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Your search keyword '"Hierl M"' showing total 2 results
Start Over Author "Hierl M" Publisher elsevier science ltd
2 results on '"Hierl M"'

1. Synthesis and activity of substituted carbamates as potentiators of the alpha4beta2 nicotinic acetylcholine receptor.

Author

Springer SK, Woodin KS, Berry V, Boezio AA, Cao L, Clarkin K, Harmange JC, Hierl M, Knop J, Malmberg AB, McDermott JS, Nguyen HQ, Waldon D, Albrecht BK, and McDonough SI

Subjects
Acetylcholine chemistry, Calcium chemistry, Carbamates chemistry, Drug Design, Humans, Models, Chemical, Nervous System metabolism, Neurons metabolism, Patch-Clamp Techniques, Pyrazoles chemistry, Pyridines chemistry, Receptors, Nicotinic metabolism, Structure-Activity Relationship, Chemistry, Pharmaceutical methods, Receptors, Nicotinic chemistry
Abstract

The synthesis and structure-activity relationship of a series of carbamate potentiators of alpha4beta2 nAChR is reported herein. These compounds were highly selective for alpha4beta2 over other nAChR subtypes. In addition, compounds increased the response of alpha4beta2 nAChRs to acetylcholine, as measured with patch-clamp electrophysiology.

Published
2008
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2. Discovery and optimization of substituted piperidines as potent, selective, CNS-penetrant alpha4beta2 nicotinic acetylcholine receptor potentiators.

Author

Albrecht BK, Berry V, Boezio AA, Cao L, Clarkin K, Guo W, Harmange JC, Hierl M, Huang L, Janosky B, Knop J, Malmberg A, McDermott JS, Nguyen HQ, Springer SK, Waldon D, Woodin K, and McDonough SI

Subjects
Animals, Combinatorial Chemistry Techniques, Disease Models, Animal, Humans, Molecular Structure, Piperidines chemistry, Rats, Receptors, Nicotinic chemistry, Structure-Activity Relationship, Central Nervous System drug effects, Nicotinic Agonists pharmacology, Piperidines chemical synthesis, Piperidines pharmacology, Receptors, Nicotinic drug effects
Abstract

The discovery of a series of small molecule alpha4beta2 nAChR potentiators is reported. The structure-activity relationship leads to potent compounds selective against nAChRs including alpha3beta2 and alpha3beta4 and optimized for CNS penetrance. Compounds increased currents through recombinant alpha4beta2 nAChRs, yet did not compete for binding with the orthosteric ligand cytisine. High potency and efficacy on the rat channel combined with good PK properties will allow testing of the alpha4beta2 potentiator mechanism in animal models of disease.

Published
2008
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