38585-74-9Relevant articles and documents
Synthesis, Antiviral Potency, in Vitro ADMET, and X-ray Structure of Potent CD4 Mimics as Entry Inhibitors That Target the Phe43 Cavity of HIV-1 gp120
Curreli, Francesca,Kwon, Young Do,Belov, Dmitry S.,Ramesh, Ranjith R.,Kurkin, Alexander V.,Altieri, Andrea,Kwong, Peter D.,Debnath, Asim K.
, p. 3124 - 3153 (2017/04/21)
In our attempt to optimize the lead HIV-1 entry antagonist, NBD-11021, we present in this study the rational design and synthesis of 60 new analogues and determination of their antiviral activity in a single-cycle and a multicycle infection assay to derive a comprehensive structure-activity relationship (SAR). Two of these compounds, NBD-14088 and NBD-14107, showed significant improvement in antiviral activity compared to the lead entry antagonist in a single-cycle assay against a large panel of Env-pseudotyped viruses. The X-ray structure of a similar compound, NBD-14010, confirmed the binding mode of the newly designed compounds. The in vitro ADMET profiles of these compounds are comparable to that of the most potent attachment inhibitor BMS-626529, a prodrug of which is currently undergoing phase III clinical trials. The systematic study presented here is expected to pave the way for improving the potency, toxicity, and ADMET profile of this series of compounds with the potential to be moved to the early preclinical development.
Synthesis and properties of NLO chromophores with fine-tuned gradient electronic structures
Ma, Xiaohua,Ma, Fei,Zhao, Zhenhua,Song, Naiheng,Zhang, Jianping
supporting information; experimental part, p. 2975 - 2985 (2010/05/02)
A novel series of heterocycle-based NLO chromophores based on different combinations of auxiliary donor (i.e., benzene, thiophene and pyrrole) and auxiliary acceptor (i.e., thiazole with different regiochemistries) were designed and synthesized. Due to the different electron-rich and poor nature of the auxiliary donors and acceptors, respectively, the resulting NLO chromophores have systematically varied ground-state electronic structures, as evidenced by the 1H NMR, CV and UV-vis investigations. The nonlinear optical properties of the resulting NLO chromophores were studied by UV-vis spectroscopy, Hyper-Rayleigh scattering (HRS), and semi-empirical computations. All the chromophores have very large molecular hyperpolarizabilities (β1000 nm) in the range of 704-1500 × 10-30 esu (or β0, 318-768 × 10-30 esu), which showed a great sensitivity to the gradient electronic structures. Upon increasing the electron density from benzene to thiophene and to pyrrole, substantial increases in β0 were observed; significantly larger β0 values were also observed for NLO chromophores based on "matched" thiazole (C2 is connected to the acceptor) than those based on "un-matched" thiazole (C5 is connected to the acceptor). TGA investigations showed good thermal stability for the resulting NLO chromophores. However, with the increase of electron density of the auxiliary donor, a decrease in thermal and photochemical stability was observed. It is interesting to note that NLO chromophores based on triarylamine as the donor and thiazole as the auxiliary acceptor exhibited not only high thermal stability but also very large β0 values.
Rapid and efficient synthesis of stable isotope labeled [ 13C4, D4]-5-(hydroxymethyl)thiazole: Versatile building block for biologically interesting compounds
Lin, Ronghui,Salter, Rhys,Gong, Yong
body text, p. 110 - 113 (2009/10/24)
5-(Hydroxymethyl)thiazole is a versatile building block for many biologically active compounds. A rapid and efficient four- step synthesis of its stable isotope labeled counterpart with four 13C and four deuterium atoms in 32% total yield is reported. Condensation of [13C 2]-chloro acetic acid with [13C]-thiourea gave [ 13C3]-2,4-thiazolidinedione. Reaction of [ 13C3]-2,4-thiazolidinedione with phosphorus oxybromide and [13C, D]-DMF (Me2N13CDO) produced [ 13C4 D]-2,4-dibromo- thiazole-5-carboxaldehyde. The resultant aldehyde was then reduced by sodium borodeuteride to [ 13C4, D2]-(2,4-dibromo- thiazol-5-yl)-methanol. Catalytic deuteration of [13C4, D2]-(2,4- dibromo-thiazol-5-yl)-methanol by palladium black with deuterium gas at 1 atm pressure and room temperature produced completely de-brominated [ 13C4, D4]-5-(hydro- xymethyl)thiazole. De-bromination of the 2,4-dibromothiazole by the catalysis of palladium black provides a simple and convenient synthetic method for the stable isotope labeled and potentially radioactive isotope labeled thiazole compounds. Copyright
