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US 12,264,171 B2Granted
GPR40 agonists
AssigneeKallyope, Inc.
InventorsIyassu Sebhat, Shuwen He
Life of this patent
Estimating the term…
Abstract
This disclosure is directed, at least in part, to GPR40 agonists useful for the treatment of conditions or disorders involving the gut-brain axis. In some embodiments, the GPR40 agonists are gut-restricted compounds. In some embodiments, the GPR40 agonists are full agonists or partial agonists. In some embodiments, the condition or disorder is a metabolic disorder, such as diabetes, obesity, nonalcoholic steatohepatitis (NASH), or a nutritional disorder such as short bowel syndrome.
Claims6
A compound of Formula (2):
- or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein:
- Z is —P(═O)(R5)OR6;
- R5 is C1-C6 alkyl;
- R6 is hydrogen or C1-C6 alkyl;
- R1, R2, and R3 are each independently hydrogen, halogen, or C1-C4 alkyl;
- R4 is unsubstituted C3-C6 cycloalkyl;
- L1 is *—CH2—O—;
- wherein * represents the connection to Ring B;
- Ring B is piperidine, which is unsubstituted or substituted with 1, 2, 3, or 4 RB substituents;
- each RB is independently halogen, C1-C6 alkyl, or C1-C6 fluoroalkyl;
- L2 is a bond;
- Ring A is aryl, which is unsubstituted or substituted with 1, 2, or 3 RA substituents;
- each RA is independently halogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 fluoroalkyl, -LA-CN, -LA-OH, -LA-OR10, -LA-NR11R11, -LA-C(═O)R10, -LA-C(═O)OR11, -LA-OC(═O)R11, -LA-C(═O)NR11R11, -LA-NR11C(═O)R11, -LA-NR11C(═O)NR11R11, -LA-OC(═O)NR11R11, -LA-NR11C(═O)OR10, -LA-OC(═O)OR10, -LA-aryl, -LA-heteroaryl, -LA-(C3-C10 cycloalkyl), or -LA-(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-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 alkyl), and —O—(C1-C6 fluoroalkyl);
- each LA is independently a bond or C1-C6 alkylene;
- wherein the alkylene is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —CN, —OH, —O—(C1-C6 alkyl), and C1-C6 alkyl;
- each R10 is independently C1-C6 alkyl;
- 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-C6 alkyl and C1-C6 hydroxyalkyl;
- and
- each R11 is independently hydrogen, C1-C6 alkyl, 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-C6 alkyl and C1-C6 hydroxyalkyl;
- or two R11 on 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-C6 alkyl and C1-C6 hydroxyalkyl.
20 more elements
Dependencies are inferred from the claim text.