Synthesis of new chemical entities from paracetamol and NSAIDs with improved pharmacodynamic profile.
It was envisaged to combine high antipyretic activity of paracetamol into commonly used NSAIDs. To achieve this goal new chemical entities were synthesized by chemically combining paracetamol and NSAIDs, and biologically evaluated for their antipyretic, analgesic, anti-inflammatory and ulcerogenic potential. The acid chloride of parent NSAIDs was reacted with excess of p-aminophenol to yield the desired p-amidophenol derivatives (1B-7B). Acetate derivatives (1C-7C) of these phenols (1B-7B) were also prepared by their treatment with acetic anhydride, in order to see the impact of blocking the free phenolic group on the biological activity of the derivatives. All the synthesized p-amidophenol derivatives showed improved antipyretic activity than paracetamol with retention of anti-inflammatory activity of their parent NSAIDs. These compounds elicited no ulcerogenicity unlike their parent drugs.
Yadav
Mange Ram
MR
Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, The M.S. University of Baroda, Vadodara 390 001, India. mryadav11@yahoo.co.in
Nimekar
Datta M
DM
Ananthakrishnan
A
A
Brahmkshatriya
Pathik S
PS
Shirude
Shrikant T
ST
Giridhar
Rajani
R
Parmar
Arvind
A
Balaraman
R
R
D000082:Acetaminophen / Q000737:chemistry*; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002351:Carrageenan / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000737:chemistry; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D010636:Phenols; D000082:Acetaminophen; D002351:Carrageenan; D051546:Cyclooxygenase 2