Xiaokui Wang

Novel fatty acid synthase (FAS) inhibitors: Design, synthesis, biological evaluation, and molecular docking studies

Several novel series of C75 derivatives were synthesized and evaluated for their FAS inhibitory activities. The results showed compound 4-methylene-2-octyl-5-oxo-tetrahydro-thiophene-3-carboxylic acid (1c) had more effective FAS inhibitory (IC(50) was 2.56 microM and T.I. was 9.26) and potent anti-tumor activities on HL60 and Hela cells in vitro (IC(50) were 5.38 microM and 46.10 microM, respectively).

Synthesis and biological evaluation of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors.

We have developed a series of substituted 4-(thiophen-2-ylmethyl)-2H-phthalazin-1-ones as potent PARP-1 inhibitors. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to, or higher than AZD-2281. Among these compounds, 18q appeared to be the most notable one, which displayed an 8-fold improvement in enzymatic activity compared to AZD-2281. These efforts lay the foundation for our further investigation.

1-Oxo-3-substitute-isothiochroman-4-carboxylic acid compounds: Synthesis and biological activities of FAS inhibition

A new series 1-oxo-3-substitute-isothiochroman-4-carboxylic acid compounds have been designed and synthesized. Screening of these molecules for FAS inhibition in vitro has indicated that compounds 2c and 2d showed more effective FAS inhibition activities and higher therapeutic index than C75.

Asymmetric Synthesis and Absolute Configuration Assignment of a New Type of Bedaquiline Analogue

Bedaquiline is the first FDA-approved new chemical entity to fight multidrug-resistant tuberculosis in the last forty years. Our group replaced the quinoline ring with a naphthalene ring, leading to a new type of triarylbutanol skeleton. An asymmetric synthetic route was established for our bedaquiline analogues, and the goal of assigning their absolute configurations was achieved by comparison of experimental and calculated electronic circular dichroism spectra, and was confirmed by the combined use of circular dichroism and NMR spectroscopy.

An Efficient Synthesis of Enantiopure (R)-heteroarylpyrimidine Analogs

An efficient synthesis of enantiopure (R)-heteroarylpyrimidine analogs is described here, which involves introduction of a chiral group, formation and separation of diasteroisomers and final transformation of an amide to an ester. The absolute configuration of the enantiopure HAPs is confirmed by X-ray analysis of their intermediates.

Facile One-Pot Method for the Synthesis of Polysubstituted Phthalide Derivatives

Abstract A new three-component cyclization method is described involving two starting materials, ethyl 4-chloroacetoacetate and aldehydes, catalyzed by piperidine, acid, and iodine. Ten corresponding polysubstituted phthalides are formed with good yields (44–78%). A mechanism of the reaction is also proposed. GRAPHICAL ABSTRACT