High affinity and selectivity on 5-HT1A receptor of 1-aryl-4-[1-tetralin)alkyl]piperazines. 2.
Several 4-alkyl-1-arylpiperazines that present a tetralin moiety on the terminal part of the side chain were synthesized in order to increase the selectivity on the 5-HT1A versus D-2, alpha 1, sigma, and other 5-HT receptors. Many changes have been effected on previous structures of type 3(1-aryl-4-[3-(1,2-dihydronaphthalen-4-yl)-n-propyl]piperazines). Several synthetic procedures were followed to obtain the final products, depending on the presence or absence of a double bond, as well as of a heteroatom on the side chain. In the first case versatile use of Grignard reaction was made, whereas in the second one usual synthetic ways were applied. Final compounds were evaluated for in vitro activity on dopamine D-1 and D-2, serotonin 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT2, alpha 1 adrenergic, and sigma receptors by radioreceptor binding assay. For the 2-MeO-Ph, 2-pyridyl, and unsubstituted phenyl N-piperazine derivatives, low IC50 values (0.3 nM) on 5-HT1A receptors and high selectivity values were observed.
Perrone
R
R
Dipartimento Farmaco-chimico, Università di Bari, Italy.
Berardi
F
F
Colabufo
N A
NA
Leopoldo
M
M
Tortorella
V
V
Fiorentini
F
F
Olgiati
V
V
Ghiglieri
A
A
Govoni
S
S
D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006168:Guinea Pigs; D007536:Isomerism; D007700:Kinetics; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology
D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes