(5-氟-2-羟基苯基)-(1-苯基吡唑-4-基)甲酮 | 288401-60-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (5-氟-2-羟基苯基)-(1-苯基吡唑-4-基)甲酮
• 中文别名: 5′-氟-2′-羟苯基-1-苯基-1H-吡唑-4-基甲酮
• 英文名称: 4-fluoro-2-(1-phenyl-1H-pyrazole-4-carbonyl)phenol
• 英文别名: (5-fluoro-2-hydroxyphenyl)(1-phenyl-1H-pyrazol-4-yl)methanone；(5-fluoro-2-hydroxyphenyl)-(1-phenylpyrazol-4-yl)methanone
• CAS: 288401-60-5
• 化学式: C₁₆H₁₁FN₂O₂
• 分子量: 282.274
• InChiKey: LUIKVPFJGVQNCR-UHFFFAOYSA-N

物化性质

• 熔点：
  116-119 °C(lit.)
• 沸点：
  440.7±35.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)
• 溶解度：
  0.7 [ug/mL]
• 稳定性/保质期：

  常温常压下稳定，避免与强氧化剂接触。

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338

反应信息

• 作为反应物：
  描述：

  (5-氟-2-羟基苯基)-(1-苯基吡唑-4-基)甲酮 在 lithium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 12.0h， 生成 4-fluoro-2-(1-phenyl-1H-pyrazole-4-carbonyl)phenoxyethanoic acid
  参考文献：
  名称：

  Novel Selective Orally Active CRTH2 Antagonists for Allergic Inflammation Developed from in Silico Derived Hits

  摘要：

  Hits from an in silico derived focused library for CRTH2 were transformed into highly selective antagonists with favorable ADME properties. Oral administration of 4-bromo-2-( 1-phenyl-1H-pyrazole-4-carbonyl) phenoxyacetic acid ( 19) inhibited peribronchial eosinophilia and mucus cell hyperplasia in a mouse model of allergic asthma, supporting the therapeutic potential of this novel compound class. In addition, this selective pharmacological tool compound provides further evidence for CRTH2 as a relevant therapeutic target for treatment of Th2- and eosinophil-related inflammation.

  DOI：

  10.1021/jm060657g
• 作为产物：
  描述：

  6-氟色同-3-甲醛 、 苯肼 以 四氢呋喃 为溶剂， 生成 (5-氟-2-羟基苯基)-(1-苯基吡唑-4-基)甲酮
  参考文献：
  名称：

  In vitro cytotoxicity of hydrazones, pyrazoles, pyrazolo-pyrimidines, and pyrazolo-pyridine synthesized from 6-substituted 3-formylchromones

  摘要：

  通过6-取代（H，Me，F）3-甲酰基香豆素 1a–c 与 N-取代的肼 2a–c 和氨基吡唑 3 反应，制备了吡唑 4a–f，肼酮 5a–c 和 6a–c，吡唑并[1,5-a]嘧啶 7a，b，和吡唑并[3,4-b]吡啶 8，产率良好（80–95%）。通过盐水虾致死实验评估了合成化合物的细胞毒性。IC₅₀ 值在80和300 μm 之间。氟取代降低了IC₅₀ 值。

  DOI：

  10.1515/znb-2014-0236

文献信息

• SYNTHESIS OF SOME NEW 3-BENZOPYRANOPYRIDINYL AND 3-PYRAZOLYL 1,2-BENZISOXAZOLES FROM o-HYDROXYHETEROARYL KETONES DERIVED FROM 3- FORMYLCHROMONE
  作者：G. Jagath Reddy、D. Latha、C. Thirupathaiah、K. Srinivasa Rao

  DOI：10.1515/hc.2003.9.4.391

  日期：2003.1

  (2a-r). Reaction of 1 with Phenylhydrazine gives Vol. 9, No. 4, 2003 Synthesis of some new 3-benzo pyraopyridinyl and 3-pyrazolyl 1,2-benzisoxazoles from o-hydroxy heteroarylketones derivedfrom 3-formylchromone hydroxybenzoylpyrazoles (6a-e) in good yields. The corresponding o-hydroxyketoximes 3a-q and 7a-e were obtained from o-hydroxyketones 2a-r and 6a-e by refluxing with hydroxylamine hydrochloride in

  一系列 3-苯并吡喃并吡啶基和吡唑基 1,2-苯并异恶唑 (5 & 9) 已从 3-甲酰基色酮 (1) 衍生的邻羟基芳基酮 (2 & 6) 制备。介绍 各种 3-取代 1,2-苯并异恶唑已被报道具有生理特性，例如抗惊厥和解痉活性。最近有报道称，两种 3-哌啶基取代的苯并异恶唑，即阿巴哌酮盐酸盐和伊潘立酮显示出有希望的抗精神病活性。此外，据报道几种吡唑衍生物和苯并吡喃并吡啶具有多种类型的生物活性。此外，由于存在不饱和酮基，3-甲酰基色酮 1 是一种非常活泼的中间体，在 C3 上有一个共轭的第二个羰基，在 C2 上有一个非常活泼的中心，这允许迈克尔加成亲核试剂并打开 γ-吡喃酮环。这些特性使 1 成为一种多功能合成子，可以很容易地从中获得各种邻羟基杂芳基酮。继续我们对基于 3-甲酰基色酮 (1) 的杂环的研究，并考虑到与 1,2-苯并异恶唑、吡唑和苯并吡喃吡啶相关的生物学特性，我们对从中间体邻羟基杂芳基酮合成
• CRTH2 Receptor Ligands For Medicinal Uses
  申请人：Ulven Trond

  公开号：US20090099189A1

  公开（公告）日：2009-04-16

  Compounds of formula (I) are useful for the treatment of disease responsive to modulation of CRTH2 receptor activity, such as asthma, rhinitis, allergic airway syndrome, and allergic rhinobronchitis, wherein A represents a carboxyl group —COON, or a carboxyl bioisostere; A 1 , is hydrogen or methyl; ring Ar 1 is an optionally substituted phenyl ring 5- or 6-membered monocyclic heteroaryl ring, in which AA 1 CHO— and L2 are linked to adjacent ring atoms; rings Are 2 , Ar 3 each independently represent a phenyl or 5- or 6-membered monocyclic heteroaryl ring, or a bicyclic ring system consisting of a 5- or 6-membered carbocyclic or heterocyclic ring which is benz-fused or fused to a 5- or 6-membered monocyclic heteroaryl ring, said ring or ring system being optionally substituted; t is 0 or 1; L2 and L3 are linker radicals as defined in the description.

  式(I)的化合物可用于治疗对CRTH2受体活性调节敏感的疾病，例如哮喘、鼻炎、过敏性气道综合症和过敏性鼻支气管炎，其中A代表羧基—COON或羧基生物同位素；A1为氢或甲基；环Ar1是一个可选取代的苯环5-或6-成员的单环杂环，其中AA1CHO—和L2与相邻的环原子连接；环Are2，Ar3各自独立地表示一个苯环或5-或6-成员的单环杂环，或由一个5-或6-成员的碳环或杂环组成的双环系统，该环或环系统被苯并或与一个5-或6-成员的单环杂环融合，该环或环系统是可选取代的；t为0或1；L2和L3是如描述中所定义的连接基团。
• CRTH2 receptor ligands for medicinal uses
  申请人：Ulven Trond

  公开号：US20110269763A1

  公开（公告）日：2011-11-03

  Compounds of formula (I) are useful for the treatment of disease responsive to modulation of CRTH2 receptor activity, such as asthma, rhinitis, allergic airway syndrome, and allergic rhinobronchitis: wherein A represents a carboxyl group —COOH, or a carboxyl bioisostere; A 1 is hydrogen or methyl; ring Ar 1 is an optionally substituted phenyl ring or 5- or 6-membered monocyclic heteroaryl ring, in which AA 1 CHO— and L2 are linked to adjacent ring atoms; rings Ar 2 , Ar 3 each independently represent a phenyl or 5- or 6-membered monocyclic heteroaryl ring, or a bicyclic ring system consisting of a 5- or 6-membered carbocyclic or heterocyclic ring which is benz-fused or fused to a 5- or 6-membered monocyclic heteroaryl ring, said ring or ring system being optionally substituted; t is 0 or 1; L2 and L3 are linker radicals as defined in the description.

  式(I)的化合物可用于治疗对CRTH2受体活性调节敏感的疾病，例如哮喘、鼻炎、过敏性气道综合症和过敏性鼻支气管炎：其中A代表羧基—COOH或羧基生物同位素；A1为氢或甲基；环Ar1为可选取代的苯环或5-或6-成员的单环杂环，其中AA1CHO—和L2连接到相邻的环原子上；环Ar2、Ar3各自独立地表示苯环或5-或6-成员的单环杂环，或由5-或6-成员的碳环或杂环组成的双环系统，该环或环系统是苯并或与5-或6-成员的单环杂环融合，该环或环系统是可选的取代；t为0或1；L2和L3是如描述中定义的连接基。
• Synthesis of novel 6-substituted-3-formyl chromone derivatives as anti-leishmanial agents and their possible mechanism of action in Leishmania donovani
  作者：Elier Galarraga、Angel E. Santorelli、Neudo Urdaneta、André Rey-Cibati、Mariana Valladares-Delgado、Luis José Díaz-Pérez、Laura Milano-Franco、Gustavo Benaim

  DOI：10.1016/j.molstruc.2023.135081

  日期：2023.5

  Eleven new compounds, including the hydrazones 4a-h, pyrazole 5, and pyrazole-oximes 7b-c, were synthesized by condensation reaction between 6-substituted (-H, -Me, -F) 3-formylchromones 1a-c with N-substituted hydrazines 2a-d and hydroxylamine hydrochloride 3. The synthesized compounds were evaluated for their in vitro antileishmanial activity to determine the IC50 values. Compounds 4b, 4c and 4e

  通过6-取代的(-H, -Me, -F) 3-甲酰色酮1a-c与N -的缩合反应合成了11个新化合物，包括腙4a-h、吡唑5和吡唑肟7b-c 。取代肼2a-d和盐酸羟胺3。评估合成化合物的体外抗利什曼原虫活性以确定IC 50值。化合物4b、4c和4e表现出最强的抗利什曼动物活性，IC 50值在 1.6 – 4.7 µ m之间. 对于上述化合物的抗利什曼动物活性，提出了一个似是而非的作用机制。我们还研究了这三种化合物对代表哺乳动物宿主细胞的巨噬细胞的影响。与L. donovani的结果相比，在该系统上获得的结果大约大一个数量级，从而支持这些化合物作为抗利什曼病药物前体的潜力。
• CRTH2 Receptor Ligands for Medical Use
  申请人：7TM Pharma A/S

  公开号：EP2336113A1

  公开（公告）日：2011-06-22

  4-Bromo-2-[1-(2,6-dichlorophenyl)-1H-pyrazole-4-carbonyl]phenoxyl acetic acid is useful for the treatment of disease responsive to modulation of CRTH2 receptor activity, such as asthma, rhinitis, allergic airway syndrome, and allergic rhinobronchitis.

  4-溴-2-[1-（2,6-二氯苯基）-1H-吡唑-4-甲酰基]苯氧乙酸可用于治疗对调节 CRTH2 受体活性有反应的疾病，如哮喘、鼻炎、过敏性气道综合征和过敏性鼻支气管炎。