Pd(0) Amination of Benzimidazoles as an Efficient Method Towards New (Benzimidazolyl)piperazines ... more Pd(0) Amination of Benzimidazoles as an Efficient Method Towards New (Benzimidazolyl)piperazines with High Affinity for the 5-HT 1A Receptor.-Some new (benzimidazolyl)amines are synthesized via Pd(0) amination of bromobenzimidazole derivatives. Among them, benzimidazolyl piperazine derivatives like (VI) exhibit high in vitro binding affinity for 5-HT 1A
Based on a computational model for 5-HT 1A R-ligand interaction and QSAR studies, we have designe... more Based on a computational model for 5-HT 1A R-ligand interaction and QSAR studies, we have designed and synthesized a new series of arylpiperazines 2-8 which exhibit high 5-HT 1A R affinity and selectivity over a 1-adrenergic receptors. Among them, compound CSP-2503 (4) has been pharmacologically characterized as a 5-HT 1A R agonist at somatodendritic and postsynaptic sites, endowed with anxiolytic properties.
To continue our early study on the structural modifications of clioquinol, more 8-hydroxyquinolin... more To continue our early study on the structural modifications of clioquinol, more 8-hydroxyquinolinederived Mannich bases were synthesized and examined for growth-inhibitory effect. Taken Mannich base 1 as our lead compound, upon replacement of either sulfonyl group with methylene group or piperazine ring with ethylenediamine group resulted in an appreciable increase in potency. On the other hand, as 8-hydroxyquinoline was replaced with phenol, 3-hydroxypyridine and 1-naphthol, a dramatic decrease in activity was observed, indicating that 8-hydroxyquinoline is a crucial scaffold for activity. Further 3D-QSAR analysis on HeLa cells revealed that both steric and electronic effects contributed equally to growth inhibition. Taken together, the structure-activity relationships obtained from both in vitro data and CoMFA model warrant a valuable reference for further study.
Pd(0) Amination of Benzimidazoles as an Efficient Method Towards New (Benzimidazolyl)piperazines ... more Pd(0) Amination of Benzimidazoles as an Efficient Method Towards New (Benzimidazolyl)piperazines with High Affinity for the 5-HT 1A Receptor.-Some new (benzimidazolyl)amines are synthesized via Pd(0) amination of bromobenzimidazole derivatives. Among them, benzimidazolyl piperazine derivatives like (VI) exhibit high in vitro binding affinity for 5-HT 1A
Based on a computational model for 5-HT 1A R-ligand interaction and QSAR studies, we have designe... more Based on a computational model for 5-HT 1A R-ligand interaction and QSAR studies, we have designed and synthesized a new series of arylpiperazines 2-8 which exhibit high 5-HT 1A R affinity and selectivity over a 1-adrenergic receptors. Among them, compound CSP-2503 (4) has been pharmacologically characterized as a 5-HT 1A R agonist at somatodendritic and postsynaptic sites, endowed with anxiolytic properties.
To continue our early study on the structural modifications of clioquinol, more 8-hydroxyquinolin... more To continue our early study on the structural modifications of clioquinol, more 8-hydroxyquinolinederived Mannich bases were synthesized and examined for growth-inhibitory effect. Taken Mannich base 1 as our lead compound, upon replacement of either sulfonyl group with methylene group or piperazine ring with ethylenediamine group resulted in an appreciable increase in potency. On the other hand, as 8-hydroxyquinoline was replaced with phenol, 3-hydroxypyridine and 1-naphthol, a dramatic decrease in activity was observed, indicating that 8-hydroxyquinoline is a crucial scaffold for activity. Further 3D-QSAR analysis on HeLa cells revealed that both steric and electronic effects contributed equally to growth inhibition. Taken together, the structure-activity relationships obtained from both in vitro data and CoMFA model warrant a valuable reference for further study.
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Papers by David Ayala