4-methylthiomandelic acid | 109086-16-0

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-methylthiomandelic acid
• 英文别名: Hydroxy-(4-methylsulfanyl-phenyl)-acetic acid；2-hydroxy-2-(4-methylsulfanylphenyl)acetic acid
• CAS: 109086-16-0
• 化学式: C₉H₁₀O₃S
• 分子量: 198.243
• InChiKey: OHCFPPVMJBLAMW-UHFFFAOYSA-N

物化性质

• 沸点：
  394.4±32.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2930909090

反应信息

• 作为反应物：
  描述：

  4-methylthiomandelic acid 在 PPA 作用下， 生成
  参考文献：
  名称：

  Pyrroloisoquinoline antidepressants. 3. A focus on serotonin

  摘要：

  A collection of hexahydropyrroloisoquinoline derivatives (1-22), which represent a class of compounds that inhibit the neuronal uptake of dopamine (DA), norepinephrine (NE), and serotonin (5-HT), was investigated in vivo for serotonin-potentiating properties in the mouse head-twitch and rat serotonin syndrome assays. The p-methylthio compound 3b (McN-5652-Z) was found to possess exceptional activity in these assays, and the activity was attributable almost exclusively to the (+)-6S,10bR enantiomer. Ten closely related analogues were synthesized, tested, and compared among themselves and with some previously prepared compounds, both in vivo and in vitro. Several trans diastereomers exhibited strong inhibition of 5-HT uptake and substantial potentiation of 5-HT, while the cis diastereomers (3a, 4a, and 10a) tested were virtually devoid of such activity. Although 3b was only moderately selective in inhibiting the uptake of 5-HT vs NE, its 10-substituted analogues 4b, 7b-9b had improved 5-HT selectivity relative to NE, to the extent of 20-25 times (150-200 times relative to DA). Of these more selective compounds (in vitro), only 4b and 7b had substantial activity in vivo. Sulfoxide 11b appeared to function as a prodrug of 3b in vivo.

  DOI：

  10.1021/jm00172a018
• 作为产物：
  描述：

  三溴甲烷 、 4-(甲基巯基)苯甲醛 在 氢氧化钾 、 lithium bromide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以7.6 g的产率得到4-methylthiomandelic acid
  参考文献：
  名称：

  吡咯并异喹啉抗抑郁药。2.深入探讨构效关系。

  摘要：

  一系列吡咯并[2,1-a]异喹啉和相关化合物由于对丁苯那嗪诱导的上睑下垂和镇静作用以及对生物胺吸收的抑制作用而被检测为抗抑郁样活性。因此，我们已经鉴定出有史以来报道的一些最有效的TBZ诱导上睑下垂拮抗剂和一些最有效的多巴胺，去甲肾上腺素和血清素摄取抑制剂（在大鼠脑突触体中）。在这方面，特别值得注意的化合物分别是52b，29b，22b和48b。生物活性主要由反式异构体表现出来。而且，通过拆分四种化合物7b，24b，37b和48b，发现生物活性与（+）对映异构体亚组（在589 nm在MeOH中测得的盐）相关，对应于6S，10bR的绝对构型7b，37b，和48b，以及24b的6R，10bR配置。在（+）-24b X HBr上进行X射线测定，确定了其绝对构型；通过（+）-（R）-2-苯基吡咯烷开始的对映体特异性合成，验证了其他化合物的构型。关于侧苯环，研究了多种取代方式。那些特别不利的取代基是3'

  DOI：

  10.1021/jm00391a028

文献信息

• HEXAHYDRO-PYRROLO-ISOQUINOLINE COMPOUNDS
  申请人：Apodaca Richard

  公开号：US20060293316A1

  公开（公告）日：2006-12-28

  Certain hexahydro-pyrrolo-isoquinoline compounds are histamine H 3 receptor and serotonin transporter modulators useful in the treatment of histamine H 3 receptor- and serotonin-mediated diseases.

  某些六氢吡咯异喹啉化合物是组胺H3受体和血清素转运蛋白调节剂，在治疗组胺H3受体和血清素介导的疾病方面具有用处。
• [EN] SUBSTITUTED alpha -HYDROXY ACID CASPASE INHIBITORS AND THE USE THEREOF<br/>[FR] ACIDES alpha -HYDROXY SUBSTITUES INHIBITEURS DE CASPASES ET LEURS UTILISATIONS
  申请人：CYTOVIA INC

  公开号：WO2001016093A1

  公开（公告）日：2001-03-08

  The present invention is directed to novel substituted α-hydroxy acid thereof, represented by general Formula (I), where R1-R5, X and Z are defined herein. The present invention also relates to the discovery that compounds having Formula (I) are potent inhibitors of caspases and apoptotic cell death. Therefore, the inhibitors of this invention can retard or block cell death in a variety of clinical conditions in which the loss of cells, tissues or entire organs occurs.

  本发明涉及一种新的取代α-羟基酸及其衍生物，其通式表示为（I），其中R1-R5，X和Z的定义如本文所述。本发明还涉及到化合物具有公式（I），是半胱天冬酶和凋亡细胞死亡的有效抑制剂的发现。因此，本发明的抑制剂可以延缓或阻止在细胞、组织或整个器官丢失的多种临床情况中的细胞死亡。
• The structure of McN-5652
  作者：Oliver Schulze、Ulrich Schmidt、Jürgen Voss、Bruno Nebeling、Gunadi Adiwidjaja、Klaus Scharwächter

  DOI：10.1016/s0968-0896(01)00117-1

  日期：2001.8

  The configuration of the diastereoisomers of 6-(4-methylthiophenyl)-1,2,3,5,6,10b-hexahydropyrrolo[2, I-a]isoquinoline I (McN-5652) is determined and unequivocally assigned by NMR spectroscopy (NOE measurements) and an X-ray structural analysis of the trans dia stereo isomer. The enantiomers of cis-1 are separated by preparative HPLC on a chiral phase. One of the enantiomers of cis-1 represents the precursor for imaging the serotonin 5-HT transporter with positron emission tomography (PET). (C) 2001 Elsevier Science Ltd. All rights reserved.
• Efficient synthesis of enantiomerically pure thioester precursors of [11C]McN-5652 from racemic McN-5652
  作者：J. Zessin、P. Gucker、S. M. Ametamey、J. Steinbach、P. Brust、F. X. Vollenweider、B. Johannsen、P. A. Schubiger

  DOI：10.1002/(sici)1099-1344(19991230)42:13<1301::aid-jlcr298>3.0.co;2-2

  日期：1999.12.30

  An improved synthesis of the enantiomerically pure thioester precursors of [C-11](+)-McN-5652 ([C-11](+)-1), and [C-11](-)-McN5652 ([C-11](-)-1) starting from racemic McN-5652 ((+/-)-1) is described. The Synthetic method includes the resolution of (+/-)-1 by:repeated crystallization of the (+)- and (-)-di-p-toluoyltartrates yielding (+)-McN-5652 ((+)-1) and (-)-McN-5652 ((-)-1), each with >98% enantiomeric purity. S-Demethylation of (+/-)-1, (+)-1 and (-)-1, respectively was achieved by:treatment with sodium amide at low temperatures (-78 degrees C) followed by conversion of the intermediate thiols 2 with acetyl chloride to give the corresponding thioester precursors (+/-)-3, (+)-3 oy:(-)-3. This demethylation method almost completely suppressed the isomerization of the pharmacologically active trans diastereomer into the inactive cis form. Chiral HPLC analyses confirmed that the S-demethylation proceeded without any racemization. C-11-labelling of(+)-3 or (-)-3 yields :enantiomerically pure [C-11](+)-McN-5652 or [C-11](-)-McN5652, each in 22 % radiochemical yield (decay-corrected, related to [C-11]CO2) and a specific radioactivity of 74 GBq/mu mol (2 Ci/mu mol) at the end of synthesis (EOS).
• MARYANOFF, BRUCE E.;VAUGHT, JEFFRY L.;SHANK, RICHARD P.;MECOMSEY, DAVID F+, J. MED. CHEM., 33,(1990) N0, C. 2793-2797
  作者：MARYANOFF, BRUCE E.、VAUGHT, JEFFRY L.、SHANK, RICHARD P.、MECOMSEY, DAVID F+

  DOI：——

  日期：——