N-[2-(nitrooxy)ethyl]-2-[1-(4-fluorophenyl)-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrrol-3-yl]acetamide | 1363374-26-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: N-[2-(nitrooxy)ethyl]-2-[1-(4-fluorophenyl)-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrrol-3-yl]acetamide
• 英文别名: N-[(2-nitroxy)ethyl]-2-[1-(4-fluorophenyl)-2-methyl-5-(4-methylsulphonylphenyl)-1H-pyrrol-3-yl]acetamide；N-[(2-nitrooxy)ethyl]-2-[1-(4-fluorophenyl)-2-methyl-5-(4-methylsulphonylphenyl)-1H-pyrrol-3-yl]acetamide；2-[[2-[1-(4-Fluorophenyl)-2-methyl-5-(4-methylsulfonylphenyl)pyrrol-3-yl]acetyl]amino]ethyl nitrate
• CAS: 1363374-26-8
• 化学式: C₂₂H₂₂FN₃O₆S
• 分子量: 475.498
• InChiKey: IVQJGLCSKNJIAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  132
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-[1-(4-fluorophenyl)-2-methyl-5-(4-methylsulphonylphenyl)-1H-pyrrol-3-yl]acetic acid 、 2-nitroxyethylammonium nitrate 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 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以81%的产率得到N-[2-(nitrooxy)ethyl]-2-[1-(4-fluorophenyl)-2-methyl-5-[4-(methylsulfonyl)phenyl]-1H-pyrrol-3-yl]acetamide
  参考文献：
  名称：

  Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors

  摘要：

  We report herein the development, synthesis, physicochemical and pharmacological characterization of a novel class of pharmacodynamic hybrids that selectively inhibit cyclooxygenase-2 (COX-2) isoform and present suitable nitric oxide releasing properties. The replacement of the ester moiety with the amide group gave access to in vivo more stable and active derivatives that highlighted outstanding pharmacological properties. In particular, the glycine derivative proved to be extremely active in suppressing hyperalgesia and edema. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.008

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。
• 1,5-DIARYL-2-ALKYLPYRROLE-3-SUBSTITUTED NITRO ESTERS, SELECTIVE COX-2 INHIBITORS AND NITRIC OXIDE DONORS
  申请人：Rottapharm Biotech S.r.l.

  公开号：EP2614050B1

  公开（公告）日：2016-01-20
• US9162979B2
  申请人：——

  公开号：US9162979B2

  公开（公告）日：2015-10-20
• Enhancing the pharmacodynamic profile of a class of selective COX-2 inhibiting nitric oxide donors
  作者：Mariangela Biava、Claudio Battilocchio、Giovanna Poce、Salvatore Alfonso、Sara Consalvi、Angela Di Capua、Vincenzo Calderone、Alma Martelli、Lara Testai、Lidia Sautebin、Antonietta Rossi、Carla Ghelardini、Lorenzo Di Cesare Mannelli、Antonio Giordani、Stefano Persiani、Milena Colovic、Melania Dovizio、Paola Patrignani、Maurizio Anzini

  DOI：10.1016/j.bmc.2013.12.008

  日期：2014.1

  We report herein the development, synthesis, physicochemical and pharmacological characterization of a novel class of pharmacodynamic hybrids that selectively inhibit cyclooxygenase-2 (COX-2) isoform and present suitable nitric oxide releasing properties. The replacement of the ester moiety with the amide group gave access to in vivo more stable and active derivatives that highlighted outstanding pharmacological properties. In particular, the glycine derivative proved to be extremely active in suppressing hyperalgesia and edema. (C) 2013 Elsevier Ltd. All rights reserved.