ethyl (7-hydroxy-2-naphthalenyl)acetate | 99318-12-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl (7-hydroxy-2-naphthalenyl)acetate
• 英文别名: Ethyl 2-(7-hydroxynaphthalen-2-yl)acetate
• CAS: 99318-12-4
• 化学式: C₁₄H₁₄O₃
• 分子量: 230.263
• InChiKey: UNNVTTNDKZRNJK-UHFFFAOYSA-N

物化性质

• 熔点：
  68-69 °C
• 沸点：
  389.2±17.0 °C(Predicted)
• 密度：
  1.203±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (7-hydroxy-2-naphthalenyl)acetate 在 六甲基磷酰三胺 、 lithium aluminium tetrahydride 、 盐酸羟胺 、 水 、 potassium carbonate 、 三乙胺 作用下， 以 吡啶 、 乙醇 为溶剂， 反应 24.5h， 生成 N-(7-propoxynaphthalene-2-ethyl)hydroxylamine
  参考文献：
  名称：

  5-脂氧合酶抑制剂的设计与合成

  摘要：

  基于对5-脂氧合酶的底物特异性和已知的反应立体化学过程，开发了酶活性位点的假设模型，并用于设计两种类型的5-脂氧合酶的选择性抑制剂。两种抑制剂类型均使用芳族环代替底物的（Z）-烯烃，并被设计为模拟花生四烯酸的非极性末端。一种抑制剂类型与已知的环氧合酶抑制剂类似，使用羧酸与酶的O结合中心相互作用，而另一种抑制剂则采用羟胺功能与预计在酶活性位点的酪氨酸或半胱氨酸自由基相互作用。 。选择性5-脂氧合酶抑制剂是7-（己氧基）萘-2-乙酸（1）和N-甲基；-N（7-丙氧基萘-2-乙基）羟胺（2）。讨论了两种抑制剂的构效关系。

  DOI：

  10.1002/hlca.19880710528
• 作为产物：
  描述：

  7-甲氧基-1-萘满酮 在 sodium tetrahydroborate 、 三甲基氯硅烷 、 4-甲基苯磺酸吡啶 、 四氯苯醌 、 sodium hydride 、 碳酸氢钠 、 间氯过氧苯甲酸 、 sodium iodide 、 zinc(II) iodide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 甲苯 、 乙腈 、 xylene 、 苯 为溶剂， 反应 18.5h， 生成 ethyl (7-hydroxy-2-naphthalenyl)acetate
  参考文献：
  名称：

  New Platelet Fibrinogen Receptor Glycoprotein IIb-IIIa Antagonists:  Orally Active Series of N-Alkylated Amidines with a 6,6-Bicyclic Template

  摘要：

  The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4-(morpholino-formimidoyl)benzamido]-3,4-dihydro-2H-1-benzopyran-3-yl]acetate hydrochloride ((S)-4 . HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl groups of already known GPIIb-IIIa antagonists led to the synthesis of nine amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the compounds 10a,c,e having an amide bond and 1,2,3,4-tetrahydronaphthalene or 3,4-dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46-57 nM in human platelet aggregation assay in vitro, but low oral activities. N-Alkylation of the amidino group coupled with the ester prodrug approach afforded MS-180 ((S)-4 . HCl), which generates in vivo the corresponding carboxylic acid (S)-3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively) and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)-4 . HCl) to fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The maximal inhibitions were observed 2-4 h after dosing with dose dependency (60% inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg, respectively) and the extent of the inhibitions paralleled the plasma concentration of the active species (S)-3. On the basis of these studies, we selected MS-180 ((S)-4 . HCl) as a candidate for clinical evaluation as a drug for the treatment and prevention of thrombosis in patients.

  DOI：

  10.1021/jm9801859

文献信息

• STRASSER, MICHAEL;COOPER, PHILIP;DEWALD, BEATRICE;PAYNE, TREVOR, HELV. CHIM. ACTA, 71,(1988) N 5, C. 1156-1176
  作者：STRASSER, MICHAEL、COOPER, PHILIP、DEWALD, BEATRICE、PAYNE, TREVOR

  DOI：——

  日期：——
• Design and Synthesis of 5-Lipoxygenase Inhibitors
  作者：Michael Strasser、Philip Cooper、Beatrice Dewald、Trevor Payne

  DOI：10.1002/hlca.19880710528

  日期：1988.8.10

  substrate specificity for 5-lipoxygenase and the known stereochemical course of the reaction, a hypothetical model of the enzyme active site was developed and used to design 2 types of selective inhibitors of 5-lipoxygenase. Both inhibitor types used aromatic rings in place of (Z)-olefins of the substrate and were designed to mimic the nonpolar end of arachidonic acid. One inhibitor type used a carboxylic-acid

  基于对5-脂氧合酶的底物特异性和已知的反应立体化学过程，开发了酶活性位点的假设模型，并用于设计两种类型的5-脂氧合酶的选择性抑制剂。两种抑制剂类型均使用芳族环代替底物的（Z）-烯烃，并被设计为模拟花生四烯酸的非极性末端。一种抑制剂类型与已知的环氧合酶抑制剂类似，使用羧酸与酶的O结合中心相互作用，而另一种抑制剂则采用羟胺功能与预计在酶活性位点的酪氨酸或半胱氨酸自由基相互作用。 。选择性5-脂氧合酶抑制剂是7-（己氧基）萘-2-乙酸（1）和N-甲基；-N（7-丙氧基萘-2-乙基）羟胺（2）。讨论了两种抑制剂的构效关系。
• New Platelet Fibrinogen Receptor Glycoprotein IIb-IIIa Antagonists:  Orally Active Series of <i>N</i>-Alkylated Amidines with a 6,6-Bicyclic Template
  作者：Kunio Okumura、Toshiyuki Shimazaki、Yoji Aoki、Hiroyuki Yamashita、Eishi Tanaka、Shinichi Banba、Kouhei Yazawa、Kenji Kibayashi、Hitoshi Banno

  DOI：10.1021/jm9801859

  日期：1998.10.1

  The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4-(morpholino-formimidoyl)benzamido]-3,4-dihydro-2H-1-benzopyran-3-yl]acetate hydrochloride ((S)-4 . HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl groups of already known GPIIb-IIIa antagonists led to the synthesis of nine amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the compounds 10a,c,e having an amide bond and 1,2,3,4-tetrahydronaphthalene or 3,4-dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46-57 nM in human platelet aggregation assay in vitro, but low oral activities. N-Alkylation of the amidino group coupled with the ester prodrug approach afforded MS-180 ((S)-4 . HCl), which generates in vivo the corresponding carboxylic acid (S)-3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively) and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)-4 . HCl) to fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The maximal inhibitions were observed 2-4 h after dosing with dose dependency (60% inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg, respectively) and the extent of the inhibitions paralleled the plasma concentration of the active species (S)-3. On the basis of these studies, we selected MS-180 ((S)-4 . HCl) as a candidate for clinical evaluation as a drug for the treatment and prevention of thrombosis in patients.