Structure-Activity Relationship Studies of Central Nervous System Agents. 13.4-[3-(Benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)piperazine, a New Putative 5-HT1A Receptor Antagonist, and Its Analogs

Abstract

A new set of 4-alkyl-1-(o-methoxyphenyl)piperazines containing a terminal benzotriazole fragment were synthesized, and their 5-HT1A and 5-HT2 affinity was determined. It was shown that the benzotriazole moiety contributes to both the 5-HT1A and 5-HT2 receptor affinity. It was demonstrated in several behavioral models that 4-[3-(benzotriazol-1- yl)propyl]-1-(2-methoxyphenyl)piperazine (11) is a new, potent presynaptic and postsynaptic 5-HT1A receptor antagonist. However, it is not selective for 5-HT1A versus alpha 1 receptors.

A study on application of impregnated synthetic peptide TLC stationary phases for the screening of 5‐HT1A ligands. Part 2

“…Statistical values of the above Table 3. Structure, 5-HT 1A receptor affinities, migration decrease (∆R f ) and the calculated log P data of the tested compounds 1-22 a Data taken from the literature: 1-3 (Mokrosz et al, 1994b), 4, 5, 9, 10 (Paluchowska et al, 1999), 7 (Mokrosz et al, 1994c), 8 (Mokrosz et al, 1994a), 11-15 (Paluchowska et al, 2001), 16, 17 (Paluchowska et al, 2003a,b), 18 (Byrtus et al, 1996), 19 (Byrtus et al, 2001), 20-22 (Chlon et al, 2001). b log P c was calculated using a PrologP 5.1 program (CompuDrug Ltd., Hungary).…”

Conformational Restriction in Novel NAN‐190 and MP3022 Analogs and Their 5‐HT1A Receptor Activity

“…It was shown that the LLR in rats, induced by the wellknown 5-HT 1A receptor agonist 8-OH-DPAT, depends on stimulation of postsynaptic 5-HT 1A receptors [14,17]. Furthermore, this symptom is sensitive to 5-HT 1A receptor antagonists, including WAY 100635, MP3022, and NAN-190 [3,11,18]. Hence, the ability of the tested compounds to inhibit 8-OH-DPAT-induced LLR was regarded as antagonistic activity.…”

“…The cis and trans stereoisomers were successfully separated and pharmacologically characterized. The previously described flexible analogs 6a -9a were used as reference structures [11,12].…”

α1- andα2-Adrenoreceptor Antagonist Profiles of 1- and 2-[ω-(4-Arylpiperazin-1-yl)alkyl]-1,2,3-benzotriazoles

“…Therefore, the w-bromoalkyl derivatives 33 and 34 were prepared by reacting 28 with an excess of the suitable oligomethylene dibromide in the presence of KF/Al 2 O 3 prepared according to Texier ± Boullet et al [30] (Method B). This procedure has been used before by Mokrosz et al [23] and by us [14] for the preparation of 1-and 2-(4-bromobutyl)benzotriazole. The 1-and 2-substituted isomers were separated as usual.…”

“…Of the additional known compounds included in this study, 22 and 25 had been prepared before by Mokrosz et al [23] by reacting the unsubstituted benzotriazole with 1-(3-bromopropyl)-4-(2-methoxyphenyl)piperazine; and compounds 23 and 26 had been prepared by the same authors from the unsubstituted benzotriazole. In the present work, we found it convenient to synthesize compounds 22 and 25 via the 1-and 2-(3-tosyloxypropyl)benzotriazole in analogy to Method A, especially since we have prepared the required tosylates before [31].…”