匹伐他汀杂质76 | 123185-91-1

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 匹伐他汀杂质76
• 英文名称: cis-(4R,6S)-2,2-dimethyl-6-formyl-1,3-dioxane-4-acetic acid
• 英文别名: 2-[(4R,6S)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid
• CAS: 123185-91-1
• 化学式: C₉H₁₄O₅
• 分子量: 202.207
• InChiKey: HCQRTPSDEFPKCT-RQJHMYQMSA-N

物化性质

• 沸点：
  348.2±32.0 °C(Predicted)
• 密度：
  1.220±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  匹伐他汀杂质76 在 盐酸 、 sodium hydroxide 、 正丁基锂 、 1-环已基-2-吗啉乙基碳二亚胺对甲苯磺酸盐 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 36.75h， 生成 BMY-21950
  参考文献：
  名称：

  Synthesis, biological profile, and quantitative structure-activity relationship of a series of novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors

  摘要：

  A series of 9,9-bis(4-fluorophenyl)-3,5-dihydroxy-8-(alkyltetrazol-5-yl)- 6,8-nonadienoic acid derivatives 1 were synthesized and found to inhibit competitively the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The analogues having 1N-methyltetrazol-5-yl attached to the C8-position (3a, 4a, R1 = R2 = F) are the most active in suppressing cholesterol biosynthesis in both in vitro and in vivo models: the IC50 for the chiral form of 3a is 19 nM, Ki = 4.3 x 10(-9)M when Km for HMG-CoA is 28 x 10(-6) M;1 the ED50 (oral) value corresponding to the lactone derivative (4a, BMY 22089) is approximately 0.1 mg/kg. Further, BMY 21950 is nearly 2 orders of magnitude more active in parenchymal heptaocytes, from which most of the serum cholesterol originates, than in other cell preparations (such as spleen, testes, ileum, adrenal, and ocular lens epithelial cells; Table III). This apparent tissue specificity may be highly beneficial since the blocking of cholesterol biosynthesis in other vital organs could eventually lead to undesirable side effects. In addition to the chemical synthesis and biological evaluation, a theoretical study aimed at relating the HMG-CoA reductase inhibitory potency to the three-dimensional structure of the inhibitors was undertaken. With a combination of molecular mapping and 3D-QSAR techniques, it was possible to determine a logical candidate for the conformation of the bound inhibitor and to quantitatively relate inhibitory potency to the shape and size of both the binding site and the C8-substituent.

  DOI：

  10.1021/jm00173a013
• 作为产物：
  描述：

  tert-butyl (E)-5-hydroxy-3-oxo-7-phenylhept-6-enoate 在 sodium tetrahydroborate 、 三乙基硼 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 匹伐他汀杂质76
  参考文献：
  名称：

  HMG-CoA还原酶的有效，组织选择性合成抑制剂。

  摘要：

  DOI：

  10.1021/jm00129a004

文献信息

• NOVEL INTERMEDIATES FOR THE PREPARATION OF HMG-CoA REDUCTASE INHIBITORS
  申请人：Pandya Vishwesh Pravinchandra

  公开号：US20130150579A1

  公开（公告）日：2013-06-13

  The present invention provides a process for preparing novel intermediates of Formula wherein, R 1 can be hydrogen, C 1 -C 4 alkyl, halogen, nitro, hydroxy, or C 1 -C 4 alkoxy; R x can be selected from hydrophobic residue of HMG-CoA reductase inhibitors; which can be effectively used for the preparation of HMG-CoA reductase inhibitors such as rosuvastatin and pharmaceutically acceptable salts thereof.

  本发明提供了一种制备新型中间体的过程，其中，R1可以是氢、C1-C4烷基、卤素、硝基、羟基或C1-C4烷氧基；Rx可以选择自HMG-CoA还原酶抑制剂的疏水残基；可以有效用于制备HMG-CoA还原酶抑制剂，如罗伐司汀及其药用可接受的盐。
• Process for Preparing Pitavastatin, Intermediates and Pharmaceuctically Acceptable Salts Thereof
  申请人：Satyanarayana Reddy Manne

  公开号：US20120016129A1

  公开（公告）日：2012-01-19

  Processes for preparing pravastatin, intermediates and pharmaceutically acceptable salts thereof are provided Crystalline forms of pravastatin, intermediates and pharmaceutically acceptable salts thereof are also disclosed.

  提供了制备普伐他汀、中间体和药用可接受盐的工艺。还公开了普伐他汀、中间体和药用可接受盐的结晶形式。
• [EN] A NOVEL, GREEN AND COST EFFECTIVE PROCESS FOR SYNTHESIS OF TERT-BUTYL (3R,5S)-6-OXO-3,5-DIHYDROXY-3,5-O-ISOPROPYLIDENE-HEXANOATE<br/>[FR] NOUVEAU PROCÉDÉ ÉCOLOGIQUE ET ÉCONOMIQUE POUR LA SYNTHÈSE DE TERT-BUTYL (3R,5S)-6-OXO-3,5-DIHYDROXY-3,5-O-ISOPROPYLIDÈNE-HEXANOATE
  申请人：LUPIN LTD

  公开号：WO2014203045A1

  公开（公告）日：2014-12-24

  The present invention provides a process of preparation of an intermediate useful for the preparation of statins more particularly the present invention relates to an eco-friendly and cost effective process for the preparation of tert -butyl (3R,5S)-6-oxo-3,5-dihydroxy- 3,5-O-isopropylidene-hexanoate [I].

  本发明提供了一种制备中间体的过程，该中间体用于制备他汀类药物，更具体地说，本发明涉及一种环保且具有成本效益的过程，用于制备叔丁基(3R,5S)-6-氧化-3,5-二羟基-3,5- O-异丙基亚戊酸酯[I]。
• [EN] IMIDAZOLE-BASED HMG-COA REDUCTASE INHIBITORS<br/>[FR] INHIBITEURS DE L'HMG-COA REDUCTASE UTILISANT UN IMIDAZOLE
  申请人：WARNER LAMBERT CO

  公开号：WO2005079790A1

  公开（公告）日：2005-09-01

  HMG-Co-A reductase inhibitor compounds useful as hypocholesterolemic and hypolipidemic agents are provided. Also provided are pharmaceutical compositions of the compounds. Methods of making and methods of using the compounds are also provided.

  提供了作为降胆固醇和降脂血症药物有用的HMG-CoA还原酶抑制剂化合物。还提供了这些化合物的药物组合物。同时还提供了制备这些化合物的方法和使用这些化合物的方法。
• Antihypercholesterolemic tetrazol-1-yl compounds
  申请人：Bristol-Myers Squibb Company

  公开号：EP0355820A1

  公开（公告）日：1990-02-28

  Compounds of the formula wherein R¹, R², R³, and R⁴ each are independently hydrogen, halogen, C₁₋₄alkyl, C₁₋₄alkoxy or trifluoromethyl; R is hydrogen, C₁₋₄alkyl or phenyl; R⁵ is hydrogen, a hydrolyzable ester group or a cation to form a non-toxic pharmaceutically acceptalbe salt, are novel antihypercholesterolemic agents which inhibit cholesterol biosynthesis. Intermediates and processes for their preparation are disclosed.

  式中的化合物 其中 R¹、R²、R³ 和 R⁴ 各自独立地为氢、卤素、C₁₋₄烷基、C₁₋₄烷氧基或三氟甲基； R 是氢、C₁₋₄烷基或苯基； R⁵ 是氢、可水解的酯基或阳离子，以形成无毒的药学上可接受的盐、 是新型抗胆固醇药物，可抑制胆固醇的生物合成。本研究还公开了用于制备这些药物的中间体和工艺。