N-(2-chloroethyl)-N'-[3-(2-ethoxycarbonyl)indolyl]urea | 119704-29-9

• 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: N-(2-chloroethyl)-N'-[3-(2-ethoxycarbonyl)indolyl]urea
• 英文别名: ethyl 3-(2-chloroethylcarbamoylamino)-1H-indole-2-carboxylate
• CAS: 119704-29-9
• 化学式: C₁₄H₁₆ClN₃O₃
• 分子量: 309.752
• InChiKey: SEGANAYFJWHABF-UHFFFAOYSA-N

物化性质

• 沸点：
  495.4±45.0 °C(Predicted)
• 密度：
  1.370±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  83.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2-chloroethyl)-N'-[3-(2-ethoxycarbonyl)indolyl]urea 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以91%的产率得到2,3,5,6-tetrahydro-5-oxooxazolo<3',2':1,2>pyrimido<5,4-b>indole
  参考文献：
  名称：

  嘧啶并[5,4-b]吲哚衍生物。1.一类新的有效和选择性的α1肾上腺素受体配体。

  摘要：

  通过放射性配体受体结合测定评估了许多3-取代的嘧啶并[5,4-b]吲哚-2,4-二酮（7-23）的体外α1肾上腺素受体亲和力。一些带有（苯基哌嗪基）烷基侧链的化合物是有效的α1肾上腺素受体配体。从大鼠皮膜置换[3H]吡唑嗪最活跃的衍生物是3- [2- [4-（2-甲氧基苯基）哌嗪-1-基]乙基]嘧啶基[5,4-b]吲哚e-2， 4-二酮（10）（Ki = 0.21 nM）。结构的离散修饰导致对alpha 1的选择性（大于10,000倍）比alpha 2，beta 2和5HT1A受体更高。一些化合物也对5HT1A受体具有亲和力。最具选择性的α1配体是3- [2- [4-（2-氯苯基）哌嗪-1-基]乙基]嘧啶基[5,4-b]吲哚-2,4-二酮（13）。

  DOI：

  10.1021/jm00110a014
• 作为产物：
  描述：

  3-氨基-2-吲哚羧酸乙酯 生成 N-(2-chloroethyl)-N'-[3-(2-ethoxycarbonyl)indolyl]urea
  参考文献：
  名称：

  MONGE, A.;PALOP, J. A.;GONI, T.;PARRADO, P.;MARTINEZ, F.;FERNANDEZ-ALVARE+, AN. QUIM. REAL SOC. ESP. QUIM., 84,(1988) N 1, 38-41

  摘要：

  DOI：

文献信息

• Synthesis of novel 5<i>H</i>-Pyrimido[5,4-<i>b</i>]mdole-(1<i>H</i>,3<i>H</i>)2,4-diones as potential ligands for the cloned α₁-adrenoceptor subtypes
  作者：G. Romeo、F. Russo、A. De Blasi

  DOI：10.1002/jhet.5570380213

  日期：2001.3

  A new series of 3-[ω-[4-(4-substituted phenyl)piperazin-1-yl]alkyl]-5H-pyrimido[5,4-b]indole-(1H,3H)-2,4-diones (3–10 and 12–13) were synthesized from the N-(2-chloroethyl)-N'-[3-(2-ethoxycarbonyl)indolyl] urea (1) or the N-(3-chloropropyl)-N'-[3-(2-ethoxycarbonyl)indolyl] urea (2) and a number of 1-(4-substi-tuted-phenyl)piperazines. 3-[2-[4-(4-Aminophenyl)piperazin-1-yl]ethyl]-5H-pyrimido[5,4-b]indole-(1H

  一系列新的3- [ω-[4-（4-取代的苯基）哌嗪-1-基]烷基] -5 H-嘧啶基[5,4- b ]吲哚-（1 H，3 H）-2，从N-（2-氯乙基）-N' -[3-（2-乙氧羰基）吲哚基]尿素（1）或N-（3-氯丙基）合成4-二酮（3-10和12-13） - N” - [3-（2-乙氧羰基）吲哚基]脲（2）和若干的1-（4- substi-tuted -苯基）哌嗪。3- [2- [4-（4-氨基苯基）哌嗪-1-基]乙基] -5 H-嘧啶基[5,4- b ]吲哚-（1 H，3 H）2,4-二酮（通过还原母体硝基化合物8获得14）。在结合测定中针对克隆的α1A，α1B和α1D肾上腺素受体亚型测试了获得的5 H-嘧啶基[5,4- b ]吲哚-（1 H，3 H）2,4-二酮衍生物。一些化合物表现出良好的亲和性和选择性的α 1D肾上腺素能受体亚型。
• [11C]RN5: A new agent for the in vivo imaging of myocardial α1-adrenoceptors
  作者：Mario Matarrese、Rosa M Moresco、Giuseppe Romeo、Elia A Turolla、Pasquale Simonelli、Sergio Todde、Sara Belloli、Assunta Carpinelli、Fulvio Magni、Filippo Russo、Marzia Galli Kienle、Ferruccio Fazio

  DOI：10.1016/s0014-2999(02)02454-8

  日期：2002.10

  procedure consisted of O-methylation of des-methyl precursor with [11C]methyl iodide in the presence of potassium hydroxide in dimethylformamide (DMF) at 80 degrees C. [11C]RN5 was obtained in >99% radiochemical purity in 25 min with a radiochemical yield in the 20-30% range, end of synthesis (EOS) (non-decay corrected) and a specific radioactivity of 92.5+/-18.5 GBq/micromol. Pre-clinical studies in rats

  正电子发射体Carbon-11的放射性标记及对大鼠3- [2- [4-（2- [11C]甲氧基苯基）哌嗪-1-基]乙基]嘧啶基[5,4-b]吲哚的生物学评价据报道有-2,4-二酮（[11C] RN5），α1-肾上腺素受体拮抗剂（K（i）= 0.21 nM）作为用于正电子发射断层扫描（PET）非侵入性评估α1-肾上腺素受体的推定放射性配体。放射性合成程序包括在80°C的二甲基甲酰胺（DMF）中，在氢氧化钾存在下，用[11C]甲基碘将去甲基前体与[11C]甲基碘进行O-甲基化。在25分钟内以> 99％的放射化学纯度获得[11C] RN5放射化学产率在20％至30％范围内，合成结束（EOS）（未衰减校正），比放射性为92.5 +/- 18.5 GBq / micromol。在大鼠进行的临床前研究表明，心脏，脾脏，肾上腺，肺和肾脏，但不在大脑中。对大剂量不同肾上腺素能拮抗剂的抑制研究表明，心肌吸收[11C]
• New Pyrimido[5,4-<i>b</i>]indoles as Ligands for α₁-Adrenoceptor Subtypes
  作者：Giuseppe Romeo、Luisa Materia、Fabrizio Manetti、Alfredo Cagnotto、Tiziana Mennini、Ferdinando Nicoletti、Maurizio Botta、Filippo Russo、Kenneth P. Minneman

  DOI：10.1021/jm0307741

  日期：2003.7.1

  A new series of compounds were designed as structural analogues of the alpha(1)-AR ligand RN5 (4), characterized by a tricyclic 5H-pyrimido[5,4-b]indole-(1H,3H)2,4-dione system connected through an alkyl. chain to a phenylpiperazine (PP) moiety. These compounds were synthesized and tested in binding assays on human alpha(1A)-AR, alpha(1B)-AR, and alpha(1D)-AR subtypes expressed in HEK293 cells. Several structural modifications were performed on the PP moiety, the tricyclic system, and the connecting alkyl chain. Many of the new molecules showed a preferential affinity for the alpha(1D)-AR subtype. Some compounds, including 39 and 40, displayed substantial alpha(1D)-AR selectivity with respect to alpha(1A)-AR, alpha(1B)-AR, serotonergic 5-HT1A, 5-HT1B, 5-HT2A, and dopaminergic D-1 and D-2 receptors. Two conformationally rigid analogues of 4, useful for studying the architecture of the receptor/ligand complex, were also prepared and tested. A subset of the new compounds was then used to evolve a preliminary pharmacophore model for alpha(1D)-AR antagonists, based on a more generalized model we had developed for alpha(1)-AR antagonists. This new model rationalized the relationships between structural properties and biological data of the pyrimido[5,4-b]indole compounds, as well as other compounds.
• Romeo; Russo; Guccione, Il Farmaco, 1995, vol. 50, # 6, p. 471 - 477
  作者：Romeo、Russo、Guccione、Barbarulo、De Blasi

  DOI：——

  日期：——
• New pyrimido[5,4-b]indoles and [1]benzothieno[3,2-d]pyrimidines: High affinity ligands for the α1-adrenoceptor subtypes
  作者：Giuseppe Romeo、Luisa Materia、Gabriella Marucci、Maria Modica、Valeria Pittalà、Loredana Salerno、Maria Angela Siracusa、Michela Buccioni、Piero Angeli、Kenneth P. Minneman

  DOI：10.1016/j.bmcl.2006.09.034

  日期：2006.12

  A number of new pyrimido[5,4-b]indole and [1]benzothieno[3,2-d]pyrimidine derivatives were synthesized and evaluated for their binding and functional properties at alpha(1)-adrenergic receptor (alpha(1)-AR) subtypes. They behaved as potent alpha(1)-AR antagonists. In binding experiments, some of them (RC24 and RC23) showed very high affinity for the alpha(1D)-AR subtype. (c) 2006 Elsevier Ltd. All rights reserved.