Non-imidazole histamine H-3 ligands: part V. synthesis and preliminary pharmacological investigation of 1-[2-thiazol-4-yl- and 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazine derivatives

作者：Guryn Roman; Staszewski Marek; Walczynski Krzysztof^*

来源：Medicinal Chemistry Research, 2013, 22(8): 3640-3652.

DOI：10.1007/s00044-012-0372-8

• Histamine H-3-receptor
• H-3-antagonists
• 1-[2-thiazol-4-yl-(2-aminoethyl)]- and 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazine derivatives

Series of 1-[2-thiazol-4-yl-(2-aminoethyl)]- and 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazine derivatives have been prepared and in vitro tested as H-3-receptor antagonists (the electrically evoked contraction of the guinea-pig jejunum). It appeared that by comparison of homologous pairs, the 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazines (3a,b and 4a-d) have much higher potency than their analogous 1-[2-thiazol-4-yl-(2-aminoethyl)]-4-n-propylpiperazines (2a-k). Based on the obtained results, we observed the 5-position of 2-methyl-2-R-aminoethyl substituents in the thiazole ring is favourable for histamine H-3 receptor antagonist activity, whereas its presence in position 4 leads, almost in each case, to strong decrease of activity.

• 出版日期2013-8