N-[(4-fluorophenyl)methyl]-3-hydroxy-9-[methyl(morpholinosulfonyl)amino]-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide | 1010816-05-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: N-[(4-fluorophenyl)methyl]-3-hydroxy-9-[methyl(morpholinosulfonyl)amino]-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide
• 英文别名: N-[(4-fluorophenyl)methyl]-3-hydroxy-9-[methyl(morpholin-4-ylsulfonyl)amino]-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide
• CAS: 1010816-05-3；724444-14-8；724444-16-0
• 化学式: C₂₁H₂₆FN₅O₆S
• 分子量: 495.532
• InChiKey: IUWUIPCTVGUKAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  140
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  4-吗啉磺酰氯 、 N-(4-fluorobenzyl)-3-hydroxy-9-(methylamino)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxamide hydrochloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以43%的产率得到N-[(4-fluorophenyl)methyl]-3-hydroxy-9-[methyl(morpholinosulfonyl)amino]-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxamide
  参考文献：
  名称：

  设计和合成作为有效的和口服生物利用的HIV-1整合酶抑制剂的双环嘧啶酮。

  摘要：

  HIV整合酶是HIV基因组编码的三种酶之一，对于病毒复制至关重要，但是作为上市药物的整合酶抑制剂是最近才开始出现的。在这项研究中，我们显示了从N-甲基嘧啶酮结构向双环嘧啶酮的演变。引入适当取代的氨基部分可调节分子的物理化学性质，并在抑制HIV-1感染在细胞培养中扩散方面赋予纳米摩尔活性。广泛的SAR研究导致了磺酰胺（R）-22b，它以7 nM的IC50抑制了链转移，并以44 nM的CIC95抑制了MT4细胞中的HIV感染，

  DOI：

  10.1021/jm701164t

文献信息

• [EN] TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDINES AND RELATED COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS<br/>[FR] TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDINES ET COMPOSES CONNEXES CONVENANT COMME INHIBITEURS DE L'INTEGRASE DU VIH
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2004058756A1

  公开（公告）日：2004-07-15

  Tetrahydro-4H-pyrido[1,2-a]pyrimidines and related compounds of Formula (A): are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein n is an integer equal to zero, 1, 2 or 3, and R1, R3, R4, R12, R14, R16, R30, R32, R34 and R36 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment 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.

  Tetrahydro-4H-pyrido[1,2-a]pyrimidines及其相关化合物的化学式（A）如下：被描述为HIV整合酶的抑制剂和HIV复制的抑制剂，其中n是一个等于零、1、2或3的整数，而R1、R3、R4、R12、R14、R16、R30、R32、R34和R36在此处被定义。这些化合物对预防和治疗HIV感染以及预防、延缓艾滋病发作和治疗艾滋病具有用处。这些化合物可作为化合物本身或作为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作为药物组合物的成分，可选择性地与其他抗病毒药物、免疫调节剂、抗生素或疫苗结合使用。
• [EN] TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDINES AND RELATED COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS<br/>[FR] TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDINES ET COMPOSES ASSOCIES UTILISES EN TANT QU'INHIBITEURS DE L'INTEGRASE DU VIH
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2004058757A1

  公开（公告）日：2004-07-15

  Tetrahydro-4H-pyrido[1,2-a]pyrimidines and related compounds of Formula (I): are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein n is an integer equal to zero, 1 or 2, and R1, R3, R4, R12 and R14 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment 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.

  描述了公式（I）中的四氢-4H-吡啶并[1,2-a]嘧啶及其相关化合物作为HIV整合酶抑制剂和HIV复制抑制剂，其中n是等于零、1或2的整数，R1、R3、R4、R12和R14在此定义。这些化合物对于预防和治疗HIV感染以及预防、延缓发病和治疗艾滋病非常有用。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HIV感染和艾滋病。这些化合物及其盐可作为成分用于制药组合物中，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。
• Tetrahydro--4h-pyrido[1,2-a}pyrimidines and related compounds useful as hiv integrase inhibitors
  申请人：Crescenzi Benedetta

  公开号：US20060046985A1

  公开（公告）日：2006-03-02

  Tetrahydro-4H-pyrido[1,2-a]pyrimidines and related compounds of Formula (A): are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein n is an integer equal to zero, 1, 2 or 3, and R 1 , R 3 , R 4 , R 12 , R 14 , R 16 , R 30 , R 32 , R 34 and R 36 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment 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.

  描述了式（A）的四氢-4H-吡啶并[1,2-a]嘧啶和相关化合物作为HIV整合酶抑制剂和HIV复制抑制剂，其中n是等于零、1、2或3的整数，R1、R3、R4、R12、R14、R16、R30、R32、R34和R36在此定义。这些化合物对预防和治疗HIV感染以及预防、延缓AIDS的发生和治疗都很有用。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HIV感染和AIDS。这些化合物及其盐可以作为药物组成部分使用，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。
• Tetrahydro-4H-pyrido[1,2-a] pyrimidines useful as HIV integrase inhibitors
  申请人：Crescenzi Benedetta

  公开号：US20080176869A1

  公开（公告）日：2008-07-24

  Tetrahydro-4H-pyrido[1,2-a]pyrimidines and related compounds of Formula A: are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein n is an integer equal to zero, 1, 2 or 3, and R 1 , R 3 , R 4 , R 12 , R 14 , R 16 , R 30 , R 32 , R 34 and R 36 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment 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.

  化合物A的四氢-4H-吡啶并[1,2-a]嘧啶和相关化合物被描述为HIV整合酶抑制剂和HIV复制抑制剂，其中n是等于0、1、2或3的整数，R1、R3、R4、R12、R14、R16、R30、R32、R34和R36在此定义。这些化合物对于预防和治疗HIV感染以及预防、延迟发病和治疗艾滋病非常有用。这些化合物可作为化合物本身或作为药物可接受的盐形式用于对抗HIV感染和艾滋病。这些化合物及其盐可作为药物组合中的成分，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。
• TETRAHYDRO-4H-PYRIDO [1, 2-A] PYRIMIDINES AND RELATED COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS
  申请人：ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.

  公开号：EP1578748A1

  公开（公告）日：2005-09-28