Exploring SAR features in diverse library of 4-cyanomethyl-pyrazole-3-carboxamides suitable for further elaborations as CB1 antagonists
| Autor: | Pia Karina Nørregaard, Emelie Bjurling, Peter Aadal Nielsen, Niklas Sköld, Thomas Högberg, Jean-Marie Receveur, Cooper Martin |
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| Rok vydání: | 2009 |
| Předmět: |
Nitrile
medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Carboxamide Pyrazole Biochemistry Chemical synthesis Chemical library Small Molecule Libraries chemistry.chemical_compound Structure-Activity Relationship Receptor Cannabinoid CB1 Amide Drug Discovery medicine Moiety Humans Molecular Biology Chemistry Organic Chemistry Amides Blood-Brain Barrier Benzene derivatives Molecular Medicine |
| Zdroj: | Bioorganicmedicinal chemistry letters. 20(1) |
| ISSN: | 1464-3405 |
| Popis: | A chemically diverse library of secondary and tertiary 4-cyanomethyl-1,5-diphenyl-1H-pyrazole-3-carboxamides was synthesized to enable mapping of the SAR, in the eastern amide region, with regard to CB1 antagonist activity, This study was initiated as a prelude to the design and synthesis of possible CB1 antagonists that do not readily pass the blood-brain-barrier. In general a range of modifications were found to be tolerated in this part of the molecule, although polar and especially charged groups did to a degree reduce the CB1 antagonistic activity. Several compounds with single-digit or even sub-nanomolar potency, suitable for further elaboration of the nitrile moiety, were identified. |
| Databáze: | OpenAIRE |
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