136451-69-9Relevant academic research and scientific papers
[2(4,5-diaryl-2 oxazoyl substituted phenoxy alkanoic acid and esters
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, (2008/06/13)
Oxazole derivatives having Formula I or II are disclosed which are useful as inhibitors of mammalian blood platelet aggregation. STR1 Formula I and Formula XIX compounds are those wherein n is 7-9 and R is hydrogen or lower alkyl. Formula II compounds are those wherein R is hydrogen, lower alkyl or together with CO2 is tetrazol-1-yl; R1 is phenyl or thienyl; X is a divalent connecting group selected from the group consisting of CH2 CH2, CH=CH, and CH2 O; Y is a divalent connecting group attached to the 3 or 4 phenyl position selected from the group consisting of OCH2, CH2 CH2 and CH=CH. Formula XX compounds are those wherein the OCH2 CO2 R moiety is attached to the 3 or 4 phenyl position and R is hydrogen or lower alkyl.
Nonprostanoid prostacyclin mimetics. 2. 4,5-Diphenyloxazole derivatives
Meanwell,Rosenfeld,Trehan,Wright,Brassard,Buchanan,Federici,Fleming,Gamberdella,Zavoico,Seiler
, p. 3483 - 3497 (2007/10/02)
4,5-Diphenyl-2-oxazolenonanoic acid (18b) was synthesized and found to inhibit ADP-induced aggregation of human platelets with an IC50 of 2.5 μM. Acid 18b displaced [3H]iloprost from human platelet membranes in a concentration-dependent fashion, consistent with 18b inhibiting platelet function by acting as a prostacyclin mimetic. By inserting a phenoxy ring into the side-chain moiety of 18b and systematically varying the pattern of substitution and length of the tethers, more potent inhibitors of platelet aggregation were identified. A phenoxy ring inserted centrally in the side chain proved to be the optimal arrangement but significant activity was observed when the aromatic ring was bound directly to the 2 position of the heterocycle. The meta-substituted cis-(ethenylphenoxy)acetic acid 37 is the most potent platelet aggregation inhibitor synthesized as part of this study with an IC50 of 0.18 μM. Acid 37 displaces [3H]iloprost from human platelet membranes with an IC50 of 6 nM. The trans-olefinic isomer of 37 (25p) is 72-fold weaker as an inhibitor of ADP-induced platelet aggregation, but the saturated derivative 25w (BMY 42393) is intermediate in potency. Structure-activity studies using 25w as a template focused on modification of the tethers intervening between the side-chain phenyl ring and the oxazole and carboxylate termini and substitution of the phenyl ring. These studies revealed that biological activity was sensitive to both the identity of the concatenating atoms and the pattern of ring substitution. The structure- activity relationships provide insight into the topographical relationship between the diphenylated oxazole ring and the carboxylic acid terminus that comprise the nonprostanoid prostacyclin mimetic pharmacophore.
