tert-butoxycarbonyl-D-(5-hydroxy)tryptophan | 102838-87-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: tert-butoxycarbonyl-D-(5-hydroxy)tryptophan
• 英文别名: Boc-D-Trp(5-OH)-OH；Boc-5-hydroxy-D-tryptophan；(2R)-3-(5-hydroxy-1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 102838-87-9
• 化学式: C₁₆H₂₀N₂O₅
• 分子量: 320.345
• InChiKey: JELADEDZLOFFTA-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  112
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butoxycarbonyl-D-(5-hydroxy)tryptophan 在 盐酸 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 Quinoline-3-carboxylic acid [(R)-1-dipentylcarbamoyl-2-(5-hydroxy-1H-indol-3-yl)-ethyl]-amide
  参考文献：
  名称：

  Cholecystokinin (CCK) antagonists: (R)-tryptophan-based hybrid antagonists of high affinity and selectivity for CCK-A receptors

  摘要：

  The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a novel series of benzotript-based hybrid antagonists N-alpha-(3'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (9, A-67396), N-alpha-(4',8'-dihydroxy-2'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (23, A-70276), and N-alpha-(3'-quinolylcarbonyl)-(R)-5'-hydroxytryptophan di-n-pentylamide (36, A-71134) which possess respectively binding affinities of 23, 21, and 11 nM for the pancreatic CCK-A receptor and which inhibit CCK8-induced amylase secretion. Compound 9 possesses a selectivity of > 500-fold for the pancreatic CCK-A receptor over the CCK-B receptor 1.

  DOI：

  10.1021/jm00116a002

文献信息

• COMPOUNDS AND METHOD OF USE
  申请人：Ferro Therapeutics, Inc.

  公开号：US20190263802A1

  公开（公告）日：2019-08-29

  This present disclosure relates to compounds with ferroptosis inducing activity, a method of treating a subject with cancer with the compounds, and combination treatments with a second therapeutic agent.

  本公开涉及具有诱导铁死亡活性的化合物，一种使用这些化合物治疗癌症患者的方法，以及与第二种治疗药物的联合治疗。
• Design and Synthesis of Peptidomimetic Factor VIIa Inhibitors
  作者：Takuya Shiraishi、Shojiro Kadono、Masayuki Haramura、Hirofumi Kodama、Yoshiyuki Ono、Hitoshi Iikura、Tohru Esaki、Takaki Koga、Kunihiro Hattori、Yoshiaki Watanabe、Akihisa Sakamoto、Kazutaka Yoshihashi、Takehisa Kitazawa、Keiko Esaki、Masateru Ohta、Haruhiko Sato、Toshiro Kozono

  DOI：10.1248/cpb.58.38

  日期：——

  Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as a promising target for developing new anticoagulant drugs. In previous reports, we described a S3 subsite found in the X-ray crystal structure of compound 2 that bound to FVIIa/soluble tissue factor (sTF). Based on the X-ray crystal structure information and with the aim of improving the inhibition activity for FVIIa/TF and selectivity against other serine proteases, we synthesized derivatives by introducing substituents at position 5 of the indole ring of compound 2. Among them, compound 16 showed high selectivity against other serine proteases. Contrary to our expectations, compound 16 did not occupy the S3-subsite; X-ray structure analysis revealed that compound 16 improved selectivity by forming hydrogen bonds with Gln217, Thr99 and Asn100.

  选择性因子VIIa-组织因子复合物（FVIIa/TF）抑制被认为是开发新抗凝药物的一个有前景的靶点。在之前的报告中，我们描述了在化合物2的X射线晶体结构中发现的S3亚位点，该亚位点与FVIIa/可溶性组织因子（sTF）结合。基于X射线晶体结构信息，并旨在提高对FVIIa/TF的抑制活性及对其他丝氨酸蛋白酶的选择性，我们通过在化合物2的吲哚环的5位引入取代基合成了衍生物。其中，化合物16对其他丝氨酸蛋白酶显示了较高的选择性。与我们的预期相反，化合物16并未占据S3亚位点；X射线结构分析揭示，化合物16通过与Gln217、Thr99和Asn100形成氢键，提高了选择性。
• Cholecystokinin (CCK) antagonists: (R)-tryptophan-based hybrid antagonists of high affinity and selectivity for CCK-A receptors
  作者：James F. Kerwin、Frank Wagenaar、Hana Kopecka、Chun Wel Lin、Thomas Miller、David Witte、Michael Stashko、Alex M. Nadzan

  DOI：10.1021/jm00116a002

  日期：1991.12

  The intriguing structural similarities of glutamic acid based cholecystokinin (CCK) antagonists (A-64718 and A-65186) and the benzodiazepine CCK antagonist MK-329 (L-364,718) have been reported. Efforts to include the weak CCK antagonist benzotript into this construct utilizing a similar approach have resulted in a novel series of benzotript-based hybrid antagonists N-alpha-(3'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (9, A-67396), N-alpha-(4',8'-dihydroxy-2'-quinolylcarbonyl)-(R)-tryptophan di-n-pentylamide (23, A-70276), and N-alpha-(3'-quinolylcarbonyl)-(R)-5'-hydroxytryptophan di-n-pentylamide (36, A-71134) which possess respectively binding affinities of 23, 21, and 11 nM for the pancreatic CCK-A receptor and which inhibit CCK8-induced amylase secretion. Compound 9 possesses a selectivity of > 500-fold for the pancreatic CCK-A receptor over the CCK-B receptor 1.