70319-57-2Relevant academic research and scientific papers
Discovery and structure-activity relationships of pyrrolone antimalarials
Murugesan, Dinakaran,Mital, Alka,Kaiser, Marcel,Shackleford, David M.,Morizzi, Julia,Katneni, Kasiram,Campbell, Michael,Hudson, Alan,Charman, Susan A.,Yeates, Clive,Gilbert, Ian H.
supporting information, p. 2975 - 2990 (2013/05/23)
In the pursuit of new antimalarial leads, a phenotypic screening of various commercially sourced compound libraries was undertaken by the World Health Organisation Programme for Research and Training in Tropical Diseases (WHO-TDR). We report here the detailed characterization of one of the hits from this process, TDR32750 (8a), which showed potent activity against Plasmodium falciparum K1 (EC50 ～ 9 nM), good selectivity (>2000-fold) compared to a mammalian cell line (L6), and significant activity against a rodent model of malaria when administered intraperitoneally. Structure-activity relationship studies have indicated ways in which the molecule could be optimized. This compound represents an exciting start point for a drug discovery program for the development of a novel antimalarial.
Reactions of "Cp2Ti=CH2" Sources with Acid Anhydrides and Imides
Cannizzo, Louis F.,Grubbs, Robert H.
, p. 2316 - 2323 (2007/10/02)
The reaction of Cp2H2 (3a) with acid anhydrides gave Cp2Ti(OC(O)R)(OC(R)=CH2) (4) in moderate yields.Reaction of 4 with 3a and anhydrides produced 2O (5) and Cp2Ti(OC(O)R)2 (7), respectively.The enolate 4c (R = Ph) reacted with benzaldehyde to form the dehydrated aldol product chalcone (8).Selected 2,5-pyrrolidinediones upon treatment with 1 equiv of Cp2TiCH2*AlMe2Cl (1) or 3a yielded mixtures of 5-methylene-2-pyrrolidinones and 2,5-dimethylenepyrrolidines while use of 2 equiv of 1 or 3a gave exclusively the dimethylene products, potential "dienamine" precursors of 1,2,5-trisubstituted pyrroles.Regioselective methylene transfer was observed for 3,3-dimethyl-2,5-pyrrolidinediones, giving 3,3-dimethyl-5-methylene-2-pyrrolidinones in high yields.Treatment of 1-(3-butenyl)-3,3-dimethyl-5-methylene-2-pyrrolidinone (12n) (formed from the parent 2,5-pyrrolidinedione and 1) with HCO2H gave the cyclized product 1-aza-4-(formyloxy)-6,8,8-trimethylbicyclononan-9-one (14a) exemplifying a potential method for the synthesis of alkaloid analogues.Reaction of 3,3-dimethyl-2,6-piperidinediones with either 1 or 3a formed mixtures of the single methylene-transfer products 3,3-dimethyl-5-methylene-2-piperidinones and titanium enolates of the starting 2,6-piperidinediones.The enolate (16d) of 3,3-dimethyl-1-(2,6-dimethylphenyl)-2,6-piperidinedione was unreactive toward benzaldehyde, even upon prolonged heating.
