Synthesis and biochemical evaluation of (R)-5-acyloxymethyl- and (S)-5-acylaminomethyl-3-(1H-pyrrol-1-yl)-2-oxazolidinones as new anti-monoamine oxidase (anti-MAO) agents

被引：6
|
作者：
Mai, A
Artico, M [1 ]
Valente, S
Cerbara, I
Befani, O
Turini, P
Dalla Vedova, L
Agostinelli, E
机构：
[1] Univ Roma La Sapienza, Dipartimento Studi Farmaceut, Ple A Moro 5, I-00185 Rome, Italy
[2] Univ Roma La Sapienza, Dipartimento Sci Biochim A Rossi Fanelli, I-00185 Rome, Italy
[3] Univ Roma La Sapienza, CNR, Ctr Biol Mol, I-00185 Rome, Italy
来源：
ARKIVOC | 2004年
关键词：
MAO-A; MAO inhibitors (MAOIs); 2-oxazolidinones; 3-(H-1-pyrrol-1-yl)-2-oxazolidinones; antidepressant agents;
D O I：
10.3998/ark.5550190.0005.504
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
(R)-5-Acyloxymethyl- and (S)-5-acylaminomethyl-3-(1H-pyrrol-1-yl)-2-oxazolidinones 2a-s were synthesized as pyrrole analogues of toloxatone (Humoryl(R)), an anti-MAO agent used in clinical therapy because of its antidepressant properties. Their ability to inhibit the enzymatic isoforms MAO-A and MAO-B was evaluated. From the data most 2a-s showed high reversibility and selective MAO-A inhibitory activity. They exhibited an inhibitory potency (KiMAO-A) of 0.16-0.90 muM comparable to that found for toloxatone (KiMAO-A = 0.38 muM), the A isoform being 11-fold more selective. The results indicate that 2a-s show promise as new antidepressant agents.
引用
收藏
页码：32 / 43
页数：12
相关论文
共 50 条
  • [1] 3-(1H-pyrrol-1-yl)-2-oxazolidinones as reversible, highly potent, and selective inhibitors of monoamine oxidase type A
    Mai, A
    Artico, M
    Esposito, M
    Sbardella, G
    Massa, S
    Befani, O
    Turini, P
    Giovannini, V
    Mondovì, B
    JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (06) : 1180 - 1183
  • [2] Synthesis and biological evaluation of new N-alkyl 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides as cannabinoid receptor ligands
    Silvestri, Romano
    Ligresti, Alessia
    La Regina, Giuseppe
    Piscitelli, Francesco
    Gatti, Valerio
    Lavecchia, Antonio
    Brizzi, Antonella
    Pasquini, Serena
    Allara, Marco
    Fantini, Noemi
    Carai, Mauro Antonio Maria
    Bigogno, Chiara
    Rozio, Marco Giulio
    Sinisi, Roberta
    Novellino, Ettore
    Colombo, Giancarlo
    Di Marzo, Vincenzo
    Dondio, Giulio
    Corelli, Federico
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2010, 45 (12) : 5878 - 5886
  • [3] Design, Synthesis and Evaluation of Some Novel 1-phenyl-3-(5-phenyl-1H-imidazol-1-yl) Thiourea Derivatives as Anti-HIV Agents
    Singh, Rohit
    Ganguly, Swastika
    INDIAN JOURNAL OF PHARMACEUTICAL EDUCATION AND RESEARCH, 2018, 52 (04) : 655 - 665
  • [4] Synthesis of new 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives as anti-MRSA and anti-H. pylori agents
    Tabei, Arash
    Ejtemaei, Ramona
    Mahboubi, Arash
    Saniee, Parastoo
    Foroumadi, Alireza
    Dehdari, Alireza
    Almasirad, Ali
    BMC CHEMISTRY, 2022, 16 (01)
  • [5] Synthesis of new 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives as anti-MRSA and anti-H. pylori agents
    Arash Tabei
    Ramona Ejtemaei
    Arash Mahboubi
    Parastoo Saniee
    Alireza Foroumadi
    Alireza Dehdari
    Ali Almasirad
    BMC Chemistry, 16
  • [6] Synthesis, cannabinoid receptor affinity, molecular modeling studies and in vivo pharmacological evaluation of new substituted 1-aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamides. 2. Effect of the 3-carboxamide substituent on the affinity and selectivity profile
    Silvestri, Romano
    Ligresti, Alessia
    La Regina, Giuseppe
    Piscitelli, Francesco
    Gatti, Valerio
    Brizzi, Antonella
    Pasquini, Serena
    Lavecchia, Antonio
    Allara, Marco
    Fantini, Noemi
    Carai, Mauro Antonio Maria
    Novellino, Ettore
    Colombo, Giancarlo
    Di Marzo, Vincenzo
    Corelli, Federico
    BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (15) : 5549 - 5564
  • [7] Design, synthesis, and biological evaluation of N-[1-(6′-chloropyridazin-3′-yl)-3-(4"-substitutedphenyl)-1H-pyrazole-5-yl]alkanamides as anti-inflammatory agents
    Aggarwal, Ranjana
    Swati
    Kumar, Vinod
    Singh, Randhir
    Kajal, Anu
    Saini, Deepika
    DRUG DEVELOPMENT RESEARCH, 2022, 83 (03) : 811 - 822
  • [8] Synthesis and Biological Evaluation of Substituted N-[3-(1HPyrrol-1-yl)methyl]-1,2,5,6-tetrahydropyridin-1-yl]benzamide/benzene Sulfonamides as Anti-Inflammatory Agents
    Gangapuram, Madhavi
    Mazzio, Elizabeth
    Eyunni, Suresh
    Soliman, Karam F. A.
    Redda, Kinfe K.
    ARCHIV DER PHARMAZIE, 2014, 347 (05) : 360 - 369
  • [9] Synthesis and biological screening of 5-(alkyl(1H-indol-3-yl))-2-(substituted)-1,3,4-oxadiazoles as antiproliferative and anti-inflammatory agents
    Rapolu, Sreevani
    Alla, Manjula
    Bommena, Vittal Rao
    Murthy, Ramalinga
    Jain, Nishant
    Bommareddy, Venkata Ramya
    Bommineni, Madhava Reddy
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 66 : 91 - 100
  • [10] Synthesis and Analgesic and Anti-inflammatory Activity of 4-(2-Aryl-3-aroyl-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrol-1-yl)benzoic Acids
    V. L. Gein
    D. V. Chalkov
    A. V. Romanova
    O. V. Bobrovskaya
    S. V. Chashchina
    M. V. Dmitriev
    Russian Journal of Organic Chemistry, 2025, 61 (1) : 16 - 25
12345