(S)-N-(α-ethylbenzyl)-3-[(3-oxo)pyrrolidin-1-ylmethyl]-2-phenylquinoline-4-carboxamide | 216372-71-3

• 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: (S)-N-(α-ethylbenzyl)-3-[(3-oxo)pyrrolidin-1-ylmethyl]-2-phenylquinoline-4-carboxamide
• 英文别名: 3-[(3-oxopyrrolidin-1-yl)methyl]-2-phenyl-N-[(1S)-1-phenylpropyl]quinoline-4-carboxamide
• CAS: 216372-71-3
• 化学式: C₃₀H₂₉N₃O₂
• 分子量: 463.579
• InChiKey: JKOJWCTZVWAKHY-SANMLTNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  草酰氯 、 (S)-N-(α-ethylbenzyl)-3-[(3-(S)-hydroxy)pyrrolidin-1-ylmethyl]-2-phenylquinoline-4-carboxamide 在 三乙醇胺 作用下， 以 正己烷 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 生成 (S)-N-(α-ethylbenzyl)-3-[(3-oxo)pyrrolidin-1-ylmethyl]-2-phenylquinoline-4-carboxamide
  参考文献：
  名称：

  Quinoline-4-carboxamide derivatives as NK-2 and NK-3 receptor antagonists

  摘要：

  化合物的通式（I）的化合物、溶剂化合物或其盐，其中，Ar是可选取代的芳基或C5-7环烷基烯基基团，或C5-7环烷基基团或可选取代的单环或融合环芳香杂环基团；R是C1-6烷基、C3-7环烷基、C3-7环烷基烷基、可选取代的苯基或苯基C1-6烷基、包含最多四个氧和氮的五元杂环芳香环，羟基C1-6烷基，氨基C1-6烷基，C1-6烷基氨基烷基，二C1-6烷基氨基烷基，C1-6酰胺基烷基，C1-6烷氧基烷基，C1-6烷基羰基，羧基，C1-6烷氧基羧酸酯，C1-6烷氧基羧酸酯C1-6烷基，氨基羰基，C1-6烷基氨基羰基，二C1-6烷基氨基羰基，卤代C1-6烷基；或R是一个基团-(CH2)p-，其中p为2或3，该基团与Ar的一个碳原子形成一个环；R1代表氢或最多四个可选取代基团，所选取的基团包括C1-6烷基，C1-6烯基，芳基，C1-6烷氧基，羟基，卤素，硝基，氰基，羧基，羧酰胺基，磺酰胺基，C1-6烷氧基羧酸酯，三氟甲基，酰氧基，邻苯二甲酰亚胺基，氨基或单烷基和双C1-6烷基氨基；R2表示一个基团-(CH2)n-NY1Y2，其中n是1到9之间的整数，Y1和Y2是独立选择的氢，C1-6烷基，C1-6烷基取代羟基，C1-6烷基氨基或双（C1-6烷基）氨基，C1-6烷基或Y1和Y2与它们连接的氮原子一起表示一个可选取代的N-连接的单环或融合环杂环基团；R3是支链或线性C1-6烷基、C3-7环烷基、C4-7环烷基烷基、可选取代的芳基或可选取代的单环或融合环芳香杂环基团；R4表示氢或C1-6烷基；一种包含该化合物的制药组合物、制备该化合物的方法以及该化合物在医学上的用途。

  公开号：

  US20010012846A1

文献信息

• Quinoline-4-carboxamide derivatives asNK-2 and NK-3 receptor antagonists
  申请人：Maria Giardina Arnaldo Giuseppe

  公开号：US20050159428A1

  公开（公告）日：2005-07-21

  A compound, or a solvate or a salt thereof, of formula (I): wherein, Ar is an optionally substituted aryl or a C 5-7 cycloalkdienyl group, or a C 5-7 cycloalkyl group or an optionally substituted single or fused ring aromatic heterocyclic group; R is C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkylalkyl, optionally substituted phenyl or phenyl C 1-6 alkyl, an optionally substituted five-membered heteroaromatic ring comprising up to four heteroatoms selected from O and N, hydroxy C 1-6 alkyl, amino C 1-6 alkyl, C 1-6 alkylaminoalkyl, di C 1-6 alkylaminoalkyl, C 1-6 acylaminoalkyl, C 1-6 alkoxyalkyl, C 1-6 alkylcarbonyl, carboxy, C 1-6 alkoxycarbonyl, C 1-6 alkoxycarbonyl C 1-6 alkyl, aminocarbonyl, C 1-6 alkylaminocarbonyl, di C 1-6 alkylaminocarbonyl, halogeno C 1-6 alkyl; or R is a group —(CH 2 ) p — wherein p is 2 or 3 which group forms a ring with a carbon atom of Ar; R 1 represents hydrogen or up to four optional substituents selected from the list consisting of: C 1-6 alkyl, C 1-6 alkenyl, aryl, C 1-6 alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, C 1-6 alkoxycarbonyl, trifluoromethyl, acyloxy, phthalimido, amino or mono- and di-C 1-6 alkylamino; R 2 represents a moiety —(CH 2 ) n —NY 1 Y 2 wherein n is an integer in the range of from 1 to 9, Y 1 and Y 2 are independently selected from hydrogen; C 1-6 -alkyl; C 1-6 alkyl substituted with hydroxy, C 1-6 alkylamino or bis(C 1-6 alkyl)amino; C 1-6 -alkenyl; aryl or aryl-C 1-6 -alkyl or Y 1 and Y 2 together with the nitrogen atom to which they are attached represent an optionally substituted N-linked single or fused ring heterocyclic group; R 3 is branched or linear C 1-6 alkyl, C 3-7 cycloalkyl, C 4-7 cycloalkylalkyl, optionally substituted aryl, or an optionally substituted single or fused ring aromatic heterocyclic group; and R 4 represents hydrogen or C 1-6 alkyl; a pharmaceutical composition comprising such a compound, process for preparing such a compound and the use of such a compound in medicine.

  化合物的化学式为（I）的化合物、溶剂化合物或盐，其中，Ar是可选取代的芳基或C5-7环烷基烯基基团，或C5-7环烷基基团或可选取代的单环或融合环芳杂环基团；R是C1-6烷基，C3-7环烷基，C3-7环烷基烷基，可选取代的苯基或苯基C1-6烷基，由最多四个氧和氮中选择的杂原子组成的可选取代的五元杂环芳香环，羟基C1-6烷基，氨基C1-6烷基，C1-6烷基氨基烷基，二C1-6烷基氨基烷基，C1-6酰胺基烷基，C1-6烷氧基烷基，C1-6烷基羰基，羧基，C1-6烷氧基羧基，C1-6烷氧基羧基C1-6烷基，氨基羰基，C1-6烷基氨基羰基，二C1-6烷基氨基羰基，卤代C1-6烷基；或R是一个基团—（CH2）p—，其中p为2或3，该基团与Ar的一个碳原子形成环；R1代表氢或最多四个可选取代基团，所选基团包括：C1-6烷基，C1-6烯基，芳基，C1-6烷氧基，羟基，卤素，硝基，氰基，羧基，羧酰胺基，磺酰胺基，C1-6烷氧基羰基，三氟甲基，酰氧基，邻苯二甲酰亚胺基，氨基或单烷基和双C1-6烷基氨基；R2表示基团—（ ）n—NY1Y2，其中n为1至9的整数，Y1和Y2独立选择自氢、C1-6烷基、用羟基、C1-6烷基氨基或双（C1-6烷基）氨基取代的C1-6烷基、C1-6烯基、芳基或芳基-C1-6烷基，或Y1和Y2与它们连接的氮原子一起表示可选取代的N-连接的单环或融合环杂环基团；R3是支链或线性C1-6烷基，C3-7环烷基，C4-7环烷基烷基，可选取代的芳基，或可选取代的单环或融合环芳杂环基团；R4表示氢或C1-6烷基；包含该化合物的制药组合物、制备该化合物的方法以及在医药中使用该化合物。
• Quinoline-4-carboxamide as NK-2 and NK-3 receptor antagonists
  申请人：Maria Glardina Arnaldo Giuseppe

  公开号：US20060205735A1

  公开（公告）日：2006-09-14

  A compound, or a solvate or a salt thereof, of formula (I): wherein, Ar is an optionally substituted aryl or a C 5-7 cycloalkdienyl group, or a C 5-7 cycloalkyl group or an optionally substituted single or fused ring aromatic heterocyclic group; R is C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkylalkyl, optionally substituted phenyl or phenyl C 1-6 alkyl, an optionally substituted five-membered heteroaromatic ring comprising up to four heteroatoms selected from O and N, hydroxy C 1-6 alkyl, amino C 1-6 alkyl, C 1-6 alkylaminoalkyl, di C 1-6 alkylaminoalkyl, C 1-6 acylaminoalkyl, C 1-6 alkoxyalkyl, C 1-6 alkylcarbonyl, carboxy, C 1-6 alkoxycarbonyl, C 1-6 alkoxycarbonyl C 1-6 alkyl, aminocarbonyl, C 1-6 alkylaminocarbonyl, di C 1-6 alkylaminocarbonyl, halogeno C 1-6 alkyl; or R is a group —(CH 2 ) p — wherein p is 2 or 3 which group forms a ring with a carbon atom of Ar; R 1 represents hydrogen or up to four optional substituents selected from the list consisting of: C 1-6 alkyl, C 1-6 alkenyl, aryl, C 1-6 alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, C 1-6 alkoxycarbonyl, trifluoromethyl, acyloxy, phthalimido, amino or mono- and di-C 1-6 alkylamino; R 2 represents a moiety —(CH 2 ) n —NY 1 Y 2 wherein n is an integer in the range of from 1 to 9, Y 1 and Y 2 are independently selected from hydrogen; C 1-6 -alkyl; C 1-6 alkyl substituted with hydroxy, C 1-6 alkylamino or bis (C 1-6 alkyl) amino; C 1-6 -alkenyl; aryl or aryl-C 1-6 -alkyl or Y 1 and Y 2 together with the nitrogen atom to which they are attached represent an optionally substituted N-linked single or fused ring heterocyclic group; R 3 is branched or linear C 1-6 alkyl, C 3-7 cycloalkyl, C 4-7 cycloalkylalkyl, optionally substituted aryl, or an optionally substituted single or fused ring aromatic heterocyclic group; and R 4 represents hydrogen or C 1-6 alkyl; a pharmaceutical composition comprising such a compound, process for preparing such a compound and the use of such a compound in medicine.

  化合物，或其溶剂化物或盐的化合物，其化学式为（I）：其中，Ar是一个可选取代的芳基或C5-7环戊二烯基团，或C5-7环烷基团或一个可选取代的单环或融合环芳杂环基团；R是C1-6烷基，C3-7环烷基，C3-7环烷基烷基，可选取代的苯基或苯基C1-6烷基，一个可选取代的五元杂环芳香环，其中包含最多四个从O和N中选择的杂原子，羟基C1-6烷基，氨基C1-6烷基，C1-6烷基氨基烷基，二C1-6烷基氨基烷基，C1-6酰胺基烷基，C1-6烷氧基烷基，C1-6烷基羰基，羧基，C1-6烷氧基羧基，C1-6烷氧基羧基C1-6烷基，氨基羰基，C1-6烷基氨基羰基，二C1-6烷基氨基羰基，卤代C1-6烷基；或R是一个基团-（CH2）p-，其中p为2或3，该基团形成一个与Ar的碳原子环；R1表示氢或来自以下列表中的最多四个可选取代基团之一：C1-6烷基，C1-6烯基，芳基，C1-6烷氧基，羟基，卤素，硝基，氰基，羧基，羧酰胺基，磺酰胺基，C1-6烷氧基羰基，三氟甲基，酰氧基，邻苯二甲酰亚胺基，氨基或单-和二-C1-6烷基氨基；R2表示一个基团-（ ）n-NY1Y2，其中n为1到9的整数，Y1和Y2独立选择自氢，C1-6烷基；C1-6烷基取代羟基，C1-6烷基氨基或双（C1-6烷基）氨基；C1-6烯基；芳基或芳基-C1-6烷基或Y1和Y2与它们附着的氮原子一起表示一个可选取代的N-连接的单环或融合环杂环基团；R3是支链或线性C1-6烷基，C3-7环烷基，C4-7环烷基烷基，可选取代的芳基，或一个可选取代的单环或融合环芳杂环基团；R4表示氢或C1-6烷基；包括这种化合物的制药组合物，制备这种化合物的方法以及在医学中使用这种化合物的用途。
• QUINOLINE-4-CARBOXAMIDE AS NK-2 AND NK-3 RECEPTOR ANTAGONISTS
  申请人：Giardina Arnaldo Maria Giuseppe

  公开号：US20070197546A1

  公开（公告）日：2007-08-23

  A compound, or a solvate or a salt thereof, of formula (I): wherein, Ar is an optionally substituted aryl or a C 5-7 cycloalkdienyl group, or a C 5-7 cycloalkyl group or an optionally substituted single or fused ring aromatic heterocyclic group,; R is C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkylalkyl, optionally substituted phenyl or phenyl C 1-6 alkyl, an optionally substituted five-membered heteroaromatic ring comprising up to four heteroatoms selected from O and N, hydroxy C 1-6 alkyl, amino C 1-6 alkyl, C 1-6 alkylaminoalkyl, di C 1-6 alkylaminoalkyl, C 1-6 acylaminoalkyl, C 1-6 alkoxyalkyl, C 1-6 alkylcarbonyl, carboxy, C 1-6 alkoxycarbonyl, C 1-6 alkoxycarbonyl C 1-6 alkyl, aminocarbonyl, C 1-6 alkylaminocarbonyl, di C 1-6 alkylaminocarbonyl, halogeno C 1-6 alkyl; or R is a group —(CH 2 ) p — wherein p is 2 or 3 which group forms a ring with a carbon atom of Ar; R 1 represents hydrogen or up to four optional substituents selected from the list consisting of: C 1-6 alkyl, C 1-6 alkenyl, aryl, C 1-6 alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, C 1-6 alkoxycarbonyl, trifluoromethyl, acyloxy, phthalimido, amino or mono- and di-C 1-6 alkylamino; R 2 represents a moiety —(CH 2 ) n —NY 1 Y 2 wherein n is an integer in the range of from 1 to 9, Y 1 and Y 2 are independently selected from hydrogen; C 1-6 -alkyl; C 1-6 alkyl substituted with hydroxy, C 1-6 alkylamino or bis (C 1-6 alkyl) amino; C 1-6 -alkenyl; aryl or aryl-C 1-6 -alkyl or Y 1 and Y 2 together with the nitrogen atom to which they are attached represent an optionally substituted N-linked single or fused ring heterocyclic group; R 3 is branched or linear C 1-6 alkyl, C 3-7 cycloalkyl, C 4-7 cycloalkylalkyl, optionally substituted aryl, or an optionally substituted single or fused ring aromatic heterocyclic group; and R4 represents hydrogen or C 1-6 alkyl; a pharmaceutical composition comprising such a compound, process for preparing such a compound and the use of such a compound in medicine.

  化合物，或其溶剂化合物或盐，其化学式为（I）：其中，Ar是可选择取代的芳基或C5-7环烯基基团，或C5-7环烷基团或可选择取代的单环或融合环芳杂环基团；R是C1-6烷基，C3-7环烷基，C3-7环烷基烷基，可选择取代的苯基或苯基C1-6烷基，包含最多四个杂原子（O和N）的可选择取代的五元杂环芳香环，羟基C1-6烷基，氨基C1-6烷基，C1-6烷基氨基烷基，二C1-6烷基氨基烷基，C1-6酰胺基烷基，C1-6烷氧基烷基，C1-6烷基羰基，羧基，C1-6烷氧羰基，C1-6烷氧羰基C1-6烷基，氨基羰基，C1-6烷基氨基羰基，二C1-6烷基氨基羰基，卤代C1-6烷基；或R是一个基团-（CH2）p-，其中p为2或3，该基团与Ar的一个碳原子形成环；R1表示氢或最多四个可选择的取代基，选自以下列表：C1-6烷基，C1-6烯基，芳基，C1-6烷氧基，羟基，卤素，硝基，氰基，羧基，羧酰胺基，磺酰胺基，C1-6烷氧羰基，三氟甲基，酰氧基，邻苯二甲酰亚胺基，氨基或单-和二-C1-6烷基氨基；R2表示一个基团-（ ）n-NY1Y2，其中n是1到9的整数，Y1和Y2独立选择自氢，C1-6烷基，C1-6烷基取代羟基，C1-6烷基氨基或双（C1-6烷基）氨基，C1-6烯基，芳基或芳基-C1-6烷基，或Y1和Y2与它们所连接的氮原子一起表示可选择取代的N-连接单环或融合环杂环基团；R3是支链或线性C1-6烷基，C3-7环烷基，C4-7环烷基烷基，可选择取代的芳基，或可选择取代的单环或融合环芳杂环基团；R4表示氢或C1-6烷基；包括这种化合物的药物组合物，制备这种化合物的方法以及在医学上使用这种化合物的用途。
• Combination treatment for depression and anxiety
  申请人：Pfizer Inc.

  公开号：US20040006135A1

  公开（公告）日：2004-01-08

  The present invention relates to a method of treating depression or anxiety in a mammal, including a human, by administering to the mammal a CNS-penetrant NK-1 receptor antagonist (e.g., a substance P receptor antagonist) in combination with an NK-3 antagonist agent. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a CNS-penetrant NK-1 receptor antagonist and an NK-3 antagonist.

  本发明涉及一种治疗哺乳动物（包括人类）的抑郁症或焦虑症的方法，该方法通过给哺乳动物（包括人类）注射一种中枢神经系统渗透的NK-1受体拮抗剂（例如物质P受体拮抗剂）与NK-3拮抗剂药物的组合来实现。本发明还涉及含有药学上可接受载体、中枢神经系统渗透的NK-1受体拮抗剂和NK-3拮抗剂的药物组合物。
• Combination, for treating depression and anxiety, containing an NK-3 receptor antagonist and a CNS penetrant NK-1 receptor antagonist
  申请人：Pfizer Products Inc.

  公开号：EP1192952A2

  公开（公告）日：2002-04-03

  The present invention relates to a method of treating depression or anxiety in a mammal, including a human, by administering to the mammal a CNS-penetrant NK-1 receptor antagonist (e.g. a substance P receptor antagonist) in combination with an NK-3 antagonist agent. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, a CNS-penetrant NK-1 receptor antagonist and an NK-3 antagonist.

  本发明涉及一种治疗哺乳动物（包括人类）抑郁症或焦虑症的方法，其方法是向哺乳动物施用中枢神经系统穿透性NK-1受体拮抗剂（例如P物质受体拮抗剂）与NK-3拮抗剂联合制剂。它还涉及含有药学上可接受的载体、中枢神经系统穿透性 NK-1 受体拮抗剂和 NK-3 拮抗剂的药物组合物。