ethyl 4-[(4,6-dimethyl-1H-benzimidazol-2-yl)amino]piperidine-1-carboxylate | 856706-19-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: ethyl 4-[(4,6-dimethyl-1H-benzimidazol-2-yl)amino]piperidine-1-carboxylate
• CAS: 856706-19-9
• 化学式: C₁₇H₂₄N₄O₂
• 分子量: 316.403
• InChiKey: OWTJXAZOOLMPBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  70.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-[(4,6-dimethyl-1H-benzimidazol-2-yl)amino]piperidine-1-carboxylate 、 2-(氯甲基)-6-甲基吡啶-3-醇盐酸盐 在 potassium carbonate 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 24.0h， 生成 Ethyl 4-[[1-[(3-hydroxy-6-methylpyridin-2-yl)methyl]-4,6-dimethylbenzimidazol-2-yl]amino]piperidine-1-carboxylate 、 Ethyl 4-[[1-[(3-hydroxy-6-methylpyridin-2-yl)methyl]-5,7-dimethylbenzimidazol-2-yl]amino]piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] MORPHOLINYL CONTAINING BENZIMIDAZOLES AS INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS REPLICATION
  [FR] BENZIMIDAZOLES CONTENANT DU MORPHOLINYLE EN TANT QU'INHIBITEURS DE LA REPLICATION DU VIRUS RESPIRATOIRE SYNCYTIAL

  摘要：

  本发明涉及含有对呼吸道合胞病毒复制具有抑制活性的吗啉基苯并咪唑的化合物，其具有式（I），一种前药、N-氧化物、加合盐、季铵盐、金属配合物或其立体化异构体，其中G是直键或可选择地取代的C1-10烷二基；R1是Ar1或单环或双环杂环；Q是R7，R7取代的吡咯烷基、R7取代的哌啶基或R7取代的同构异哌啶基；R2a和R3a中的一个选自卤素、可选择单取代或多取代的Cl-6烷基、可选择单取代或多取代的C2-6烯基、硝基、羟基、Ar2、N(R4aR4)、N(R4aR4)磺酰基、N(R4aR4b)羰基、C1-6烷氧基、Ar2氧基、Ar2Cl-6烷氧基、羧基、Cl-6烷氧羰基或-C(=Z)Ar2；R2a和R3a中的另一个是氢；如果R2a与氢不同，则R2b是氢、C1-6烷基或卤素，R3b是氢；如果R3a与氢不同，则R3b是氢、C1-6烷基或卤素，R2b是氢。还涉及其制备以及包含这些化合物的组合物，以及其作为药物的用途。

  公开号：

  WO2005058871A1
• 作为产物：
  描述：

  2-chloro-4,6-dimethyl-1H-benzoimidazole 、 4-氨基-1-哌啶甲酸乙酯 反应 12.0h， 以72%的产率得到ethyl 4-[(4,6-dimethyl-1H-benzimidazol-2-yl)amino]piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] MORPHOLINYL CONTAINING BENZIMIDAZOLES AS INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS REPLICATION
  [FR] BENZIMIDAZOLES CONTENANT DU MORPHOLINYLE EN TANT QU'INHIBITEURS DE LA REPLICATION DU VIRUS RESPIRATOIRE SYNCYTIAL

  摘要：

  本发明涉及含有对呼吸道合胞病毒复制具有抑制活性的吗啉基苯并咪唑的化合物，其具有式（I），一种前药、N-氧化物、加合盐、季铵盐、金属配合物或其立体化异构体，其中G是直键或可选择地取代的C1-10烷二基；R1是Ar1或单环或双环杂环；Q是R7，R7取代的吡咯烷基、R7取代的哌啶基或R7取代的同构异哌啶基；R2a和R3a中的一个选自卤素、可选择单取代或多取代的Cl-6烷基、可选择单取代或多取代的C2-6烯基、硝基、羟基、Ar2、N(R4aR4)、N(R4aR4)磺酰基、N(R4aR4b)羰基、C1-6烷氧基、Ar2氧基、Ar2Cl-6烷氧基、羧基、Cl-6烷氧羰基或-C(=Z)Ar2；R2a和R3a中的另一个是氢；如果R2a与氢不同，则R2b是氢、C1-6烷基或卤素，R3b是氢；如果R3a与氢不同，则R3b是氢、C1-6烷基或卤素，R2b是氢。还涉及其制备以及包含这些化合物的组合物，以及其作为药物的用途。

  公开号：

  WO2005058871A1

文献信息

• [EN] MORPHOLINYL CONTAINING BENZIMIDAZOLES AS INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS REPLICATION<br/>[FR] BENZIMIDAZOLES CONTENANT DU MORPHOLINYLE EN TANT QU'INHIBITEURS DE LA REPLICATION DU VIRUS RESPIRATOIRE SYNCYTIAL
  申请人：TIBOTEC PHARM LTD

  公开号：WO2005058871A1

  公开（公告）日：2005-06-30

  The present invention concerns morpholinyl containing benzimidazoles having inhibitory activity on the replication of the respiratory syncytial virus and having the formula (I), a prodrug, N-oxide, addition salt, quaternary amine, metal complex or stereochemically isomeric form thereof wherein G is a direct bond or optionally substituted C1-10alkanediyl; Rl is Ar1 or a monocyclic or bicyclic heterocycle Q is R7, pyrrolidinyl substituted with R7, piperidinyl substituted with R7 or homopiperidinyl substituted with R7; one of R2a and R3a is selected from halo, optionally mono- or polysubstituted Cl-6alkyl, optionally mono- or polysubstituted C2-6alkenyl, nitro, hydroxy, Ar2, N(R4aR4), N(R4aR4)sulfonyl, N(R4aR4b)carbonyl, C1-6alkyloxy, Ar2oxy, Ar2Cl-6alkyloxy, carboxyl, Cl-6alkyloxycarbonyl, or -C(=Z)Ar2; and the other one of R2a and R3a is hydrogen; in case R2a is different from hydrogen then R2b is hydrogen, C1-6alkyl or halogen and R3b is hydrogen; in case R3a is different from hydrogen then R3b is hydrogen, C1-6alkyl or halogen and R2b is hydrogen. It further concerns the preparation thereof and compositions comprising these compounds, as well as the use thereof as a medicine.

  本发明涉及含有对呼吸道合胞病毒复制具有抑制活性的吗啉基苯并咪唑的化合物，其具有式（I），一种前药、N-氧化物、加合盐、季铵盐、金属配合物或其立体化异构体，其中G是直键或可选择地取代的C1-10烷二基；R1是Ar1或单环或双环杂环；Q是R7，R7取代的吡咯烷基、R7取代的哌啶基或R7取代的同构异哌啶基；R2a和R3a中的一个选自卤素、可选择单取代或多取代的Cl-6烷基、可选择单取代或多取代的C2-6烯基、硝基、羟基、Ar2、N(R4aR4)、N(R4aR4)磺酰基、N(R4aR4b)羰基、C1-6烷氧基、Ar2氧基、Ar2Cl-6烷氧基、羧基、Cl-6烷氧羰基或-C(=Z)Ar2；R2a和R3a中的另一个是氢；如果R2a与氢不同，则R2b是氢、C1-6烷基或卤素，R3b是氢；如果R3a与氢不同，则R3b是氢、C1-6烷基或卤素，R2b是氢。还涉及其制备以及包含这些化合物的组合物，以及其作为药物的用途。
• Piperdine-amino-benzimidazole derivatives as inhibitors of respiratory syncytial virus replication
  申请人：Bonfanti Jean-Francois

  公开号：US20070093659A1

  公开（公告）日：2007-04-26

  The present invention concerns piperidine-amino-benzimidazoles having inhibitory activity on the replication of the respiratory syncytial virus and having the formula their prodrugs, N-oxides, addition salts, quaternary amines, metal complexes and stereochemically isomeric forms wherein Q is C 1-6 alkyl optionally substituted with trifluoromethyl, C 3-7 cycloalkyl, Ar 2 , hydroxy, C 1-4 alkoxy, C 1-4 alkylthio, Ar 2 -oxy-, Ar 2 -thio-, Ar 2 (CH 2 ) n oxy, Ar 2 (CH 2 ) n thio, hydroxycarbonyl, aminocarbonyl, C 1-4 alkylcarbonyl, Ar 2 carbonyl, C 1-4 alkoxycarbonyl, Ar 2 (CH 2 ) n carbonyl, aminocarbonyloxy, C 1-4 alkylcarbonyloxy, Ar 2 carbonyloxy, Ar 2 (CH 2 ) n carbonyloxy, C 1-4 alkoxy-carbonyl(CH 2 ) n oxy, mono- or di(C 1-4 alkyl)aminocarbonyl, mono- or di(C 1-4 alkyl)-aminocarbonyloxy, aminosulfonyl, mono- or di(C 1-4 alkyl)aminosulfonyl or a heterocycles selected from the group consisting of pyrrolidinyl, pyrrolyl, dihydropyrrolyl, imidazolyl, triazolyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxothiomorpholinyl, pyridyl and tetrahydropyridyl, wherein each of said heterocycle may optionally be substituted with oxo or C 1-6 alkyl; G is a direct bond or optionally substituted C 1-10 alkanediyl; R 1 is Ar 1 or a monocyclic or bicyclic heterocycle; one of R 2a and R 3a is C 1-6 alkyl and the other one of R 2a and R 3a is hydrogen; in case R 2a is different from hydrogen then R 2b is hydrogen or C 1-6 alkyl, and R 3b is hydrogen; in case R 3a is different from hydrogen then R 3b is hydrogen or C 1-6 alkyl, and R 2b is hydrogen; t is 1, 2 or 3; Ar 1 is phenyl or substituted phenyl; and Ar 2 is phenyl or substituted phenyl. It further concerns their preparation and compositions comprising them, as well as their use as a medicine.

  本发明涉及具有对呼吸合胞病毒复制具有抑制活性的哌啶基氨基苯并咪唑，其具有以下式子，它们的前药，N-氧化物，加成盐，季铵盐，金属配合物和立体化学异构体形式，其中Q是C1-6烷基，可选地被三氟甲基取代，C3-7环烷基，Ar2，羟基，C1-4烷氧基，C1-4烷基硫基，Ar2-氧基，Ar2-硫基，Ar2(CH2)noxy，Ar2(CH2)nthio，羟基羧酸，氨基羧酸，C1-4烷基羧酸，Ar2羧酸，C1-4烷氧羧酸，Ar2(CH2)ncarbonyl，氨基羧酸氧酯，C1-4烷基羧酸氧酯，Ar2羧酸氧酯，Ar2(CH2)ncarbonyloxy，C1-4烷氧基羧酸(CH2)noxy，单一或二(C1-4烷基)氨基羧酸，单一或二(C1-4烷基)氨基羧酸氧酯，氨基磺酰基，单一或二(C1-4烷基)氨基磺酰基或从吡咯烷基，吡咯基，二氢吡咯基，咪唑基，三唑基，哌啶基，同源哌啶基，哌嗪基，吗啉基，噻吗啉基，1-氧代噻吗啉基，1,1-二氧代噻吗啉基，吡啶基和四氢吡啶基中选择的杂环，其中每个所述杂环可选地被氧代或C1-6烷基取代；G是直接键或可选地取代的C1-10烷二基；R1是Ar1或单环或双环杂环；R2a和R3a中的一个是C1-6烷基，另一个是氢；在R2a与氢不同的情况下，R2b是氢或C1-6烷基，R3b是氢；在R3a与氢不同的情况下，R3b是氢或C1-6烷基，R2b是氢；t为1、2或3；Ar1为苯基或取代苯基；Ar2为苯基或取代苯基。本发明还涉及它们的制备和包含它们的组合物，以及它们作为药物的用途。
• MORPHOLINYL CONTAINING BENZIMIDAZOLES AS INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS REPLICATION
  申请人：Bonfanti Jean-Francois

  公开号：US20080280881A1

  公开（公告）日：2008-11-13

  The present invention concerns morpholinyl containing benzimidazoles having inhibitory activity on the replication of the respiratory syncytial virus and having the formula a prodrug, N-oxide, addition salt, quaternary amine, metal complex or stereochemically isomeric form thereof wherein G is a direct bond or optionally substituted C 1-10 alkanediyl; R 1 is Ar 1 or a monocyclic or bicyclic heterocycle Q is R 7 , pyrrolidinyl substituted with R 7 , piperidinyl substituted with R 7 or homopiperidinyl substituted with R 7 ; one of R 2a and R 3a is selected from halo, optionally mono- or polysubstituted C 1-6 alkyl, optionally mono- or polysubstituted C 2-6 alkenyl, nitro, hydroxy, Ar 2 , N(R 4a R 4b ), N(R 4a R 4b )sulfonyl, N(R 4a R 4b )carbonyl, C 1-6 alkyloxy, Ar 2 oxy, Ar 2 C 1-6 alkyloxy, carboxyl, C 1-6 alkyloxycarbonyl, or —C(=Z)Ar 2 ; and the other one of R 2a and R 3a is hydrogen; in case R 2a is different from hydrogen then R 2b is hydrogen, C 1-6 alkyl or halogen and R 3b is hydrogen; in case R 3a is different from hydrogen then R 3b is hydrogen, C 1-6 alkyl or halogen and R 2b is hydrogen. It further concerns the preparation thereof and compositions comprising these compounds, as well as the use thereof as a medicine.

  本发明涉及含有吗啡啉基的苯并咪唑，具有对呼吸道合胞病毒复制的抑制活性，其具有以下式子: 其中G为直接键或可选取代的C1-10烷二基；R1为Ar1或单环或双环杂环；Q为R7、用R7取代的吡咯烷基、用R7取代的哌啶基或用R7取代的同型哌啶基；R2a和R3a中的一个选自卤素、可选单或多取代的C1-6烷基、可选单或多取代的C2-6烯基、硝基、羟基、Ar2、N(R4aR4b)、N(R4aR4b)磺酰基、N(R4aR4b)羰基、C1-6烷氧基、Ar2氧基、Ar2C1-6烷氧基、羧基、C1-6烷氧羰基或—C(=Z)Ar2；而R2a和R3a中的另一个为氢；若R2a不为氢，则R2b为氢、C1-6烷基或卤素，而R3b为氢；若R3a不为氢，则R3b为氢、C1-6烷基或卤素，而R2b为氢。 此外，本发明还涉及其制备方法和包含这些化合物的组合物，以及其作为药物的用途。
• PIPERIDINE-AMINO-BENZIMIDAZOLE DERIVATIVES AS INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS REPLICATION
  申请人：BONFANTI Jean-Francois

  公开号：US20080146613A1

  公开（公告）日：2008-06-19

  The present invention concerns piperidine-amino-benzimidazoles having inhibitory activity on the replication of the respiratory syncytial virus and having the formula their prodrugs, N-oxides, addition salts, quaternary amines, metal complexes and stereochemically isomeric forms wherein Q is C 1-6 alkyl optionally substituted with trifluoromethyl, C 3-7 cycloalkyl, Ar 2 , hydroxy, C 1-4 alkoxy, C 1-4 alkylthio, Ar 2 -oxy-, Ar 2 -thio-, Ar 2 (CH 2 ) n oxy, Ar 2 (CH 2 ) n thio, hydroxycarbonyl, aminocarbonyl, C 1-4 alkyl-carbonyl, Ar 2 -carbonyl, C 1-4 alkoxycarbonyl, Ar 2 (CH 2 ) n carbonyl, aminocarbonyloxy, C 1-4 alkylcarbonyloxy, Ar 2 -carbonyloxy, Ar 2 (CH 2 ) n carbonyloxy, C 1-4 alkoxy-carbonyl(CH 2 ) n oxy, mono- or di(C 1-4 alkyl)aminocarbonyl, mono- or di(C 1-4 alkyl)-aminocarbonyloxy, aminosulfonyl, mono- or di(C 1-4 alkyl)aminosulfonyl or a heterocycles selected from the group consisting of pyrrolidinyl, pyrrolyl, dihydropyrrolyl, imidazolyl, triazolyl, piperidinyl, homopiperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxothiomorpholinyl, pyridyl and tetrahydropyridyl, wherein each of said heterocycle may optionally be substituted with oxo or C 1-6 alkyl; G is a direct bond or optionally substituted C 1-10 alkanediyl; R 1 is Ar 1 or a monocyclic or bicyclic heterocycle; one of R 2a and R 3a is C 1-6 alkyl and the other one of R 2a and R 3a is hydrogen; in case R 2a is different from hydrogen then R 2b is hydrogen or C 1-6 alkyl, and R 3b is hydrogen; in case R 3a is different from hydrogen then R 3b is hydrogen or C 1-6 alkyl, and R 2b is hydrogen; t is 1, 2 or 3; Ar 1 is phenyl or substituted phenyl; and Ar 2 is phenyl or substituted phenyl. It further concerns their preparation and compositions comprising them, as well as their use as a medicine.

  本发明涉及对呼吸道合胞病毒复制具有抑制活性的哌啶基氨基苯并咪唑，其具有以下式子： 其中Q是C1-6烷基，可选地取代三氟甲基，C3-7环烷基，Ar2，羟基，C1-4烷氧基，C1-4烷基硫基，Ar2-氧基，Ar2-硫基，Ar2(CH2)noxy，Ar2(CH2)nthio，羟基羧酸，氨基羧酸，C1-4烷基羧酸，Ar2-羧酸，C1-4烷氧基羧酸，Ar2(CH2)ncarbonyl，氨基羧酸氧酸酯，C1-4烷基羧酸氧酸酯，Ar2-羧酸氧酸酯，Ar2(CH2)ncarbonyloxy，C1-4烷氧基-羧酸(CH2)noxy，单烷基或双烷基氨基羧酸，单烷基或双烷基氨基羧酸氧酸酯，氨基磺酰基，单烷基或双烷基氨基磺酰基或从吡咯烷基，吡咯基，二氢吡咯基，咪唑基，三唑基，哌啶基，同型哌啶基，哌嗪基，吗啉基，硫代吗啉基，1-氧代硫代吗啉基，1,1-二氧代硫代吗啉基，吡啶基和四氢吡啶基中选择的杂环，其中每个所述杂环可以选择地用氧代或C1-6烷基取代；G是直接键或可选取代的C1-10烷基二基基；R1是Ar1或单环或双环杂环；R2a和R3a中的一个是C1-6烷基，另一个是氢；如果R2a不同于氢，则R2b是氢或C1-6烷基，而R3b是氢；如果R3a不同于氢，则R3b是氢或C1-6烷基，而R2b是氢；t为1、2或3；Ar1为苯基或取代苯基；Ar2为苯基或取代苯基。本发明还涉及它们的制备和包含它们的组合物，以及它们作为药物的用途。
• Morpholinyl containing benzimidazoles as inhibitors of respiratory syncytial virus replication
  申请人：Bonfanti Jean-Francois

  公开号：US20070043022A1

  公开（公告）日：2007-02-22

  The present invention concerns morpholinyl containing benzimidazoles having inhibitory activity on the replication of the respiratory syncytial virus and having the formula a prodrug, N-oxide, addition salt, quaternary amine, metal complex or stereochemically isomeric form thereof wherein G is a direct bond or optionally substituted C 1-10 alkanediyl; R 1 is Ar 1 or a monocyclic or bicyclic heterocycle Q is R 7 , pyrrolidinyl substituted with R 7 , piperidinyl substituted with R 7 or homopiperidinyl substituted with R 7 ; one of R 2a and R 3a is selected from halo, optionally mono- or polysubstituted C 1-6 alkyl, optionally mono- or polysubstituted C 2-6 alkenyl, nitro, hydroxy, Ar 2 , N(R 4a R 4b ) N(R 4a R 4b )sulfonyl, N(R 4a R 4b )carbonyl, C 1-6 alkyloxy, Ar 2 oxy, Ar 2 C 1-6 alkyloxy, carboxyl, C 1-6 alkyloxycarbonyl, or —C(=Z)Ar 2 ; and the other one of R 2a and R 3a is hydrogen; in case R 2a is different from hydrogen then R 2b is hydrogen, C 1-6 alkyl or halogen and R 3b is hydrogen; in case R 3a is different from hydrogen then R 3b is hydrogen, C 1-6 alkyl or halogen and R 2b is hydrogen. It further concerns the preparation thereof and compositions comprising these compounds, as well as the use thereof as a medicine.

  本发明涉及含有morpholinyl的苯并咪唑类化合物，具有抑制呼吸道合胞病毒复制的活性，其具有以下式子：a prodrug，N-oxide，加合盐，季铵盐，金属络合物或其立体化学异构体形式，其中G是直链键或可选取代的C1-10烷二基；R1是Ar1或单环或双环杂环；Q是R7，用R7取代的吡咯烷基，用R7取代的哌啶基或用R7取代的同源哌啶基；R2a和R3a中的一个选自卤素，可选取代的C1-6烷基，可选取代的C2-6烯基，硝基，羟基，Ar2，N（R4aR4b），N（R4aR4b）磺酰基，N（R4aR4b）羰基，C1-6烷氧基，Ar2氧基，Ar2C1-6烷氧基，羧基，C1-6烷氧羰基或-C（=Z）Ar2；R2a和R3a中的另一个是氢；如果R2a与氢不同，则R2b是氢，C1-6烷基或卤素，而R3b是氢；如果R3a与氢不同，则R3b是氢，C1-6烷基或卤素，而R2b是氢。本发明进一步涉及其制备方法和包含这些化合物的组合物，以及将其用作药物的用途。