ethyl 6-fluoroheptanoate | 178622-29-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 6-fluoroheptanoate
• CAS: 178622-29-2
• 化学式: C₉H₁₇FO₂
• 分子量: 176.231
• InChiKey: NERCLTSMMORYSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  12
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 6-fluoroheptanoate 在 N-溴代丁二酰亚胺(NBS) 、 lithium aluminium tetrahydride 、 碳酸氢钠 、 三苯基膦 作用下， 以 乙醚 、 乙腈 、 苯 为溶剂， 反应 23.42h， 生成 N-(4-{4-[Ethyl-(6-fluoro-heptyl)-amino]-butyl}-phenyl)-methanesulfonamide
  参考文献：
  名称：

  Progress toward the Development of a Safe and Effective Agent for Treating Reentrant Cardiac Arrhythmias:  Synthesis and Evaluation of Ibutilide Analogues with Enhanced Metabolic Stability and Diminished Proarrhythmic Potential

  摘要：

  A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.

  DOI：

  10.1021/jm0004289
• 作为产物：
  描述：

  ethyl 6-hydroxyheptanoate 在 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.66h， 以38.5%的产率得到ethyl 6-fluoroheptanoate
  参考文献：
  名称：

  Progress toward the Development of a Safe and Effective Agent for Treating Reentrant Cardiac Arrhythmias:  Synthesis and Evaluation of Ibutilide Analogues with Enhanced Metabolic Stability and Diminished Proarrhythmic Potential

  摘要：

  A series of ibutilide analogues with fluorine substituents on the heptyl side chain was prepared and evaluated for class III antiarrhythmic activity, metabolic stability, and proarrhythmic potential. It was found that fluorine substituents stabilized the side chain to metabolic oxidation. Many of the compounds also retained the ability to increase the refractoriness of cardiac tissue at both slow and fast pacing rates. The potential for producing polymorphic ventricular tachycardia in the rabbit model was dependent on the chirality of the benzylic carbon. The S-enantiomers generally had less proarrhythmic activity than the corresponding racemates. One compound from this series (45E, trecetilide fumarate) had excellent antiarrhythmic activity and metabolic stability and was devoid of proarrhythmic activity in the rabbit model. It was chosen for further development.

  DOI：

  10.1021/jm0004289

文献信息

• [EN] ANTIARRHYTHMIC (S)-ENANTIOMERS OF METHANESULFONAMIDES<br/>[FR] ENANTIOMERES (S) DE METHANE-SULFONAMIDES ANTIARYTHMIQUES
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：WO1996021643A1

  公开（公告）日：1996-07-18

  (EN) (S)-Enantiomeric methanesulfonamides are structurally depicted by formula (I) or its pharmacologically acceptable salts where R3 is a C1-9 alkyl substituted with one fluorine atom. These compounds are useful as Class III antiarrhythmic agents without the undesirable side effect of polymorphic ventricular tachycardia (PVT) and are stable against rapid metabolism. Use of the compounds of formula (I) in the preparation of compositions for treating cardiac arrhythmias are also described.(FR) Méthane-sulfonamides énantiomères (S) décrits, au point de vue de la structure, par la formule (I) ou les sels pharmacologiquement acceptables du composé décrit par celle-ci, où R3 est un alkyle en C1-C9 substitué avec un atome de fluor. Ces composés sont utiles en tant qu'agents antiarythmiques de classe III n'ayant pas l'effet secondaire indésirable qu'est la tachycardie ventriculaire polymorphe et sont stables vis-à-vis d'un métabolisme rapide. L'invention décrit également l'utilisation desdits composés de formule (I) dans des préparations servant au traitement d'arythmies cardiaques.

  （EN）（S）-对映甲磺酰胺的结构式如公式（I）或其药学上可接受的盐所示，其中R3是一个C1-9烷基，被一个氟原子取代。这些化合物可用作III类抗心律失常药物，不会产生多形性室性心动过速（PVT）的不良副作用，并且稳定不易被迅速代谢。本发明还描述了将公式（I）化合物用于制备治疗心律失常的组合物的用途。 （FR）（S）-对映甲磺酰胺的结构式如公式（I）或其药学上可接受的盐所示，其中R3是一个C1-9烷基，被一个氟原子取代。这些化合物可用作III类抗心律失常药物，不会产生多形性室性心动过速（PVT）的不良副作用，并且稳定不易被迅速代谢。本发明还描述了将公式（I）化合物用于制备治疗心律失常的组合物的用途。
• 4-(4-METHANESULFONAMIDOPHENYL)BUTYLAMINE DERIVATIVES WITH ANTIARRHYTHMIC ACTIVITY
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0781273A1

  公开（公告）日：1997-07-02
• ANTIARRHYTHMIC (S)-ENANTIOMERS OF METHANESULFONAMIDES
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：EP0802900A1

  公开（公告）日：1997-10-29
• US5874475A
  申请人：——

  公开号：US5874475A

  公开（公告）日：1999-02-23
• [EN] 4-(4-METHANESULFONAMIDOPHENYL)BUTYLAMINE DERIVATIVES WITH ANTIARRHYTHMIC ACTIVITY<br/>[FR] DERIVES 4-(4-METHANESULFONAMIDOPHENYL)BUTYLAMINE EXERÇANT UNE ACTIVITE ANTIARHYTHMIQUE
  申请人：PHARMACIA & UPJOHN COMPANY

  公开号：WO1996008471A1

  公开（公告）日：1996-03-21

  (EN) Methanesulfonamides are structurally depicted by formula (I), or its pharmacologically acceptable salts where R3 is a C1-7 alkyl substituted with C3-7 cycloalkyl, or a C1-10 alkyl substituted with one to eight fluorine atoms, one to three hydroxy, one to three C1-5 acyloxy or one to three C1-4 alkoxy substituents. These compounds are useful as Class III antiarrhythmic agents and are stable against rapid metabolism. Methods for treating cardiac arrhythmias with the compounds of formula (I) as well as compositions thereof are also described.(FR) Méthanesulfonamides de la formule (I), ou leurs sels pharmaceutiquement acceptables. Dans cette formule, R3 et un C1-7 alkyle substitué par un C3-7 cycloalkyle, ou un C1-10 alkyle substitué par 1 à 8 atomes de fluore, 1 à 3 substituants hydroxy, 1 à 3 substituants C1-5 acyloxy ou 1 à 3 substituants de C1-4 alcoxy. Ces composés se révèlent utiles comme agents antiarhythmiques de la classe III et se révèlent stables par rapport à un métabolisme rapide. L'invention porte également sur des méthodes de traitement des arhythmies cardiaques à l'aide de composés de la formule (I) ainsi que de compositions issues de ces composés.