The identification of cyclooxygenase-1 inhibitors from 4-thiazolidinone combinatorial libraries

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 6, 1996, Pages 707-712

  Look, Gary C ^a   Schullek, John R ^a   Holmes, Christopher P ^a   Chinn, Jason P ^a   Gordon, Eric M ^a   Gallop, Mark A ^a  

^a AFFYMAX RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 THIAZOLIDINONE DERIVATIVE; IBUPROFEN; PHENYLBUTAZONE; PROSTAGLANDIN SYNTHASE; PROSTAGLANDIN SYNTHASE INHIBITOR;

ARTICLE; DRUG DESIGN; DRUG SCREENING; DRUG SYNTHESIS; ENZYME INHIBITION; STRUCTURE ACTIVITY RELATION;

EID: 0029981645     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00097-2     Document Type: Article

References (34)

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24. The methylation procedure for the thiazolidinones was validated by HPLC studies of the conversion of the free acid thiazolidinones to their methyl ester analogs.
25. This correlates well with the data reported in the Walsh patent where thiazolidinone acids are typically less potent than the esters. Additionally, the Walsh patent shows no great variation in the biological activity between the cis and trans diastereoisomers of a given thiazolidinone.
26. The loading of the TentaGel S AC resin used was 280 μmol/g whereas the yield after amino acid loading was 30-60 μmol/g due to inefficient ester formation. These low yields were not expected to compromise the integrity of the libraries as the free unreacted alcohol sites of the resin would not participate in subsequent reactions during the thiazolidinone synthesis.
27. 50 determinations were independently synthesized in solution and purified by silica gel chromatography. The structures of the purified compounds were confirmed by NMR and MS analysis.
28. Prepared with the di-tert-butyl acetal of N,N-dimethylformamide.
29. 6 equation presented
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32. Using the assay described in Ref. 13, compound 7 was determined here to be 40-fold less potent than reported by Walsh (3 μM vs 70 nM). However, we have run assays using known literature standards (eg. ibuprofen and phenylbutazone) and our numbers are consistent with the published data.
33. 50's were determined by measuring the oxygen uptake.
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