Non-Imidazole Histamine H3 Ligands, Part 2: New 2-Substituted Benzothiazoles as Histamine H3 Antagonists

• Published in: Archiv der Pharmazie (Weinheim) 1999-11, Vol.332 (11), p.389-398
• Main Authors: Walczynski, Krzysztof, Guryn, Roman, Zuiderveld, Obbe P., Timmerman, Henk
• Format: Article
• Language: English
• Subjects: 2-(1-piperazinyl)benzothiazoles; 2-(1-piperidinyl)- and 2-(4-piperidinyl)benzothiazoles; 2-(1-pyrrolidinyl)benzothiazole; 2-[1-(4-amino)piperidinyl]benzothiazoles; 2-ethanediamino)- and 2-; 2‐(1,2‐ethanediamino)‐ and 2‐(1,3‐propanediamino)benzothiazoles; 3-propanediamino)benzothiazoles; Animals; Biological and medical sciences; Guinea Pigs; H3 antagonists; Histamine Antagonists - chemical synthesis; Histamine Antagonists - chemistry; Histamine Antagonists - pharmacology; Histamine H3 receptor; Medical sciences; Miscellaneous; Molecular Structure; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/(SICI)1521-4184(199911)332:11<389::AID-ARDP389>3.0.CO;2-U

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.