2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 3: Synthesis and activity of isosteric analogs

Hiroyuki Kai; Yasuhide Morioka; Yuji Koriyama; Kazuya Okamoto; Yasushi Hasegawa; Maki Hattori; Katsumi Koike; Hiroki Chiba; Shunji Shinohara; Yuka Iwamoto; Kohji Takahashi; Norihiko Tanimoto

doi:10.1016/j.bmcl.2008.10.070

2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 3: Synthesis and activity of isosteric analogs

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6444-7. doi: 10.1016/j.bmcl.2008.10.070. Epub 2008 Oct 19.

Authors

Hiroyuki Kai¹, Yasuhide Morioka, Yuji Koriyama, Kazuya Okamoto, Yasushi Hasegawa, Maki Hattori, Katsumi Koike, Hiroki Chiba, Shunji Shinohara, Yuka Iwamoto, Kohji Takahashi, Norihiko Tanimoto

Affiliation

¹ Shionogi Research Laboratories, Shionogi & Co., Ltd, 12-4, Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan. hiroyuki.kai@shionogi.co.jp

PMID: 18977140
DOI: 10.1016/j.bmcl.2008.10.070

Abstract

Structure-activity relationships and efforts to optimize the pharmacokinetic profile of isosteric analogs of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid receptor agonists are described. Among those examined, compound 25 showed potent affinity for cannabinoid receptor 1 (CB1) and receptor 2 (CB2). This compound displayed oral bioavailability and analgesic activity.

MeSH terms

Administration, Oral
Animals
Biological Availability
Cannabinoid Receptor Agonists*
Cell Line, Tumor
Chemistry, Pharmaceutical / methods
Drug Design
Humans
Kinetics
Mice
Models, Chemical
Rats
Structure-Activity Relationship
Thiazines / chemical synthesis*
Thiazines / pharmacokinetics
Thiazines / pharmacology*
Thiourea / chemistry

Substances

Cannabinoid Receptor Agonists
Thiazines
Thiourea