Synthesis and evaluation of some gastrointestinal sparing anti-inflammatory aminoethyl ester derivatives of naphthalene-based NSAIDs.
To overcome the local gastric toxicity associated with use of common non-steroidal anti-inflammatory drugs (NSAIDs), some aminoalcohol esters of NSAIDs bearing structural resemblance to the aminoalcohol ester class of anticholinergics were specially designed and synthesized. Besides blocking the acidic carboxyl group to overcome the local gastric irritation, the anticholinergic activity was incorporated with the expected advantage of reducing the gastric toxicity by decreasing gastric acid secretions and motility. Derivatives of naproxen and 6-methoxy-2-napthylacetic acid (6-MNA) were synthesized. The hydrolysis studies in buffers revealed the majority of the compounds to be sufficiently stable with a high enzymatic susceptibility in 80% human serum. Most of the derivatives exhibited a fairly good anticholinergic action against acetylcholine with a significant reduction in ulcerogenicity while retaining the anti-inflammatory potency of the parent drug. The combination of anti-inflammatory and anticholinergic activities, with a simultaneous reduction of the acidic character, may lead to development of therapeutically better compounds than the parent NSAIDs for long-term oral anti-inflammatory therapy.
Halen
Parmeshwari K
PK
Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, The M.S. University of Baroda, Vadodara, Gujarat, India.
Raval
Manisha K
MK
Chagti
Kewal K
KK
Giridhar
Rajani
R
Yadav
Mange R
MR
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D004487:Edema / Q000517:prevention & control; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects; D006207:Half-Life; D007408:Intestinal Absorption; D008297:Male; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009281:Naphthalenes