Granted Patent B2

US 12,649,749 · App. 18/004,922 · Granted Jun 9, 2026

Inventors: Zhenghua Gu (Shanghai, CN); Dongqin Wang (Shanghai, CN); Youhong Hu (Shanghai, CN)

Assignee: NEUSCO BIOTECH LIMITED

C07D498/14

Abstract

Claims (42)

1 . A compound of Formula (I) or a pharmaceutically acceptable salt thereof,

wherein

n 1 , and n 2 are each independently 0, 1, or 2;

R 1 is selected from H, cyano, alkyl, deuterated alkyl, deuterated alkoxy, hydroxyalkyl, haloalkyl, haloalkoxy, cycloalkyl, alkoxy;

R 2 is selected from H, cyano, halogen, alkyl, deuterated alkyl, deuterated alkoxy, hydroxyalkyl, haloalkyl, haloalkoxy, cycloalkyl, alkoxy;

X 1 and X 2 are each independently selected from alkylene, —O—, —S—, or —NR′—,

R′ is selected from H, alkyl, deuterated alkyl, or cycloalkyl;

Ar is an arylene group or a heteroarylene group, wherein hydrogen atoms in the arylene or heteroarylene are optionally substituted by 1 or more substituents, and the substituents are each independently selected from halogen, alkyl, deuteroalkyl, haloalkyl, alkoxy, deuteroalkoxy, haloalkoxy, hydroxy, hydroxyalkyl, cyano, amino, monoalkyl- or dialkyl-substituted amino, nitro, carboxyl, —C(O)—H, cycloalkyl, aryl, or heteroaryl;

Y is H, halogen, alkyl, haloalkyl, haloalkoxy, cycloalkyl, alkoxy, deuterated alkyl, deuterated alkoxy, hydroxy, hydroxyalkyl, cyano, —OAr′, —SAr′, —NR″—Ar′, —NR″R″, or —R′″—Ar′;

Ar′ is selected from aryl or heteroaryl, wherein hydrogen atoms in the aryl or heteroaryl are optionally substituted with one or more substituents, the substituents are each independently selected from halogen, alkyl, deuterated alkyl, haloalkyl, alkoxy, hydroxy, hydroxyalkyl, haloalkoxy, deuteroalkyl, deuterated alkoxy, cyano, amino, nitro, carboxyl, —C(O)—H, cycloalkyl, aryl, or heteroaryl;

R″ is H, alkyl, or cycloalkyl;

R′″ is alkylene;

wherein, halogens in the “halogen” “haloalkyl” and “haloalkoxy” are each independently selected from F, Cl, Br, or I;

the alkyl in the “alkyl” “deuterated alkyl” “deuterated alkoxy” “hydroxyalkyl” “haloalkyl” “haloalkoxy”, “alkoxy” and “mono- or di-alkyl substituted amino” are each independently C 1 -C 10 linear or branched alkyl;

“alkylenes” are each independently C 1 -C 10 linear or branched alkylene;

“cycloalkyl” is C 3 -C 10 monocyclic or bicyclic cycloalkyl;

“aryl” is 6- to 10-membered aryl;

“arylene” is 6- to 10-membered arylene;

“heteroaryl” is 5- to 10-membered heteroaryl ring containing 1-3 heteroatoms selected from N, O, and S;

“heteroarylene” is 5- to 10-membered heteroarylene ring containing 1-3 heteroatoms selected from N, O, and S.

2 . The compound or a salt thereof according to claim 1 , wherein, alkyls in the “alkyl” “deuterated alkyl” “deuterated alkoxy” “hydroxyalkyl” “haloalkyl” “haloalkoxy”, “alkoxy” and “mono- or di-alkyl substituted amino” are each independently C 1 -C 7 linear or branched alkyl; “alkylenes” are each independently C 1 -C 7 linear or branched alkylene; “cycloalkyl” is C 3 -C 7 monocyclic cycloalkyl;

“aryl” is phenyl or naphthyl;

“arylene” is phenylene or naphthylene;

“heteroaryl” is 5- to 10-membered heteroaryl ring containing 1-2 heteroatoms selected from N, O, and S; “heteroarylene” is 5- to 10-membered heteroaromatic ring containing 1-2 heteroatoms selected from N, O, and S.

3 . The compound or a salt thereof according to claim 1 , wherein

n 1 is 0 or 1; n 2 is 1,

R 1 and R 2 are each independently selected from H, —CH 2 OH, —CH 2 CH 2 OH, cyano, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, isopentyl, 1-ethylpropyl, neopentyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 3-ethylpentyl, or 2,2,3-trimethylbutyl, —CD 3 , —C 2 D 5 , or —C 3 D 7 , —OCD 3 , —OC 2 D 5 , or —OC 3 D 7 , —CF 3 , —C 2 F 5 , or —C 3 F 7 , C 1 -C 7 haloalkoxy, C 1 -C 7 alkoxy, cyclopropanyl, cyclobutanyl, cyclopentanyl;

X 1 is —CH 2 —, ethylene, n-propylene, isopropylene, n-butylene, or isobutylene, —O—, —S—; X 2 is —O— or —S—;

Ar is phenylene or pyridyl, wherein hydrogen atoms in the phenylene or pyridyl are optionally substituted with 1, 2, or 3 substituents, the substituents are each independently selected from F, Cl, Br, I, —CN, —Me, —CF 3 , —C 2 H 5 , —C 3 H 7 , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, —CD 3 , —OCD 3 , —OMe, or —OCF 3 ;

Y is H, —F, —Cl, —Br, —I, methyl, ethyl, n-propyl, isopropyl, —CD 3 , —OCD 3 , —CF 3 , —CHF 2 , —CH 2 F, —CH 2 CF 3 , —OCF 3 , —OCHF 2 , —OCH 2 F, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, —OCH 3 , —OC 2 H 5 , —OC 3 H 7 , or —OAr′;

Ar′ is selected from phenyl, pyridyl, pyrimidyl, thienyl, pyrrolyl, pyrazolyl, or quinolinyl, wherein hydrogen atoms in the phenyl, pyridyl, pyrimidyl, thienyl, pyrrolyl, pyrazolyl, or quinolinyl ring are each independently optionally substituted with 1, 2, or 3 substituents, the substituents are each independently selected from F, Cl, Br, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, isopentyl, 1-ethylpropyl, neopentyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 3-ethylpentyl, or 2,2,3-trimethylbutyl, —CD 3 , —OCD 3 , —CF 3 , —CHF 2 , —CH 2 F, —CH 2 CF 3 , —OCH 3 , —OC 2 H 7 , —OC 3 H 7 , —OCF 3 , —OCHF 2 , —OCH 2 F, —OCH 2 CF 3 , hydroxyl, —CH 2 OH, —OCH 2 CH 2 OH, —CN, or cyclopropanyl, cyclobutanyl, cyclopentanyl, or cyclohexanyl.

4 . The compound of Formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound of Formula (I) is selected from the following compounds:

5 . The compound of Formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the pharmaceutically acceptable salt is selected from a group consisting of an alkali metal salt, an alkaline earth metal salt, an ammonium salt, an organic base salt, and an organic acid salt of the compound of Formula (I).

6 . A preparation method of the compound of Formula (I) or its pharmaceutically acceptable salt according to claim 1 , comprises the following synthetic route:

wherein, in the synthetic route, the DIPEA represents N,N-diisopropylethylamine, the TEA represents triethylamine.

7 . A pharmaceutical composition comprising an effective amount of the compound of Formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

8 . The compound of Formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein

the pharmaceutically acceptable salt is selected from a group consisting of salts formed by the compound of Formula (I) and an organic base, and wherein the organic base is selected from a group consisting of trialkylamine, pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, dimethylaniline, N-alkylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5, 1,8-diazabicyclo[5.4.0]undecene-7, and 1,4-diazabicyclo[2.2.2]octane;

or the pharmaceutically acceptable salt is selected from a group consisting of salts formed by the compound of Formula (I) and an acid, wherein the acid is selected from a group consisting of hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid, or carbonic acid, formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, citric acid, citric acid, tartaric acid, carbonic acid, picric acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, glutamic acid, and pamoic acid.

9 . The pharmaceutical composition according to claim 7 , wherein the pharmaceutical composition is in a dosage form selected from a group consisting of oral formulations, rectal formulations, and parenteral formulations.

10 . The pharmaceutical composition according to claim 9 , wherein the dosage form is selected from a group consisting of solid formulation, liquid formulation, tablet, powder, granule, capsule, aqueous oily suspension, syrup, solution for injection, aqueous and oily suspension.

11 . The compound or a salt thereof according to claim 2 , wherein the compound represented by the Formula (I) is a tautomer, a mesomer, a racemate, an enantiomer, a diastereoisomer, or a mixture thereof.

Assignments (1)

Priority Claims (1)

Continuity (1)

References Cited (20)