西地那非杂质35 | 220060-39-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 西地那非杂质35
• 英文名称: 3-ethyl-1,3-dihydro-8-[[[2-[4-(hydroxymethyl)-1-piperidinyl]phenyl]methyl]amino]-2H-imidazo[4,5-g]quinazoline-2-thione
• 英文别名: thioquinapiperifil；3-Ethyl-8-[2-(4-hydroxymethylpiperidino)benzylamino]-2,3-dihydro-1H-imidazo[4,5-g]quinazoline-2-thione；3-ethyl-8-[[2-[4-(hydroxymethyl)piperidin-1-yl]phenyl]methylamino]-1H-imidazo[4,5-g]quinazoline-2-thione
• CAS: 220060-39-9
• 化学式: C₂₄H₂₈N₆OS
• 分子量: 448.592
• InChiKey: NMKUPEWPVORTPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  6

制备方法与用途

生物活性

Thioquinapiperifil (KF31327 free base) 是一种有效的、选择性的非竞争性磷酸二酯酶（PDE-5）抑制剂，其IC50值为0.074 nM。这种化合物可用于研究性成熟。

靶点

• PDE5：0.074 nM (IC50)
• PDE1：380 nM (IC50)
• PDE2：670 nM (IC50)
• PDE3：38 nM (IC50)
• PDE4：800 nM (IC50)

体外研究

Thioquinapiperifil 可以在膳食补充剂中找到。Thioquinapiperifil（KF31327 free base）浓度依赖性地抑制血小板聚集。在没有硝酸甘油的情况下，更高浓度的1 μM和10 μM Thioquinapiperifil （KF31327 free base）才可抑制血小板聚集。Thioquinapiperifil（KF31327 free base）能显著增加环磷酸鸟苷水平，在10 μM浓度下尤为明显。在5分钟孵育后，Thioquinapiperifil （KF31327）处理细胞的平均环磷酸鸟苷水平为0.95±0.17 pmol/108个细胞。

反应信息

• 作为反应物：
  描述：

  西地那非杂质35 在 盐酸 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以89%的产率得到3-ethyl-1,3-dihydro-8-[[[2-[4-(hydroxymethyl)-1-piperidinyl]phenyl]methyl]amino]-2H-imidazo[4,5-g]quinazoline-2-thione dihydrochloride
  参考文献：
  名称：

  Development of a Practical Synthetic Route of a PDE V Inhibitor KF31327

  摘要：

  An efficient route suitable for a large-scale preparation of KF31327 (1), a potent phosphodiesterase V inhibitor, has been developed. We selected 7-chloro-2,4(1H,3H)-quinazolinedione (15) as a starting material, which gave the desired 6-nitro compound with good selectivity. In the chlorination of 7-ethylamino-6-nitro-2,4(1H,3H)-quinazolinedione (17), reaction conditions were optimized to minimize the amount of phosphorus oxychloride, and 2,4-dichloro-7-ethylamino-6-nitroquinazoline (14) was obtained in excellent yield. After the selective substitution at C4 position, the chloro substituent at C2 position was successfully removed by hydrogenation concomitant with the reduction of nitro group. The construction of the imidazothione ring was achieved by using phenyl isothiocyanate as a thiocarbonyl donor instead of extremely flammable carbon disulfide. Multikilograms of drug substance have been successfully prepared by these procedures.

  DOI：

  10.1021/op010025y
• 作为产物：
  描述：

  7-chloro-6-nitro-2,4(1H,3H)-quinazolinedione 在 palladium 10% on activated carbon 、 sodium formate 、 三乙胺 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 丙醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 25.0h， 生成 西地那非杂质35
  参考文献：
  名称：

  Development of a Practical Synthetic Route of a PDE V Inhibitor KF31327

  摘要：

  An efficient route suitable for a large-scale preparation of KF31327 (1), a potent phosphodiesterase V inhibitor, has been developed. We selected 7-chloro-2,4(1H,3H)-quinazolinedione (15) as a starting material, which gave the desired 6-nitro compound with good selectivity. In the chlorination of 7-ethylamino-6-nitro-2,4(1H,3H)-quinazolinedione (17), reaction conditions were optimized to minimize the amount of phosphorus oxychloride, and 2,4-dichloro-7-ethylamino-6-nitroquinazoline (14) was obtained in excellent yield. After the selective substitution at C4 position, the chloro substituent at C2 position was successfully removed by hydrogenation concomitant with the reduction of nitro group. The construction of the imidazothione ring was achieved by using phenyl isothiocyanate as a thiocarbonyl donor instead of extremely flammable carbon disulfide. Multikilograms of drug substance have been successfully prepared by these procedures.

  DOI：

  10.1021/op010025y

文献信息

• Method of inhibiting neoplastic cells with imidazoquinazoline derivatives
  申请人：——

  公开号：US20020193389A1

  公开（公告）日：2002-12-19

  A method for inhibiting neoplasia, particularly cancerous and precancerous lesions by exposing the affected cells to imidazoquinazoline derivatives.

  通过将受影响的细胞暴露于咪唑喹啉衍生物，抑制新生物的方法，特别是癌症和癌前病变。
• IMIDAZOQUINAZOLINE DERIVATIVES
  申请人：Kyowa Hakko Co., Ltd.

  公开号：EP0863144A1

  公开（公告）日：1998-09-09

  The present invention provides imidazoquinazoline derivatives represented by formula (I): wherein R1 represents hydrogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted bicycloalkyl, substituted or unsubstituted tricycloalkyl or the like, R2 represents hydrogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted bicycloalkyl, substituted or unsubstituted tricycloalkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted aralkyl or the like, R3 represents hydrogen, substituted lower alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted bicycloalkyl, substituted or unsubstituted tricycloalkyl, substituted or unsubstituted lower alkenyl, substituted or unsubstituted aralkyl or the like, and R2 and R3 are combined to represent a substituted or unsubstituted N-containing heterocyclic group, X represents O or S, or pharmaceutically acceptable salts thereof, which have potent and selective cyclic guanosine 3',5'-monophosphate (cGMP)-specific phosphodiesterase (PDE) inhibitory activity and are useful for treating or ameliorating cardiovascular diseases such as thrombosis, angina pectoris, hypertension, heart failure, arterial sclerosis, as well as asthma, impotence and the like.

  本发明提供了由式(I)代表的咪唑喹唑啉衍生物： 其中 R1 代表氢、取代或未取代的低级烷基、取代或未取代的环烷基、取代或未取代的二环烷基、取代或未取代的三环烷基或类似物，R2 代表氢、取代或未取代的低级烷基、取代或未取代的环烷基、取代或未取代的二环烷基、取代或未取代的三环烷基、取代或未取代的四环烷基、取代或未取代的五环烷基或类似物、R3代表氢、取代或未取代的低级烷基、取代或未取代的环烷基、取代或未取代的双环烷基、取代或未取代的三环烷基、取代或未取代的低级烯基、取代或未取代的芳烷基或类似物、取代或未取代的三环烷基、取代或未取代的低级烯基、取代或未取代的芳烷基或类似基团，R2 和 R3 结合代表取代或未取代的含 N 杂环基团，X 代表 O 或 S 或其药学上可接受的盐、它们具有强效和选择性环鸟苷-3',5'-单磷酸（cGMP）特异性磷酸二酯酶（PDE）抑制活性，可用于治疗或改善心血管疾病，如血栓形成、心绞痛、高血压、心力衰竭、动脉硬化以及哮喘、阳痿等。
• Composition comprising a pde4 inhibitor and a pde5 inhibitor
  申请人：Dunkern Torsten

  公开号：US20060094723A1

  公开（公告）日：2006-05-04

  The invention relates to the combined administration of a PDE4 inhibitor and a PDE5 inhibitor for the treatment of a disease in which phosphodiesterase 4 (PDE4) and/or phosphodiesterase 5 (PDE5) is detrimental.

  本发明涉及联合使用 PDE4 抑制剂和 PDE5 抑制剂治疗磷酸二酯酶 4（PDE4）和/或磷酸二酯酶 5（PDE5）有害的疾病。
• Composition comprising a pulmonary surfactant and a pde5 inhibitor for the treatment of lung diseases
  申请人：Wollin Stefan-Lutz

  公开号：US20060148693A1

  公开（公告）日：2006-07-06

  The invention relates to the combined administration of a pulmonary surfactant and a PDE5 inhibitor for the treatment of a disease in which pulmonary surfactant malfunction and/or phosphodiesterase 5 (PDE5) activity is detrimental.

  本发明涉及肺表面活性物质和PDE5抑制剂的联合用药，用于治疗肺表面活性物质功能障碍和/或磷酸二酯酶5（PDE5）活性有害的疾病。
• COMPOSITION COMPRISING A PDE4 INHIBITOR AND A PDE5 INHIBITOR
  申请人：ALTANA Pharma AG

  公开号：EP1628682A2

  公开（公告）日：2006-03-01