Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: structure-activity relationship elucidation.
The optimisation of affinity and selectivity in a novel series of dual 5-HT5A/5-HT7 receptor ligands is described. Brain penetrant 2-aminodihydroquinazolines with low nanomolar affinities were identified.
Peters
Jens-Uwe
JU
Discovery Chemistry, Pharma Division, F. Hoffmann-La Roche Ltd, CH-4070 Basel, Switzerland. jens-uwe.peters@roche.com
Lübbers
Thomas
T
Alanine
Alexander
A
Kolczewski
Sabine
S
Blasco
Francesca
F
Steward
Lucinda
L
D001921:Brain / Q000378:metabolism; D006146:Guanidines / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008024:Ligands; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D011799:Quinazolines / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006146:Guanidines; D008024:Ligands; D011743:Pyrimidines; D011799:Quinazolines; D011985:Receptors, Serotonin; C078730:serotonin 5 receptor; C104425:serotonin 7 receptor