1,5-Diaryl-2-ethyl pyrrole derivatives as antimycobacterial agents: Design, synthesis, and microbiological evaluation

被引：70

作者：

Biava, Mariangela ^{[1
]}

Porretta, Giulio C. ^{[1
]}

Poce, Giovanna ^{[1
]}

De Logu, Alessandro ^{[2
]}

Meleddu, Rita ^{[2
]}

De Rossi, Edda ^{[3
]}

Manetti, Fabrizio ^{[4
]}

Botta, Maurizio ^{[4
]}

机构：

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

[2] Dipartimento Sci & Tecnol Biomed, Sez Microbiol Med, I-09123 Cagliari, Italy

[3] Univ Pavia, Dipartimento Genet & Microbiol, I-27100 Pavia, Italy

[4] Univ Siena, Dipartimento Farmaco Chim Tecnol, I-53100 Siena, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 11期

关键词：

BM; 212; 1,5-Diarylpyrroles; Mycobacterium tuberculosis; Pharmacophoric model; Antitubercular agents; MULTIDRUG-RESISTANT TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; ANTITUBERCULOSIS DRUGS; COINFECTION; UPDATE; HIV; TB;

D O I：

10.1016/j.ejmech.2009.06.005

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

During the search of novel antitubercular drugs related to BM 212, new diarylpyrroles were designed and synthesized on the basis of a structure-activity relationship analysis of many pyrroles previously described by us. Among them, 1-(4-fluorophenyl)-2-ethyl-3-(thiomorpholin-4-yl)methyl-5-(4-methylphenyl)-1H-pyrrole (2b) proved to be particularly active, with a minimum inhibitory concentration (MIC, expressed as mu g/mL) and a protection index (PI) better than or comparable to those of reference compounds. Also the remaining compounds were very active, although their MIC and PI were in general lower than those of their parent 2-methyl analogues. (C) 2009 Elsevier Masson SAS. All rights reserved.

引用

页码：4734 / 4738

页数：5

共 31 条

[1] *ACC INC, 2004, CERIUS2 VERS 4 8 1
[2] [Anonymous], 2006, MMWR Morbidity Weekly, V55, P1176
[3] New small-molecule synthetic antimycobacterials
Ballell, L
Field, RA
Duncan, K
Young, RJ
[J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (06) : 2153 - 2163
[4] Biava M., 2006, Infectious Disorders - Drug Targets, V6, P159, DOI 10.2174/187152606784112173
[5] Antimycobacterial compounds. Optimization of the BM 212 structure, the lead compound for a new pyrrole derivative class
Biava, M
Porretta, GC
Poce, G
Deidda, D
Pompel, R
Tafi, A
Manetti, F
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (04) : 1221 - 1230
[6] Importance of the thiomorpholine introduction in new pyrrole derivatives as antimycobacterial agents analogues of BM 212
Biava, M
Porretta, GC
Deidda, D
Pompei, R
Tafi, A
Manetti, F
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (04) : 515 - 520
[7] BIAVA M, Patent No. 2006092822
[8] 1,5-Diphenylpyrrole derivatives as antimycobacterial agents. Probing the influence on antimycobacterial activity of lipophilic substituents at the phenyl rings
Biava, Mariangela
Porretta, Giulio Cesare
Poce, Giovanna
De Logu, Alessandro
Saddi, Manuela
Meleddu, Rita
Manetti, Fabrizio
De Rossi, Edda
Botto, Maurizio
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (12) : 3644 - 3648
[9] Antimycobacterial agents. Novel diarylpyrrole derivatives of BM212 endowed with high activity toward mycobacterium tuberculosis and low cytotoxicity
Biava, Mariangela
Cesare Porretta, Giulio
Poce, Giovanna
Supino, Sibilla
Deidda, Delia
Pompei, Raffaello
Molicotti, Paola
Manetti, Fabrizio
Botta, Maurizio
[J]. JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (16) : 4946 - 4952
[10] Tuberculosis and HIV co-infection - A practical therapeutic approach
Breen, Ronan A. M.
Swaden, Leonie
Ballinger, Jayne
Lipman, Marc C. I.
[J]. DRUGS, 2006, 66 (18) : 2299 - 2308

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