170279-92-2Relevant academic research and scientific papers
Substituted phenyl compounds
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, (2008/06/13)
Compounds of formula (I) are described wherein R1is hydrogen, -(lower alkyl)q(CO2R6or OH), —CN, —C(R7)═NOR8, NO2, —O(lower alkyl)R9, —C≡C—R10, —CR11═C(R12)(R13), —C(═O)CH2C(═O)CO2H, —CO(R14), alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, thiocarbamoyl, substituted carbamoyl, substituted thiocarbamoyl, sulphamoyl or an optionally substituted nitrogen-containing ring, m, n, o and p are independently zero or 1 and R2, R3, R4and R5are various groups; and physiologically acceptable salts, N-oxides and prodrugs thereof. The compounds have endothelin antagonist activity and are useful as pharmaceuticals.
Selective endothelin A receptor antagonists. 2. Discovery and structure-activity relationships of 5-ketopentanoic acid derivatives
Astles,Brown,Harris,Harper,McCarthy,Porter,Smith,Walsh
, p. 515 - 522 (2007/10/03)
The second in this series of papers describes the further progress made in the discovery of a potent and selective endothelin ET(A) receptor antagonist for the potential treatment of diseases in which endothelin has been shown to have a pathophysiological role including hypertension, ischaemic diseases and atherosclerosis. We describe herein the synthesis and structure-activity relationships of a novel series of 5-ketopentanoic acid derivatives exemplified by the lead compound 1 (IC50 0.72 μM, rat aortic ET(A)R). Optimisation of the in vitro binding of 1 led to the identification of a more potent compound (37) which exhibited an IC50 300-fold selectivity for the ET(A) receptor over the ET(B) receptor. This compound demonstrated functional antagonism of endothelin-induced vasoconstriction in vitro.
