(2S)-3-[4-[5-[(2-methylpropan-2-yl)oxycarbonylamino]pentoxy]phenyl]-2-(phenylmethoxycarbonylamino)propanoic acid | 142355-78-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-3-[4-[5-[(2-methylpropan-2-yl)oxycarbonylamino]pentoxy]phenyl]-2-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 142355-78-0
• 化学式: C₂₇H₃₆N₂O₇
• 分子量: 500.592
• InChiKey: QABRYWWMFCIFIB-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  36
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-3-[4-[5-[(2-methylpropan-2-yl)oxycarbonylamino]pentoxy]phenyl]-2-(phenylmethoxycarbonylamino)propanoic acid 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 生成 2-(S)-<<(benzyloxy)carbonyl>amino>-3-<4-<(5-N-aminopentyl)oxy>phenyl>propionic acid
  参考文献：
  名称：

  Non-Peptide Fibrinogen Receptor Antagonists. 2. Optimization of a Tyrosine Template as a Mimic for Arg-Gly-Asp

  摘要：

  Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation. Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation. Compound 23m (L-700,462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of > 24 000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors. Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with iv infusions of 0.1-10 mu g/kg/min of 23m in anesthetized dogs, with 10 mu g/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol. Platelet aggregatability returned rapidly after the termination of the 23m infusions. These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.

  DOI：

  10.1021/jm00042a007
• 作为产物：
  描述：

  5-(N-叔丁氧羰基氨基)-1-戊醇 在 四溴化碳 、 sodium hydride 、 三苯基膦 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 49.0h， 生成 (2S)-3-[4-[5-[(2-methylpropan-2-yl)oxycarbonylamino]pentoxy]phenyl]-2-(phenylmethoxycarbonylamino)propanoic acid
  参考文献：
  名称：

  Non-Peptide Fibrinogen Receptor Antagonists. 2. Optimization of a Tyrosine Template as a Mimic for Arg-Gly-Asp

  摘要：

  Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation. Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation. Compound 23m (L-700,462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of > 24 000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors. Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with iv infusions of 0.1-10 mu g/kg/min of 23m in anesthetized dogs, with 10 mu g/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol. Platelet aggregatability returned rapidly after the termination of the 23m infusions. These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.

  DOI：

  10.1021/jm00042a007

文献信息

• Inhibiting osteoclast-mediated bone resorption using aminoalkyl-substituted phenyl derivatives
  申请人：MERCK & CO. INC.

  公开号：EP0528586A1

  公开（公告）日：1993-02-24

  Compounds of the general formula and the pharmaceutically acceptable salts thereof wherein    n is an integer of from 0 to 6;    Y is CH₂, O, SO₂, -CONH-, -NHCO-, or    R¹ and R² are independently       hydrogen,       C₁₋₈ alkyl,       heterocyclyl C₀₋₄ alkyl,       aryl C₀₋₄ alkyl,       amino C₁₋₄ alkyl,       C₁₋₄ alkylamino C₁₋₄ alkyl, or       C₃₋₈ cycloalkyl    wherein R¹ and R² may be unsubstituted or substituted with one or more groups chosen from R³, where    R³ is       hydrogen,       C₁₋₆ alkyl,       hydroxy C₀₋₄ alkyl,       carboxy C₀₋₄ alkyl,       C₁₋₄ alkyloxy C₀₋₄ alkyl,       heterocyclyl C₀₋₄ alkyl,       aryl C₀₋₄ alkyl,       halogen, or       CF₃;    R⁴ is       C₁₋₆ alkyl,       heterocyclyl C₀₋₄ alkyl, or       aryl C₀₋₄ alkyl;    R⁵ is       hydrogen,       C₁₋₆ alkyl,       aryl C₀₋₃ alkyl, or       C₁₋₆ alkylcarbonyloxyethyl are used for the manufacture of a medicament for treating osteoporosis by inhibiting the bone resorption activity of osteoclasts.

  通式化合物 及其药学上可接受的盐类 其中 n 是 0 至 6 的整数； Y 是 CH₂、O、SO₂、-CONH-、-NHCO- 或 R¹ 和 R² 独立地为 氢、 C₁₋₈烷基、 杂环 C₀₋₄ 烷基、 芳基 C₀₋₄烷基 氨基 C₁₋₄烷基、 C₁₋₄ 烷基氨基 C₁₋₄ 烷基，或 C₃₋₈ 环烷基 其中 R¹ 和 R² 可以是未取代的，也可以被一个或多个选自 R³ 的基团取代，其中 R³ 是 氢 C₁₋₆ 烷基、 羟基 C₀₋₄烷基、 羧基 C₀₋₄烷基、 C₁₋₄ 烷氧基 C₀₋₄ 烷基、 杂环 C₀₋₄ 烷基、 芳基 C₀₋₄烷基、 卤素，或 CF₃； R⁴ 是 C₁₋₆ 烷基、 杂环 C₀₋₄ 烷基，或 芳基 C₀₋₄烷基； R⁵ 是 氢、 C₁₋₆烷基、 芳基 C₀₋₃烷基，或 C₁₋₆烷基碳酰氧基乙基 用于制造通过抑制破骨细胞的骨吸收活性来治疗骨质疏松症的药物。
• US5217994A
  申请人：——

  公开号：US5217994A

  公开（公告）日：1993-06-08
• Non-Peptide Fibrinogen Receptor Antagonists. 2. Optimization of a Tyrosine Template as a Mimic for Arg-Gly-Asp
  作者：Melissa S. Egbertson、Charles T.-C. Chang、Mark E. Duggan、Robert J. Gould、Wasyl Halczenko、George D. Hartman、William L. Laswell、Joseph J. Lynch、Robert J. Lynch

  DOI：10.1021/jm00042a007

  日期：1994.8

  Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation. Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation. Compound 23m (L-700,462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of > 24 000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors. Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with iv infusions of 0.1-10 mu g/kg/min of 23m in anesthetized dogs, with 10 mu g/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol. Platelet aggregatability returned rapidly after the termination of the 23m infusions. These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.