2-[4-(1,3-二恶烷-2-基)苯基]乙醇 | 163164-07-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二恶烷
• 中文名称: 2-[4-(1,3-二恶烷-2-基)苯基]乙醇
• 英文名称: 4-(1,3-dioxan-2-yl)phenylethanol
• 英文别名: 2-(4-[1.3]dioxane-2-yl-phenyl)-ethanol；2-[4-(1,3-Dioxan-2-yl)phenyl]ethanol
• CAS: 163164-07-6
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: YLSPFIYPFYVVDV-UHFFFAOYSA-N

物化性质

• 沸点：
  358.1±37.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[4-(1,3-二恶烷-2-基)苯基]乙醇 在 盐酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 16.5h， 生成 ethyl (E)-7-[4-[2-(4-formylphenyl)ethoxy]phenyl]-7-pyridin-3-ylhept-6-enoate
  参考文献：
  名称：

  A Novel Approach to Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors Based on the Link of 1,3-Dioxane-Thromboxane Receptor Antagonists and -Thromboxane Synthase Inhibitors

  摘要：

  A new class of dual-acting racemic thromboxane receptor antagonist/thromboxane synthase inhibitors is reported, based on the novel approach of linking the known thromboxane synthase inhibitors (TXSI) dazoxiben (2) or isbogrel(11) (separately) to thromboxane receptor antagonists (TXRA) from the 1,3-dioxane series, such as ICI 192605 (10). Dual activity was observed in vitro with inhibition of human microsomal thromboxane synthase in the range IC50 = 0.01-1.0 mu M and receptor antagonist activity by inhibition of U46619-induced human platelet aggregation in the range pA(2) = 5.5-7.0. The in vitro results also showed that very large groups could be tolerated at the selected substitution positions of the TXRA and TXSI components. Oral activity was observed in ex vivo tests in both rats and dogs at a dose of 10 mg/kg. Thus, (E)-7-[4-[[4-[(2SR,4SR,5RS)-5-[(Z)-5-carboxypent-2-enyl]-4-(2-hydroxyphenyl)-1,3-dioxan-2-yl]benzyl]oxy]phenyl]-7-(3-pyridyl)hept-6-enoic acid (110) was both an antagonist (pA(2) = 6.7) and a synthase inhibitor (IC50 = 0.02 mu M). On oral dosing (10 mg/kg) to rats and dogs, 110 showed significant TXRA activity [concentration ratio >64 (rat, 3 h) and >59 +/- 11.3 (dog, 2 h) vs ex vivo U46619-induced platelet aggregation]. Inhibition of thromboxane synthase at the respective time points in these experiments was 81 +/- 4.4% (rat) and 69 +/- 4.8% (dog).

  DOI：

  10.1021/jm00010a005
• 作为产物：
  描述：

  2-(4-溴苯乙氧基)四氢-2H-吡喃 在 盐酸 、 正丁基锂 、 对甲苯磺酸 作用下， 以 丙酮 、 甲苯 为溶剂， 反应 5.0h， 生成 2-[4-(1,3-二恶烷-2-基)苯基]乙醇
  参考文献：
  名称：

  A Novel Approach to Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors Based on the Link of 1,3-Dioxane-Thromboxane Receptor Antagonists and -Thromboxane Synthase Inhibitors

  摘要：

  A new class of dual-acting racemic thromboxane receptor antagonist/thromboxane synthase inhibitors is reported, based on the novel approach of linking the known thromboxane synthase inhibitors (TXSI) dazoxiben (2) or isbogrel(11) (separately) to thromboxane receptor antagonists (TXRA) from the 1,3-dioxane series, such as ICI 192605 (10). Dual activity was observed in vitro with inhibition of human microsomal thromboxane synthase in the range IC50 = 0.01-1.0 mu M and receptor antagonist activity by inhibition of U46619-induced human platelet aggregation in the range pA(2) = 5.5-7.0. The in vitro results also showed that very large groups could be tolerated at the selected substitution positions of the TXRA and TXSI components. Oral activity was observed in ex vivo tests in both rats and dogs at a dose of 10 mg/kg. Thus, (E)-7-[4-[[4-[(2SR,4SR,5RS)-5-[(Z)-5-carboxypent-2-enyl]-4-(2-hydroxyphenyl)-1,3-dioxan-2-yl]benzyl]oxy]phenyl]-7-(3-pyridyl)hept-6-enoic acid (110) was both an antagonist (pA(2) = 6.7) and a synthase inhibitor (IC50 = 0.02 mu M). On oral dosing (10 mg/kg) to rats and dogs, 110 showed significant TXRA activity [concentration ratio >64 (rat, 3 h) and >59 +/- 11.3 (dog, 2 h) vs ex vivo U46619-induced platelet aggregation]. Inhibition of thromboxane synthase at the respective time points in these experiments was 81 +/- 4.4% (rat) and 69 +/- 4.8% (dog).

  DOI：

  10.1021/jm00010a005

文献信息

• New carboxamide compounds having melanin concentrating hormone antagonistic activity, pharmaceutical preparations comprising these compounds and process for their manufacture
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20040242572A1

  公开（公告）日：2004-12-02

  The present invention relates to carboxamide compounds of general formula I 1 wherein the groups and residues A, B, W, X, Y, Z, R 1 , R 2 , R 3 and k have the meanings given in claim 1. Moreover the invention relates to process for preparing the above mentioned carboxamides as well as pharmaceutical compositions containing at least one carboxamide according to the invention. In view of their MCH-receptor antagonistic activity the pharmaceutical compositions according to the invention are suitable for the treatment of metabolic disorders and/or eating disorders, particularly obesity, bulimia, anorexia, hyperphagia and diabetes.

  本发明涉及具有通式I的羧酰胺化合物 1 其中，A、B、W、X、Y、Z、R 1 、R 2 、R 3 和k的含义如权利要求1中所述。此外，本发明还涉及制备上述羧酰胺的方法以及含有至少一种根据本发明的羧酰胺的药物组合物。由于它们对MCH受体的拮抗活性，根据本发明的药物组合物适合用于治疗代谢紊乱和/或饮食紊乱，特别是肥胖症、厌食症、暴食症、糖尿病。
• NEUE CARBONS UREAMID-VERBINDUNGEN MIT MCH-ANTAGONISTISCHER W IRKUNG, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL UND VERFAHREN ZU IHRER HERSTELLUNG
  申请人：BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG

  公开号：EP1534689A1

  公开（公告）日：2005-06-01
• [DE] NEUE CARBONSÄUREAMID-VERBINDUNGEN MIT MCH-ANTAGONISTISCHER WIRKUNG, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL UND VERFAHREN ZU IHRER HERSTELLUNG<br/>[EN] NOVEL CARBOXAMIDE COMPOUNDS HAVING AN MCH-ANTAGONISTIC EFFECT, MEDICAMENTS CONTAINING SAID COMPOUNDS, AND METHODS FOR THE PRODUCTION THEREOF<br/>[FR] NOUVEAUX COMPOSES CARBOXAMIDE EXERCANT UNE ACTION ANTAGONISTE SUR LA MCH, MEDICAMENTS CONTENANT CES COMPOSES ET LEURS PROCEDES DE PRODUCTION
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2004024702A1

  公开（公告）日：2004-03-25

  Die vorliegende Erfindung betrifft Carbonsäureamid-Verbindungen der allgemeinen Formel (I), in der die Gruppen und Reste A, B, W, X, Y, Z, R1, R2, R3 und k die in Anspruch 1 angegebenen Bedeutungen aufweisen. Ferner betrifft die Erfindung Verfahren zur Herstellung der zuvor genannten Carbonsäureamide sowie Arzneimittel enthaltend mindestens ein erfindungsgemässes Carbonsäureamid. Auf Grund der MCH-Rezeptor antagonistischen Aktivität eignen sich die erfindungsgemässen Arzneimittel zur Behandlung von metabolischen Störungen und/oder Essstörungen, insbesondere von Obesitas, Bulimie, Anorexie, Hyperphagia und Diabetes.
• A Novel Approach to Dual-Acting Thromboxane Receptor Antagonist/Synthase Inhibitors Based on the Link of 1,3-Dioxane-Thromboxane Receptor Antagonists and -Thromboxane Synthase Inhibitors
  作者：Norman Ackerley、Andrew G. Brewster、George R. Brown、David S. Clarke、Alan J. Foubister、Stephen J. Griffin、Julian A. Hudson、Michael J. Smithers、Paul R. O. Whittamore

  DOI：10.1021/jm00010a005

  日期：1995.5

  A new class of dual-acting racemic thromboxane receptor antagonist/thromboxane synthase inhibitors is reported, based on the novel approach of linking the known thromboxane synthase inhibitors (TXSI) dazoxiben (2) or isbogrel(11) (separately) to thromboxane receptor antagonists (TXRA) from the 1,3-dioxane series, such as ICI 192605 (10). Dual activity was observed in vitro with inhibition of human microsomal thromboxane synthase in the range IC50 = 0.01-1.0 mu M and receptor antagonist activity by inhibition of U46619-induced human platelet aggregation in the range pA(2) = 5.5-7.0. The in vitro results also showed that very large groups could be tolerated at the selected substitution positions of the TXRA and TXSI components. Oral activity was observed in ex vivo tests in both rats and dogs at a dose of 10 mg/kg. Thus, (E)-7-[4-[[4-[(2SR,4SR,5RS)-5-[(Z)-5-carboxypent-2-enyl]-4-(2-hydroxyphenyl)-1,3-dioxan-2-yl]benzyl]oxy]phenyl]-7-(3-pyridyl)hept-6-enoic acid (110) was both an antagonist (pA(2) = 6.7) and a synthase inhibitor (IC50 = 0.02 mu M). On oral dosing (10 mg/kg) to rats and dogs, 110 showed significant TXRA activity [concentration ratio >64 (rat, 3 h) and >59 +/- 11.3 (dog, 2 h) vs ex vivo U46619-induced platelet aggregation]. Inhibition of thromboxane synthase at the respective time points in these experiments was 81 +/- 4.4% (rat) and 69 +/- 4.8% (dog).