209214-30-2

Upstream product

• 1485-00-3 5-((E)-2-nitroethenyl)-1,3-benzodioxole 
• 2881-83-6 ethyl 4-methoxybenzoylacetate 
• 173864-47-6 ethyl c-(1,3-benzodioxol-5-yl)-r-2-(4-methoxyphenyl)pyrrolidine-t-3-carboxylate 
• 173864-47-6 (2R,3S,4S)-4-Benzo[1,3]dioxol-5-yl-2-(4-methoxy-phenyl)-pyrrolidine-3-carboxylic acid ethyl ester 
• 173864-45-4 Ethyl 2-(4-methoxybenzoyl)-3-(3.4-methylenedioxy-phenyl)-4-nitro-butanoate 
• 173864-46-5 ethyl 2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-4,5-dihydro-3H-pyrrole-3-carboxylate 
• 24424-99-5 di-tert-butyl dicarbonate 

Downstream Products

• 178739-03-2 ethyl (2R,3R,4S)-5-(4-methoxyphenyl)-3-(3,4-(methylenedioxy)phenyl)pyrrolidine-3-carboxylate 
• 1253782-55-6 (2R,3R,4S)-tert-butyl 3-(2-(2H-tetrazol-5-yl)ethylcarbamoyl)-4-(benzo[d]-[1,3]dioxol-6-yl)-2-(4-methoxyphenyl)pyrrolidine-1-carboxylate 
• 1253782-61-4 (2R,3R,4S)-tert-butyl 3-(4-(2-methylimidazo[1,2-b]pyridazin-3-yl)thiazol-2-ylcarbamoyl)-4-(benzo[d][1,3]dioxol-6-yl)-2-(4-methoxyphenyl)pyrrolidine-1-carboxylate 
• 1253782-57-8 (2R,3R,4S)-tert-butyl 3-(4-(4-methylpiperazin-1-yl)phenylcarbamoyl)-4-(benzo[d][1,3]dioxol-6-yl)-2-(4-methoxyphenyl)pyrrolidine-1-carboxylate 
• 1253782-60-3 (2R,3R,4S)-tert-butyl 3-((S)-1-phenylethylcarbamoyl)-4-(benzo[d][1,3]-dioxol-6-yl)-2-(4-methoxyphenyl)pyrrolidine-1-carboxylate 
• 1253782-59-0 (2R,3R,4S)-tert-butyl 3-((R)-1-phenylethylcarbamoyl)-4-(benzo[d][1,3]-dioxol-6-yl)-2-(4-methoxyphenyl)pyrrolidine-1-carboxylate 
• 1253782-56-7 (2R,3R,4S)-tert-butyl 3-(2-aminophenylcarbamoyl)-4-(benzo[d][1,3]dioxol-6-yl)-2-(4-methoxyphenyl)pyrrolidine-1-carboxylate 
• 1253782-58-9 (2R,3R,4S)-tert-butyl 3-(4-(4-ethylpiperazin-1-yl)phenylcarbamoyl)-4-(benzo[d][1,3]dioxol-6-yl)-2-(4-methoxyphenyl)pyrrolidine-1-carboxylate 

Relevant academic research and scientific papers

Synthesis of (2R,3R,4S)-N-Boc-2,4-diarylpyrrolidine-3-carboxamides

A synthesis of (2R,3R,4S)-N-boc-2,4-diarylpyrrolidine-3-carboxylic amides (i-vii) via HATU, BOP and Mukaiyama mediated coupling of (2R,3R,4S)-1-(tert- butoxycarbonyl)-4-(benzo[d][1,3]dioxol-6-yl)-2-(4-methoxyphenyl) pyrrolidine-3-carboxylic acid (13) with amine (a1-g1) has been developed. Under HATU coupling conditions, the products were achieved in good yields comparatively than BOP and Mukaiyama reagent. The structures of compounds i-vii were elucidated on the basis of spectral and chemical studies.

ENDOTHELIN ANTAGONISTS

A compound of the formula (I): STR1 or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

2,4-diarylpyrrolidine-3-carboxylic acids - Potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722

We have discovered a novel class of endothelin (ET) receptor antagonists through pharmacophore analysis of the existing non-peptide ET antagonists. On the basis of this analysis, we determined that a pyrrolidine ring might replace the indan ring in SB 209670. The resultant compounds were readily prepared and amenable to extensive SAR studies. Thus a series of N-substituted trans,trans-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)pyrrolidine-3-carboxylic acids (8) have been synthesized and evaluated for binding at ETA and ETB receptors. Compounds with N-acyl and simple N-alkyl substituents had weak activity. Compounds with N-alkyl substituents containing ethers, sulfoxides, or sulfones showed increased activity. Much improved activity resulted from compounds where the N-substituents were acetamides. Compound 17u (A-127722) with the N,N-dibutylacetamide substituent is the best of the series. It has an IC50 = 0.36 nM for inhibition of ET-1 radioligand binding at the ETA receptor, with a 1000-fold selectivity for the ETA vs the ETB receptor. It is also a potent inhibitor (IC50 = 0.16 nM) of phosphoinositol hydrolysis stimulated by ET-1, and it antagonized the ET-1-induced contraction of the rabbit aorta with a pA2 = 9.20. The compound has 70% oral bioavailability in rats.