Rational design of novel pyrrolidine derivatives as orally active neurokinin-3 receptor antagonists.
The rational design of a novel series of pyrrolidine derivatives as neurokinin-3 receptor antagonists is reported starting from a selective neurokinin-1 receptor antagonist. Typical representatives in this series showed in vivo efficacy after oral administration in a NK3 mediated functional assay. This series of NK3 antagonists shows promise to deliver a novel antipsychotic.
Ratni
Hassen
H
F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, Preclinical Research, CH-4070 Basel, Switzerland. hasane.ratni@roche.com
Ballard
Theresa M
TM
Bissantz
Caterina
C
Hoffmann
Torsten
T
Jablonski
Philippe
P
Knoflach
Frederic
F
Knust
Henner
H
Malherbe
Parichehr
P
Nettekoven
Matthias
M
Patiny-Adam
Angelique
A
Riemer
Claus
C
Schmitt
Monique
M
Spooren
Will
W
D000284:Administration, Oral; D015195:Drug Design; D008958:Models, Molecular; D011759:Pyrrolidines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors*
D011759:Pyrrolidines; D018042:Receptors, Neurokinin-3; C032519:pyrrolidine