1,2,3,4-四氢-7-碘异喹啉 | 72299-62-8

• 物质功能分类: 医药中间体 - 杂环化合物 - 喹啉类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: 1,2,3,4-四氢-7-碘异喹啉
• 中文别名: [1,1'-双(二苯基膦基)二茂铁]二氯化钯；7-碘-1,2,3,4-四氢异喹啉；1,1'-双(二苯膦基)二茂铁二氯化钯；[1,1'-双(二苯基膦)二茂铁]二氯化钯(II)
• 英文名称: 7-Iodo-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 7-Iodtetrahydroisochinolin
• CAS: 72299-62-8
• 化学式: C₉H₁₀IN
• 分子量: 259.09
• InChiKey: FFCFXJXBXUOFIU-UHFFFAOYSA-N

物化性质

• 沸点：
  305.2±42.0 °C(Predicted)
• 密度：
  1.678±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  1,2,3,4-四氢-7-碘异喹啉 在 copper(l) iodide 、 四(三苯基膦)钯 、 caesium carbonate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 49.67h， 生成 3-[(7-ethynyl-3,4-dihydro-1H-isoquinolin-2-yl)sulfonyl]benzoic acid
  参考文献：
  名称：

  3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: Highly Potent and Selective Inhibitors of the Type 5 17-β-Hydroxysteroid Dehydrogenase AKR1C3

  摘要：

  A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acid as a novel, highly potent (low nM), and isoform-selective (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both breast and prostate cancer. Crystal structure studies showed that the carboxylate group occupies the oxyanion hole in the enzyme, while the sulfonamide provides the correct twist to allow the dihydroisoquinoline to bind in an adjacent hydrophobic pocket. SAR studies around this lead showed that the positioning of the carboxylate was critical, although it could be substituted by acid isosteres and amides. Small substituents on the dihydroisoquinoline gave improvements in potency. A set of "reverse sulfonamides" showed a 12-fold preference for the R stereoisomer. The compounds showed good cellular potency, as measured by inhibition of AKR1C3 metabolism of a known dinitrobenzamide substrate, with a broad rank order between enzymic and cellular activity, but amide analogues were more effective than predicted by the cellular assay.

  DOI：

  10.1021/jm3007867
• 作为产物：
  描述：

  7-iodo-N-acetyl-1,2,3,4-tetrahydroisoquinoline 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以87%的产率得到1,2,3,4-四氢-7-碘异喹啉
  参考文献：
  名称：

  Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

  摘要：

  7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the aa-adrenoceptor. To design a selective (PNMT vs alpha(2)-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and alpha(2)-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quantitative structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pK(i) = 0.599 pi - 0.0725MR + 1.55 sigma(m) + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the alpha(2)-adrenoceptor (alpha(2) pK(i) = 0.599 pi - 0.0542MR - 0.951 sigma(m) + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7-substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative molecular field analysis (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the alpha(2)-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position, These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs alpha(2)-adrenoceptor affinity) inhibitors of PNMT.

  DOI：

  10.1021/jm980429p

文献信息

• [EN] SPIRO[CYCLOBUTANE-1,3'-INDOLIN]-2'-ONE DERIVATIVES AS BROMODOMAIN INHIBITORS<br/>[FR] DÉRIVÉS SPIRO[CYCLOBUTANE-1,3'-INDOLIN]-2'-ONES EN TANT QU'INHIBITEURS DE BROMODOMAINE
  申请人：ORION CORP

  公开号：WO2015092118A1

  公开（公告）日：2015-06-25

  The present invention provides novel spiro[cyclobutane-1,3'-indolin]-2'- derivatives of formula (I) in which Cy, R1, R2, L and 'm' are have the meaning given in the specification, and pharmaceutically acceptable salts thereof. The compounds of formula (I) are useful as bromodomain inhibitors in the treatment or prevention of diseases or disorders where bromodomain inhibition is desired.

  本发明提供了式(I)的新颖的螺[环丁烷-1,3'-吲哚]-2'-衍生物，其中Cy、R1、R2、L和'm'的含义如规范中所述，并且其药学上可接受的盐。式(I)的化合物在治疗或预防需要溴结构域抑制的疾病或紊乱中作为溴结构域抑制剂是有用的。
• Inhibitors of farnesyl-protein transferase
  申请人：Merck & Co., Inc.

  公开号：US05977134A1

  公开（公告）日：1999-11-02

  The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras.

  本发明涉及抑制法尼基-蛋白转移酶（FTase）和致癌基因蛋白Ras的法尼醇化的化合物。该发明还涉及含有本发明化合物的化疗组合物以及抑制法尼基-蛋白转移酶和致癌基因蛋白Ras法尼醇化的方法。
• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• [EN] μ-OPIOID RECEPTOR AGONIST AND PREPARATION METHOD THEREFOR AND USE THEREOF IN FIELD OF MEDICINE<br/>[FR] AGONISTE DU RÉCEPTEUR μ-OPIOÏDE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION EN MÉDECINE<br/>[ZH] μ-阿片受体激动剂及其制备方法和在医药领域的应用
  申请人：SHANGHAI SYNERGY PHARMACEUTICAL SCIENCES CO LTD

  公开号：WO2019052557A1

  公开（公告）日：2019-03-21

  一类μ-阿片受体激动剂及其制备方法和在医药领域的应用，属于药物化学领域。所述μ-阿片受体激动剂对G蛋白信号通路的选择性显著提高，不仅能表现出优异的药效作用，而且在安全性方面也得到显著改善。
• INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
  申请人：MERCK & CO., INC.

  公开号：EP1045843A1

  公开（公告）日：2000-10-25