(R)-4-benzyl-3-(3,3-dimethylbutanoyl)oxazolidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (R)-4-benzyl-3-(3,3-dimethylbutanoyl)oxazolidin-2-one
• 英文别名: (R)-4-Benzyl-3-(3,3-dimethylbutyryl)oxazolidin-2-one；(4R)-4-benzyl-3-(3,3-dimethylbutanoyl)-1,3-oxazolidin-2-one
• 化学式: C₁₆H₂₁NO₃
• 分子量: 275.348
• InChiKey: DCCLDZPTFZUXDH-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-4-benzyl-3-(3,3-dimethylbutanoyl)oxazolidin-2-one 在 lithium aluminium tetrahydride 、 正丁基锂 、 双氧水 、 二异丙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醚 、 水 为溶剂， 反应 23.0h， 生成 (R)-2,3,3-Trimethyl-1-butanol
  参考文献：
  名称：

  Rational Design of Thermodynamic and Kinetic Binding Profiles by Optimizing Surface Water Networks Coating Protein-Bound Ligands

  摘要：

  A previously studied congeneric series of thermolysin inhibitors addressing the solvent-accessible S-2' pocket with different hydrophobic substituents showed modulations of the surface water layers coating the protein-bound inhibitors. Increasing stabilization of water molecules resulted in an enthalpically more favorable binding signature, overall enhancing affinity. Based on this observation, we optimized the series by designing tailored P-2' substituents to improve and further stabilize the surface water network. MD simulations were applied to predict the putative water pattern around the bound ligands. Subsequently, the inhibitors were synthesized and characterized by high-resolution crystallography, microcalorimetry, and surface plasmon resonance. One of the designed inhibitors established the most pronounced water network of all inhibitors tested so far, composed of several fused water polygons, and showed 50-fold affinity enhancement with respect to the original methylated parent ligand. Notably, the inhibitor forming the most perfect water network also showed significantly prolonged residence time compared to the other tested inhibitors.

  DOI：

  10.1021/acs.jmedchem.6b00998
• 作为产物：
  描述：

  3,3-二甲基-1-丁酸 、 (R)-4-苄基-2-噁唑烷酮 在 三甲基乙酰氯 、 三乙胺 、 lithium chloride 、 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以84.38%的产率得到(R)-4-benzyl-3-(3,3-dimethylbutanoyl)oxazolidin-2-one
  参考文献：
  名称：

  FUNCTIONALIZED HETEROCYCLIC COMPOUNDS AS ANTIVIRAL AGENTS

  摘要：

  本发明公开了以下式(I)的化合物，或其药学上可接受的盐：这些化合物抑制由乙型肝炎病毒（HBV）编码的蛋白质或干扰乙型肝炎病毒的生命周期功能，并且还可用作抗病毒剂。本发明还涉及包括上述化合物的药物组合物，用于给患有HBV感染的受试者使用。该发明还涉及通过给予包含本发明化合物的药物组合物来治疗受试者的HBV感染的方法。

  公开号：

  US20210292320A1

文献信息

• [EN] BETA-TETRAZOLYL-PROPIONIC ACIDS AS METALLO-BETA-LACTAMASE INHIBITORS<br/>[FR] ACIDES BÊTA-TÉTRAZOLYLE-PROPIONIQUES UTILES EN TANT QU'INHIBITEURS DES MÉTALLO-BÊTA-LACTAMASES
  申请人：MERCK SHARP & DOHME

  公开号：WO2015171474A1

  公开（公告）日：2015-11-12

  The present invention relates to compounds of formula I that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

  本发明涉及公式I的化合物，这些化合物是金属β-内酰胺酶抑制剂，以及这些化合物的合成和与β-内酰胺类抗生素一起使用以克服抗性的用途。
• Quinolizinone compound and use thereof as HIV integrase inhibitor
  申请人：Satoh Motohide

  公开号：US20060084665A1

  公开（公告）日：2006-04-20

  A pharmaceutical agent having an anti-HIV action, particularly, a pharmaceutical agent having an integrase inhibitory action, is provided. The present invention relates to a quinolizinone compound represented by the following formula [I] wherein each symbol is as defined in the specification, a pharmaceutically acceptable salt thereof, and an anti-HIV agent containing same as an active ingredient. The compound of the present invention has an HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compounds can become a more effective anti-HIV agent. Since the compound has a high inhibitory activity specific for integrases, the compound can provide a safe pharmaceutical agent for human with a fewer side effects.

  提供一种具有抗HIV作用的药物代理，特别是一种具有整合酶抑制作用的药物代理。本发明涉及以下式[I]所表示的喹诺利酮化合物，其中每个符号如规范中所定义，其药学上可接受的盐，以及含有其作为活性成分的抗HIV剂。本发明的化合物具有HIV整合酶抑制作用，并可用作预防或治疗艾滋病的抗HIV剂。此外，通过与其他抗HIV剂（如蛋白酶抑制剂、逆转录酶抑制剂等）的联合使用，这些化合物可以成为更有效的抗HIV剂。由于该化合物具有针对整合酶的高抑制活性，因此该化合物可以为人类提供一种副作用较少的安全药物代理。
• Development of Methods for Convergent Synthesis of Chloroalkene Dipeptide Isosteres and Its Application
  作者：Takuya Kobayakawa、Chika Azuma、Yuki Watanabe、Shunsuke Sawamura、Atsuhiko Taniguchi、Yoshio Hayashi、Kohei Tsuji、Hirokazu Tamamura

  DOI：10.1021/acs.joc.0c03019

  日期：2021.4.2

  Improved methods of convergent synthesis for peptidomimetic utilizing a chloroalkene dipeptide isostere (CADI) are reported. In this synthesis, Fmoc- or Boc-protected carboxylic acids can be produced from N- and C-terminal analogues corresponding to each amino acid starting material via an Evans syn aldol reaction, followed by a [3.3] sigmatropic rearrangement utilizing the Ichikawa allylcyanate rearrangement

  报道了使用氯烯烃二肽等排物（CADI）的拟肽收敛合成的改进方法。在该合成中，可以通过Evans syn aldol反应，由与每种氨基酸原料相对应的N和C末端类似物，生产Fmoc-或Boc保护的羧酸，然后利用Ichikawa烯丙基氰酸酯重排进行[3.3]σ重排。反应。通过这种策略，可以将Fmoc保护的CADI直接用于固相肽合成。使用这种方法，我们还确定了含CADI的环[-Lys-Leu-Val-Phe-Phe-]拟肽，它是比母体肽更好的淀粉样β聚集抑制剂。
• Thrombin Inhibitors
  申请人：CHOBANIAN Harry

  公开号：US20150315141A1

  公开（公告）日：2015-11-05

  Compounds of the invention, which may be useful in inhibiting thrombin and associated thrombotic occlusions, have the following structure: or a pharmaceutically acceptable salt thereof, wherein m is 0 or 1; R is a heterocycle, —(CR 8 R 9 ) 1-2 NH 2 , or —(CR 8 R 9 ) 1-2 OH, wherein R 8 and R 9 , each time in which they occur, are independently H, C 1-6 alkyl, —CH 2 F, —CHF 2 , CF 3 or —CH 2 OH; W is a) —CHR 1 R 2 , where R 1 is —C(CH 3 ) 3 , and R 2 is —(CH 2 ) 1-2 OH, b) a 5- or 6-membered unsubstituted or substituted heterocycle having 1 or 2 heteroatoms selected from N and O, wherein substituted heterocycle is substituted with R 3 , c) a 9- or 10-membered unsubstituted or substituted heterocycle having 1 or 2 heteroatoms selected from N, O and S, wherein substituted heterocycle is mono-substituted with R 3 , or disubstituted with R 3 and R 4 , or d) a 3-, 4-, or 5-membered carbocyclic ring which is unsubstituted, mono-substituted with R 3 , di-substituted with R 3 and R 4 , or tri-substituted with R 3 , R 4 and R 5 ; R 3 is —CF 3 , —COOH, —COOR 7 , —C(O)R 6 , —CH(OH)R 6 , —CH 2 R 6 , R 6 , =O, halogen, R 7 , —OH, —NH 2 , or —NHSO 2 R 7 ; and R 10 is H or C 1-6 alkyl.

  本发明的化合物可用于抑制凝血酶和相关的血栓闭塞，具有以下结构：或其药学上可接受的盐，其中m为0或1；R是杂环，-(CR8R9)1-2NH2，或-(CR8R9)1-2OH，其中每次出现时R8和R9独立且为H、C1-6烷基、-CH2F、-CHF2、CF3或-CH2OH；W是a) -CHR1R2，其中R1为-C(CH3)3，R2为-(CH2)1-2OH，b) 1个或2个异原子从N和O中选择的5-或6-成员未取代或取代的杂环，其中取代的杂环取代为R3，c) 1个或2个异原子从N、O和S中选择的9-或10-成员未取代或取代的杂环，其中取代的杂环为单取代的R3，或双取代的R3和R4，或d) 未取代的3-、4-或5-成员碳环，单取代的R3，双取代的R3和R4，或三取代的R3、R4和R5；R3为-CF3、-COOH、-COOR7、-C（O）R6、-CH（OH）R6、-CH2R6、R6、=O、卤素、R7、-OH、-NH2或-NHSO2R7；R10为H或C1-6烷基。
• Design and synthesis of novel 2,7-dialkyl substituted 5(S)-amino-4(S)-hydroxy-8-phenyl-octanecarboxamides as in vitro potent peptidomimetic inhibitors of human renin
  作者：Richard Göschke、Nissim Claude Cohen、Jeanette M. Wood、Jürgen Maibaum

  DOI：10.1016/s0960-894x(97)10067-1

  日期：1997.11

  Novel low-molecular weight transition-state peptidomimetic renin inhibitors characterized by an all-carbon X-phenyl substituted octanecarboxamide skeleton have been discovered based on a topographical design approach. The in vitro most potent inhibitors 21, 25 and 26 incorporating a strong H-bond acceptor group linked to the benzyl spacer of the (P-3-P-1)-unit had IC(50)s in the low nanomolar range against human renin. (C) 1997 Elsevier Science Ltd.