6-[[(4-cyanophenyl)carbonyl]amino]-1,2,3,4-tetrahydro-1-oxonaphthylene-2-acetic acid ethyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 6-[[(4-cyanophenyl)carbonyl]amino]-1,2,3,4-tetrahydro-1-oxonaphthylene-2-acetic acid ethyl ester
• 英文别名: ethyl 2-[6-[(4-cyanobenzoyl)amino]-1-oxo-3,4-dihydro-2H-naphthalen-2-yl]acetate
• 化学式: C₂₂H₂₀N₂O₄
• 分子量: 376.412
• InChiKey: ZLBNUSDWNGJMSR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  96.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-amino-1-oxo-1,2,3,4-tetrahydronaphthyl acetic acid 在 盐酸 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 14.0h， 生成 6-[[(4-cyanophenyl)carbonyl]amino]-1,2,3,4-tetrahydro-1-oxonaphthylene-2-acetic acid ethyl ester
  参考文献：
  名称：

  Fused Bicyclic Gly-Asp β-Turn Mimics with Specific Affinity for GPIIb-IIIa

  摘要：

  Disubstituted isoquinolones 2 and 3 have affinity for GPIIb-IIIa and represent leads for further structural evaluation. Structure-activity studies centered on the bicyclic beta-turn mimic contained in these molecules indicated that this moiety could accommodate a variety of modifications. Specifically, monocyclic, 6,5-bicyclic, and 6,7-bicyclic structures provide compounds with affinity for GPIIb-IIIa. Within the 6,6-series, isoquinoline, tetralin, tetralone, and benzopyran nuclei yield potent antagonists that are specific for GPIIb-IIIa. Attachment of the arginine isostere (benzamidine) to the supporting nucleus can be accomplished with an ether or amide linkage, although the latter enhances activity. Several compounds in this series provided measurable blood levels after oral dosing. Conversion of the acid moiety in these molecules to an ester generally provided compounds which gave greater systemic exposure after oral administration. Absolute bioavailabilities in the rat for the ethyl ester prodrug derivatives of the tetralin, tetralone, and benzopyran analogues of 3 were 28%, 23%, and 24%, respectively.

  DOI：

  10.1021/jm990365y

文献信息

• Fused Bicyclic Gly-Asp β-Turn Mimics with Specific Affinity for GPIIb-IIIa
  作者：Matthew J. Fisher、Ann E. Arfstan、Ulrich Giese、Bruce P. Gunn、Cathy S. Harms、Vien Khau、Michael D. Kinnick、Terry D. Lindstrom、Michael J. Martinelli、Hans-Jürgen Mest、Michael Mohr、John M. Morin、Jeffrey T. Mullaney、Anne Nunes、Michael Paal、Achim Rapp、Gerd Rühter、Ken J. Ruterbories、Daniel J. Sall、Robert M. Scarborough、Theo Schotten、Birgit Sommer、Wolfgang Stenzel、Richard D. Towner、Suzane L. Um、Barbara G. Utterback、Robert T. Vasileff、Silke Vöelkers、Virginia L. Wyss、Joseph A. Jakubowski

  DOI：10.1021/jm990365y

  日期：1999.11.1

  Disubstituted isoquinolones 2 and 3 have affinity for GPIIb-IIIa and represent leads for further structural evaluation. Structure-activity studies centered on the bicyclic beta-turn mimic contained in these molecules indicated that this moiety could accommodate a variety of modifications. Specifically, monocyclic, 6,5-bicyclic, and 6,7-bicyclic structures provide compounds with affinity for GPIIb-IIIa. Within the 6,6-series, isoquinoline, tetralin, tetralone, and benzopyran nuclei yield potent antagonists that are specific for GPIIb-IIIa. Attachment of the arginine isostere (benzamidine) to the supporting nucleus can be accomplished with an ether or amide linkage, although the latter enhances activity. Several compounds in this series provided measurable blood levels after oral dosing. Conversion of the acid moiety in these molecules to an ester generally provided compounds which gave greater systemic exposure after oral administration. Absolute bioavailabilities in the rat for the ethyl ester prodrug derivatives of the tetralin, tetralone, and benzopyran analogues of 3 were 28%, 23%, and 24%, respectively.