bromoacetyl isocyanate | 16913-73-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: bromoacetyl isocyanate
• 英文别名: bromoacetylisocyanate；2-bromoacetyl isocyanate
• CAS: 16913-73-8
• 化学式: C₃H₂BrNO₂
• 分子量: 163.958
• InChiKey: UUWKHTUDASRUMV-UHFFFAOYSA-N

物化性质

• 沸点：
  160.7±23.0 °C(Predicted)
• 密度：
  1.77±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  7
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  TX-1888 、 bromoacetyl isocyanate 以 二氯甲烷 为溶剂， 反应 0.5h， 以96%的产率得到[(2S)-1-methoxy-3-(2-nitroimidazol-1-yl)propan-2-yl] N-(2-bromoacetyl)carbamate
  参考文献：
  名称：

  Angiogenesis inhibitor TX-1898: syntheses of the enantiomers of sterically diverse haloacetylcarbamoyl-2-nitroimidazole hypoxic cell radiosensitizers

  摘要：

  (R)- and (S)-Epichlorohydrins were used to prepare the enantiomers of sterically diverse haloacetylcarbamoyl-2-nitroimidazoles that function as hypoxic cell radiosensitizers. The synthetic design allowed for introduction of a side chain of varying bulk that permitted an examination of the steric effects on enantio-discrimination in biological assay systems. The single stereocenter also connected the two pharmacophores-a 2-nitroimidazole moiety critical to hypoxic cell radiosensitization, and a haloacetylcarbamoyl group to function as an anti-angiogenesis pharmacophore. In the chick embryo chorioallantoic membrane (CAM) assay, the R-enantiomers possessing the bulky p-tert-butylphenyl group showed higher anti-angiogenic activity than the corresponding S-enantiomers, while there were no differences in the activity between the enantiomers containing the less bulky methyl and tert-butyl groups. Among the compounds we report, R-p-tert-butylphenyl-bromoacetylcarbamoyl-2-nitroimidazole, TX-1898, was found to be the most promising candidate for further development of as anti-angiogenic hypoxic cell radiosensitizer. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.039
• 作为产物：
  描述：

  草酰氯 、 2-溴乙酰胺 生成 bromoacetyl isocyanate
  参考文献：
  名称：

  Thiophene-Anthranilamides as Highly Potent and Orally Available Factor Xa Inhibitors

  摘要：

  There remains a high unmet medical need for a safe oral therapy for thrombotic disorders. The serine protease factor Xa (fXa), with its central role in the coagulation cascade, is among the more promising targets for anticoagulant therapy and has been the subject of intensive drug discovery efforts. Investigation of a hit from high-throughput screening identified a series of thiophene-substituted anthranilamides as potent nonamidine fXa inhibitors. Lead optimization by incorporation of hydrophilic groups led to the discovery of compounds with picomolar inhibitory potency and micromolar in vitro anticoagulant activity. Based on their high potency, selectivity, oral pharmacokinetics, and efficacy in a rat venous stasis model of thrombosis, compounds ZK 814048 (10b), ZK 810388 (13a), and ZK 813039 (17m) were advanced into development.

  DOI：

  10.1021/jm070125f

文献信息

• Thiophene-Anthranilamides as Highly Potent and Orally Available Factor Xa Inhibitors
  作者：Bin Ye、Damian O. Arnaiz、Yuo-Ling Chou、Brian D. Griedel、Rushad Karanjawala、Wheeseong Lee、Michael M. Morrissey、Karna L. Sacchi、Steven T. Sakata、Kenneth J. Shaw、Shung C. Wu、Zuchun Zhao、Marc Adler、Sarah Cheeseman、William P. Dole、Janice Ewing、Richard Fitch、Dao Lentz、Amy Liang、David Light、John Morser、Joseph Post、Galina Rumennik、Babu Subramanyam、Mark E. Sullivan、Ron Vergona、Janette Walters、Yi-Xin Wang、Kathy A. White、Marc Whitlow、Monica J. Kochanny

  DOI：10.1021/jm070125f

  日期：2007.6.1

  There remains a high unmet medical need for a safe oral therapy for thrombotic disorders. The serine protease factor Xa (fXa), with its central role in the coagulation cascade, is among the more promising targets for anticoagulant therapy and has been the subject of intensive drug discovery efforts. Investigation of a hit from high-throughput screening identified a series of thiophene-substituted anthranilamides as potent nonamidine fXa inhibitors. Lead optimization by incorporation of hydrophilic groups led to the discovery of compounds with picomolar inhibitory potency and micromolar in vitro anticoagulant activity. Based on their high potency, selectivity, oral pharmacokinetics, and efficacy in a rat venous stasis model of thrombosis, compounds ZK 814048 (10b), ZK 810388 (13a), and ZK 813039 (17m) were advanced into development.
• Antiparasitic 5-nitrothiazoles and 5-nitro-4-thiazolines. 2
  作者：Peter J. Islip、Michael D. Closier、John E. Weale

  DOI：10.1021/jm00267a015

  日期：1973.9
• Nitrofuryl heterocyclics. 1
  作者：M. D. Closier、Peter J. Islip

  DOI：10.1021/jm00298a013

  日期：1970.7.1
• Nitrofuryl heterocyclics. 3
  作者：Peter J. Islip、Madelaine R. Johnson

  DOI：10.1021/jm00269a023

  日期：1973.11
• Design, synthesis, and biological activity of anti-angiogenic hypoxic cell radiosensitizer haloacetylcarbamoyl-2-nitroimidazoles
  作者：Hitoshi Hori、Cheng-Zhe Jin、Masatoshi Kiyono、Soko Kasai、Mariko Shimamura、Seiichi Inayama

  DOI：10.1016/s0968-0896(96)00274-x

  日期：1997.3

  We designed, synthesized, and evaluated haloacetylcarbamoyl-2-nitroimidazoles, including chloro (KIN-1800, TX-1835, and TX-1836) and bromo derivatives (TX-1844, TX-1845, and TX-1846), as potential hypoxic cell radiosensitizers with antiangiogenic activities. To establish biological function owing to the haloacetylcarbamoyl group in the side-chain, we compared their in vitro radiosensitizing activities with those of their parent 2-nitroimidazoles without haloacetylcarbamoyl groups: misonidazole (MISO), TX-1831, and TX-1832, respectively. Both tert-butoxy substituted derivatives, TX-1835 and TX-1845, were more potent radiosensitizers than TX-1831. The p-tert-butylphenoxy-substituted derivatives, TX-1836 and TX-1846, and the methoxy-substituted derivatives, KIN-1800 and TX-1844, were stronger radiosensitizers than TX-1832 and MISO. We examined the antiangiogenic activities of these 2-nitroimidazole derivatives containing haloacetylcarbamoyl group by the rat lung endothelial (RLE) cell proliferation assay and chick embryo chorioallantoic membrane (chick CAM) angiogenesis assay and showed that haloacetylcarbamoyl-2-nitroimidazoles were more potent angiogenic inhibitors than the corresponding desacetylcarbamoyl-2-nitroimidazoles. The in vivo chick CAM angiogenesis assay showed that the strong bromoacetylcarbamoyl-2-nitroimidazole radiosensitizers, such as TX-1845 and TX-1846, were the strongest angiogenic inhibitors among them. We concluded that the bromoacetylcarbamoyl-2-nitroimidazole radiosensitizers, such as TX-1845 and TX-1846, are promising as anti-angiogenic hypoxic cell radiosensitizers. (C) 1997 Elsevier Science Ltd.