5-((tert-butoxycarbonyl)(methyl)amino)pentanoic acid | 124073-08-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 5-((tert-butoxycarbonyl)(methyl)amino)pentanoic acid
• 英文别名: 5-[(Tert-butoxycarbonyl)(methyl)amino]pentanoic acid；5-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]pentanoic acid
• CAS: 124073-08-1
• 化学式: C₁₁H₂₁NO₄
• 分子量: 231.292
• InChiKey: KYNLCVANIZMWBO-UHFFFAOYSA-N

物化性质

• 沸点：
  345.1±21.0 °C(Predicted)
• 密度：
  1.073±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-((tert-butoxycarbonyl)(methyl)amino)pentanoic acid 在 吡啶 、 亚磷酸三苯酯 、 sodium carbonate 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 0.04h， 生成 (E)-2-((1-methylpiperidin-2-ylidene)amino)-5-nitro-N-phenylbenzamide
  参考文献：
  名称：

  一锅，（的区域专一组件ë）从δ-和γ氨基酸-benzamidines通过分子内重排氨基喹唑啉†

  摘要：

  描述了由喹唑啉酮的区域特异性重排产生的新型N-联苯甲idine的有效生成。该方法学研究探索了反应参数，包括变化的溶剂和温度的影响以及结构核心上变化的电子取代基。就反应条件和反应范围而言，对转化进行了广泛的优化，从而形成了始终如一地以高收率提供各种功能化am的方案。该方法可实现以前无法实现的区域结构衍生化，并且多步过程也简化为可伸缩的五步序列，可有效地从N中获得药理学上独特的（E）-苯甲酰胺基s-BOC保护的γ-和δ-氨基酸。

  DOI：

  10.1039/c5ob02378e
• 作为产物：
  描述：

  5-氨基颉草酸 在 sodium hydride 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 20.0h， 生成 5-((tert-butoxycarbonyl)(methyl)amino)pentanoic acid
  参考文献：
  名称：

  Antimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures

  摘要：

  Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development., We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.2-55 nM). A set of carboxylate derivatives demonstrated markedly improved in vitro metabolic stability (t(1/2) > 2 h). A selected ligand showed significant in vivo efficacy with 73% of parasitemia reduction in a mouse model. Five new cocrystal structures with PvSHMT were solved at 2.3-2.6 angstrom resolution, revealing a unique water-mediated interaction with Tyr63 at the end of the para-aminobenzoate channel. They also displayed the high degree of conformational flexibility of the Cys364-loop lining this channel.

  DOI：

  10.1021/acs.jmedchem.7b00008

文献信息

• [EN] HYDROXYMETHYL SUBSTITUTED DIHYDROISOXAZOLE DERIVATIVES USEFUL AS ANTIBIOTIC AGENTS<br/>[FR] DERIVES DE DIHYDROISOXAZOLE A SUBSTITUTION HYDROXYMETHYLE POUVANT SERVIR D'AGENTS ANTIBIOTIQUES
  申请人：ASTRAZENECA AB

  公开号：WO2004078753A1

  公开（公告）日：2004-09-16

  Compounds of the formula (I), or a pharmaceutically-acceptable salt, or an in-vivo-hydrolysable ester thereof, (I) R1a is NH(C=W)R5 or (a); W is O or S; R2 and R3 are for example H or F; R1 is for example hydrogen, or halogen; R5 is selected from hydrogen, (2-6C)alkyl (optionally substituted); R6 and R7 are independently selected from hydrogen, and (1-4C)alkyl (optionally substituted); wherein R4 is either a hydroxymethyl substituent on C-4' of the isoxazoline ring; or R4 is a hydroxymethyl substituent on C-5' of the isoxazoline ring and the stereochemistry at C-5' of the isoxazoline ring and at C-5 of the oxazolidinone ring is selected, such that the compound of formula (I) is a single diastereomer; are useful as antibacterial agents; and processes for their manufacture and pharmaceutical compositions containing them are described.

  公式（I）的化合物，或其药学上可接受的盐，或其体内可水解的酯，（I）中R1a是NH(C=W)R5或（a）；W是O或S；R2和R3例如是H或F；R1例如是氢或卤素；R5从氢，（2-6C）烷基（可选地取代）中选择；R6和R7独立地从氢和（1-4C）烷基（可选地取代）中选择；其中R4是异噁唑环的C-4'上的羟甲基取代基；或R4是异噁唑环的C-5'上的羟甲基取代基，且异噁唑环的C-5'和噁唑烷酮环的C-5的立体化学被选择，使得公式（I）的化合物是单一对映体；它们作为抗菌剂是有用的；并描述了它们的制备方法和含有它们的药物组合物。
• [EN] BIFUNCTIONAL DEGRADERS AND THEIR METHODS OF USE<br/>[FR] AGENTS DE DÉGRADATION BIFONCTIONNELS ET LEURS MÉTHODES D'UTILISATION
  申请人：NOVARTIS AG

  公开号：WO2021053495A1

  公开（公告）日：2021-03-25

  Described herein are bifunctional degrader compounds, their various targets, their preparation, pharmaceutical compositions comprising them, and their use in the treatment of conditions, diseases, and disorders mediated by various target proteins.

  本发明描述了双功能降解剂化合物、它们的多种靶点、它们的制备方法、包含它们的药物组合物，以及它们在治疗由各种靶点蛋白质介导的条件、疾病和失调症中的用途。
• Synthesis of Cucurbitacin B Derivatives as Potential Anti-Hepatocellular Carcinoma Agents
  作者：Weizhi Ge、Xinyi Chen、Fangzhi Han、Zhongquan Liu、Tianpeng Wang、Mengmeng Wang、Yue Chen、Yahui Ding、Quan Zhang

  DOI：10.3390/molecules23123345

  日期：——

  Cucurbitacin B shows potent activity against tumor cells, but its high toxicity limits its application in the clinic. A series of cucurbitacin B derivatives was synthesized and evaluated for their anti-hepatocellular carcinoma (HCC) activities against the HepG-2 cell line. These compounds were also tested for their toxicity against the L-O2 normal cell line. The compound with the most potential, 10b

  葫芦素B对肿瘤细胞显示有效活性，但其高毒性限制了其在临床中的应用。合成了一系列葫芦素B衍生物，并评估了它们对HepG-2细胞系的抗肝细胞癌（HCC）活性。还测试了这些化合物对L-O2正常细胞系的毒性。潜力最大的化合物10b对HepG-2细胞系表现出有效的活性，IC50值为0.63μM。此外，化合物10b的TI值最高（4.71），比其母体化合物葫芦素B高14.7倍。初步的分子机理研究表明10b可以抑制P-STAT3诱导线粒体凋亡。途径。
• [EN] NEW BICYCLIC DERIVATIVES HAVING BETA2 ADRENERGIC AGONIST AND M3 MUSCARINIC ANTAGONIST ACTIVITIES<br/>[FR] NOUVEAUX DÉRIVÉS BICYCLIQUES PRÉSENTANT UNE ACTIVITÉ AGONISTE DU RÉCEPTEUR BÊTA-2 ADRÉNERGIQUE ET UNE ACTIVITÉ ANTAGONISTE DU RÉCEPTEUR MUSCARINIQUE M3
  申请人：ALMIRALL SA

  公开号：WO2016046390A1

  公开（公告）日：2016-03-31

  The present invention relates to novel compounds having β2 adrenergic agonist and M3 muscarinic antagonist dual activity, to pharmaceutical compositions containing them, to the process for their preparation and to their use in respiratory therapies.

  本发明涉及具有β2肾上腺素受体激动剂和M3肌样受体拮抗剂双重活性的新化合物，包含它们的药物组合物，它们的制备过程以及它们在呼吸疗法中的应用。
• [EN] INHIBITORS OF ARGININE GINGIPAIN<br/>[FR] INHIBITEURS D'ARGININE GINGIPAÏNE
  申请人：CORTEXYME INC

  公开号：WO2017083433A1

  公开（公告）日：2017-05-18

  The present invention relates generally to therapeutics targeting the bacterium Porphyromonas gingivalis, including its proteases arginine gingipain A/B (Rgp), and their use for the treatment of disorders associated with P. gingivalis infection, including brain disorders such as Alzheimer's disease. In certain embodiments, the invention provides compounds according to Formula I, as described herein, and pharmaceutically acceptable salts thereof.

  本发明通常涉及治疗靶向细菌 Porphyromonas gingivalis 的治疗药物，包括其蛋白酶精氨酸龈蛋白酶 A/B（Rgp），以及它们用于治疗与 P. gingivalis 感染相关的疾病，包括脑部疾病如阿尔茨海默病。在某些实施例中，本发明提供根据本文所述的 Formula I 的化合物及其药用盐。