Synthesis and neurokinin antagonist activity of 2-benzylidene- and 2-benzyl-3-benzylamino quinuclidines.
Molecular modeling studies based on the potent NK-1 antagonist CP-96,345 led us to the identification of some 2-benzylidene- and 2-benzyl-3-benzylaminoquinuclidine derivatives as potential antagonists at the NK receptor subtypes. The synthesized compounds, whose Z/E isomerism has been defined by X-ray analysis, show only moderate potency on the three neurokinin receptors. The possible reasons of the low potency exhibited by the tested compounds are discussed.
Caliendo
G
G
Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, Italy.
Greco
G
G
Perissutti
E
E
Santagada
V
V
Silipo
C
C
Vittoria
A
A
Turbanti
L
L
Renzetti
A R
AR
Benedetti
E
E
Pedone
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008958:Models, Molecular; D008969:Molecular Sequence Data; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C066892:CP 96345