己醛,2-丁基-2-[[(甲磺酰)氧代]甲基]- | 197378-59-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 中文名称: 己醛,2-丁基-2-[[(甲磺酰)氧代]甲基]-
• 英文名称: 2-butyl-2-formylhexyl methanesulfonate
• 英文别名: (2-Butyl-2-formylhexyl) methanesulfonate
• CAS: 197378-59-9
• 化学式: C₁₂H₂₄O₄S
• 分子量: 264.386
• InChiKey: GIETUGHQOUVHNX-UHFFFAOYSA-N

物化性质

• 沸点：
  386.9±25.0 °C(Predicted)
• 密度：
  1.051±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  10
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  68.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  己醛,2-丁基-2-[[(甲磺酰)氧代]甲基]- 在 lithium sulfide 、 bromotriphenylphosphonium bromide 、 二异丁基氢化铝 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.67h， 生成 2-[[[2-(bromomethyl)-4-fluorophenyl]sulfonyl]methyl]-2-butylhexanal
  参考文献：
  名称：

  Discovery of Potent, Nonsystemic Apical Sodium-Codependent Bile Acid Transporter Inhibitors (Part 2)

  摘要：

  In the preceding paper several compounds were reported as potent apical. sodium-codependent bile acid transporter (ASBT) inhibitors. Since the primary site for active bile acid reabsorption is via ASBT, which is localized on the luminal surface of the distal ileum, we reasoned that a nonsystemic inhibitor would be desirable to minimize or eliminate potential systemic side effects of an absorbed drug. To ensure bioequivalency and product stability, it was also essential that we identify a nonhygroscopic inhibitor in its most stable crystalline form. A series of benzothiepines were prepared to refine the structure-activity relationship of the substituted phenyl ring at the 5-position of benzothiepine ring and to identify potent, crystalline, nonhygroscopic, and efficacious ASBT inhibitors with low systemic exposure.

  DOI：

  10.1021/jm0402162
• 作为产物：
  描述：

  二-正丁基乙醛 在 三乙胺 作用下， 反应 18.0h， 生成 己醛,2-丁基-2-[[(甲磺酰)氧代]甲基]-
  参考文献：
  名称：

  Discovery of Potent, Nonsystemic Apical Sodium-Codependent Bile Acid Transporter Inhibitors (Part 1)

  摘要：

  Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codependent bile acid transporter (ASBT) inhibitor would lower the serum cholesterol without the potential systemic side effects of an absorbed drug. A series of novel benzothiepines (3R,3R'-2,3,4,5-tetrahydro-5-aryl-l-benzothiepin-4-ol 1,1-dioxides) were synthesized and tested for their ability to inhibit the apical sodium dependent bile acid transport (ASBT)-mediated uptake of [C-14]taurocholate (TC) in H14 cells. A 3R,4.R,5R13S,4S,5S racemate was found to have greater potency than the other three possible racemates. Addition of electron-donating groups such as a dimethylamino substituent at the 7 position greatly enhanced potency, and incorporation of a long-chain quaternary ammonium substituent on the 5-phenyl ring was useful in minimizing systemic exposure of this locally active ASBT inhibitor while also increasing water solubility and maintaining potency. The reported results describe the synthesis and SAR development of this benzothiepine class of ASBT inhibitors resulting in an 6000-fold improvement in ASBT inhibition with desired minimal systemic exposure of this locally acting drug candidate.

  DOI：

  10.1021/jm040215+

文献信息

• Novel benzothiazepine and bensothiepine compounds
  申请人：Sasahara Takehiko

  公开号：US20070190041A1

  公开（公告）日：2007-08-16

  A pharmaceutical useful as a therapeutic agent and a preventive agent for hyperlipemia, and a pharmaceutical useful as a therapeutic agent and a preventive agent for hepatic disorders associated with cholestasis, particularly, primary biliary cirrhosis and primary sclerosing cholangitis, and a pharmaceutical useful as a therapeutic agent and a preventive agent for obesity, fatty liver and steatohepatitis are provided. A benzothiazepine or benzothiepine compound represented by the following formula (1A) having a thioamide bond and a quaternary ammonium substitutent:

  提供了一种药物，可用作治疗和预防高脂血症的治疗剂和预防剂，以及一种药物，可用作治疗和预防与胆汁淤积有关的肝脏疾病，特别是原发性胆汁性肝硬化和原发性硬化性胆管炎的治疗剂和预防剂，以及一种药物，可用作治疗和预防肥胖症、脂肪肝和脂肪性肝炎的治疗剂和预防剂。化合物的苯并噻吩或苯并噻环代表如下式（1A），具有硫酰胺键和季铵取代基：
• NOVEL BENZOTHIAZEPINE AND BENZOTHIEPINE COMPOUNDS
  申请人：Asahi Kasei Pharma Corporation

  公开号：EP1719768B1

  公开（公告）日：2012-04-25
• US7973030B2
  申请人：——

  公开号：US7973030B2

  公开（公告）日：2011-07-05
• Discovery of Potent, Nonsystemic Apical Sodium-Codependent Bile Acid Transporter Inhibitors (Part 1)
  作者：Samuel J. Tremont、Len F. Lee、Horng-Chih Huang、Bradley T. Keller、Shyamal C. Banerjee、Scott R. Both、Andrew J. Carpenter、Ching-Cheng Wang、Danny J. Garland、Wei Huang、Claude Jones、Kevin J. Koeller、Steve A. Kolodziej、James Li、Robert E. Manning、Matthew W. Mahoney、Raymond E. Miller、Deborah A. Mischke、Nigam P. Rath、Theresa Fletcher、Emily J. Reinhard、Michael B. Tollefson、William F. Vernier、Grace M. Wagner、Steve R. Rapp、Judy Beaudry、Kevin Glenn、Karen Regina、Joe R. Schuh、Mark E. Smith、Jay S. Trivedi、David B. Reitz

  DOI：10.1021/jm040215+

  日期：2005.9.1

  Elevated plasma levels of low-density lipoprotein (LDL) cholesterol are a major risk factor for atherosclerosis leading to coronary artery disease (CAD), which remains the main cause of mortality in Western society. We believe that by preventing the reabsorption of bile acids, a minimally absorbed apical sodium-codependent bile acid transporter (ASBT) inhibitor would lower the serum cholesterol without the potential systemic side effects of an absorbed drug. A series of novel benzothiepines (3R,3R'-2,3,4,5-tetrahydro-5-aryl-l-benzothiepin-4-ol 1,1-dioxides) were synthesized and tested for their ability to inhibit the apical sodium dependent bile acid transport (ASBT)-mediated uptake of [C-14]taurocholate (TC) in H14 cells. A 3R,4.R,5R13S,4S,5S racemate was found to have greater potency than the other three possible racemates. Addition of electron-donating groups such as a dimethylamino substituent at the 7 position greatly enhanced potency, and incorporation of a long-chain quaternary ammonium substituent on the 5-phenyl ring was useful in minimizing systemic exposure of this locally active ASBT inhibitor while also increasing water solubility and maintaining potency. The reported results describe the synthesis and SAR development of this benzothiepine class of ASBT inhibitors resulting in an 6000-fold improvement in ASBT inhibition with desired minimal systemic exposure of this locally acting drug candidate.
• Discovery of Potent, Nonsystemic Apical Sodium-Codependent Bile Acid Transporter Inhibitors (Part 2)
  作者：Horng-Chih Huang、Samuel J. Tremont、Len F. Lee、Bradley T. Keller、Andrew J. Carpenter、Ching-Cheng Wang、Shyamal C. Banerjee、Scott R. Both、Theresa Fletcher、Danny J. Garland、Wei Huang、Claude Jones、Kevin J. Koeller、Steve A. Kolodziej、James Li、Robert E. Manning、Matthew W. Mahoney、Raymond E. Miller、Deborah A. Mischke、Nigam P. Rath、Emily J. Reinhard、Michael B. Tollefson、William F. Vernier、Grace M. Wagner、Steve R. Rapp、Judy Beaudry、Kevin Glenn、Karen Regina、Joe R. Schuh、Mark E. Smith、Jay S. Trivedi、David B. Reitz

  DOI：10.1021/jm0402162

  日期：2005.9.1

  In the preceding paper several compounds were reported as potent apical. sodium-codependent bile acid transporter (ASBT) inhibitors. Since the primary site for active bile acid reabsorption is via ASBT, which is localized on the luminal surface of the distal ileum, we reasoned that a nonsystemic inhibitor would be desirable to minimize or eliminate potential systemic side effects of an absorbed drug. To ensure bioequivalency and product stability, it was also essential that we identify a nonhygroscopic inhibitor in its most stable crystalline form. A series of benzothiepines were prepared to refine the structure-activity relationship of the substituted phenyl ring at the 5-position of benzothiepine ring and to identify potent, crystalline, nonhygroscopic, and efficacious ASBT inhibitors with low systemic exposure.