Synthesis and biological evaluation of 3-(1H-indol-3-yl)pyrazole-5-carboxylic acid derivatives

Abstract

A series of novel compounds bearing a 3-(1H-indol-3-yl)pyrazole-5-carboxylic acid nucleus were synthesized. Analytical and spectral data confirmed the structures of the new compounds. The structures of the regioisomers in this series were determined by (1)H-NMR spectra. The title compounds were evaluated for their endothelin-1 antagonist activities. In the in vitro functional assay, compounds 23, 24, 28 and 29 exhibited significant efficacy at the concentration of 1 μg/mL, and compounds 5b, 5c, 26 and 28 were as potent as the positive control bosentan at high concentration. In the experiment to assess prevention of endothelin-1-induced sudden death in mice, compound 5b showed comparable activity to bosentan, and 30 was more potent than bosentan. The final compounds were also screened for antibacterial activity against four Gram-positive and -negative bacteria. Some of the tested compounds showed weak antibacterial activity.

Synthesis of novel indole-isoxazole hybrids and evaluation of their cytotoxic activities on hepatocellular carcinoma cell lines

“…The synthesis of the title compounds was accomplished as outlined in Scheme 1 . Diethyl oxalate has been treated with 3-acetylindole ( 1) in the presence of a base to obtain ethyl 4-(1 H -indol-3-yl)-2,4-dioxobutanoate ( 2) [ 42 , 43 ]. This intermediate was reacted with hydroxylamine hydrochloride to provide ethyl 3-(1 H -indol-3-yl)isoxazole-5-carboxylate ( 3) [ 23 ], which was then hydrolyzed by using LiOH into 3-(1 H -indol-3-yl)isoxazole-5-carboxylic acid ( 4) .…”

Recent Developments in the Synthesis of Indole‐Pyrazole Hybrids

“…[78] The Zhang et al synthesized several regioisomeric 3-pyrazolylindoles starting from 3-acetylindole (173) using the methods described in Scheme 34 and evaluated their cytotoxic, antibacterial and endothelin-1 antagonist activities. [79,80] 3-Acetylin- ) and evaluated some of the compounds in vitro antitumor properties. [83] As shown in Scheme 37, synthesis of the desired hybrids began with indole [84] 5-Indolylpyrazol-3-one (234) and 4-indolylpyrazol-3-one (237) were synthesized as shown in Scheme 39 and evaluated for their Chk1 inhibition activity and in vitro antiproliferative activities by Conchon et al [85] Compound 234 was obtained by the treatment of indole (232) with ethyl malonyl chloride in the presence of diethylaluminium chloride (a Lewis acid) in DCM followed by cyclization with hydrazine hydrate in refluxing EtOH.…”

“…Zhang et al. synthesized several regioisomeric 3‐pyrazolylindoles starting from 3‐acetylindole ( 173 ) using the methods described in Scheme 34 and evaluated their cytotoxic, antibacterial and endothelin‐1 antagonist activities [79,80] . 3‐Acetylindole ( 173 ) on treatment with diethyl oxalate in the presence of sodium ethoxide (NaOEt) followed by cyclization with hydrazine hydrate resulted the mixture of regioisomeric 3‐pyrazolylindoles bearing the ester group on the pyrazole ring ( 191 & 192 ).…”

A multi-component reaction for the direct access to 4,4'-(phenylmethylene)bis(1H-pyrazol-5-ol)-3-carboxylates using nano-NiZr4(PO4)6 in water

“…Pyrazoles constitute a signi cant family of heterocyclic compounds for their potential pharmaceutical applications such as anti-cancer [1], antidepressants [2], antiviral [3], anti-in ammatory [4], anti-malarial [5], antibacterial [6], and antiallergic [7] activities. Ecient creation of complex molecules of chemical and biological importance is a challenging issue and has gained substantial interest in recent years [8][9].…”