Evaluation of WO2017018805: 1,3,4-oxadiazole sulfamide derivatives as selective HDAC6 inhibitors

WO2017018805:1,3,4-恶二唑磺酰胺衍生物作为选择性 HDAC6 抑制剂的评估

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作者:Yuan-Yuan Liang, Cheng-Mei Zhang, Zhao-Peng Liu

Abstract

There are great potential in the development of selective HDAC6 inhibitors for the treatment of infectious diseases, neoplasms, endocrine diseases, and other diseases associated with HDAC6 activity. Areas covered: The application claims 1,3,4-oxadiazole sulfamide derivatives as selective HDAC6 inhibitors for the treatment of infectious diseases, neoplasms, endocrine, nutritional, and metabolic diseases; mental and behavioral disorders; neurological diseases; diseases of the eye and adnexa; cardiovascular diseases; respiratory diseases; digestive diseases; diseases of the skin and subcutaneous tissue; disease of the musculoskeletal system and connective tissue; or congenital malformations, deformations and chromosomal abnormalities. Many of the exemplified compounds showed nanomole potency against HDAC6 and were more than 5000-fold selectivity for HDAC6 over HDAC1. Expert opinion: These 1,3,4-oxadiazole sulfamide derivatives have a unique zinc-binding group (ZBG) that provide good leads for the discovery of potent selective HDAC6 inhibitors for the treatment of a variety of diseases associated with HDAC6 activity.

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