3-Phenyl-5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]indole-2-carbonitrile, a potent inhibitor of prostaglandin synthetase and of platelet aggregation

Abstract

A number of indoles containing the 2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl side chain have been prepared by standard methods. Alternate, novel syntheses of indole-2-carboxamides and indole-2-carbonitriles have been developed. The title compound, 7e, was found to be a potent inhibitor of bovine prostaglandin synthetase in vitro and to lower serum prostaglandin levels after oral or intraperitoneal administration to rats. Consistent with prostaglandin synthetase inhibition, 7e prevented arachidonic acid induced diarrhea in mice and also collagen, ADP, or epinephrine induced platelet aggregation in human platelet-rich plasma. In contrast to many prostaglandin synthetase and platelet-aggregation inhibitors, 7e had neither ulcerogenicity nor systemic antiinflammatory activity in rats.

Potential Inhibitors of Platelet Aggregation from Plant Sources, III

“…Because the chemical structures of DBA and EDB are fairly simple and various structural analogs of them are readily available, 30 different dihydroxybenzoic acid derivatives including various positional isomers of dihydroxybenzoic acids, their methyl and ethyl esters, mono-and di-methylated analogs at the phenolic functions, etc., were secured to investigate the structure-activity relationships. The results are tabulated in Table 3-Among the various positional isomers of dihydroxybenzoic acids [1-6], 2,4dihydroxy acid [2] was most inhibitory against both AAand collagen-induced aggregations. The 2,3-isomer [7] was a better inhibitor than the other isomer [3-6] against AA-induced aggregation; however, it was less inhibitory than 2.…”

Chemically modulated graphene quantum dot for tuning the photoluminescence as novel sensory probe

“…The diazonium salt of HFHPB-N2 + was synthesized according to a previous report42. 2-(4-Aminophenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.200 g, Alfa Aesar) was dissolved in a 50 ml round bottom flask with dry THF (5 ml) under a N 2 atmosphere.…”

A Practical Guide to Prepare and Synthetically Modify Graphene Quantum Dots

“…Carbon–carbon bond formation between two separate aryl groups is a major area of organic chemistry, however to date, this type of chemistry has been rarely applied to GQDs . The reaction between GQDs and diazonium 41 (synthesized in‐house following a previously reported procedure), to give GQD 43 ( Scheme )[106a] has been described and it is likely that this reaction occurs via a Gomberg–Bachmann mechanism; a radical pathway where N 2 is expelled. These reactions are typically performed in basic mediums and do not require anhydrous conditions making water‐soluble GQDs amenable to this type of chemistry.…”