首页> 外国专利> COMPOUND 44CARBOXYPHTHALATO*1*22DIAMINOO CYCLOHEXANU*PLATINA*2**ITS ALKALI METAL SALT AND ITS USE TO MICE LEUCOCYTE ALLEVIATION

COMPOUND 44CARBOXYPHTHALATO*1*22DIAMINOO CYCLOHEXANU*PLATINA*2**ITS ALKALI METAL SALT AND ITS USE TO MICE LEUCOCYTE ALLEVIATION

机译:化合物44邻苯二甲酸邻苯二甲醛* 1 * 22花生四环素*铂* 2 **其碱金属盐及其在小鼠白细胞消除中的用途

摘要

IMAGE Y=H, alk met 4-Carboxyphthalato(1,2-diaminocyclohexane) platinum(II) (and alkali metal salts thereof) has shown antileukemic activity in mice against murine leukemia L1210. It is effective in dosages of 5-60 mg/kg of body weight and is potentiated in a treatment with cyclophosphamide (CY) (50 mg/kg of body weight) to which may be added 5-fluorouracil (5-FU) (75 mg/kg of body weight) or hydroxyurea (HU) (1000 mg/kg of body weight). Some previous platinum chelate compounds show dosage limitation due to renal impairment but the free carboxyl of the present Pt compound offers a possible route of oral administration and absorption by the stomach. The Pt compound may be prepared by reacting the known dichloro(1,2-diaminocyclohexane) platinum(II) (NSC 194814) with silver nitrate to replace chloro with nitro. Subsequently, benzene tricarboxylic acid is added to form an off-white precipitate (2 hrs, dark, 5 DEG C.) of the desired product which is preferably utilized as the alkali metal salt. The 4-carboxyphthalato(1,2-diaminocyclohexane)-platinum(II) and alkali metal salts thereof may be combined in multiple drug regimen with substantially improved yield cures over the parent compound. For example, the compound denoted Pt-307 may be combined in a dual regimen with cyclophosphamide (CY) and in a triple drug regimen of Pt-307 plus cyclophosphamide (CY) and either 5-fluorouracil (5-FU) or hydroxyurea (HU) as the third component. Additionally, the present compound (NSC 271674) has shown superior results in testing for renal toxicity against the parent compound (NSC 119875, cis-dichlorodiamino platinum II) and further the present compound appears to be active against strains of murine leukemia wherein the same NSC 119875 has exhausted its activity.
机译:<图像> Y = H,烷基的4-羧邻苯二甲酸(1,2-二氨基环己烷)铂(II)(及其碱金属盐)在小鼠中显示出抗鼠白血病L1210的抗白血病活性。它的有效剂量为5-60 mg / kg体重,并在用环磷酰胺(CY)(50 mg / kg体重)的治疗中予以加强,可向其中添加5-氟尿嘧啶(5-FU)(75 mg / kg体重)或羟基脲(HU)(1000 mg / kg体重)。某些先前的铂螯合物由于肾功能不全而显示出剂量限制,但是本发明Pt化合物的游离羧基提供了口服给药和被胃吸收的可能途径。可以通过使已知的二氯(1,2-二氨基环己烷)铂(II)(NSC 194814)与硝酸银反应,用硝基取代氯来制备Pt化合物。随后,加入苯三羧酸以形成所需产物的灰白色沉淀(2小时,黑暗,5℃),其优选用作碱金属盐。可以将4-羧基邻苯二甲酸(1,2-二氨基环己烷)-铂(II)及其碱金属盐组合在多种药物方案中,与母体化合物相比,其固化率大大提高。例如,表示为Pt-307的化合物可以与环磷酰胺(CY)双重使用,也可以与Pt-307加环磷酰胺(CY)和5-氟尿嘧啶(5-FU)或羟基脲(HU )作为第三部分。另外,本发明的化合物(NSC 271674)在测试对母体化合物(NSC 119875,顺式-二氯二氨基铂II)的肾脏毒性方面显示出优异的结果,并且本发明的化合物似乎对其中相同的NSC的鼠白血病毒株具有活性。 119875已耗尽其活动。

著录项

  • 公开/公告号JPS5446752A

    专利类型

  • 公开/公告日1979-04-12

    原文格式PDF

  • 申请/专利权人 US GOVERNMENT;

    申请/专利号JP19780105428

  • 发明设计人 GUREN ROI GEIRU;POORU SHIYUWARUTSU;

    申请日1978-08-29

  • 分类号A61K31/555;A61P43/00;C07F15/00;

  • 国家 JP

  • 入库时间 2022-08-22 21:12:50

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