With Caspase - 3 inhibitory activity of benzisothiazole - 3 - one - 2 - amide compounds
The invention relates to a benzisothiazole-3-ketone-2-amide compound with Caspase-3 inhibiting activity. The benzisothiazole-3-ketone-2-amide compound has the Caspase-3 inhibiting activity, can be used for treating diseases mediated by Caspase-3, belongs to the field of pharmaceutical chemistry, and has a structural formula (I) as shown in the specification.
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Paragraph 0107; 0127-0129
(2018/11/04)
Design, synthesis and evaluation of 1,2-benzisothiazol-3-one derivatives as potent caspase-3 inhibitors
A number of 1,2-benzisothiazol-3-one derivatives were prepared through structural modification of the original compound from high-throughput screening. Some analogues (e.g., 6b, 6r, 6s and 6w) were identified as novel and potent caspase inhibitors with IC50 of nanomolar. Structure-activity relationship (SAR) studies for caspase-3 inhibition were evaluated in vitro. Molecular modeling studies provided further insight into the interaction of this class of compounds with activated caspase-3. The present small molecule caspase-3 inhibitor with novel structures different from structures of known caspase inhibitors revealed a new direction for therapeutic strategies directed against diseases involving abnormally up-regulated apoptosis.