SOMATOSTATIN MODULATORS AND USES THEREOF

摘要

Described herein are compounds that are somatostatin modulators, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders that would benefit from modulation of somatostatin activity.

主权项

1. A compound that has the structure of Formula (I), or a pharmaceutically acceptable salt, solvate, diastereomeric mixture, individual enantiomers or prodrug thereof: wherein: A1, A2, and A3 are independently N or CRA; each RA is independently hydrogen, halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4fluoroalkyl, unsubstituted or substituted C1-C4alkoxy, unsubstituted or substituted C1-C4fluoroalkoxy, —CN, —OH, —CO2R14, —C(═O)NR14R15, —NR14R15, —NR14C(═O)NHR15, —NR14C(═O)(C1-C4alkyl), —C(═NOR)R15, —SR14, —S(═O)(C1-C4alkyl), —SO2(C1-C4alkyl), or —SO2NR14R15; R1 is unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bicyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, unsubstituted or substituted bicyclic heterocycle, —(C1-C4alkylene)-(unsubstituted or substituted monocyclic carbocycle or unsubstituted or substituted bicyclic carbocycle), or —(C1-C4 alkylene)-(unsubstituted or substituted monocyclic heterocycle or unsubstituted or substituted bicyclic heterocycle), wherein if R1 is substituted then R1 is substituted with 1-2 R16 and 0-2 R17; R2 is unsubstituted or substituted C1-C6alkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted bicyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, unsubstituted or substituted bicyclic heterocycle, —(C1-C4 alkylene)-(unsubstituted or substituted monocyclic carbocycle or unsubstituted or substituted bicyclic carbocycle), or —(C1-C4 alkylene)-(unsubstituted or substituted monocyclic heterocycle or unsubstituted or substituted bicyclic heterocycle), wherein if R2 is substituted then R2 is substituted with 1-2 R18 and 0-2 R19; R3 and R4 are independently hydrogen, unsubstituted or substituted C1-C6 alkyl, or unsubstituted or substituted C3-C6cycloalkyl, wherein any substituted group of R3 and R4 is substituted with 1-4 R20; or R3 and R4 are taken together with the nitrogen atom to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring or an unsubstituted or substituted bicyclic 9- to 12-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R20; R5, R6, R7, and R8 are each independently selected from the group consisting of hydrogen, unsubstituted or substituted C1-C6 alkyl, and unsubstituted or substituted C1-C6 fluoroalkyl, unsubstituted or substituted monocyclic carbocycle, unsubstituted or substituted monocyclic heterocycle, wherein any substituted group of R5, R6, R7, and R8 is substituted with 1-4 R20; R9 is hydrogen, unsubstituted or substituted C1-C6 alkyl, unsubstituted or unsubstituted or substituted benzyl, wherein if R9 is substituted then R9 is substituted with 1-4 R20; or R4 and any one of R5, R7, or R9 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring or an unsubstituted or substituted bicyclic 9- to 12-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R20; or R5 and R6 are taken together with the carbon atom to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered carbocyclic ring, wherein if the carbocyclic ring is substituted then the carbocyclic ring is substituted with 1-4 R20; or R5 and any one of R7 or R9 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring or a bicyclic 9- to 12-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R20; or R7 and R9 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring or an unsubstituted or substituted bicyclic 9- to 12-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R20 R10 and R11 are each independently selected from the group consisting of hydrogen, and unsubstituted or substituted C1-C6 alkyl, wherein any substituted group of R10 and R11 is substituted with 1-4 R20; or R10 and R11 are taken together with the carbon atom to which they are attached to form —C(═O); or R7 and R11 are taken together with the intervening atoms to which they are attached to form an unsubstituted or substituted monocyclic 4- to 7-membered heterocyclic ring or an unsubstituted or substituted bicyclic 9- to 12-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R20 R12 is hydrogen, or C1-C4 alkyl; or R12 and R9 are taken together with the intervening atoms to which they are attached to form a monocyclic 4- to 7-membered heterocyclic ring, wherein if the heterocyclic ring is substituted then the heterocyclic ring is substituted with 1-4 R20; R13 is hydrogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4fluoroalkyl, unsubstituted or substituted C1-C4alkoxy, unsubstituted or substituted C1-C4fluoroalkoxy, —CN, —CO2R14, —C(═O)NR14R15, —NR14R15, —NR14C(═O)NHR15, —NR14C(═O)(C1-C4alkyl), —C(═NOR14)R15, or —SR14; each R14 and R15 are independently selected from hydrogen, and unsubstituted or substituted C1-C4alkyl; each R16, R17, R18 and R19 is independently hydrogen, halogen, unsubstituted or substituted C1-C4alkyl, unsubstituted or substituted C1-C4alkoxy, unsubstituted or substituted C1-C4fluoroalkyl, unsubstituted or substituted C1-C4fluoroalkoxy, unsubstituted or substituted heterocycle, —CN, —OH, —CO2R14, —C(═O)NR14R15, —NR14R15, —NR14C(═O)NHR15, —NR14C(═O)R15, —C(═NOR14)R15, —SR14, —S(═O)(C1-C4alkyl), —SO2(C1-C4alkyl), or —SO2NR14R15, wherein if any group of R16, R17, R18 and R19 is substituted then the substituted group of R16, R17, R18 and R19 is substituted with 1-4 R20; each R20 is independently halogen, heterocycle, —CN, —OR14, —CO2R14, —C(═O)NR14R15, —NR14R15, —NR14C(═O)NHR15, —NR14C(═O)R15, —C(═NOR14)R15, —SR14, —S(═O)(C1-C4alkyl), —SO2(C1-C4alkyl), or —SO2NR14R15; and m is 1, 2, 3, or 4.