1-mercapto-1,1-pentamethylenethan-2-ol | 212574-88-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醇
• 英文名称: 1-mercapto-1,1-pentamethylenethan-2-ol
• 英文别名: (1-Sulfanylcyclohexyl)methanol；(1-sulfanylcyclohexyl)methanol
• CAS: 212574-88-4
• 化学式: C₇H₁₄OS
• 分子量: 146.254
• InChiKey: IVIKKGRVMUVRMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  21.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-mercapto-1,1-pentamethylenethan-2-ol 在 吡啶 、 sulfur 、 N,N-二异丙基乙胺 、 三氯化磷 作用下， 以 乙腈 、 苯 为溶剂， 反应 12.58h， 生成 5’-O-DMT-N²-isobutyryl-2’-deoxyguanosine-3’-O-(2-thio-4,4-pentamethylene-1,3,2-oxathiaphospholane)
  参考文献：
  名称：

  Deoxyribonucleoside 3‘-O-(2-Thio- and 2-Oxo-“spiro”-4,4-pentamethylene-1,3,2-oxathiaphospholane)s:  Monomers for Stereocontrolled Synthesis of Oligo(deoxyribonucleoside phosphorothioate)s and Chimeric PS/PO Oligonucleotides

  摘要：

  New monomers, 5'-O-DMT-deoxyribonucleoside 3'-O-(2-thio-"spiro"-4,4-pentamethylene-1,3,2-oxathiaphospholane)s, were prepared and used for the stereocontrolled synthesis of PS-Oligos via the oxathiaphospholane approach. These monomers and their Zero analogues were used for the synthesis of "chimeric" constructs (PS/PO-Oligos) possessing phosphate and P-stereodefined phosphorothioate internucleotide linkages. The yield of a single coupling step is approximately 92-95%, and resulting oligomers are free of nucleobase- and sugar-phosphorothioate backbone modifications. Thermal dissociation studies showed that for heteroduplexes formed by [R-P]-, [S-P]-, or [mix]-PS/PO-T-10 with dA(12), dA(30), Or poly(dA), for each template, the melting temperatures, as well as free Gibbs' energies of dissociation process, are virtually equal. Stereochemical evidence derived from crystallographic analysis of one of the oxathiaphospholane monomers strongly supports the participation of pentacoordinate intermediates in the mechanism of the oxathiaphospholane ring-opening condensation.

  DOI：

  10.1021/ja973801j
• 作为产物：
  描述：

  1-[(2-formylcyclohexyl)disulfanyl]cyclohexanecarbaldehyde 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 1-mercapto-1,1-pentamethylenethan-2-ol
  参考文献：
  名称：

  双氯芬酸的亚硝基硫醇酯：保留胃肠道的前药的合成和药理学表征。

  摘要：

  尽管其广泛使用，双氯芬酸仍具有非甾体抗炎药（NSAIDs）常见的胃肠道疾病，可通过同时服用胃肠道细胞保护剂（如一氧化氮（NO））来减轻。已合成了一系列含有亚硝基硫醇（-S-NO）部分作为NO供体官能团的新型双氯芬酸酯，并在体内对其生物利用度，药理活性和胃刺激性进行了评估。所有S-NO-双氯芬酸衍生物均作为口服生物可利用的前药，对小鼠口服后15分钟内在血浆中产生大量的双氯芬酸。在等摩尔口服剂量下，S-NO-双氯芬酸衍生物（20a-21b）在角叉菜胶诱发的爪水肿试验和小鼠苯基苯醌诱发的扭体试验中显示出与双氯芬酸相当的大鼠抗炎和镇痛活性。所有测试的S-NO-双氯芬酸衍生物（20a-21b）都是保胃的，与大鼠中等摩尔剂量的双氯芬酸引起的胃损害相比，它们引起的胃损害明显更少。双氯芬酸的亚硝基硫醇酯包含一类新的NO供体化合物，具有作为非甾体类抗炎药的治疗潜力，具有增强的胃安全性。所有测试的S-NO-双

  DOI：

  10.1021/jm000178w

文献信息

• Exploration of Pyrrolobenzodiazepine (PBD)-Dimers Containing Disulfide-Based Prodrugs as Payloads for Antibody–Drug Conjugates
  作者：Zhonghua Pei、Chunjiao Chen、Jinhua Chen、Josefa dela Cruz-Chuh、Reginald Delarosa、Yuzhong Deng、Aimee Fourie-O’Donohue、Isabel Figueroa、Jun Guo、Weiwei Jin、S. Cyrus Khojasteh、Katherine R. Kozak、Brandon Latifi、James Lee、Guangmin Li、Eva Lin、Liling Liu、Jiawei Lu、Scott Martin、Carl Ng、Trung Nguyen、Rachana Ohri、Gail Lewis Phillips、Thomas H. Pillow、Rebecca K. Rowntree、Nicola J. Stagg、David Stokoe、Sheila Ulufatu、Vishal A. Verma、John Wai、Jing Wang、Keyang Xu、Zijin Xu、Hui Yao、Shang-Fan Yu、Donglu Zhang、Peter S. Dragovich

  DOI：10.1021/acs.molpharmaceut.8b00431

  日期：2018.9.4

  (PBD) monomers containing various disulfide-based prodrugs were evaluated for their ability to undergo activation (disulfide cleavage) in vitro in the presence of either glutathione (GSH) or cysteine (Cys). A good correlation was observed between in vitro GSH stability and in vitro cytotoxicity toward tumor cell lines. The prodrug-containing compounds were typically more potent against cells with relatively

  许多含有各种二硫化物系前药的细胞毒性pyrrolobenzodiazepine（PBD）的单体对它们进行活化（二硫化物断开）的能力进行了评价在体外在任一谷胱甘肽（GSH）或半胱氨酸（Cys）的存在。在体外GSH稳定性和体外对肿瘤细胞系的细胞毒性之间观察到良好的相关性。含前药的化合物通常对细胞内GSH含量较高的细胞（例如KPL-4细胞）更有效。随后，由PBD二聚体构建了几种抗体-药物结合物（ADC），这些结合物结合了选定的基于二硫键的前药。此类HER2偶联物在体外对KPL-4细胞表现出有效的抗增殖活性以抗原依赖性方式。然而，大多数这样的实体中所含的二硫键前药对来自各种物种的全血来说是不稳定的。含有巯基苯酚的二硫键前药的一种靶向HER2的偶联物是这种稳定性趋势的例外。它在KPL-4体内功效模型中显示出强效活性，其活性比相应的母体ADC所展示的活性弱约三倍。与不含前药的母体ADC相比，相同的含前
• Nucleoside 3′-<i>O</i>-(2-Oxo-“<i>Spiro</i>”-4.4-Pentamethylene-1.3.2-Oxathiaphospholane)S: Monomers For Stereocontrolled Synthesis Of Oligo(Nucleoside Phosphorothioate/Phosphate)S
  作者：Boleslaw Karwowski、Piotr Guga、Anna Kobylariska、Wojciech J. Stec

  DOI：10.1080/07328319808004710

  日期：1998.9

  Attempts at synthesis of "chimeric" oligonucleotide constructs (PO/PS-Oligos) possessing phosphate and P-stereodefined phosphorothioate internucleotide linkages via combined phosphoramidite/oxathiaphospholane methods were unsuccessful. Therefore, novel monomers for oxathiaphospholane method, namely 5'-O-DMT-deoxyribonucleoside 3'-O-(2-oxo-spiro-4.4-pentamethylene-1.3.2-oxathiaphospholane)s, were prepared and used together with their diastereomerically pure 2-thio analogues for the stereocontrolled synthesis off "chimeric" oligonucleotide constructs (PO/PS-Oligos).
• Deoxyribonucleoside 3‘-<i>O</i>-(2-Thio- and 2-Oxo-“spiro”-4,4-pentamethylene-1,3,2-oxathiaphospholane)s:  Monomers for Stereocontrolled Synthesis of Oligo(deoxyribonucleoside phosphorothioate)s and Chimeric PS/PO Oligonucleotides
  作者：Wojciech J. Stec、Bolesław Karwowski、Małgorzata Boczkowska、Piotr Guga、Maria Koziołkiewicz、Marek Sochacki、Michał W. Wieczorek、Jarosław Błaszczyk

  DOI：10.1021/ja973801j

  日期：1998.7.1

  New monomers, 5'-O-DMT-deoxyribonucleoside 3'-O-(2-thio-"spiro"-4,4-pentamethylene-1,3,2-oxathiaphospholane)s, were prepared and used for the stereocontrolled synthesis of PS-Oligos via the oxathiaphospholane approach. These monomers and their Zero analogues were used for the synthesis of "chimeric" constructs (PS/PO-Oligos) possessing phosphate and P-stereodefined phosphorothioate internucleotide linkages. The yield of a single coupling step is approximately 92-95%, and resulting oligomers are free of nucleobase- and sugar-phosphorothioate backbone modifications. Thermal dissociation studies showed that for heteroduplexes formed by [R-P]-, [S-P]-, or [mix]-PS/PO-T-10 with dA(12), dA(30), Or poly(dA), for each template, the melting temperatures, as well as free Gibbs' energies of dissociation process, are virtually equal. Stereochemical evidence derived from crystallographic analysis of one of the oxathiaphospholane monomers strongly supports the participation of pentacoordinate intermediates in the mechanism of the oxathiaphospholane ring-opening condensation.
• Nitrosothiol Esters of Diclofenac:  Synthesis and Pharmacological Characterization as Gastrointestinal-Sparing Prodrugs^,
  作者：Upul K. Bandarage、Liqing Chen、Xinqin Fang、David S. Garvey、Alicia Glavin、David R. Janero、L. Gordon Letts、Gregory J. Mercer、Joy K. Saha、Joseph D. Schroeder、Matthew J. Shumway、S. William Tam

  DOI：10.1021/jm000178w

  日期：2000.10.1

  irritation. All S-NO-diclofenac derivatives acted as orally bioavailable prodrugs, producing significant levels of diclofenac in plasma within 15 min after oral administration to mice. At equimolar oral doses, S-NO-diclofenac derivatives (20a-21b) displayed rat antiinflammatory and analgesic activities comparable to those of diclofenac in the carrageenan-induced paw edema test and the mouse phenylbenzoquinone-induced

  尽管其广泛使用，双氯芬酸仍具有非甾体抗炎药（NSAIDs）常见的胃肠道疾病，可通过同时服用胃肠道细胞保护剂（如一氧化氮（NO））来减轻。已合成了一系列含有亚硝基硫醇（-S-NO）部分作为NO供体官能团的新型双氯芬酸酯，并在体内对其生物利用度，药理活性和胃刺激性进行了评估。所有S-NO-双氯芬酸衍生物均作为口服生物可利用的前药，对小鼠口服后15分钟内在血浆中产生大量的双氯芬酸。在等摩尔口服剂量下，S-NO-双氯芬酸衍生物（20a-21b）在角叉菜胶诱发的爪水肿试验和小鼠苯基苯醌诱发的扭体试验中显示出与双氯芬酸相当的大鼠抗炎和镇痛活性。所有测试的S-NO-双氯芬酸衍生物（20a-21b）都是保胃的，与大鼠中等摩尔剂量的双氯芬酸引起的胃损害相比，它们引起的胃损害明显更少。双氯芬酸的亚硝基硫醇酯包含一类新的NO供体化合物，具有作为非甾体类抗炎药的治疗潜力，具有增强的胃安全性。所有测试的S-NO-双