Design, synthesis, and biological activities of pyrrolylethanoneamine derivatives, a novel class of monoamine oxidases inhibitors

被引：26

作者：

Di Santo, R

Costi, R

Roux, A

Artico, M

Befani, O

Meninno, T

Agostinelli, E

Palmegiani, P

Turini, P

Cirilli, R

Ferretti, R

Gallinella, B

La Torre, F

机构：

[1] Univ Roma La Sapienza, Dipartimento Studi Farmaceut, Ist Pasteur, Fdn Cenci Bolognetti, I-00185 Rome, Italy

[2] Univ Roma La Sapienza, Dipartimento Sci Biochim, I-00185 Rome, Italy

[3] Univ Roma La Sapienza, CNR, Ist Biol & Patol Mol, I-00185 Rome, Italy

[4] Ist Super Sanita, Dipartimento Farmaco, I-00161 Rome, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 13期

关键词：

D O I：

10.1021/jm050172c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pyrrolylethanoneamines 1-12,18-23 and related amino alcohols 13-15, 24-27 were synthesized and tested against monoamine oxidases A and B (MAO-A and MAO-B) enzymes. In general, aminoketones 1-12, 18-23 were found to be potent and selective MAO-A inhibitors. In particular, 18 was more potent and selective against the MAO-A isoenzyme than reference drugs. Interestingly, amino alcohol 25 selectively inhibited MAO-B enzyme and could be a lead compound for designing more potent and selective MAO-B inhibitors.

引用

页码：4220 / 4223

页数：4

共 28 条

[1] REACTIONS OF TRIETHYL PHOSPHITE WITH 2-HALOACETYL-FURAN, 2-HALOACETYL-THIOPHENE, 2-HALOACETYL-PYRROLE AND 2-HALOACETYL-N-METHYLPYRROLE [J].

ARCORIA, A ;

FISICHELLA, S ;

MACCARONE, E ;

SCARLATA, G .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1975, 12 (01) :215-218

[2]

Basford R. E., 1967, METHOD ENZYMOL, V10, P96

[3] Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders [J].

Binda, C ;

Newton-Vinson, P ;

Hubálek, F ;

Edmondson, DE ;

Mattevi, A .

NATURE STRUCTURAL BIOLOGY, 2002, 9 (01) :22-26

[4] STUDIES IN STEROECHEMISTRY .32. MODELS FOR 1,2-ASYMMETRIC INDUCTION [J].

CRAM, DJ ;

WILSON, DR .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1963, 85 (09) :1245-&

[5]

DAPRADA M, 1990, J NEUR TR S, V29, P279

[6]

DAPRADA M, 1989, J PHARMACOL EXP THER, V248, P400

[7]

DAVIES B, 1978, LANCET, V1, P172

[8] INTERACTIONS OF MONOAMINE-OXIDASE WITH SUBSTRATES AND INHIBITORS [J].

DOSTERT, PL ;

BENEDETTI, MS ;

TIPTON, KF .

MEDICINAL RESEARCH REVIEWS, 1989, 9 (01) :45-89

[9] 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

[10] Monoamine oxidase A inhibitory potency and flavin perturbation are influenced by different aspects of pirlindole inhibitor structure [J].

Hynson, RMG ;

Wouters, J ;

Ramsay, RR .

BIOCHEMICAL PHARMACOLOGY, 2003, 65 (11) :1867-1874

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