US 12,421,282 B2
Compositions and methods for the treatment of metabolic and liver disorders
Brian Lian, Rancho Santa Fe, CA (US); Geoffrey E. Barker, Carlsbad, CA (US); Kader Yagiz, San Diego, CA (US); Maureen Barnes, San Diego, CA (US); and Erland Stevens, Davidson, CA (US)
Assigned to Viking Therapeutics, Inc., San Diego, CA (US)
Appl. No. 18/274,952
Filed by Viking Therapeutics, Inc., San Diego, CA (US)
PCT Filed Sep. 12, 2022, PCT No. PCT/US2022/076306
§ 371(c)(1), (2) Date Jul. 28, 2023,
PCT Pub. No. WO2023/044290, PCT Pub. Date Mar. 23, 2023.
Claims priority of provisional application 63/244,406, filed on Sep. 15, 2021.
Prior Publication US 2024/0239843 A1, Jul. 18, 2024
Int. Cl. C07K 14/00 (2006.01); A61K 38/00 (2006.01); A61P 1/16 (2006.01)
CPC C07K 14/001 (2013.01) [A61P 1/16 (2018.01); A61K 38/00 (2013.01)] 42 Claims
 
1. A compound having the structure of formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
Aib is 2-aminoisobutyric acid;
each instance of J1, J2, and J3 is independently an amino acid selected from the group consisting of Aib, a naturally occurring amino acid, and an unnatural amino acid;
U1 is -(J4)n1-(J5)n2-(J6)n3-(J7)n4-;
U2 is -(J3)n5-(J9)n6-(J10)n7-(J11)n8-;
each instance of J4, J5, J6, J7, J8, J9, J10, and J11 is independently a naturally occurring amino acid or an unnatural amino acid;
each of n1, n2, n3, n4, n5, n6, n7, and n8 is independently 0 or 1, provided that the sum n1+n2+n3+n4+n5+n6+n7+n8 is 4;
R1 is selected from the group consisting of —C(═O)(OZ1), —P(═O)(X)(Y) and a 5-10 membered heteroaryl containing 1-2 heteroatoms selected from the group consisting of N, O and S, the heteroaryl optionally substituted with 1-2 R7 independently selected from the group consisting of halogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, —OR5, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl;
R2 is selected from the group consisting of —C(═O)(OZ2), —P(═O)(X)(Y) and a 5-10 membered heteroaryl containing 1-2 heteroatoms selected from the group consisting of N, O and S, the heteroaryl optionally substituted with 1-2 R7 independently selected from the group consisting of halogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, —OR5, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl;
each R7 is independently selected from the group consisting of halogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkoxy, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl;
X and Y each are independently selected from the group consisting of —OR4, NR5R6, C1-6 alkyl and haloC1-6 alkyl;
each R4 is independently selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6 alkyl, C6-10 aryl and C7-11 arylalkyl;
each R5 is independently hydrogen or C1-6 alkyl;
each R6 is independently hydrogen or C1-6 alkyl; and
Z1 and Z2 each are independently selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkoxy, C3-10 cycloalkyl and C6-10 aryl;
provided that at least one of the following applies:
J5 is T or V;
J6 is S; and/or
each of n4, n6, n7, and n8 is zero.