Design, synthesis and biological evaluation of novel selective thiol-based histone deacetylase(HDAC) VI inhibitors bearing indeno[1,2-c]pyrazole or benzoindazole scaffold

Xu, Qihao; Yu, Shujia; Cai, Yuanqiang; Yang, Jinyu; Zhao, Liang; Liú, Dan

doi:10.1007/s40242-018-7239-6

Cited by 1 publication

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“…Further effort by Xu et al [95] aimed to improve HDAC selectivity by altering the cap motive. Most of the compounds displayed moderate inhibitory activity with 114 being the most selective for HDAC6 (Figure 25) [95].…”

Section: Pyrazolesmentioning

confidence: 99%

Significance of Five-Membered Heterocycles in Human Histone Deacetylase Inhibitors

2023

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Five-membered heteroaromatic rings, in particular, have gained prominence in medicinal chemistry as they offer enhanced metabolic stability, solubility and bioavailability, crucial factors in developing effective drugs. The unique physicochemical properties and biological effects of five-membered heterocycles have positioned them as key structural motifs in numerous clinically effective drugs. Hence, the exploration of five-ring heterocycles remains an important research area in medicinal chemistry, with the aim of discovering new therapeutic agents for various diseases. This review addresses the incorporation of heteroatoms such as nitrogen, oxygen and sulfur into the aromatic ring of these heterocyclic compounds, enhancing their polarity and facilitating both aromatic stacking interactions and the formation of hydrogen bonds. Histone deacetylases are present in numerous multiprotein complexes within the epigenetic machinery and play a central role in various cellular processes. They have emerged as important targets for cancer, neurodegenerative diseases and other therapeutic indications. In histone deacetylase inhibitors (HDACi’s), five-ring heterocycles perform various functions as a zinc-binding group, a linker or head group, contributing to binding activity and selective recognition. This review focuses on providing an up-to-date overview of the different five-membered heterocycles utilized in HDACi motifs, highlighting their biological properties. It summarizes relevant publications from the past decade, offering insights into the recent advancements in this field of research.

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Section: Pyrazolesmentioning

confidence: 99%