8-(benzyloxy)-5-<2-<(1-phenyl-2-methylprop-2-yl)amino>-1-hydroxyethyl>carbostyril | 128232-08-6

• 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: 8-(benzyloxy)-5-<2-<(1-phenyl-2-methylprop-2-yl)amino>-1-hydroxyethyl>carbostyril
• 英文别名: 8-(benzyloxy)-5-[2-(1-phenyl-2-methlyprop-2-yl)-amino]-1-hydroxyethyl carbostyril；8-(benzyloxy)-5-{2-[(1-phenyl-2-methylprop-2-yl)amino]-1-hydroxyethyl}carbostyril；5-[1-hydroxy-2-[(2-methyl-1-phenylpropan-2-yl)amino]ethyl]-8-phenylmethoxy-1H-quinolin-2-one
• CAS: 128232-08-6
• 化学式: C₂₈H₃₀N₂O₃
• 分子量: 442.558
• InChiKey: AOAZKMQSBJWCCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(benzyloxy)-5-<2-<(1-phenyl-2-methylprop-2-yl)amino>-1-hydroxyethyl>carbostyril 在 palladium on activated charcoal 、 ammonium formate 作用下， 以 甲醇 为溶剂， 生成 8-hydroxy-5-<2-<(1-phenyl-2-methylprop-2-yl)amino>-1-hydroxyethyl>carbostyril
  参考文献：
  名称：

  从β2肾上腺素受体缓慢解离的基于8-羟基羰基乙炔的激动剂的结构亲和力概况。

  摘要：

  已显示几种基于羧甲基的β-激动剂与β2-肾上腺素能受体（β2AR）紧密结合并缓慢解离。在本研究中，有助于其结合特性的8-羟基-5- [2-[（（1-苯基-2-甲基丙-2-基）氨基] -1-羟基乙基]-卡斯蒂替利（11a）的结构特征使用一系列合成的类似物研究了beta2AR上的α-氨基丁酸。确定了k（off），该值由受体密度降低，Ki和配体诱导的受体降低的DDT1 MF-2（DDT）细胞中cAMP降低的速率估算。所有衍生物均在亚纳摩尔至中纳摩尔范围内刺激cDT在DDT细胞中的积累，并引起与（-）异丙肾上腺素相同的最大刺激。具有包含2-甲基丁基的侧链N-取代的11a的衍生物，与11a相比，苯乙基和异丙基具有更高的k（off）值和更低的亲和力。将侧链叔α碳和苯基之间的亚甲基数量从11a中的1增加到3或将其数量减少到0也导致k（off）和Ki值更高的衍生物。此外，用邻苯二酚代替11a的8-羟基碳炔

  DOI：

  10.1007/pl00005339
• 作为产物：
  描述：

  (8-苯基甲氧基喹啉-5-基)甲醇 在 乙酸酐 、 sodium hydride 、 二甲基亚砜 、 间氯过氧苯甲酸 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 32.0h， 生成 8-(benzyloxy)-5-<2-<(1-phenyl-2-methylprop-2-yl)amino>-1-hydroxyethyl>carbostyril
  参考文献：
  名称：

  Carbostyril derivatives having potent .beta.-adrenergic agonist properties

  摘要：

  Derivatives carrying a substituent in the para position of the phenyl group of 8-hydroxy-5-[2-[(1-phenyl-2-methylprop-2-yl)amino]-1-hydroxyethyl] carbostyril (10) were prepared and their effects on beta-adrenoceptors evaluated in vitro. Unsubstituted compound 10, iodo 11, amino 12, and bromoacetamido 13 derivatives (all racemic) bound to the receptor with 15-100-fold lower dissociation constants than that of (-)-isoproterenol. All the above compounds stimulated adenylate cyclase more potently than (-)-isoproterenol. The intrinsic activities of compounds 10 and 12 were equal to that of (-)-isoproterenol. The intrinsic activities of compounds 11 and 13 were 1.3 and 1.2 times that of (-)-isoproterenol, respectively. Treatment of membrane preparations with bromoacetamido derivative 13 resulted in an irreversible loss of binding sites, and thus, 13 seems to be an alkylating affinity label for beta-adrenoceptors.

  DOI：

  10.1021/jm00392a006

文献信息

• BAKER, STEPHEN P.;PITHA, JOSEF
  作者：BAKER, STEPHEN P.、PITHA, JOSEF

  DOI：——

  日期：——
• MILECKI, JAN;BAKER, STEPHEN P.;STANDIFER, KELLY M.;ISHIZU, TAKASHI;CHIDA,+, J. MED. CHEM., 30,(1987) N 9, 1563-1566
  作者：MILECKI, JAN、BAKER, STEPHEN P.、STANDIFER, KELLY M.、ISHIZU, TAKASHI、CHIDA,+

  DOI：——

  日期：——
• US4894219A
  申请人：——

  公开号：US4894219A

  公开（公告）日：1990-01-16
• Carbostyril derivatives having potent .beta.-adrenergic agonist properties
  作者：Jan Milecki、Stephen P. Baker、Kelly M. Standifer、Takashi Ishizu、Yasuhiro Chida、John W. Kusiak、Josef Pitha

  DOI：10.1021/jm00392a006

  日期：1987.9

  Derivatives carrying a substituent in the para position of the phenyl group of 8-hydroxy-5-[2-[(1-phenyl-2-methylprop-2-yl)amino]-1-hydroxyethyl] carbostyril (10) were prepared and their effects on beta-adrenoceptors evaluated in vitro. Unsubstituted compound 10, iodo 11, amino 12, and bromoacetamido 13 derivatives (all racemic) bound to the receptor with 15-100-fold lower dissociation constants than that of (-)-isoproterenol. All the above compounds stimulated adenylate cyclase more potently than (-)-isoproterenol. The intrinsic activities of compounds 10 and 12 were equal to that of (-)-isoproterenol. The intrinsic activities of compounds 11 and 13 were 1.3 and 1.2 times that of (-)-isoproterenol, respectively. Treatment of membrane preparations with bromoacetamido derivative 13 resulted in an irreversible loss of binding sites, and thus, 13 seems to be an alkylating affinity label for beta-adrenoceptors.
• Structure-affinity profile of 8-hydroxycarbostyril-based agonists that dissociate slowly from the β2-adrenoceptor
  作者：M. D. Deyrup、S. T. Nowicki、N. G. J. Richards、D. H. Otero、J. K. Harrison、S. P. Baker

  DOI：10.1007/pl00005339

  日期：1999.3.5

  its k(off). Only those derivatives with the lowest k(off)-values induced a decrease in the receptor density of DDT cell membranes following a preincubation and extensive washing. The data show that the 8-hydroxycarbostyril nucleus in conjunction with substitutions on the tertiary alpha carbon of the side chain and positioning of the phenyl group are important characteristics determining the high affinity

  已显示几种基于羧甲基的β-激动剂与β2-肾上腺素能受体（β2AR）紧密结合并缓慢解离。在本研究中，有助于其结合特性的8-羟基-5- [2-[（（1-苯基-2-甲基丙-2-基）氨基] -1-羟基乙基]-卡斯蒂替利（11a）的结构特征使用一系列合成的类似物研究了beta2AR上的α-氨基丁酸。确定了k（off），该值由受体密度降低，Ki和配体诱导的受体降低的DDT1 MF-2（DDT）细胞中cAMP降低的速率估算。所有衍生物均在亚纳摩尔至中纳摩尔范围内刺激cDT在DDT细胞中的积累，并引起与（-）异丙肾上腺素相同的最大刺激。具有包含2-甲基丁基的侧链N-取代的11a的衍生物，与11a相比，苯乙基和异丙基具有更高的k（off）值和更低的亲和力。将侧链叔α碳和苯基之间的亚甲基数量从11a中的1增加到3或将其数量减少到0也导致k（off）和Ki值更高的衍生物。此外，用邻苯二酚代替11a的8-羟基碳炔