Regioselective synthesis of indazolo[2,3-a]quinazolines enabled by I2/S-facilitated annulation relay dehydrogenative aromatization of cyclohexanones.

A method for concise and efficient synthesis of indazolo[2,3-a]quinazolines has been developed via a sequential annulation of 3-aminoindazoles and dehydrogenative aromatization of cyclohexanones. This high regioselectivity is attributed to the fact that the Mannich reaction is superior to the aldol reaction in this system. It is worth mentioning that this convenient process is successfully extended to 3-aminopyrazoles for assembling another class of medicinally prevalent pyrazolo[1,5-a]quinazolines.

Deaminative Cyclization of Tertiary Amines for the Synthesis of 2-Arylquinoline Derivatives with a Nonsubstituted Vinylene Fragment.

With triethylamine as a vinylene source, a convenient protocol for the regioselective synthesis of ß,γ-nonsubstituted 2-arylquinolines from aldehydes and arylamines has been accomplished. The deaminative cyclization is also extended to long-chain tertiary alkylamines, enabling diverse alkyl groups to be concurrently installed into the pyridine rings. This process demonstrates a new conversion pathway for the simultaneous dual C(sp3)-H bond functionalization of tertiary amines, wherein the transient acyclic enamines generated in situ undergo the Povarov reaction.

Recent advances in 3-aminoindazoles as versatile synthons for the synthesis of nitrogen heterocycles.

Nitrogen-based heterocycles are an important class of structural scaffolds distributed in biologically active natural products, medicinal chemistry, and agrochemicals. Hence, there is increasing interest in the development of novel synthetic strategies for the construction of these privileged structural motifs. Recently, 3-aminoindazoles have emerged as versatile synthons participating in a variety of condensation annulation, denitrogenative transannulation and rearrangement ring expansion reactions, which provide efficient synthetic routes for the formation of nitrogen heterocycles. This review systematically highlights for the first time the most recent advances in 3-aminoindazoles to provide a deep understanding of using 3-aminoindazoles as versatile synthons in organic transformations for synthetic and medicinal chemists.

Circadian gene Clock participates in mitochondrial apoptosis pathways by regulating mitochondrial membrane potential, mitochondria out membrane permeablization and apoptosis factors in AML12 hepatocytes.

Circadian rhythms help organisms adapt to changes of external environment by regulating energy metabolism and remaining the balance of homeostasis. Numerous researches have proved that the physiological function of liver was precisely controlled by circadian rhythms. Clock, one of core circadian genes, has been demonstrated to regulate the oxidative phosphorylation process of mitochondrial, which provides energy for living cells and acts as one of the hub for apoptosis. However, whether Clock gene regulates mitochondrial apoptosis pathways in liver cells remains less explored. In the present study, we used lentiviral vector to establish a stable AML12 cell lines which were capable of expressing specific shRNA to interfere the expression of Clock gene and investigated the effect of Clock on mitochondrial apoptosis pathways. Herein, we found that the interference of Clock gene could significantly suppress mitochondrial apoptosis pathways by stabilizing mitochondrial membrane potential and inhibiting mitochondria out membrane permeablization, which might be a result of lower expression of BAD and BIM proteins. Moreover, the interference of Clock gene could downregulate the expression of mitochondrial apoptosis factors, i.e. AIF, CYCS, APAF-1 and SMAC, which will suppress the formation of apoptosome and the process of DNA degradation to further inhibit apoptosis process. This work provides an insight on the important role of Clock gene participating in mitochondrial apoptosis pathways of hepatocytes and unveils a probable pathogenesis of how circadian rhythm regulates liver diseases.