2-(bromomethyl)-1-methyl-5-nitro-1H-pyrrole | 1017279-01-4

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-(bromomethyl)-1-methyl-5-nitro-1H-pyrrole
• 英文别名: 2-(Bromomethyl)-1-methyl-5-nitropyrrole
• CAS: 1017279-01-4
• 化学式: C₆H₇BrN₂O₂
• 分子量: 219.038
• InChiKey: VTPPFPRFOCYUOH-UHFFFAOYSA-N

物化性质

• 沸点：
  323.0±27.0 °C(Predicted)
• 密度：
  1.70±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  50.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(bromomethyl)-1-methyl-5-nitro-1H-pyrrole 在 盐酸 、 草酰氯 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 34.0h， 生成 (E)-1-(5-amino-1-(chloromethyl)-1H-benzo[e]indol-3(2H)-yl)-3-(4-((methyl((1-methyl-5-nitro-1H-pyrrol-2-yl)methyl)amino)methyl)phenyl)prop-2-en-1-one dihydrochloride
  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：

  2-(hydroxymethyl)-1-methyl-5-nitropyrrole 在 溴 、 三苯基膦 作用下， 以 乙腈 为溶剂， 反应 0.58h， 以92%的产率得到2-(bromomethyl)-1-methyl-5-nitro-1H-pyrrole
  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

• Discovery of a highly efficient nitroaryl group for detection of nitroreductase and imaging of hypoxic tumor cells
  作者：Shushu Wang、Xiaojun Wu、Yuqing Zhang、Dong Zhang、Boyu Xie、Zhixiang Pan、Kunfu Ouyang、Tao Peng

  DOI：10.1039/d1ob00356a

  日期：——

  and treatment. As a well-established biomarker of hypoxia, nitroreductase (NTR) has been widely exploited in the development of hypoxia-responsive fluorescent probes on the basis of its enzymatic activity to reduce nitroaryl groups. However, studies on the relationship between the nitroaryl structure and the probe performance for optimal probe design are still rare. Here we report a comparative investigation

  缺氧是实体瘤的病理标志。因此，检测缺氧对肿瘤诊断和治疗具有重要意义。作为一种公认的缺氧生物标志物，硝基还原酶（NTR）基于其还原硝基芳基的酶活性，已被广泛用于开发缺氧响应荧光探针。然而，关于硝基芳基结构与最佳探针设计的探针性能之间关系的研究仍然很少。在这里，我们报告了硝基芳基的比较研究和最佳硝基芳基结构的鉴定，以开发新的荧光探针，在检测 NTR 和低氧肿瘤细胞成像方面具有极高的效率。具体来说，我们合成了一系列含有不同硝基芳基的试卤灵荧光探针，N-甲基-咪唑基作为最佳的硝基芳基，比用于 NTR 检测的最广泛使用的 4-硝基苯基更有效。然后通过理论分子对接研究了结构-性能关系，揭示了2-硝基-N-甲基-咪唑基与NTR结合和反应的独特特征。我们进一步将 2-硝基-N-甲基-咪唑基结合到近红外 (NIR) 半花青荧光团中，并开发了用于检测 NTR 和缺氧肿瘤细胞的 NIR 荧光探针 NFP-7。NFP-7在体外对
• PRODRUG FORMS OF KINASE INHIBITORS AND THEIR USE IN THERAPY
  申请人：Smaill Jeffrey Bruce

  公开号：US20120077811A1

  公开（公告）日：2012-03-29

  The invention provides novel prodrug compounds comprising a kinase inhibitor and a reductively-activated fragmenting aromatic nitroheterocycle or aromatic nitrocarbocycle trigger, where the compound carries a positive charge. In preferred embodiments, the compounds are of Formula I: where: X is any negatively charged counterion; R 1 is a group of the formula —(CH 2 ) n Tr, where Tr is an aromatic nitroheterocycle or aromatic nitrocarbocycle and —(CH 2 ) n Tr acts as a reductively-activated fragmenting trigger; and n is an integer from 0 to 6; R 2 , R 3 and R 4 may each independently be selected from aliphatic or aromatic groups of a tertiary amine kinase inhibitor (R 2 )(R 3 )(R 4 )N, or two of R 2 , R 3 , and R 4 may form an aliphatic or aromatic heterocyclic amine ring of a kinase inhibitor, or one of R 2 , R 3 and R 4 may be absent and two of R 2 , R 3 and R 4 form an aromatic heterocyclic amine ring of a kinase inhibitor. The compounds of the invention are useful in treating proliferative diseases such as cancer.

  本发明提供了新型的前药化合物，包括一种激酶抑制剂和一种还原活化的破裂芳香族硝基杂环或芳香族硝基碳杂环触发剂，其中该化合物带有正电荷。在优选实施例中，该化合物为式I：其中：X是任何带负电的反离子；R1是公式—(CH2)nTr的基团，其中Tr是芳香族硝基杂环或芳香族硝基碳杂环，—(CH2)nTr作为还原活化的破裂触发器；n是0到6的整数；R2、R3和R4可以各自独立地选择来自三级胺激酶抑制剂的脂肪族或芳香族基团(R2)(R3)(R4)N，或者R2、R3和R4中的两个可以形成激酶抑制剂的脂肪族或芳香族杂环胺环，或者R2、R3和R4中的一个可以缺失，R2、R3和R4中的两个可以形成激酶抑制剂的芳香族杂环胺环。该发明的化合物可用于治疗增殖性疾病，如癌症。
• Synthesis of substituted 5-bromomethyl-4-nitroimidazoles and use for the preparation of the hypoxia-selective multikinase inhibitor SN29966
  作者：Guo-Liang Lu、Amir Ashoorzadeh、Robert F. Anderson、Adam V. Patterson、Jeff B. Smaill

  DOI：10.1016/j.tet.2013.08.037

  日期：2013.10

  5-Bromomethyl-4-nitroimidazoles have utility as bioreductive trigger precursors for the preparation of hypoxia-selective prodrugs. Here we describe an efficient two-step synthesis of 5-(bromomethyl)-1-methyl-4-nitro-1H-imidazole, a preferred precursor, employing an N-bromosuccinimide mediated radical bromination. Use of this precursor to prepare SN29966, a promising hypoxia-selective irreversible pan-ErbB inhibitor is reported along with the preparation of four other prodrug candidates. 5-Bromomethyl-4-nitroimidazole analogues bearing electron-donating and electron-withdrawing substituents at the N-1 and C-2 positions are also described. (C) 2013 Elsevier Ltd. All rights reserved.
• US9073916B2
  申请人：——

  公开号：US9073916B2

  公开（公告）日：2015-07-07
• [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.