title: 2-Amino-4-benzyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridines: novel selective beta3-adrenoceptor agonists.
abstract: Trimetoquinol (TMQ, 7) is a potent nonselective beta-adrenoceptor (AR) agonist. Replacement of the catechol moiety of TMQ with a 2-aminothiazole group resulted in novel thiazolopyridine derivatives 9-11 which have been synthesized and evaluated for biological activity on human beta1-, beta2-, and beta3-AR. The Bischler-Napieralski reaction has been employed as a novel approach to construct the 2-amino-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine ring system. Although in radioligand binding studies analogues 9 and 10 did not show selectivity toward beta3-AR, they exhibited a high degree of selective beta3-AR agonist activity in functional assays. Moreover, the beta3-AR agonist activity of the 2-aminothiazole derivatives is abolished by N-acetylation (analogue 11) or ring opening (analogue 25). This illustrates the importance of the intact 2-amino-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine ring for beta3-AR activity.
authors.affiliation: Department of Pharmaceutical Sciences, University of Tennessee, Memphis, Tennessee 38163, USA.
authors.forename: W
authors.initials: W
authors.lastname: Zheng
authors.forename: V I
authors.initials: VI
authors.lastname: Nikulin
authors.forename: A A
authors.initials: AA
authors.lastname: Konkar
authors.forename: S S
authors.initials: SS
authors.lastname: Vansal
authors.forename: G
authors.initials: G
authors.lastname: Shams
authors.forename: D R
authors.initials: DR
authors.lastname: Feller
authors.forename: D D
authors.initials: DD
authors.lastname: Miller
mesh_terms: D000318:Adrenergic beta-Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D022702:Receptors, Adrenergic, beta-3; D020218:Response Elements; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D000242:Cyclic AMP; D008156:Luciferases