title: Non-imidazole histamine H3 ligands, part IV: SAR of 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazine derivatives.
abstract: 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).
authors.affiliation: Department of Synthesis and Technology of Drugs, Medical University, Muszyńskiego Street 1, 90-145 Łódź, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Frymarkiewicz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Walczyński
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D006634:Histamine H1 Antagonists; D054828:Histamine H3 Antagonists; D007093:Imidazoles; D010879:Piperazines; D018100:Receptors, Histamine H3; D000077489:Piperazine; C029899:imidazole