SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF A SERIES OF DIHYDRO-1H-PYRROLO[1,2-A]IMIDAZOLE-2,5(3H,6H)-DIONES, A NOVEL CLASS OF POTENT COGNITION ENHANCERS

被引：69

作者：

PINZA, M ^{[1
]}

FARINA, C ^{[1
]}

CERRI, A ^{[1
]}

PFEIFFER, U ^{[1
]}

RICCABONI, MT ^{[1
]}

BANFI, S ^{[1
]}

BIAGETTI, R ^{[1
]}

POZZI, O ^{[1
]}

MAGNANI, M ^{[1
]}

DORIGOTTI, L ^{[1
]}

机构：

[1] SMITHKLINE BEECHAM FARMACEUT,RES LABS,I-20021 BARANZATE,ITALY

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 36卷 / 26期

关键词：

D O I：

10.1021/jm00078a011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones were synthesized. These bicylic derivatives contain both the 2-pyrrolidinone and 4-imidazolidinone nuclei, already recognized as important for cognition enhancing activity. In addition, these structures maintain the backbone of piracetam and oxiracetam with the acetamide side chain restricted in a folded conformation. Their ability to reverse scopolamine-induced amnesia was assessed in a one trial, step-through, passive avoidance paradigm. The main features observed are a potent antiamnestic activity after ip administration (minimal effective dose being between 0.3 and 1 mg/kg ip for most compounds), the presence of a bell-shaped dose-response curve and, generally, a reduction of biological activity after po administration. However, the unsubstituted compound (15, dimiracetam) shows no evidence of a bell-shaped dose-response curve and completely retains activity when given orally, being 10-30 times more potent than the reference drug oxiracetam.

引用

页码：4214 / 4220

页数：7

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