Frymarkiewicz Anna, Walczyński Krzysztof
Department of Synthesis and Technology of Drugs, Medical University, Muszyńskiego Street 1, 90-145 Łódź, Poland.
Eur J Med Chem. 2009 Apr;44(4):1674-81. doi: 10.1016/j.ejmech.2008.09.019. Epub 2008 Sep 30.
A series of 1-[[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propyl]piperazine 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-methyl-2-phenylalkylaminoethyl)]-4-n-propyl]piperazine derivatives (4c1-4c3) have slightly higher activity than their 1-[2-thiazol-5-yl-(2-methyl-2-alkylaminoethyl)]-4-n-propylpiperazine analogues (4b1-4b3). In the 2-methylalkylamide series (4a1-4a3) a somewhat lower activity was observed. The most potent compound of the series is the 1-[2-thiazol-5-yl-(2-methyl-2-phenylpropylaminoethyl)]-4-n-propylpiperazine (4c2) with pA(2)=8.27 (its alkyl analogue (4b2) showed pA(2)=7.53 and the corresponding amide (4a2) displayed pA(2)=7.36). Selected compounds (4b1, 4b2, 4c1 and 4c2) were also tested (in vitro) for H(1) antagonistic effects in vitro applying standard methods (guinea pig ileum). None showed any H(1) antagonistic activity (pA(2)<4).
已制备了一系列1-[[2-噻唑-5-基-(2-氨基乙基)]-4-正丙基]哌嗪衍生物，并作为H(3)受体拮抗剂进行了体外测试（豚鼠空肠的电诱发收缩）。通过同源对的比较发现，1-[[2-噻唑-5-基-(2-甲基-2-苯基烷基氨基乙基)]-4-正丙基]哌嗪衍生物（4c1-4c3）的活性略高于其1-[2-噻唑-5-基-(2-甲基-2-烷基氨基乙基)]-4-正丙基哌嗪类似物（4b1-4b3）。在2-甲基烷基酰胺系列（4a1-4a3）中观察到活性略低。该系列中最有效的化合物是1-[2-噻唑-5-基-(2-甲基-2-苯基丙基氨基乙基)]-4-正丙基哌嗪（4c2），其pA(2)=8.27（其烷基类似物（4b2）的pA(2)=7.53，相应的酰胺（4a2）的pA(2)=7.36）。还采用标准方法（豚鼠回肠）对选定的化合物（4b1、4b2、4c1和4c2）进行了体外H(1)拮抗作用测试。均未显示出任何H(1)拮抗活性（pA(2)<4）。
