Non-imidazole histamine H-3 ligands, part 2: New 2-substituted benzothiazoles as histamine H-3 antagonists

New, non-imidazole histamine H-3 receptor antagonists were prepared and in vitro tested as H-3 receptor antagonists measured as the electrically evoke d contraction of the guinea-pig jejunum. The 2-(1-piperidinyl)- and 2-(1-py rrolidinyl)benzothiazoles show no or very poor activity; 2-[1-(4-amino)pipe ridinyl]- and 2-(1,2-ethanediamino)- and 2-(1,3-propanediamino)derivatives of benzothiazole possess weak activity at H-3 receptors, whereas 2-(4-piper idinyl)benzothiazoles and 2-[1-(4-pipzrazinyl)]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 poten t H-3 receptor antagonists with pA(2) values ranging from 7.0 to 7.2. The s tructure-activity relationships for different substitution patterns are dis cussed.