Design, synthesis and biological evaluation of novel analgesic agents targeting both cyclooxygenase and TRPV1.
Bioorg Med Chem
; 24(4): 849-57, 2016 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-26795113
ABSTRACT
Multitarget-directed ligands might offer certain advantages over traditional single-target drugs and/or drug combinations. In the present study, a series of novel analgesic agents targeting both cyclooxygenase and TRPV1 were prepared and evaluated in an effort to optimize properties of previously described lead compounds from piperazine, ethanediamine cores. These compounds were evaluated for antagonism of hTRPV1 activation by capsaicin and the ability to inhibit Ovine COX-1 and human recombinant COX-2 in vitro. The favorable potentials of these test compounds were further characterized in preliminary analgesic and side-effects tests in vivo. On the basis of comprehensive evaluations, compound 8d which showed strong TRPV1 antagonistic activity, middle COX-2 inhibition, weak ulcerogenic action and had no hyperthermia side-effect was considered as a safe candidate for the further development of analgesic drugs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pain
/
Piperazines
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Drug Design
/
Diamines
/
Analgesics
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Bioorg Med Chem
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2016
Document type:
Article
Affiliation country:
China
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM