cis-2,2-dimethyl-6-(2-phenylethenyl)-1,3-dioxane-4-acetic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: cis-2,2-dimethyl-6-(2-phenylethenyl)-1,3-dioxane-4-acetic acid
• 英文别名: 2-[(4S,6R)-2,2-dimethyl-6-[(E)-2-phenylethenyl]-1,3-dioxan-4-yl]acetic acid
• 化学式: C₁₆H₂₀O₄
• 分子量: 276.332
• InChiKey: YWACBBGYAKTLGI-CFYKVZDHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  cis-2,2-dimethyl-6-(2-phenylethenyl)-1,3-dioxane-4-acetic acid 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
• 作为产物：
  描述：

  2,2-dimethyl-6-(2-phenylethenyl)-1,3-dioxane-4-acetic acid methyl ester 以 甲醇 、 sodium hydroxide 为溶剂， 以7.2 g (90%)的产率得到cis-2,2-dimethyl-6-(2-phenylethenyl)-1,3-dioxane-4-acetic acid
  参考文献：
  名称：

  Antihypercholesterolemic tetrazol-1-yl compounds

  摘要：

  该文献描述的是一种化合物，其化学式为##STR1##其中R.sup.1，R.sup.2，R.sup.3和R.sup.4各自独立地为氢，卤素，C.sub.1-4烷基，C.sub.1-4烷氧基或三氟甲基；R为氢，C.sub.1-4烷基或苯基；A为##STR2## R.sup.5为氢，可水解酯基或阳离子，以形成非毒性药用可接受盐，这些新型抗高胆固醇药物可以抑制胆固醇生物合成。文献还披露了制备这些化合物的中间体和过程。

  公开号：

  US04870187A1

文献信息

• Antihypercholesterolemic tetrazole compounds
  申请人：Bristol-Meyers Company

  公开号：US04897490A1

  公开（公告）日：1990-01-30

  Compounds of the formula ##STR1## wherein R.sup.1 and R.sup.4 each are independently hydrogen, halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, or trifluoromethyl; R.sup.2, R.sup.3, R.sup.5 and R.sup.6 each are independently hydrogen, halogen C.sub.1-4 alkyl or C.sub.1-4 alkoxy; tet is ##STR2## n is an integer of from 0 to 2, inclusive; A is ##STR3## R.sup.7 is hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy(lower) alkyl or (2-methoxyethoxy)methyl; X is --OH or .dbd.O; and R.sup.8 is hydrogen, a hydrolyzable ester group or a cation to form a non-toxic pharmaceutically acceptable salt, are novel antihypercholesterolemic agents which inhibit cholesterol biosynthesis. Intermediates and processes for their preparation are disclosed.

  式为##STR1##的化合物，其中R.sup.1和R.sup.4分别独立地是氢、卤素、C.sub.1-4烷基、C.sub.1-4氧烷基或三氟甲基；R.sup.2、R.sup.3、R.sup.5和R.sup.6分别独立地是氢、卤素、C.sub.1-4烷基或C.sub.1-4氧烷基；tet为##STR2##；n是0到2之间的整数；A为##STR3##；R.sup.7为氢、C.sub.1-4烷基、C.sub.1-4氧烷基(较低)烷基或(2-甲氧基乙氧基)甲基；X为--OH或.dbd.O；R.sup.8为氢、可水解酯基团或阳离子，以形成一种无毒的药用可接受盐，这些化合物是新型抗高胆固醇药物，可抑制胆固醇生物合成。揭示了它们的中间体和制备方法。
• Intermediates for antihypercholesterolemic tetrazole compounds
  申请人：Bristol-Myers Company

  公开号：US04824959A1

  公开（公告）日：1989-04-25

  This invention provides novel intermediates of the formula ##STR1## in substantially the cis or cis-(4R,6S) form wherein R.sup.9 and R.sup.10 each are C.sub.1-4 alkyl or R.sup.9 and R.sup.10, taken together with the carbon atom to which they are attached, is cyclopentyl, cyclohexyl or cycloheptyl; and R.sup.12 is hydrogen, C.sub.1-4 alkyl or a metal cation and processes thereof which are useful for the preparation of antihypercholesterolemic agents.

  本发明提供了新的中间体的公式##STR1##，其基本上是顺式或顺式-(4R,6S)形式，其中R.sup.9和R.sup.10各自为C.sub.1-4烷基或R.sup.9和R.sup.10连同它们所附着的碳原子，为环戊基，环己基或环庚基; 而R.sup.12是氢，C.sub.1-4烷基或金属阳离子，以及其制备抗高胆固醇药物的过程。
• [EN] CONDENSED PYRIDINE TYPE MEVALONOLACTONE INTERMEDIATE AND PROCESS FOR ITS PRODUCTION<br/>[FR] INTERMEDIAIRE CONDENSE DE SYNTHESE DU MEVALONOLACTONE DE TYPE PYRIDINE ET PROCEDE DE FABRICATION DE CET INTERMEDIAIRE
  申请人：NISSAN CHEMICAL INDUSTRIES LTD.

  公开号：WO1995011898A1

  公开（公告）日：1995-05-04

  (EN) The present invention provides a synthetic condensed pyridine type mevalonolactone intermediate of formula (1), wherein Z is (a) or (b), each of R9a and R9b is a hydroxyl-protecting group, and R10 is methyl, ethyl, propyl, isopropyl, tert-butyl, tetrahydropyranyl, allyl, benzyl, triphenylmethyl, trimethylsilyl or tert-butyldimethylsilyl. The intermediate is useful for producing a 7-position substituted (E, 3R, 5S)-3,5-dihydroxy-6-heptenoic acid or its 1,5-lactone or its enantiomer which has an activity as an HMG-CoA reductase inhibitor and which is useful as a hypercholesterolemia therapeutic agent.(FR) L'invention concerne un intermédiaire condensé de synthèse du mévalonolactone de type pyridine, présentant la formule (1) dans laquelle Z représente (a) ou (b), chaque R9a et R9b représente un groupe protecteur hydroxyle, et R10 représente méthyle, éthyle, propyle, isopropyle, tert-butyle, tétrahydropyranyle, allyle, benzyle, triphénylméthyle, triméthylsilyle ou tert-butyldiméthylsilyle. Cet intermédiaire est utile pour produire un acide hepténoïque (E,3R,5S)-3,5-dihydroxy-6 substitué en position 7 ou son 1,5-lactone ou son énantiomère qui présente une activité comme inhibiteur de la HMG-CoA réductase, et peut être utilisé comme agent thérapeutique de l'hypercholestérolémie.

  本发明提供了一种合成的紧凑型吡啶型甲烷酸内酯中间体，其化学式为（1），其中Z为（a）或（b），R9a和R9b均为羟基保护基，R10为甲基、乙基、丙基、异丙基、叔丁基、四氢吡喃基、烯丙基、苄基、三苯基甲基、三甲基硅基或叔丁基二甲基硅基。该中间体可用于生产7位取代的（E，3R，5S）-3,5-二羟基-6-庚烯酸或其1,5-内酯或其对映体，其具有作为HMG-CoA还原酶抑制剂的活性，可用作治疗高胆固醇血症的药物。
• Synthesis, biological profile, and quantitative structure-activity relationship of a series of novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
  作者：S. Y. Sit、R. A. Parker、I. Motoc、W. Han、N. Balasubramanian、J. D. Catt、P. J. Brown、W. E. Harte、M. D. Thompson、J. J. Wright

  DOI：10.1021/jm00173a013

  日期：1990.11

  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.
• HAN, WILLIAM T.;WRIGHT, JOHN J.
  作者：HAN, WILLIAM T.、WRIGHT, JOHN J.

  DOI：——

  日期：——