N-(4-fluorobenzyl)-3-hydroxy-9,9-dimethyl-4-oxo-8-(2H-tetrazol-5-ylmethyl)-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-(4-fluorobenzyl)-3-hydroxy-9,9-dimethyl-4-oxo-8-(2H-tetrazol-5-ylmethyl)-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamide
• 英文别名: N-[(4-fluorophenyl)methyl]-3-hydroxy-9,9-dimethyl-4-oxo-8-(1H-tetrazol-5-ylmethyl)-6,7-dihydropyrazino[1,2-a]pyrimidine-2-carboxamide；N-[(4-fluorophenyl)methyl]-3-hydroxy-9,9-dimethyl-4-oxo-8-(2H-tetrazol-5-ylmethyl)-6,7-dihydropyrazino[1,2-a]pyrimidine-2-carboxamide
• 化学式: C₁₉H₂₁FN₈O₃
• 分子量: 428.426
• InChiKey: SZMXBVLFEKAFCW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(4-fluorobenzyl)-3-hydroxy-9,9-dimethyl-4-oxo-8-(2H-tetrazol-5-ylmethyl)-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamide 在 sodium hydroxide 、 N,N-二乙基吡啶-4-胺 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 N-(4-fluorobenzyl)-3-hydroxy-9,9-dimethyl-8-[(1-methyl-1H-tetrazol-5-yl)methyl]-4-oxo-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamide trifluoroacetate
  参考文献：
  名称：

  WO2006/103399

  摘要：

  公开号：
• 作为产物：
  描述：

  N,N'-双芴甲氧羰基-L-赖氨酸 、 Gly-Phe-Leu-Wang resin 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 反应 0.5h， 生成 N-(4-fluorobenzyl)-3-hydroxy-9,9-dimethyl-4-oxo-8-(2H-tetrazol-5-ylmethyl)-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamide
  参考文献：
  名称：

  Glycosylation of lysine-containing pentapeptides by glucuronic acid: new insights into the Maillard reaction

  摘要：

  The formation of glycosylation products in model systems consisting Of D-glucuronic acid (GlcA) and lysine-containing peptides, such as Lys-Gly-Gly-Phe-Leu (1), Gly-Lys-Gly-Phe-Leu (4) and Ac-Gly-Lys-Gly-Phe-Leu (6), was examined to evaluate the site specificity as well as the extent and nature of the modification. Peptides were reacted with GlcA either in solution or under dry-heating conditions. From the incubations performed in solution (MeOH), the corresponding (1-deoxy-D-fructofuranos-1-yluronic acid)-peptide derivatives (Amadori compounds) were isolated. Whereas reaction of 1 resulted in the formation of mono-glycosylated Amadori compound 2 with the sugar moiety attached to the N(epsilon)-amino group of the Lys residue and its di-glycosylated analogue 3, exposure of 4 to GlcA afforded only di-glycosylated peptide 5. From the incubation of GlcA with Ac-Gly-Lys-Gly-Phe-Leu (6) performed under mild dry-heating conditions (50 degrees C) in an environment of 75% relative humidity, besides Amadori compound 7, two new Maillard reaction products were isolated that contained 3-hydroxypyridinium (8) and 3-hydroxy-picolinic acid moiety (9). The mechanism for the formation of pyridinium products is discussed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2009.11.031

文献信息

• N-(4-Fluorobenzyl)-3-hydroxy-9,9-dimethyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamides a novel class of potent HIV-1 integrase inhibitors
  作者：Alessia Petrocchi、Philip Jones、Michael Rowley、Fabrizio Fiore、Vincenzo Summa

  DOI：10.1016/j.bmcl.2009.05.098

  日期：2009.8

  A novel class of tetrahydro-pyrazinopyrimidine-2-carboxamides have been identified as HIV-1 integrase inhibitors. Optimization of the initial lead culminated in the discovery of a series of compounds with high potency on the enzyme and an antiviral cell-based activity equivalent to that showed by Raltegravir, the first in class HIV-1 integrase inhibitor.

  一类新型的四氢吡喃并嘧啶-2-羧酰胺已被鉴定为HIV-1整合酶抑制剂。初始铅的优化最终发现了一系列对酶具有高效力的化合物，其抗病毒细胞活性与Raltegravir（第一种HIV-1整合酶抑制剂）所显示的活性相当。
• HIV Integrase Inhibitors
  申请人：Summa Vincenzo

  公开号：US20090253681A1

  公开（公告）日：2009-10-08

  Compounds of Formula I are inhibitors of FHV integrase and inhibitors of FHV replication (I), wherein m, n, X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 ; R 8 , R 9 and R 10 are defined herein. The compounds are useful for the prophylaxis or treatment of infection by HTV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds are employed against HTV infection and ADDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

  式I的化合物是FHV整合酶的抑制剂和FHV复制的抑制剂（I），其中m，n，X，R1，R2，R3，R4，R5，R6，R7；R8，R9和R10在此被定义。这些化合物可用于预防或治疗HTV感染以及预防、治疗或延缓艾滋病的发病。这些化合物可作为化合物本身或药学上可接受的盐的形式用于对抗HTV感染和ADDS。这些化合物及其盐可作为药物组成部分，可选择与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。
• HIV integrase inhibitors
  申请人：Instituto di Ricerchi di Biologia Molecolare P. Angeletti S.p.A.

  公开号：US07981879B2

  公开（公告）日：2011-07-19

  Compounds of Formula I are inhibitors of FHV integrase and inhibitors of FHV replication (I), wherein m, n, X, R1, R2, R3, R4, R5, R6, R7; R8, R9 and R10 are defined herein. The compounds are useful for the prophylaxis or treatment of infection by HTV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds are employed against HTV infection and ADDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

  化学式为I的化合物是FHV整合酶的抑制剂和FHV复制的抑制剂（I），其中m，n，X，R1，R2，R3，R4，R5，R6，R7；R8，R9和R10如此定义。这些化合物对于预防或治疗HTV感染以及预防，治疗或延缓艾滋病的发作非常有用。这些化合物作为化合物本身或以药学上可接受的盐的形式用于对抗HTV感染和艾滋病，并可作为药物组成部分的成分，可选择与其他抗病毒药物，免疫调节剂，抗生素或疫苗组合使用。
• HIV INTEGRASE INHIBITORS
  申请人：Summa Vincenzo

  公开号：US20110257162A1

  公开（公告）日：2011-10-20

  Compounds of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: wherein m, n, X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are defined herein. The compounds are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

  公式I的化合物是HIV整合酶抑制剂和HIV复制抑制剂，其中m，n，X，R1，R2，R3，R4，R5，R6，R7，R8，R9和R10在此定义。这些化合物对于预防或治疗HIV感染以及预防，治疗或延迟艾滋病的发作非常有用。这些化合物可以作为化合物本身或以药学上可接受的盐的形式用于对抗HIV感染和艾滋病。这些化合物及其盐可以作为药物组成部分，可选地与其他抗病毒药物，免疫调节剂，抗生素或疫苗组合使用。
• US7981879B2
  申请人：——

  公开号：US7981879B2

  公开（公告）日：2011-07-19