1-norvalinamide

• 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: 1-norvalinamide
• 英文别名: L-norvalinamide；L-norvalylamide；norvalinamide；norvalylamide；(2S)-2-aminopentanamide
• 化学式: C₅H₁₂N₂O
• mdl: MFCD19203305
• 分子量: 116.163
• InChiKey: UZRUKLJLGXLGDM-BYPYZUCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  69.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-norvalinamide 、 N,N'-disuccinimidyl-2,2'-dithiosalicylate 以 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Optimization of unique, uncharged thioesters as inhibitors of HIV replication

  摘要：

  A combinatorial chemistry approach was employed to prepare a restricted library of N-substituted S-acyl-2-mercapto-benzamide thioesters. It was shown that many members of this chemotype display anti-HIV activity via their ability to interact with HIV-1, HIV-2, SIV-infected cells, cell-free virus, and chronically and latently infected cells in a manner consistent with targeting of the highly conserved HIV-1 NCp7 zinc fingers. Compounds were initially screened using two different in vitro antiviral assays and evaluated for stability in neutral buffer containing 10% pooled human Serum using a spectrophotometric assay. These data revealed that there was no significant correlation between thioester stability and antiviral activity, however, a slight inverse correlation between serum stability and virucidal activity was noted. Based on the virucidal capability and the ability to select lead compounds to inhibit virus expression from latently infected TNFalpha-induced U1 cells, we next determined if these compounds could prevent HIV cell-to-cell transmission. Several thioesters demonstrated potent inhibition of HIV cell-to-cell transmission with EC50 values in the 80-100 nM range. Thus, we have optimized a series of restricted thioesters and provided evidence that serum stability is not required for antiviral activity. Moreover, selected compounds show potential for development as topical microbicides. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.09.032
• 作为产物：
  描述：

  L-正缬氨酸 在 氯化亚砜 、 氨 作用下， 以 甲醇 为溶剂， 反应 48.0h， 生成 1-norvalinamide
  参考文献：
  名称：

  High肽对高比放射性。第1部分。[13-（3 H 4）Norvaline]-α-MSH和[2,23-Bis（（3 H 2）酪氨酸）] ACTH（1-24）† ‡的合成和生物学性质

  摘要：

  使用新型tri化装置将α-MSH和ACTH（1-24）tri化至高比放射性（> 100 Ci / mmol），可以在稍高的压力下进行tri化反应。这样可以缩短反应时间，并尽可能减少对分子的损害。ti化反应的起始化合物为[13-炔丙基甘氨酸]α-MSH和[2,23-Bis（3'，5'-二碘酪氨酸）] ACTH（1-24）。两种tri化都是定量的，并产生高纯度，完整的生物活性以及比放射性分别为115 Ci / mmol和100 Ci / mmol的产物。

  DOI：

  10.1002/hlca.19850680711

文献信息

• Discovery of 1,5-Dihydro-4<i>H</i>-imidazol-4-one Derivatives as Potent, Selective Antagonists of CXC Chemokine Receptor 2
  作者：Jinxin Che、Zhilong Wang、Zheyuan Shen、Weihao Zhuang、Huazhou Ying、Yongzhou Hu、Youhong Hu、Xin Xie、Xiaowu Dong

  DOI：10.1021/acsmedchemlett.1c00113

  日期：2021.5.13

  CXC chemokine receptors 1 (CXCR1) and 2 (CXCR2) have been demonstrated to have critical roles in cancer metastasis. Because they share high homology sequences, it is still unclear how to design selective CXCR1 or CXCR2 antagonists. Based on a pharmacophore model we built, compound 2 bearing a 1,5-dihydro-4H-imidazol-4-one scaffold was identified as a selective CXCR2 antagonist with a low CXCR1 antagonism

  CXC 趋化因子受体 1 (CXCR1) 和 2 (CXCR2) 已被证明在癌症转移中具有关键作用。由于它们具有高度同源性序列，目前尚不清楚如何设计选择性CXCR1或CXCR2拮抗剂。基于我们建立的药效团模型，带有 1,5-二氢-4 H-咪唑-4-酮支架的化合物2被鉴定为具有低 CXCR1 拮抗偏好的选择性 CXCR2 拮抗剂。经过进一步的优化和构效关系研究，化合物C5克服了化合物2的缺点，具有更高的选择性。它表现出优异的口服生物利用度和体外抗癌转移活性。分子蛋白复合物的进一步动态模拟表明，CXCR2的氨基酸残基K320对C5的选择性贡献最大。该研究为设计新型CXCR2选择性拮抗剂提供了重要线索， C5可以作为研究CXCR1和CXCR2生物学功能差异的分子工具。
• Process for N5-formylating tetrahydropteridines
  申请人：South Alabama Medical Science Foundation, USA

  公开号：US05198547A1

  公开（公告）日：1993-03-30

  Intermediates and a process for the synthesis of 6-monosubstituted tetrahydropteridine C6-stereoisomers, including (6S)-tetrahydrofolic acid. The intermediates are shown in their two enantiomeric forms as follows: ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and represent hydrogen, methyl, hydroxy, amino, alkyl or dialkylamino, alkoxy, benzyloxy, or benzylthio; R.sub.3 represents an alkene, alkyne, cycloalkyl, benzyl, alkyl (substituted with hydroxy, acetoxy, benzyloxy, alkoxy, alkylthio, amino, carboxy, oxo, or phosphate), a protected aldehyde, or ##STR2## wherein n=1 or 2, R.sub.4 is hydrogen, formyl, methyl, or propargyl, and ZZ represents an amino acid or amino acid polymer. Also, a process for tetrahydropteridine N5-formylation for the preparation of, for example, N5-formyl-(6S)-tetrahydrofolic acid.

  一种合成6-单取代四氢喜树碱C6-立体异构体（包括（6S）-四氢叶酸）的中间体和方法。其中中间体以它们的两个对映异构体形式显示如下： ##STR1## 其中R.sub.1和R.sub.2相同或不同，代表氢、甲基、羟基、氨基、烷基或二烷基氨基、烷氧基、苄氧基或苄硫基；R.sub.3代表烯烃、炔烃、环烷基、苄基、烷基（用羟基、乙酰氧基、苄氧基、烷氧基、烷基硫基、氨基、羧基、氧代或磷酸酯取代）、受保护的醛基，或##STR2## 其中n = 1或2，R.sub.4是氢、甲酰基、甲基或丙炔基，ZZ代表氨基酸或氨基酸聚合物。此外，还提供一种四氢喜树碱N5-甲酰化的方法，用于制备例如N5-甲酰-(6S)-四氢叶酸。