trans-7-[1-(2-Benzothiazolyl)-5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-4-yl]-5-hydroxy-3-oxo-6-heptenoic acid, ethyl ester | 133258-57-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: trans-7-[1-(2-Benzothiazolyl)-5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-4-yl]-5-hydroxy-3-oxo-6-heptenoic acid, ethyl ester
• 英文别名: ethyl (E)-7-[1-(1,3-benzothiazol-2-yl)-5-(4-fluorophenyl)-3-propan-2-ylpyrazol-4-yl]-5-hydroxy-3-oxohept-6-enoate
• CAS: 133258-57-8
• 化学式: C₂₈H₂₈FN₃O₄S
• 分子量: 521.612
• InChiKey: VTXVEOCMGDZYLY-BUHFOSPRSA-N

物化性质

• 沸点：
  730.7±70.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  trans-7-[1-(2-Benzothiazolyl)-5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-4-yl]-5-hydroxy-3-oxo-6-heptenoic acid, ethyl ester 在 sodium tetrahydroborate 、 三乙基硼 、 三甲基乙酸 作用下， 生成 (R*,S*,trans)-7-[1-(2-Benzothiazolyl)-5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-4-yl]-3,5-dihydroxy-6-heptenoic acid, ethyl ester
  参考文献：
  名称：

  Inhibitors of cholesterol biosynthesis. 6. trans-6-[2-(2-N-heteroaryl-3,5-disubstituted-pyrazol-4-yl)ethyl/ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-ones

  摘要：

  A series of N-heteroaryl-substituted mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase both in vitro and in vivo, and to lower plasma cholesterol in a hypercholesterolemic dog model. The goal of the strategy employed was to design an inhibitor which possessed the pharmacological properties of lovastatin (1), and the physicochemical properties (increased hydrophilicity) of pravastatin (2). Two compounds 20a and 20b, were more potent than lovastatin at inhibiting cholesterol biosynthesis both in vitro and in vivo. In terms of plasma cholesterol lowering, 20a was much more efficacious than lovastatin. In addition to possessing increased biological activity, these compounds are significantly less lipophilic than lovastatin, in fact, 20b has a CLOGP value comparable to pravastatin.

  DOI：

  10.1021/jm00089a022
• 作为产物：
  描述：

  2-肼基苯并噻唑 在 manganese(IV) oxide 、 N-溴代丁二酰亚胺(NBS) 、 正丁基锂 、 bis(triphenylphosphine)palladium(II)-chloride 、 sodium hydride 、 二异丁基氢化铝 、 三乙胺 作用下， 以 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 32.0h， 生成 trans-7-[1-(2-Benzothiazolyl)-5-(4-fluorophenyl)-3-(1-methylethyl)-1H-pyrazol-4-yl]-5-hydroxy-3-oxo-6-heptenoic acid, ethyl ester
  参考文献：
  名称：

  Inhibitors of cholesterol biosynthesis. 6. trans-6-[2-(2-N-heteroaryl-3,5-disubstituted-pyrazol-4-yl)ethyl/ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-ones

  摘要：

  A series of N-heteroaryl-substituted mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase both in vitro and in vivo, and to lower plasma cholesterol in a hypercholesterolemic dog model. The goal of the strategy employed was to design an inhibitor which possessed the pharmacological properties of lovastatin (1), and the physicochemical properties (increased hydrophilicity) of pravastatin (2). Two compounds 20a and 20b, were more potent than lovastatin at inhibiting cholesterol biosynthesis both in vitro and in vivo. In terms of plasma cholesterol lowering, 20a was much more efficacious than lovastatin. In addition to possessing increased biological activity, these compounds are significantly less lipophilic than lovastatin, in fact, 20b has a CLOGP value comparable to pravastatin.

  DOI：

  10.1021/jm00089a022

文献信息

• Trans-6-(2-(N-heteroaryl-3,5-disubstituted)pyrazol-4-yl)-ethyl)-or
  申请人：Warner-Lambert Company

  公开号：US04957971A1

  公开（公告）日：1990-09-18

  Certain trans-6-[2-(N-heteroaryl-3,5-disubstituted) pyrazol-4-yl)ethyl]- or ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-ones and the corresponding ring-opened acids, esters and N-oxides derived therefrom which 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-(N-杂环芳基-3,5-二取代)吡唑-4-基)乙基]-或乙烯基]四氢-4-羟基-2H-吡喃-2-酮及其相应的环开放酸、酯和N-氧化物是酶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，因此是有用的降脂或降胆固醇剂。还公开了含有这些化合物的制药组合物以及使用这些制药组合物抑制胆固醇生物合成的方法。
• Trans-6-(2-(n-heteroaryl-3,5-disubstituted)pyrazol-4-yl)-ethyl- or
  申请人：Warner-Lambert Company

  公开号：US05102893A1

  公开（公告）日：1992-04-07

  Certain trans-6-[2-(N-heteroaryl-3,5-disubstituted) pyrazol-4-yl)ethyl]- or ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-ones and the corresponding ring-opened acids, esters and N-oxides derived therefrom which are potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA reductase) and are thus useful hydrolipidemic or hypocholesterolemic agents. Pharmaceutical compositions containing such compounds, and a method of inhibiting the biosynthesis of cholesterol employing such pharmaceutical compositions are also disclosed.

  本发明涉及某些特定的trans-6-[2-(N-杂环芳基-3,5-二取代)吡唑-4-基)乙基]-或乙烯基]四氢-4-羟基-2H-吡喃-2-酮及其相应的开环酸、酯和N-氧化物。它们是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剂。本发明还涉及含有这种化合物的药物组合物，以及使用这种药物组合物抑制胆固醇生物合成的方法。
• PICARD, JOSEPH A.;ROTH, BRUCE D.;SLISKOVIC, DRAGO R.
  作者：PICARD, JOSEPH A.、ROTH, BRUCE D.、SLISKOVIC, DRAGO R.

  DOI：——

  日期：——
• Inhibitors of cholesterol biosynthesis. 6. trans-6-[2-(2-N-heteroaryl-3,5-disubstituted-pyrazol-4-yl)ethyl/ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-ones
  作者：D. R. Sliskovic、C. J. Blankley、B. R. Krause、R. S. Newton、J. A. Picard、W. H. Roark、B. D. Roth、C. Sekerke、M. K. Shaw、R. L. Stanfield

  DOI：10.1021/jm00089a022

  日期：1992.5

  A series of N-heteroaryl-substituted mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase both in vitro and in vivo, and to lower plasma cholesterol in a hypercholesterolemic dog model. The goal of the strategy employed was to design an inhibitor which possessed the pharmacological properties of lovastatin (1), and the physicochemical properties (increased hydrophilicity) of pravastatin (2). Two compounds 20a and 20b, were more potent than lovastatin at inhibiting cholesterol biosynthesis both in vitro and in vivo. In terms of plasma cholesterol lowering, 20a was much more efficacious than lovastatin. In addition to possessing increased biological activity, these compounds are significantly less lipophilic than lovastatin, in fact, 20b has a CLOGP value comparable to pravastatin.