136451-81-5Relevant 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. 3. Structural variations of the diphenyl heterocycle moiety
Meanwell,Rosenfeld,Trehan,Romine,Wright,Brassard,Buchanan,Federici,Fleming,Gamberdella,Zavoico,Seiler
, p. 3498 - 3512 (2007/10/02)
4,5-Diphenyl-2-oxazolenonanoic acid (2) and 2-[3-[2-(4,5-diphenyl-2- oxazolyl)ethyl]phenoxy]acetic acid (3) were previously identified as nonprostanoid prostacyclin (PGI2) mimetics that inhibit ADP-induced aggregation of human platelets in vitro. The effects on biological activity of substitution and structural modification of the 4- and 5-phenyl rings of 3 was examined. Potency showed a marked sensitivity to the introduction of substituents to these aromatic rings and only the bis-4-methyl derivative 9j, IC50 = 0.34 μM, demonstrated enhanced potency compared to the parent structure 3, IC50 = 1.2 μM. Substitution at the ortho or meta positions of the phenyl rings, replacement by thiopheneyl or cyclohexyl moieties, or constraining in a planar phenanthrene system resulted in compounds that were less effective inhibitors of ADP-induced platelet aggregation. In contrast, variation of the heterocycle moiety revealed a much less stringent SAR and many 5- and 6-membered heterocycles were found to effectively substitute for the oxazole ring of 2 and 3. The diphenylmethyl moiety functioned as an effective isostere for 4,5-diphenylated heterocycles since 13aad showed similar platelet inhibitory activity to 3. With the exception of the 3,4,5- triphenylpyrazole derivative 13g, compounds presenting the (m- ethylphenoxy)acetic acid side chain discovered with 3 demonstrated enhanced potency compared to the analogously substituted alkanoic acid derivative. The structure-activity findings led to a refinement of a model of the nonprostanoid PGI2 mimetic pharmacophore.
