Synthesis and analgesic activity of hydrochlorides and quaternary ammoniums of epibatidine incorporated with amino acid ester.
Hydrochloride derivatives 5a-c and quaternary ammonium derivatives 6a-c of epibatidine incorporated with amino acid ester were synthesized and evaluated for their in vivo analgesic activity and toxicity. Among all tested compounds, compound 6c has the most potent analgesic activity. The quaternary ammonium salts 6a and 6c showed better analgesic activity than the corresponding hydrochlorides 5a and 5c. Both 5a-c and 6a-c showed significantly lower toxicity than epibatidine itself.
Dong
Jing-Chao
JC
School of Pharmaceutical Sciences, Peking University, Beijing 100083, PR, China.
Wang
Xin
X
Li
Run-Tao
RT
Zhang
Hong-Mei
HM
Cheng
Tie-Ming
TM
Li
Chang-Ling
CL
D000596:Amino Acids; D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006851:Hydrochloric Acid / Q000494:pharmacology; D051379:Mice; D010146:Pain / Q000517:prevention & control; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000596:Amino Acids; D018712:Analgesics, Non-Narcotic; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011725:Pyridines; D000644:Quaternary Ammonium Compounds; C082748:epibatidine; D006851:Hydrochloric Acid