93547-75-2Relevant academic research and scientific papers
A mechanistic study of carbonyl activation under solvent-free conditions: Evidence drawn from the synthesis of imidazoles
Pradhan, Kiran,Tiwary, Bipransh Kumar,Hossain, Mossaraf,Chakraborty, Ranadhir,Nanda, Ashis Kumar
, p. 10743 - 10749 (2016/02/05)
Syntheses of various imidazoles and their derivatives, imidazole N-oxides and 1-hydroxyimidazole 3-oxides, from sterically different dicarbonyl moieties provided insights into the self-catalytic effect of the condensed phase reactions of carbonyl compounds. The self-catalytic activity in solvent-free multi-component syntheses was investigated using a combination of methods viz., reactivity, spectroscopy and theory. While IR spectroscopic studies revealed that reacting molecules were polarised in bulk, quantum mechanical calculations of associated HCHO monomers suggest an increase in the average dipole moment of each monomer and provide evidence for the presence of cooperative effects. A comparative study of the kinetics of un-catalysed and catalysed reactions with the help of HPLC provided insights into the mechanism.
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.
