195708-39-5Relevant articles and documents
ERβ ligands. Part 4: Synthesis and structure-activity relationships of a series of 2-phenylquinoline derivatives
Vu, An T.,Cohn, Stephen T.,Manas, Eric S.,Harris, Heather A.,Mewshaw, Richard E.
, p. 4520 - 4525 (2007/10/03)
A new class of estrogen receptor β (ERβ) ligands based on the 2-phenylquinoline scaffold was prepared. Several analogues with C4 substitution displayed high affinity (3-5 nM) and significant selectivity (up to 83-fold) for ERβ. The best compound, 13b, was profiled as a selective partial agonist for ERβ at 1 μM in a cell-based transcriptional assay. Uterine weight bioassay of 13b indicated no activation of ERα in vivo.
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.
