2-<(4-hydroxyphenyl)thio>ethylamine hydrochloride | 91281-33-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-<(4-hydroxyphenyl)thio>ethylamine hydrochloride
• 英文别名: 2-[(4-hydroxyphenyl)thio]ethylamine hydrochloride；4-S-cysteaminylphenol hydrochloride；4-(2-aminoethylsulfanyl)phenol;hydrochloride
• CAS: 91281-33-3
• 化学式: C₈H₁₁NOS*ClH
• 分子量: 205.708
• InChiKey: WTPGWOJFNSMSLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.86
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  71.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-<(4-hydroxyphenyl)thio>ethylamine hydrochloride 反应 2.0h， 以80%的产率得到3,4-dihydro-2H-benzo[b][1,4]thiazine-6,7-dione
  参考文献：
  名称：

  Biomimetic oxidation of the antimelanoma agent 4-S-cysteaminylphenol and related catechol thioethers: Isolation and reaction behaviour of novel dihydrobenzothiazinequinones

  摘要：

  Enzymatic and chemical oxidation of 4-S-cysteaminylpheno1 (1) and 4-S-cysteaminylcatechol (2) leads to the formation of the hitherto unknown dihydrobenzothiazine-6,7-quinone 4 via intramolecular cyclisation of the o-quinone 6. Oxidation of 4-S-cysteinylcatechol (3) gives the corresponding dihydrobenzothiazinequinone 9, which undergoes rearrangement with partial decarboxylation to give 6,7-dihydroxybenzothiazine derivatives, isolated as 8 and 5 after reduction and acetylation of the mixture. Oxidation of 2 and 3 with periodate or iodate gives mainly the iodinated quinones 7 and 13, respectively.

  DOI：

  10.1016/s0040-4020(01)85349-7
• 作为产物：
  描述：

  N-乙酰基-4-S-半胱胺基酚 在 盐酸 作用下， 反应 12.0h， 以70%的产率得到2-<(4-hydroxyphenyl)thio>ethylamine hydrochloride
  参考文献：
  名称：

  Antihypertensive activities of phenyl aminoethyl sulfides, a class of synthetic substrates for dopamine .beta.-hydroxylase

  摘要：

  Four sulfur-containing analogues of phenylpropylamine were synthesized and evaluated as substrates for dopamine beta-hydroxylase (DBH) and monoamine oxidase (MAO). All four phenyl aminoethyl sulfides were shown to be good substrates for DBH whereas only the two analogues not possessing a methyl group alpha to the terminal amino group were substrates for MAO. All four analogues were tested for acute antihypertensive activity in an animal model for hypertension, the spontaneously hypertensive rat (SHR). Two of the analogues, both of which should partition readily across the blood-brain barrier, did not appreciably reduce systemic blood pressure in the 6-h testing period. However, the two analogues that were designed to be relatively restricted to peripheral sites of action caused a dramatic drop in blood pressure in SHR of 25% within 1-1.5-h postinjection, with the analogue designed to be both restricted to the periphery and MAO inactive, causing a more prolonged antihypertensive activity.

  DOI：

  10.1021/jm00376a024

文献信息

• Synthesis of 11C-Labelled Amides by Palladium-Mediated Carboxamination Using [11C]Carbon Monoxide, in situ Activated Amines and 1,2,2,6,6-Pentamethylpiperidine
  作者：Farhad Karimi、Bengt Langström

  DOI：10.1002/ejoc.200200586

  日期：2003.6

  Twenty-seven 11C-labelled amides were synthesised using [11C]carbon monoxide in low concentrations, palladium(0), organohalides and amines in a small micro-autoclave (200 μL). The focus of the study was to improve the radiochemical yields in this palladium-mediated amide synthesis when employing less-reactive amines, such as methylamine, [(2R)-1-ethylpyrrolidin-2-yl]methylamine (40) and 2-(pyridin-2-yl)ethanamine

  在小型微型高压釜 (200 μL) 中，使用低浓度的 [11C] 一氧化碳、钯 (0)、有机卤化物和胺合成了 27 种 11C 标记的酰胺。该研究的重点是在使用反应性较低的胺，如甲胺、[(2R)-1-乙基吡咯烷-2-基]甲胺 (40) 和 2-(吡啶-2-基）乙胺（41）。将 1,2,2,6,6-五甲基哌啶（哌啶）与胺底物结合使用时，放射化学产率得到提高。11C 标记的酰胺主要以高放射化学产率（在 16-94% 的范围内）获得，比放射性在 650 到 1250 GBq/μmol 之间变化。合成 1-(1,3-Benzodioxol-5-yl[13C]carbonyl)piperidine (6a) 以验证标记位置 (δ = 169。8 ppm)，使用 13C NMR 光谱。目标化合物的放射化学纯度由分析型 HPLC 测定并超过 95%。(© Wiley-VCH Verlag GmbH & Co
• Phenylethylamine derivatives and their use in the treatment of melanoma
  申请人：——

  公开号：US20040029967A1

  公开（公告）日：2004-02-12

  Novel mono- and dihydroxy phenylethylamine derivatives useful in treating melanoma are provided having the formulae (Ia, Ib or Ic). In the above formulae, R a is hydrogen or —COOR b, R b is hydrogen or C 1-6 alkyl; R e and R e independently represent hydrogen and hydroxy, R f is hydrogen, C 1-4? alkyl or halogen, X is —CHOH—, —CH 2 -oxygen or sulphur, m is zero or 1, W is oxygen or sulphur, and —ODrug, —NHDrug and —N(Drug) 2 each represent a residue of a therapeutically active agent. The above compounds are prodrugs which are inactive until metabolised by enzymes expressed by host melanoma cells. The invention allows a greater amount of active agent to be used while reducing systemic side effects. 1

  提供了用于治疗黑色素瘤的新型单氢和二羟基苯乙胺衍生物，其化学式为（Ia、Ib或Ic）。在上述化学式中，R是氢或—COORb，Rb是氢或C1-6烷基；Re和Re独立表示氢和羟基，Rf是氢、C1-4烷基或卤素，X是—CHOH—、—CH2-氧或硫，m为零或1，W是氧或硫，而—ODrug、—NHDrug和—N（Drug）2分别表示治疗活性剂的残基。上述化合物是一种前药，在被宿主黑色素瘤细胞表达的酶代谢之前是无效的。该发明允许使用更多的活性剂而减少全身副作用。
• [EN] PHENYLETHYLAMINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF MELANOMA<br/>[FR] DERIVES DE PHENYLETHYLAMINE ET LEUR UTILISATION DANS LE TRAITEMENT DE MELANOME
  申请人：RILEY PATRICK ANTHONY

  公开号：WO2002008174A1

  公开（公告）日：2002-01-31

  Novel mono- and dihydroxy phenylethylamine derivatives useful in treating melanoma are provided having the formulae (Ia, Ib or Ic). In the above formulae, Ra is hydrogen or -COORb, Rb is hydrogen or C¿1-6? alkyl; R?e and Re¿ independently represent hydrogen and hydroxy, Rf is hydrogen, C¿1-4? alkyl or halogen, X is -CHOH-, -CH2-oxygen or sulphur, m is zero or 1, W is oxygen or sulphur, and -ODrug, -NHDrug and -N(Drug)2 each represent a residue of a therapeutically active agent. The above compounds are prodrugs which are inactive until metabolised by enzymes expressed by host melanoma cells. The invention allows a greater amount of active agent to be used while reducing systemic side effects.

  本发明提供了一种在治疗黑色素瘤方面有用的新型单和双羟基苯乙胺衍生物，其化学式为（Ia，Ib或Ic）。在上述化学式中，Ra为氢或-COORb，Rb为氢或C1-6烷基；Re和Re'独立地表示氢和羟基，Rf为氢，C1-4烷基或卤素，X为-CHOH-，-CH2-氧或硫，m为零或1，W为氧或硫，-ODrug，-NHDrug和-N（Drug）2分别表示治疗活性剂的残基。上述化合物是前药，在被宿主黑色素瘤细胞表达的酶代谢之前是不活性的。本发明允许使用更多的活性剂而减少全身副作用。
• Melanocyte-Directed enzyme prodrug therapy (MDEPT)
  作者：Allan M. Jordan、Tariq H. Khan、Hugh Malkin、Helen M.I. Osborn、Andrew Photiou、Patrick A. Riley

  DOI：10.1016/s0968-0896(01)00039-6

  日期：2001.6

  Evaluation of second generation prodrugs for MDEPT, by oximetry, has highlighted structural properties that are advantageous and disadvantageous for efficient oxidation using mushroom tyrosinase. In particular, a sterically undemanding prodrug bis-(2-chloroethyl)amino-4-hydroxyphenylaminomethanone 28 was synthesised and found to be oxidised by mushroom tyrosinase at a superior rate to tyrosine methyl ester, the carboxylic acid of which is the natural substrate for tyrosinase. The more sterically demanding phenyl mustard prodrugs 9 and 10 were oxidised by mushroom tyrosinase at a similar rate to tyrosine methyl ester. In contrast, tyramine chain elongation via heteroatom insertion was detrimental and the rate of mushroom tyrosinase oxidation of phenyl mustard prodrugs 21 and 22 decreased by 10 nanomol/min. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Dihydro-1,4-benzothiazine-6,7-dione, the ultimate toxic metabolite of 4-S-Cysteaminylphenol and 4-S-Cysteaminylcatechol
  作者：Katsutoshi Hasegawa、Shosuke Ito、Shigeki Inoue、Kazumasa Wakamatsu、Hiroyuki Ozeki、Isao Ishiguro

  DOI：10.1016/s0006-2952(97)00075-0

  日期：1997.5

  4-S-Cysteaminylphenol (4-S-CAP) and the corresponding catechol 4-S-cysteaminylcatechol (4-S-CAC) have been evaluated for melanocytotoxicity. It was shown recently that tyrosinase oxidation of these substrates produces a violet pigment, dihydro-1,4-benzothiazine-6,1-dione (BQ). In this study we examined whether BQ is the ultimate toxic metabolite produced in melanoma cells from 4-S-CAP/4-S-CAC. Biochemical experiments showed that (1) BQ was formed by autoxidation of 4-S-CAC as well as by tyrosinase oxidation of 4-S-CAP/4-S-CAC, (2) BQ reacted rapidly with thiols such as reduced glutathione (GSH), and (3) BQ inhibited the activity of alcohol dehydrogenase, an SH enzyme. In vitro experiments showed that (1) the cytotoxicity of 4-S-CAC was mostly prevented by catalase and superoxide dismutase, (2) Ba was highly cytotoxic to B16 melanoma cells (IC50 being 3.9 mu M as compared with 507 mu M for 4-S-CAP), (3) BQ was metabolized rapidly to a GSH adduct in melanoma cells, and (4) the same GSH adduct was also formed upon incubation of melanoma cells with 4-S-CAP, the reaction being tyrosinase dependent. In vivo experiments showed that intratumoral administration of BQ (0.5 mu mol) inhibited the subcutaneous growth of B16 melanoma nearly as effectively as 4-S-CAP/4-S-CAC (20 mu mol). These results indicate that BQ is the ultimate toxic metabolite produced by tyrosinase oxidation of 4-S-CAP/4-S-CAC. BQ deprives melanoma cells of GSH and may inactivate SH enzymes essential for DNA synthesis and cell proliferation by covalent binding through their cysteine residues, thereby exerting melanocytotoxicity. Cytotoxicity of 4-S-CAC depends mostly on autoxidation producing BQ and active oxygens. (C) 1997 Elsevier Science Inc.