New 2-substituted 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine having highly active and potent central alpha 2-antagonistic activity as potential antidepressants.
The synthesis and biological activity of a series of benzofuro[3,2-c]pyridines and a benzothieno[3,2-c]pyridine are described. These compounds exhibit high affinity for the alpha 2-adrenoceptor, with high selectivity versus the alpha 1-receptor. Compound 1 also shows potent in vivo central activity and has been selected for further biological and clinical evaluation.
Kennis
L E
LE
Department of Medicinal Chemistry, Janssen Research Foundation, Beerse, Belgium. lkennis@janbe.jnj.com
Bischoff
F P
FP
Mertens
C J
CJ
Love
C J
CJ
Van den Keybus
F A
FA
Pieters
S
S
Braeken
M
M
Megens
A A
AA
Leysen
J E
JE
D000316:Adrenergic alpha-Agonists / Q000378:metabolism / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D016466:CHO Cells; D003000:Clonidine / Q000378:metabolism / Q000494:pharmacology; D006224:Cricetinae; D006801:Humans; D008297:Male; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D014991:Xylazine / Q000378:metabolism / Q000494:pharmacology; D015016:Yohimbine / Q000378:metabolism / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000928:Antidepressive Agents; D011725:Pyridines; D018341:Receptors, Adrenergic, alpha-2; D014991:Xylazine; D015016:Yohimbine; D003000:Clonidine; D011224:Prazosin