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 was written by Aguilar, Angelo;Lu, Jianfeng;Liu, Liu;Du, Ding;Bernard, Denzil;McEachern, Donna;Przybranowski, Sally;Li, Xiaoqin;Luo, Ruijuan;Wen, Bo;Sun, Duxin;Wang, Hengbang;Wen, Jianfeng;Wang, Guangfeng;Zhai, Yifan;Guo, Ming;Yang, Dajun;Wang, Shaomeng. And the article was included in Journal of Medicinal Chemistry in 2017.Synthetic Route of C10H17NO2 This article mentions the following:
The authors 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 the authors describe an extensive structure-activity relationship study of this class of MDM2 inhibitors, which led to the discovery of 60 (AA-115/APG-115, 4-((3R,4S,5R)-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). Compound 60 has a very high affinity to MDM2 (Ki < 1 nM), potent cellular activity, and an excellent oral pharmacokinetic profile. Compound 60 is capable of achieving complete and long-lasting tumor regression in vivo and is currently in phase I clin. trials for cancer treatment. In the experiment, the researchers used many compounds, for example, Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (cas: 135908-33-7Synthetic Route of C10H17NO2).
Methyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (cas: 135908-33-7) belongs to esters. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Esters contain a carbonyl center, which gives rise to 120鎺?C閳ユ弲閳ユ彊 and O閳ユ弲閳ユ彊 angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C閳ユ彊閳ユ弲 bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. Synthetic Route of C10H17NO2
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics