卡折来新 | 119813-10-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 卡折来新
• 英文名称: carzelesin
• 英文别名: N-[2-[(8S)-8-(chloromethyl)-4-(C-hydroxy-N-phenylcarbonimidoyl)oxy-1-methyl-7,8-dihydro-3H-pyrrolo[3,2-e]indole-6-carbonyl]-1H-indol-5-yl]-6-(diethylamino)-1-benzofuran-2-carboximidic acid
• CAS: 119813-10-4
• 化学式: C₄₁H₃₇ClN₆O₅
• 分子量: 729.235
• InChiKey: BBZDXMBRAFTCAA-AREMUKBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  53
• 可旋转键数：
  10
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  136
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  卡折来新 生成 苯胺 、 U-76,074 、 N-[2-[(8S)-8-(chloromethyl)-4-hydroxy-1-methyl-7,8-dihydro-3H-pyrrolo[3,2-e]indole-6-carbonyl]-1H-indol-5-yl]-6-(diethylamino)-1-benzofuran-2-carboxamide
  参考文献：
  名称：

  Systematic Study on the Chemical Stability of the Prodrug Antitumor Agent Carzelesin (U-80,244)

  摘要：

  The chemical stability of the novel anticancer agent carzelesin in aqueous buffer/acetonitrile (1:1, v/v) mixtures has been investigated utilizing a stability-indicating reversed-phase high-performance liquid chromatographic assay. The degradation kinetics of carzelesin has been studied as a function of pH, buffer composition, ionic strength, and temperature. Degradation of carzelesin follows (pseudo-) first-order kinetics. A pH-rate profile, using rate constants extrapolated to zero buffer concentration, was constructed demonstrating that carzelesin is most stable in the pH region 1-4. The degradation rate of carzelesin was not significantly affected by buffer components and by the ionic strength. In addition to the formation of the degradation products U-76,073, U-76,074, and aniline in alkaline medium and in acetate buffer solution, another degradation product was formed in acetate buffer solution. In perchloric acid buffer solution (pH* < 3), U-76,073 and U-76,074 could not be detected as degradation products.

  DOI：

  10.1021/js960005n
• 作为产物：
  描述：

  (3S)-3-acetoxymethyl-5-amino-6-benzyloxy-1-(t-butoxycarbonyl)-2,3-dihydroindole 在 10% palladium on active carbon 盐酸 、 四氯化碳 、 palladium diacetate 、 dimethyl sulfide borane 、 甲酸铵 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 51.0h， 生成 卡折来新
  参考文献：
  名称：

  Novel Syntheses of Optically Active CC-1065, U-73,975(Adozelesin), U-80,244(Carzelesin), U-77,779 (Bizelesin), KW-2189, and DU-86

  摘要：

  The title syntheses were achieved by the method featuring oxidative cyclization of the enamino esters [(S)-13 and (S)-24] derived from the 5-aminoindoline [(S)-12], acylation with various structural types of indole-2-carboxylic acids, and formation of cyclopropapyrroloindole moieties.

  DOI：

  10.3987/com-97-7920

文献信息

• B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof
  申请人：MacroGenics, Inc.

  公开号：US10961311B2

  公开（公告）日：2021-03-30

  The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such B7-H3-binding molecules, and to methods involving the use of any of such B7-H3-binding molecules in the treatment of cancer and other diseases and conditions. The invention also particularly pertains to a molecule that comprises the human B7-H3 binding domain of a humanized anti-human B7-H3 antibody conjugated to at least one drug moiety (a “B7-H3-ADC”). The invention is also directed to pharmaceutical compositions that contain such B7-H3-ADCs, and to methods involving the use of any of such B7-H3-ADCs in the treatment of cancer and other diseases and conditions.

  本发明涉及能够与人类和非人类 B7-H3 结合的新型 B7-H3 结合分子，特别是与非人灵长类动物（如猕猴）的 B7-H3 具有交叉反应的分子。此外，本发明还涉及包含可变轻链和/或可变重链（VH）域的 B7-H3 结合分子，这些分子已被人源化和/或去免疫化，以便在给受试者用药时显示出较低的免疫原性。本发明尤其涉及双特异性、三特异性或多特异性 B7-H3 结合分子，包括双特异性二抗体、双特异性抗体、双特异性抗体、三价结合分子等，这些分子包含：(i) 这种 B7-H3 结合可变区；(ii) 能够与效应细胞表面存在的分子表位结合的结构域。本发明还涉及含有任何此类 B7-H3 结合分子的药物组合物，以及涉及使用任何此类 B7-H3 结合分子治疗癌症及其他疾病和病症的方法。本发明还特别涉及一种分子，该分子包括与至少一种药物分子（"B7-H3-ADC"）共轭的人源化抗人 B7-H3 抗体的人 B7-H3 结合域。本发明还涉及含有此类 B7-H3-ADC 的药物组合物，以及涉及使用任何此类 B7-H3-ADC 治疗癌症及其他疾病和病症的方法。
• CC-1065 ANALOGS
  申请人：THE UPJOHN COMPANY

  公开号：EP0340243B1

  公开（公告）日：1994-09-28
• TREATMENT FOR INHIBITING NEOPLASTIC LESIONS USING INCENSOLE AND/OR FURANOGERMACRENS
  申请人：Shanahan-Prendergast, Elizabeth

  公开号：EP1351678A2

  公开（公告）日：2003-10-15
• NOVEL B7-H3 BINDING MOLECULES, ANTIBODY DRUG CONJUGATES THEREOF AND METHODS OF USE THEREOF
  申请人：MacroGenics, Inc.

  公开号：US20190127471A1

  公开（公告）日：2019-05-02

  The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such B7-H3-binding molecules, and to methods involving the use of any of such B7-H3-binding molecules in the treatment of cancer and other diseases and conditions. The invention also particularly pertains to a molecule that comprises the human B7-H3 binding domain of a humanized anti-human B7-H3 antibody conjugated to at least one drug moiety (a “B7-H3-ADC”). The invention is also directed to pharmaceutical compositions that contain such B7-H3-ADCs, and to methods involving the use of any of such B7-H3-ADCs in the treatment of cancer and other diseases and conditions.
• US5332837A
  申请人：——

  公开号：US5332837A

  公开（公告）日：1994-07-26