3-(4-(1-methylethyl)-piperazin-1-ylmethyl)-2-phenylquinoline-4-carboxylic acid azepan-1-ylamide

• 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: 3-(4-(1-methylethyl)-piperazin-1-ylmethyl)-2-phenylquinoline-4-carboxylic acid azepan-1-ylamide
• 英文别名: 3-(4-(1-methylethyl)piperazin-1-ylmethyl)-2-phenyl-quinoline-4-carboxylic acid azepan-1-ylamide；N-(azepan-1-yl)-2-phenyl-3-[(4-propan-2-ylpiperazin-1-yl)methyl]quinoline-4-carboxamide
• 化学式: C₃₀H₃₉N₅O
• 分子量: 485.673
• InChiKey: ARMADUQHXPUZLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  51.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-氨基高哌啶 、 3-(4-(1-methylethyl)-piperazin-1-ylmethyl)-2-phenyl-quinoline-4-carboxylic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.0h， 以17%的产率得到3-(4-(1-methylethyl)-piperazin-1-ylmethyl)-2-phenylquinoline-4-carboxylic acid azepan-1-ylamide
  参考文献：
  名称：

  [EN] SUBSTITUTED QUINOLINE-4-CARBOXYLIC HYDRAZIDES AS NK-2/NK-3 RECEPTOR LIGANDS
  [FR] HYDRAZIDES D'ACIDE CARBOXYLIQUE DE 4-QUINOLEINE SUBSTITUES EN TANT QUE LIGANDS DU RECEPTEUR DE NK-2/NK-3

  摘要：

  本发明公开了一种化合物，其化学式为（I）：其中：R1是芳基或杂环芳基；R2是羟基，C1-6烷氧基，C1-6烷基，氨基，NR'R'或C1-6烷基-NR'R'，其中R'和R'分别选择自氢和C1-4烷基，且R'和R'与它们连接的氮原子一起形成一个饱和的含氮3-7成员杂环，该杂环可以包含另一个氮原子，并且可以被上述定义的NR'R'取代，或者R2是被上述定义的NR'R'取代的C1-6烷氧基；R3是氢或C1-6烷基；R4是氢，C1-8烷基，C2-8烯基，C2-8炔基，C3-8环烷基，芳基或芳基C1-6烷基；R5是氢，C1-8烷基，C2-8烯基，C2-8炔基，C3-8环烷基，芳基，芳基C1-6烷基或C1-6烷氧羰基；或者R4和R5，与它们连接的氮原子一起形成一个C3-C10单环或双环饱和环；X和Y分别选择自氢，羟基，硝基，氨基，氰基，三氟甲基，卤素和C1-4烷基；或其药用盐；作为治疗精神分裂症、COPD、哮喘或肠易激综合征的NK-2/NK-3配体。

  公开号：

  WO2004072045A1

文献信息

• Substituted quinoline-4-carboxylic hydrazides as nk-2/nk-3 receptor ligands
  申请人：Chambers Stuart Mark

  公开号：US20060089348A1

  公开（公告）日：2006-04-27

  The present invention discloses a compound of formula (I): wherein: R 1 is an aryl or heteroaryl ring; R 2 is hydroxy, C 1-6 alkoxy, C 1-6 alkyl, amino, NR′R″ or C 1-6 alkyl-NR′R″ where R′ and R″ are independently chosen from hydrogen and C 1-4 alkyl and where R′ and R″, together with the nitrogen atom to which they are attached, form a saturated nitrogen-containing 3-7 membered heterocycle optionally containing a further nitrogen atom and optionally substituted by NR′R″ as defined above or R 2 is C 1-6 alkoxy substituted by NR′R″ as defined above; R 3 is hydrogen or C 1-6 alkyl; R 4 is hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3-8 cycloalkyl, aryl or aryl C 1-6 alkyl; R 5 is hydrogen, C 1-8 alkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 3 -8 cycloalkyl, aryl, aryl C 1-6 alkyl or C 1-6 alkoxycarbonyl; or R 4 and R 5 , together with the nitrogen atom to which they are attached, form a C 3 -C 10 mono- or bicyclic saturated ring; X and Y are independently chosen from hydrogen, hydroxy, nitro, amino, cyano, CF 3 , halogen and C 1-4 alkyl; or a pharmaceutically acceptable salt thereof; as NK-2/NK-3 ligands for treating schizophrenia, COPD, asthma or irritable bowel syndrome.

  本发明揭示了一种化合物，其化学式为（I）：其中：R1为芳基或杂环芳基环；R2为羟基，C1-6烷氧基，C1-6烷基，氨基，NR′R″或C1-6烷基-NR′R″，其中R′和R″分别选择氢和C1-4烷基，且R′和R″与它们所连接的氮原子一起形成一个饱和的含氮3-7成员杂环，可选地含有进一步的氮原子，并可选地被上述定义的NR′R″或R2为C1-6烷氧基所取代；R3为氢或C1-6烷基；R4为氢，C1-8烷基，C2-8烯基，C2-8炔基，C3-8环烷基，芳基或芳基C1-6烷基；R5为氢，C1-8烷基，C2-8烯基，C2-8炔基，C3-8环烷基，芳基，芳基C1-6烷基或C1-6烷氧羰基；或R4和R5与它们所连接的氮原子一起形成C3-C10单环或双环饱和环；X和Y分别选择自氢，羟基，硝基，氨基，氰基，CF3，卤素和C1-4烷基；或其药学上可接受的盐；作为NK-2 / NK-3配体，用于治疗精神分裂症，慢性阻塞性肺疾病，哮喘或肠易激综合征。
• Substituted quinoline-4-carboxylic hydrazides as NK-2/NK-3 receptor ligands
  申请人：Merck Sharp & Dohme

  公开号：US07482457B2

  公开（公告）日：2009-01-27

  The present invention discloses a compound of formula (I): wherein: R1 is an aryl or heteroaryl ring; R2 is hydroxy, C1-6 alkoxy, C1-6 alkyl, amino, NR′R″ or C1-6 alkyl-NR′R″ where R′ and R″ are independently chosen from hydrogen and C1-4 alkyl and where R′ and R″, together with the nitrogen atom to which they are attached, form a saturated nitrogen-containing 3-7 membered heterocycle optionally containing a further nitrogen atom and optionally substituted by NR′R″ as defined above or R2 is C1-6 alkoxy substituted by NR′R″ as defined above; R3 is hydrogen or C1-6 alkyl; R4 is hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, aryl or aryl C1-6 alkyl; R5 is hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, aryl, aryl C1-6 alkyl or C1-6 alkoxycarbonyl; or R4 and R5, together with the nitrogen atom to which they are attached, form a C3-C10 mono- or bicyclic saturated ring; X and Y are independently chosen from hydrogen, hydroxy, nitro, amino, cyano, CF3, halogen and C1-4 alkyl; or a pharmaceutically acceptable salt thereof; as NK-2/NK-3 ligands for treating schizophrenia, COPD, asthma or irritable bowel syndrome.

  本发明揭示了化合物（I）的结构：其中：R1是芳基或杂环芳基环；R2是羟基，C1-6烷氧基，C1-6烷基，氨基，NR′R″或C1-6烷基-NR′R″，其中R′和R″分别选择氢和C1-4烷基，R′和R″与它们所连接的氮原子一起形成一个饱和的含氮3-7环杂环，该杂环可选择性地含有进一步的氮原子，并可选择性地被上述定义的NR′R″取代，或者R2是被上述定义的NR′R″取代的C1-6烷氧基；R3是氢或C1-6烷基；R4是氢，C1-8烷基，C2-8烯基，C2-8炔基，C3-8环烷基，芳基或芳基C1-6烷基；R5是氢，C1-8烷基，C2-8烯基，C2-8炔基，C3-8环烷基，芳基，芳基C1-6烷基或C1-6烷氧羰基；或者R4和R5，与它们所连接的氮原子一起，形成C3-C10单环或双环饱和环；X和Y分别选择自氢，羟基，硝基，氨基，氰基，CF3，卤素和C1-4烷基；或其药学上可接受的盐；作为NK-2/NK-3配体，用于治疗精神分裂症，慢性阻塞性肺疾病，哮喘或肠易激综合症。
• SUBSTITUTED QUINOLINE-4-CARBOXYLIC HYDRAZIDES AS NK-2/NK-3 RECEPTOR LIGANDS
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP1594844A1

  公开（公告）日：2005-11-16
• COMBINATION THERAPY WITH NK3 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF SCHIZOPHRENIA
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP1778287A2

  公开（公告）日：2007-05-02
• Combination Therapy For The Treatment Of Schizophrenia
  申请人：Danjou Philippe

  公开号：US20070203119A1

  公开（公告）日：2007-08-30

  The present invention relates to a combination of a NK3 receptor antagonist with a 5HT2A receptor antagonist and/or a D2 receptor antagonist, and the use of the combination in treating schizophrenia and associated conditions.