Synthesis, local anesthetic activity and QSAR studies for a set of N-[2-(alkylamino)ethyl]benzotriazol- x-yl acetamides

• Published in: European journal of medicinal chemistry Vol. 30; no. 7; pp. 603 - 608
• Main Authors: Caliendo, G, Di Carlo, R, Greco, G, Grieco, P, Meli, R, Novellino, E, Perissutti, E, Santagada, V
• Format: Journal Article
• Language: English
• Published: PARIS CEDEX 15 Elsevier Masson SAS 1995; Elsevier
• Subjects: acute toxicity; anesthetic activity; Anesthetics. Neuromuscular blocking agents; benzotriazole; Biological and medical sciences; Chemistry, Medicinal; Life Sciences & Biomedicine; Medical sciences; Neuropharmacology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; QSAR; Science & Technology; anesthetic activity; QSAR; acute toxicity; benzotriazole; ACUTE TOXICITY; ANESTHETIC ACTIVITY; BENZOTRIAZOLE; QUANTITATIVE STRUCTURE; Nitrogen heterocycle; Toxicity; Acute; Rodentia; Rabbit; Lagomorpha; Local anesthetic; Vertebrata; Mammalia; Position isomer; Structure activity relation; Mouse; Animal; Tertiary amine; Bicyclic compound; Carboxamide; Aromatic compound; Chemical synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/0223-5234(96)88275-4

A set of N-[2-(alkylamino)ethyl]benzotriazol- x-yl acetamides were synthesized and tested for local anesthetic activity. The compounds were designed by varying independently the hydrophobicity and size of the side chains. Anesthetic activity was assessed by different tests using lidocaine as a reference: rabbit corneal and mouse tail anesthesia. These two anesthetic activities were correlated with calculated log P values and significant linear dependences were observed. The three most potent compounds of the series were evaluated in the rat sciatic nerve block assay and their acute toxicity in mice was also assessed. Compound 4b ( N-[2-(diethylamino)ethyl]benzotriazol-2-yl acetamide), which has an anesthetic activity comparable to that of lidocaine, was also characterized by a more favorable therapeutic index.