Synthesis, modelling and NK1 antagonist evaluation of a non-rigid cyclopropane-containing analogue of CP-99,994.
A non-rigid cyclopropane-containing diamine analogue of CP-99,994 was synthesised and was found to have only moderate NK1 receptor binding affinity. Molecular dynamics calculations of the conformational space of the former compound gave good correlation between observed activity and a recently published pharmacophore model, lending predictive value to the latter.
Aitken
D J
DJ
Laboratoire de Chimie Thérapeutique associé au CNRS et à l'Université René Descartes (UMR 8638), Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France. aitken@chisg1.univ-bpclermont.fr
Ongeri
S
S
Vallée-Goyet
D
D
Gramain
J C
JC
Husson
H P
HP
D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine