54614-93-6Relevant articles and documents
Synthesis and structure-activity relationships of new 2-phenoxybenzamides with antiplasmodial activity
Dolensky, Johanna,Hermann, Theresa,Hochegger, Patrick,Kaiser, Marcel,M?ser, Pascal,Pferschy-Wenzig, Eva-Maria,Saf, Robert,Seebacher, Werner,Weis, Robert
, (2021/11/08)
The 2-phenoxybenzamide 1 from the Medicines for Malaria Venture Malaria Box Project has shown promising multi-stage activity against different strains of P. falciparum. It was successfully synthesized via a retrosynthetic approach. Subsequently, twenty-one new derivatives were prepared and tested for their in vitro activity against blood stages of the NF54 strain of P. falciparum. Several insights into structure-activity relationships were revealed. The antiplasmodial activity and cytotoxicity of compounds strongly depended on the substitution pattern of the anilino partial structure as well as on the size of substituents. The diaryl ether partial structure had further impacts on the activity. Additionally, several physicochemical and pharmacokinetic parameters were calculated (log P, log D7.4 and ligand efficiency) or determined experimentally (passive permeability and CYP3A4 inhibition). The tert-butyl-4-{4-[2-(4-fluorophenoxy)-3-(trifluoromethyl)benzamido]phenyl}piperazine-1-carboxylate possesses high antiplasmodial activity against P. falciparum NF54 (PfNF54 IC50 = 0.2690 μM) and very low cytotoxicity (L-6 cells IC50 = 124.0 μM) resulting in an excellent selectivity index of 460. Compared to the lead structure 1 the antiplasmodial activity was improved as well as the physicochemical and some pharmacokinetic parameters.
Nanoceria as an efficient and green catalyst for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions
Garad, Dnyaneshwar N.,Ingale, Ajit P.,Shinde, Sandeep V.,Ukale, Dattatraya
supporting information, p. 1656 - 1668 (2021/04/05)
Nanocerium oxide mediated an efficient and green protocol has been described for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions at ambient temperature. Various aliphatic, aromatic and heteroaromatic amines were protected using developed protocol and several functional groups such as alcohol, phenol and ester were well tolerated under these conditions. The rapid reaction rate, mild conditions, very good functional group tolerance, excellent yield, solvent-free, easy recovery products and excellent catalyst recyclability are the advantages of this protocol. This makes the protocol feasible, economical and environmentally benign.
Chemoselective: N-tert -butyloxycarbonylation of amines in glycerol
Ingale, Ajit P.,More, Vishal K.,Gangarde, Uddhav S.,Shinde, Sandeep V.
supporting information, p. 10142 - 10147 (2018/06/18)
A catalyst-free, efficient and green protocol has been developed for the chemoselective N-Boc protection of amines by using glycerol as a solvent at room temperature. A variety of functionalized amines, such as aliphatic, aromatic as well as heteroaromatic were protected using the developed protocol. N-tert-Butyloxycarbonylation derivatives were formed without the formation of isocyanate, urea, N,N-di-t-Boc, or oxazolidinone as side products. The operational simplicity, cleaner reaction, rapid reaction convergence, functional group tolerance, excellent yield, high selectivity, catalyst-free feature and solvent recyclability are the distinct advantages of this protocol. Owing to these merits, this protocol is feasible, economical and environmentally benign.