3-(bromomethyl)-2-phenylquinoline-4-carboxylic cid | 224633-15-2

• 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: 3-(bromomethyl)-2-phenylquinoline-4-carboxylic cid
• 英文别名: 3-(bromomethyl)-2-phenylquinoline-4-carboxylic acid；3-(bromomethyl)-2-phenylquinoline-4-carboxylate
• CAS: 224633-15-2
• 化学式: C₁₇H₁₂BrNO₂
• 分子量: 342.192
• InChiKey: LMUARGWTJOUFDZ-UHFFFAOYSA-N

物化性质

• 沸点：
  506.1±50.0 °C(Predicted)
• 密度：
  1.527±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(bromomethyl)-2-phenylquinoline-4-carboxylic cid 在 sodium azide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以99.7%的产率得到methyl 3-(azidomethyl)-2-phenylquinoline-4-carboxylate
  参考文献：
  名称：

  Alkylsulphonamide Quinolines

  摘要：

  式I中的化合物，其中R1、A、R2、R3、R4、R5、R8、n、m、q和r如规范中所述，药用盐，制备方法，含有该化合物的药物组合物，以及使用该化合物的方法。

  公开号：

  US20080293765A1
• 作为产物：
  描述：

  3-甲基-2-苯基-4-喹啉羧酸 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 24.0h， 生成 3-(bromomethyl)-2-phenylquinoline-4-carboxylic cid
  参考文献：
  名称：

  Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 2. Identification of (S)-N-(1-Phenylpropyl)-3-hydroxy-2- phenylquinoline-4-carboxamide (SB 223412)

  摘要：

  Optimization of the previously reported 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonist 14, with regard to potential metabolic instability of the ester moiety and affinity and selectivity for the human neurokinin-3 (hNK-3) receptor, is described. The ester functionality could be successfully replaced by the ketone (31) or by lower alkyl groups (Et, 21, or n-Pr, 24). Investigation of the substitution pattern of the quinoline ring resulted in the identification of position 3 as a key position to enhance hNK-3 binding affinity and selectivity for the hNK-3 versus the hNK-2 receptor. All of the chemical groups introduced at this position, with the exception of halogens, increased the hNK-3 binding affinity, and compounds 53 (3-OH, SE 223412, hNK-3-CHO binding K-i = 1.4 nM) and 55 (3-NHz, hNK-3-CHO binding K-i = 1.2 nM) were the most potent compounds of this series. Selectivity studies versus the other neurokinin receptors (hNK-8-CHO and hNK-1-CHO) revealed that 53 is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 mu M. In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits). Overall, the biological data indicate that (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (53, SE 223412) may serve as a pharmacological tool in animal models of disease to assess the functional and pathophysiological role of the NK-3 receptor and to establish therapeutic indications for non-peptide NK-3 receptor antagonists.

  DOI：

  10.1021/jm980633c

文献信息

• Quinoline derivatives as neurokinin receptor antagonists
  申请人：Carling William Robert

  公开号：US20090054440A1

  公开（公告）日：2009-02-26

  The present invention relates to substituted quinoline hydrazides of Formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , X, Y and Z are defined herein, pharmaceutical compositions comprising them and their use in treating diseases mediated by neurokinin-2 and/or neurokinin-3 (NK-3) receptors. These compounds can thus be used in methods of treatment to suppress and treat such disorders.

  本发明涉及式(I)所示的取代喹啉酰肼：其中R1、R2、R3、R4、R5、X、Y和Z在此定义，包含它们的药物组合物及其在治疗由神经激肽-2和/或神经激肽-3 (NK-3)受体介导的疾病中的用途。因此，这些化合物可用于治疗方法，以抑制和治疗这些疾病。
• Quinoline derivatives as nk-3 antagonists
  申请人：——

  公开号：US20040097518A1

  公开（公告）日：2004-05-20

  Certain compounds of formula (I) below or a pharmaceutically acceptable salt or hydrate thereof: 1 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： 1 制备这些化合物的方法，包含这些化合物的药物组合物以及这些化合物和组合物在医学上的用途。
• Quinoline derivatives as nk-3 and nk-2 antagonists
  申请人：——

  公开号：US20040082589A1

  公开（公告）日：2004-04-29

  Certain compounds of formula (I) below or a pharmaceutically acceptable salt or hydrate thereof: 1 wherein: R 1 is H or alkyl; R 2 is aryl, cycloalkyl or heteroaryl; R 3 is H or C 1-3 alkyl, optionally substituted by one or more fluorines; R 4 is H, R 8 NR 9 R 10 , R 11 R 13 or R 11 R 12 R 13 ; R 8 is a single bond or alkyl; R 9 and R 10 are selected independently from H, alkyl, cycloalkyl or cycloalkylC 1-3 alkyl, aryl or arylC 1-3 alkyl, or R 9 and R 10 together with the nitrogen atom to which they are attached form a saturated or unsaturated heterocyclic ring which is optionally substituted by one or more fluorines; R 11 is alkyl, alkenyl, aryl, heteroaryl, cycloalkyl, arylalkyl or cycloalkylalkyl, optionally substituted one or more times by C 1-3 alkyl, phenyl and/or phenylC 1-3 alkyl; R 12 is alkyl or alkoxy, optionally substituted one or more times by C 1-3 alkyl and/or by phenyl; R 13 is H or COO R 14 ; R 14 is H or alkyl; R 5 is branched or linear alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, or a single or fused ring aromatic heterocyclic group; R 6 represents H or up to three substituents independently selected from the list consisting of: alkyl, alkenyl, aryl, alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, alkoxycarbonyl, trifluoromethyl, acyloxy, amino or mono- or di-alkylamino; R 7 is H or halo; a is 1-6; and any of R 2 , R 5 , R 8 , R 9 , R 10 , R 11 , R 12 and R 14 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.

  以下公式（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为芳香基、环烷基或杂环芳基； R3为H或C1-3烷基，可选择性地被一个或多个氟代取代； R4为H、R8NR9R10、R11R13或R11R12R13； R8为单键或烷基； R9和R10分别选自H、烷基、环烷基或环烷基C1-3烷基、芳香基或芳香基C1-3烷基，或R9和R10与它们所连接的氮原子一起形成一个饱和或不饱和的杂环环，该环可选择性地被一个或多个氟代取代； R11为烷基、烯烃基、芳香基、杂环芳基、环烷基、芳香基烷基或环烷基烷基，可选择性地被C1-3烷基、苯基和/或苯基C1-3烷基取代一次或多次； R12为烷基或烷氧基，可选择性地被C1-3烷基和/或苯基取代一次或多次； R13为H或COOR14； R14为H或烷基； R5为支链或线性烷基、环烷基、环烷基烷基、芳香基、芳香基烷基或单环或融合环的芳香杂环基团； R6代表H或最多三个独立选择的取代基，所述取代基来自以下列表：烷基、烯烃基、芳香基、烷氧基、羟基、卤素、硝基、氰基、羧基、羧酰胺基、磺酰胺基、烷氧羰基、三氟甲基、酰氧基、氨基或单烷基或二烷基胺基； R7为H或卤素； a为1-6； R2、R5、R8、R9、R10、R11、R12和R14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； 制备这种化合物的方法，包括这种化合物的制药组合物以及这种化合物和组合物在医学上的使用。
• Quinoline-4-carboxamide derivatives as NK-3 and NK-2 receptor antagonists
  申请人：Farina Carlo

  公开号：US20050176762A1

  公开（公告）日：2005-08-11

  A compound of formula (I) as detailed in the specification or a pharmaceutically acceptable salt or solvate thereof, a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds in medicine.

  公式（I）的化合物，其详细说明或其药学上可接受的盐或溶剂，制备这种化合物的过程，包含这种化合物的药物组合物以及这种化合物在医学上的用途。
• Quinoline-4-carboxamide derivatives as nk-3 and nk-2 receptor antagonists
  申请人：——

  公开号：US20040152726A1

  公开（公告）日：2004-08-05

  A compound of formula (I) as detailed in the specification or a pharmaceutically acceptable salt or solvate thereof, a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds in medicine. Figure (I) wherein: R 1 is H or alkyl; R 2 is aryl or cycloalkyl or heteroaryl; R 3 is H or alkyl, wherein the group may be optionally substituted by one or more fluorine atoms; R 4 is NR 8 R 9 ; R 8 is H, lakyl or R 11 R 12 and R 9 is H, alkyl or R 13 R 14 ; or R 8 and R 9 together with the N atom to wich they are attached form a heterocyclic ring comprising 4-8 ring members, said ring members optionally including in addition to said N atom one or more further heteroatoms selected from N, O or S; and further detailed in the specification. 1

  公式（I）的化合物，如规范中所述，或其药学上可接受的盐或溶剂，制备这种化合物的方法，包括这种化合物的制药组合物以及这种化合物在医学上的用途。其中：R1为H或烷基；R2为芳基、环烷基或杂环芳基；R3为H或烷基，该基团可以选择性地被一个或多个氟原子取代；R4为NR8R9；R8为H、烷基或R11R12，R9为H、烷基或R13R14；或R8和R9与它们连接的N原子一起形成一个杂环环，包括4-8个环成员，所述环成员可以选择性地包括除所述N原子之外的一个或多个进一步的杂原子，所述杂原子选择自N、O或S；更多详细信息请参见规范。