US 2026/0053794 A1Published application

Somatostatin receptor 2 agonists and uses thereof

OwnerDongcheng DAI, Cui LI +1inventors

InventorsDongcheng DAI, Cui LI, He ZHANG

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Abstract

The subject matter described herein is directed to somatostatin receptor activating compounds, methods of making the compounds, pharmaceutical compositions, and their use in the treatment of diseases associated with somatostatin receptors.

Claims40

Dependent claims

A compound of Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
g is 1 or 0;
Z is absent, —N(H)—C(═O)— or —C(═O)—NH—;
Ring B is phenyl or pyridinyl, each of which is mono-substituted with RB1 or di-substituted with one RB1 and one RB2, wherein:
RB1 and RB2 are independently hydrogen, cyano, C1-C6 alkyl, halogen, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, hydroxy, C1-C6 alkoxy, —O—C2-C6 alkenyl, —NH—(CH2)1-5—NH2, —O—(CH2)q2—O—(CH2)r2—CH3, or —C(O)—NRNaRNb,
each RNa and RNb is independently hydrogen or C1-C6 alkyl, and
q2 and r2 are independently an integer from 1 to 4;
Ring C is 4- to 10-membered monocyclic or bicyclic fused heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, each of which is substituted with RC1, RC2, and RC3, wherein:
said heterocyclyl or heteroaryl contains 1, 2, 3, or 4 ring heteroatoms selected from N, O, and S,
RC1 is hydrogen or is bonded to R1, R3, or R6,
RC2 and RC3 are independently hydrogen, halogen, cyano, C1-C6 alkyl, hydroxy, —C(═O)NH2, —O—C2-C6 alkenyl, —C1-C6 alkoxy, —NH—(CH2)1-5—NH2, —O-piperidinyl, or —O—(CH2)qC—O—(CH2)rC—CH3, and
qC and rC are independently an integer from 1 to 4;
R1 is hydrogen or halogen, or
R1 and Z together with the ring to which each is attached form a fused bicyclic ring, optionally substituted with one or two R8, or
R1 and RC1 together with the ring to which each is attached form a fused tricyclic ring;
R2 is hydrogen or halogen, or
R2 and RB1 together with the ring to which each is attached form a fused tricyclic ring;
R3, if present, is a group covalently bound to RC1;
A is:
i. —NR4R5, wherein:
R4 is optionally substituted C1-C6 alkyl, —NH—C1-C6 alkyl-NHR4a, or —C1-C6 alkyl-NHR4a, wherein the optional substituents are selected from the group consisting of halogen and hydroxy,
R4 is hydrogen or methyl, and
R5 is hydrogen or optionally substituted C1-C6 alkyl,
wherein the optional substituents are selected from the group consisting of halogen and hydroxy, or
R5 and RB1 together with the N to which R5 is attached and Ring B to which RB1 is attached form a fused heterocyclyl, or
R5 and RC1 together with the N to which R5 is attached and Ring C to which RC1 is attached form a fused heterocyclyl, or
R5 and R8 together with the N to which R is attached and the ring to which R8 is attached form a fused heterocyclyl;
ii. spirocyclic, substituted with —NH—R6 or RS, wherein RS is hydrogen or —C(═O)—C1-C6 alkyl;
or
iii. —O—(C3-C8 cycloalkyl), 5- to 11-membered heterocyclyl, or 5- to 6-membered heteroaryl, each of which is mono-substituted with —NH—R6 or di-substituted with one RF and one RG, wherein:
RF is hydroxy, hydroxy-C1-C6 alkyl, nitro, —C(═O)H,
—C1-C6 alkoxy, —C(═NH)—NH2, —NH—C(═NH)—NH2,
—C(═O)—C1-C6 alkyl, —(C═O)—O—C1-C6 alkyl,
or —(C1-C6 alkyl)x-NRF1RF2,
x is 0 or 1,
RF1 and RF2 are independently H, —(C═O)—O—C1-C6-alkyl, or C1-C6 alkyl, and
RG is hydrogen or —C1-C6 alkoxy;
or
RG together with RC1 form a —O—(CH2)k—O—, wherein k is an integer from 1 to 5;
or
RF and RG together form carboxy;
and
R6 and RC1 form:
wherein
represents the attachment point of R6;
provided that the compound is not one of:

43 more elements

A compound having a structure of Formula Ia or Ib:

wherein:
Ring B is phenyl or pyridinyl, each of which is mono-substituted with RB1 or di-substituted with one RB1 and one RB2, wherein:
RB1 and RB2 are independently hydrogen, cyano, C1-C6 alkyl, halogen, halo-C1-C6 alkyl, hydroxy-C1-C6 alkyl, hydroxy, C1-C6 alkoxy,
—O—C2-C6 alkenyl, —NH—(CH2)1-5—NH2, —O—(CH2)q2—O—(CH2)r2—CH3, or —C(O)—NRNaRNb,
each RNa and RNb is independently hydrogen or C1-C6 alkyl, and
q2 and r2 are independently an integer from 1 to 4;
Ring C is 4- to 10-membered monocyclic or bicyclic fused heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl, each of which is substituted with RC1, RC2, and RC3, wherein:
said heterocyclyl or heteroaryl contains 1, 2, 3, or 4 ring heteroatoms selected from N, O, and S,
RC1 is hydrogen, is bonded to R6, or is as further defined,
RC2 and RC3 are independently hydrogen, halogen, cyano, C1-C6 alkyl, hydroxy, —C(═O)NH2, —O—C2-C6 alkenyl, —C1-C6 alkoxy, —NH—(CH2)1-5—NH2, —O-piperidinyl, or —O—(CH2)qC—O—(CH2)rC—CH3, and
qC and rC are independently an integer from 1 to 4;
R2 is hydrogen or halogen, or
R2 and RB1 together with the ring to which each is attached form a fused tricyclic ring;
A is:
i. —NR4R5, wherein:
R4 is optionally substituted C1-C6 alkyl, —NH—C1-C6 alkyl-NHR4a,
or —C1-C6 alkyl-NHR4a, wherein the optional substituents are selected from the group consisting of halogen and hydroxy,
R4a is hydrogen or methyl, and
R5 is hydrogen or optionally substituted C1-C6 alkyl, wherein the optional substituents are selected from the group consisting of halogen and hydroxy, or
R5 and RB1 together with the N to which R5 is attached and Ring B to which RB1 is attached form a fused heterocyclyl, or
R5 and RC1 together with the N to which R5 is attached and Ring C to which RC1 is attached form a fused heterocyclyl, or
R5 and R8 together with the N to which R is attached and the ring to which R8 is attached form a fused heterocyclyl:
ii. spirocylic, substituted with —NH—R6 or RS, wherein RS is hydrogen or —C(═O)—C1-C6 alkyl;
or
iii. —O—(C3-C8 cycloalkyl), 5- to 11-membered heterocyclyl, or 5- to 6-membered heteroaryl, each of which is mono-substituted with —NH—R6 or di-substituted with one RF and one RG, wherein:
RF is hydroxy, hydroxy-C1-C6 alkyl, nitro, —C(═O)H,
—C1-C6alkoxy, —C(═NH)—NH2, —NH—C(═NH)—NH2,
—C(═O)—C1-C6 alkyl, —(C═O)—O—C1-C6 alkyl, or —(C1-C6 alkyl)x-NRF1RF2,
x is 0 or 1,
RF1 and RF2 are independently H, —(C═O)—O—C1-C6-alkyl, or C1-C6 alkyl, and
RG is hydrogen or —C1-C6 alkoxy;
or
RG together with RC1 form a —O—(CH2)k—O—, wherein k is an integer from 1 to 5;
or
RF and RG together form carboxy;
and
R6 and RC1 form:
wherein
represents the attachment point of R6;
X1 and X2 are independently O, N, N—R8, S, or C—R8;
R8 is as defined in (i), or
R8 is hydrogen, optionally substituted C1-C6 alkyl, or —C(═O)OR8a, wherein the optional substituents are selected from the group consisting of halogen, —NH2, and hydroxy;
and
R8a is hydrogen or C1-C6 alkyl;
provided that the compound is not:

42 more elements

Dependencies are inferred from the claim text.

Facts

Application: 19/190,582Filed 25 Apr 2025
Priority: WO PCT/CN2022/12830128 Oct 2022
Published: 26 Feb 2026
Term ends: Not estimatedThe source records don’t support an estimate.

Classification23 codes

A61K 31/4745
Ortho- or peri-condensed with heterocyclic ring systems: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
C07D 213/78
With hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals,…:…
A61K 31/4436
Containing further heterocyclic ring systems: containing a heterocyclic ring having sulfur as a ring hetero atom
A61K 31/444
Containing further heterocyclic ring systems: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone

Family

Application19/190,582Continuation
US 2026/0053794 A1This patent

From the US filing history. Foreign family members aren’t listed.

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