ethyl 3-[5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]-3-oxopropanoate | 1404530-79-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 3-[5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]-3-oxopropanoate
• 英文别名: Ethyl 3-[5-Methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]-3-oxopropanoate；Ethyl 3-[5-methyl-1-(4-nitrophenyl)pyrazol-4-yl]-3-oxopropanoate；ethyl 3-[5-methyl-1-(4-nitrophenyl)pyrazol-4-yl]-3-oxopropanoate
• CAS: 1404530-79-5
• 化学式: C₁₅H₁₅N₃O₅
• 分子量: 317.301
• InChiKey: HHGJDNLALZFANH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 3-[5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]-3-oxopropanoate 在 盐酸 、 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 水 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 环己烷 、 水 、 1,2-二氯乙烷 、 mineral oil 为溶剂， 反应 98.5h， 生成
  参考文献：
  名称：

  N-[6-(4-Butanoyl-5-methyl-1H-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist

  摘要：

  In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.

  DOI：

  10.1021/jm500588w
• 作为产物：
  描述：

  ethyl 2-[(dimethylamino)methylene]-3-oxobutanoate 在 水 、 N,N'-羰基二咪唑 、 potassium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 5.0h， 生成 ethyl 3-[5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]-3-oxopropanoate
  参考文献：
  名称：

  N-[6-(4-Butanoyl-5-methyl-1H-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist

  摘要：

  In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.

  DOI：

  10.1021/jm500588w

文献信息

• DERIVATIVES OF N-[(1H-PYRAZOL-1-YL)ARYL]-1H-INDOLE OR 1H-INDAZOLE-3-CARBOXAMIDE, PREPARATION THEREOF AND APPLICATIONS THEREOF IN THERAPEUTICS
  申请人：Badorc Alain

  公开号：US20120277205A1

  公开（公告）日：2012-11-01

  The present invention relates to compounds corresponding to formula (I): in which: A represents a divalent aromatic radical; X represents a —CH— group or a nitrogen atom; R 1 represents a (C 1 -C 4 )alkyl or a (C 1 -C 4 )alkoxy; R 2 represents a group Alk; R 3 represents a hydroxyl or a group —NR 7 R 8 ; R 4 represents a hydrogen atom, a halogen atom, a cyano, a phenyl, a group Alk, a group OAlk or a group —NR 9 R 10 ; R 5 represents a hydrogen atom, a halogen atom or a group Alk; R 6 represents a hydrogen atom, a halogen atom, a cyano, a group —COOAlk or a —CONH 2 group.

  该发明涉及与式(I)对应的化合物：其中：A代表二价芳香基团；X代表一个—CH—基团或一个氮原子；R1代表(C1-C4)烷基或(C1-C4)烷氧基；R2代表一个烷基基团；R3代表一个羟基或一个基团—NR7R8；R4代表氢原子、卤素原子、氰基、苯基、烷基基团、氧烷基团或基团—NR9R10；R5代表氢原子、卤素原子或一个烷基基团；R6代表氢原子、卤素原子、氰基、基团—COOAlk或基团—CONH2。
• [EN] DERIVATIVES OF N- [(1H-PYRAZOL-1-YL) ARYL] - 1H - INDOLE OR 1H - INDAZOLE - 3 - CARBOXAMIDE, THEIR PREPARATION AND THEIR USE AS P2Y12 ANTAGONISTS<br/>[FR] DÉRIVÉS DE N-[(1H-PYRAZOL-1-YL) ARYL]-1H-INDOLE OU 1H-INDAZOLE-3-CARBOXAMIDE, LEUR PRÉPARATION ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DE P2Y12
  申请人：SANOFI SA

  公开号：WO2012146318A1

  公开（公告）日：2012-11-01

  The present invention relates to compounds corresponding to formula (I) and their use as P2Y12 antagonists for the treatment of cardiovascular diseases.

  本发明涉及与式（I）对应的化合物及其作为P2Y12拮抗剂用于治疗心血管疾病。
• <i>N</i>-[6-(4-Butanoyl-5-methyl-1<i>H</i>-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1<i>H</i>-indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist
  作者：Christophe Boldron、Angélina Besse、Marie-Françoise Bordes、Stéphanie Tissandié、Xavier Yvon、Benjamin Gau、Alain Badorc、Tristan Rousseaux、Guillaume Barré、Jérôme Meneyrol、Gernot Zech、Marc Nazare、Valérie Fossey、Anne-Marie Pflieger、Sandrine Bonnet-Lignon、Laurence Millet、Christophe Briot、Frédérique Dol、Jean-Pascal Hérault、Pierre Savi、Gilbert Lassalle、Nathalie Delesque、Jean-Marc Herbert、Françoise Bono

  DOI：10.1021/jm500588w

  日期：2014.9.11

  In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.