N-[3-[2-[6-[(9aS)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-5-fluoro-2-methylpyrimidin-4-yl]hydrazinyl]-2-(cyclopentylmethyl)-3-oxopropyl]-N-hydroxyformamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-[3-[2-[6-[(9aS)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-5-fluoro-2-methylpyrimidin-4-yl]hydrazinyl]-2-(cyclopentylmethyl)-3-oxopropyl]-N-hydroxyformamide
• 化学式: C₂₂H₃₄FN₇O₄
• 分子量: 479.5
• InChiKey: SWHNZGMQMGFQGW-ZVAWYAOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  10

文献信息

• [EN] PROCESS FOR PREPARING PEPTIDE DEFORMYLASE INHIBITORS<br/>[FR] PROCÉDÉS DE PRÉPARATION D'INHIBITEURS DE LA PEPTIDE DÉFORMYLASE
  申请人：GLAXOSMITHKLINE IP NO 2 LTD

  公开号：WO2014141181A1

  公开（公告）日：2014-09-18

  The present invention relates to processes for making 2-(alkyl)-3-[2-(5-fluoro-4-pyrimidinyl) hydrazino]-3-oxopropyl}hydroxyformamide compounds of Formula (I), or pharmaceutically acceptable salts thereof and corresponding intermediates thereof, where such compounds are useful in the inhibition of bacterial peptide deformylase (PDF) activity and in treatment methods for bacterial infections.

  本发明涉及制备Formula(I)中的2-(烷基)-3-[2-(5-氟-4-嘧啶基)肼基]-3-氧代丙基}羟基甲酰胺化合物或其药用可接受的盐及相应的中间体的方法，其中这些化合物在抑制细菌肽变形酶（PDF）活性和治疗细菌感染的方法中具有用途。
• Spiro three-membered ring, spiro five-membered ring peptide deformylase inhibitor and use thereof in antibacteria and anti-tumor
  申请人：Rudong Ruien Pharmaceutical Technology Co. Ltd

  公开号：US10738028B2

  公开（公告）日：2020-08-11

  Disclosed are the anti-bacterial activity and the anti-tumor activity of a class of new spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor. The spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor of the present invention, as a class of new anti-bacterial agent, are effective against many antibiotic-resistant Gram-positive strains by inhibiting the activity of the peptide deformylase required in the synthesis of bacterial proteins, and do not affect the synthetic process of the main proteins of the human body, thus selectively killing bacteria. The spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor of the present invention, as a class of new anti-bacterial agent, can affect the energy balance of the cancer cells through inhibiting the peptide deformylase of the mitochondria in the cells, so that the mitochondrial membrane is depolarized, ATP is exhausted and cell apoptosis is promoted, and has good inhibitory activities on many cancer cell strains such as colorectal cancer, leukemia, lung cancer, gastric cancer, cervical cancer, breast cancer, prostatic cancer, liver cancer and osteosarcoma at relatively lower concentrations. The structure of exemplary invention spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitors are represented by one or more of:

  本发明公开了一类新型螺三元环和螺五元环肽变形酶抑制剂的抗菌活性和抗肿瘤活性。本发明的螺三元环和螺五元环肽基变形酶抑制剂作为一类新型抗菌剂，通过抑制细菌蛋白质合成过程中所需的肽基变形酶的活性，对多种抗生素耐药的革兰氏阳性菌株有效，且不影响人体主要蛋白质的合成过程，从而选择性地杀灭细菌。本发明的螺三元环、螺五元环肽变形酶抑制剂作为一类新型抗菌剂，通过抑制细胞内线粒体的肽变形酶，使线粒体膜去极化，从而影响癌细胞的能量平衡、在相对较低的浓度下，对大肠癌、白血病、肺癌、胃癌、宫颈癌、乳腺癌、前列腺癌、肝癌、骨肉瘤等多种癌细胞株具有良好的抑制活性。示例性发明螺三元环和螺五元环肽变形酶抑制剂的结构由以下一种或多种表示：
• SPIRO THREE-MEMBERED RING, SPIRO FIVE-MEMBERED RING PEPTIDE DEFORMYLASE INHIBITOR AND USE THEREOF IN ANTIBACTERIA AND ANTI-TUMOR
  申请人：Rudong Ruien Pharmaceutical Technology Co.Ltd

  公开号：US20190194165A1

  公开（公告）日：2019-06-27

  Disclosed are the anti-bacterial activity and the anti-tumor activity of a class of new spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor. The spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor of the present invention, as a class of new anti-bacterial agent, are effective against many antibiotic-resistant Gram-positive strains by inhibiting the activity of the peptide deformylase required in the synthesis of bacterial proteins, and do not affect the synthetic process of the main proteins of the human body, thus selectively killing bacteria. The spiro three-membered ring and spiro five-membered ring peptide deformylase inhibitor of the present invention, as a class of new anti-bacterial agent, can affect the energy balance of the cancer cells through inhibiting the peptide deformylase of the mitochondria in the cells, so that the mitochondrial membrane is depolarized, ATP is exhausted and cell apoptosis is promoted, and has good inhibitory activities on many cancer cell strains such as colorectal cancer, leukemia, lung cancer, gastric cancer, cervical cancer, breast cancer, prostatic cancer, liver cancer and osteosarcoma at relatively lower concentrations.