6-(4-chlorophenyl)-3-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1,2,4-triazol-1-yl)propyl]thieno[3,2-d]pyrimidin-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 6-(4-chlorophenyl)-3-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1,2,4-triazol-1-yl)propyl]thieno[3,2-d]pyrimidin-4-one
• 英文别名: 6-(4-chlorophenyl)-3-[(2R,3R)-3-(2,4-difluorophenyl)-3-hydroxy-4-(1,2,4-triazol-1-yl)butan-2-yl]thieno[3,2-d]pyrimidin-4-one
• 化学式: C₂₄H₁₈ClF₂N₅O₂S
• 分子量: 513.955
• InChiKey: FSKFOGDDOUMDPE-JBEBIEQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氨基-5-(4-氯苯基)-2-噻吩甲酸 在 N-甲基吡咯烷酮 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 6-(4-chlorophenyl)-3-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1,2,4-triazol-1-yl)propyl]thieno[3,2-d]pyrimidin-4-one
  参考文献：
  名称：

  New Azole Antifungals. 2. Synthesis and Antifungal Activity of Heterocyclecarboxamide Derivatives of 3-Amino-2-aryl-1-azolyl-2-butanol

  摘要：

  A series of 92 azole antifungals containing an amido alcohol unit was synthesized. The nature and substitution of the amide portion was systematically modified in search of improved antifungal activity, especially against filamentous fungi. The compounds were tested in vitro against a variety of clinically important pathogens and in vivo (po) in a murine candidosis model. Thiazole and thiophene carboxamides carrying both a substituted phenyl ring and a small alkyl. group were best suited for activity against filamentous fungi. In a subset of these compounds, the amide portion was conformationally locked by means of a pyrimidone ring and it was proven that only an orthogonal orientation of the phenyl ring yields bioactive products. A tendency to display long plasma elimination half-lives was observed in both series. Two compounds, 74 and 107, representative of the open and cyclic amides, respectively, were chosen for further studies, based on their excellent activity in in vivo murine models of candidosis and aspergillosis. This work describes the SARs found within this series. The next paper displays the results obtained in a related series of compounds, the quinazolinones.

  DOI：

  10.1021/jm970726e

文献信息

• [EN] NEW PYRIMIDONE DERIVATIVES WITH ANTIFUNGAL ACTIVITY<br/>[FR] NOUVEAUX DERIVES PYRIMIDONE A ACTIVITE ANTIFONGIQUE
  申请人：J. URIACH & CIA. S.A.

  公开号：WO1997005130A1

  公开（公告）日：1997-02-13

  (EN) Compounds of general formula (I) and their salts and solvates are antifungal agents and as such are useful in the treatment of various fungal infections. Pharmaceutical compositions including these compounds and processes for their preparation are also provided.(FR) Les composés de la formule générale (I) et leurs sels et solvates sont des agents antifongiques. Il sont utiles pour le traitement de différentes infections fongiques. L'invention concerne également des compositions pharmaceutiques comprenant ces composés et des procédés permettant leur préparation.

  化合物的一般式（I）及其盐和溶剂物是抗真菌剂，因此可用于治疗各种真菌感染。还提供了包括这些化合物的制药组合物和其制备方法。
• Azole antifungal compositions
  申请人：Lenn Jon

  公开号：US10251885B2

  公开（公告）日：2019-04-09

  The present invention relates generally to antifugal compositions. In an embodiment, the antifungal compositions are effective for application to nails and surrounding skin, and comprise at least one volatile solvent, at least one film forming substance, and at least one pyrimidone derivative of formula I, such as albaconazole. These compositions are capable of treating an infection caused by fungi, such as onychomychosis.

  本发明一般涉及抗真菌组合物。在一个实施方案中，抗真菌组合物对指甲和周围皮肤有效，包含至少一种挥发性溶剂、至少一种成膜物质和至少一种式 I 的嘧啶酮衍生物，如阿巴康唑。这些组合物能够治疗由真菌引起的感染，如甲癣。
• PYRIMIDONE DERIVATIVES WITH ANTIFUNGAL ACTIVITY
  申请人：J. URIACH & CIA. S.A.

  公开号：EP0783501B1

  公开（公告）日：2001-01-10
• AZOLE ANTIFUNGAL COMPOSITIONS
  申请人：Palau Pharma, S.A.

  公开号：EP2434892B1

  公开（公告）日：2015-08-19
• [EN] AZOLE ANTIFUNGAL COMPOSITIONS<br/>[FR] COMPOSITIONS ANTIFONGIQUES À BASE D'AZOLE
  申请人：STIEFEL LABORATORIES

  公开号：WO2010138674A1

  公开（公告）日：2010-12-02

  The present invention relates generally to antifugal compositions. In an embodiment, the antifungal compositions are effective for application to nails and surrounding skin, and comprise at least one volatile solvent, at least one film forming substance, and at least one pyrimidone derivative of formula I, such as albaconazole. These compositions are capable of treating an infection caused by fungi, such as onychomychosis.