Synthesis and Biological Evaluation of 2‐Hydroxy‐3‐[(2‐aryloxyethyl)amino]propyl 4‐[(Alkoxycarbonyl)amino]benzoates

Abstract

A series of twenty substituted 2-hydroxy-3-[(2-aryloxyethyl)amino]propyl 4-[(alkoxycarbonyl)amino]benzoates were prepared and characterized. As similar compounds have been described as potential antimycobacterials, primary in vitro screening of the synthesized carbamates was also performed against two mycobacterial species. 2-Hydroxy-3-[2-(2,6-dimethoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, 2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride, and 2-hydroxy-3-[2-(2-methoxyphenoxy)ethylamino]-propyl 4-(butoxycarbonylamino)benzoate hydrochloride showed higher activity against M. avium subsp. paratuberculosis and M. intracellulare than the standards ciprofloxacin, isoniazid, or pyrazinamide. Cytotoxicity assay of effective compounds was performed using the human monocytic leukaemia THP-1 cell line. Compounds with predicted amphiphilic properties were also tested for their effects on the rate of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. All butyl derivatives significantly stimulated the rate of PET, indicating that the compounds can induce conformational changes in thylakoid membranes resulting in an increase of their permeability and so causing uncoupling of phosphorylation from electron transport.

An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors

“…Epoxides 7a–9a and 13a (see below) were prepared from 4-aminobenzoic acid through reaction with methyl, ethyl, propyl and butyl chloroformiates giving appropriate 4-[(alkoxycarbonyl) amino]benzoic acids. Chlorides of these acids formed by thionyl chloride treatment gave desired epoxides 7a–9a and 13a after reaction with 2,3-epoxypropan-1-ol [53]. In the last step final compounds 7–9 were prepared by a reaction of the epoxides with 1-(4-phenyl)piperazine and then converted to the hydrochloride salts using ethereal HCl to enhance their solubility in water [55].…”

“…Synthesis of 2-hydroxy-3-[2-(4-methoxyphenoxy)ethylamino] propyl 4-(propoxycarbonylamino)benzoate hydrochloride ( 13 ) was described in Tengler et al [53]. The first main intermediate, oxiran-2-ylmethyl 4-[(propoxycarbonyl)amino]benzoate ( 13a ) was synthesized according to Scheme 3.…”

“…The epoxide ring was opened by addition of the second main intermediate, 2-(4-methoxyphenoxy) ethanamine ( 13b ) prepared by Gabriel synthesis from 4-methoxyphenol via 1-(2-bromoethoxy)-4-methoxybenzene and 2-[2-(4-methoxyphenoxy)ethyl]-1 H -isoindole-1,3(2 H )-dione, see Scheme 5. The higher aqueous-soluble hydrochloride salt was prepared from the acquired base using ethereal HCl, as described in Tengler et al [53]. …”

Preparation and Photosynthesis-Inhibiting Activity of <em>N</em>-(n-Alkoxy)phenylamides of 2-Hydroxynaphthalene-1-carboxylic acid

“…For individual substituents in the aniline part of the discussed compounds also electronic Hammett's σ parameters were predicted using the same software; they ranged from -0.29 to -0.27 for ortho-and parasubstituted compounds and from 0.10 to 0.14 for meta-substituted compounds. Experience has shown that a parameter representing the volume of the substituents on each compound relative to other members of the same series may often be correlated with biological measurement [23][24][25], therefore molar volume MV [cm -3 ] was also calculated. The predicted molecular descriptors of the studied compounds are shown in Table 1.…”

In vitro radical scavenging and cytotoxic activities of novel hybrid selenocarbamates

“…22 Taking into account our previous experience in selenocyanate and diselenide chemistry [23][24][25] and the fact that we have recently reported some carbamates as potential antiproliferative drugs, 26 we decided to further extend our research by synthesising thirty new hybrid compounds in which selenocyanate or diselenide and carbamate moieties were combined. In these compounds the carbamate function, a group commonly found in antitumour active http compounds [27][28][29][30][31][32] acts as a link between the central and ending scaffolds, thus enabling their chemical accessibility and increasing polarity in this area as compared to our previously described structures. 23,[33][34][35] Besides, this group might facilitate the hydrolysis of the compounds towards anionic species that could act as prodrugs (Fig.…”