2-mercapto-5-fluoroaniline hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯硫酚类
• 英文名称: 2-mercapto-5-fluoroaniline hydrochloride
• 英文别名: 2-amino-4-fluorothiophenol hydrochloride；(5-Fluoro-2-sulfanylphenyl)azanium;chloride；(5-fluoro-2-sulfanylphenyl)azanium;chloride
• 化学式: C₆H₆FNS*ClH
• 分子量: 179.646
• InChiKey: JDSDBDMAPVLZGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.12
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  27
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯-1,1,1-三乙氧基乙烷 、 2-mercapto-5-fluoroaniline hydrochloride 以 乙醇 为溶剂， 以88%的产率得到2-(氯甲基)-5-氟-1,3-苯并噻唑
  参考文献：
  名称：

  Mylari, Banavara L.; Scott, Pamela J.; Zembrowski, William J., Synthetic Communications, 1989, vol. 19, # 16, p. 2921 - 2924

  摘要：

  DOI：

文献信息

• Discovery of 3-[(4,5,7-Trifluorobenzothiazol-2-yl)methyl]indole-<i>N</i>-acetic Acid (Lidorestat) and Congeners as Highly Potent and Selective Inhibitors of Aldose Reductase for Treatment of Chronic Diabetic Complications
  作者：Michael C. Van Zandt、Michael L. Jones、David E. Gunn、Leo S. Geraci、J. Howard Jones、Diane R. Sawicki、Janet Sredy、Jorge L. Jacot、A. Thomas DiCioccio、Tatiana Petrova、Andre Mitschler、Alberto D. Podjarny

  DOI：10.1021/jm0492094

  日期：2005.5.1

  Recent efforts to identify treatments for chronic diabetic complications have resulted in the discovery of a novel series of highly potent and selective 3-[(benzothiazol-2-yl)methyl]indole-N-alkanoic acid aldose reductase inhibitors. The lead candidate, 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat, 9) inhibits aldose reductase with an IC(50) of 5 nM, while being 5400

  最近鉴定慢性糖尿病并发症的治疗方法的努力导致发现了一系列新型的高效和选择性的3-[（（苯并噻唑-2-基）甲基]吲哚-N-链烷酸醛糖还原酶抑制剂。主要候选化合物3-[（（4,5,7-三氟苯并噻唑-2-基）甲基]吲哚-N-乙酸（利多司他，9）抑制醛糖还原酶，IC（50）为5 nM，是5400倍对醛还原酶的活性较低，醛还原酶是一种与活性醛解毒有关的酶。在为期5天的STZ诱导的糖尿病大鼠模型中，它可降低神经和晶状体山梨糖醇的水平，ED（50）分别为1.9和4.5 mg / kg / d po。在3个月的糖尿病干预模型中（糖尿病1个月，随后2个月以5 mg / kg / d po进行药物治疗），相对于糖尿病对照，它可以使多元醇正常化，并减少运动神经传导速度不足59％。它具有良好的药代动力学特征（F，82％; t（1/2），5.6 h; Vd，0.694 L / kg），并且在目标组织中的良好药物渗透
• Methods for reducing uric acid levels
  申请人：——

  公开号：US20010044437A1

  公开（公告）日：2001-11-22

  Disclosed are methods of reducing serum uric acid levels, the methods comprising administration of substituted indolealkanoic acids to patients in need of such treatment. Also disclosed are such compounds useful in the treatment of gout and related diseases. Also disclosed are pharmaceutical compositions containing the compounds.

  揭示了降低血清尿酸水平的方法，该方法包括向需要此类治疗的患者施用取代的吲哚烷基酸。还揭示了这些化合物在痛风和相关疾病治疗中的用途。还揭示了含有这些化合物的药物组合物。
• Process for preparing chloromethyl thiazoles or oxazoles, and
  申请人：Pfizer Inc.

  公开号：US04723010A1

  公开（公告）日：1988-02-02

  Chloromethyl group substituted heterocyclic compounds of the formulae ##STR1## wherein X is O or S; Y together with the two carbons to which Y is attached forms phenyl, pyridyl or pyrimidyl, each of which may be substituted by R; R is one of iodo or trifluoromethylthio or one or two of fluoro, chloro, bromo, (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy, (C.sub.1 -C.sub.4)alkylthio, (C.sub.1 -C.sub.4)alkylsulfinyl, (C.sub.1 -C.sub.4)alkylsulfonyl or trifluoromethyl; and R.sup.1 is hydrogen or R, are prepared by reacting a bifunctional compound of the formulae ##STR2## with a 2-chloro-1,1,1-tri(C.sub.1 -C.sub.6)alkoxyethane. Most of the compounds of formulae I and II are novel. These compounds are intermediates of use in the preparation of compounds having pharmaceutical activity. The 2-chloro-1,1,1-tri(C.sub.1 -C.sub.6)alkoxyethanes are prepared from the corresponding tri(C.sub.1 -C.sub.6)alkoxyethanes by chlorination with N-chlorosuccinimide or with chlorine in pyridine and a chlorohydrocarbon cosolvent.

  公式为##STR1##的氯甲基取代的杂环化合物，其中X为O或S；Y与Y连接的两个碳原子一起形成苯基、吡啶基或嘧啶基，每个基可能被R取代；R为碘或三氟甲硫基中的一个，或者是氟、氯、溴、(C.sub.1 -C.sub.4)烷基、(C.sub.1 -C.sub.4)烷氧基、(C.sub.1 -C.sub.4)烷硫基、(C.sub.1 -C.sub.4)烷基亚硫酰基、(C.sub.1 -C.sub.4)烷基磺酰基或三氟甲基中的一个或两个；R.sup.1为氢或R，通过将公式为##STR2##的双官能团化合物与2-氯-1,1,1-三(C.sub.1 -C.sub.6)烷氧基乙烷反应制备。大多数公式I和II的化合物是新颖的。这些化合物是制备具有药用活性化合物的中间体。2-氯-1,1,1-三(C.sub.1 -C.sub.6)烷氧基乙烷是通过将相应的三(C.sub.1 -C.sub.6)烷氧基乙烷与N-氯琥珀酰亚胺或在吡啶和氯气中以及氯氢烃共溶剂中氯化而制备的。
• Catechol diethers as selective PDE.sup.IV inhibitors
  申请人：Pfizer Inc.

  公开号：US05814651A1

  公开（公告）日：1998-09-29

  This invention relates to 4-substituted catechol diether compounds which are selective inhibitors of phosphodiesterase (PDE) type IV. The compounds of the present invention are useful in inhibiting PDE.sub.IV and in the treatment of AIDS, asthma, bronchitis, chronic obstructive airways disease, psoriasis, allergic rhinitis, dermatitis and other inflammatory diseases. This invention also relates to pharmaceutical compositions comprising the compounds hereof. ##STR1##

  这项发明涉及4-取代儿茶酚二醚化合物，这些化合物是选择性磷酸二酯酶（PDE）IV型抑制剂。本发明的化合物在抑制PDE.sub.IV和治疗艾滋病、哮喘、支气管炎、慢性阻塞性气道疾病、牛皮癣、过敏性鼻炎、皮炎和其他炎症性疾病方面具有用处。该发明还涉及包含这些化合物的药物组合物。
• Novel and Potent Aldose Reductase Inhibitors: 4-Benzyl- and 4-(Benzothiazol-2-ylmethyl)-3,4-dihydro-3-oxo-2H-1,4-benzothiazine-2-acetic Acid Derivatives.
  作者：Tomoji AOTSUKA、Hiroshi HOSONO、Toshio KURIHARA、Yoshiyuki NAKAMURA、Tetsuo MATSUI、Fujio KOBAYASHI

  DOI：10.1248/cpb.42.1264

  日期：——

  A number of 1, 4-benzothiazine-2-acetic acid derivatives (1, 2 and 3) and their bioisosteres (15b, 16, 18 and 20b) were synthesized and evaluated in vitro for the ability to inhibit aldose reductase (AR) in porcine lens. The compounds which exhibited potent activity in vitro were also assayed in vivo for inhibitory activity against sorbitol accumulation in the erythrocytes, sciatic nerve and lens of streptozotocin-diabetic rats. The 4-(substituted benzothiazol-2-ylmethyl)-1, 4-benzothiazine-2-acetic acid derivatives (2 and 3) showed more potent AR inhibitory activity than did the 4-(4-bromo-2-fluorobenzol)-1, 4-benzothiazine-2-acetic acid derivatives (1). 4-(4, 5, 7-Trifluorobenzothiazol-2-ylmethyl)-3, 4-dihydro-3-oxo-2H-1, 4-benzothiazine-2-acetic acid (2q, SPR-210) showed not only a potent AR-inhibitory activity in vitro (IC50 9.5×10-9 M) but also a significant reduction in sorbitol accumulation in rat sciatic nerve (ID50 0.1 mg/kg) and lens (ID50 9.8 mg/kg). Optical resolution of the racemic SPR-210 was achieved by means of a diastereomer salt method using (-)-brucine. The biological activities of both enantiomers, (+)- and (-)-SPR-210, were comparable to that of the racemate.

  合成了多种1,4-苯并噻唑-2-乙酸衍生物（1、2和3）及其生物等效物（15b、16、18和20b），并在体外评估其抑制猪眼晶状体醇糖还原酶（AR）的能力。在体外表现出强效活性的化合物，也在体内测定其对链脲菌素糖尿病大鼠的红细胞、坐骨神经和晶状体中甜菜糖积累的抑制活性。4-(取代苯并噻唑-2-亚甲基)-1,4-苯并噻唑-2-乙酸衍生物（2和3）比4-(4-溴-2-氟苯)-1,4-苯并噻唑-2-乙酸衍生物（1）显示出更强的AR抑制活性。4-(4,5,7-三氟苯并噻唑-2-亚甲基)-3,4-二氢-3-氧-2H-1,4-苯并噻唑-2-乙酸（2q, SPR-210）不仅在体外表现出强效的AR抑制活性（IC50 9.5×10^-9 M），而且在大鼠坐骨神经（ID50 0.1 mg/kg）和晶状体（ID50 9.8 mg/kg）中显著降低了甜菜糖的积累。通过使用(-)-布克因的互变异构盐方法实现了消旋体SPR-210的光学分解。两种对映体（+）-和(-)-SPR-210的生物活性与消旋体相当。