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Discovery of Highly Potent 2-Sulfonyl-Pyrimidinyl Derivatives for Apoptosis Inhibition and Ischemia Treatment.

ABSTRACT: A series of 2-sulfonyl-pyrimidinyl derivatives was developed as apoptosis inhibitors. These represent the first class of apoptosis inhibitors that function through stabilizing mitochondrial respiratory complex II. Starting from a phenotypic screen hit with micromolar activity, we optimized the cellular apoptosis inhibition activity of 2-sulfonyl-pyrimidinyl derivatives to picomolar level (compound 42, also named as TC9-305). The therapeutic potential of these new apoptosis inhibitors was further demonstrated by their neuroprotective effect on an ischemic animal model.

SUBMITTER: Li L

PROVIDER: S-EPMC5392758 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Discovery of Highly Potent 2-Sulfonyl-Pyrimidinyl Derivatives for Apoptosis Inhibition and Ischemia Treatment.

Li Li L Jiang Xian X Huang Shaoqiang S Ying Zhengxin Z Zhang Zhaolan Z Pan Chenjie C Li Sisi S Wang Xiaodong X Zhang Zhiyuan Z

ACS medicinal chemistry letters 20170301 4

A series of 2-sulfonyl-pyrimidinyl derivatives was developed as apoptosis inhibitors. These represent the first class of apoptosis inhibitors that function through stabilizing mitochondrial respiratory complex II. Starting from a phenotypic screen hit with micromolar activity, we optimized the cellular apoptosis inhibition activity of 2-sulfonyl-pyrimidinyl derivatives to picomolar level (compound <b>42</b>, also named as TC9-305). The therapeutic potential of these new apoptosis inhibitors was ...[more]

PMID: 28435527

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