5-氨基-1-苄基-3-甲基-1H-吡唑-4-羧酸乙酯 | 303066-82-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 5-氨基-1-苄基-3-甲基-1H-吡唑-4-羧酸乙酯
• 英文名称: ethyl 5-amino-1-benzyl-3-methyl-1H-pyrazole-4-carboxylate
• 英文别名: ethyl 5-amino-1-benzyl-3-methylpyrazole-4-carboxylate
• CAS: 303066-82-2
• 化学式: C₁₄H₁₇N₃O₂
• mdl: MFCD00502756
• 分子量: 259.308
• InChiKey: ZIVXPMIRBSHHAM-UHFFFAOYSA-N

物化性质

• 沸点：
  422.8±45.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-氨基-1-苄基-3-甲基-1H-吡唑-4-羧酸乙酯 在 palladium dihydroxide 甲醇 、 磺酰氯 、 氢气 、 sodium methylate 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 25.0~100.0 ℃ 、344.73 kPa 条件下， 反应 64.0h， 生成 (6aR,9aS)-3,5-dimethyl-5,6a,7,8,9,9a-hexahydrocyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(1H)-one
  参考文献：
  名称：

  Synthesis and Evaluation of Polycyclic Pyrazolo[3,4-d]pyrimidines as PDE1 and PDE5 cGMP Phosphodiesterase Inhibitors

  摘要：

  Polycyclic pyrazolo[3,4-d]pyrimidines (represented by 3 and 4) were synthesized as analogues of the recently reported polycyclic guanine phosphodiesterase (PDE) inhibitors. From the structure-activity relationship (SAR) development of a series of compounds, it was discovered that C-3 benzyl and N-2 methyl disubstitution on the pyrazole ring gave the best combination of potency and selectivity for PDE1 and PDE5 cGMP PDEs as represented by compound 4c: PDE1, IC50 = 60 nM; PDE3, IC50 = 55 000 nM; PDE5, IC50 = 75 nM. These compounds were also evaluated in vivo and found to be good orally active antihypertensives in laboratory animal models. Finally, comparisons were made of the in vitro and in vivo profiles of the pyrazolo[3,4-d]pyrimidine compound 4c with those of two representative guanine compounds.

  DOI：

  10.1021/jm970495b
• 作为产物：
  描述：

  2-氰基-3-乙氧基巴豆酸乙酯 、 benzylhydrazine dihydrochloride 在 N,N-二异丙基乙胺 作用下， 以 乙醇 为溶剂， 以4.45 g的产率得到5-氨基-1-苄基-3-甲基-1H-吡唑-4-羧酸乙酯
  参考文献：
  名称：

  [EN] SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS AS NADPH OXIDASE INHIBITORS
  [FR] COMPOSÉS HÉTÉROCYCLIQUES BICYCLIQUES SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE NADPH OXYDASE

  摘要：

  本申请涉及取代的融合杂环芳基和杂环化合物，用作烟酰胺腺嘌呤二核苷酸磷酸酶抑制剂（NADPH氧化酶抑制剂），其制备方法，包含这些化合物的药物组合物，以及这些化合物或组合物在治疗或预防由NADPH氧化酶介导的各种疾病、症状和/或障碍中的用途。 (分子式I)

  公开号：

  WO2018203298A1

文献信息

• Facile synthesis of 1-substituted 4,5-diaminopyrazoles and its application toward the synthesis of pyrazolo[3,4- b ]pyrazines
  作者：Tun-Cheng Chien、Ronald A. Smaldone、Leroy B. Townsend

  DOI：10.1016/j.tetlet.2004.03.142

  日期：2004.5

  5-aminopyrazole-4-carboxylates. The acyl azides undergo a Curtius rearrangement followed by quenching with alcohols to form the corresponding carbamates. The 1-substituted 5-amino-4-benzyloxycarbonylaminopyrazoles were unblocked by catalytic hydrogenolysis to give the desired 4,5-diaminopyrazoles. These 4,5-diaminopyrazoles were immediately condensed with glyoxal to afford 1-substituted pyrazolo[3,4-b]pyrazines.

  由适当的5-氨基吡唑-4-羧酸酯制备1-取代的5-氨基吡唑-4-羰基叠氮化物。酰基叠氮化物经历Curtius重排，然后用醇淬灭以形成相应的氨基甲酸酯。通过催化氢解解封1-取代的5-氨基-4-苄氧基羰基氨基吡唑，得到所需的4，5-二氨基吡唑。立即将这些4，5-二氨基吡唑与乙二醛缩合，得到1-取代的吡唑并[3，4- b ]吡嗪。
• SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS AS NADPH OXIDASE INHIBITORS
  申请人：Glenmark Pharmaceuticals S.A.

  公开号：EP3619209A1

  公开（公告）日：2020-03-11
• [EN] SUBSTITUTED BICYCLIC HETEROCYCLIC COMPOUNDS AS NADPH OXIDASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES BICYCLIQUES SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE NADPH OXYDASE
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2018203298A1

  公开（公告）日：2018-11-08

  The present application relates to substituted fused heteroaryl and heterocyclic compounds, useful as nicotinamide adenine dinucleotide phosphate oxidase inhibitors (NADPH oxidase inhibitors), processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment or prevention of various diseases, conditions and/or disorders mediated by NADPH oxidase. (Formula I)

  本申请涉及取代的融合杂环芳基和杂环化合物，用作烟酰胺腺嘌呤二核苷酸磷酸酶抑制剂（NADPH氧化酶抑制剂），其制备方法，包含这些化合物的药物组合物，以及这些化合物或组合物在治疗或预防由NADPH氧化酶介导的各种疾病、症状和/或障碍中的用途。 (分子式I)
• Synthesis and Evaluation of Polycyclic Pyrazolo[3,4-<i>d</i>]pyrimidines as PDE1 and PDE5 cGMP Phosphodiesterase Inhibitors
  作者：Yan Xia、Samuel Chackalamannil、Michael Czarniecki、Hsingan Tsai、Henry Vaccaro、Renee Cleven、John Cook、Ahmad Fawzi、Robert Watkins、Hongtao Zhang

  DOI：10.1021/jm970495b

  日期：1997.12.1

  Polycyclic pyrazolo[3,4-d]pyrimidines (represented by 3 and 4) were synthesized as analogues of the recently reported polycyclic guanine phosphodiesterase (PDE) inhibitors. From the structure-activity relationship (SAR) development of a series of compounds, it was discovered that C-3 benzyl and N-2 methyl disubstitution on the pyrazole ring gave the best combination of potency and selectivity for PDE1 and PDE5 cGMP PDEs as represented by compound 4c: PDE1, IC50 = 60 nM; PDE3, IC50 = 55 000 nM; PDE5, IC50 = 75 nM. These compounds were also evaluated in vivo and found to be good orally active antihypertensives in laboratory animal models. Finally, comparisons were made of the in vitro and in vivo profiles of the pyrazolo[3,4-d]pyrimidine compound 4c with those of two representative guanine compounds.