New Arylpiperazinylalkyl Derivatives of 8‐Alkoxy‐purine‐2, 6‐dione and Dihydro[1, 3]oxazolo[2, 3‐f]purinedione Targeting the Serotonin 5‐HT1A/5‐HT2A/5‐HT7 and Dopamine D2 Receptors. Issue 4 (13th March 2015)

• Record Type: Journal Article
• Authors: Chłoń‐Rzepa, Grażyna; Zagórska, Agnieszka; Bucki, Adam; Kołaczkowski, Marcin; Pawłowski, Maciej; Satała, Grzegorz; Bojarski, Andrzej J.; Partyka, Anna; Wesołowska, Anna; Pękala, Elżbieta; Słoczyńska, Karolina
• Is Part Of: Archiv der Pharmazie. Volume 348:Issue 4(2015:Apr.)
• Page Start: 242
• Page End: 253
• Publication Date: 2015-03-13
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201500015
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201500015-sec-0001" sec-type="section"> <p>To obtain potential antidepressants and/or antipsychotics, a series of new long‐chain arylpiperazine derivatives of 8‐alkoxy‐purine‐2, 6‐dione (<bold>10</bold>–<bold>24</bold>) and dihydro[1, 3]oxazolo[2, 3‐<italic>f</italic>]purinedione (<bold>30</bold>–<bold>34</bold>) were synthesized and their serotonin (5‐HT_1A, 5‐HT_2A, 5‐HT₆, 5‐HT₇) and dopamine (D₂) receptor affinities were determined. The study allowed the identification of some potent 5‐HT_1A/5‐HT₇/D₂ ligands with moderate affinity for 5‐HT_2A sites. The binding mode of representative compounds from both chemical classes (<bold>11</bold> and <bold>31</bold>) in the site of 5‐HT_1A receptor was analyzed in computational studies. In functional <italic>in vitro</italic> studies, the selected compounds <bold>15</bold> and <bold>16</bold> showed antagonistic properties for the evaluated receptors. 8‐Methoxy‐7‐{4‐[4‐(2‐methoxyphenyl)‐piperazin‐1‐yl]‐butyl}‐1, 3‐dimethyl‐purine‐2, 6‐dione (<bold>15</bold>) showed a lack of activity in terms and under the conditions of the forced swim, four plate and amphetamine‐induced hyperactivity tests in mice, probably as a result of its high first pass effect in the liver.</p> </sec> </abstract>