2-氯-3H-苯并咪唑-5-羧酸乙酯 | 857035-29-1

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物 - 羧酸酯及其衍生物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: 2-氯-3H-苯并咪唑-5-羧酸乙酯
• 中文别名: 2-氯-1H-苯并[D]咪唑-6-羧酸乙酯
• 英文名称: 2-chloro-3H-benzoimidazole-5-carboxylic acid ethyl ester
• 英文别名: Ethyl 2-chloro-1H-benzo[D]imidazole-6-carboxylate；ethyl 2-chloro-3H-benzimidazole-5-carboxylate
• CAS: 857035-29-1
• 化学式: C₁₀H₉ClN₂O₂
• 分子量: 224.647
• InChiKey: LVIQNMQUZOMYAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  -20°C，干燥密封保存

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  2-氧代-2,3-二氢-1H-苯并[D]咪唑-5-羧酸乙酯	2-oxo-2,3-dihydro-1H-benzoimidazole-5-carboxylic acid ethyl ester	634602-84-9	C10H10N2O3	206.201

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  2-丁基氨基-3H-苯并咪唑-5-羧酸乙酯	2-butylamino-3H-benzoimidazole-5-carboxylic acid ethyl ester	1009646-61-0	C14H19N3O2	261.324
  2-氯-1H-苯并咪唑-6-甲醇	(2-chloro-3H-benzoimidazol-5-yl)methanol	857070-66-7	C8H7ClN2O	182.609
  ——	2-phenethylamino-3H-benzoimidazole-5-carboxylic acid ethyl ester	1009646-67-6	C18H19N3O2	309.368
  ——	2-[3-(4-methylpiperazin-1-yl)propylamino]-3H-benzoimidazole-5-carboxylic acid ethyl ester	1009646-50-7	C18H27N5O2	345.445
  ——	ethyl 2-(3-piperidin-1-ylpropylamino)-3H-benzimidazole-5-carboxylate	857035-57-5	C18H26N4O2	330.43
  ——	2-(3-morpholin-4-ylpropylamino)-3H-benzoimidazole-5-carboxylic acid ethyl ester	857070-62-3	C17H24N4O3	332.403
  ——	2-[(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)amino]-3H-benzoimidazole-5-carboxylic acid ethyl ester	1009646-55-2	C16H21N3O4	319.36
  ——	2-(1-benzylpiperidin-4-ylamino)-3H-benzoimidazole-5-carboxylic acid ethyl ester	857035-30-4	C22H26N4O2	378.474

反应信息

• 作为反应物：
  描述：

  2-氯-3H-苯并咪唑-5-羧酸乙酯 在 lithium aluminium tetrahydride 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以95%的产率得到2-氯-1H-苯并咪唑-6-甲醇
  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-氧代-2,3-二氢-1H-苯并[D]咪唑-5-羧酸乙酯 在 盐酸 、 三氯氧磷 作用下， 以 水 为溶剂， 反应 6.0h， 以83%的产率得到2-氯-3H-苯并咪唑-5-羧酸乙酯
  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] 5- OR 6-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES AS INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS REPLICATION<br/>[FR] DERIVES DE BENZIMIDAZOLE SUBSTITUES EN 5- OU 6- UTILISES EN TANT QU'INHIBITEURS DE LA REPLICATION DU VIRUS RESPIRATOIRE SYNCITIAL
  申请人：TIBOTEC PHARM LTD

  公开号：WO2005058874A1

  公开（公告）日：2005-06-30

  The present invention concerns 5- or 6-substituted-benzimidazole derivatives 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 Q is Ar2, R6, pyrrolidinyl substituted with R6, piperidinyl substituted with R6 or homopiperidinyl substituted with R6, G is a direct bond or optionally substituted C1-10alkanediyl; R1 is Arl or a monocyclic or bicyclic heterocycle; one of R 2a and R2b is cyanoCl-6alkyl, cyanoC2-6alkenyl, Ar3Cl-6alkyl, Het­-C1-6alky1, N(R8aR8b)Cl-6alkyl, Ar3C2-6alkenyl, Het-C2-6alkenyl, Ar3 aminoCl-6alkyl, Het­aminoCl-6alkyl, Ar3thioC1-6 alkyl, Het-thioC1-6alkyl, Ar3sulfonylC1-6 alkyl, Het­sulfonylC1-6alkyl, Ar3aminocarbonyl, Het-aminocarbonyl, Ar3(CH2)naminocarbonyl, Het-(CH2)naminocarbonyl, Ar3carbonylamino, Het-carbonylamino, Ar3(CH2)ncarbonylamino, Het-(CH2)ncarbonylamino, and the other one of R2a and R2b is hydrogen; in case R2a is hydrogen, then R3 is hydrogen; in case R2b is hydrogen, the R3 is hydrogen or C1-6alkyl. 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5-或6-取代苯并咪唑衍生物，其具有���下式(I)的结构：一种前药、N-氧化物、加成盐、季铵盐、金属配合物或其立体化异构体，其中Q为Ar2、R6、用R6取代的吡咯烷基、用R6取代的哌啶基或用R6取代的环己胺基，G为直链键或可选择取代的C1-10烷二基；R1为Arl或单环或双环杂环；R2a和R2b中的一个为氰基C1-6烷基、氰基C2-6烯基、Ar3C1-6烷基、Het-C1-6烷基、N(R8aR8b)C1-6烷基、Ar3C2-6烯基、Het-C2-6烯基、Ar3氨基C1-6烷基、Het氨基C1-6烷基、Ar3硫基C1-6烷基、Het-硫基C1-6烷基、Ar3磺酰基C1-6烷基、Het-磺酰基C1-6烷基、Ar3氨基羰基、Het-氨基羰基、Ar3(CH2)n氨基羰基、Het-(CH2)n氨基羰基、Ar3羰基氨基、Het-羰基氨基、Ar3(CH2)n羰基氨基、Het-(CH2)n羰基氨基，R2a和R2b中的另一个为氢；如果R2a为氢，则R3为氢；如果R2b为氢，则R3为氢或C1-6烷基。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。
• BICYCLIC NITROGEN-CONTAINING AROMATIC HETEROCYCLIC AMIDE COMPOUND
  申请人：ASTELLAS PHARMA INC.

  公开号：US20150266869A1

  公开（公告）日：2015-09-24

  [Problem] A compound which is useful as an agent for treating breast cancer is provided. [Means for Solution] As a result of intensive studies on a compound having a Complex I inhibitory effect and an AMPK activation effect, the present inventors found that a bicyclic nitrogen-containing aromatic heterocyclic amide compounds of the present invention has an excellent Complex I inhibitory effect and the AMPK activation effect, furthermore, has a cell proliferation inhibitory effect with respect to not only human PIK3CA mutation-positive breast cancer cell lines in which MCT4 is not expressed but also human breast cancer cell lines which do not have mutation of PIK3CA in which MCT4 is not expressed, and exhibits an anti-tumor effect in a human PIK3CA mutation-positive breast cancer cell line MDA-MB-453 cell in a cancer-bearing mouse in which the MCT4 is not expressed, thereby completing the present invention. A bicyclic nitrogen-containing aromatic heterocyclic amide compound of the present invention can be used as an agent for treating breast cancer, in particular, breast cancer in which the MCT4 is not expressed, and among others, PIK3CA mutation-positive breast cancer in which the MCT4 is not expressed.

  提供一种作为治疗乳腺癌药物的化合物。通过对具有复合I抑制作用和AMPK激活作用的化合物进行深入研究，本发明人发现，本发明的含有双环氮杂芳香族酰胺化合物具有优异的复合I抑制作用和AMPK激活作用，此外，对于不仅在其中MCT4不表达的人类PIK3CA突变阳性乳腺癌细胞系，还对于其中MCT4不表达的不具有PIK3CA突变的人类乳腺癌细胞系，具有细胞增殖抑制作用，并在MCT4不表达的癌症携带小鼠的人类PIK3CA突变阳性乳腺癌细胞系MDA-MB-453细胞中表现出抗肿瘤作用，从而完成了本发明。本发明的含有双环氮杂芳香族酰胺化合物可用作治疗乳腺癌的药物，尤其是MCT4不表达的乳腺癌，以及其他MCT4不表达的PIK3CA突变阳性乳腺癌。
• 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。
• 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。
• Selection of a Respiratory Syncytial Virus Fusion Inhibitor Clinical Candidate. 2. Discovery of a Morpholinopropylaminobenzimidazole Derivative (TMC353121)
  作者：Jean-François Bonfanti、Christophe Meyer、Frédéric Doublet、Jérôme Fortin、Philippe Muller、Laurence Queguiner、Tom Gevers、Peggy Janssens、Heidi Szel、Rudy Willebrords、Philip Timmerman、Koen Wuyts、Pieter van Remoortere、Frans Janssens、Piet Wigerinck、Koen Andries

  DOI：10.1021/jm701284j

  日期：2008.2.1

  A preceding paper (Bonfanti et al. J. Med Chem. 2007, 50, 4572-4584) reported the optimization of the pharmacokinetic profile of substituted benzimidazoles by reducing their tissue retention. However, the modifications that were necessary to achieve this goal also led to a significant drop in anti-RSV activity. This paper describes a molecular modeling study followed by a lead optimization program that led to the recovery of the initial potent antiviral activity and the selection of TMC353121 as a clinical candidate.