Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists

Torsten Hoffmann; Michael Bös; Heinz Stadler; Patrick Schnider; Walter Hunkeler; Thierry Godel; Guido Galley; Theresa M Ballard; Guy A Higgins; Sonia M Poli; Andrew J Sleight

doi:10.1016/j.bmcl.2005.11.047

Design and synthesis of a novel, achiral class of highly potent and selective, orally active neurokinin-1 receptor antagonists

Bioorg Med Chem Lett. 2006 Mar 1;16(5):1362-5. doi: 10.1016/j.bmcl.2005.11.047. Epub 2005 Dec 5.

Authors

Torsten Hoffmann¹, Michael Bös, Heinz Stadler, Patrick Schnider, Walter Hunkeler, Thierry Godel, Guido Galley, Theresa M Ballard, Guy A Higgins, Sonia M Poli, Andrew J Sleight

Affiliation

¹ F. Hoffmann-La Roche Ltd, Pharma Research, CH-4070 Basel, Switzerland. [email protected]

PMID: 16332435
DOI: 10.1016/j.bmcl.2005.11.047

Abstract

The discovery of a novel, achiral pyridine class of potent and orally active neurokinin-1 (NK(1)) receptor antagonists is described. The evaluation of this class is briefly outlined, leading to the identification of netupitant 21 and befetupitant 29, two new proprietary chemical entities with high affinity and excellent CNS penetration.

MeSH terms

Administration, Oral
Amines / chemistry
Animals
CHO Cells
Cricetinae
Cross-Linking Reagents / chemistry
Drug Design*
Humans
Molecular Structure
Neurokinin-1 Receptor Antagonists*
Pyridines / chemical synthesis
Pyridines / chemistry
Pyridines / pharmacology
Pyrimidines / chemistry
Receptors, Neurokinin-1 / metabolism
Sensitivity and Specificity
Structure-Activity Relationship
Substrate Specificity

Substances

Amines
Cross-Linking Reagents
Neurokinin-1 Receptor Antagonists
Pyridines
Pyrimidines
Receptors, Neurokinin-1
netupitant
befetupitant