2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1H-pyrrol-3-acetic acid | 853055-09-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1H-pyrrol-3-acetic acid
• 英文别名: 2-[1-phenyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrrol-3-yl]acetic acid；[2-methyl-5-(4-methylsulphonyl)phenyl-1-phenyl-1H-pyrrol-3-yl]acetic acid；[5-(4-Methanesulfonyl-phenyl)-2-methyl-1-phenyl-1H-pyrrol-3-yl]-acetic acid；2-[2-methyl-5-(4-methylsulfonylphenyl)-1-phenylpyrrol-3-yl]acetic acid
• CAS: 853055-09-1
• 化学式: C₂₀H₁₉NO₄S
• 分子量: 369.441
• InChiKey: WJRHOGLBMOCHHB-UHFFFAOYSA-N

物化性质

• 熔点：
  156-158 °C
• 沸点：
  609.0±55.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  84.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1H-pyrrol-3-acetic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 2-(methylsulphonyloxy)ethyl-2-[1-phenyl-2-methyl-5-(4-methylsulphonylphenyl)-1H-pyrrol-3-yl]acetate
  参考文献：
  名称：

  1,5-Diaryl-2-alkylpyrrole-3-Substituted Nitro Esters, Selective COX-2 Inhibitors and Nitric Oxide Donors

  摘要：

  提供的是1,5-二芳基-2-烷基吡咯-3-取代硝基酯，其分子式为(I)。这类化合物是强效且选择性的COX-2抑制剂，能够以在浓度上足以抵消由于选择性COX-2抑制引起的副作用的NO释放，而不会引起低血压效应。公式(I)包括的化合物中，基团R'和R"为：—H，—F，—Cl，—Br，—CH3，—CF3，—OCH3，—SCH3，R1为甲基，乙基，三氟甲基，羟甲基，甲氧甲基，且吡咯环上-3位的取代基为链状，其中X、Y、Z、W和R2分别为：X为羰基或—(CHR3)—基团，Y为氧原子或—NR3—基团，Z为羰基或—(CHR3)—基团，或[—CH(COOH)—]基团，或—(NR3)—基团，W为用一或两个(—O—NO2)基团取代的脂肪链，R2为：—H，—OH，—OCH3，或—NHR3。R3为：—H，—CH3，—CH2CH3，[—CH2(CH3)2]。R′″为甲基磺酰基或磺酰胺基。还提供了用于制备和使用此类化合物的药物配方和方法。

  公开号：

  US20130165494A1
• 作为产物：
  描述：

  2-methyl-5-(4-(methylsulfonyl)phenyl)-1-phenyl-1H-pyrrole 在 吡啶 、 三乙基硅烷 、 氢氧化钾 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 2-methyl-5-[4-(methylsulfonyl)phenyl]-1-phenyl-1H-pyrrol-3-acetic acid
  参考文献：
  名称：

  1,5-Diarylpyrrole-3-acetic Acids and Esters as Novel Classes of Potent and Highly Selective Cyclooxygenase-2 Inhibitors

  摘要：

  A small set of substituted 1,5-diarylpyrrole-3-acetic and -glyoxylic acid derivatives have been synthesized, and their cyclooxygenase (COX-1 and COX-2) inhibiting properties have been evaluated. Some compounds proved to be highly selective COX-2 inhibitors, and their affinity data have been rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-2 binding site.

  DOI：

  10.1021/jm049121q

文献信息

• Novel Ester and Acid Derivatives of the 1,5-Diarylpyrrole Scaffold as Anti-Inflammatory and Analgesic Agents. Synthesis and in Vitro and in Vivo Biological Evaluation
  作者：Mariangela Biava、Giulio C. Porretta、Giovanna Poce、Claudio Battilocchio、Fabrizio Manetti、Maurizio Botta、Stefano Forli、Lidia Sautebin、Antonietta Rossi、Carlo Pergola、Carla Ghelardini、Nicoletta Galeotti、Francesco Makovec、Antonio Giordani、Paola Anzellotti、Paola Patrignani、Maurizio Anzini

  DOI：10.1021/jm901269y

  日期：2010.1.28

  (COX-2) inhibitors (coxibs) was developed to circumvent the major side effects of cyclooxygenase-1 (COX-1) and COX-2 inhibitors (stomach ulceration and nephrotoxicity). As a consequence, coxibs are extremely valuable in treating acute and chronic inflammatory conditions. However, the use of coxibs, such as rofecoxib (Vioxx), was discontinued because of the high risk of cardiovascular adverse events. More

  开发了新一代的选择性环氧合酶2（COX-2）抑制剂（coxibs），以规避环氧合酶1（COX-1）和COX-2抑制剂的主要副作用（胃溃疡和肾毒性）。结果，考昔布在治疗急性和慢性炎性疾病中非常有价值。但是，由于心血管不良事件的高风险，已停止使用罗非昔布（Vioxx）等考昔布。最近的临床发现强调了通过适当的COX-1与COX-2选择性可以如何缓解Coxib的心血管毒性。我们先前报道了一组对COX-2有选择性的取代的1,5-二芳基吡咯衍生物。在这里，我们描述了新的1,5-二芳基吡咯的合成及其在体外，离体的抑制作用，以及体内对COX同工酶及其止痛活性的研究。异丙基-2-甲基-5- [4-（甲基磺酰基）苯基] -1-苯基-1选择该系列的代表成员H-吡咯-3-乙酸酯（10a）进行药代动力学和代谢研究。
• 3-SUBSTITUTED-1,5-DIARLY-2-ALKYL-PYRROLES HIGHLY SELECTIVE AND ORALLY EFFECTIVE COX-2 INHIBITORS
  申请人：Cappelli Andrea

  公开号：US20090264500A1

  公开（公告）日：2009-10-22

  This invention relates to 3-substituted-1,5-diaryl-2-alkyl-pyrroles of Formula I, pharmaceutical compositions containing them, and to their use for the pharmacological treatment of pain and COX-2 over-activation associated disorders. Compounds of this invention are new pyrrole derivatives bearing in position-3 of the pyrrole ring, several variously functionalized, not aliphatic, side chains which confer to the compounds a relevant COX-2 potency and selectivity along with a remarkable oral efficacy. Phenyl rings in position-1 and -5 are variously substituted, but compounds of particular interest are those substituted in position-5 with 4-methylsulphonyl-phenyl or with 4-aminosulphonyl-phenyl groups.

  本发明涉及式I的3-取代-1,5-二芳基-2-烷基-吡咯衍生物，包含它们的药物组合物，以及它们用于治疗与疼痛和COX-2过度激活相关的疾病的药理学治疗。本发明的化合物是新的吡咯衍生物，在吡咯环的3位上带有几个不同官能团化的非脂肪侧链，这些侧链赋予化合物显著的COX-2效力和选择性以及卓越的口服效力。在1位和5位的苯环上有不同的取代基，但特别感兴趣的化合物是在5位上用4-甲基磺酰基苯基或4-氨基磺酰基苯基基团取代的化合物。
• [EN] 1,5-DIARYL-2-ALKYLPYRROLE-3-SUBSTITUTED NITRO ESTERS, SELECTIVE COX-2 INHIBITORS AND NITRIC OXIDE DONORS<br/>[FR] NITROESTERS DE L,5-DIARYL-2-ALKYLPYRROLE 3-SUBSTITUÉS, INHIBITEURS SÉLECTIFS DE COX-2 ET DONNEURS D'OXYDE NITRIQUE
  申请人：ROTTAPHARM SPA

  公开号：WO2012032479A8

  公开（公告）日：2012-07-12
• Novel Analgesic/Anti-Inflammatory Agents: Diarylpyrrole Acetic Esters Endowed with Nitric Oxide Releasing Properties
  作者：Mariangela Biava、Giulio Cesare Porretta、Giovanna Poce、Claudio Battilocchio、Salvatore Alfonso、Michele Rovini、Salvatore Valenti、Gianluca Giorgi、Vincenzo Calderone、Alma Martelli、Lara Testai、Lidia Sautebin、Antonietta Rossi、Giuseppina Papa、Carla Ghelardini、Lorenzo Di Cesare Mannelli、Antonio Giordani、Paola Anzellotti、Annalisa Bruno、Paola Patrignani、Maurizio Anzini

  DOI：10.1021/jm200715n

  日期：2011.11.24

  The design of compounds that are able to inhibit cyclooxygenase (COX) and to release nitric oxide (NO) should give rise to drugs endowed with an overall safer profile for the gastrointestinal and cardiovascular systems. Herein we report a new class of pyrrole-derived nitrooxy esters (11a-j), cyclooxygenase-2 (COX-2) selective inhibitors endowed with NO releasing properties, with the goal of generating new molecules able to both strongly inhibit this isoform and reduce the related adverse side effects. Taking into account the metabolic conversion of nitrooxy esters into corresponding alcohols, we also studied derivatives 12a-j. All compounds proved to be very potent and selective COX-2 inhibitors; nitrooxy derivatives displayed interesting ex vivo NO-dependent vasorelaxing properties. Compounds 11c, 11d, 12c, and 12d were selected for further in vivo studies that highlited good anti-inflammatory and antinociceptive activities. Finally, two selected compounds (11c and 12c) tested in human whole blood (HWB) assay proved to be preferential inhibitors of COX-2.
• WO2008/14821
  申请人：——

  公开号：——

  公开（公告）日：——