5-Benzyl-4,8,11,11-tetramethyl-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 5-Benzyl-4,8,11,11-tetramethyl-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-one
• 化学式: C₁₈H₂₁N₅O
• 分子量: 323.398
• InChiKey: XZXFCSVKXLUIFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  53.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  ethyl 3-amino-5-benzyl-1-methyl-1H-pyrazole-4-carboxylate 在 甲醇 、 磺酰氯 、 sodium methylate 、 三乙胺 、 三氯氧磷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 63.0h， 生成 5-Benzyl-4,8,11,11-tetramethyl-1,3,4,8,10-pentazatricyclo[7.3.0.02,6]dodeca-2,5,9-trien-7-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

文献信息

• Organic compounds
  申请人：Fienberg Allen A.

  公开号：US10010553B2

  公开（公告）日：2018-07-03

  The present invention relates to a new use of phosphodiesterase 1 (PDE1) inhibitors for the treatment of psychosis, schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder, delusional disorder, mania, or bipolar disorder.

  本发明涉及一种磷酸二酯酶1（PDE1）抑制剂的新用途，用于治疗精神病、精神分裂症、情感分裂症、精神分裂症、精神病性障碍、妄想性障碍、躁狂症或双相情感障碍。
• Combinations of PDE1 inhibitors and NEP inhibitors and associated methods
  申请人：Intra-Cellular Therapies, Inc.

  公开号：US10285992B2

  公开（公告）日：2019-05-14

  The invention relates to the combination of inhibitors of phosphodiesterase 1 (PDE1) and inhibitors of Neprilysin (NEP) useful for the treatment of certain cardiovascular diseases or related disorders, e.g., hypertension, congestive heart disease, and post-myocardial infarction. In another embodiment, the invention relates to the combination of inhibitors of PDE1 and inhibitors of NEP for the treatment of diseases or disorders characterized by disruption of or damage to various cGMP/PKG mediated pathways in the cardiovascular system (e.g., in cardiac tissue or in arterial smooth muscle).

  本发明涉及磷酸二酯酶1（PDE1）抑制剂和NEPrilysin（NEP）抑制剂的组合，用于治疗某些心血管疾病或相关疾病，如高血压、充血性心脏病和心肌梗塞后。在另一个实施方案中，本发明涉及 PDE1 抑制剂和 NEP 抑制剂的组合，用于治疗以心血管系统（如心脏组织或动脉平滑肌）中各种 cGMP/PKG 介导的通路被破坏或损害为特征的疾病或紊乱。
• Combinations of PDE1 inhibitors and NEP inhibitors
  申请人：INTRA-CELLULAR THERAPIES, INC.

  公开号：US11166956B2

  公开（公告）日：2021-11-09

  The invention relates to the combination of inhibitors of phosphodiesterase 1 (PDE1) and inhibitors of Neprilysin (NEP) useful for the treatment of certain cardiovascular diseases or related disorders, e.g., hypertension, congestive heart disease, and post-myocardial infarction. In another embodiment, the invention relates to the combination of inhibitors of PDE1 and inhibitors of NEP for the treatment of diseases or disorders characterized by disruption of or damage to various cGMP/PKG mediated pathways in the cardiovascular system (e.g., in cardiac tissue or in arterial smooth muscle).

  本发明涉及磷酸二酯酶1（PDE1）抑制剂和NEPrilysin（NEP）抑制剂的组合，用于治疗某些心血管疾病或相关疾病，如高血压、充血性心脏病和心肌梗塞后。在另一个实施方案中，本发明涉及 PDE1 抑制剂和 NEP 抑制剂的组合，用于治疗以心血管系统（如心脏组织或动脉平滑肌）中各种 cGMP/PKG 介导的通路被破坏或损害为特征的疾病或紊乱。
• PDE1 inhibitors for ophthalmic disorders
  申请人：Davis Robert

  公开号：US11464781B2

  公开（公告）日：2022-10-11

  Compounds that inhibit phosphodiesterase 1 (PDE1) are useful to treat glaucoma or elevated intraocular pressure. The PDE1 inhibitors may be administered as monotherapy or in combination with additional intraocular-pressure lowering agents. In addition, the invention provides ophthalmic compositions comprising PDE 1 inhibitors and optionally one or more additional intraocular pressure-lowering agents. Topical and systemic therapy may be used.

  抑制磷酸二酯酶 1 (PDE1) 的化合物可用于治疗青光眼或眼压升高。PDE1 抑制剂可作为单药或与其他降低眼压的药物联合使用。此外，本发明还提供了包含 PDE 1 抑制剂和一种或多种额外的眼压降低剂的眼科组合物。可采用局部和全身疗法。
• ORGANIC COMPOUNDS
  申请人：Mates Sharon

  公开号：US20100087450A1

  公开（公告）日：2010-04-08

  The present invention relates to a new use of phosphodiesterase 1 (PDE1) inhibitors for the treatment and/or prophylaxis of narcolepsy.