Design and synthesis of novel 1,2,4-triazole derivatives as soluble epoxide hydrolases inhibitors

Introduction: Soluble epoxide hydrolase (sEH) inhibitors have been shown to effectively increase the levels of epoxyeicosatrienoic acids and reduce the levels of dihydroxyeicosatrienoic acids, which may be translated to therapeutic potentials for hypertension, diabetes, stroke, dyslipidemia, pain, immunological disorders, eye diseases, neurological diseases and other indications. Since most sEH inhibitors have poor pharmacokinetic properties, development of novel inhibitors is a great deal of attention. Methods and Results: Based on the structure activity relationship of soluble epoxide hydrolase inhibitors and docking studies, some novel compounds with amide moiety and triazole ring as a first and second pharmacophore respectively were designed. These structures were synthesized through 4 step reaction with proper yields. Initially, 4-nitrobenzoyl chloride was reacted with hydrazine hydrate and then in the presence of benzonitrile and catalytic amounts of copper iodide, 1,2,4-triazole was closed. Final products were obtained by reduction of nitro group and reaction with various benzoyl chlorides. Docking studies on the designed sEH inhibitors confirm that the amide groups of the analogues fit properly in the active site of sEH and have a suitable distance from the amino acids of Tyr466 and Asp335 for effective hydrogen bonding. These novel compounds were synthesized in appropriate yield and their structure was approved by instrumental methods including IR, Mass, HNMR and CNMR spectroscopies. Conclusions: In conclusion, some novel amide-based soluble epoxide hydrolase enzyme inhibitors with a 1,2,4-tri azole as a novel secondary pharmacophore were designed, synthesized and structurally approved by IR, NMR and Mass spectra

A green, synthesis of spiro-indene-2,6′-thiazines from tetramethylguanidine-heterocumulene and ninhydrin-malononitrile adducts

<p></p> <p>A useful and simple strategy for the synthesis of spiro(indene-2,6′-thiazine) <i>via</i> a four-component reaction between ninhydrin, malononitrile, tetramethylguanidine and heterocumulene in water at room temperature is described. The use of simple and readily available starting materials, no column chromatography, good to high yields, and short reaction times are important features of this protocol.</p

Highly regioselective, base-catalyzed, biginelli-type reaction of aldehyde, phenylacetone and urea/thiourea kinetic vs. thermodynamic control

<p>An efficient one-pot regioselective synthesis of various novel 3,4-dihydropyrimidin-2(1<i>H</i>)-one (DHPMs) via a three-component Biginelli-type condensation of aldehyde, phenylacetone and urea/thiourea under two different based-catalyzed conditions is described. In kinetic control path, lithium <i>N</i>, <i>N</i>-diisopropylamide (LDA-20 mol % generated <i>in situ</i> from <i>n</i>-BuLi and diisopropylamine) was used as the base, in tetrahydroforane (THF) as the solvent at 0°C. Thermodynamic control path was run with NaH as the base, in EtOH as the solvent under reflux status. The simple procedure, mild base-catalytic reaction conditions, no column chromatography and good to high yields are important features of this protocol.</p

Synthesis of Functionalized <i>N</i>-Sulfonylamidines from <i>N</i>-Sulfonylketenimines and 2-Aminobenzimidazole

<div><p></p><p>The synthesis of a novel class of N-(1H-benzo[d]imidazol-2-yl)-2-alkyl-N′-sulfonylacetamidines via a copper-catalyzed, three-component coupling reaction of 1H-benzo[d]imidazol-2-amine, sulfonyl azides, and terminal alkynes is described.</p></div