[Synthesis and anti-inflammatory analgesic activities of phenylfuroxan-coupled diclofenac].
OBJECTIVE
To search for new derivatives of diclofenac (DC) having higher potency than the parent drug and lacking its undesirable effects.


METHODS
Coupling DC with NO donor 3-hydroxymethyl-4-phenylfuroxan and its isomer through esterification, evaluating anti-inflammatory and analgesic activities, observing side effects in the rat gastrointestinal (GI) tract and assessing NO releasing ability both in vitro and in vivo.


RESULTS
Fifteen new compounds including nine target ones (II1-9) were synthesized, and their structures were determined by IR, 1HNMR, MS and elemental analysis. Compounds II3 and II9 showed anti-inflammatory activity comparable to DC. Compound II2 showed stronger anti-inflammatory and analgesic activities and less GI side effect than DC, and released NO in vivo.


CONCLUSIONS
Compound II2 is worthy to be intensively studied.
Li
Rui-wen
RW
Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
Zhang
Yi-hua
YH
Ji
Hui
H
Yu
Xiao-lin
XL
Peng
Si-xun
SX
D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004008:Diclofenac / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D004064:Digestive System / Q000187:drug effects; D004487:Edema / Q000188:drug therapy; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology; D010069:Oxadiazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
C479281:3-hydroxymethyl-4-phenylfuroxan; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003497:Cyclic N-Oxides; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D004008:Diclofenac; D009569:Nitric Oxide