3α-tertbutyldimethylsilyloxy-7α,12α-dihydroxy-5β-cholan-24-oic acid | 75897-59-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3α-tertbutyldimethylsilyloxy-7α,12α-dihydroxy-5β-cholan-24-oic acid
• 英文别名: 3α-(t-butyldimethylsilyloxy)-7α,12α-dihydroxy-5β-cholan-24-oic acid；3alpha-(t-Butyldimethylsilyloxy)-7alpha,12alpha-dihydroxy-5beta-cholan-24-oic acid；(4R)-4-[(3R,5R,7R,8R,9S,10S,12S,13R,14S,17R)-3-[tert-butyl(dimethyl)silyl]oxy-7,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid
• CAS: 75897-59-5
• 化学式: C₃₀H₅₄O₅Si
• 分子量: 522.841
• InChiKey: VVNXTBIIXXNPCX-KAXFFRCJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.48
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.97
• 拓扑面积：
  87
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3α-tertbutyldimethylsilyloxy-7α,12α-dihydroxy-5β-cholan-24-oic acid 、 贝母素乙 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.5h， 以58.9%的产率得到5α,14α-cevanin-6-O-20β-hydroxy-3β-yl-3α-tertbutyldimethylsilyloxy-7α,12α-dihydroxy-5β-cholan-24-oate
  参考文献：
  名称：

  Structural analysis and antitussive evaluation of five novel esters of verticinone and bile acids

  摘要：

  Shedan-Chuanbei powder, a complex of traditional Chinese medicine preparation, which consists of Snake Bile (Chinese name "Shedan") and Fritillariae Cirrhosae (Chinese name "Chuanbei"), is the most popular antitussive and expectorant formulation in Chinese communities. However, the clinical application of Shedan-Chuanbei powder is now stringently limited because of the shortage of the two crude medicinal materials, especially for the sake of animal protection. In addition, the inherent defects of the most of the complex of traditional Chinese medicine such as the indistinct basal phartnacodynamic materials and the difficulties in quality control had blocked them heading into the international medicinal market. So we attempted to seek new substitute for Shedan-Chuanbei powder for antitussive drugs. In order to gain some new compounds with better bioactivity and attenuated toxicity, we tried to combine two kinds of drugs through ester bond. Enlightened with "combination principle" in drug discovery, we synthesized five novel esters of verticinone and bile acids, both of which are the major bioactive components in Shedan-Chuanbei powder. We then evaluated the antitussive activity and the acute toxicity of the five ester-linked compounds. The five ester-linked Compounds had much more potent antitussive activity and expectorant activity than single bile acids at the same doses, and had equivalent antitussive activity and expectorant activity in comparison with about double moles dose of the monomer verticinone. Especially, cholic acid-verticinone ester had much more potent antitussive effects than the monomer verticinone or cholic acid at the same dose. A further acute toxicity study showed that the LD50 values of the five ester-linked compounds exceeded 3.5 g/kg by intraperitoneal injection in mice. Based on the studies of pharmacology and acute toxicity, the five ester-linked compounds have synergic pharmacodynamic action and attenuated toxicity compared with single verticinone and single bile acids. (C) 2008 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2008.12.007
• 作为产物：
  描述：

  methyl 3α-O-(tert-butyl-dimethylsilanyloxy)-7α,12α-dihydroxy-5β-cholan-24-oate 在 sodium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 12.0h， 以93.8%的产率得到3α-tertbutyldimethylsilyloxy-7α,12α-dihydroxy-5β-cholan-24-oic acid
  参考文献：
  名称：

  Structural analysis and antitussive evaluation of five novel esters of verticinone and bile acids

  摘要：

  Shedan-Chuanbei powder, a complex of traditional Chinese medicine preparation, which consists of Snake Bile (Chinese name "Shedan") and Fritillariae Cirrhosae (Chinese name "Chuanbei"), is the most popular antitussive and expectorant formulation in Chinese communities. However, the clinical application of Shedan-Chuanbei powder is now stringently limited because of the shortage of the two crude medicinal materials, especially for the sake of animal protection. In addition, the inherent defects of the most of the complex of traditional Chinese medicine such as the indistinct basal phartnacodynamic materials and the difficulties in quality control had blocked them heading into the international medicinal market. So we attempted to seek new substitute for Shedan-Chuanbei powder for antitussive drugs. In order to gain some new compounds with better bioactivity and attenuated toxicity, we tried to combine two kinds of drugs through ester bond. Enlightened with "combination principle" in drug discovery, we synthesized five novel esters of verticinone and bile acids, both of which are the major bioactive components in Shedan-Chuanbei powder. We then evaluated the antitussive activity and the acute toxicity of the five ester-linked compounds. The five ester-linked Compounds had much more potent antitussive activity and expectorant activity than single bile acids at the same doses, and had equivalent antitussive activity and expectorant activity in comparison with about double moles dose of the monomer verticinone. Especially, cholic acid-verticinone ester had much more potent antitussive effects than the monomer verticinone or cholic acid at the same dose. A further acute toxicity study showed that the LD50 values of the five ester-linked compounds exceeded 3.5 g/kg by intraperitoneal injection in mice. Based on the studies of pharmacology and acute toxicity, the five ester-linked compounds have synergic pharmacodynamic action and attenuated toxicity compared with single verticinone and single bile acids. (C) 2008 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2008.12.007

文献信息

• Ligand analog-irreversible enzyme inhibitor conjugates and methods for
  申请人：Abbott Laboratories

  公开号：US04273866A1

  公开（公告）日：1981-06-16

  The present invention encompasses a method for determining ligands in test samples comprising intermixing with the test sample a ligand analog-irreversible enzyme inhibitor conjugate and a binding protein bindable to the ligand and the ligand analog-irreversible enzyme inhibitor conjugate and wherein the amount of ligand analog-irreversible enzyme inhibitor conjugate bound by the binding protein is related to the amount of ligand in the test sample, said binding protein inactivating the irreversible enzyme inhibitor when bound to the ligand analog portion of the conjugate; intermixing an enzyme which is irreversibly inhibited by the ligand analog-irreversible enzyme inhibitor conjugate unbound by the binding protein; and intermixing substrate to the enzyme and monitoring the enzyme substrate reaction. The invention also includes ligand analog-irreversible enzyme inhibitor conjugates useful as reagents in practicing the method. Methods and reagents of the present are particularly useful in determining drugs, hormones, and the like in biological fluids.

  本发明涵盖了一种测定试样中配体的方法，包括将配体类似物-不可逆酶抑制剂共轭物和可与配体及配体类似物-不可逆酶抑制剂共轭物结合的结合蛋白与试样混合，其中结合蛋白结合的配体类似物-不可逆酶抑制剂共轭物的数量与试样中配体的数量相关，当结合蛋白与共轭物的配体类似物部分结合时，结合蛋白失活不可逆酶抑制剂。将未被结合蛋白结合的配体类似物-不可逆酶抑制剂与酶混合，该酶被配体类似物-不可逆酶抑制剂不可逆抑制，然后将底物混合到酶中并监测酶底物反应。本发明还包括作为试剂在实践该方法中有用的配体类似物-不可逆酶抑制剂共轭物。本发明的方法和试剂在测定生物液中的药物、激素等方面特别有用。
• Ligand analog-irreversible enzyme inhibitor conjugates
  申请人：Abbott Laboratories

  公开号：US04550163A1

  公开（公告）日：1985-10-29

  The present invention encompasses a method for determining ligands in test samples comprising intermixing with the test sample a ligand analog-irreversible enzyme inhibitor conjugate and a binding protein bindable to the ligand and the ligand analog-irreversible enzyme inhibitor conjugate and wherein the amount of ligand analog-irreversible enzyme inhibitor conjugate bound by the binding protein is related to the amount of ligand in the test sample, said binding protein inactivating the irreversible enzyme inhibitor when bound to the ligand analog portion of the conjugate; intermixing an enzyme which is irreversibly inhibited by the ligand analog-irreversible enzyme inhibitor conjugate unbound by the binding protein; and intermixing substrate to the enzyme and monitoring the enzyme substrate reaction. The invention also includes ligand analog-irreversible enzyme inhibitor conjugates useful as reagents in practicing the method. Methods and reagents of the present are particularly useful in determining drugs, hormones, and the like in biological fluids.

  本发明涵盖了一种测定试样中配体的方法，包括将配体类似物-不可逆酶抑制剂共轭物和可结合于配体和配体类似物-不可逆酶抑制剂共轭物的结合蛋白与试样混合，其中结合蛋白结合的配体类似物-不可逆酶抑制剂共轭物的数量与试样中配体的数量相关，所述结合蛋白在结合到共轭物的配体类似物部分时失活不可逆酶抑制剂；混合一种被配体类似物-不可逆酶抑制剂共轭物未结合的不可逆酶抑制的酶；混合底物到酶中，并监测酶底物反应。本发明还包括作为试剂在实践该方法中有用的配体类似物-不可逆酶抑制剂共轭物。本发明的方法和试剂特别适用于测定生物液体中的药物、激素等。