Synthesis, biological evaluation and in silico modeling of novel integrase strand transfer inhibitors (INSTIs) was written by Ivashchenko, Andrey A.;Ivanenkov, Yan A.;Koryakova, Angela G.;Karapetian, Ruben N.;Mitkin, Oleg D.;Aladinskiy, Vladimir A.;Kravchenko, Dmitry V.;Savchuk, Nikolai P.;Ivashchenko, Alexander V.. And the article was included in European Journal of Medicinal Chemistry in 2020.Application In Synthesis of Thiazol-2-ylmethanamine This article mentions the following:
Although a relatively wide range of therapeutic options is currently available for the treatment of HIV/AIDS, it is still among the most serious and virulent diseases and is associated with a high mortality rate. Integrase strand transfer inhibitors (INSTIs), e.g., FDA-approved dolutegravir (DTG), bictegravir (BIC) and cabotegravir (CAB), have recently been included in standard highly active antiretroviral therapy (HAART) schemes as one of the five major components responsible for the most beneficial clin. outcome. In this paper, we describe a combinatorial amide synthesis, biol. evaluation and in silico modeling of new INSTIs containing heteroaromatic bioisosteric substitution instead of the well-studied halogen-substituted benzyl fragment. With the focus on the mentioned diversity point, a medium-sized library of compounds was selected for synthesis. A biol. study revealed that many mols. were highly active INSTIs (EC50 < 10 nM). Two compounds 1{4} and 1{26} demonstrated picomolar antiviral activity that was comparable with CAB and were more active than DTG and BIC. Mol. docking study was performed to evaluate the binding mode of compounds in the active site of HIV-1 IN. In rats, lead compound 1{26} showed two-fold greater bioavailability than CAB and had a similar half-life. Compound 1{26} and its sodium salt were considerably more soluble in water than the parent drugs. Both mols. were very stable in human liver microsomes and plasma, demonstrated high affinity towards plasma proteins and did not show cytochrome (CYP) inhibition. This benefit profile indicates the great potential of these mols. as attractive candidates for subsequent evaluation as oral long-acting drugs and long-acting nanosuspension formulations for i.m. injection. In the experiment, the researchers used many compounds, for example, Thiazol-2-ylmethanamine (cas: 55661-33-1Application In Synthesis of Thiazol-2-ylmethanamine).
Thiazol-2-ylmethanamine (cas: 55661-33-1) belongs to thiazole derivatives. The thiazole ring has been identified as a central feature of numerous natural products, perhaps the most famous example of which is epothilone. Electrophilic attack at nitrogen depends on the presence of electron density at nitrogen as well as the position and nature of substituent linked to the thiazole ring.Application In Synthesis of Thiazol-2-ylmethanamine
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica