6-(2,3-dihydro-3-oxo-1,2-benzisothiazol-2-yl-1,1-dioxide)hexanoic acid | 83747-23-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 6-(2,3-dihydro-3-oxo-1,2-benzisothiazol-2-yl-1,1-dioxide)hexanoic acid
• 英文别名: 6-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)hexanoic acid；N-saccharinhexanoic acid；6-(1,1-dioxide-3-oxo-2H-benzo[d]isothiazol-2-yl)hexanoic acid；N-saccharinheaxnoic acid；6-(1,1,3-trioxo-1,2-benzothiazol-2-yl)hexanoic acid
• CAS: 83747-23-3
• 化学式: C₁₃H₁₅NO₅S
• 分子量: 297.332
• InChiKey: BMEUMLHBRFDNDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  糖精	saccharin	81-07-2	C7H5NO3S	183.188

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	6-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)-N-hydroxyhexanamide	1001349-39-8	C13H16N2O5S	312.346

反应信息

• 作为反应物：
  描述：

  6-(2,3-dihydro-3-oxo-1,2-benzisothiazol-2-yl-1,1-dioxide)hexanoic acid 在 三乙胺 、 氯甲酸异丁酯 、 盐酸羟胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.17h， 以32%的产率得到6-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl)-N-hydroxyhexanamide
  参考文献：
  名称：

  Design, synthesis and preliminary bioactivity studies of 1,2-dihydrobenzo[d]isothiazol-3-one-1,1-dioxide hydroxamic acid derivatives as novel histone deacetylase inhibitors

  摘要：

  Histone deacetylase (HDAC) is a clinically validated target for antitumor therapy. In order to increase HDAC inhibition and efficiency, we developed a novel series of saccharin hydroxamic acids as potent HDAC inhibitors. Among them, compounds 11e, 11m, 11p exhibited similar or better HDACs inhibitory activity compared with the approved drug SAHA. Further biological evaluation indicated that compound 11m had potent antiproliferative activities against MDA-MB-231 and PC-3. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.045
• 作为产物：
  描述：

  ethyl 6-(1,1-dioxide-3-oxo-2H-benzo[d]isothiazol-2-yl)hexanoate 在 盐酸 、 水 作用下， 以68%的产率得到6-(2,3-dihydro-3-oxo-1,2-benzisothiazol-2-yl-1,1-dioxide)hexanoic acid
  参考文献：
  名称：

  EP2045246

  摘要：

  公开号：

文献信息

• Design, synthesis and preliminary bioactivity evaluations of 8-hydroxyquinoline derivatives as matrix metalloproteinase (MMP) inhibitors
  作者：Chen Chen、Xinying Yang、Hao Fang、Xuben Hou

  DOI：10.1016/j.ejmech.2019.111563

  日期：2019.11

  Matrix metalloproteinases (MMPs) play important roles in many diseases including cancer. With moderate metal-binding affinity, 8-hydroxyquinoline has gained much interest in current drug design and development. Specially, it has been reported that 8-hydroxyquinoline derivatives serve as MMP-2 inhibitors with micromolar IC50 values. In the current study, a series of 8-hydroxyquinoline derivatives were

  基质金属蛋白酶（MMP）在包括癌症在内的许多疾病中都起着重要作用。具有适度的金属结合亲和力，8-羟基喹啉在当前的药物设计和开发中引起了很多兴趣。特别地，已经报道8-羟基喹啉衍生物用作具有微摩尔IC 50值的MMP-2抑制剂。在当前的研究中，设计并合成了一系列8-羟基喹啉衍生物，作为新的MMP-2和MMP-9抑制剂。活性最强的化合物5e和5h不仅对亚微摩尔水平的IC 50表现出对MMP-2 / 9的良好抑制活性，而且在A549细胞系中具有强大的抗增殖，抗侵袭和抗血管生成活性。免疫印迹也显示5e和5h下调A549细胞系中MMP-2和MMP-9的表达。此外，流式细胞术分析表明化合物5e可以促进A549细胞的体外凋亡。分子对接分析还揭示了MMP-2和MMP-9活性位点中5e的有利结合模式。
• Hypolipidemic activity of phthalimide derivatives. 3. A comparison of phthalimide and 1,2-benzisothiazolin-3-one 1,1-dioxide derivatives to phthalimidine and 1,2-benzisothiazoline 1,1-dioxide congeners
  作者：James M. Chapman、George H. Cocolas、Iris H. Hall

  DOI：10.1021/jm00356a023

  日期：1983.2

  ne 1,1-dioxide analogues for their hypolipidemic activity in mice and to compare them to their respective phthalimide congeners. In addition, a series of 1,2-benzisothiazoline 1,1-dioxide and phthalimidine analogues was prepared, and their hypolipidemic activity was compared to the phthalimide analogues. These studies show that the respective congeners of 1,2-benzisothiazolin-3-one 1,1-dioxide compared

  以前已经观察到链长为四个碳或氧原子的N-取代的邻苯二甲酰亚胺衍生物在啮齿动物中以20（mg / kg）/天ip的剂量表现出有效的降血脂活性。还观察到1,2-苯并噻唑啉-3-一1,1-二氧化物（糖精）核本身在相同剂量下具有活性。进行了一项研究，以检查一系列1,2-苯并噻唑啉-3-酮1,1-二氧化物类似物在小鼠中的降血脂活性，并将它们与各自的邻苯二甲酰亚胺同系物进行比较。此外，制备了一系列1,2-苯并噻唑啉1,1-二氧化物和邻苯二甲酰亚胺类似物，并将它们的降血脂活性与邻苯二甲酰亚胺类似物进行了比较。这些研究表明1,2-苯并噻唑啉-3-酮1，1-二氧化物在减少20（mg / kg）/天ip的雄性CF1小鼠血清甘油三酸酯和胆固醇水平方面优于邻苯二甲酰亚胺同类物。在糖精衍生物中，3-氧-1,2-苯并噻唑啉-2-丙酸1,1-二氧化物最有效地降低16天服药后的血清胆固醇水平53％，3-氧-1,2-苯并噻唑啉服用14天后，-2-戊酸1
• DERIVATIVES OF BENZO[D] ISOTHIAZOLES AS HISTONE DEACETYLASE INHIBITORS
  申请人：Universidad De Granada

  公开号：EP2045246A1

  公开（公告）日：2009-04-08

  The invention relates to derivatives of benzo[d]isothiazoles as histone deacetylase inhibitors, selected from among compounds of general formula (Ia) and (Ib) or one of the salts thereof, particularly one of the pharmaceutically acceptable salts thereof, or one of the corresponding solvates thereof. These compounds are histone deacetylase enzyme inhibitors and are suitable as pharmacologically active agents in a medicament for the treatment and/or prophylaxis of disorders or diseases associated to histone deacetylases. The invention also describes a process for obtaining the mentioned compounds and the pharmaceutical compositions containing them

  本发明涉及作为组蛋白去乙酰化酶抑制剂的苯并[d]异噻唑衍生物，它们选自通式(Ia)和(Ib)化合物或其盐类之一，特别是其药学上可接受的盐类之一，或其相应的溶解物之一。这些化合物是组蛋白去乙酰化酶抑制剂，可作为药理活性剂用于治疗和/或预防与组蛋白去乙酰化酶有关的紊乱或疾病。本发明还描述了获得上述化合物和含有这些化合物的药物组合物的过程
• Synthesis and in vivo evaluation of non-hepatotoxic acetaminophen analogs
  作者：Anthony L. Vaccarino、Dennis Paul、Pranab K. Mukherjee、Elena B. Rodríguez de Turco、Victor L. Marcheselli、Liang Xu、Mark L. Trudell、J.M. Minguez、M.P. Matía、Carlos Sunkel、Julio Alvarez-Builla、Nicolas G. Bazan

  DOI：10.1016/j.bmc.2006.07.054

  日期：2007.3

  A series of acetaminophen (APAP) analogs, 2-(1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)-N-(4-hydroxyphenyl)alkanecarboxamides, bearing a heterocyclic moiety linked to the p-acylaminophenol fragment, were prepared in a general project to develop APAP analogs with modulated pharmacokinetic profiles. Unexpectedly, the products described maintained the in vivo analgesic profile, while the characteristic hepatotoxicity of APAP was consistently reduced. One of the products, 5a, was studied in vivo in comparison with APAP. Compound 5a displayed an analgesic efficacy comparable to that of APAP. A relatively high acute oral dose of 5a (6 mmol/kg) produced no measurable toxicity, whereas the equimolar dose of APAP increased transaminase activity, depleted hepatic and renal glutathione, and resulted in mortality. In human hepatocytes (HEPG-2) and in human primary cultures of normal liver cells, APAP, but not 5a, was associated with apoptotic cell death, Fas-ligand up-regulation, and CAR (constitutive androstane receptor) activation, contributing to a favorable safety profile of 5a as an orally delivered analgesic. (c) 2006 Elsevier Ltd. All rights reserved.
• CHAPMAN, J. M. ,, JR;COCOLAS, G. H.;HALL, I. H., J. MED. CHEM., 1983, 26, N 2, 243-246
  作者：CHAPMAN, J. M. ,, JR、COCOLAS, G. H.、HALL, I. H.

  DOI：——

  日期：——