A series of 10,11-dihydro-5H-dibenzo [b,f]azepine hydroxamates (4-15) were synthesized, behaving as histone deacetylase inhibitors, and examined for their influence on vascular cognitive impairment (VCI), which correlated with dementia. The results revealed that (E)-3-(4-(((3-(3-chloro-10,11-dihydro-5H-dibenzo [b,f]azepin-5-yl)propyl)amino)methyl)phenyl)-N-hydroxy-acrylamide (13) increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy in in vivo study. It is also able to increase the level of histone acetylation (H3K14 or H4K5) in the cortex and hippocampus of chronic cerebral hypoperfusion (CCH) mice; as a result, it could be a potential HDAC inhibitor for the treatment of vascular cognitive impairment.

中文翻译：

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10,11-二氢-5H-二苯并[b，f]氮杂异羟肟酸酯对血管性认知障碍的保护作用。

合成了一系列10,11-二氢-5H-二苯并[b，f]氮杂羟肟酸酯（4-15），其表现为组蛋白脱乙酰基酶抑制剂，并检查了它们对与痴呆症相关的血管性认知障碍（VCI）的影响。结果表明，（E）-3-（4-（（（3-（3-chloro-10,11-dihydro-5H-dibenzo [b，f] azepin-5-yl）propyl）amino）methyl）phenyl ）-N-羟基丙烯酰胺（13）在体内研究中可增加脑血流量（CBF），减轻认知障碍并改善海马萎缩。它还能够增加慢性脑灌注不足（CCH）小鼠的皮质和海马中的组蛋白乙酰化水平（H3K14或H4K5）；因此，它可能是用于治疗血管性认知障碍的潜在HDAC抑制剂。