【结 构 式】 |
【药物名称】Lobaplatin, D-19466 【化学名称】cis-[trans-1,2-Cyclobutanebis(methylamine)][(S)-lactato-O1,O2]platinum(II) 【CA登记号】135558-11-1, 131374-93-1 ([cis-(1R*,2R*)]-isomer) 【 分 子 式 】C9H18N2O3Pt 【 分 子 量 】397.34541 |
【开发单位】Zentaris (Originator), Hainan Chang An (Licensee) 【药理作用】Breast Cancer Therapy, Leukemia Therapy, Lung Cancer Therapy, Myeloid Leukemia Therapy, Oncolytic Drugs, Small Cell Lung Cancer Therapy, Antimitotic Drugs, Platinum Complexes |
合成路线1
The synthesis of the ligand begins with a thermal or photochemical head-to-head dimerization of acrylonitrile (I). The mixture of the resulting cis- and trans-1,2-cyclobutanedicarbonitrile(II a-b) is separated by distillation and the trans-compound (II b) is then transformed to 1,2-bis(aminomethyl)cyclobutane (III) by reduction with lithiumalanat. The dichloroplatinum complex (IV) is conveniently prepared from diamine (III) and potassium tetrachloroplatinate. This complex reacts with silver nitrate to give the nitrato-complex (V), which was not isolated. After passing through a column of a strong anion exchanger in the OH-form, the activated complex reacts in aqueous solution with L-lactic acid to form the lactato-complex D-19466 as a diastereomeric mixture. The general reaction sequence is outlined in scheme 14986401a.
【1】 Aulenbacher, P.; Engel, J.; Hilgard, P.; Gunther, E.; Voegeli, R.; Lobaplatin. Drugs Fut 1992, 17, 10, 883. |
【2】 Schumacher, W.; Engel, J.; Respondek, J.; Voegeli, R.; Hilgard, P.; D-19466, a new cyclobutane-platinum complex with antitumor activity. J Cancer Res Clin Oncol 1990, 116, 5, 439-42. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(II-b) | 13347 | 1,2-Cyclobutanedicarbonitrile; trans-Cyclobutane-1,2-dicarbonitrile | 3211-20-9 | C6H6N2 | 详情 | 详情 |
(II-a) | 63575 | (1R,2S)-1,2-cyclobutanedicarbonitrile | C6H6N2 | 详情 | 详情 | |
(I) | 10848 | 2-Ethyl-2-(4-pyridinyl)pentanedinitrile | C12H13N3 | 详情 | 详情 | |
(III) | 13348 | [2-(Aminomethyl)cyclobutyl]methylamine; [2-(Aminomethyl)cyclobutyl]methanamine | C6H14N2 | 详情 | 详情 | |
(IV) | 13349 | 1,2-Bis(aminomethyl)cyclobutane dichloro platinum complex | C6H14Cl2N2Pt | 详情 | 详情 | |
(V) | 13351 | 1,2-Bis(aminomethyl)cyclobutane diacqua platinum complex dinitrate | C6H14N2Pt | 详情 | 详情 |