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Discovery of Imidazoisoindole Derivatives as Highly Potent and Orally Active Indoleamine-2,3-dioxygenase Inhibitors.

ABSTRACT: A novel series of imidazoisoindoles were identified as potent indoleamine-2,3-dioxygenase (IDO) inhibitors. Lead optimization toward improving potency and eliminating CYP inhibition resulted in the discovery of lead compound 25, a highly potent IDO inhibitor with favorable pharmacokinetic properties. In the MC38 xenograft model in hPD-1 transgenic mice, 25 in combination with the anti-PD-1 monoclonal antibody (SHR-1210) achieved a synergistic antitumor effect superior to each single agent.

SUBMITTER: Tu W

PROVIDER: S-EPMC6580535 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Discovery of Imidazoisoindole Derivatives as Highly Potent and Orally Active Indoleamine-2,3-dioxygenase Inhibitors.

Tu Wangyang W Yang Fanglong F Xu Guoji G Chi Jiangtao J Liu Zhiwei Z Peng Wei W Hu Bing B Zhang Lei L Wan Hong H Yu Nan N Jin Fangfang F Hu Qiyue Q Zhang Lianshan L He Feng F Tao Weikang W

ACS medicinal chemistry letters 20190603 6

A novel series of imidazoisoindoles were identified as potent indoleamine-2,3-dioxygenase (IDO) inhibitors. Lead optimization toward improving potency and eliminating CYP inhibition resulted in the discovery of lead compound 25, a highly potent IDO inhibitor with favorable pharmacokinetic properties. In the MC38 xenograft model in hPD-1 transgenic mice, 25 in combination with the anti-PD-1 monoclonal antibody (SHR-1210) achieved a synergistic antitumor effect superior to eac ...[more]

PMID: 31223453

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