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【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)
      cis-[(1R*,2R*)-1,2-Cyclobutanebis(methylamino)-N,N'][(2S)-2-hydroxypropanoato(2-)-O1,O2]platinum

【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
Extended Information