{1-[4-((S)-1-Cyclohexyl-ethylcarbamoyl)-2-phenyl-quinolin-3-ylmethyl]-piperidin-4-yl}-carbamic Acid 9H-fluoren-9-ylmethyl Ester | 345235-03-2

• 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: {1-[4-((S)-1-Cyclohexyl-ethylcarbamoyl)-2-phenyl-quinolin-3-ylmethyl]-piperidin-4-yl}-carbamic Acid 9H-fluoren-9-ylmethyl Ester
• 英文别名: {1-[4-((S)-1-cyclohexyl-ethylcarbamoyl)-2-phenyl-quinolin-3-ylmethyl)-piperidin-4-yl}-carbamic acid 9H-fluoren-9-ylmethyl ester；9H-fluoren-9-ylmethyl N-[1-[[4-[[(1S)-1-cyclohexylethyl]carbamoyl]-2-phenylquinolin-3-yl]methyl]piperidin-4-yl]carbamate
• CAS: 345235-03-2
• 化学式: C₄₅H₄₈N₄O₃
• 分子量: 692.901
• InChiKey: AOOOPVWRUFBZEE-PMERELPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  52
• 可旋转键数：
  10
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {1-[4-((S)-1-Cyclohexyl-ethylcarbamoyl)-2-phenyl-quinolin-3-ylmethyl]-piperidin-4-yl}-carbamic Acid 9H-fluoren-9-ylmethyl Ester 在 哌啶 作用下， 以 乙腈 为溶剂， 生成 3-(4-Amino-piperidin-1-ylmethyl)-2-phenyl-quinoline-4-carboxylic acid (1-cyclohexyl-ethyl)-amide
  参考文献：
  名称：

  逐步调节喹啉速激肽受体拮抗剂中神经激肽3和神经激肽2受体的亲和力和选择性。

  摘要：

  描述了使用相同的2-苯基喹啉模板从人神经激肽3受体（hNK-3R）选择拮抗剂逐步转化为有效和组合的hNK-3R和hNK-2R拮抗剂的逐步化学修饰方法。用hNK-3和hNK-2受体的3-D模型对接研究来驱动化学设计并加快对两种受体的有效和联合拮抗作用的鉴定。（S）-（+）-N-（1-环己基乙基）-3-[（4-吗啉-4-基）哌啶-1-基]甲基-2-苯基喹啉-4-羧酰胺（化合物25，SB-400238 ：hNK-3R结合亲和力，K（i）= 0.8 nM； hNK-2R结合亲和力，K（i）= 0.8 nM）成为这种方法的最佳例子。进一步的研究导致鉴定（S）-（+）-N-（1,2,2-三甲基丙基）-3-[（4-哌啶-1-基）哌啶-1-基]甲基-2-苯基喹啉-4-羧酰胺（化合物28，SB-414240：hNK-3R结合亲和力，K（i）= 193 nM；hNK-2R结合亲和力，K（i）= 1.0 nM）

  DOI：

  10.1021/jm000501v
• 作为产物：
  描述：

  3-溴甲基-2-苯基喹啉-4-羧酸甲酯 在 盐酸 、 TEA 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 22.0h， 生成 {1-[4-((S)-1-Cyclohexyl-ethylcarbamoyl)-2-phenyl-quinolin-3-ylmethyl]-piperidin-4-yl}-carbamic Acid 9H-fluoren-9-ylmethyl Ester
  参考文献：
  名称：

  逐步调节喹啉速激肽受体拮抗剂中神经激肽3和神经激肽2受体的亲和力和选择性。

  摘要：

  描述了使用相同的2-苯基喹啉模板从人神经激肽3受体（hNK-3R）选择拮抗剂逐步转化为有效和组合的hNK-3R和hNK-2R拮抗剂的逐步化学修饰方法。用hNK-3和hNK-2受体的3-D模型对接研究来驱动化学设计并加快对两种受体的有效和联合拮抗作用的鉴定。（S）-（+）-N-（1-环己基乙基）-3-[（4-吗啉-4-基）哌啶-1-基]甲基-2-苯基喹啉-4-羧酰胺（化合物25，SB-400238 ：hNK-3R结合亲和力，K（i）= 0.8 nM； hNK-2R结合亲和力，K（i）= 0.8 nM）成为这种方法的最佳例子。进一步的研究导致鉴定（S）-（+）-N-（1,2,2-三甲基丙基）-3-[（4-哌啶-1-基）哌啶-1-基]甲基-2-苯基喹啉-4-羧酰胺（化合物28，SB-414240：hNK-3R结合亲和力，K（i）= 193 nM；hNK-2R结合亲和力，K（i）= 1.0 nM）

  DOI：

  10.1021/jm000501v

文献信息

• Novel compounds
  申请人：——

  公开号：US20040102633A1

  公开（公告）日：2004-05-27

  Certain compounds of formula (I) below or a pharmaceutically acceptable salt or hydrate thereof: wherein: R 1 is H or alkyl; R 2 is —R 8 R 9 ; R 8 is a single bond or alkyl, optionally substituted one or more times by hydroxy; R 9 is aryl or cycloalkyl or heteroaryl, optionally substituted one or more times by hydroxy, alkoxy, or alkoxyalkyl; R 3 is H or alkyl or cycloalkyl or cycloalkylalkyl, optionally substituted one or more times by hydroxy or by one or more fluorines; R 4 is —NR 10 R 11 ; R 10 and R 11 are independently selected from H or alkyl, or R 10 and R 11 together with the nitrogen atom to which they are attached form a saturated or unsaturated heterocyclic ring comprising 3-8 ring members, which heterocyclic ring is unsubstituted or is substituted one or more times by one or more substituents R 12 ; R 12 is oxo or —R 13 R 14 R 15 , wherein R 13 is a single bond or alkyl, R 14 is OC(O) or C(O)O, and R 15 is H or alkyl; R 5 is an alkyl, cycloalkyl, cycloalkylalkyl, aryl, or single or fused ring aromatic heterocyclic group, which group is unsubstituted or is substituted one or more times by one or more substituents selected from halo such as fluoro, alkyl or haloalkyl such as fluoroalkyl; R 6 represents H or up to three substituents independently selected from the list consisting of: alkyl, alkenyl, aryl, alkoxy or a hydroxylated derivative thereof, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, alkoxycarbonyl, haloalkyl such as trifluoromethyl, acyloxy, amino, mono- or di-alkylamino, alkoxyamido, alkoxycarboxylate or an esterified derivative thereof; R 7 is H or halo; a is 1-6; and any of R 1 , R 3 , R 5 , R 8 , R 9 , R 10 , R 11 and R 12 may optionally be substituted one or more times by halo, hydroxy, amino, cyano, nitro, carboxy or oxo; a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds and composition in medicine.

  以下式（I）的某些化合物或其药学上可接受的盐或水合物： 其中： R1为H或烷基； R2为—R8R9； R8为单键或烷基，可以被羟基替代一次或多次； R9为芳基或环烷基或杂环烷基，可以被羟基、烷氧基或烷氧基烷基替代一次或多次； R3为H或烷基或环烷基或环烷基烷基，可以被羟基或一次或多次氟原子替代； R4为—NR10R11； R10和R11独立选择自H或烷基，或者R10和R11连同它们连接的氮原子形成一个由3-8个环成员组成的饱和或不饱和杂环，该杂环未被取代或被一个或多个取代基R12取代一次或多次； R12为氧代或—R13R14R15，其中R13为单键或烷基，R14为OC（O）或C（O）O，R15为H或烷基； R5为烷基、环烷基、环烷基烷基、芳基或单环或融合环芳基杂环基，该基未被取代或被一个或多个取代基选自卤素如氟、烷基或卤代烷基如氟代烷基取代一次或多次； R6代表H或最多三个独立选择自以下列表中的取代基：烷基、烯烃基、芳基、烷氧基或其羟基衍生物、羟基、卤素、硝基、氰基、羧基、羧胺基、磺胺基、烷氧羰基、卤代烷基如三氟甲基、酰氧基、氨基、单烷基或二烷基氨基、烷氧胺基、烷氧羧酸酯或其酯化衍生物； R7为H或卤素； a为1-6； 以及R1、R3、R5、R8、R9、R10、R11和R12中的任何一个可以选择性地被卤素、羟基、氨基、氰基、硝基、羧基或氧代基取代一次或多次； 制备这种化合物的过程，包括这种化合物的药物组合物以及这种化合物和组合物在医学中的应用。
• NOVEL COMPOUNDS
  申请人：GlaxoSmithKline S.p.A.

  公开号：EP1339691A1

  公开（公告）日：2003-09-03
• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXOSMITHKLINE SPA

  公开号：WO2002044154A1

  公开（公告）日：2002-06-06

  Certain compounds of formula (I) below or a pharmaceutically acceptable salt or hydrate thereof, wherein R1 is H or alkyl; R2 is R8R9; R8 is a single bond or alkyl, optionally substituted one or more times by hydroxy; R9 is aryl or cycloalkyl or heteroaryl, optionally substituted one or more times by hydroxy, alkoxy ou alkoxyalkyl; R3 is H or alkyl or cycloalkyl or cycloalkylalkyl, optionally substituted one or more times by hydroxy or by one or more fluorines; R4 is NR10R11; R10 and R11 Are independently selected from H or alkyl, or R10 and R11 together with the nitrogen atom to which they are attached form a saturated or unsaturated heterocyclic ring comprising 3-8 ring menbers, which heterocyclic ring is unsubstituted or is substituted one or more times by one or more substituents R12; R12 is oxo or R13R14R15, wherein R13 Is a single bond or alkyl, R14 is OC(O) or C(O)O, and R15 is H or alkyl; R5 is an alkyl, cycloalkyl, cycloalkylalkyl, aryl or single or fused ring aromatic heterocyclic group, which group is unsubstituted or is substituted one or more times by one or more substituents selected from halo such as fluoro, alkyl or haloalkyl such as fluoroalkyl; R6 represents H or up to three substituents independently selected from the list consisting of: alkyl, alkenyl, aryl, alkoxy or a hydroxylated derivative thereof, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, alkoxycarbonyl, haloalkyl such as trifluoromethyl, acyloxy, amino, mono- or di- alkylamino, alkoxyamido, alkoxycarboxylate or an esterified derivative thereof; R7 is H or halo; a is 1-6; and any of R1, R3, R5, R8, R10, R11 and R12 May optionally be substituted one or more times by halo, hydroxy, amino, cyano, nitro, carboxy or oxo; a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds and composition in medicine.
• Stepwise Modulation of Neurokinin-3 and Neurokinin-2 Receptor Affinity and Selectivity in Quinoline Tachykinin Receptor Antagonists
  作者：Frank E. Blaney、Luca F. Raveglia、Marco Artico、Stefano Cavagnera、Catherine Dartois、Carlo Farina、Mario Grugni、Stefania Gagliardi、Mark A. Luttmann、Marisa Martinelli、Guy M. M. G. Nadler、Carlo Parini、Paola Petrillo、Henry M. Sarau、Mark A. Scheideler、Douglas W. P. Hay、Giuseppe A. M. Giardina

  DOI：10.1021/jm000501v

  日期：2001.5.1

  Further studies led to the identification of (S)-(+)-N-(1,2,2-trimethylpropyl)-3-[(4-piperidin-1-yl)piperidin-1-yl]methyl-2-phenylquinoline-4-carboxamide (compound 28, SB-414240: hNK-3R binding affinity, K(i) = 193 nM; hNK-2R binding affinity, K(i) = 1.0 nM) as the first hNK-2R-selective antagonist belonging to the 2-phenylquinoline chemical class. Since some members of this chemical series showed a significant

  描述了使用相同的2-苯基喹啉模板从人神经激肽3受体（hNK-3R）选择拮抗剂逐步转化为有效和组合的hNK-3R和hNK-2R拮抗剂的逐步化学修饰方法。用hNK-3和hNK-2受体的3-D模型对接研究来驱动化学设计并加快对两种受体的有效和联合拮抗作用的鉴定。（S）-（+）-N-（1-环己基乙基）-3-[（4-吗啉-4-基）哌啶-1-基]甲基-2-苯基喹啉-4-羧酰胺（化合物25，SB-400238 ：hNK-3R结合亲和力，K（i）= 0.8 nM； hNK-2R结合亲和力，K（i）= 0.8 nM）成为这种方法的最佳例子。进一步的研究导致鉴定（S）-（+）-N-（1,2,2-三甲基丙基）-3-[（4-哌啶-1-基）哌啶-1-基]甲基-2-苯基喹啉-4-羧酰胺（化合物28，SB-414240：hNK-3R结合亲和力，K（i）= 193 nM；hNK-2R结合亲和力，K（i）= 1.0 nM）