8 cycloalkyl, —C(O) OH, —C(O)NR8R9, —SO2—C1-6 alkyl, and —N(R17)C(O)—C1-6 alkyl;
R15 is H or C1-6 alkyl;
R17 is H or C1-6 alkyl;
R18 is H or C1-6 alkyl;
n is 1;
m is 1;
p is 2; and
q is 0;
or a pharmaceutically acceptable salt thereof.