{6-[4-(tert-Butoxycarbonylamino-imino-methyl)-benzyloxy]-chroman-2-yl}-acetic acid | 181073-93-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: {6-[4-(tert-Butoxycarbonylamino-imino-methyl)-benzyloxy]-chroman-2-yl}-acetic acid
• 英文别名: 2-[6-[[4-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenyl]methoxy]-3,4-dihydro-2H-chromen-2-yl]acetic acid
• CAS: 181073-93-8
• 化学式: C₂₄H₂₈N₂O₆
• 分子量: 440.496
• InChiKey: QURDEWJESJGMIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  三氟乙酸 、 {6-[4-(tert-Butoxycarbonylamino-imino-methyl)-benzyloxy]-chroman-2-yl}-acetic acid 生成 rac-(6-(4-(aminoiminomethyl)phenylmethoxy)-3,4-dihydro-2H-1-benzopyran-2-yl)acetic acid trifluoroacetate
  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
• 作为产物：
  描述：

  ethyl rac-(3,4-dihydro-6-hydroxy-2H-1-benzopyran-2-yl)acetate 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 {6-[4-(tert-Butoxycarbonylamino-imino-methyl)-benzyloxy]-chroman-2-yl}-acetic acid
  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

• [EN] GLYCOPROTEIN IIb/IIIa ANTAGONISTS<br/>[FR] ANTAGONISTES DE LA GLYCOPROTEINE IIb/IIIa
  申请人：ELI LILLY AND COMPANY

  公开号：WO1996022288A1

  公开（公告）日：1996-07-25

  (EN) This invention relates to certain bicyclic compounds having a nucleus formed of two fused six membered rings, for example, benzopyran, isoquinoline, isoquinolone, tetrahydronaphthalene, dihydronaphthalene, or tetralone, substituted with both basic and acidic functionality, which are useful in inhibition of platelet aggregation.(FR) Cette invention se rapporte à certains composés bicycliques possédant un noyau constitué de deux cycles hexagonaux fusionnés, par exemple, benzopyrane, isoquinoline, isoquinolone, tétrahydronaphtalène, dihydronaphtalène ou tétralone, remplacés par une fonctionnalité à la fois basique et acide. Ces composés sont utilisés dans l'inhibition de l'agrégation plaquettaire.

  该发明涉及某些具有由两个融合的六元环组成的核的双环化合物，例如苯并吡喃、异喹啉、异喹啉酮、四氢萘、二氢萘或四酮，被基础和酸性官能团取代，可用于抑制血小板聚集。
• Glycoprotein llb/llla antagonists
  申请人：——

  公开号：US20030130342A1

  公开（公告）日：2003-07-10

  This invention relates to certain bicyclic compounds having a nucleus formed of two fused six membered rings, for example, benzopyran, isoquinoline, isoquinolone, tetrahydronaphthalene, dihydronaphthalene, or tetralone, substituted with both basic and acidic functionality, which are useful in inhibition of platelet aggregation.

  本发明涉及某些自行车环化合物，其核由两个融合的六元环组成，例如苯并吡喃，异喹啉，异喹啉酮，四氢萘，二氢萘或四酮，同时带有酸性和碱性官能团，对于抑制血小板聚集具有用处。
• GLYCOPROTEIN IIb/IIIa ANTAGONISTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP0804431B1

  公开（公告）日：2002-07-24
• US5731324A
  申请人：——

  公开号：US5731324A

  公开（公告）日：1998-03-24
• US6020362A
  申请人：——

  公开号：US6020362A

  公开（公告）日：2000-02-01