Boc-(D,L)-Dch-OH | 177795-78-7

• 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: Boc-(D,L)-Dch-OH
• 英文别名: 3,3-Dicyclohexyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 177795-78-7
• 化学式: C₂₀H₃₅NO₄
• 分子量: 353.502
• InChiKey: ACUROTZKSJCGCE-UHFFFAOYSA-N

物化性质

• 沸点：
  501.5±33.0 °C(Predicted)
• 密度：
  1.079±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Boc-(D,L)-Dch-OH 在 lithium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 Boc-D-Ala(dicHex)-Pro-OH
  参考文献：
  名称：

  Potent Noncovalent Thrombin Inhibitors That Utilize the Unique Amino Acid d-Dicyclohexylalanine in the P3 Position. Implications on Oral Bioavailability and Antithrombotic Efficacy

  摘要：

  In an effort to prepare orally bioavailable analogs of our previously reported thrombin inhibitor 1, we have synthesized a series of compounds that utilize the unique amino acid D-dicyclohexylalanine as a P3 Ligand. The resulting compounds are extremely potent and selective thrombin inhibitors, and the N-terminal Boc derivative 8 exhibited excellent oral bioavailability and pharmacokinetics in both rats and dogs. The des-Boc analog 6 was not orally bioavailable in rats. The high level of oral bioavailability observed with 8 appears to be a direct function of its increased lipophilicity versus other close analogs. Although increased lipophilicity may serve to increase the oral absorption of tripeptide thrombin inhibitors, it also appears to have detrimental effects on the antithrombotic properties observed with the compounds. Compound 6 performed extremely well in our in vivo antithrombotic assay, while the much more lipophilic but essentially equipotent analog 8 performed poorly. We have found that in general with this series of thrombin inhibitors as well as with other unreported series, increased lipophilicity and the associated increases in plasma protein binding have detrimental effects on 2X APTT values and subsequent performance in in vivo antithrombotic models.

  DOI：

  10.1021/jm970140s
• 作为产物：
  描述：

  2-氨基-3,3-二苯基丙酸盐酸盐 在 铱 sodium hydroxide 、 氢气 、 溶剂黄146 作用下， 以 1,4-二氧六环 为溶剂， 20.0 ℃ 、427.47 kPa 条件下， 反应 50.0h， 生成 Boc-(D,L)-Dch-OH
  参考文献：
  名称：

  Potent Noncovalent Thrombin Inhibitors That Utilize the Unique Amino Acid d-Dicyclohexylalanine in the P3 Position. Implications on Oral Bioavailability and Antithrombotic Efficacy

  摘要：

  In an effort to prepare orally bioavailable analogs of our previously reported thrombin inhibitor 1, we have synthesized a series of compounds that utilize the unique amino acid D-dicyclohexylalanine as a P3 Ligand. The resulting compounds are extremely potent and selective thrombin inhibitors, and the N-terminal Boc derivative 8 exhibited excellent oral bioavailability and pharmacokinetics in both rats and dogs. The des-Boc analog 6 was not orally bioavailable in rats. The high level of oral bioavailability observed with 8 appears to be a direct function of its increased lipophilicity versus other close analogs. Although increased lipophilicity may serve to increase the oral absorption of tripeptide thrombin inhibitors, it also appears to have detrimental effects on the antithrombotic properties observed with the compounds. Compound 6 performed extremely well in our in vivo antithrombotic assay, while the much more lipophilic but essentially equipotent analog 8 performed poorly. We have found that in general with this series of thrombin inhibitors as well as with other unreported series, increased lipophilicity and the associated increases in plasma protein binding have detrimental effects on 2X APTT values and subsequent performance in in vivo antithrombotic models.

  DOI：

  10.1021/jm970140s

文献信息

• [EN] AMINOPYRIDINE DERIVATIVES AS KALLIKREIN INHIBITORS<br/>[FR] DÉRIVÉS AMINOPYRIDINE COMME INHIBITEURS DE LA KALLICRÉINE
  申请人：VANTIA LTD

  公开号：WO2011051671A1

  公开（公告）日：2011-05-05

  The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (such as asthma or COPD); and methods of treating patients with such compounds; wherein R1 - R10 and A1 are as defined herein.

  本发明提供了式(I)的化合物：包含这种化合物的组合物；在治疗中使用这种化合物（如哮喘或慢性阻塞性肺病）；以及使用这种化合物治疗患者的方法；其中R1-R10和A1如本文所定义。
• [EN] AZAINDOLE DERIVATIVES<br/>[FR] DÉRIVÉS AZAINDOLE
  申请人：VANTIA LTD

  公开号：WO2011051672A1

  公开（公告）日：2011-05-05

  The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (such as asthma or COPD); and methods of treating patients with such compounds; wherein R1 to R20 and A1 are as defined herein.

  本发明提供了公式(I)的化合物：包含此类化合物的组合物；此类化合物在治疗（如哮喘或慢性阻塞性肺病COPD）中的应用；以及使用此类化合物治疗患者的方法；其中R1至R20和A1如本文所述定义。
• [EN] AMINOTHIAZOLE DERIVATIVES USEFUL AS KLK1 INHIBITORS<br/>[FR] DÉRIVÉS AMINOTHIAZOLE UTILES COMME INHIBITEURS DE LA KLK1
  申请人：VANTIA LTD

  公开号：WO2011051673A1

  公开（公告）日：2011-05-05

  The present invention provides compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (such as asthma or COPD); and methods of treating patients which such compounds; wherein R1 to R17 and A1 are as defined herein.

  本发明提供了公式(I)的化合物：包含此类化合物的组合物；此类化合物在治疗（如哮喘或慢性阻塞性肺病（COPD））中的应用；以及使用此类化合物治疗患者的方法；其中R1至R17和A1如本文所述定义。
• Certain thiol inhibitors of endothelin-converting enzyme
  申请人：——

  公开号：US20020082218A1

  公开（公告）日：2002-06-27

  Disclosed as endothelin converting enzyme inhibitors are the compounds of the formula 1 wherein the variables have the meanings as defined hereinbefore.

  披露的内皮素转化酶抑制剂是具有以下公式的化合物，其中变量的含义如前文所定义。
• Thrombin inhibitors
  申请人：Abbott GmbH & Co., KG

  公开号：US06740647B1

  公开（公告）日：2004-05-25

  Novel five-membered heterocyclic amidines, their preparation and use as competitive inhibitors of trypsin-like serine proteases, especially thrombin and kininogenases such as kallikrein. Pharmaceutical compositions which contain the compounds as active ingredients, and use of the compounds as thrombin inhibitors, anticoagulants and antiinflammatory agents.

  新型五元杂环胺基化物，其制备和用作胰蛋白酶样丝氨酸蛋白酶的竞争性抑制剂，特别是血栓素和激肽原酶如激肽原酶的抑制剂。含有这些化合物作为活性成分的药物组合物，以及将这些化合物用作血栓素抑制剂、抗凝剂和抗炎药剂。