10-carboxy-(20S)-camptothecin | 151585-82-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: 10-carboxy-(20S)-camptothecin
• 英文别名: 10-carboxycamptothecin；(19S)-19-ethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-7-carboxylic acid
• CAS: 151585-82-9
• 化学式: C₂₁H₁₆N₂O₆
• 分子量: 392.368
• InChiKey: SJEVFPQEARWJCK-NRFANRHFSA-N

物化性质

• 沸点：
  834.9±65.0 °C(predicted)
• 密度：
  1.63±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  10-carboxy-(20S)-camptothecin 、 4-(4-aminobutanoylamino)-N-[5-[[5-[[4-[[5-[[5-[[5-[3-(dimethylamino)propylcarbamoyl]-1-methyl-pyrrol-3-yl]carbamoyl]-1-methyl-pyrrol-3-yl]carbamoyl]-1-methyl-pyrrol-3-yl]amino]-4-oxo-butyl]carbamoyl]-1-methyl-pyrrol-3-yl]carbamoyl]-1-methyl-pyrrol-3-yl]-1-methyl-pyrrole-2-carboxamide 在 N-羟基丁二酰亚胺 、 N,N'-二环己基碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 二甲基亚砜 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Directing Topoisomerase I Mediated DNA Cleavage to Specific Sites by Camptothecin Tethered to Minor- and Major-Groove Ligands

  摘要：

  The covalent linkage of a hairpin polyamide, which binds in the minor groove, to camptothecin provides an efficient system to direct topoisomerase I mediated DNA cleavage to specific sites. These conjugates are equally as potent at targeting the enzyme to a single site in a DNA fragment as camptothecin conjugates of ligands that bind in the major groove (triplex-forming oligonucleotides).

  DOI：

  10.1002/1521-3773(20010817)40:16<3045::aid-anie3045>3.0.co;2-a
• 作为产物：
  描述：

  10-cyano-(20S)-camptothecin 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 30.0h， 以87%的产率得到10-carboxy-(20S)-camptothecin
  参考文献：
  名称：

  植物抗肿瘤剂。30.新型喜树碱类似物的合成和结构活性。

  摘要：

  已经制备了具有许多环A取代基的20S，20RS和20R构型的大量喜树碱（CPT）类似物。拓扑异构酶I（TI）抑制数据（IC50）已通过标准程序获得。通常，具有20S构型的化合物在9或10位上被氨基，卤代或羟基取代会导致TI抑制作用增强。20RS构型的化合物在体外和体内活性较低，而20R构型的化合物则无活性。在TI抑制试验中，在A环上具有10,11-亚甲二氧基取代的化合物显示出显着的效能增强。在包括L-1210小鼠白血病测定法在内的各种体内测定法中确定的某些类似物的活性通常与TI抑制作用一致。制备了许多水溶性类似物，例如20-甘氨酸酯，9-甘氨酰胺或水解的内酯盐，并在体外和体内试验中进行了测试。通常，就L-1210分析中的TI抑制作用和寿命延长而言，这些化合物的活性均不如CPT。然而，某些20-甘氨酸酯在静脉内给药后显示出良好的体内活性。

  DOI：

  10.1021/jm00070a013

文献信息

• COMPOUNDS AND THEIR USE FOR SPECIFIC AND SIMULTANEOUS INHIBITION OF GENES INVOLVED IN DISEASES AND RELATED DRUGS
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP1606405A2

  公开（公告）日：2005-12-21
• Compounds and Their Use for Specific and Simultaneous Inhibition of Genes Involved In Diseases and Related Drugs
  申请人：Arimondo Paola Barbara

  公开号：US20080108581A1

  公开（公告）日：2008-05-08

  The invention relate to the use of a compound of formula A-B—C Wherein A is a DNA sequence-specific ligand capable of simultaneously and specifically recognizing a sequence common to genes of pathological interest; B is a linker arm, said linker arm being bound to the 3′ end of A; C is a topoisomerase I posion; for the preparation of a drug for the treatment of a disease brought about by the expression of a gene and said gene is inhibited by the stabilized topoisomerase I-mediated DNA cleavage. Application, particularly, for the treatment of infective microorganism or virus, dismetabolic disease and autoimmune disease.
• [EN] COMPOUNDS AND THEIR USE FOR SPECIFIC AND SIMULTANEOUS INHIBITION OF GENES INVOLVED IN DISEASES AND RELATED DRUGS<br/>[FR] COMPOSES ET LEUR UTILISATION DANS L'INHIBITION SPECIFIQUE ET SIMULTANEE DE GENES IMPLIQUES DANS DES PATHOLOGIES ET MEDICAMENTS CORRESPONDANTS
  申请人：INST NAT SANTE RECH MED

  公开号：WO2004083365A2

  公开（公告）日：2004-09-30

  The invention relate to the use of a compound of formula A-B-C Wherein A is a DNA sequence-specific ligand capable of simultaneously and specifically recognizing a sequence common to genes of pathological interest; B is a linker arm, said linker arm being bound to the 3' end of A; C is a topoisomerase I posion; for the preparation of a drug for the treatment of a disease brought about by the expression of a gene and said gene is inhibited by the stabilized topoisomerase I-mediated DNA cleavage. Application, particularly, for the treatment of infective microorganism or virus, dismetabolic disease and autoimmune disease.