Non-imidazole histamine H3 ligands, Part 2: New 2-substituted benzothiazoles as histamine H3 antagonists.
New, non-imidazole histamine H3 receptor antagonists were prepared and in vitro tested as H3 receptor antagonists measured as the electrically evoked contraction of the guinea-pig jejunum. The 2-(1-piperidinyl)- and 2-(1-pyrrolidinyl)benzothiazoles show no or very poor activity; 2-[1-(4-amino)piperidinyl]- and 2-(1,2-ethanediamino)- and 2-(1,3-propanediamino)derivatives of benzothiazole possess weak activity at H3 receptors, whereas 2-(4-piperidinyl)benzothiazoles and 2-[1-(4-piperazinyl)]benzothiazoles show moderate to good activity. Lipophilic and not-too-bulky substituents like n-propyl attached to the nitrogen at the piperazine or piperidine ring lead to potent H3 receptor antagonists with pA2 values ranging from 7.0 to 7.2. The structure-activity relationships for different substitution patterns are discussed.
Walczyński
K
K
Department of Synthesis and Technology of Drugs, Medical Academy, Lódz, Poland.
Guryn
R
R
Zuiderveld
O P
OP
Timmerman
H
H
D000818:Animals; D006168:Guinea Pigs; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology
D006633:Histamine Antagonists; D013844:Thiazoles