64893-54-5Relevant articles and documents
Development of Potent 3-Br-isoxazoline-Based Antimalarial and Antileishmanial Compounds
Basilico, Nicoletta,Conti, Paola,Coser, Consuelo,Galbiati, Andrea,Parapini, Silvia,Tamborini, Lucia,Taramelli, Donatella,Zana, Aureliano
supporting information, p. 1726 - 1732 (2021/11/01)
Starting from the structure of previously reported 3-Br-isoxazoline-based covalent inhibitors of P. falciparum glyceraldehyde 3-phosphate dehydrogenase, and with the intent to improve their metabolic stability and antimalarial activity, we designed and synthesized a series of simplified analogues that are characterized by the insertion of the oxadiazole ring as a bioisosteric replacement for the metabolically labile ester/amide function. We then further replaced the oxadiazole ring with a series of five-membered heterocycles and finally combined the most promising structural features. All the new derivatives were tested in vitro for antimalarial as well as antileishmanial activity. We identified two very promising new lead compounds, endowed with submicromolar antileishmanial activity and nanomolar antiplasmodial activity, respectively, and a very high selectivity index with respect to mammalian cells.
Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design, synthesis, molecular docking studies and ADMET prediction
Ibrahim, Tarek S.,Moustafa, Amr H.,Almalki, Ahmad J.,Allam, Rasha M.,Althagafi, Abdulhamid,Md, Shadab,Mohamed, Mamdouh F. A.
, p. 1067 - 1078 (2021/05/28)
Two series of chalcone/aryl carboximidamide hybrids 4a–f and 6a–f were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their in?vivo anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds 4c, 4d, 6c and 6d were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, 4c, 4d, 6c and 6d showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, 4c, 6a and 6e displayed good COX2 inhibitory activity while 4c, 6a and 6c exhibited the highest 5LOX inhibitory activity. Compounds 4c, 4d, 6c and 6d fit nicely into the pocket of iNOS protein (PDB ID: 1r35) via the important amino acid residues. Prediction of physicochemical parameters exhibited that 4c, 4d, 6c and 6d had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides 4c, 4d, 6c and 6d, in particular 4d and 6d, could be used as promising lead candidates as potent anti-inflammatory agents.
Optimization of the synthesis of het/aryl-amidoximes using an efficient green chemistry
Albayati, Mustafa R.,Mohamed, Mamdouh F. A.,Moustafa, Amr H.
supporting information, p. 1217 - 1231 (2020/03/19)
This work focuses on optimizing an efficient green synthesis of arylamidoximes from appropriate nitrile and hydroxylamine hydrochloride in water and triethylamine (1.6 mol equivalent) as a base at room temperature for 6 h. This new green synthetic methodology is compared with previously known methods. The main advantages of this new process reported are good yield, easier work-up and short reaction times. Moreover, some of the synthesized arylamidoximes converted to 1,2,4-oxadiazole derivatives 13a,b and 14via the reaction with (4-acetylphenoxy)acetic acid 12.
