2-(2-hydroxyphenyl)-1h-indole 5-carboxamidine | 179748-10-8

• 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: 2-(2-hydroxyphenyl)-1h-indole 5-carboxamidine
• 英文别名: 2-(2-hydroxyphenyl)-1H-indole-5-carboximidamide
• CAS: 179748-10-8
• 化学式: C₁₅H₁₃N₃O
• 分子量: 251.288
• InChiKey: JPGNPKIYCTXJPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  85.9
• 氢给体数：
  4
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-(5-bromo-1H-indol-2-yl)phenol 在 盐酸 、 氨 作用下， 以 喹啉 、 乙醇 为溶剂， 反应 35.0h， 生成 2-(2-hydroxyphenyl)-1h-indole 5-carboxamidine
  参考文献：
  名称：

  Derivatives of 5-amidine indole as inhibitors of thrombin catalytic activity

  摘要：

  Substituted 5-amidine indoles were constructed based upon a computational analysis of putative modes of binding to thrombin utilizing coordinates from the crystal structure of BMS-183,507-alpha-thrombin complex. These analogs display competitive kinetics for the inhibition of human cr-thrombin. The most potent member of this series 17, shows marked potency for thrombin with an inhibition constant, K-i of 260 nM. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0960-894x(96)00229-6

文献信息

• 4-SUBSTITUTED-2-(5-SUBSTITUTED-1H-INDOL-2-YL)PHENOL DERIVATIVES, METHODS FOR PREPARING THE PHENOL DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS FOR INHIBITING CELL PROLIFERATION AND MIGRATION INCLUDING THE PHENOL DERIVATIVES
  申请人：KOREA UNIVERSITY RESEARCH AND BUSINESS FOUNDATION

  公开号：US20170129879A1

  公开（公告）日：2017-05-11

  Disclosed are 4-substituted-2-(5-substituted-1H-indol-2-yl)phenol derivatives for controlling the proliferation and migration of kinase-overexpressed cells. The phenol derivatives are represented by Formula 1: wherein X is selected from the group consisting of hydrogen, halogen, a cyano group, a trifluoromethyl (CF 3 ) group, an amidine (C(═NH)NH 2 ) group, and a 5-methyl-1,2,4-oxadiazole group, Y is selected from the group consisting of hydrogen, halogen, a phenyl group substituted with one or two substituents selected from the group consisting of halogen, methoxy, nitro, trifluoromethyl, and aminomethyl, CO—R′, COOR′, OH, O—R′, and NH—R′, each R′ is independently selected from the group consisting of C 1 -C 18 alkyl, alkenyl, alkynyl, and —Z-alkyl (wherein Z is a heteroatom selected from the group consisting of O, S, and N or is —(CH 2 ) m —), and m is an integer from 0 to 5. Also disclosed are methods for preparing the phenol derivatives and pharmaceutical compositions for inhibiting cell proliferation and migration including the phenol derivatives. The phenol derivatives and the pharmaceutical compositions can effectively inhibit the proliferation and migration of kinase-overexpressed cells and can be used for the prevention or treatment of various solid cancers and metastatic cancers.

  本发明涉及用于控制激酶过度表达细胞增殖和迁移的4-取代-2-(5-取代-1H-吲哚-2-基)酚衍生物。该酚衍生物由下式表示：其中X从氢、卤素、氰基、三氟甲基（CF3）基团、酰胺基（C(═NH)NH2）基团和5-甲基-1,2,4-噁二唑基团中选择，Y从氢、卤素、苯基（苯环）取代物中选择，该取代物取自卤素、甲氧基、硝基、三氟甲基和氨甲基中选择，CO—R′、COOR′、OH、O—R′和NH—R′中的每个R′从C1-C18烷基、烯基、炔基和—Z-烷基（其中Z是从O、S和N中选择的杂原子或为—(CH2)m—）中独立选择，m为0到5的整数。还公开了制备该酚衍生物的方法和包括该酚衍生物的抑制细胞增殖和迁移的药物组合物。该酚衍生物和药物组合物能够有效抑制激酶过度表达细胞的增殖和迁移，并可用于预防或治疗各种实体癌症和转移性癌症。
• 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。
• 4-substituted-2-(5-substituted-1H-indol-2-yl)phenol derivatives, methods for preparing the phenol derivatives and pharmaceutical compositions for inhibiting cell proliferation and migration including the phenol derivatives
  申请人：KOREA UNIVERSITY RESEARCH AND BUSINESS FOUNDATION

  公开号：US10155753B2

  公开（公告）日：2018-12-18

  Disclosed are 4-substituted-2-(5-substituted-1H-indol-2-yl)phenol derivatives for controlling the proliferation and migration of kinase-overexpressed cells. The phenol derivatives are represented by Formula 1: wherein X is selected from the group consisting of hydrogen, halogen, a cyano group, a trifluoromethyl (CF3) group, an amidine (C(═NH)NH2) group, and a 5-methyl-1,2,4-oxadiazole group, Y is selected from the group consisting of hydrogen, halogen, a phenyl group substituted with one or two substituents selected from the group consisting of halogen, methoxy, nitro, trifluoromethyl, and aminomethyl, CO—R′, COOR′, OH, O—R′, and NH—R′, each R′ is independently selected from the group consisting of C1-C18 alkyl, alkenyl, alkynyl, and —Z-alkyl (wherein Z is a heteroatom selected from the group consisting of O, S, and N or is —(CH2)m—), and m is an integer from 0 to 5. Also disclosed are methods for preparing the phenol derivatives and pharmaceutical compositions for inhibiting cell proliferation and migration including the phenol derivatives. The phenol derivatives and the pharmaceutical compositions can effectively inhibit the proliferation and migration of kinase-overexpressed cells and can be used for the prevention or treatment of various solid cancers and metastatic cancers.

  本发明公开了 4-取代-2-(5-取代-1H-吲哚-2-基)苯酚衍生物，用于控制激酶表达细胞的增殖和迁移。苯酚衍生物由式 1 表示： 其中X选自由氢、卤素、氰基、三氟甲基(CF3)、脒基(C(═NH)NH2)和5-甲基-1,2,4-噁二唑基组成的组，Y选自由氢、卤素、被一个或两个选自由卤素组成的取代基取代的苯基、甲氧基、硝基、三氟甲基和脒甲基、CO-R′、COOR′、OH、OH-R′和NH-R′组成的组、甲氧基、硝基、三氟甲基和氨基甲基、CO-R′、COOR′、OH、O-R′和 NH-R′，每个 R′独立地选自由 C1-C18 烷基、烯基、炔基、炔烃基、炔烃基、炔烃基和炔烃基组成的组、烯基、炔基和-Z-烷基（其中 Z 是选自由 O、S 和 N 组成的组的杂原子或 -(CH2)m-），且 m 是 0 至 5 的整数。还公开了苯酚衍生物的制备方法和包括苯酚衍生物的抑制细胞增殖和迁移的药物组合物。苯酚衍生物和药物组合物能有效抑制激酶表达细胞的增殖和迁移，可用于预防或治疗各种实体癌和转移性癌症。
• Development of Serine Protease Inhibitors Displaying a Multicentered Short (<2.3 Å) Hydrogen Bond Binding Mode:  Inhibitors of Urokinase-Type Plasminogen Activator and Factor Xa
  作者：Erik Verner、Bradley A. Katz、Jeffrey R. Spencer、Darin Allen、Jason Hataye、Witold Hruzewicz、Hon C. Hui、Aleksandr Kolesnikov、Yong Li、Christine Luong、Arnold Martelli、Kesavan Radika、Roopa Rai、Miles She、William Shrader、Paul A. Sprengeler、Sean Trapp、Jing Wang、Wendy B. Young、Richard L. Mackman

  DOI：10.1021/jm0100638

  日期：2001.8.1

  Novel scaffolds that bind to serine proteases through a unique network of short hydrogen bonds to the catalytic Ser195 have been developed. The resulting potent serine protease inhibitors were designed from lead molecule 2-(2-hydroxyphenyl)1H-benzoimidazole-5-carboxamidine, 6b, which is known to display several modes of binding. For instance, 6b can recruit zinc and bind in a manner similar to that reported by bis(5-amidino-2-benzimidazolyl)methane (BABIM) (Nature 1998, 391, 608-612).(1) Alternatively, 6b can bind in the absence of zinc through a multicentered network of short (<2.3 Angstrom) hydrogen bonds. The lead structure was optimized in the zinc-independent binding mode toward a panel of six human serine proteases to yield optimized inhibitors such as 2-(3-bromo-2-hydroxy-5-methylphenyl)-1H-indole-5-carboxamidine, 22a, and 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine, 22f. Structure-activity relationships determined that, apart from the amidine function, an indole or benzimidazole and an ortho substituted phenol group were also essential components for optimal potency. The affinities (K-i) of 22a and 22f, for example, bearing these groups ranged from 8 to 600 nM toward a panel of six human serine proteases. High-resolution crystal structures revealed that the binding mode of these molecules in several of the enzymes was identical to that of 6b and involved short (<2.3 Angstrom) hydrogen bonds among the inhibitor hydroxyl oxygen, Ser195, and a water molecule trapped in the oxyanion hole. In summation, novel and potent trypsin-like serine protease inhibitors possessing a unique mode of binding have been discovered.
• Design, synthesis and biological evaluation of PSMA/hepsin-targeted heterobivalent ligands
  作者：Milan Subedi、Il Minn、Jianbo Chen、YunHye Kim、Kiwon Ok、Yong Woo Jung、Martin G. Pomper、Youngjoo Byun

  DOI：10.1016/j.ejmech.2016.04.033

  日期：2016.8

  Cell surface biomarkers such as prostate-specific membrane antigen (PSMA) and hepsin have received considerable attention as targets for imaging prostate cancer (PCa) due to their high cell surface expression in such tumors and easy access for imaging probes. Novel amidine-containing indole analogs (13-21) as hepsin inhibitors were designed and synthesized. These compounds showed in vitro inhibitory activity against hepsin with IC50 values from 5.9 to 70 μM. Based on the SAR of amidine-derived analogs, the novel heterobivalent compound 30, targeting both hepsin and PSMA, was synthesized by linking compound 18 with Lys-urea-Glu, the key scaffold for the specific binding to PSMA, followed by the conjugation of the optical dye SulfoCy7. Compound 30 exhibited inhibitory activities against PSMA and hepsin, with IC50 values of 28 nM and 2.8 μM, respectively. In vitro cell uptake and preliminary in vivo optical imaging studies of 30 showed selective binding and retention in both PSMA and hepsin high-expressing PC3/ML-PSMA-HPN cells as compared with low-expressing PC3/ML cells.