Design, Synthesis, and Structure-Activity Relationship Studies of 3,4,6-Triphenylpyran-2-ones as Selective Cyclooxygenase-2 Inhibitors was written by Rao, P. N. Praveen;Uddin, Jashim Md.;Knaus, Edward E.. And the article was included in Journal of Medicinal Chemistry in 2004.COA of Formula: C10H11FO2 This article mentions the following:
A group of regioisomeric 3,4,6-triphenylpyran-2-ones with a MeSO2 pharmacophore at the para-position of either a C-3 Ph or a C-4 Ph substituent on the central six-membered pyran-2-one ring were prepared and evaluated in vitro for their abilities to inhibit the isoenzymes COX-1 and COX-2. Structure-activity relationship (SAR) data, acquired by substituent modification at the para-position of the C-6 Ph ring attached to the central pyranone, showed that 6-(4-methoxyphenyl)-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-one (I)was the most potent and selective COX-2 inhibitor (COX-2 IC50 = 0.02 μM; COX-1 IC50 > 100 μM) with a high COX-2 selectivity index (SI > 5000) relative to the reference drugs celecoxib and rofecoxib. I was a more potent oral antiinflammatory agent (ID50 = 5.6 mg/kg) than celecoxib in a carrageenan-induced rat paw edema assay. In a 4% NaCl-induced abdominal constriction assay, a 5 mg/kg oral dose of I exhibited good analgesic activity at different time intervals producing 37.5 and 69% inhibition of writhing at 30 and 60 min, resp. In contrast, the corresponding 6-(4-methoxyphenyl)-4-(4-methanesulfonylphenyl)-3-phenylpyran-2-one regioisomer was a less potent and selective COX-2 inhibitor (COX-2 IC50 = 0.45 μM; SI = 70). A mol. modeling study for I indicated that the p-OMe substituent on the C-6 Ph ring interacts with the COX-2 binding site amino acids Ile345, Val349, Leu359, Leu531, and Met535 and that the OMe substituent may be responsible for proper orientation of the C-3 p-SO2Me-Ph ring within the COX-2 secondary pocket (Gln192, Arg513, and Phe518). These results show that the COX-2 selectivity and potency of 3,4,6-triphenylpyranone regioisomers can be modulated by appropriate placement of the p-SO2Me pharmacophore on either the C-3 or C-4 Ph moiety. In addition, electronic properties at the para-position of a C-6 Ph substituent on the central pyranone ring govern COX-2 inhibitory potency and selectivity by controlling the orientation of the p-SO2Me pharmacophore within the COX-2 secondary pocket. In the experiment, the researchers used many compounds, for example, Ethyl 2-(4-fluorophenyl)acetate (cas: 587-88-2COA of Formula: C10H11FO2).
Ethyl 2-(4-fluorophenyl)acetate (cas: 587-88-2) belongs to esters. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits, including apples, durians, pears, bananas, pineapples, and strawberries. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.COA of Formula: C10H11FO2
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics