5-[allyl(tert-butoxycarbonyl)amino]-3-(tert-butoxycarbonyl)-1-methyl-1,2-dihydro-3H-benzo[e]indole | 1017279-11-6

• 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
• 英文名称: 5-[allyl(tert-butoxycarbonyl)amino]-3-(tert-butoxycarbonyl)-1-methyl-1,2-dihydro-3H-benzo[e]indole
• 英文别名: Tert-butyl 1-methyl-5-[(2-methylpropan-2-yl)oxycarbonyl-prop-2-enylamino]-1,2-dihydrobenzo[e]indole-3-carboxylate
• CAS: 1017279-11-6
• 化学式: C₂₆H₃₄N₂O₄
• 分子量: 438.567
• InChiKey: LLWQRCXTHVOGTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 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：

  5-[allyl(tert-butoxycarbonyl)amino]-3-(tert-butoxycarbonyl)-1-methyl-1,2-dihydro-3H-benzo[e]indole 在 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 camphor-10-sulfonic acid 、 sodium benzenesulfonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 111.0h， 生成 N-4-((E)-3-{5-[bis(tert-butoxycarbonyl)]-amino-1-methyl-1,2-dihydro-3H-benzo[e]indol-3-yl}-3-oxo-1-propenyl)benzyl-N,N-dimethyl-N-[(1-methyl-5-nitro-2-pyrrolyl)methyl]ammonium bromide
  参考文献：
  名称：

  Weight loss effects of quaternary salts of 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indoles; structure–activity relationships

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.12.007
• 作为产物：
  描述：

  allyl-[3-(allyl-tert-butoxycarbonyl-amino)-4-iodo-naphthalen-1-yl]-carbamic acid tert-butyl ester 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 苯 为溶剂， 反应 0.25h， 以77%的产率得到5-[allyl(tert-butoxycarbonyl)amino]-3-(tert-butoxycarbonyl)-1-methyl-1,2-dihydro-3H-benzo[e]indole
  参考文献：
  名称：

  Weight loss effects of quaternary salts of 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indoles; structure–activity relationships

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2011.12.007

文献信息

• [EN] INDOLINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE L'INDOLINE ET LEURS UTILISATIONS
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2008039087A2

  公开（公告）日：2008-04-03

  (EN) The present invention relates to compounds which are indoline derivatives of formula (I), wherein Rl, R2, R3, R4 and n are as defined in the specification, intermediates used in their synthesis and pharmaceutical compositions containing these compounds. The invention is also concerned with methods utilising these compounds in prophylactic or therapeutic treatment of obesity, weight gain, metabolic disorders resulting in obesity or weight gain and associated conditions such as high blood glucose and triglycerides, and Type II diabetes.(FR) La présente invention concerne des composés qui sont des dérivés de l'indoline, ainsi que des intermédiaires utilisés pour leur synthèse et des compositions pharmaceutiques contenant lesdits composés. L'invention concerne également des procédés utilisant ces composés dans le traitement prophylactique ou thérapeutique de l'obésité, du gain de poids, des troubles métaboliques ayant pour conséquence obésité ou gain de poids et des troubles associés tels qu'une glycémie élevée, un taux élevé de triglycérides et le diabète de type II.
• 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.