N-(9-hydroxy-9H-fluorene-2-carbonyl)guanidine hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-(9-hydroxy-9H-fluorene-2-carbonyl)guanidine hydrochloride
• 英文别名: N-(diaminomethylene)-9-hydroxy-9H-fluorene-2-carboxamide hydrochloride；N-carbamimidoyl-9-hydroxy-9H-fluorene-2-carboxamide;hydrochloride
• 化学式: C₁₅H₁₃N₃O₂*ClH
• 分子量: 303.748
• InChiKey: KJPICQIEXXARFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.58
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  102
• 氢给体数：
  4
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  9-芴酮-2-羧酸 在 sodium tetrahydroborate 、 N,N'-羰基二咪唑 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.75h， 生成 N-(9-hydroxy-9H-fluorene-2-carbonyl)guanidine hydrochloride
  参考文献：
  名称：

  EP1728784

  摘要：

  公开号：

文献信息

• Synthesis and structure–activity relationships of new carbonyl guanidine derivatives as novel dual 5-HT2B and 5-HT7 receptor antagonists
  作者：Ayako Moritomo、Hiroyoshi Yamada、Toshihiro Watanabe、Hirotsune Itahana、Shinobu Akuzawa、Minoru Okada、Mitsuaki Ohta

  DOI：10.1016/j.bmc.2013.10.010

  日期：2013.12

  To identify potent dual 5-HT2B and 5-HT7 receptor antagonists, we synthesized a series of novel carbonyl guanidine derivatives and examined their structure–activity relationships. Among these compounds, N-(9-hydroxy-9H-fluorene-2-carbonyl)guanidine (10) had a good in vitro profile, that is, potent affinity for human 5-HT2B and 5-HT7 receptor subtypes (Ki = 1.8 nM and Ki = 17.6 nM, respectively) and

  为了鉴定有效的双重5-HT 2B和5-HT 7受体拮抗剂，我们合成了一系列新型羰基胍衍生物，并研究了它们的结构-活性关系。在这些化合物中，N-（9-羟基-9 H-芴-2-羰基）胍（10）具有良好的体外特性，即对人5-HT 2B和5-HT 7受体亚型的有效亲和力（ķ我 = 1.8纳米和ķ我 = 17.6纳米，）和高选择性超过5-HT 2A，5-HT 2C，α 1，d 2和M 1受体。当口服时，化合物10还对豚鼠的5-HT诱导的硬脑膜蛋白渗出具有抑制作用。
• Flourene Derivative
  申请人：Yamada Hiroyoshi

  公开号：US20080200551A1

  公开（公告）日：2008-08-21

  This invention relates to a novel fluorene derivative having a characteristic structure in which guanidino group or the like functional group is linked to the fluorene structure via carbonyl group, or a salt thereof. The compound of the invention has an advantage in that it has high affinity for serotonin receptor subtypes, particularly for 5-HT 2B receptor and 5-HT 7 receptor, and shows excellent pharmacological effects in comparison with the conventional compounds which have only one of the antagonistic activities of 5-HT 2B receptor and 5-HT 7 receptor, this is useful as a prophylactic antimigraine agent having high safety and excellent effect.

  这项发明涉及一种新颖的芴衍生物，其具有特征结构，其中脲基或类似的官能团通过羰基与芴结构连接，或其盐。该化合物具有优点，即它对5-HT2B受体和5-HT7受体等血清素受体亚型具有高亲和力，并与仅具有5-HT2B受体和5-HT7受体拮抗活性之一的传统化合物相比，显示出出色的药理效应，因此可用作具有高安全性和出色效果的预防性抗偏头痛剂。
• Prophylactic Antimigraine Agents
  申请人：Akuzawa Shinobu

  公开号：US20080161419A1

  公开（公告）日：2008-07-03

  The present invention relates to prophylactic antimigraine agents comprising as an active ingredient a dual antagonist for the 5-HT 2B and 5-HT 7 receptors, the antagonist having a binding affinity selective for the 5-HT 2B and 5-HT 7 receptors. Since these prophylactic antimigraine agents show an excellent pharmacological effect in comparison with the cases in which a 5-HT 2B receptor antagonist having a selective binding affinity to the 5-HT 2B receptor or a 5-HT 7 receptor antagonist having a selective binding affinity to the 5-HT 7 receptor is used alone, they are useful as drugs which are excellent in prophylaxis of migraine and in which the side effects found in the existing prophylactic antimigraine agents are reduced.

  本发明涉及预防偏头痛的药物，其作为活性成分包括对5-HT2B和5-HT7受体的双重拮抗剂，该拮抗剂具有选择性结合5-HT2B和5-HT7受体的结合亲和力。由于这些预防性抗偏头痛药物与仅使用具有选择性结合亲和力的5-HT2B受体拮抗剂或5-HT7受体拮抗剂相比，表现出优异的药理作用，因此它们是在预防偏头痛方面优秀的药物，其中减少了现有预防偏头痛药物中发现的副作用。
• Medicament For Irritable Bowel Syndrome
  申请人：Akuzawa Shinobu

  公开号：US20080171788A1

  公开（公告）日：2008-07-17

  The invention relates to a medicament for IBS, which comprises a dual antagonist for 5-HT 2B and 5-HT 7 receptors having selective binding affinities for 5-HT 2B and 5-HT 7 receptors. The pharmaceutical composition of the invention is useful as a drug which is excellent in the therapeutic effect on IBS and shows lessened side effects occurring in the existing remedies for IBS, because it showed good pharmacological actions in comparison with the case of independently using a 5-HT 2B receptor antagonist having selective binding affinity for 5-HT 2B receptor or a 5-HT 7 receptor antagonist having selective binding affinity for 5-HT 7 receptor.

  本发明涉及一种治疗肠易激综合征（IBS）的药物，包括一种对5-HT2B和5-HT7受体具有选择性结合亲和力的双重拮抗剂。本发明的制药组合物作为一种药物对IBS具有优异的治疗效果，并且与现有的IBS治疗药物相比，具有减少副作用的优点，因为与单独使用具有选择性结合亲和力的5-HT2B受体拮抗剂或5-HT7受体拮抗剂相比，它表现出良好的药理作用。
• PREVENTIVES FOR MIGRAINE
  申请人：Astellas Pharma Inc.

  公开号：EP1716867A1

  公开（公告）日：2006-11-02

  The present invention relates to prophylactic antimigraine agents comprising as an active ingredient a dual antagonist for the 5-HT2B and 5-HT7 receptors, the antagonist having a binding affinity selective for the 5-HT2B and 5-HT7 receptors. Since these prophylactic antimigraine agents show an excellent pharmacological effect in comparison with the cases in which a 5-HT2B receptor antagonist having a selective binding affinity to the 5-HT2B receptor or a 5-HT7 receptor antagonist having a selective binding affinity to the 5-HT7 receptor is used alone, they are useful as drugs which are excellent in prophylaxis of migraine and in which the side effects found in the existing prophylactic antimigraine agents are reduced.

  本发明涉及预防性抗偏头痛制剂，其活性成分包括 5-HT2B 和 5-HT7 受体双重拮抗剂，该拮抗剂对 5-HT2B 和 5-HT7 受体具有选择性结合亲和力。 与单独使用对 5-HT2B 受体具有选择性结合亲和力的 5-HT2B 受体拮抗剂或对 5-HT7 受体具有选择性结合亲和力的 5-HT7 受体拮抗剂的情况相比，这些预防性抗偏头痛药剂显示出卓越的药理作用，因此，它们可作为预防偏头痛的良药，并可减少现有预防性抗偏头痛药剂的副作用。