呋喃菲林 | 80288-49-9

• 物质功能分类: 有机原料 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 呋喃菲林
• 中文别名: 3-(2-呋喃基甲基)-3,7-二氢-1,8-二甲基-1H-嘌呤-2,6-二酮；呋喃茶碱
• 英文名称: Furafylline
• 英文别名: 3-(furan-2-ylmethyl)-1,8-dimethyl-7H-purine-2,6-dione
• CAS: 80288-49-9
• 化学式: C₁₂H₁₂N₄O₃
• 分子量: 260.25
• InChiKey: KGQZGCIVHYLPBH-UHFFFAOYSA-N

物化性质

• 熔点：
  >162°C (dec.)
• 沸点：
  543.6±60.0 °C(Predicted)
• 密度：
  1.443±0.06 g/cm3(Predicted)
• 溶解度：
  乙醇：0.33 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  82.4
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

呋拉菲林已知的人类代谢物包括3-[(呋喃-2-基)甲基]-8-羟基-1-甲基-2,3,6,7-四氢-1H-嘌呤-2,6-二酮。

Furafylline has known human metabolites that include 3-[(furan-2-yl)methyl]-8-hydroxy-1-methyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione.

来源:NORMAN Suspect List Exchange

安全信息

• 危险品运输编号：
  NONH for all modes of transport
• WGK Germany：
  3
• 海关编码：
  2939590000
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

Furafylline 是一种有效且选择性的人细胞色素 P450IA2 抑制剂，其 IC₅₀ 值为 0.07 μM。

靶点

• IC₅₀: 0.07 μM (human cytochrome P450IA2)

体内研究

Furafylline 是一种强效且选择性的细胞色素 P450IA2 抑制剂，在激酶实验中的 IC₅₀ 值为 0.07 μM。这是一种甲基黄嘌呤衍生物，作为一种长效替代药物用于治疗哮喘，取代了茶碱的使用。Furafylline 的给药与血浆中咖啡因水平升高有关，这是因为其抑制了咖啡因的氧化反应，该反应由一种或多种诱导的 P450 同工酶催化。此外，Furafylline 对其他 P450 同工酶（包括 P4501D1、P4501A1 和 P450IIIA）的人单加氧酶活性影响甚微或无影响。

文献信息

• [EN] FLUORINATED 2,4-DIAMINOPYRIMIDINE COMPOUNDS AS MER TYROSINE KINASE (MERTK) INHIBITORS AND USES THEREOF<br/>[FR] COMPOSÉS DE 2,4-DIAMINOPYRIMIDINE FLUORÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA TYROSINE KINASE MER (MERTK) ET LEURS UTILISATIONS
  申请人：TRILLIUM THERAPEUTICS INC

  公开号：WO2019006548A1

  公开（公告）日：2019-01-10

  A class of fluorinated 2,4-diaminopyrimidine compounds of Formula (I) have been prepared for use in the treatment of cancers and other MERTK related disorders. (Formula (I))

  一类氟代2,4-二氨基嘧啶化合物的化学式（I）已经制备用于治疗癌症和其他与MERTK相关的疾病。 (化学式（I))
• [EN] NOVEL AGENTS TARGETING CYP51<br/>[FR] NOUVEAUX AGENTS CIBLANT CYP51
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2015048306A1

  公开（公告）日：2015-04-02

  The invention provides inhibitors of a sterol C14-demethylase, a new series of 4- aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi CYP51 (TcCYP51) developed using structure-based drug design as well as structure -property relationship (SPR) analyses. The screening hit starting point, LP 10 (KD < 42 nM; EC50 of 0.65 μΜ), has been optimized to give the potential leads that have low nanomolar binding affinity to TcCYP51 and significant activity against T. cruzi amastigotes cultured in human myoblasts. Many of the optimized compounds have improved microsome stability, and most are selective against the T. cruzi CYP51 relative to human CYPs 1A2, 2D6 and 3A4 (<50% inhibition at 1 μΜ). A rationale for the improvement of microsome stability and selectivity of inhibitors against human metabolic CYP enzymes is presented. In addition, the binding mode of several compounds of the invention with the T. brucei CYP51 (TbCYP51) ortholog has been characterized by x-ray structure analysis. Orally active compounds and their cyclodextrin complexes have been shown to be effective against Chagas-infected mice.

  该发明提供了一种甾醇C14-去甲基酶的抑制剂，这是一种新系列基于4-氨基吡啶的首选抑制剂，通过基于结构的药物设计以及结构-性质关系（SPR）分析来瞄准Trypanosoma cruzi CYP51（TcCYP51）而开发的。筛选起始点LP 10（KD < 42 nM；EC50为0.65 μΜ）已经经过优化，产生了具有低纳摩尔级别结合亲和力和对在人类肌细胞培养的T. cruzi游离体的显著活性的潜在首选抑制剂。许多经过优化的化合物具有改善的微粒体稳定性，大多数相对于人类CYPs 1A2、2D6和3A4对T. cruzi CYP51具有选择性（在1 μΜ下<50%的抑制）。提出了改善微粒体稳定性和抑制剂对人类代谢CYP酶的选择性的理由。此外，通过X射线结构分析表征了该发明的几种化合物与T. brucei CYP51（TbCYP51）同源物的结合方式。口服活性化合物及其环糊精复合物已被证明对克氏病感染的小鼠有效。
• [EN] TRICYCLIC PI3K INHIBITOR COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS TRICYCLIQUES INHIBITEURS DE PI3K ET PROCÉDÉS D'UTILISATION
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012082997A1

  公开（公告）日：2012-06-21

  Tricyclic PI3k inhibitor compounds of Formula I with anti-cancer activity, anti- inflammatory activity, or immunoregulatory properties, and more specifically with PI3 kinase modulating or inhibitory activity are described. Methods are described for using the tricyclic PI3K inhibitor compounds of Formula I for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, organisms, or associated pathological conditions. Formula I compounds include stereoisomers, geometric isomers, tautomers, and pharmaceutically acceptable salts thereof. The dashed lines indicate an optional double bond, and at least one dashed line is a double bond. The substituents are as described.

  具有抗癌活性、抗炎活性或免疫调节特性的Formula I的三环PI3K抑制剂化合物被描述。描述了使用Formula I的三环PI3K抑制剂化合物进行体外、原位和体内诊断或治疗哺乳动物细胞、生物体或相关病理条件的方法。Formula I化合物包括立体异构体、几何异构体、互变异构体和其药用可接受盐。虚线表示可选的双键，至少有一条虚线是双键。取代基如所述。
• [EN] SUBSTITUTED PIPERIDINES AS RENIN INHIBITORS<br/>[FR] PIPÉRIDINES SUBSTITUÉES EN TANT QU'INHIBITEURS DE LA RÉNINE
  申请人：NOVARTIS AG

  公开号：WO2009098275A1

  公开（公告）日：2009-08-13

  The present invention relates to compounds of the general formula (I) and the salts thereof, preferably the pharmaceutically acceptable salts thereof; in which R has the meaning explained in the description, a process for their preparation and the use of these compounds as medicines, especially as renin inhibitors.

  本发明涉及一般式（I）的化合物及其盐，优选为其药用可接受的盐；其中R具有描述中解释的含义，其制备方法以及将这些化合物用作药物，特别是作为肾素抑制剂的用途。
• 5-Lipoxygenase-Activating Protein Inhibitor
  申请人：SCHAAB Kevin Murray

  公开号：US20090291981A1

  公开（公告）日：2009-11-26

  Described herein is the FLAP inhibitor 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxy-pyridin-3-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid, or a pharmaceutically acceptable salt thereof. Also described are methods of preparing the FLAP inhibitor, or a pharmaceutically acceptable salt thereof, including solvates, and polymorphs thereof. Also described herein are pharmaceutical compositions suitable for administration to a mammal that include the FLAP inhibitor, or a pharmaceutically acceptable salt thereof, and methods of using such pharmaceutical compositions for treating respiratory conditions or diseases, as well as other leukotriene-dependent or leukotriene mediated conditions or diseases.

  描述了一种FLAP抑制剂：3-[3-叔丁基硫基-1-[4-(6-乙氧基-吡啶-3-基)-苄基]-5-(5-甲基-吡啶-2-基甲氧基)-1H-吲哚-2-基]-2,2-二甲基丙酸，或其药用可接受盐。还描述了制备该FLAP抑制剂的方法，或其药用可接受盐，包括水合物和其多晶型。还描述了适合给予哺乳动物的药物组合物，包括FLAP抑制剂，或其药用可接受盐，以及使用此类药物组合物治疗呼吸系统疾病或疾病的方法，以及治疗其他白三烯依赖性或白三烯介导的条件或疾病的方法。