Biphenyl-containing diarylpyrimido compounds, pharmaceutically-acceptable salts thereof, composition and preparation thereof

Patent metadata

Field	Value
Publication number	US-11447501-B2
Application number	US-202016986200-A
Country	US
Kind code	B2
Filing date	Aug 5, 2020
Priority date	Aug 6, 2019
Publication date	Sep 20, 2022
Grant date	Sep 20, 2022

Abstract

A biphenyl-containing diarylpyrimido compound of formula (I), which is prepared by reacting a 4-chloropyrimidine derivative with a biphenyl derivative in a solvent in the presence of a base. A pharmaceutically-acceptable salt of the compound (I) and a pharmaceutical composition containing the compound (I) or a pharmaceutically-acceptable salt thereof are also provided.

First claim

What is claimed is:

1. A biphenyl-containing diarylpyrimido compound of formula (I):

wherein:
R 1 is selected from the group consisting of hydrogen, cyano, nitro, hydroxyl, halogen, amino, C 3 -C 6 cycloalkoxy, C 3 -C 6 cycloalkylamino, substituted C 1 -C 6 alkyl, substituted C 2 -C 6 alkenyl, substituted C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, carboxyl, ester group, amido and sulfonamido;
R 2 is selected from the group consisting of cyano, nitro, hydroxyl, halogen, amino, C 3 -C 6 cycloalkoxy, C 3 -C 6 cycloalkylamino, substituted C 1 -C 6 alkyl, substituted C 2 -C 6 alkenyl, substituted C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, carboxyl, ester group, amido and sulfonamido;
X is selected from the group consisting of —CH 2 —, —NH—, —O—, —S—, —S(O)— and —S(O) 2 —; and

is selected from the group consisting of unsubstituted and substituted benzene ring; thiophene, thiazole, oxazole, isoxazole, pyrazolone, furan, pyridine, azine and an oxide thereof; cyclopentadiene; tetrahydrothiophene; sulphoxide; sulfone; tetrahydrofuran; and substituted cycloalkane.

2. The biphenyl-containing diarylpyrimido compound of claim 1 , wherein the biphenyl-containing diarylpyrimido compound of formula (I) is prepared through steps of:
reacting a 4-chloropyrimidine derivative (II) with a biphenyl derivative (III) in a solvent in the presence of a base to produce the biphenyl-containing diarylpyrimido compound, as shown in the following scheme:

3. The biphenyl-containing diarylpyrimido compound of claim 2 , wherein the solvent is selected from the group consisting of acetone, acetonitrile, toluene, dichloromethane, tetrahydrofuran, N,N-dimethylformamide, N,N-dimethylacetamide, ethanol, isopropanol, n-butanol and isobutanol, and a combination thereof.

4. The biphenyl-containing diarylpyrimido compound of claim 2 , wherein the base is an inorganic base or an organic base;
wherein the inorganic base is selected from the group consisting of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium hydroxide and sodium hydrogen, and a combination thereof; and the organic base is selected from the group consisting of N,N-dimethylaminopyridine, triethylamine, diisopropylethylamine, tributylamine, potassium tert-butoxide, and a combination thereof.

5. The biphenyl-containing diarylpyrimido compound of claim 2 , wherein a molar ratio of the 4-chloropyrimidine derivative (II) to the biphenyl derivative (III) to the base is 1:1-1.5:1.5-3.

6. The biphenyl-containing diarylpyrimido compound of claim 2 , wherein a molar ratio of the 4-chloropyrimidine derivative (II) to the biphenyl derivative (III) to the base is 1:1.1:2.5.

7. The biphenyl-containing diarylpyrimido compound of claim 2 , wherein the reaction is performed at 30-100° C. for 4-10 h.

8. A pharmaceutically-acceptable salt of the biphenyl-containing diarylpyrimido compound of claim 1 , wherein the pharmaceutically-acceptable salt is selected from the group consisting of hydrochloride, hydrobromide, sulfate, phosphate, acetate, mesylate, tosylate, tartrate, citrate, fumarate and malate.

9. A pharmaceutical composition for treating acquired immunodeficiency syndrome (AIDS), comprising the biphenyl-containing diarylpyrimido compound of claim 1 or the pharmaceutically-acceptable salt of claim 8 as an active ingredient, and a pharmaceutically-acceptable carrier.

10. A method of treating AIDS in a patient in need thereof, comprising:
administering a therapeutically effective amount of the pharmaceutical composition of claim 9 to the patient.

Assignees

• Univ Fudan
• Fudan Univeristy

Inventors

• Chen Fener
• Sang Yali
• Zhuang Chunlin

Classifications

• C07D495/04 Primary

  Ortho-condensed systems · CPC title

• A61P31/18

  for HIV · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title