2 -Arylimino -5,6 -dihydro -4H-1,3 -thiazines as a new class of cannabinoid receptor agonists. Part 2 Orally bioavailable compounds

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 14; pp. 3925 - 3929
• Main Authors: KAI, Hiroyuki, MORIOKA, Yasuhide, IWAMOTO, Yuka, TAKAHASHI, Kohji, YAMAGUCHI, Yoshitaka, BABA, Takahiko, YOSHIKAWA, Takayoshi, TAKENAKA, Hideyuki, TOMIDA, Minoru, TAKAHASHI, Tadashi, HATTORI, Maki, HANASAKI, Kohji, KOIKE, Katsumi, CHIBA, Hiroki, SHINOHARA, Shunji, KANEMASA, Toshiyuki
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 15.07.2007
• Subjects: Administration, Oral; Analgesics; Biological and medical sciences; Biological Availability; Cannabinoid Receptor Agonists; Medical sciences; Miscellaneous; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Thiazines - administration & dosage; Thiazines - pharmacokinetics; Thiazines - pharmacology; CB1 cannabinoid receptor; Agonist; Intravenous administration; Cannabinoid receptor agonist; Rat; Selectivity; Pain; Structure activity relation; Bicyclic compound; Chemical synthesis; Human; Sulfur nitrogen heterocycle; Pharmacokinetic profile; Oral bioavailability; Rodentia; Benzene derivatives; Oral administration; 1,3-Thiazine; CB2 cannabinoid receptor; Bioavailability; In vitro; Naphthalene derivatives; Spiran; In vivo; Vertebrata; CB2; Mammalia; Analgesic; CB1; Mouse; Animal; Organic fluorine compounds; Affinity; Pharmacokinetics
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2007.04.099

Structure-activity relationships and efforts to optimize the pharmacokinetic profile of a class of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid receptor agonists are described. Among the compounds examined, compound 14 showed potent affinity and high selectivity for CB2, and compound 23 showed potent affinities against CB1 and CB2. These compounds displayed oral bioavailability.