allyl-[3-(allyl-tert-butoxycarbonyl-amino)-4-iodo-naphthalen-1-yl]-carbamic acid tert-butyl ester | 483349-26-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: allyl-[3-(allyl-tert-butoxycarbonyl-amino)-4-iodo-naphthalen-1-yl]-carbamic acid tert-butyl ester
• 英文别名: N,N'-bis(tert-butoxycarbonyl)-N,N'-bis(allyl)-1-iodo-2,4-naphthalenediamine；N,N'-bis[allyl(tert-butyloxycarbonyl)]-1-iodo-2,4-naphthalenediamine；1-iodonaphthalene-2,4-(bis-tert-butyl allylcarbamate)；tert-butyl N-[1-iodo-4-[(2-methylpropan-2-yl)oxycarbonyl-prop-2-enylamino]naphthalen-2-yl]-N-prop-2-enylcarbamate
• CAS: 483349-26-4
• 化学式: C₂₆H₃₃IN₂O₄
• 分子量: 564.464
• InChiKey: GPRXZJBZBQSBSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  allyl-[3-(allyl-tert-butoxycarbonyl-amino)-4-iodo-naphthalen-1-yl]-carbamic acid tert-butyl ester 在 四氯化碳 、 三正丁基氢锡 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三苯基膦 、 三氟乙酸 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 溶剂黄146 、 苯 为溶剂， 反应 16.25h， 生成 5-allylamino-1-(chloromethyl)-3-[(2E)-3-(4-methoxyphenyl)-2-propenoyl]-1,2-dihydro-3H-benzo[e]indole
  参考文献：
  名称：

  3-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚（氨基-CBI）的新短合成。

  摘要：

  公开了一种来自Martius Yellow的3-取代的5-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚的新的短合成物。合成的关键步骤是三个有效的区域选择性反应（碘化，5-exo-trig芳基自由基-烯烃环化和羧化）。

  DOI：

  10.1021/jo0263115
• 作为产物：
  描述：

  1,3-萘二胺 在 N-碘代丁二酰亚胺 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 allyl-[3-(allyl-tert-butoxycarbonyl-amino)-4-iodo-naphthalen-1-yl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  3-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚（氨基-CBI）的新短合成。

  摘要：

  公开了一种来自Martius Yellow的3-取代的5-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚的新的短合成物。合成的关键步骤是三个有效的区域选择性反应（碘化，5-exo-trig芳基自由基-烯烃环化和羧化）。

  DOI：

  10.1021/jo0263115

文献信息

• [EN] PROCESSES FOR PREPARING 3-SUBSTITUTED 1-(CHLOROMETHYL)-1,2-DIHYDRO-3H-[RING FUSED INDOL-5-YL(AMINE-DERIVED)] COMPOUNDS AND ANALOGUES THEREOF, AND TO PRODUCTS OBTAINED THEREFROM<br/>[FR] PROCEDE DE PREPARATION DE COMPOSES DE 3-SUBSTITUE 1-(CHLOROMETHYL)-1,2-DIHYDRO-3H [-5-YL A CYCLES FUSIONNES (DERIVES D'AMINE)] ET DE LEURS ANALOGUES, ET PRODUITS DERIVES
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2003097635A1

  公开（公告）日：2003-11-27

  The invention provides processes of preparing 3-substituted 1-(chloromethyl)-1,2-dihydro-3H-[ring fused indol-5-yl(amine-derived)] compounds of formula (I) and its analogues, or a physiologically functional derivative thereof, (I), wherein A and B together may represent a fused optionally substituted benzene, naphthalene, pyridine, furan or a pyrrole ring, where the optional substituents are represented by Y; X is halogen or OSO2R , and W is selected from NO2, NHOH, N(R3)2NHR3, NHCO2R3, N(phthaloyl) or NH2, or W is further selected from the group (a) , wherein J is selected from OH or R, and P is a group which is a substrate suitable for a nitroreductase or carboxypeptidase enzyme. The invention is also directed to the use of compounds of formula (I) prepared by the processes of the invention as cytotoxins for cancer therapy and as prodrugs for gene-directed enzyme-prodrug therapy (GDEPT) and antibody-directed enzyme-prodrug therapy (ADEPT).

  该发明提供了制备公式（I）及其类似物的3-取代1-(氯甲基)-1,2-二氢-3H-[环融合吲哚-5-基（衍生自胺基）]化合物的过程，或其生理功能衍生物，其中A和B一起可以表示一个融合的可选取代苯、萘、吡啶、呋喃或吡咯环，其中可选取代基由Y表示；X为卤素或OSO2R，W从NO2、NHOH、N(R3)2NHR3、NHCO2R3、N(邻苯二甲酰基)或NH2中选择，或W进一步从群（a）中选择，其中J从OH或R中选择，P是适用于硝基还原酶或羧肽酶的底物基团。该发明还涉及通过该发明的过程制备的公式（I）化合物作为抗癌细胞毒素以及基因导向酶-前药疗法（GDEPT）和抗体导向酶-前药疗法（ADEPT）的前药的用途。
• [EN] ISOQUINOLIDINOBENZODIAZEPINE (IQB)-1(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI) DIMERS<br/>[FR] DIMÈRES D'ISOQUINOLIDINOBENZODIAZÉPINE (IQB)-1(CHLOROMÉTHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI)
  申请人：CELLERANT THERAPEUTICS INC

  公开号：WO2018071455A1

  公开（公告）日：2018-04-19

  Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.

  本文提供了异喹啉苯二氮卓啶（IQB）-1（氯甲基）-2,3-二氢-1H-苯并[e]吲哚（CBI）二聚体，包括它们的抗体药物结合物，以及用于杀灭细胞和治疗疾病的方法。
• Isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers
  申请人：Cellerant Therapeutics, Inc.

  公开号：US10350218B2

  公开（公告）日：2019-07-16

  Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.

  本文提供了异喹啉并二氮杂卓（IQB）-1（氯甲基）-2,3-二氢-1H-苯并[e]吲哚（CBI）二聚体、包含它们的抗体-药物共轭物以及用于杀死细胞和治疗疾病的方法。
• Weight loss effects of quaternary salts of 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indoles; structure–activity relationships
  作者：Moana Tercel、Ralph J. Stevenson、Guo-Liang Lu、Stephen M. Stribbling、William R. Wilson、Michele A. Tatnell、Rebecca N. Marnane、Kathleen G. Mountjoy、William A. Denny

  DOI：10.1016/j.bmc.2011.12.007

  日期：2012.1

  Quaternary salt analogues based on the DNA minor groove binder and adenine N3 alkylating agent 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indole (aminoCBI) show remarkable effects on the body weight of mice (a long-term failure to gain weight relative to matched controls with no loss of appetite or perceptible deterioration in health) following administration of a single (non-toxic) dose between about 0.5-5 mu mol/kg. The nature of the quaternizing group was not important, but a related hydroxyCBI analogue was much less effective. Compounds where the chloro group was replaced by a hydrogen or hydroxy group (thus abrogating DNA alkylating capability) showed no weight control activity. It is speculated, based on other studies, that the marked long-term weight control effect is due to inhibition of bile flow into the intestine and reduced absorption of triglycerides, together with accelerated cell death in spleen and white adipose tissues due to drug accumulation there. This class of compound may serve as interesting tools for further study of these phenomena. (C) 2011 Elsevier Ltd. All rights reserved.
• ISOQUINOLIDINOBENZODIAZEPINE (IQB)-1(CHLOROMETHYL)-2,3-DIHYDRO-1H-BENZO[E]INDOLE (CBI) DIMERS
  申请人：Cellerant Therapeutics, Inc.

  公开号：US20180177795A1

  公开（公告）日：2018-06-28

  Provided herein are isoquinolidinobenzodiazepine (IQB)-1(chloromethyl)-2,3-dihydro-1H-benzo[e]indole (CBI) dimers, antibody-drug conjugates comprising them and methods of use for killing cells and treating disease.