4-(2-chloroacetamido) Benzoic Acid Derivatives as Local Anesthetic Agents: Design, Synthesis, and Characterization

Abstract

Local anesthetic activity was investigated with an assumed hypothesis that the essential alkyl substituted nitrogen having strong ionization characteristics (pKa in basic side) generally found in local anesthetics can be replaced by amide nitrogen, having chloro methyl group attached to the carbonyl carbon of amide. In this type of arrangement, the inductive effect exerted by chlorine provided enough ionization character to amide nitrogen. Eight esters, ten amides and one imidazole derivatives of 4-(2-chloroacetamido) benzoic acid were synthesized by Fischer’s esterification, Schotten-Baumann and substitution reactions. The synthesized derivatives (A1–A18 and A.im) were characterized by various instrumental techniques.ACD Lab Suite® was used to determine various physiochemical properties of synthesized molecules. Initially, infiltration local anesthetic activity was determined by Bianchi’s method. Five compounds (A1, A2, A4, A10, and A.im) showed promising local anesthetic activity, where the comparison was made with lignocaine HCl, thus conforming assumed hypothesis. However, the studied compounds have potency lower than that of lignocaine HCl. Compounds showing promising activity with low toxicity were studied further by in-vivo rat sciatic nerve block method using increasing doses. A.im was studied for topological similarity with lignocaine HCl where it showed good local anesthetic activity and was relatively very less toxicity. The reduced toxicity of these molecules may be attributed due to the carbonyl chloro methyl side chain. Further structural advancement may be done by researchers to increase the potency of these compounds since they are relatively less toxic than lignocaine.

A Theobromine Derivative with Anticancer Properties Targeting VEGFR‐2: Semisynthesis, in silico and in vitro Studies

“…The aforementioned promising outcomes of the in silico studies of T-1-AFPB motivated us to synthesize it as presented in Scheme 1. The chloroacetamide derivative 2 [37] was produced by acetylating p-aminobenzoic acid 1 with chloroacetyl chloride in DMF. A carboxylic acid derivative 2 reacted with SOCl 2 to produce the corresponding acyl chloride 3.…”

“…A carboxylic acid derivative 2 reacted with SOCl 2 to produce the corresponding acyl chloride 3. [37] Mixing of the highly reactive acid chloride 3 with 4-fluoroaniline in acetonitrile in the presence of triethylamine produced the…”

Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as anticancer agents and apoptosis inducers

“…At first, acetylation of p -amino benzoic acid 15 with chloroacetyl chloride in DMF in the presence of NaHCO 3 provided the key product 4–(2-chloroacetamido)benzoic acid 16 . Compound 16 was acylated using thionyl chloride to produce the benzoyl chloride derivative 17 52 . Furthermore, stirring of compound 17 with commercially available amines namely, ethylamine, n -butylamine, sec -butylamine, tert - butylamine, cyclopentylamine, cyclohexylamine, 4-aminoacetophenone, 3-chloroaniline, 4-chloroaniline, 2,5-dichloroaniline, 4-fluoroaniline, 2-hydroxyaniline, 4-hydroxyaniline, and 2-hydroxy-4-nitroaniline at room temperature in acetonitrile/TEA mixture afforded the corresponding intermediates 18a – n , respectively.…”

“…All the reagents, chemicals, and apparatus were presented in Supplementary data . Compounds 8 , 9 , 10 , 11 , 12 , 13 , 14 , 16 , 17 , 20a – c , and 21a – c were prepared in accordance with the reported procedures 41 , 42 , 44 , 49 , 50 , 52 .…”