Natural and synthetic geiparvarins are strong and selective MAO-B inhibitors. Synthesis and SAR studies

被引：86

作者：

Carotti, A

Carrieri, A

Chimichi, S

Boccalini, M

Cosimelli, B

Gnerre, C

Carotti, A

Carrupt, PA

Testa, B

机构：

[1] Dipartimento Farmaco Chim, I-70125 Bari, Italy

[2] Dipartimento Chim Organ U Schiff, I-50019 Sesto Fiorentino, Firenze, Italy

[3] Dipartimento Chim Organ A Mangini, I-40127 Bologna, Italy

[4] Univ Lausanne, Inst Chim Therapeut, CH-1015 Lausanne, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 24期

关键词：

D O I：

10.1016/S0960-894X(02)00798-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Natural geiparvarin 1 and a number of its analogues were prepared and tested as inhibitors of both monoamine oxidase isoforms, MAO-B and MAO-A. The desmethyl congener 6 of geiparvarin, proved potent and selective MAO-B inhibitor (PIC50 = 7.55 vs 4.62). X-ray crystallography and molecular modelling studies helped the understanding of the observed structure-activity relationships. (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：3551 / 3555

页数：5

相关论文

共 33 条

[11] SYNTHESIS AND ANTIULCER ACTIVITY OF NOVEL 5-(2-ETHENYL SUBSTITUTED)-3(2H)-FURANONES [J].

FELMAN, SW ;

JIRKOVSKY, I ;

MEMOLI, KA ;

BORELLA, L ;

WELLS, C ;

RUSSELL, J ;

WARD, J .

JOURNAL OF MEDICINAL CHEMISTRY, 1992, 35 (07) :1183-1190

[12] Inhibition of monoamine oxidases by functionalized coumarin derivatives: Biological activities, QSARs, and 3D-QSARs [J].

Gnerre, C ;

Catto, M ;

Leonetti, F ;

Weber, P ;

Carrupt, PA ;

Altomare, C ;

Carotti, A ;

Testa, B .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (25) :4747-4758

[13] TISSUE DISTRIBUTION OF HUMAN MONOAMINE OXIDASE-A AND OXIDASE-B MESSENGER-RNA [J].

GRIMSBY, J ;

LAN, NC ;

NEVE, R ;

CHEN, K ;

SHIH, JC .

JOURNAL OF NEUROCHEMISTRY, 1990, 55 (04) :1166-1169

[14] BIOCHEMISTRY AND PHARMACOLOGY OF MOCLOBEMIDE, A PROTOTYPE RIMA [J].

HAEFELY, W ;

BURKARD, WP ;

CESURA, AM ;

KETTLER, R ;

LOREZ, HP ;

MARTIN, JR ;

RICHARDS, JG ;

SCHERSCHLICHT, R ;

DUPRADA, M .

PSYCHOPHARMACOLOGY, 1992, 106 :S6-S14

[15] Pharmacological and biochemical actions of simple coumarins: Natural products with therapeutic potential [J].

Hoult, JRS ;

Paya, M .

GENERAL PHARMACOLOGY-THE VASCULAR SYSTEM, 1996, 27 (04) :713-722

[16] SYNTHESIS AND CONFIGURATIONAL ASSIGNMENT OF GEIPARVARIN - A NOVEL ANTI-TUMOR AGENT [J].

JERRIS, PJ ;

SMITH, AB .

JOURNAL OF ORGANIC CHEMISTRY, 1981, 46 (03) :577-585

[17]

Kennedy RO, 1997, COUMARINS BIOL APPL

[18] INHIBITION OF MONOAMINE OXIDASE-B BY 5H-INDENO[1,2-C]PYRIDAZINES - BIOLOGICAL-ACTIVITIES, QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS (QSARS) AND 3D-QSARS [J].

KNEUBUHLER, S ;

THULL, U ;

ALTOMARE, C ;

CARTA, V ;

GAILLARD, P ;

CARRUPT, PA ;

CAROTTI, A ;

TESTA, B .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (19) :3874-3883

[19]

MAHER PA, 2000, OXIDAT STRESS DIS, V5, P177

[20] GEIPARVARIN ANALOGS .4. SYNTHESIS AND CYTOSTATIC ACTIVITY OF GEIPARVARIN ANALOGS BEARING A CARBAMATE MOIETY OR A FUROCOUMARIN FRAGMENT ON THE ALKENYL SIDE-CHAIN [J].

MANFREDINI, S ;

BARALDI, PG ;

BAZZANINI, R ;

GUARNERI, M ;

SIMONI, D ;

BALZARINI, J ;

DECLERCQ, E .

JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (15) :2401-2405

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