	US 12,264,171 B2
	GPR40 agonists
Iyassu Sebhat, Jersey City, NJ (US); and Shuwen He, Fanwood, NJ (US)
Assigned to KALLYOPE, INC., New York, NY (US)
Filed by Kallyope, Inc., New York, NY (US)
Filed on May 16, 2022, as Appl. No. 17/745,126.
Application 17/745,126 is a continuation of application No. PCT/US2021/019975, filed on Feb. 26, 2021.
Claims priority of provisional application 63/147,980, filed on Feb. 10, 2021.
Claims priority of provisional application 63/117,074, filed on Nov. 23, 2020.
Claims priority of provisional application 63/076,113, filed on Sep. 9, 2020.
Claims priority of provisional application 62/983,438, filed on Feb. 28, 2020.
Prior Publication US 2022/0289772 A1, Sep. 15, 2022
Int. Cl. C07F 9/38 (2006.01); A61K 31/10 (2006.01); A61K 31/662 (2006.01); A61K 31/675 (2006.01); C07C 309/24 (2006.01); C07F 9/30 (2006.01); C07F 9/58 (2006.01); C07F 9/59 (2006.01)

CPC C07F 9/3808 (2013.01) [A61K 31/10 (2013.01); A61K 31/662 (2013.01); A61K 31/675 (2013.01); C07C 309/24 (2013.01); C07F 9/301 (2013.01); C07F 9/58 (2013.01); C07F 9/59 (2013.01)]

6 Claims

1. A compound of Formula (2):

or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:

Z is —P(═O)(R⁵)OR⁶;

R⁵is C₁-C₆alkyl;

R⁶is hydrogen or C₁-C₆alkyl;

R¹, R², and R³are each independently hydrogen, halogen, or C₁-C₄alkyl;

R⁴is unsubstituted C₃-C₆cycloalkyl;

L¹is *—CH₂—O—;

wherein * represents the connection to Ring B;

Ring B is piperidine, which is unsubstituted or substituted with 1, 2, 3, or 4 R^Bsubstituents;

each R^Bis independently halogen, C₁-C₆alkyl, or C₁-C₆fluoroalkyl;

L²is a bond;

Ring A is aryl, which is unsubstituted or substituted with 1, 2, or 3 R^Asubstituents;

each R^Ais independently halogen, C₁-C₁₀alkyl, C₂-C₁₀alkenyl, C₂-C₁₀alkynyl, C₁-C₁₀fluoroalkyl, -L^A-CN, -L^A-OH, -L^A-OR¹⁰, -L^A-NR¹¹R¹¹, -L^A-C(═O)R¹⁰, -L^A-C(═O)OR¹¹, -L^A-OC(═O)R¹¹, -L^A-C(═O)NR¹¹R¹¹, -L^A-NR¹¹C(═O)R¹¹, -L^A-NR¹¹C(═O)NR¹¹R¹¹, -L^A-OC(═O)NR¹¹R¹¹, -L^A-NR¹¹C(═O)OR¹⁰, -L^A-OC(═O)OR¹⁰, -L^A-aryl, -L^A-heteroaryl, -L^A-(C₃-C₁₀cycloalkyl), or -L^A-(3- to 10-membered heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, fluoroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, —CN, —OH, C₁-C₆alkyl, C₁-C₆fluoroalkyl, C₁-C₆hydroxyalkyl, —O—(C₁-C₆alkyl), and —O—(C₁-C₆fluoroalkyl);

each L^Ais independently a bond or C₁-C₆alkylene; wherein the alkylene is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —CN, —OH, —O—(C₁-C₆alkyl), and C₁-C₆alkyl;

each R¹⁰is independently C₁-C₆alkyl; wherein each alkyl is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, —OH, C₁-C₆alkyl and C₁-C₆hydroxyalkyl; and

each R¹¹is independently hydrogen, C₁-C₆alkyl, or monocyclic heteroaryl; wherein each alkyl and heteroaryl is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, —OH, C₁-C₆alkyl and C₁-C₆hydroxyalkyl;

or two R¹¹on the same nitrogen atom are taken together with the nitrogen to which they are attached to form a 3- to 6-membered N-heterocycloalkyl; wherein the heterocycloalkyl is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, —OH, C₁-C₆alkyl and C₁-C₆hydroxyalkyl.