Synthesis and local anaesthetic activity of 2-substituted-N-(2-diethylaminoethyl)-acetamides.
The synthesis of 2-substituted-N-(2-diethylaminoethyl)acetamide oxalates (6a, 6b) and the evaluation of their in vivo local anaesthetic activities are described. The compounds 6a and 6b were obtained starting from 4-acetamidophenol and 1-naphthol, respectively. The in vivo local anesthetic activity was evaluated by infiltration anaesthesia, sciatic nerve block and corneal anaesthesia models. N-(2-Diethylaminoethyl)-2-(naphthalen-1-yloxy)acetamide oxalate (6b) was found to have potency, onset and duration of action comparable to that of lidocaine (2) (lidocaine hydrochloride, CAS 6108-05-0). Procaine (1) (procaine hydrochloride, CAS 51-05-8) was also used for comparison. Dissociation constants (pKa) of compounds 5a and 5b (2-substituted-N-(2-diethylaminoethyl)acetamide) have been determined to be 8.9 and 8.6, respectively.
Jindal
Dharam Paul
DP
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. dharampjindal@yahoo.co.in
Coumar
Mohane S
MS
Singh
Babita
B
Ismail
Mohammed Muhiyiden Mohammed
MM
Zambare
Girish Nilkanth
GN
Bodhankar
Subhash Laxmanrao
SL
D000081:Acetamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000772:Anesthesia, Local; D000779:Anesthetics, Local / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D003315:Cornea / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007202:Indicators and Reagents; D008012:Lidocaine / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009407:Nerve Block; D011343:Procaine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects
D000081:Acetamides; D000779:Anesthetics, Local; D007202:Indicators and Reagents; D011343:Procaine; D008012:Lidocaine