Synthesis, in vitro, and in vivo biological evaluation and molecular docking simulations of chiral alcohol and ether derivatives of the 1,5-diarylpyrrole scaffold as novel anti-inflammatory and analgesic agents

被引：21

作者：

Biava, Mariangela ^{[1
]}

Porretta, Giulio C. ^{[1
]}

Poce, Giovanna ^{[1
]}

Supino, Sibilla ^{[1
]}

Manetti, Fabrizio ^{[2
]}

Forli, Stefano ^{[2
]}

Botta, Maurizio ^{[2
]}

Sautebin, Lidia ^{[4
]}

Rossi, Antonietta ^{[4
,5
]}

Pergola, Carlo ^{[4
]}

Ghelardini, Carla ^{[6
]}

Norcini, Monica ^{[6
]}

Makovec, Francesco ^{[7
]}

Giordani, Antonio ^{[7
]}

Anzellotti, Paola ^{[8
,9
,10
]}

Cirilli, Roberto ^{[11
]}

Ferretti, Rosella ^{[11
]}

Gallinella, Bruno ^{[11
]}

La Torre, Francesco ^{[11
]}

Anzini, Maurizio ^{[2
,3
]}

Patrignani, Paola ^{[8
,9
,10
]}

机构：

[1] Univ Roma La Sapienza, Dipartimento Studi Chim & Tecnol Farm, I-00185 Rome, Italy

[2] Univ Siena, Dipartimento Farm Chim Tecnol, I-53100 Siena, Italy

[3] European Res Ctr Drug Discovery & Dev, I-53100 Siena, Italy

[4] Univ Naples Federico 2, Dipartimento Farmacol Sperimentale, I-80131 Naples, Italy

[5] IRCCS Ctr Neurolesi Bonino Pulejo, I-98124 Messina, Italy

[6] Univ Florence, Dipartimento Farmacol, I-50139 Florence, Italy

[7] Rottapharm SpA, I-20052 Monza, Italy

[8] Univ G DAnnunzio, Dept Med, I-66013 Chieti, Italy

[9] Univ G DAnnunzio, Ctr Excellence Aging, I-66013 Chieti, Italy

[10] CeSI, I-66013 Chieti, Italy

[11] Ist Super Sanita, Dipartimento Farm, I-00161 Rome, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 17期

关键词：

anti-inflammatory; NSAIDs; analgesic agents; COX-1; inhibitors; COX-2; coxibs; celecoxib;

D O I：

10.1016/j.bmc.2008.07.058

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Following our previous research on anti-inflammatory drugs (NSAIDs), we report here the synthesis of chiral 1,5-diarylpyrroles derivatives that were characterized for their in vitro inhibitory effects toward cyclooxygenase (COX) isozymes. Analysis of enzymatic affinity and COX-2 selectivity led us to the selection of one compound (+/-)-10b that was further tested in vitro in the human whole blood (HWB) and in vivo for its anti-inflammatory activity in mice. The affinity data have been rationalized through docking simulations. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：8072 / 8081

页数：10

共 36 条

[1]

1,5-diarylpyrrole-3-acetic acids and esters as novel classes of potent and highly selective cyclooxygenase-2 inhibitors [J].

Biava, M ;

Porretta, GC ;

Cappelli, A ;

Vomero, S ;

Manetti, F ;

Botta, M ;

Sautebin, L ;

Rossi, A ;

Makovec, F ;

Anzini, M .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (09) :3428-3432

[2]

HPLC enantioseparation and absolute configuration of novel anti-inflammatory pyrrole derivatives [J].

Biava, Mariangela ;

Cirilli, Roberto ;

Fares, Vincenzo ;

Ferretti, Rosella ;

Gallinella, Bruno ;

La Torre, Francesco ;

Poce, Giovanna ;

Porretta, Giulio Cesare ;

Supino, Sibilla ;

Villani, Claudio .

CHIRALITY, 2008, 20 (06) :775-780

[3]

Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity [J].

Biava, Mariangela ;

Porretta, Giulio Cesare ;

Poce, Giovanna ;

Supino, Sibilla ;

Forli, Stefano ;

Rovini, Michele ;

Cappelli, Andrea ;

Manetti, Fabrizio ;

Botta, Maurizio ;

Sautebin, Lidia ;

Rossi, Antonietta ;

Pergola, Carlo ;

Ghelardini, Carla ;

Vivoli, Elisa ;

Makovec, Francesco ;

Anzellotti, Paola ;

Patrignani, Paola ;

Anzini, Maurizio .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (22) :5403-5411

[4]

Burke A., 2005, PHARM BASIS THERAPEU, Veleventh, P671

[5]

Human pharmacology of naproxen sodium [J].

Capone, Marta L. ;

Tacconelli, Stefania ;

Sciulli, Maria G. ;

Anzellotti, Paola ;

Di Francesco, Luigia ;

Merciaro, Gabriele ;

Di Gregorio, Patrizia ;

Patrignani, Paola .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2007, 322 (02) :453-460

[6]

Pharmacodynamic of cyclooxygenase inhibitors in humans [J].

Capone, Marta L. ;

Tacconelli, Stefania ;

Di Francesco, Luigia ;

Sacchetti, Andrea ;

Sciulli, Maria G. ;

Patrignani, Paola .

PROSTAGLANDINS & OTHER LIPID MEDIATORS, 2007, 82 (1-4) :85-94

[7]

Clinical pharmacology of platelet, monocyte, and vascular cyclooxygenase inhibition by naproxen and low-dose aspirin in healthy subjects [J].

Capone, ML ;

Tacconelli, S ;

Sciulli, MG ;

Grana, M ;

Ricciotti, E ;

Minuz, P ;

Di Gregorio, P ;

Merciaro, G ;

Patrono, C ;

Patrignani, P .

CIRCULATION, 2004, 109 (12) :1468-1471

[8]

DING C, 2002, DRUGS, V5, P1168

[9]

ANTIINFLAMMATORY, ANALGESIC, ANTIPYRETIC AND RELATED PROPERTIES OF MELOXICAM, A NEW NONSTEROIDAL ANTIINFLAMMATORY AGENT WITH FAVORABLE GASTROINTESTINAL TOLERANCE [J].

ENGELHARDT, G ;

HOMMA, D ;

SCHLEGEL, K ;

UTZMANN, R ;

SCHNITZLER, C .

INFLAMMATION RESEARCH, 1995, 44 (10) :423-433

[10]

FERDINANDI ES, 1982, J PHARMACOL EXP THER, V220, P417

← 1 2 3 4 →