dimethyl 4-(thien-2-yl)-4-cyanopimelate | 65619-56-9

• 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: dimethyl 4-(thien-2-yl)-4-cyanopimelate
• 英文别名: Dimethyl 4-(2-thienyl)-4-cyanopimelate；Dimethyl 4-cyano-4-thiophen-2-ylheptanedioate
• CAS: 65619-56-9
• 化学式: C₁₄H₁₇NO₄S
• 分子量: 295.359
• InChiKey: CHIFJRILSUHVLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl 4-(thien-2-yl)-4-cyanopimelate 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以90%的产率得到4-(2-Thienyl)-4-cyano-2-carbomethoxycyclohexanone
  参考文献：
  名称：

  4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring

  摘要：

  Investigation of central nervous system activity of phenylcyclohexylamines was continued by preparation of "reversed" analogues. Following the unexpected finding of analgesic activity with 1-(dimethylamino)-1-phenylcyclohexylamine, the SAR of the series was investigated. Synthesis starts by double Michael reaction of acrylate on arylacetonitriles. Following cyclization, decarboxylation, ketalization, and saponification, the geminally substituted acid is rearranged to the isocyanate by means of (C6H5O)2PON3. Isocyanates were then converted to the title compounds. Analgesic activity is very sensitive to the nature and position of the substitutent on the aromatic ring. The most potent compounds in this series (p-CH3, p-Br) showed 50% the potency of morphine. Deletion of the ring oxygen abolishes activity.

  DOI：

  10.1021/jm00178a014
• 作为产物：
  描述：

  2-噻吩乙腈 、 丙烯酸甲酯（MA） 以 盐酸 、 叔丁醇 为溶剂， 生成 dimethyl 4-(thien-2-yl)-4-cyanopimelate
  参考文献：
  名称：

  4-Amino-4-phenylcyclohexanone ketal compositions and process of use

  摘要：

  一类新的4-氨基-4-芳基环己酮，它们的缩醛和酸盐已经合成，并发现对于缓解动物的疼痛很有用。它们的镇痛活性似乎是很高的，并且一些还表现出对镇痛引起的心血管、呼吸和行为抑制有用的麻醉拮抗活性。其中几种显示出混合的镇痛和麻醉拮抗活性。该类化合物的首选化合物是4-(间羟基苯基)-4-二甲氨基环己酮乙二醚缩醛，以及4-(间羟基苯基)-4-(正丁基甲基氨基)环己酮乙二醚缩醛，作为游离碱和其盐酸盐形式。描述了合成和中间体的过程。披露了单位剂量形式和治疗方法。

  公开号：

  US04065573A1

文献信息

• 4-Amino-4-phenylcyclohexanone ketal compositions and process of use
  申请人：The Upjohn Company

  公开号：US04065573A1

  公开（公告）日：1977-12-27

  A class of new 4-amino-4-arylcyclohexanones, their ketals, and acid addition salts have been synthesized and found to be useful for relieving pain in animals. Their analgesic activity appears to be of high order, and in addition some exhibit narcotic antagonist activity that is useful in modifying the cardiovascular, respiratory, and behavioral depression caused by other analgesics. Several show mixed analgesic and narcotic antagonist activity. Preferred compounds of the class are 4-(m-hydroxyphenyl)-4-dimethylaminocyclohexanone ethylene ketal, and 4-(m-hydroxyphenyl)-4-(n-butylmethylamino)cyclohexanone ethylene ketal as free bases and as their hydrochloride salts. Processes for synthesis and intermediates are described. Unit dosage forms and therapeutic treatments are disclosed.

  一类新的4-氨基-4-芳基环己酮，它们的缩醛和酸盐已经合成，并发现对于缓解动物的疼痛很有用。它们的镇痛活性似乎是很高的，并且一些还表现出对镇痛引起的心血管、呼吸和行为抑制有用的麻醉拮抗活性。其中几种显示出混合的镇痛和麻醉拮抗活性。该类化合物的首选化合物是4-(间羟基苯基)-4-二甲氨基环己酮乙二醚缩醛，以及4-(间羟基苯基)-4-(正丁基甲基氨基)环己酮乙二醚缩醛，作为游离碱和其盐酸盐形式。描述了合成和中间体的过程。披露了单位剂量形式和治疗方法。
• CYCLOALKYL INHIBITORS OF POTASSIUM CHANNEL FUNCTION
  申请人：Lloyd John

  公开号：US20070142333A1

  公开（公告）日：2007-06-21

  Novel cycloalkyl compounds useful as inhibitors of potassium channel function (especially inhibitors of the K v 1 subfamily of voltage gated K + channels, especially inhibitors K v 1.5 which has been linked to the ultra-rapidly activating delayed rectifier K + current I Kur ), methods of using such compounds in the prevention and treatment of arrhythmia and I Kur -associated conditions, and pharmaceutical compositions containing such compounds.

  新型环烷基化合物可作为钾通道功能抑制剂使用（特别是钾离子电压门控K+通道的Kv1亚家族的抑制剂，特别是与超快速激活延迟整流K+电流IKur相关的Kv1.5抑制剂），使用这种化合物预防和治疗心律失常和IKur相关疾病的方法，以及含有这种化合物的药物组合物。
• Cycloalkyl inhibitors of potassium channel function
  申请人：Bristol-Myers Squibb Company

  公开号：EP2253328A1

  公开（公告）日：2010-11-24

  Novel cycloalkyl compounds useful as inhibitors of potassium channel function (especially inhibitors of the Kvl subfamily of voltage gated K+ channels, especially inhibitors Kv1.5 which has been linked to the ultra-rapidly activating delayed rectifier K+ current IKur), methods of using such compounds in the prevention and treatment of arrhythmia and IKur-associated conditions, and pharmaceutical compositions containing such compounds.

  可用作钾通道功能抑制剂的新型环烷基化合物（特别是电压门控 K+ 通道 Kvl 亚家族的抑制剂，尤其是与超快速活化延迟整流 K+ 电流 IKur 有关的 Kv1.5 抑制剂）、使用此类化合物预防和治疗心律失常及 IKur 相关疾病的方法，以及含有此类化合物的药物组合物。
• 4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring
  作者：Daniel Lednicer、Philip F. Von Voigtlander、D. Edward Emmert

  DOI：10.1021/jm00178a014

  日期：1980.4

  Investigation of central nervous system activity of phenylcyclohexylamines was continued by preparation of "reversed" analogues. Following the unexpected finding of analgesic activity with 1-(dimethylamino)-1-phenylcyclohexylamine, the SAR of the series was investigated. Synthesis starts by double Michael reaction of acrylate on arylacetonitriles. Following cyclization, decarboxylation, ketalization, and saponification, the geminally substituted acid is rearranged to the isocyanate by means of (C6H5O)2PON3. Isocyanates were then converted to the title compounds. Analgesic activity is very sensitive to the nature and position of the substitutent on the aromatic ring. The most potent compounds in this series (p-CH3, p-Br) showed 50% the potency of morphine. Deletion of the ring oxygen abolishes activity.
• LEDNICER D.; VOIGTLANDER P. F.; EMMERT D. E., J. MED. CHEM., 1980, 23, NO 4, 424-430
  作者：LEDNICER D.、 VOIGTLANDER P. F.、 EMMERT D. E.

  DOI：——

  日期：——