252955-07-0Relevant articles and documents
Desymmetrization of meso-dicarbonatecyclohexene with β-Hydrazino carboxylic esters via a Pd-catalyzed allylic substitution cascade
Xu, Kai,Zheng, Yan,Ye, Yong,Liu, Delong,Zhang, Wanbin
supporting information, p. 8836 - 8841 (2020/11/30)
The desymmetrization of meso-dicarbonatecyclohexene with β-hydrazino carboxylic esters has been achieved via a RuPHOX/Pd-catalyzed allylic substitution cascade for the construction of chiral hexahydrocinnoline derivatives with high performance. Mechanistic studies reveal that the reaction exploits a pathway different from that of our previous work and that the first nitrogen nucleophilic process is the rate-determining step. The protocol could be conducted on a gram scale without any loss of catalytic behavior, and the corresponding chiral hexahydrocinnolines can undergo diverse transformations.
BICYCLIC SULFONES AND SULFOXIDES AND METHODS OF USE THEREOF
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Paragraph 0439; 0441, (2019/05/15)
The invention provides novel compounds having the general formula I: wherein R1, RB1, RB2, n, p, q, the A ring and the B ring are as described herein, pharmaceutical compositions including the compounds, and methods of usi
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ETA antagonists
Jae,Winn,Von Geldern,Sorensen,Chiou,Nguyen,Marsh,Opgenorth
, p. 3978 - 3984 (2007/10/03)
The synthesis and structure-activity relationships (SAR) of a series of pyrrolidine-3-carboxylic acids as endothelin antagonists are described. The data shows an increase in selectivity when the methoxy of Atrasentan (ABT-627) is replaced with methyl, and the benzodioxole is replaced with dihydrobenzofuran. Adding a fluorine further increases the binding activity and provides a metabolically stable and orally bioavailable ETA-selective antagonist.
Pyrrolidine-3-carboxylic acids as endothelin antagonists. 2. Sulfonamide-based ET(A)/ET(B) mixed antagonists
Jae, Hwan-Soo,Winn, Martin,Dixon, Douglas B.,Marsh, Kennan C.,Nguyen, Bach,Opgenorth, Terry J.,Von Geldern, Thomas W.
, p. 3217 - 3227 (2007/10/03)
When the N,N-dialkylacetamide side chain of the highly ET(A)-selective endothelin antagonist ABT-627 (1; [2R,3R,4S]-2-(4-methoxyphenyl)-4-(1,3- benzodioxol-5-yl)-1-[[(N,N-dibutylamino)carbonyl]methyl]pyrrolidine-3- carboxylic acid; A-147627) is replaced by N,S-dialkylsulfonami-doethyl, the resultant analogs retain ET(A) affinity, but exhibit substantial ET(B) affinity as well. Structure-activity studies reveal that modifications in the length of the two alkyl groups, and in the substitution on the anisyl ring, are important in optimizing this 'balanced' antagonist profile. In particular the combination of an N-n-propyl group, an S-alkyl chain between four and six carbons in length, and a fluorine atom ortho to the aromatic OCH3 provides compounds with sub-nanomolar affinities for both receptor subtypes, and with ET(A)/ET(B) ratios close to 1. A number of these compounds also exhibit oral bioavailabilities (in rats) in the 30-50% range and have substantial plasma half-lives. The balanced receptor-binding profile of these potent and orally bioavailable compounds complements the ET(A) selectivity observed with 1.