N-(3-(4-(ethylamino)cyclohex-1-enyl)-1H-indol-5-yl)thiophene-2-carboximidamide | 1152478-57-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-(3-(4-(ethylamino)cyclohex-1-enyl)-1H-indol-5-yl)thiophene-2-carboximidamide
• 英文别名: N'-[3-[4-(ethylamino)cyclohexen-1-yl]-1H-indol-5-yl]thiophene-2-carboximidamide
• CAS: 1152478-57-3
• 化学式: C₂₁H₂₄N₄S
• 分子量: 364.514
• InChiKey: BPVHTTZVPKXNPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  94.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-(4-(ethylamino)cyclohex-1-enyl)-1H-indol-5-yl)thiophene-2-carboximidamide 在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 反应 0.17h， 生成 N-(3-(4-(ethylamino)cyclohex-1-enyl)-1H-indol-5-yl)thiophene-2-carboximidamide dihydrochloride
  参考文献：
  名称：

  First-in-Class, Dual-Action, 3,5-Disubstituted Indole Derivatives Having Human Nitric Oxide Synthase (nNOS) and Norepinephrine Reuptake Inhibitory (NERI) Activity for the Treatment of Neuropathic Pain

  摘要：

  A family of different 3,5-disubstituted indole derivatives having 6-membered rings were designed, synthesized, and demonstrated inhibition of human nitric oxide synthase (NOS) with norepinephrine reuptake inhibitory activity (NERO. The structure-activity relationship (SAR) within the cyclohexane ring showed the cis-isomers to be more potent for neuronal NOS and selective over endothelial NOS compared to their trans-counterparts. Compounds, such as cis-(+)-37, exhibited dual nNOS and NET inhibition (IC50 of 0.56 and 1.0 mu M, respectively) and excellent selectivity (88-fold and 12-fold) over eNOS and iNOS, respectively. The lead compound (cis-(+)-37) showed lack of any direct vasoconstriction or inhibition of ACh-mediated vasorelaxation in isolated human coronary arteries. Additionally, cis-(+)-37 was effective at reversing both allodynia and thermal hyperalgesia in a standard Chung (spinal nerve ligation) rat neuropathic pain model. Overall, the data suggest that cis-(+)-37 is a promising dual action development candidate having therapeutic potential for the treatment of neuropathic pain.

  DOI：

  10.1021/jm300138g
• 作为产物：
  描述：

  5-硝基吲哚 在 盐酸 、 氢氧化钾 、 水 、 三乙酰氧基硼氢化钠 、 镍 、 溶剂黄146 、 三乙胺 、 三氟乙酸 、 肼 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 丙酮 为溶剂， 反应 96.25h， 生成 N-(3-(4-(ethylamino)cyclohex-1-enyl)-1H-indol-5-yl)thiophene-2-carboximidamide
  参考文献：
  名称：

  3,5 - SUBSTITUTED INDOLE COMPOUNDS HAVING NOS AND NOREPINEPHRINE REUPTAKE INHIBITORY ACTIVITY

  摘要：

  本发明涉及具有一氧化氮合酶（NOS）抑制活性以及对去甲肾上腺素转运蛋白（NET）具有抑制活性的新型3,5-取代吲哚化合物（I）的公式，以及含有它们的药用和诊断组合物，以及它们的医疗用途。

  公开号：

  US20090131503A1

文献信息

• 3,5 - SUBSTITUTED INDOLE COMPOUNDS HAVING NOS AND NOREPINEPHRINE REUPTAKE INHIBITORY ACTIVITY
  申请人：Annedi Subhash C.

  公开号：US20090131503A1

  公开（公告）日：2009-05-21

  The present invention relates to novel 3,5-substituted indole compounds of Formula (I) having nitric oxide synthase (NOS) inhibitory activity together with inhibitory activity at the norepinephrine transporter (NET), to pharmaceutical and diagnostic compositions containing them, and to their medical use.

  本发明涉及具有一氧化氮合酶（NOS）抑制活性以及对去甲肾上腺素转运蛋白（NET）具有抑制活性的新型3,5-取代吲哚化合物（I）的公式，以及含有它们的药用和诊断组合物，以及它们的医疗用途。
• [EN] 3,5-SUBSTITUTED INDOLE COMPOUNDS HAVING NOS AND NOREPINEPHRINE REUPTAKE INHIBITORY ACTIVITY<br/>[FR] COMPOSÉS D'INDOLE 3,5-SUBSTITUÉS AYANT UNE ACTIVITÉ D'INHIBITION DE LA RÉABSORPTION DE LA NOS ET DE LA NORADRÉNALINE
  申请人：NEURAXON INC

  公开号：WO2009062318A1

  公开（公告）日：2009-05-22

  The present invention relates to novel 3,5-substituted indole compounds of Formula (I) having nitric oxide synthase (NOS) inhibitory activity, particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other eNOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing condition such as chronic pain and psychiatric disorders.
• First-in-Class, Dual-Action, 3,5-Disubstituted Indole Derivatives Having Human Nitric Oxide Synthase (nNOS) and Norepinephrine Reuptake Inhibitory (NERI) Activity for the Treatment of Neuropathic Pain
  作者：Gabriela Mladenova、Subhash C. Annedi、Jailall Ramnauth、Shawn P. Maddaford、Suman Rakhit、John S. Andrews、Dongqin Zhang、Frank Porreca

  DOI：10.1021/jm300138g

  日期：2012.4.12

  A family of different 3,5-disubstituted indole derivatives having 6-membered rings were designed, synthesized, and demonstrated inhibition of human nitric oxide synthase (NOS) with norepinephrine reuptake inhibitory activity (NERO. The structure-activity relationship (SAR) within the cyclohexane ring showed the cis-isomers to be more potent for neuronal NOS and selective over endothelial NOS compared to their trans-counterparts. Compounds, such as cis-(+)-37, exhibited dual nNOS and NET inhibition (IC50 of 0.56 and 1.0 mu M, respectively) and excellent selectivity (88-fold and 12-fold) over eNOS and iNOS, respectively. The lead compound (cis-(+)-37) showed lack of any direct vasoconstriction or inhibition of ACh-mediated vasorelaxation in isolated human coronary arteries. Additionally, cis-(+)-37 was effective at reversing both allodynia and thermal hyperalgesia in a standard Chung (spinal nerve ligation) rat neuropathic pain model. Overall, the data suggest that cis-(+)-37 is a promising dual action development candidate having therapeutic potential for the treatment of neuropathic pain.