Discovery of 4-((3′R,4′S,5′R)-6″-Chloro-4′-(3-chloro-2-fluorophenyl)-1′-ethyl-2″-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3″-indoline]-5′-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development

Abstract

We previously reported the design of spirooxindoles with two identical substituents at the carbon-2 of the pyrrolidine core as potent MDM2 inhibitors. In this paper we describe an extensive structure-activity relationship study of this class of MDM2 inhibitors, which led to the discovery of 60 (AA-115/APG-115). Compound 60 has a very high affinity to MDM2… (More)
DOI: 10.1021/acs.jmedchem.6b01665

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@inproceedings{Aguilar2017DiscoveryO4, title={Discovery of 4-((3′R,4′S,5′R)-6″-Chloro-4′-(3-chloro-2-fluorophenyl)-1′-ethyl-2″-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3″-indoline]-5′-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development}, author={Angelo Aguilar and Jianfeng Lu and Liu Liu and Ding Du and Denzil Bernard and Donna McEachern and Sally A. Przybranowski and Xiaoqin Li and Ruijuan Luo and Bo Wen and D. Sun and Hengbang Wang and Jianfeng Wen and Guangfeng Wang and Yifan Zhai and Ming Guo and Dajun Yang and Shaomeng Wang}, booktitle={Journal of medicinal chemistry}, year={2017} }