HCl*Pro-BHA

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: HCl*Pro-BHA
• 英文别名: (2S)-N-benzhydrylpyrrolidin-1-ium-2-carboxamide;chloride
• 化学式: C₁₈H₂₀N₂O*ClH
• 分子量: 316.831
• InChiKey: VMTTXLBIJVTDCE-NTISSMGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.38
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  45.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  HCl*Pro-BHA 在 N-甲基吗啉 、 N-[(6-chlorobenzotriazol-1-yl)oxy-(dimethylamino)methylene]-dimethyl-ammonium tetrafluoroborate 作用下， 以 二甲基亚砜 为溶剂， 反应 1.84h， 生成 Boc-NMe-Ala-Cys(SStBu)-Pro-BHA
  参考文献：
  名称：

  [EN] CONJUGATED ANTICANCER SMAC ANALOGS
  [FR] ANALOGUES SMAC ANTICANCÉREUX CONJUGUÉS

  摘要：

  脂质共轭的一价和二价次级线粒体衍生的半胱氨酸蛋白酶激活剂（Smac）衍生物已被合成并用于体外和体内抗癌活性的检验。使用这些化合物治疗癌症的方法也被披露。

  公开号：

  WO2017044592A1
• 作为产物：
  描述：

  叔丁氧羰基-脯氨酰-琥珀酰亚胺 、 二苯甲胺 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.5h， 以98.7%的产率得到HCl*Pro-BHA
  参考文献：
  名称：

  [EN] CONJUGATED ANTICANCER SMAC ANALOGS
  [FR] ANALOGUES SMAC ANTICANCÉREUX CONJUGUÉS

  摘要：

  脂质共轭的一价和二价次级线粒体衍生的半胱氨酸蛋白酶激活剂（Smac）衍生物已被合成并用于体外和体内抗癌活性的检验。使用这些化合物治疗癌症的方法也被披露。

  公开号：

  WO2017044592A1

文献信息

• [EN] CONJUGATED ANTICANCER SMAC ANALOGS<br/>[FR] ANALOGUES SMAC ANTICANCÉREUX CONJUGUÉS
  申请人：UNIV CALIFORNIA

  公开号：WO2017044592A1

  公开（公告）日：2017-03-16

  Lipid-conjugated monovalent and bivalent secondary mitochondria derived activator of caspases (Smac) derivatives were synthesized and examined for in vitro and in vivo anticancer activity. Methods for treating cancer with these compounds are also disclosed.

  脂质共轭的一价和二价次级线粒体衍生的半胱氨酸蛋白酶激活剂（Smac）衍生物已被合成并用于体外和体内抗癌活性的检验。使用这些化合物治疗癌症的方法也被披露。
• [EN] COMPOUNDS THAT INHIBIT ASPARAGINE SYNTHETASE AND THEIR METHODS OF USE<br/>[FR] COMPOSÉS QUI INHIBENT L'ASPARAGINE SYNTHÉTASE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ASINEX CORP

  公开号：WO2021236475A1

  公开（公告）日：2021-11-25

  The invention is relevant to chemistry of organic compounds, pharmacology and medicine, and is related to treatment and/or prevention of a disease or condition, associated with over expressed or dysregulated glutamine-dependent asparagine synthetase, using a new family of chemical compounds having the ability to inhibit asparagine synthetase (ASMS). New chemical compounds with high inhibitory activity against asparagine synthase and promising for use in therapy. This invention also covers pharmaceutical compositions containing therapeutically effective amount of compound according to the invention and method of treatment and/or prevention of a disease or condition, associated with over-expressed or dysregulated glutamine dependent asparagine synthetase.

  这项发明涉及到有机化合物的化学、药理学和医学，与治疗和/或预防与过度表达或失调的谷氨酰胺依赖性天冬氨酸合成酶相关的疾病或症状有关，使用具有抑制天冬氨酸合成酶（ASMS）能力的新一类化学化合物。具有高抑制活性的新化学化合物对于天冬氨酸合成酶具有潜在治疗用途。该发明还涵盖含有根据该发明的化合物的治疗有效量的药物组合物，以及与过度表达或失调的谷氨酰胺依赖性天冬氨酸合成酶相关的疾病或症状的治疗和/或预防方法。
• 2-Nitrophenylcarbamoyl-(<i>S</i>)-prolyl-(<i>S</i>)-3-(2-naphthyl)alanyl-<i>N</i>-benzyl-<i>N</i>- methylamide (SDZ NKT 343), a Potent Human NK₁ Tachykinin Receptor Antagonist with Good Oral Analgesic Activity in Chronic Pain Models
  作者：C. Walpole、S. Y. Ko、M. Brown、D. Beattie、E. Campbell、F. Dickenson、S. Ewan、G. A. Hughes、M. Lemaire、J. Lerpiniere、S. Patel、L. Urban

  DOI：10.1021/jm970499g

  日期：1998.8.1

  A lead compound which had sub-micromolar affinity for the rabbit NK1 receptor but negligible affinity for rat NK1 receptors, 3a, was discovered by directed screening. 2-Substitution in the ring of the benzylthiourea substituent in the initial lead was found to be important, and halogens (Cl, Br) in this position were found to improve affinity for the human receptor. The activity of a series of 2-halo-substituted benzylthioureas was then optimized by modification of the proline diphenylmethyl amide, guided by a simple conceptual model based on structural overlay between these early antagonists and NK1 selective peptides. In this way, aromatic amino acid amides were identified which had improved affinity with respect to the starting diphenylmethyl (DPM) amides. The first sub-nanomolar ligand for the human NK1 receptor which arose from this series, 4af, combined a 2-chlorobenzylthiourea unit with a 2-naphthylalanine amide. Contemporaneously it was discovered that the benzylthiourea unit could be simplified to a phenylthiourea providing that an appropriate 2-substituent was also incorporated. Combination of these two series gave 2-NO2 phenylthiourea analogues which led directly to the analogous urea, 5f(2-nitrophenylcarbamoyl-(S)-prolyl-(S)-3-(2-naphthyl)alanyl-N-benzyl-N-methylamide, SDZ NKT 343), a highly potent ligand for the human NK1 receptor (K-i = 0.16 nM). In addition to its high in vitro potency, 5f proved to be a potent orally active analgesic in guinea pig models of chronic inflammatory and neuropathic pain. The nature of the 2-aryl substituent was found to be critical for oral activity in this series. Clinical evaluation of 5f as a novel analgesic agent is currently underway.
• Lipid-conjugated Smac analogues
  作者：Ewa D. Micewicz、Josephine A. Ratikan、Alan J. Waring、Julian P. Whitelegge、William H. McBride、Piotr Ruchala

  DOI：10.1016/j.bmcl.2015.09.017

  日期：2015.10

  A small library of monovalent and bivalent Smac mimics was synthesized based on 2 types of monomers, with general structure NMeAla-Xaa-Pro-BHA (Xaa = Cys or Lys). Position 2 of the compounds was utilized to dimerize both types of monomers employing various bis-reactive linkers, as well as to modify selected compounds with lipids. The resulting library was screened in vitro against metastatic human breast cancer cell line MDA-MB-231, and the two most active compounds selected for in vivo studies. The most active lipid-conjugated analogue M11, showed in vivo activity while administered both subcutaneously and orally. Collectively, our findings suggest that lipidation may be a viable approach in the development of new Smac-based therapeutic leads. (C) 2015 Elsevier Ltd. All rights reserved.