3-(4-fluorophenyl)-4-(4-methanesulfonylphenyl)-5H-furan-2-one | 157672-00-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 3-(4-fluorophenyl)-4-(4-methanesulfonylphenyl)-5H-furan-2-one
• 英文别名: 3-(4-fluorophenyl)-4-<4-(methylsulfonyl)phenyl>-5H-furan-2-one；3-(4-fluorophenyl)-4-[(4-methylsulfonyl)phenyl]-5H-furan-2-one；3-(4-Fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-5-hydrofuran-2-one；3-(4-fluorophenyl)-4-(4-methylsulfonylphenyl)-2 (5H)-furanone；2(5H)-Furanone, 3-(4-fluorophenyl)-4-[4-(methylsulfonyl)phenyl]-；4-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)-2H-furan-5-one
• CAS: 157672-00-9
• 化学式: C₁₇H₁₃FO₄S
• 分子量: 332.352
• InChiKey: ZRCURVJXQGLLOZ-UHFFFAOYSA-N

物化性质

• 熔点：
  170-171 °C
• 沸点：
  571.3±50.0 °C(Predicted)
• 密度：
  1.385±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  68.8
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 储存条件：
  | 室温 |

反应信息

• 作为反应物：
  描述：

  3-(4-fluorophenyl)-4-(4-methanesulfonylphenyl)-5H-furan-2-one 在 吡啶 、 氯化亚砜 、 lithium hydride 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.58h， 生成 1-<2-(4-fluorophenyl)-4,4-bis(tosylmethyl)cyclopenten-1-yl>-4-(methylsulfonyl)benzene
  参考文献：
  名称：

  Diarylspiro[2.4]heptenes as Orally Active, Highly Selective Cyclooxygenase-2 Inhibitors:  Synthesis and Structure−Activity Relationships

  摘要：

  A novel series of 5,6-diarylspiro[2.4]hept-5-enes was shown to provide highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. A study of structure-activity relationships in this series suggests that 3,4-disubstituted phenyl analogs are generally more selective than 4-substituted phenyl analogs and that replacement of the methyl sulfone group on the B-phenyl ring with a sulfonamide moiety results in compounds with superior in vivo pharmacological properties, although with lower COX-2 selectivity, Several compounds have been shown to possess promising pharmacological properties in adjuvant-induced arthritis and edema analgesia models. The absence of gastrointestinal (GI) toxicity at 200 mpk of several selected compounds in rats and mice corresponds well with the weak potency for inhibition of COX-1 observed in the enzyme assay. Methyl sulfone 55 and sulfonamide 24 were shown to have superior in vivo pharmacological profiles, low GI toxicity, and good oral bioavailability and duration of action.

  DOI：

  10.1021/jm950664x
• 作为产物：
  描述：

  2-溴-1-(4-甲磺酰基)苯乙酮 在 4 A molecular sieve 、 对甲苯磺酸 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 16.5h， 生成 3-(4-fluorophenyl)-4-(4-methanesulfonylphenyl)-5H-furan-2-one
  参考文献：
  名称：

  Diarylspiro[2.4]heptenes as Orally Active, Highly Selective Cyclooxygenase-2 Inhibitors:  Synthesis and Structure−Activity Relationships

  摘要：

  A novel series of 5,6-diarylspiro[2.4]hept-5-enes was shown to provide highly potent and selective cyclooxygenase-2 (COX-2) inhibitors. A study of structure-activity relationships in this series suggests that 3,4-disubstituted phenyl analogs are generally more selective than 4-substituted phenyl analogs and that replacement of the methyl sulfone group on the B-phenyl ring with a sulfonamide moiety results in compounds with superior in vivo pharmacological properties, although with lower COX-2 selectivity, Several compounds have been shown to possess promising pharmacological properties in adjuvant-induced arthritis and edema analgesia models. The absence of gastrointestinal (GI) toxicity at 200 mpk of several selected compounds in rats and mice corresponds well with the weak potency for inhibition of COX-1 observed in the enzyme assay. Methyl sulfone 55 and sulfonamide 24 were shown to have superior in vivo pharmacological profiles, low GI toxicity, and good oral bioavailability and duration of action.

  DOI：

  10.1021/jm950664x

文献信息

• Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use
  申请人：——

  公开号：US20010041726A1

  公开（公告）日：2001-11-15

  The present invention describes novel nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitors and novel compositions comprising at least one nitrosated and/or nitrosylated cyclooxygenase 2 (COX-2) inhibitor, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or optionally, at least one therapeutic agent, such as, steroids, nonsteroidal antiinflammatory compounds (NSAID), 5-lipoxygenase (5-LO) inhibitors, leukotriene B 4 (LTB 4 ) receptor antagonists, leukotriene A 4 (LTA 4 ) hydrolase inhibitors, 5-HT agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) inhibitors, H antagonists, antineoplastic agents, antiplatelet agents, decongestants, diuretics, sedating or non-sedating anti-histamines, inducible nitric oxide synthase inhibitors, opioids, analgesics, Helicobacter pylori inhibitors, proton pump inhibitors, isoprostane inhibitors, and mixtures thereof. The present invention also provides novel compositions comprising at least one parent COX-2 inhibitor and at least one nitric oxide donor, and, optionally, at least one therapeutic agent. The present invention also provides kits and methods for treating inflammation, pain and fever; for treating and/or improving the gastrointestinal properties of COX-2 inhibitors; for facilitating wound healing; for treating and/or preventing renal toxicity; and for treating and/or preventing other disorders resulting from elevated levels of cyclooxygenase-2.

  本发明描述了新颖的硝化和/或亚硝化环氧合酶2（COX-2）抑制剂以及包含至少一种硝化和/或亚硝化环氧合酶2（COX-2）抑制剂的新型组合物，以及可选地，至少一种捐赠、转移或释放一氧化氮、刺激内源性一氧化氮合成、提高内源性内皮源性舒张因子水平或是一氧化氮合酶底物的化合物，和/或可选地，至少一种治疗剂，如类固醇、非甾体抗炎化合物（NSAID）、5-脂氧合酶（5-LO）抑制剂、白三烯B4（LTB4）受体拮抗剂、白三烯A4（LTA4）水解酶抑制剂、5-HT激动剂、3-羟基-3-甲基戊二酰辅酶A（HMGCoA）抑制剂、H受体拮抗剂、抗肿瘤药物、抗血小板药物、解充血剂、利尿剂、镇静或非镇静抗组胺药、诱导型一氧化氮合酶抑制剂、阿片类药物、镇痛剂、幽门螺杆菌抑制剂、质子泵抑制剂、异前列腺素抑制剂以及其混合物。本发明还提供了包含至少一种母体COX-2抑制剂和至少一种一氧化氮供体的新型组合物，以及可选地，至少一种治疗剂。本发明还提供了用于治疗炎症、疼痛和发热的工具和方法；用于治疗和/或改善COX-2抑制剂的胃肠道特性；用于促进伤口愈合；用于治疗和/或预防肾毒性；以及用于治疗和/或预防由于环氧合酶-2水平升高而导致的其他疾病的工具和方法。
• Method of preventing bone loss
  申请人：Merck & Co., Inc.

  公开号：US05663195A1

  公开（公告）日：1997-09-02

  The invention encompasses a method of inhibiting bone resorption in patients in need of such inhibition to a degree sufficient to halt or retard loss of bone mass, reduce fractures, improve bone repair and prevent or treat osteoporosis comprising: the administration of a non-toxic therapeutically effective amount of a selective cyclooxygenase-2 inhibitor such as the compounds of formula I. ##STR1## The invention also encompasses certain pharmaceutical compositions for the purposes described above.

  本发明包括一种方法，用于抑制需要此类抑制的患者的骨吸收，以达到足够程度以停止或延缓骨量丢失、减少骨折、改善骨修复以及预防或治疗骨质疏松症，该方法包括：给药一种非毒性的、治疗有效的选择性环氧合酶-2抑制剂，如公式I所示的化合物。##STR1## 本发明还涵盖用于上述目的的某些药物组合物。
• Use of carotenoids and/or carotenoid derivatives/analogs for reduction/inhibition of certain negative effects of COX inhibitors
  申请人：Lockwood Samuel F.

  公开号：US20080293679A1

  公开（公告）日：2008-11-27

  Administering carotenoids, and in particular xanthophyll carotenoids, or analogs or derivatives of astaxanthin, lutein, zeaxanthin, lycoxanthin, lycophyll, or lycopene to a subject undergoing treatment with COX-2 inhibitor drugs may reduce at least a portion of the adverse side effects associated with administration of COX-2 selective inhibitor drugs. The carotenoids, or analogs or derivatives thereof may be administered to a subject prior to, at the same time as, or after the commencement of COX-2 selective inhibitor drug therapy. The carotenoids, or analogs or derivatives thereof may be administered to a subject concurrently with COX-2 selective inhibitor drugs therapy. The carotenoids, or analogs or derivatives thereof may be incorporated into pharmaceutical preparation in combination with the COX-2 selective inhibitor drug or may be administered separately. Administration of the analogs or derivatives described herein may reduce peroxidation of LDL and other lipids in the serum and plasma cell membranes of subjects undergoing COX-2 selective inhibitor drug therapy. Administration of the analogs or derivatives described herein may reduce the incidence of deleterious clinical cardiovascular events undergoing COX-2 selective inhibitor drug therapy.

  向正在接受COX-2抑制剂治疗的受试者施用类胡萝卜素，特别是黄质类胡萝卜素，或者是天然类胡萝卜素的类似物或衍生物，如虾青素、叶黄素、玉米黄质、莱科黄素、莱科菲或番茄红素，可能会减少与使用COX-2选择性抑制剂药物相关的不良副作用的至少一部分。这些类胡萝卜素，或者是其类似物或衍生物，可以在受试者开始接受COX-2选择性抑制剂药物治疗之前、同时或之后进行施用。这些类胡萝卜素，或者是其类似物或衍生物，可以与COX-2选择性抑制剂药物治疗同时进行施用。这些类胡萝卜素，或者是其类似物或衍生物，可以与COX-2选择性抑制剂药物组合在一起制成药物制剂，也可以单独施用。施用本文所述的类似物或衍生物可能会减少正在接受COX-2选择性抑制剂药物治疗的受试者血清和血浆细胞膜中低密度脂蛋白和其他脂质的过氧化。施用本文所述的类似物或衍生物可能会减少正在接受COX-2选择性抑制剂药物治疗的受试者发生有害的临床心血管事件的几率。
• Substituted cyclopentenes for the treatment of inflammation
  申请人：G.D. Searle & Co.

  公开号：US05663180A1

  公开（公告）日：1997-09-02

  A class of 1,2-diarylcyclopentenyl compounds is described for use in treating inflammation and inflammation-related disorders. Compounds of particular interest are defined by Formula III: ##STR1## wherein each of R.sup.1 and R.sup.2 is independently selected from alkyl, hydrido, hydroxyalkyl, halo, haloalkyl, alkoxycarbonyl and carboxyl; wherein R.sup.5 is selected from alkylsulfonyl, haloalkylsulfonyl and sulfamyl; and wherein B is phenyl or pyridyl, wherein B is optionally substituted at a substitutable position with alkyl, halo, alkylthio, cyano, haloalkyl, alkoxy, hydroxyalkyl and alkoxyalkyl; or a pharmaceutically-acceptable salt thereof.

  描述了一类1,2-二芳基环戊烯基化合物，用于治疗炎症和与炎症相关的疾病。特别感兴趣的化合物由以下式III定义：其中R.sup.1和R.sup.2中的每一个独立地选自烷基，氢代基，羟基烷基，卤素，卤代烷基，烷氧羰基和羧基；其中R.sup.5选自烷基磺酰基，卤代烷基磺酰基和磺胺基；B选自苯基或吡啶基，其中B在可替换位置可选择性地用烷基，卤素，烷基硫，氰基，卤代烷基，烷氧基，羟基烷基和烷氧基烷基取代；或其药学上可接受的盐。
• Synthesis of¹⁸F-labelled cyclooxygenase-2 (COX-2) inhibitors via Stille reaction with 4-[¹⁸F]fluoroiodobenzene as radiotracers for positron emission tomography (PET)
  作者：Frank R. Wüst、Aileen Höhne、Peter Metz

  DOI：10.1039/b412871k

  日期：——

  The Stille reaction with 4-[(18)F]fluoroiodobenzene as a novel approach for the synthesis of radiotracers for monitoring COX-2 expression by means of PET has been developed. Optimized reaction conditions were elaborated by screening of various catalyst systems and solvents. By using optimized reaction conditions (18)F-labelled COX-2 inhibitors [(18)F]-5 and [(18)F]-13 could be obtained in radiochemical

  已经开发了与4-[（18）F]氟碘苯的Stille反应，作为合成放射性示踪剂以通过PET监测COX-2表达的新方法。通过筛选各种催化剂体系和溶剂，详细阐述了优化的反应条件。通过使用优化的反应条件，可分别以高达94％和68％的放射化学收率获得（18）F标记的COX-2抑制剂[（18）F] -5和[（18）F] -13在4-[（（18）F]氟碘苯上）。