Methyl 4-(3-bromo-4-fluorophenyl)-2-ethyl-5-oxo-4,5,6,8-tetrahydro-1H-pyrano[3,4-b]pyridine-3-carboxylate | 372120-67-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: Methyl 4-(3-bromo-4-fluorophenyl)-2-ethyl-5-oxo-4,5,6,8-tetrahydro-1H-pyrano[3,4-b]pyridine-3-carboxylate
• 英文别名: methyl 4-(3-bromo-4-fluorophenyl)-2-ethyl-5-oxo-4,8-dihydro-1H-pyrano[3,4-b]pyridine-3-carboxylate
• CAS: 372120-67-7
• 化学式: C₁₈H₁₇BrFNO₄
• 分子量: 410.24
• InChiKey: OSRPRRJEVOCWQM-UHFFFAOYSA-N

物化性质

• 沸点：
  521.3±50.0 °C(predicted)
• 密度：
  1.53±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Methyl 4-(3-bromo-4-fluorophenyl)-2-ethyl-5-oxo-4,5,6,8-tetrahydro-1H-pyrano[3,4-b]pyridine-3-carboxylate 在 吡啶 、 pyridinium hydrobromide perbromide 作用下， 以 氯仿 为溶剂， 反应 0.58h， 生成 (+)-cis-9-(3-bromo-4-fluorophenyl)-3-methyl-5,9-dihydro-3H-furo[3,4-b]pyrano[4,3-e]pyridine-1,8(4H,7H)-dione
  参考文献：
  名称：

  Effects of Substitution on 9-(3-Bromo-4-fluorophenyl)-5,9-dihydro-3H,4H-2,6-dioxa-4- azacyclopenta[b]naphthalene-1,8-dione, a Dihydropyridine ATP-Sensitive Potassium Channel Opener

  摘要：

  Structure-activity relationships were investigated on the tricyclic dihydropyridine ( DHP) K-ATP openers 9-(3-bromo-4-fluorophenyl)-5,9- dihydro-3H, 4H-2,6-dioxa-4-azacyclopenta[ b] naphthalene-1,8-dione ( 6) and 10( 3-bromo-4-fluorophenyl)-9,10-dihydro-1H, 8H-2,7-dioxa-9-azaanthracene-4,5-dione ( 65). Substitution off the core of the DHP, absolute stereochemistry, and aromatic substitution were evaluated for KATP channel activity using Ltk-cells stably transfected with the Kir6.2/SUR2B exon 17- splice variant and in an electrically stimulated pig bladder strip assay. A select group of compounds was evaluated for in vitro inhibition of spontaneous bladder contractions. Several compounds were found to have the unique characteristic of partial efficacy in both the cell-based and electrically stimulated bladder strip assays but full efficacy in inhibiting spontaneous bladder strip contractions. For compound 23b, this profile was mirrored in vivo where it was fully efficacious in inhibiting spontaneous myogenic bladder contractions but only partially able to reduce neurogenically mediated reflex bladder contractions.

  DOI：

  10.1021/jm060549u
• 作为产物：
  描述：

  3-氧代戊酸甲酯 、 3-溴-4-氟苯甲醛 、 5-amino-2H-pyran-3(6H)-one 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 生成 Methyl 4-(3-bromo-4-fluorophenyl)-2-ethyl-5-oxo-4,5,6,8-tetrahydro-1H-pyrano[3,4-b]pyridine-3-carboxylate
  参考文献：
  名称：

  Pyrano, piperidino, and thiopyrano compounds and methods of use

  摘要：

  本发明提供了一种公式I的新化合物，可能在超极化细胞膜、打开钾通道、放松平滑肌细胞和抑制膀胱收缩方面有用。

  公开号：

  US06642222B2

文献信息

• Pyrano, piperidino, and thiopyrano compounds and methods of use
  申请人：Abbott Laboratories

  公开号：US06642222B2

  公开（公告）日：2003-11-04

  The present invention provides novel compounds of formula I which may be useful in hyperpolarizing cell membranes, opening potassium channels, relaxing smooth muscle cells, and inhibiting bladder contractions.

  本发明提供了一种公式I的新化合物，可能在超极化细胞膜、打开钾通道、放松平滑肌细胞和抑制膀胱收缩方面有用。
• Pyrano piperidino and thiopyrano compounds and methods of use
  申请人：——

  公开号：US20030055035A1

  公开（公告）日：2003-03-20

  1 The present invention provides novel compounds of formula I which may be useful in hyperpolarizing cell membranes, opening potassium channels, relaxing smooth muscle cells, and inhibiting bladder contractions.

  本发明提供了一种新型的化合物I，可用于超极化细胞膜、打开钾通道、放松平滑肌细胞和抑制膀胱收缩。
• US6642222B2
  申请人：——

  公开号：US6642222B2

  公开（公告）日：2003-11-04
• Effects of Substitution on 9-(3-Bromo-4-fluorophenyl)-5,9-dihydro-3<i>H</i>,4<i>H</i>-2,6-dioxa-4- azacyclopenta[<i>b</i>]naphthalene-1,8-dione, a Dihydropyridine ATP-Sensitive Potassium Channel Opener
  作者：Robert J. Altenbach、Michael E. Brune、Steven A. Buckner、Michael J. Coghlan、Anthony V. Daza、Adebola Fabiyi、Murali Gopalakrishnan、Rodger F. Henry、Albert Khilevich、Michael E. Kort、Ivan Milicic、Victoria E. Scott、Jamie C. Smith、Kristi L. Whiteaker、William A. Carroll

  DOI：10.1021/jm060549u

  日期：2006.11.1

  Structure-activity relationships were investigated on the tricyclic dihydropyridine ( DHP) K-ATP openers 9-(3-bromo-4-fluorophenyl)-5,9- dihydro-3H, 4H-2,6-dioxa-4-azacyclopenta[ b] naphthalene-1,8-dione ( 6) and 10( 3-bromo-4-fluorophenyl)-9,10-dihydro-1H, 8H-2,7-dioxa-9-azaanthracene-4,5-dione ( 65). Substitution off the core of the DHP, absolute stereochemistry, and aromatic substitution were evaluated for KATP channel activity using Ltk-cells stably transfected with the Kir6.2/SUR2B exon 17- splice variant and in an electrically stimulated pig bladder strip assay. A select group of compounds was evaluated for in vitro inhibition of spontaneous bladder contractions. Several compounds were found to have the unique characteristic of partial efficacy in both the cell-based and electrically stimulated bladder strip assays but full efficacy in inhibiting spontaneous bladder strip contractions. For compound 23b, this profile was mirrored in vivo where it was fully efficacious in inhibiting spontaneous myogenic bladder contractions but only partially able to reduce neurogenically mediated reflex bladder contractions.