3-methyl-2-phenylquinoline-4-carbonyl chloride | 174636-71-6

• 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-methyl-2-phenylquinoline-4-carbonyl chloride
• 英文别名: 3-Methyl-2-phenyl-chinolin-4-carbonylchlorid
• CAS: 174636-71-6
• 化学式: C₁₇H₁₂ClNO
• mdl: MFCD03421088
• 分子量: 281.741
• InChiKey: KFXNVYYLWUVEAO-UHFFFAOYSA-N

物化性质

• 沸点：
  431.6±33.0 °C(Predicted)
• 密度：
  1.253±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  3-methyl-2-phenylquinoline-4-carbonyl chloride 在 一水合肼 作用下， 生成 3-methyl-2-phenylquinoline-4-carbohydrazide
  参考文献：
  名称：

  John, Journal fur praktische Chemie (Leipzig 1954), 1931, vol. <2> 131, p. 314,318

  摘要：

  DOI：
• 作为产物：
  描述：

  3-甲基-2-苯基-4-喹啉羧酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 3-methyl-2-phenylquinoline-4-carbonyl chloride
  参考文献：
  名称：

  GSK2193874的发现：瞬态潜在电位香草醛的口服活性，有效和选择性阻滞剂4。

  摘要：

  瞬时受体电位Vanilloid 4（TRPV4）是阳离子通道的瞬时受体电位（TRP）超家族的成员。TRPV4在肺部的血管内皮中表达，并调节肺泡间隔屏障的完整性。升高的肺血管压力会引起TRPV4依赖性肺水肿，因此，抑制TRPV4代表了一种新的方法来治疗与充血性心力衰竭等疾病相关的肺水肿。在这里，我们报告发现了口服活性，有效和选择性TRPV4阻滞剂3-（1,4'-bipiperidin-1'-ylmethyl）-7-bromo-N-（1-苯基环丙基）-2- [3- （三氟甲基）苯基] -4-喹啉羧酰胺（GSK2193874，28）解决了从体内研究中观察到的意外脱靶心血管不良反应。

  DOI：

  10.1021/acsmedchemlett.7b00094

文献信息

• Quinoline-4-carboxamide derivatives, their preparation and their use as neurokinin 3 ( NK-3 ) - and neurokinin 2 ( NK-3 ) receptor antagonists
  申请人：SmithKline Beecham S.p.A.

  公开号：US20020068827A1

  公开（公告）日：2002-06-06

  A compound of formula (I): 1 or a salt thereof, or a solvate thereof, wherein, Ar is an optionally substituted aryl or a C 5-7 cycloalkdienyl 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 subtitutents 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 hydrogen, C 1-6 -alkyl, hydroxy, halogen, cyano, amino, mono- or di-C 1-6 -alkylamino, alkylsulphonylamino, mono- or di-C 1-6 -alkanoylamino wherein any alkyl group is optionally substituted with an amino group or with a mono- or di-alkylamino group, or R 2 is a moiety —X—(CH 2 ) n —Y wherein X is a bond or —O— and n is an integer in the range of from 1 to 5 providing that when X is —O— n is only an integer from 2 to 5 and Y represents a group NY 1 Y 2 wherein Y 1 and Y 2 are independently selected from hydrogen, C 1-6 -alkyl, C 1-6 -alkenyl, aryl or aryl-C 1-6 -alkyl or Y is hydroxy, halogen or 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 process for the preparation of such a compound, a pharmaceutical compositon containing such a compound and the use of such a compound or composition in medicine.

  一个式为（I）的化合物： 或其盐，或其溶剂合物，其中，Ar是可选择取代的芳基或C 5-7 环烯烃基团，或可选择取代的单个或融合环芳香杂环基团； R是C 1-6 烷基，C 3-7 环烷基，C 3-7 环烷基烷基，可选择取代的苯基或苯基C 1-6 烷基，可选择取代的含有最多四个来自O和N的杂原子的五元杂芳环，羟基C 1-6 烷基，氨基C 1-6 烷基，C 1-6 烷基氨基烷基，二C 1-6 烷基氨基烷基，C 1-6 酰胺基烷基，C 1-6 烷氧基烷基，C 1-6 烷基羰基，羧基，C 1-6 烷氧羰基，C 1-6 烷氧羰基C 1-6 烷基，氨基羰基，C 1-6 烷基氨基羰基，二C 1-6 烷基氨基羰基，卤代C 1-6 烷基；或R是一个基团—(CH 2 ) p —其中p为2或3，该基团与Ar的一个碳原子形成环； R 1 代表氢或来自以下列表中选择的最多四个可选取代基：C 1-6 烷基，C 1-6 烯基，芳基，C 1-6 烷氧基，羟基，卤素，硝基，氰基，羧基，羧胺基，磺胺基，C 1-6 烷氧羰基，三氟甲基，酰氧基，邻苯二甲酰胺基，氨基或单-和双-C 1-6 烷基氨基； R 2 代表氢，C 1-6 -烷基，羟基，卤素，氰基，氨基，单-或双-C 1-6 -烷基氨基，烷基磺酰氨基，单-或双-C 1-6 -酰胺基，其中任何烷基基团可选择地取代为氨基基团或单-或双-烷基氨基基团，或R 2 是一个基团—X—(CH 2 ) n —Y，其中X是键或—O—，n是在1到5范围内的整数，要求当X为—O—时，n仅为2到5之间的整数，Y代表一个基团NY 1 Y 2 ，其中Y 1 和Y 2 分别选择自氢，C 1-6 -烷基，C 1-6 -烯基，芳基或芳基-C 1-6 -烷基，或Y为羟基，卤素或可选择取代的N-连接的单个或融合环杂环基团， R 3 是支链或直链C 1-6 烷基，C 3-7 环烷基，C 4-7 环烷基烷基，可选择取代的芳基，或可选择取代的单个或融合环芳香杂环基团；和 R 4 代表氢或C 1-6 烷基；一种制备这种化合物的方法，含有这种化合物的药物组合物以及这种化合物或组合物在医学中的用途。
• 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。
• Quinoline derivatives(2)
  申请人：SmithKline Beecham Farmaceutici S.p.A.

  公开号：US05811553A1

  公开（公告）日：1998-09-22

  NK.sub.3 receptor antagonists of formula (I): ##STR1## are useful in treating inter alia pulmonary disorders, CNS disorders and neurodegenerative disorders.

  公式（I）的NK.sub.3受体拮抗剂：##STR1##对治疗包括肺部疾病、中枢神经系统疾病和神经退行性疾病等疾病很有用。
• Quinoline derivatives as NK3 antagonists
  申请人：SmithKline Beecham S.p.A.

  公开号：US20030195204A1

  公开（公告）日：2003-10-16

  The present invention relates to a novel use, in particular a novel pharmaceutical use for a series of quinoline derivatives.

  本发明涉及一种新的用途，特别是一种新的药物用途，用于一系列喹啉衍生物。
• 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）