Kang, Dongwei; Ruiz, F. Xavier; Feng, Da; Pilch, Alyssa; Zhao, Tong; Wei, Fenju; Wang, Zhao; Sun, Yanying; Fang, Zengjun; De Clercq, Erik; Pannecouque, Christophe; Arnold, Eddy; Liu, Xinyong; Zhan, Peng published the artcile< Discovery and Characterization of Fluorine-Substituted Diarylpyrimidine Derivatives as Novel HIV-1 NNRTIs with Highly Improved Resistance Profiles and Low Activity for the hERG Ion Channel>, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine, the main research area is HIV1 NNRTIs hERG inhibition half life hybridization bioisosterism cytotoxicity.
Our previous efforts have led to the development of two potent NNRTIs, K-5a2 and 25a, exhibiting effective anti-HIV-1 potency and resistance profiles compared with etravirine. However, both inhibitors suffered from potent hERG inhibition and short half-life. In this article, with K-5a2 and etravirine as leads, series of novel fluorine-substituted diarylpyrimidine derivatives were designed via mol. hybridization and bioisosterism strategies. The results indicated 24b was the most active inhibitor, exhibiting broad-spectrum activity (EC50 = 3.60-21.5 nM) against resistant strains, significantly lower cytotoxicity (CC50= 155μM), and reduced hERG inhibition (IC50 > 30μM). Crystallog. studies confirmed the binding of 24b and the role of the fluorine atom, as well as optimal contacts of a nitrile group with the main-chain carbonyl group of H235. Furthermore, 24b showed longer half-life and favorable safety properties. All the results demonstrated that 24b has significant promise in circumventing drug resistance as an anti-HIV-1 candidate.
Journal of Medicinal Chemistry published new progress about Anti-HIV agents (anti-HIV-1 agents). 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Recommanded Product: 2,4-Dichlorothieno[2,3-d]pyrimidine.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia