Boc-N-cyclohexylglycine benzyl ester | 172834-20-7

• 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-N-cyclohexylglycine benzyl ester
• 英文别名: Boc-N-(cyclohexyl)glycine benzyl ester；benzyl 2-[cyclohexyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetate
• CAS: 172834-20-7
• 化学式: C₂₀H₂₉NO₄
• 分子量: 347.455
• InChiKey: TXSUIJJOOZZGMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Boc-N-cyclohexylglycine benzyl ester 在 氮气 、 乙酸乙酯 、 sodium hydroxide 、 ice 、 盐酸 、 氯化钠 、 正己烷 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以provided the title compound (8.89 g) as a colorless powder的产率得到N-Boc-N-cyclohexylglycine
  参考文献：
  名称：

  Bradykinin antagonist peptides incorporating N-substituted glycines

  摘要：

  本发明提供了含有N-取代甘氨酸的缓激肽类肽，特别是用于治疗由缓激肽介导的疼痛和炎症等病症的缓激肽拮抗剂肽。

  公开号：

  US05700779A1
• 作为产物：
  描述：

  2-溴乙酸苄酯 在 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 30.0h， 生成 Boc-N-cyclohexylglycine benzyl ester
  参考文献：
  名称：

  Bradykinin Receptor Antagonists Containing N-Substituted Amino Acids:  In Vitro and in Vivo B₂ and B₁ Receptor Antagonist Activity

  摘要：

  We report a systematic probing of the structural requirements of the bradykinin (BK) type 2 (B-2) receptor for antagonist activity by incorporating N-Alkyl-amino acid residues at positions 7 and 8 of a potent antagonist sequence. Compound 1 (D-Arg(0)-Arg(1)-Pro(2)-Hyp(3)-Gly(4)-Thi(5)-Ser(6)- D-Tic(7)-N-Chg(8)-Arg(9), CP-0597)(1,2) is a potent (pA(2) = 9.3, rat uterus; pK(i) = 9.62, binding, human receptor clone) Bz receptor antagonist devoid of in vitro B-1 antagonist activity (rabbit aorta). Compound 1 exhibits high potency (ED(50) = 29.2 pmol/kg/min, iv, rabbit) and duration of action when tested in models for in vivo B-2 antagonist activity. Although devoid of activity in a classic B-1 isolated tissue assay, B-1 antagonist activity for 1 was demonstrated in vivo, in a LPS-treated, inducible BK1 receptor rabbit blood pressure model (ED(50) = 1.7 nmol/kg/min). D-Arg(0) of 1 can be formally replaced by an achiral arginine surrogate, without significant loss in antagonist potency on rat uterus (compound 11, B-2 pA(2) = 9.1). Antagonist 13 (Hyp(2), NChg(8)), pK(i) = 10.2, and agonist 4 (N-methylcyclohexyl-Gly(8)), pK(i) = 10.1, also exhibited substantial binding to guinea pig ileum membrane receptors as well as a human Bz receptor clone. Very minor structural changes in the N-alkyl amino acid residues in positions 7 and 8 can modify the activity of this class of compounds from being extremely potent antagonists to tight binding partial or full agonists. These studies have resulted in a series of compounds containing inexpensive amino acid residues but which produce broad spectrum BK receptor blocking potency and exceptional in vivo duration of action.

  DOI：

  10.1021/jm950716i

文献信息

• Bradykinin antagonist peptides incorporating N-substituted glycines
  申请人：Cortech, Inc.

  公开号：US05700779A1

  公开（公告）日：1997-12-23

  The present invention provides bradykinin type peptides containing N-substituted glycines, particularly bradykinin antagonist peptides useful for the treatment of conditions mediated by bradykinin including pain and inflammation.

  本发明提供了含有N-取代甘氨酸的激肽类肽段，特别是用于治疗由激肽介导的疾病，包括疼痛和炎症的激肽拮抗肽段。
• RILUZOLE PRODRUGS AND THEIR USE
  申请人：Biohaven Pharmaceutical Holding Company Ltd.

  公开号：US20180036290A1

  公开（公告）日：2018-02-08

  Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

  本发明的制药组合物包括替代利鲁唑前药，通过释放利鲁唑治疗包括黑色素瘤、乳腺癌、脑癌和前列腺癌等癌症。利鲁唑的前药具有增强的肝代谢稳定性，并通过口服途径输送到全身循环中，然后通过酶促或一般的生物物理释放过程在血浆中裂解释放利鲁唑。
• PHARMACEUTICAL COMPOSITIONS COMPRISING RILUZOLE PRODRUGS
  申请人：Biohaven Pharmaceutical Holding Company Ltd.

  公开号：EP4011870A1

  公开（公告）日：2022-06-15

  Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

  本发明的药物组合物包括取代的利鲁唑原药，可通过释放利鲁唑治疗癌症，包括黑色素瘤、乳腺癌、脑癌和前列腺癌。利鲁唑原药对肝脏代谢的稳定性增强，通过口服进入全身循环，然后通过酶或一般生物物理释放过程裂解，在血浆中释放利鲁唑。
• Prodrugs of riluzole and their method of use
  申请人：Biohaven Pharmaceutical Holding Company Ltd.

  公开号：US10639298B2

  公开（公告）日：2020-05-05

  Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

  本发明的药物组合物包括取代的利鲁唑原药，可通过释放利鲁唑治疗癌症，包括黑色素瘤、乳腺癌、脑癌和前列腺癌。利鲁唑原药对肝脏代谢的稳定性增强，通过口服进入全身循环，然后通过酶或一般生物物理释放过程裂解，在血浆中释放利鲁唑。
• Riluzole prodrugs and their use
  申请人：Biohaven Therapeutics Ltd.

  公开号：US10905681B2

  公开（公告）日：2021-02-02

  Pharmaceutical compositions of the invention include substituted riluzole prodrugs useful for the treatment of cancers including melanoma, breast cancer, brain cancer, and prostate cancer through the release of riluzole. Prodrugs of riluzole have enhanced stability to hepatic metabolism and are delivered into systemic circulation by oral administration, and then cleaved to release riluzole in the plasma via either an enzymatic or general biophysical release process.

  本发明的药物组合物包括取代的利鲁唑原药，可通过释放利鲁唑治疗癌症，包括黑色素瘤、乳腺癌、脑癌和前列腺癌。利鲁唑原药对肝脏代谢的稳定性增强，通过口服进入全身循环，然后通过酶或一般生物物理释放过程裂解，在血浆中释放利鲁唑。