Synthesis and structure–activity relationships of retro bis-aminopyrrolidine urea (rAPU) derived small-molecule antagonists of the melanin-concentrating hormone receptor-1 (MCH-R1). Part 2

The design, synthesis, and SAR of a series of retro bis-aminopyrrolidine ureas are described. Compounds from this series exhibited considerable binding affinity (Ki=1nM) and functional activity at MCH-R1, acceptable CYP2D6 inhibition, and good rat brain exposure. The design, synthesis, and SAR of a...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-09, Vol.16 (18), p.4922-4930
Main Authors: Hudson, Sarah, Kiankarimi, Mehrak, Rowbottom, Martin W., Vickers, Troy D., Wu, Dongpei, Pontillo, Joseph, Ching, Brett, Dwight, Wesley, Goodfellow, Val S., Schwarz, David, Heise, Christopher E., Madan, Ajay, Wen, Jenny, Ban, William, Wang, Hua, Wade, Warren S.
Format: Article
Language:English
Subjects:
Animals
Antagonists
Biological and medical sciences
CYP2D6
General and cellular metabolism. Vitamins
Hormones. Endocrine system
Inhibitory Concentration 50
Medical sciences
Melanin-concentrating hormone receptor-1
Molecular Structure
Pharmacology. Drug treatments
Pyrrolidines - chemical synthesis
Pyrrolidines - chemistry
Pyrrolidines - pharmacokinetics
Pyrrolidines - pharmacology
Rats
Receptors, Somatostatin - antagonists & inhibitors
Receptors, Somatostatin - metabolism
Retro bis-aminopyrrolidine urea
Structure-Activity Relationship
Urea - analogs & derivatives
Urea - chemical synthesis
Urea - chemistry
Urea - pharmacokinetics
Urea - pharmacology
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Summary:The design, synthesis, and SAR of a series of retro bis-aminopyrrolidine ureas are described. Compounds from this series exhibited considerable binding affinity (Ki=1nM) and functional activity at MCH-R1, acceptable CYP2D6 inhibition, and good rat brain exposure. The design, synthesis, and SAR of a series of retro bis-aminopyrrolidine ureas are described. Compounds from this series exhibited considerable binding affinity (Ki=1nM) and functional activity at MCH-R1, acceptable CYP2D6 inhibition, and good rat brain exposure.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2006.06.049