3-(nitrooxy)-propyl-[2-[1-phenyl-2-methyl-5-(4-methylsulphonylphenyl)-1H-pyrrol-3-yl]]acetate | 1346223-10-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-(nitrooxy)-propyl-[2-[1-phenyl-2-methyl-5-(4-methylsulphonylphenyl)-1H-pyrrol-3-yl]]acetate
• 英文别名: 3-nitroxypropyl 2-[1-phenyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrrol-3-yl]acetate；3-(nitrooxy)-propyl [2-(1-phenyl-2-methyl-5-(4-methylsulphonylphenyl)-1H-pyrrol-3-yl)]acetate；3-Nitrooxypropyl 2-[2-methyl-5-(4-methylsulfonylphenyl)-1-phenylpyrrol-3-yl]acetate
• CAS: 1346223-10-6
• 化学式: C₂₃H₂₄N₂O₇S
• 分子量: 472.519
• InChiKey: LEGMEBPCGVLLHN-UHFFFAOYSA-N

物化性质

• 熔点：
  116-118 °C
• 沸点：
  661.9±55.0 °C(predicted)
• 密度：
  1.30±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  129
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-methyl-5-(4-(methylsulfonyl)phenyl)-1-phenyl-1H-pyrrole 在 三乙基硅烷 、 4-二甲氨基吡啶 、 水 、 四氯化钛 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 3-(nitrooxy)-propyl-[2-[1-phenyl-2-methyl-5-(4-methylsulphonylphenyl)-1H-pyrrol-3-yl]]acetate
  参考文献：
  名称：

  Novel Analgesic/Anti-Inflammatory Agents: Diarylpyrrole Acetic Esters Endowed with Nitric Oxide Releasing Properties

  摘要：

  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.

  DOI：

  10.1021/jm200715n

文献信息

• 1,5-Diaryl-2-alkylpyrrole-3-Substituted Nitro Esters, Selective COX-2 Inhibitors and Nitric Oxide Donors
  申请人：Giordani Antonio

  公开号：US20130165494A1

  公开（公告）日：2013-06-27

  1,5-diaryl-2-alkylpyrrole-3-substituted nitro esters, of Formula (I) are provided. Such compounds are potent and selective COX-2 inhibitors which are able to release NO in concentrations that make it possible to counteract the side effects due to selective COX-2 inhibition, without giving rise to hypotensive effects. Formula (I) includes compounds wherein the groups R′ and R″ are: —H, —F, —Cl, —Br, —CH 3 , —CF 3 , —OCH 3 , —SCH 3 , R1 is methyl, ethyl, trifluoromethyl, hydroxymethyl, methoxymethyl and the substituent in position −3 of the pyrrole ring is a chain, where the groups X, Y, Z, W and R2 are: X is a carbonyl or a group —(CHR 3 )—, Y is an oxygen atom or the group —NR 3 — and Z is a carbonyl or a group —(CHR 3 )—, or a [—CH(COOH)—] group, or a group —(NR 3 )—, W is an aliphatic chain substituted with one or two (—O—NO 2 ) groups, R2 is: —H, —OH, —OCH 3 , or —NHR 3 . R 3 is: —H, —CH 3 , —CH 2 CH 3 , [—CH 2 (CH 3 ) 2 ]. R′″ is methylsulphonyl or sulphonamido. Pharmaceutical formulations and methods of making an using such formulations are also provided.

  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。
• US9162979B2
  申请人：——

  公开号：US9162979B2

  公开（公告）日：2015-10-20
• 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.