US 12,065,433 B2
Positive allosteric modulators of the muscarinic acetylcholine receptor M1
Craig W. Lindsley, Brentwood, TN (US); P. Jeffery Conn, Nashville, TN (US); Darren W. Engers, Brentwood, TN (US); and Aaron M. Bender, Spring Hill, TN (US)
Assigned to Vanderbilt University, Nashville, TN (US)
Appl. No. 17/287,442
Filed by Vanderbilt University, Nashville, TN (US)
PCT Filed Oct. 24, 2019, PCT No. PCT/US2019/057888
§ 371(c)(1), (2) Date Apr. 21, 2021,
PCT Pub. No. WO2020/086864, PCT Pub. Date Apr. 30, 2020.
Claims priority of provisional application 62/750,136, filed on Oct. 24, 2018.
Prior Publication US 2021/0355114 A1, Nov. 18, 2021
Int. Cl. C07D 405/14 (2006.01); C07D 405/10 (2006.01); C07D 413/10 (2006.01); C07D 413/14 (2006.01)
CPC C07D 405/14 (2013.01) [C07D 405/10 (2013.01); C07D 413/10 (2013.01); C07D 413/14 (2013.01); C07B 2200/05 (2013.01)] 18 Claims
 
1. A compound of formula (I-a),

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
A1 is Cyc2-Cyc3 or Cyc1;
Cyc1 is a 6-membered heteroaryl;
Cyc2 is a 6-membered aromatic ring optionally containing one nitrogen atom;
Cyc3 is a 5-membered heteroaryl;
wherein Cyc1, Cyc2, and Cyc3 are each independently optionally substituted with 1-5 substituents independently selected from the group consisting of halogen, C1-4alkyl, C1-4haloalkyl, —OC1-4alkyl, —OC1-4haloalkyl, —OC3-6cycloalkyl, —O—C1-3alkylene-C3-6cycloalkyl, OH, oxo, cyano, C3-6cycloalkyl, and —C1-3alkylene-C3-6cycloalkyl, wherein each cycloalkyl is optionally substituted with 1-4 substituents independently selected from the group consisting of halogen and C1-4alkyl;
A2 is G1;
G1 is a 4- to 12-membered saturated alicyclic ring system optionally having one carbon ring atom replaced by oxygen, wherein G1 is optionally substituted with 1-4 substituents independently selected from the group consisting of OH, C1-4alkyl, C1-4haloalkyl, —OC1-4alkyl, cyano, oxo, and C3-6cycloalkyl;
R1 is hydrogen;
R2 is hydrogen; and
R3 is C1-4alkyl or hydrogen.