Non-imidazole histamine H3 ligands. Part III. New 4-n-propylpiperazines as non-imidazole histamine H3-antagonists.
In search for a new lead of non-imidazole histamine H3-receptor antagonists, a series of 1[(2-thiazolopyridine)-4-n-propyl]piperazines, the analogous 1-[(2-oxazolopyridine)-4-npropyl]piperazines, 1-[(2-benzothiazole)-4-n-propyl]piperazine and 1-[(2-benzooxazole)4-n-propyl]piperazine were prepared and in vitro tested as H3-receptor antagonists (the electrically evoked contraction of the guinea-pig jejunum). It appeared that by comparison of homologous pairs the thiazolo derivatives have slightly higher activity than their oxazolo analogues. The most potent compound of these series is the 1-(2-thiazolo[4,5-c]pyridine)-4-n-propylpiperazine (3c) with pA2 = 7.25 (its oxazole analogue (4g) showed pA2 = 6.9). The structure-activity relationships for compounds with various positions of the nitrogen in the benzene ring for the thiazoles compared with oxazoles are discussed.
Walczyński
Krzysztof
K
Department of Synthesis and Technology of Drugs, Medical University Muszyńskiego, Muszyńskiego Street 1, 90-145 Łódź, Poland. kwalczynski@pharm.am.lodz.pl
Zuiderveld
Obbe P
OP
Timmerman
Henk
H
D000818:Animals; D015195:Drug Design; D004558:Electric Stimulation; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007422:Intestines; D008024:Ligands; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D018100:Receptors, Histamine H3 / Q000737:chemistry*; D013329:Structure-Activity Relationship
D006633:Histamine Antagonists; D008024:Ligands; D010879:Piperazines; D018100:Receptors, Histamine H3