1-[8-甲氧基-4-[(2-甲基苯基)氨基]喹啉-3-基]丁烷-1-酮 | 115607-61-9

• 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
• 中文名称: 1-[8-甲氧基-4-[(2-甲基苯基)氨基]喹啉-3-基]丁烷-1-酮
• 英文名称: 3-butyryl-4-(2-methylphenylamino)-8-methoxyquinoline
• 英文别名: 3-butyryl-8-methoxy-4-(2-methylphenylamino)quinoline；3-butyryl-4-(2-methylphenylamino)-8-methoxy-quinoline；1-[8-methoxy-4-(2-methylanilino)quinolin-3-yl]butan-1-one
• CAS: 115607-61-9
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: MAVJDLHBPIXVJL-UHFFFAOYSA-N

物化性质

• 沸点：
  473.2±45.0 °C(Predicted)
• 密度：
  1.162±0.06 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性

SKF96067 是一种可逆的 H+/K+-ATPase 抑制剂。

体外研究

SKF96067 对 K+ 刺激的 ATP 酶活性具有竞争性抑制作用，Ki 值为 0.39 ± 0.05 μM。它还抑制氢离子运输。在 pH 7.0、100 mM NaCl 和 1 mM KCl 存在的情况下，SKF96067 抑制 ATP 酶活性的 IC50 值为 60 ± 10 μM。

反应信息

• 作为反应物：
  描述：

  1-[8-甲氧基-4-[(2-甲基苯基)氨基]喹啉-3-基]丁烷-1-酮 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以68%的产率得到1-[8-Methoxy-4-(2-methylanilino)quinolin-3-yl]butan-1-ol
  参考文献：
  名称：

  Reversible inhibitors of the gastric (H+/K+)-ATPase. 3. 3-Substituted-4-(phenylamino)quinolines

  摘要：

  Previously, gastric (H+/K+)-ATPase inhibitors such as 2 have been prepared as analogues of 1a on the presumption that the 3-carbethoxy substituent plays a key role in establishing the orientation of the 4-arylamino group. In this paper we explore further the contribution made to activity by the quinoline 3-substituent. We show th bearing such a substituent, only a particular combination of properties provides high activity, both in as inhibitors of gastric acid secretion in vivo. The ability of the substituent to affect activity by restricting rotation about the C(quin)-N bond through a combination of both a pi-electron withdrawal and hydrogen bonding is supported by the current study. However, high activity is only achieved if the effect of this group on the quinoline pK(a) is kept to a minimum. 3-Acyl substituents provide an optimum combination of electronic properties. From this series, compound 17c (SK&F 96067) was shown to be a potent inhibitor of histamine-stimulated gastric acid secretion oral dosing in the Heidenhain pouch dog and was selected for further development and evaluation in man.

  DOI：

  10.1021/jm00096a018
• 作为产物：
  描述：

  3-butyryl-8-methoxy-4(1H)-quinolone 在 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 1-[8-甲氧基-4-[(2-甲基苯基)氨基]喹啉-3-基]丁烷-1-酮
  参考文献：
  名称：

  Reversible inhibitors of the gastric (H+/K+)-ATPase. 3. 3-Substituted-4-(phenylamino)quinolines

  摘要：

  Previously, gastric (H+/K+)-ATPase inhibitors such as 2 have been prepared as analogues of 1a on the presumption that the 3-carbethoxy substituent plays a key role in establishing the orientation of the 4-arylamino group. In this paper we explore further the contribution made to activity by the quinoline 3-substituent. We show th bearing such a substituent, only a particular combination of properties provides high activity, both in as inhibitors of gastric acid secretion in vivo. The ability of the substituent to affect activity by restricting rotation about the C(quin)-N bond through a combination of both a pi-electron withdrawal and hydrogen bonding is supported by the current study. However, high activity is only achieved if the effect of this group on the quinoline pK(a) is kept to a minimum. 3-Acyl substituents provide an optimum combination of electronic properties. From this series, compound 17c (SK&F 96067) was shown to be a potent inhibitor of histamine-stimulated gastric acid secretion oral dosing in the Heidenhain pouch dog and was selected for further development and evaluation in man.

  DOI：

  10.1021/jm00096a018

文献信息

• 4-amino-3-carbonyl substituted quinolines
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04806549A1

  公开（公告）日：1989-02-21

  This invention relates to novel substituted 4-aminoquinoline derivatives which are inhibitors of gastric acid secretion in mammals. A compound of the invention is 3-butyryl-4-(2-methylphenylamino)-8-methoxyquinoline.

  这项发明涉及新型的取代4-氨基喹啉衍生物，它们是哺乳动物胃酸分泌抑制剂。该发明的化合物是3-丁酰基-4-(2-甲基苯胺基)-8-甲氧基喹啉。
• [EN] 1, 3, 4-BENZOTRIAZEPIN-2-ONE SALTS AND THEIR USE AS CCK RECEPTOR LIGANDS<br/>[FR] SELS DE 1,3,4-BENZOTRIAZEPINE ET LEUR UTILISATION COMME LIGANDS DU RECEPTEUR DE CCK
  申请人：JOHNSON & JOHNSON

  公开号：WO2004101533A1

  公开（公告）日：2004-11-25

  This invention relates to pharmaceutically acceptable salts of compounds of formula (I) wherein: W is N or N+-O-; R2 is an optionally substituted C1 to C18 hydrocarbyl group wherein up to three C atoms may optionally be replaced by N, O and/or S atoms. R3 is -(CR11R12)m-X-(CR13R14)p-R9; m is 0, 1, 2, 3 or 4; p is 0, 1 or 2; X is a bond, -CR15=CR16-, -C≡C-, C(O)NH, NHC(O), C(O)NMe, NMeC(O), C(O)O, NHC(O)NH, NHC(O)O, OC(O)NH, NH, O, CO, SO2, SO2NH, C(O)NHNH, R9 is H ; C1 to C6 alkyl ; or phenyl, naphthyl, pyridyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, indolinyl, isoindolinyl, indolyl, isoindolyl or 2-pyridonyl substituted with -L-Q. R4 is an optionally substituted C1 to C18 hydrocarbyl group wherein up to three C atoms may optionally be replaced by N, O and/or S atoms ; and Such salts are useful, for example, for the treatment of gastrin related disorders.

  该发明涉及公式（I）化合物的药用可接受盐，其中：W为N或N+-O-；R2为可选择取代的C1至C18烃基团，其中最多三个C原子可选择地被N、O和/或S原子取代。R3为-(CR11R12)m-X-(CR13R14)p-R9；m为0、1、2、3或4；p为0、1或2；X为键、-CR15=CR16-、-C≡C-、C(O)NH、NHC(O)、C(O)NMe、NMeC(O)、C(O)O、NHC(O)NH、NHC(O)O、OC(O)NH、NH、O、CO、SO2、SO2NH、C(O)NHNH；R9为H、C1至C6烷基或苯基、萘基、吡啶基、苯并咪唑基、吲哚基、喹啉基、异喹啉基、四氢异喹啉基、吲哚啉基、异吲哚啉基、吲哚基、异吲哚基或2-吡啶酰基，取代为-L-Q。R4为可选择取代的C1至C18烃基团，其中最多三个C原子可选择地被N、O和/或S原子取代；这些盐可用于治疗胃泌素相关疾病。
• [EN] BENZOTRIAZEPINE DERIVATIVES AND THEIR USE AS GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS<br/>[FR] DERIVES DE BENZOTRIAZEPINE ET LEUR UTILISATION COMME LIGANDS DES RECEPTEURS DE LA CHOLECYSTOKININE ET DE LA GASTRINE
  申请人：BLACK JAMES FOUNDATION

  公开号：WO2004098609A1

  公开（公告）日：2004-11-18

  This invention relates to a compound of formula (I). The compound is useful for the treatment of gastrin related disorders.

  这项发明涉及一种化合物，其化学式为(I)。该化合物可用于治疗与胃泌素相关的疾病。
• Gastrin and cholecystokinin receptor ligands (III)
  申请人：——

  公开号：US20030191116A1

  公开（公告）日：2003-10-09

  Compounds of formula (I) and their pharmaceutically acceptable salts are ligands at gastrin and/or cholecystokinin receptors. X and Y are independently ═N—, —N(R 5 )—(R 5 being selected from H, Me, Et, Pr, Bn, OH and —CH 2 COOR 6 , wherein R 6 represents H, Me, Et, Pr or Bn), ═CH—, —O— or —S—; n is from 1 to 4; A is an optionally substituted 5- or 6-membered carbocyclic ring wherein (a) 1 or 2 C atoms may optionally be replaced by N, O and/or S atoms, (b) A is fused with the aromatic group in formula (I) to form a fused bicycle, and (c) the ring containing X and Y is linked to a C atom of A; R 1 is H or C 1 to C 15 hydrocarbyl wherein up to three C atoms may optionally be replaced by N, O and/or S atoms and up to three H atoms may optionally be replaced by halogen atoms; R 2 is selected from H, Me, Et, Pr and OH, each R 2 being independently selected from H, Me, Et, Pr and OH when n is greater than 1; R 3 (when n is 1) is selected from H, Me, Et and Pr; or (when n is greater than 1) each R 3 is independently selected from H, Me, Et and Pr, or two R 3 groups on neighbouring carbn atoms are linked to form a C 3 to C 6 carbocylic ring, or two R 3 groups are absent from neighbouring carbon atoms which are linked by a double bond; or R 2 and R 3 on the same carbon atom together represent an ═O group; R 4 is C 1 to C 15 hydrocarbyl wherein up to two C atoms may optionally be replaced by N, O and/or S atoms and up to three H atoms may optionally be replaced by halogen atoms; V is —CO—NH—SO 2 —Ph, —SO 2 —NH—CO—Ph, —CH 2 OH, or a group of the formula —R 7 U, (wherein U is —COOH, tetrazolyl, —CONHOH or —SO 3 H; and R 7 is a bond; C 1 to C 6 hydrocarbylene, optionally substituted by hydroxy, amino or acetamido; —O—(C 1 to C 3 alkylene)—; —SO 2 NR 8 —CHR 9 —; —CO—NR 8 —CHR 9 —, R 8 and R 9 being independently selected from H and methyl; or —NH—(CO) c —CH 2 , c being 0 or 1); or a pharmaceutically acceptable salt thereof. Compositions comprising a compound a formula (I) are also described. 1

  公式（I）的化合物及其药学上可接受的盐是胃泌素和/或胆囊收缩素受体的配体。X和Y分别独立为═N—、—N(R5)—（R5选自H、Me、Et、Pr、Bn、OH和—CH2COOR6，其中R6代表H、Me、Et、Pr或Bn）、═CH—、—O—或—S—；n为1至4；A是一个可选择替代的5-或6-成员碳环，其中（a）1或2个C原子可选择替换为N、O和/或S原子，（b）A与公式（I）中的芳香基融合形成一个融合的双环，并且（c）含有X和Y的环与A的一个C原子连接；R1为H或C1至C15烃基，其中最多可有三个C原子可选择替换为N、O和/或S原子，最多可有三个H原子可选择替换为卤素原子；R2选自H、Me、Et、Pr和OH，当n大于1时，每个R2独立选择自H、Me、Et、Pr和OH；R3（当n为1时）选自H、Me、Et和Pr；或（当n大于1时）每个R3独立选择自H、Me、Et和Pr，或相邻碳原子上的两个R3基团连接形成一个C3到C6的碳环，或相邻碳原子上缺少两个R3基团，这两个基团由双键连接；或同一碳原子上的R2和R3共同表示一个═O基团；R4为C1至C15烃基，其中最多可有两个C原子可选择替换为N、O和/或S原子，最多可有三个H原子可选择替换为卤素原子；V为—CO—NH—SO2—Ph、—SO2—NH—CO—Ph、—CH2OH或式—R7U的基团（其中U为—COOH、四唑基、—CONHOH或—SO3H；而R7为键；C1至C6烃基亚烷，可选择地被羟基、氨基或乙酰胺基替代；—O—（C1至C3烷基）—；—SO2NR8—CHR9—；—CO—NR8—CHR9—，R8和R9独立选择自H和甲基；或—NH—（CO）c—CH2，c为0或1）；或其药学上可接受的盐。还描述了包含公式（I）化合物的组合物。
• [EN] BENZOTRIAZEPINE DERIVATIVES AND THEIR USE AS GASTRIN AND CHOLECYSTOKININ RECEPTOR LIGANDS<br/>[FR] DERIVES DE BENZOTRIAZEPINE ET LEUR UTILISATION EN TANT QUE LIGANDS DE RECEPTEUR DE LA GASTRINE ET DE LA CHOLECYSTOKININE
  申请人：BLACK JAMES FOUNDATION

  公开号：WO2004098610A1

  公开（公告）日：2004-11-18

  This invention relates to a compound of formula (I). The compound is useful for the treatment of gastrin related disorders.

  这项发明涉及一种化合物，其化学式为（I）。该化合物可用于治疗与胃泌素相关的疾病。