1-甲基-2-氧代-4-甲氧基-1,2,5,6-四氢吡啶-3-甲酸乙酯 | 851726-49-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 中文名称: 1-甲基-2-氧代-4-甲氧基-1,2,5,6-四氢吡啶-3-甲酸乙酯
• 英文名称: ethyl 4-methoxy-1-methyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carboxylate
• 英文别名: ethyl 4-methoxy-1-methyl-6-oxo-2,3-dihydropyridine-5-carboxylate
• CAS: 851726-49-3
• 化学式: C₁₀H₁₅NO₄
• 分子量: 213.233
• InChiKey: SUXRQZKWFUREDJ-UHFFFAOYSA-N

物化性质

• 沸点：
  401.5±45.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-甲基-2-氧代-4-甲氧基-1,2,5,6-四氢吡啶-3-甲酸乙酯 、 1-(4-氟苄基)哌嗪-2-酮 以 乙二醇 为溶剂， 反应 0.33h， 以25%的产率得到8-(4-fluorobenzyl)-10-hydroxy-2-methyl-3,4,7,8-tetrahydropyrido-[3',4':4,5]pyrrolo[1,2-a]pyrazine-1,9(2H,6H)-dione
  参考文献：
  名称：

  8-Hydroxy-3,4-dihydropyrrolo[1,2-a]pyrazine-1(2H)-one HIV-1 integrase inhibitors

  摘要：

  A series of potent novel 8-hydroxy-3,4-dihydropyrrolo[1,2-a] pyrazine-1(2H)-one HIV-1 integrase inhibitors was identified These compounds inhibited the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 12 is active against replication of HIV-1 in cell culture with a CIC95 of 0.31 mu M. Further SAR exploration led to the preparation of pseudosymmetrical tricyclic pyrrolopyrazine inhibitors 23 and 24 with further improvement in antiviral activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.09.086
• 作为产物：
  描述：

  ethyl 1-methyl-4-hydroxy-5,6-dihydro-1H-pyridin-2-one-3-carboxylate 、 重氮甲烷 以 四氢呋喃 、 乙醚 为溶剂， 生成 1-甲基-2-氧代-4-甲氧基-1,2,5,6-四氢吡啶-3-甲酸乙酯
  参考文献：
  名称：

  [EN] HYDROXY PYRIDOPYRROLOPYRAZINE DIONE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS
  [FR] COMPOSES PYRIDOPYRROLOPYRAZINE DIONE HYDROXY UTILES COMME INHIBITEURS DE L'INTEGRASE DU VIH

  摘要：

  羟基取代的吡啶吡咯吡唑二酮化合物是HIV整合酶的抑制剂，也是HIV复制的抑制剂。在一个实施例中，二酮化合物具有以下式（I）：（I）其中a、b、A、B、R1、R2、R3、R4、R5、R6、R7和R8在此处定义。这些化合物对预防和治疗HIV感染以及预防、延迟发病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中的成分，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。

  公开号：

  WO2005041664A1

文献信息

• Respiratory syncytial virus replication inhibitors
  申请人：Janssens Eduard Frans

  公开号：US20060058309A1

  公开（公告）日：2006-03-16

  The present invention concerns compounds of formula (I), prodrugs, N-oxides, addition salts, quaternary amines, metal complexes and stereochemically isomeric forms thereof wherein -a 1 =a 2 -a 3 =a 4 - represents a radical of formula —CH═CH—CH═CH—; —N═CH—CH═CH—; —CH═N—CH═CH—; —CH═CH—N═CH—; CH═CH—CH═N—; wherein each hydrogen atom may optionally be substituted; Q is a radical of formulae (b-1), (b-2), (b-3), (b-4), (b-5), (b-6), (b-7) and (b-8), wherein Alk is C 1-6 alkanediyl; Y 1 is a bivalent radical of formula —NR 2 — or —CH(NR 2 R 4 ); X 1 is NR 4 , S, S(═O), S(═O) 2 , O, CH 2 , C(═O), CH(═CH 2 ), CH(OH), CH(CH 3 ), CH(OCH 3 ), CH(SCH 3 ), CH(NR 5a R 5b ), CH 2 —NR 4 or NR 4 —CH 2 ; X 2 is a direct bond, CH 2 , C(═O), NR 4 , C 1-4 alkyl-NR 4 , NR 4 —C 1-4 alkyl, t is 2 to 5; u is 1 to 5; v is 2 or 3; and whereby each hydrogen in Alk and in (b-3), (b-4), (b-5), (b-6), (b-7) and (b-8), may optionally be replaced by R 3 ; provided that when R 3 is hydroxy or C 1-6 alkyloxy, then R 3 cannot replace a hydrogen atom in the α position relative to a nitrogen atom; G is a direct bond or optionally substituted C 1-10 alkanediyl; R 1 is an optionally substituted bicyclic heterocycle; R 2 is hydrogen, formyl, C 1-6 alkylcarbonyl, Hetcarbonyl, pyrrolidinyl, piperidinyl, homopiperidinyl, C 3-7 cycloalkyl or C 1-10 alkyl substituted with N(R 6 ) 2 and optionally with another substituent; R 3 is hydrogen, hydroxy, C 1-6 alkyl, C 1-6 alkyloxy, arylC 1-6 alkyl or arylC 1-6 alkyloxy, R 4 is hydrogen, C 1-6 alkyl or arylC 1-6 alkyl; R 5a , R 5b , R 5c and R 5d are hydrogen or C 1-6 alkyl; or R 5a and R 5b , or R 5c and R 5d taken together from a bivalent radical of formula —(CH 2 ) S — wherein S is 4 or 5; R 6 is hydrogen, C 1-4 alkyl, formyl, hydroxyC 1-6 alkyl, C 1-6 alkylcarbonyl or C 1-6 alkyloxycarbonyl; aryl is optionally substituted phenyl; Het is pyridyl, pyrimidinyl, pyryzinyl, pyridazinyl; as respiratory syncytial virus replication inhibitors; their preparation, compositions containing them and their use as a medicine.

  本发明涉及公式（I）的化合物，前药，N-氧化物，加成盐，季铵盐，金属配合物和立体化学异构体，其中-a1 = a2-a3 = a4-表示公式—CH = CH-CH = CH-;—N = CH-CH = CH-;—CH = N-CH = CH-;—CH = CH-N = CH-; CH = CH-CH = N-;其中每个氢原子可以选择被取代；Q是公式（b-1），（b-2），（b-3），（b-4），（b-5），（b-6），（b-7）和（b-8）的基团，其中Alk是C1-6烷基二亚基；Y1是公式—NR2—或—CH（NR2R4）的双价基团；X1是NR4，S，S（═O），S（═O）2，O，CH2，C（═O），CH（═ ），CH（OH），CH（CH3），CH（O ），CH（S ），CH（NR5aR5b）， —NR4或NR4— ；X2是直接键， ，C（═O），NR4，C1-4烷基-NR4，NR4—C1-4烷基，t为2至5；u为1至5；v为2或3；其中Alk和（b-3），（b-4），（b-5），（b-6），（b-7）和（b-8）中的每个氢可以选择被R3取代；但是当R3为羟基或C1-6烷氧基时，R3不能取代氮原子相对的α位置上的氢原子；G是直接键或可选择取代的C1-10烷基二亚基；R1是可选择取代的双环杂环；R2是氢，甲酰基，C1-6烷基羰基，Hetcarbonyl，吡咯烷基，哌啶基，同半哌啶基，C3-7环烷基或C1-10烷基，其被N（R6）2和可选择另一个取代基取代；R3是氢，羟基，C1-6烷基，C1-6烷氧基，芳基C1-6烷基或芳基C1-6烷氧基；R4是氢，C1-6烷基或芳基C1-6烷基；R5a，R5b，R5c和R5d是氢或C1-6烷基；或R5a和R5b，或R5c和R5d一起形成公式—（ ）S—的双价基团，其中S为4或5；R6是氢，C1-4烷基，甲酰基，羟基C1-6烷基，C1-6烷基羰基或C1-6烷氧羰基；芳基是可选择取代的苯基；Het是吡啶基，嘧啶基，吡啶啉基，吡嗪啉基；作为呼吸道合胞病毒复制抑制剂；它们的制备，含有它们的组合物以及它们作为药物的用途。
• Hydroxy pyridopyrrolopyrazine dione compounds useful as hiv integrase inhibitors
  申请人：Wai S. John

  公开号：US20070093496A1

  公开（公告）日：2007-04-26

  Hydroxy-substituted pyridopyrrolopyrazine dione compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dione compounds are of Formula (I): (I) wherein a, b, A, B, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are defined herein. The 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.

  羟基取代的吡啶吡咯吡嗪二酮化合物是HIV整合酶抑制剂和HIV复制抑制剂。在一种实施例中，二酮化合物为公式（I）：（I）其中a，b，A，B，R1，R2，R3，R4，R5，R6，R7和R8如本文所定义。这些化合物对预防和治疗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药用盐的形式用于对抗HIV感染和艾滋病。这些化合物及其盐可用作制药组合物中的成分，可选与其他抗病毒药物，免疫调节剂，抗生素或疫苗组合使用。
• Hydroxy pyridopyrrolopyrazine dione compounds useful as HIV integrase inhibitors
  申请人：Merck & Co., Inc.

  公开号：US07435735B2

  公开（公告）日：2008-10-14

  Hydroxy-substituted pyridopyrrolopyrazine dione compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dione compounds are of Formula (I): (I) wherein a, b, A, B, R1, R2, R3, R4, R5, R6, R7 and R8 are defined herein. The 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.

  羟基取代的吡啶吡咯吡嗪二酮化合物是HIV整合酶的抑制剂和HIV复制的抑制剂。在一种实施例中，二酮化合物的公式为（I）：（I），其中a，b，A，B，R1，R2，R3，R4，R5，R6，R7和R8在此定义。这些化合物对预防和治疗HIV感染以及预防，延迟发病和治疗艾滋病非常有用。这些化合物可作为制剂本身或作为药学上可接受的盐来对抗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，可与其他抗病毒药物，免疫调节剂，抗生素或疫苗组合使用。
• EP1677599A4
  申请人：——

  公开号：EP1677599A4

  公开（公告）日：2008-10-22
• HYDROXY PYRIDOPYRROLOPYRAZINE DIONE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1677599A1

  公开（公告）日：2006-07-12