178739-03-2Relevant academic research and scientific papers
CRYSTALLINE FORM 1 OF ATRASENTAN HXDROCHLORIDE
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Page/Page column 24, (2008/06/13)
Atrasentan Hydrochloride Crystalline Form 1, compositions containing it and methods of treatment of diseases and inhibition of adverse physiological events using it are disclosed.
CRYSTALLINE FORM 3 OF ATRASENTAN HYDROCHLORIDE
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Page/Page column 17, (2008/06/13)
Atrasentan Hydrochloride Crystalline Form 3, compositions containing it and methods of treatment of diseases and inhibition of adverse physiological events using it are disclosed
Enantioselective synthesis of the pyrrolidine core of endothelin antagonist ABT-627 (Atrasentan) via 1,2-oxazines
Buchholzl, Monika,Reissig, Hans-Ulrich
, p. 3524 - 3533 (2007/10/03)
Diastereoselective syntheses of the pyrrolidine core 6a of the endothelin antagonist ABT-627 (Atrasentan) either as a racemic mixture or as an enantiopure compound are presented. The crucial steps of these syntheses utilized the highly diastereoselective
Endothelin antagonists
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, (2008/06/13)
A compound of the formula (I): 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.
Endothelin antagonists
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, (2008/06/13)
A compound of the formula (I): 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.
Enantioselective Michael reactions of chiral secondary enaminoesters with 2-substituted nitroethylenes. Syntheses of trans,trans-2,4-disubstituted pyrrolidine-3-carboxylates
Revial, Gilbert,Lim, Sethy,Viossat, Bernard,Lemoine, Pascale,Tomas, Alain,Duprat, Arthur F.,Pfau, Michel
, p. 4593 - 4600 (2007/10/03)
The Michael reaction of chiral 3-substituted secondary enaminoesters with 2-substituted nitroethylenes leads to (Z)-adducts, with good to excellent diastereoselectivity. The nitro group of these adducts was catalytically reduced to give, after cyclization and chiral amine elimination, pyrrolines or pyrrolidines after further reduction. In particular, the syntheses of ethyl (2R,3S,4S)-2,4-dimethylpyrrolidine-3-carboxylate and ethyl (2R,3R,4S)-2-(4-methoxyphenyl)-4-(3,4-(methylenedioxy)phenyl)pyrrolidine-3-ca rboxylate are described.
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 4. Side chain conformational restriction leads to ET(B) selectivity
Von Geldern, Thomas W.,Tasker, Andrew S.,Sorensen, Bryan K.,Winn, Martin,Szczepankiewicz, Bruce G.,Dixon, Douglas B.,Chiou, William J.,Wang, Liming,Wessale, Jerry L.,Adler, Andy,Marsh, Kennan C.,Nguyen, Bach,Opgenorth, Terry J.
, p. 3668 - 3678 (2007/10/03)
When the dialkylacetamide side chain of the ETA-selective antagonist ABT-627 is replaced with a 2,6-dialkylacetanilide, the resultant analogues show a complete reversal of receptor selectivity, preferring ETB over ETA. By optimizing the aniline substitution pattern, as well as the alkoxy group on the 2-aryl substituent, it is possible to prepare antagonists with subnanomolar affinity for ETB and with selectivities in excess of 4000-fold. A number of these compounds also show promising pharmacokinetic profiles; a useful balance of properties is found in A-192621 (38). Pharmacology studies with A-192621 serve to reveal the role of the ETB receptor in modulating blood pressure; the observed hypertensive response to persistent ETB blockade is consistent with previous postulates and indicates that ETB-selective antagonists may not be suitable as agents for long-term systemic therapy.
ENDOTHELIN ANTAGONISTS
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, (2008/06/13)
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.
ENDOTHELIN ANTAGONISTS
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, (2008/06/13)
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
Winn, Martin,Von Geldern, Thomas W.,Opgenorth, Terry J.,Jae, Hwan-Soo,Tasker, Andrew S.,Boyd, Steven A.,Kester, Jeffrey A.,Mantei, Robert A.,Bal, Radhika,Sorensen, Bryan K.,Wu-Wong, Jinshyun R.,Chiou, William J.,Dixon, Douglas B.,Novosad, Eugene I.,Hernandez, Lisa,Marsh, Kennan C.
, p. 1039 - 1048 (2007/10/03)
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.
