Non-imidazole histamine H3 ligands. Part I. Synthesis of 2-(1-piperazinyl)- and 2-(hexahydro-1H-1,4-diazepin-1-yl)benzothiazole derivatives as H3-antagonists with H1 blocking activities.
New 2-(1-Piperazinyl)- and 2-(hexahydro-1H-1,4-diazepin-1-yl)benzothiazoles were prepared and tested as H1- and H3-receptor antagonists. A number of compounds showed weak H1-antagonistic activity, with pA2 values ranging from 5.5 to 6.1. The simple alkyl substituted, 2-[1-(4-methyl and 4-ethyl)piperazinyl] analogues show increasing, moderate H3-antagonistic activity (pA2 = 6.0, and pA2 = 7.0). The compounds with 4-phenylalkyl substitution, for both the piperazinyl and the hexahydro-1H-1,4-diazepin-1-yl homologues series, regardless of the different physicochemical properties of the para substituents at the phenyl ring, showed weak H3-antagonistic activity with pA2 values ranging from 4.4 to 5.6.
Walczyński
K
K
Department of Synthesis and Technology of Drugs, Medical Academy, Lódź, Poland.
Guryn
R
R
Zuiderveld
O P
OP
Timmerman
H
H
D000818:Animals; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D018100:Receptors, Histamine H3; D013844:Thiazoles