US 12,221,442 B2
Heterocyclic GLP-1 agonists
Qinghua Meng, Shanghai (CN); Weiqiang Xing, Shanghai (CN); Haizhen Zhang, Shanghai (CN); Xichen Lin, Shanghai (CN); Hui Lei, Shanghai (CN); and Andrew Jennings, San Francisco, CA (US)
Assigned to Gasherbrum Bio, Inc., South San Francisco, CA (US)
Filed by Gasherbrum Bio, Inc., South San Francisco, CA (US)
Filed on Jan. 26, 2024, as Appl. No. 18/424,580.
Application 18/424,580 is a continuation of application No. 17/950,073, filed on Sep. 21, 2022, granted, now 11,926,626.
Application 17/950,073 is a continuation of application No. PCT/CN2021/115064, filed on Aug. 27, 2021.
Claims priority of application No. PCT/CN2020/112149 (WO), filed on Aug. 28, 2020.
Prior Publication US 2024/0246962 A1, Jul. 25, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/04 (2006.01); A61K 45/06 (2006.01); C07D 405/14 (2006.01); C07D 417/14 (2006.01)
CPC C07D 471/04 (2013.01) [A61K 45/06 (2013.01); C07D 405/14 (2013.01); C07D 417/14 (2013.01)] 4 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or solvate thereof, wherein the moiety:

OG Complex Work Unit Chemistry
is represented by the moiety of Formula (I-A):

OG Complex Work Unit Chemistry
wherein:
L3 is —O—;
custom character indicates an optional single or double bond, as allowed by valence;
X3, X5, and X8 are C; X2 and X4 are N; X6 and X1 are CH; and X1 is CH or N;
T1 is C(═O)OH;
T2 is hydrogen or (C1-C6) alkyl which is optionally substituted with (C1-C6) alkoxy, (C1-C6) thioalkoxy, (C1-C6) haloalkoxy, S(O)2(C1-C6 alkyl), (C3-C6) cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, or 5- to 6-membered heteroaryl, wherein each of the (C3-C6) cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted with 1-4 RT;
each RT is independently selected from the group consisting of OH, SH, CN, NO2, halogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C1-C6)cyanoalkyl, (C1-C6)hydroxyalkyl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C3-C6)cycloalkyl, amino, (C1-C6)alkylamino, and di(C1-C6)alkylamino;
n1 is 0, 1, or 2;
W1 is CRY1 or N;
each occurrence of RY is independently selected from the group consisting of halogen, CN, —OH, oxo, (C1-C6)alkyl, (C1-C3)haloalkyl, (C1-C3)alkoxy, and (C1-C3)haloalkoxy;
RY1 and RY2 are independently selected from the group consisting of hydrogen, halogen, CN, —OH, (C1-C6)alkyl, (C1-C3)haloalkyl, (C1-C3)alkoxy, and (C1-C3)haloalkoxy; or
when W1 is CRY1; the RY1 and RY2 groups taken together form (C1-C4)alkylene, wherein one of the CH2 units of the (C1-C4)alkylene is optionally replaced by a heteroatom selected from the group consisting of O, S, NH, and N(C1-3)alkyl;
each of B1, B2, B3, and B4 is independently selected from the group consisting of CR1 and N;
each R1 is selected from the group consisting of hydrogen, halogen, CN, (C1-C6)alkyl, (C1-C6)haloalkyl; (C1-C3)alkyl(C3-C6)cycloalkyl, (C1-C3)alkyl(3- to 5-membered heterocycloalkyl), and —C(O)NR2R3;
each R2 and R3 is independently selected from the group consisting of hydrogen and (C1-C6)alkyl;
L4 is selected from the group consisting of: —C(RcRc)—; —O—; —S—; —N(C1-3 alkyl)-; —C(═O)—; and —S(O)1-2—,
L5 is selected from the group consisting of: a bond; —C(RcRc)—; —O—; —S—; —N(H)—; —N(C1-3 alkyl)-; —C(═O)—; and —S(O)1-2—,
provided that when L4 is —O—, —S—, or —N(C1-3 alkyl)-, then L5 is a bond, —C(RcRc)—, —C(═O), or —S(O)1-2—, and
provided that when L5 is —O—, —S—, —N(H)—, or —N(C1-3 alkyl)-, then L4 is —C(RcRc)—, —C(═O), or —S(O)1-2—;
each occurrence of Rc is independently selected from the group consisting of: hydrogen, halogen, CN, —OH, (C1-C6)alkyl, (C1-C3)haloalkyl, (C3-C8)cycloalkyl, (C1-C3)alkoxy, and (C1-C3)haloalkoxy; or
a pair of Rc taken together with the carbon atom to which each is attached forms a (C3-C8)cycloalkyl ring;
Ring C is selected from the group consisting of phenyl, 5- to 6-membered heteroaryl, (C3-C6)cycloalkyl, (C5-C10)bicycloalkyl, 5- to 10-membered bicycloheteroaryl, and 3- to 6-membered heterocycloalkyl;
each Rb is independently selected from the group consisting of (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, halogen, (C3-C6)cycloalkyl, and CN; and
b is an integer selected from 0-3.