100870-73-3Relevant articles and documents
Pyridine-based, microwave-assisted one-pot synthetic protocol for the synthesis of ethyl 3-substituted-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates
Mundra, Sourabh,Mahesh, Radhakrishnan
, p. 4207 - 4219 (2016)
Pyridine has been used for one-pot, two-component synthesis of ethyl 3-substituted-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives in moderate to good yields by condensing N-substituted thioureas with diethyl ethoxymalonate under microwave irradiation.
A novel class of Plasmodial ClpP protease inhibitors as potential antimalarial agents
Mundra, Sourabh,Thakur, Vandana,Bello, Angelica M.,Rathore, Sumit,Asad, Mohd,Wei, Lianhu,Yang, Jane,Chakka, Sai Kumar,Mahesh, Radhakrishnan,Malhotra, Pawan,Mohmmed, Asif,Kotra, Lakshmi P.
, p. 5662 - 5677 (2017/10/09)
The prokaryotic ATP-dependent ClpP protease, localized in the relict plastid of malaria parasite, represents a potential drug target. In the present study, we utilized in silico structure-based screening and medicinal chemistry approaches to identify a novel pyrimidine series of compounds inhibiting P. falciparum ClpP protease activity and evaluated their antiparasitic activities. Structure-activity relationship indicated that morpholine moiety at C2, an aromatic substitution at N3 and a 4-oxo moiety on the pyrimidine are important for potent inhibition of ClpP enzyme along with antiparasiticidal activity. Compound 33 exhibited potent antiparasitic activity (EC?? 9.0 ± 0.2 μM), a 9-fold improvement over the antiparasitic activity of the hit molecule 6. Treatment of blood stage P. falciparum cultures with compound 33 caused morphological and developmental abnormalities in the parasites; further, compound 33 treatment hindered apicoplast development indicating the targeting of apicoplast.
