104562-48-3Relevant academic research and scientific papers
Identification of a novel pyrrole derivative endowed with antimycobacterial activity and protection index comparable to that of the current antitubercular drugs streptomycin and rifampin
Biava, Mariangela,Porretta, Giulio Cesare,Poce, Giovanna,Battilocchio, Claudio,Alfonso, Salvatore,Logu, Alessandro De,Serra, Nadia,Manetti, Fabrizio,Botta, Maurizio
experimental part, p. 8076 - 8084 (2011/01/13)
A hit optimization procedure based on isosteric and bioisosteric replacement of decorating groups at both the N1 and the C5 phenyl rings of 1,5-diarylpyrroles led to identification of 4-((1-(4-fluorophenyl)-2-methyl-5- (4-(methylthio)phenyl)-1H-pyrrol-3-yl)methyl)thiomorpholine that is characterized by a very high activity toward both Mycobacterium tuberculosis 103471 and H37Rv strains (MIC values of 0.125 μg/mL), and a safe profile in terms of cytotoxicity (CC50 of >128 μg/mL) and protection index (>1000). Antitubercular activity and protection index of the new compound are comparable to those found for the current antitubercular drugs streptomycin and rifampin.
Inhibitors of Cholesterol Biosynthesis. 1. trans-6-(2-Pyrrol-1-ylethyl)-4-hydroxypyran-2-ones, a Novel Series of HMG-CoA Reductase Inhibitors. 1. Effects of Structural Modifications at the 2- and 5-Positions of the Pyrrole Nucleus
Roth, B. D.,Ortwine, D. F.,Hoefle, M. L.,Stratton, C. D.,Sliskovic, D. R.,et al.
, p. 21 - 31 (2007/10/02)
A novel series of trans-6-(2-pyrrol-1-ylethyl)-4-hydroxypyran-2-ones and their dihydroxy acid derivatives were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase in vitro.A systematic study of substitution at the 2- and 5-positions of the pyrrole ring revealed that optimum potency was realized with the 2-(4-fluorophenyl)-5-isopropyl derivative 8x (Table III), which possessed 30percent of the in vitro activity of the potent fungal metabolite compactin (I).A molecular modeling analysis led to the description of a pharmacophore model characterized by (A) length limits of 5.9 and 3.3 Angstroem for the 2- and 5-substituents, respectively, as well as an overall width limit of 10.6 Angstroem across the pyrrole ring from the 2- to the 5-substituent and (B) an orientation of the ethyl(ene) bridge to the 4-hydroxypyran-2-one ring nearly perpendicular to the planes of the parent pyrrole, hexahydronaphthalene, and phenyl rings of the structures examined (Figure 3, θ = 80-110 deg).Attempts to more closely mimic compactin's polar isobutyric ester side chain with the synthesis of 2-phenylpyrroles containing polar phenyl substituents resulted in analogues (Table III, 8m-p) with equal or slightly reduced potencies when compared to the 2-pyrroles, supporting the hypothesis that inhibitory potency is relatively insensitive to side-chain polarity or charge distribution in this area.
DIMETHYLALUMINIUM METHANESELENOLATE - A USEFUL REAGENT FOR THE PREPARATION OF SELENOESTERS. A NEW FRIEDEL-CRAFTS ACYLATION PROCEDURE PROMOTED BY Cu(I)
Kozikowski, Alan P.,Ames, Anthony
, p. 4821 - 4834 (2007/10/02)
The preparation of a new aluminium reagent, dimethylaluminium methaneselenolate (Me2AlSeMe) is described.The reactivity of this aluminium reagent toward a variety of organic substrates has been studied.Me2AlSeMe will convert O-alkyl esters to selenoesters in high yield.These selenoesters function as extremely reactive acyl transfer agents and are converted to acids, esters, and amides on reaction with water, alcohols or amines in the presence of a selenophilic metal cation.The selenoesters will, moreover, acylate reactive arenes and heterocyclic compounds when cuprous triflate is employed as the selenophilic metal cation.This latter transformation constitutes a new transition metal promoted variant of the Friedel-Crafts acylation reaction.
