Synthesis of pyrazolo-enaminones, bipyrazoles and pyrazolopyrimidines and evaluation of antioxidant and antimicrobial properties

A novel pyrazolo-enaminones, bipyrazoles and bipyrazolopyridines from 1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)butane-1,3-dione and 4-methyl-2-phenyl-2H-pyrazolo[3,4-b]pyridine-3,6(3aH,7H)-dione have been synthesized by assisted heating with microwave radiation without any catalyst. The pyridine and pyrazole ring formation has been developed from easily accessible enamino keto esters by formylation followed by intramolecular cyclization. The general applicability for the synthesis of the important pyrazolo-enaminones, bipyrazoles and pyrazolo-pyridines heterocycles was attributed to simplicity of operation, synthesis without catalyst, energy efficiency (shorter reaction time under microwave irradiation), good yields, more environmentally friendly and more cost-effective procedure. The antioxidant activity of new heterocyclic compounds was evaluated by free radical scavenging by DPPH assay. Several of these compounds showed good activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria

Convenient approach for the synthesis of ONO-LB-457, a potent leukotriene B4 receptor antagonist

International audienceThis study reports a new approach for the synthesis of 5-[2-(2-carboxyethyl)-3-[6-(4-methoxyphenyl)-(5E)-hexen-1-yloxy]phenoxy]pentanoic acid V (ONO-LB-457), previously described by Konno and col. and which is considered a highly potent and orally active LTB₄ receptor antagonist. This compound acts as an inhibitor of aggregation and chemotaxis, in addition to LTB₄-induced human neutrophil degranulation.In this work, the preparation of ONO-LB-457 was proposed through a convergent synthesis focused on the preparation of two fragments. First, the preparation of 5-hydroxychroman-2-one (4) from 2,6-dimethoxybenzaldehyde and malonic acid, involving a Knoevenagel reaction, followed by a reduction of the olefin and intramolecular cyclization catalyzed by Lewis acid (tribromide) was achieved with an overall yield of 57%. Second, preparation of (E)-6-(4-methoxyphenyl)hex-5-en-1-yl-methanesulfonate (18) from 5-bromovaleric acid (15) involving a Wittig reaction. The desired compound V (ONO-LB-457) was obtained by nucleophilic substitution of (E)-6-(4-methoxyphenyl)hex-5-en-1-yl-methanesulfonate (18) with the ring-opened phenolic diester 14 followed by hydrolysis, in seven steps with an overall yield of about 11%