Abstract
A novel series of 1,2,4-triazolyl 5-azaspiro[2.4]heptanes with high affinity and selectivity at the dopamine (DA) D3 receptor (D3R) is described. Some of these compounds also have high selectivity over the hERG channel and were characterized with respect to their pharmacokinetic properties both in vitro and in vivo during lead identification and early lead optimization phases. A few derivatives with overall favorable developability characteristics were selected for further late lead optimization studies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CHO Cells
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Cricetulus
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Crystallography, X-Ray
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Ether-A-Go-Go Potassium Channels / metabolism
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Heptanes / chemistry*
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Heptanes / pharmacology*
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Humans
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Models, Molecular
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Receptors, Dopamine D3 / antagonists & inhibitors*
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Receptors, Dopamine D3 / metabolism
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Spiro Compounds / chemistry*
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Spiro Compounds / pharmacology*
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Structure-Activity Relationship
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Triazoles / chemistry
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Triazoles / pharmacology
Substances
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Ether-A-Go-Go Potassium Channels
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Heptanes
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Receptors, Dopamine D3
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Spiro Compounds
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Triazoles