204267-33-4

Usage

InChI:InChI=1/C31H32N2O6/c1-21-19-22(2)33-30(32-21)39-28(29(34)35)31(24-11-7-5-8-12-24,25-13-9-6-10-14-25)38-18-17-23-15-16-26(36-3)27(20-23)37-4/h5-16,19-20,28H,17-18H2,1-4H3,(H,34,35)

Upstream product

• 35144-22-0 4,6-dimethyl-2-methylsulfonylpyrimidine 
• 204268-05-3 3-<2-(3,4-dimethoxyphenyl)ethoxy>-2-hydroxy-3,3-diphenylpropionic acid 
• 204268-10-0 (S)-3-<2-(3,4-dimethoxyphenyl)ethoxy>-2-hydroxy-3,3-diphenylpropionic acid 
• 204268-09-7 (S)-3-<2-(3,4-dimethoxyphenyl)ethoxy>-2-hydroxy-3,3-diphenylpropionic acid methyl ester 
• 7417-21-2 2-(3,4-dimethoxyphenyl)ethyl alcohol 
• 204268-04-2 3-<2-(3,4-dimethoxyphenyl)ethoxy>-2-hydroxy-3,3-diphenylpropionic acid methyl ester 
• 76527-25-8 3,3-diphenyloxirane-2-carboxylic acid methyl ester 
• 178306-51-9 (S)-2-hydroxy-3-methoxy-3,3-diphenyl propionic acid 
• 177036-78-1 (S)-2-hydroxy-3-methoxy-3,3-diphenylpropionic acid methyl ester 
• 178306-52-0 (S)-2-hydroxy-3-methoxy-3,3-diphenylpropionic acid 

Relevant academic research and scientific papers

Azinyloxy, and phenoxy-diaryl-carboxylic acid derivatives, their preparation and use as mixed ETA/ETB endothelin receptor antagonists

The invention relates to carboxylic acid derivatives of the formula I where the radicals have the meanings stated in the description, and to their use as drugs.

Discovery and synthesis of (S)-3-[2-(3,4-dimethoxyphenyl)ethoxy]-2(4,6- dimethylpyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 302872), a novel orally active mixed ET(A)/ET(B) receptor antagonist

Structural variation of the endothelin A-selective antagonist (S)-3- methoxy-2-(4,6-dimethoxy-pyrimidin-2-yloxy)-3,3-diphenylpropionic acid (LU 135252) led to analogues which retain ETA affinity but exhibit substantial ET(B) affinity as well. The most active derivative obtained is (S)-3-[2- (3,4-dimethoxyphenyl)ethoxy]-2-(4,6-dimethylpyrimidin-2-yloxy)-3,3- diphenylpropionic acid (LU 302872), which can be prepared in enantiomerically pure form in eight steps via an acid-catalyzed transetherification. It has a K(i) = 2.15 nM for binding to the ETA receptor and a K(i) = 4.75 nM for binding to the ET(B) receptor, is orally available, and antagonizes the big ET-induced blood pressure increase in rats and the big ET-induced bronchospasm in guinea pigs each time at a dose of 10 mg/kg.