Synthesis, antiplatelet activity and comparative molecular field analysis of substituted 2-amino-4 H -pyrido[1,2- a ]pyrimidin-4-ones, their congeners and isosteric analogues
| Autor: | G, Roma, N, Cinone, M, Di Braccio, G, Grossi, G, Leoncini, M G, Signorello, A, Carotti, A, Carott |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Steric effects Quantitative structure–activity relationship Magnetic Resonance Spectroscopy Molecular model Stereochemistry Clinical Biochemistry Ionophore Pharmaceutical Science Pyrimidinones In Vitro Techniques Biochemistry Chemical synthesis Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Humans natural sciences Molecular Biology Bicyclic molecule Chemistry Organic Chemistry Phosphodiesterase Lactam Molecular Medicine Platelet Aggregation Inhibitors |
| Zdroj: | Bioorganic & Medicinal Chemistry. 8:751-768 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/s0968-0896(00)00010-9 |
| Popis: | 2-(1-Piperazinyl)-4H-pyrido[1,2-a]pyrimidin-4-one Chart 5 , Scheme 2 Download : Download high-res image (50KB) Download : Download full-size image Chart 5 . Download : Download high-res image (186KB) Download : Download full-size image Scheme 2 . is a recently described in vitro inhibitor of human platelet aggregation which specifically inhibits the activity of high affinity cAMP phosphodiesterase. A number of substitution derivatives, isosteres, and analogues of Chart 5 , Scheme 2 were now synthesized and tested in vitro for their inhibitory activity on human platelet aggregation induced in platelet-rich plasma by ADP, collagen, or the Ca2+ ionophore A23187. Among the most effective compounds, the 6-methyl, 8-methyl and 6,8-dimethyl derivatives of Chart 5 , Scheme 2 resulted nearly as active as the lead when platelet aggregation was induced by ADP or A23187, but less active when collagen was the inducer. On the basis of present results and those previously obtained by us in this and 2-aminochromone structural fields, we have developed a statistically significant 3-D QSAR model, using comparative molecular field analysis (CoMFA), describing the variation of the antiplatelet activity in terms of molecular steric and electrostatic potential changes. |
| Databáze: | OpenAIRE |
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