Novel Anti-inflammatory Agents Based on Pyrazole Based Dimeric Compounds; Design, Synthesis, Docking and in Vivo Activity

Series of pyrazole ester prodrugs analogues have been synthesized and found to contain highly potent inhibitors of the cyclooxygenase-2 (COX-2) enzyme. The paper describes synthesis of the target pyrazole analogues. The structure of the synthesized mutual ester prodrugs (6—8c) were confirmed by 1H-,...

Full description

Saved in:
Bibliographic Details
Published inChemical & Pharmaceutical Bulletin Vol. 58; no. 5; pp. 634 - 638
Main Authors Tewari, Ashish Kumar, Srivastava, Priyanka, Singh, Ved Prakash, Singh, Amit, Goel, Raj Kumar, Mohan, Chethampadi Gopi
Format Journal Article
LanguageEnglish
Japanese
Published TOKYO The Pharmaceutical Society of Japan 01.05.2010
Pharmaceutical Society of Japan
Pharmaceutical Soc Japan
Japan Science and Technology Agency
Subjects
Animals
Anti-Inflammatory Agents - chemical synthesis
Anti-Inflammatory Agents - chemistry
Anti-Inflammatory Agents - pharmacology
Carrageenan
Catalytic Domain
Chemistry
Chemistry, Medicinal
Chemistry, Multidisciplinary
cyclooxygenase
Cyclooxygenase 2 - chemistry
Cyclooxygenase 2 - pharmacology
Dimerization
docking
Drug Design
Edema - chemically induced
Edema - drug therapy
Female
Life Sciences & Biomedicine
Male
Models, Molecular
Molecular Structure
NMR
Pharmacology & Pharmacy
Physical Sciences
prodrug
pyrazole
Pyrazoles - chemical synthesis
Pyrazoles - chemistry
Pyrazoles - pharmacology
Rats
Rats, Wistar
Science & Technology
Subcutaneous Tissue - drug effects
prodrug
docking
NMR
GENERAL-SYNTHESIS
DRUGS
pyrazole
SELECTIVE INHIBITORS
cyclooxygenase
COX-2 INHIBITORS
FUTURE
Online AccessGet full text

Cover

More Information
Summary:Series of pyrazole ester prodrugs analogues have been synthesized and found to contain highly potent inhibitors of the cyclooxygenase-2 (COX-2) enzyme. The paper describes synthesis of the target pyrazole analogues. The structure of the synthesized mutual ester prodrugs (6—8c) were confirmed by 1H-, 13C-NMR mass spectroscopy (MS) and their purity were ascertained by TLC and elemental analyses. The biological in vivo evaluation of these compounds in experimental models (carrageenan-induced oedema) proved the presence of anti-inflammatory activity. Docking studies into the catalytic site of COX-2 were used to identify potential anti-inflammatory lead compounds. One lead derivative was chosen endowed with good binding energies.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0009-2363
1347-5223
DOI:10.1248/cpb.58.634