2503-56-2Relevant articles and documents
Quinoline carboxamide core moiety-based compounds inhibit P. falciparum falcipain-2: Design, synthesis and antimalarial efficacy studies
Singh, Anju,Kalamuddin, Md,Maqbool, Mudasir,Mohmmed, Asif,Malhotra, Pawan,Hoda, Nasimul
, (2020/12/07)
Targeting Falcipain-2 (FP2) for the development of antimalarials is a promising and established concept in antimalarial drug discovery and development. FP2, a member of papain-family cysteine protease of the malaria parasite Plasmodium falciparum holds an important role in hemoglobin degradation pathway. A new series of quinoline carboxamide-based compounds was designed, synthesized and evaluated for antimalarial activity. We integrated molecular hybridization strategy with in-silico drug design to develop FP2 inhibitors. In-vitro results of FP2 inhibition by Qs17, Qs18, Qs20 and Qs21 were found to be in low micromolar range with IC50 4.78, 7.37, 2.14 and 2.64 μM, respectively. Among the 25 synthesized compounds, four compounds showed significant antimalarial activities. These compounds also depicted morphological and food-vacuole abnormalities much better than that of E-64, an established FP2 inhibitor. Overall these aromatic substituted quinoline carboxamides can serve as promising leads for the development of novel antimalarial agents.
Pd-catalyzed Suzuki/Sonogashira cross-coupling reaction and the direct sp3 arylation of 7-chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine
Loubidi, Mohammed,Moutardier, Ana?s,Campos, Joana F.,Berteina-Raboin, Sabine
supporting information, p. 1050 - 1054 (2018/02/14)
A rapid and efficient method is reported for the synthesis of the [1,2,4]triazolo[1,5-a]pyrimidine motif. Palladium catalyzed Suzuki and Sonogashira cross coupling reactions on 7-chloro-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine were performed. The direct sp3 arylation of compounds resulting from the Suzuki reaction was then carried out.
The synthesis and evaluation of triazolopyrimidines as anti-tubercular agents
Zuniga, Edison S.,Korkegian, Aaron,Mullen, Steven,Hembre, Erik J.,Ornstein, Paul L.,Cortez, Guillermo,Biswas, Kallolmay,Kumar, Naresh,Cramer, Jeffrey,Masquelin, Thierry,Hipskind, Philip A.,Odingo, Joshua,Parish, Tanya
, p. 3922 - 3946 (2017/07/05)
We identified a di-substituted triazolopyrimidine with anti-tubercular activity against Mycobacterium tuberculosis. Three segments of the scaffold were examined rationally to establish a structure-activity relationship with the goal of improving potency and maintaining good physicochemical properties. A number of compounds displayed sub-micromolar activity against Mycobacterium tuberculosis with no cytotoxicity against eukaryotic cells. Non-substituted aromatic rings at C5 and a two-carbon chain connecting a terminal aromatic at C7 were preferred features; the presence of NH at C7 and a lack of substituent at C2 were essential for potency. We identified compounds with acceptable metabolic stability in rodent and human liver microsomes. Our findings suggest that the easily-synthesized triazolopyrimidines are a promising class of potent anti-tubercular agents and warrant further investigation in our search for new drugs to fight tuberculosis.
