1-(4-fluorophenyl)-5-methyl-2-(2-pyridyl)-1,4-hexanedione | 115672-63-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-fluorophenyl)-5-methyl-2-(2-pyridyl)-1,4-hexanedione
• 英文别名: 1-(4-fluorophenyl)-5-methyl-2-(2-pyridinyl)hexane-1,4-dione；1-(4-fluorophenyl)-5-methyl-2-pyridin-2-ylhexane-1,4-dione
• CAS: 115672-63-4
• 化学式: C₁₈H₁₈FNO₂
• 分子量: 299.345
• InChiKey: BLIGCRVWSUXQON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  47
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-5-methyl-2-(2-pyridyl)-1,4-hexanedione 在 乙酸铵 、 manganese(IV) oxide 、 sodium hydride 、 二异丁基氢化铝 、 溶剂黄146 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 2.17h， 生成 (Z)-3-<2,3-bis(4-fluorophenyl)-5-(1-methylethyl)-1H-pyrrol-1-yl>-2-propenal
  参考文献：
  名称：

  胆固醇生物合成抑制剂。2. 3,5-二羟基-7-（N-吡咯基）-6-庚烯酸酯，一系列新型的HMG-CoA还原酶抑制剂。

  摘要：

  制备了一系列的7- [2,3-二芳基-5-（1-甲基乙基）-1H-吡咯-1-基] -3,5-二羟基-6-庚烯酸酯，并对其抑制HMG酶的能力进行了评估。 -CoA还原酶在体外。维持在相关研究中发现的最佳的5-（1-甲基乙基）取代基，可以确定在吡咯环的2、3和4位修饰的化合物的结构活性关系。在吡咯2-位上优选4-氟苯基，而在3-位上引入一系列取代的苯基和吡啶基取代基则提供了具有同等酶抑制活性和大范围亲脂性的化合物。发现五取代吡咯3h的效力比洛伐他汀大10倍。

  DOI：

  10.1021/jm00075a021
• 作为产物：
  描述：

  异丁酰醋酸甲酯 在 哌啶 、 sodium hydroxide 、 2-(2-hydroxyethyl)-3-methyl-4-benzylthiazolium chloride 、 溶剂黄146 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 27.0h， 生成 1-(4-fluorophenyl)-5-methyl-2-(2-pyridyl)-1,4-hexanedione
  参考文献：
  名称：

  Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran 2-one inhibitors of HMG-CoA reductase. 2. Effects of introducing substituents at positions three and four of the pyrrole nucleus

  摘要：

  A series of trans-tetrahydro-4-hydroxy-6-[2-(2,3,4,5-substituted-1H-pyrrol-1-yl)ethyl]-2H-pyran-2-ones and their dihydroxy acids were prepared and tested for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Inhibitory potency was found to increase substantially when substituents were introduced into positions three and four of the pyrrole ring. A systematic exploration of structure-activity relationships at these two positions led to the identification of a compound ((+)-33, (+)-(4R)-trans-2-(4-fluorophenyl)-5-(1-methylethyl)-N,3-diphenyl-1-[(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-4-carboxamide) with five times the inhibitory potency of the fungal metabolite compactin.

  DOI：

  10.1021/jm00105a056

文献信息

• Trans-6-[2-[2-(substituted-phenyl)-3- (or 4-)
  申请人：Warner-Lambert Company

  公开号：US04735958A1

  公开（公告）日：1988-04-05

  Certain trans-6-[2-[2-(substituted-phenyl)-3- (or 4-)heteroaryl-5-substituted-1H-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2H-p yran-2-ones and the corresponding lactone-ring-opened acids are potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA reductase) and are thus useful hypolipidemic or hypocholesterolemic agents. Pharmaceutical compositions containing such compounds, and a method of inhibiting the biosynthesis of cholesterol employing such pharmaceutical compositions are also disclosed.

  某些转-6-[2-[2-(取代苯基)-3-(或4-)杂环芳基-5-取代-1H-吡咯-1-基]乙基]四氢-4-羟基-2H-吡喃-2-酮和相应的开环内酯酸是酶3-羟基-3-甲基戊二酰辅酶A还原酶（HMG CoA还原酶）的有效抑制剂，因此可用作降脂或降胆固醇药物。含有这些化合物的药物组合物，以及使用这些药物组合物抑制胆固醇生物合成的方法也被披露。
• ROTH, BRUCE D.;SLISKOVIC, DRAGO R.
  作者：ROTH, BRUCE D.、SLISKOVIC, DRAGO R.

  DOI：——

  日期：——
• US4735958A
  申请人：——

  公开号：US4735958A

  公开（公告）日：1988-04-05
• [EN] TRANS-6-[2-[2-(SUBSTITUTED-PHENYL)-3- (or 4-) HETEROARYL-5-SUBSTITUTED-1H-PYRROL-1-YL]-ETHYL]TETRAHYDRO-4-HYDROXY-2H-PYRAN-2-ONE INHIBITORS OF CHOLESTEROL BIOSYNTHESIS
  申请人：WARNER-LAMBERT COMPANY

  公开号：WO1988004657A2

  公开（公告）日：1988-06-30

  (EN) Certain $i(trans)-6-[2-[2-(substituted-phenyl)-3- (or 4-)heteroaryl-5-substituted-1$i(H)-pyrrol-1-yl]ethyl]tetrahydro-4-hydroxy-2$i(H)-pyran-2-ones and the corresponding lactone-ring-opened acids are potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA reductase) and are thus useful hypolipidemic or hypocholesterolemic agents. Pharmaceutical compositions containing such compounds, and a method of inhibiting the biosynthesis of cholesterol employing such pharmaceutical compositions are also disclosed.(FR) Certaines $i(trans)-6-[2-[2-(phényle substitué)-3-(ou 4-)hétéroaryl-5-substitué-1$i(H)-pyrrol-1-yl]éthyl]tétrahydro-4-hydroxy-2$i(H)-pyran-2-ones et les acides à anneau de lactone ouvert correspondants sont des inhibiteurs puissants de l'enzyme réductase de 3-hydroxy-3-méthylglutaryl-coenzyme A (réductase de HMG CoA) et constituent par conséquent des agents hypolipidémiques ou hypocholestérolémiques utiles. Des compositions pharmaceutiques contenant de tels composés et un procédé d'inhibition de la biosynthèse du cholestérol qui utilise de telles compositions pharmaceutiques sont également décrits.
• Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran 2-one inhibitors of HMG-CoA reductase. 2. Effects of introducing substituents at positions three and four of the pyrrole nucleus
  作者：Bruce D. Roth、C. J. Blankley、A. W. Chucholowski、E. Ferguson、M. L. Hoefle、D. F. Ortwine、R. S. Newton、C. S. Sekerke、D. R. Sliskovic、M Wilson

  DOI：10.1021/jm00105a056

  日期：1991.1

  A series of trans-tetrahydro-4-hydroxy-6-[2-(2,3,4,5-substituted-1H-pyrrol-1-yl)ethyl]-2H-pyran-2-ones and their dihydroxy acids were prepared and tested for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Inhibitory potency was found to increase substantially when substituents were introduced into positions three and four of the pyrrole ring. A systematic exploration of structure-activity relationships at these two positions led to the identification of a compound ((+)-33, (+)-(4R)-trans-2-(4-fluorophenyl)-5-(1-methylethyl)-N,3-diphenyl-1-[(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-4-carboxamide) with five times the inhibitory potency of the fungal metabolite compactin.