N-(1-(2-(methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide | 1063407-60-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-(1-(2-(methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide
• 英文别名: N'-[1-[2-(methylamino)ethyl]-3,4-dihydro-2H-quinolin-6-yl]thiophene-2-carboximidamide
• CAS: 1063407-60-2
• 化学式: C₁₇H₂₂N₄S
• 分子量: 314.454
• InChiKey: OGZIQVTYHMBLMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  81.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(1-(2-(methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide 在 盐酸 作用下， 以 甲醇 、 乙醚 为溶剂， 生成 N-(1-(2-(methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide dihydrochloride
  参考文献：
  名称：

  QUINOLONE AND TETRAHYDROQUINOLONE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY

  摘要：

  本发明涉及抑制一氧化氮合酶（NOS）的喹诺酮、四氢喹啉和相关化合物，特别是那些选择性地抑制神经型一氧化氮合酶（nNOS）而不是其他NOS同工型的化合物。本发明的NOS抑制剂，单独或与其他药用活性剂结合使用，可用于治疗或预防各种医疗状况。

  公开号：

  US20080234237A1
• 作为产物：
  描述：

  phenyl methyl(2-(6-nitro-3,4-dihydroquinolin-1(2H)-yl)-ethyl)carbamate 在 palladium 10% on activated carbon 、 水 、 氢气 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 10.5h， 生成 N-(1-(2-(methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide
  参考文献：
  名称：

  1,2,3,4-Tetrahydroquinoline-Based Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: Lead Optimization Studies Resulting in the Identification of N-(1-(2-(Methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide as a Preclinical Development Candidate

  摘要：

  Numerous studies have shown that selective nNOS inhibitors could be therapeutic in many neurological disorders. Previously, we reported a series of 1,2,3,4-tetrahydroquinoline-based potent and selective nNOS inhibitors, highlighted by 1 (J. Med. Chem. 2011, 54, 5562-5575). Despite showing activity in two rodent pain models, 1 suffered from low oral bioavailability (18%) and moderate hERG channel inhibition (IC50 = 4.7 mu M). To optimize the properties of 1, we synthesized a small focused library containing various alkylamino groups on the 1-position of the 1,2,3,4-tetrahydroquinoline scaffold. The compounds were triaged based on their activity in the NOS and hERG manual patch clamp assays and their calculated physicochemical parameters. From these studies, we identified 47 as a potent and selective nNOS inhibitor with improved oral bioavailability (60%) and no hERG channel inhibition (IC50 > 30 mu M). Furthermore, 47 was efficacious in the Chung model of neuropathic pain and has an excellent safety profile, making it a promising preclinical development candidate.

  DOI：

  10.1021/jm3000449

文献信息

• Mammalian and Bacterial Nitric Oxide Synthase Inhibitors
  申请人：Northwestern University

  公开号：US20160122302A1

  公开（公告）日：2016-05-05

  Compounds and related methods for inhibition of mammalian and bacterial nitric oxide synthase.

  化合物及相关方法，用于抑制哺乳动物和细菌的一氧化氮合酶。
• US8173813B2
  申请人：——

  公开号：US8173813B2

  公开（公告）日：2012-05-08
• US9951014B2
  申请人：——

  公开号：US9951014B2

  公开（公告）日：2018-04-24
• [EN] QUINOLONE AND TETRAHYDROQUINOLINE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY<br/>[FR] QUINOLONES ET TÉTRAHYDROQUINOLÉINES ET COMPOSÉS APPARENTÉS AYANT UNE ACTIVITÉ INHIBITRICE DE NOS
  申请人：NEURAXON INC

  公开号：WO2008116308A1

  公开（公告）日：2008-10-02

  [EN] The present invention features quinolones, tetrahydroquinolines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions.
  [FR] La présente invention porte sur des quinolones, des tétraydroquinoléines et des composés apparentés qui inhibent l'oxyde nitrique synthase (NOS), en particulier sur celles et ceux qui inhibent de façon sélective l'oxyde nitrique synthase neuronal (nNOS) de préférence à d'autres isoformes de NOS. Les inhibiteurs de NOS de l'invention, individuellement ou en combinaison avec d'autres agents pharmaceutiquement actifs, peuvent être utilisés pour traiter ou prévenir divers états médicaux.
• QUINOLONE AND TETRAHYDROQUINOLONE AND RELATED COMPOUNDS HAVING NOS INHIBITORY ACTIVITY
  申请人：MADDAFORD Shawn

  公开号：US20080234237A1

  公开（公告）日：2008-09-25

  The present invention features quinolones, tetrahydroquinolines, and related compounds that inhibit nitric oxide synthase (NOS), particularly those that selectively inhibit neuronal nitric oxide synthase (nNOS) in preference to other NOS isoforms. The NOS inhibitors of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions.

  本发明涉及抑制一氧化氮合酶（NOS）的喹诺酮、四氢喹啉和相关化合物，特别是那些选择性地抑制神经型一氧化氮合酶（nNOS）而不是其他NOS同工型的化合物。本发明的NOS抑制剂，单独或与其他药用活性剂结合使用，可用于治疗或预防各种医疗状况。