136440-53-4

Upstream product

• 2818-82-8 2-methyl-4,5-diphenyl-1H-imidazole 
• 16340-56-0 1-(1-ethoxyethyl)-2-methyl-4,5-diphenyl-1H-imidazole 
• 96-32-2 bromoacetic acid methyl ester 
• 138660-85-2 3-<2-<1-(1-ethoxyethyl)-4,5-diphenyl-1H-imidazol-2-yl>ethyl>phenol 
• 131362-25-9 [3-(bromomethyl)-phenoxy]dimethyl(1,1-dimethylethyl)silane 
• 96013-77-3 3-(tert-butyldimethylsilyloxy)benzyl alcohol 
• 1025883-11-7 (3-{2-[1-(1-Ethoxy-ethyl)-4,5-diphenyl-1H-imidazol-2-yl]-ethyl}-phenoxy)-acetic acid methyl ester 

Downstream Products

• 136440-54-5 [3-[2-(4,5-diphenyl-1H-imidazol-2-yl)ethyl]phenoxy]-acetic acid 

Relevant academic research and scientific papers

Nonprostanoid prostacyclin mimetics. 3. Structural variations of the diphenyl heterocycle moiety

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.

Imidazole carboxylic acids and esters and inhibition of blood platelet aggregation therewith

Heterocyclic acids and esters useful as inhibitors of mammalian blood platelet aggregation characterized by Formula I or II are disclosed. Formula II compounds are those wherein R1 is hydrogen, lower alkyl or an alkali metal ion, and the ra