2-Amino-4-benzyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridines

Novel selective β3-adrenoceptor agonists

Weiping Zheng, Victor I. Nikulin, Anish A. Konkar, Sandeep S. Vansal, Gamal Shams, Dennis R. Feller, Duane Miller

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Trimetoquinol (TMQ, 7) is a potent nonselective β-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 β1-, β2-, and β3-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 β3-AR, they exhibited a high degree of selective β3-AR agonist activity in functional assays. Moreover, the β3- 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 β3-AR activity.

Original languageEnglish (US)
Pages (from-to)2287-2294
Number of pages8
JournalJournal of Medicinal Chemistry
Volume42
Issue number12
DOIs
StatePublished - Jun 17 1999

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Pyridines
Adrenergic Receptors
Tretoquinol
Acetylation
Human Activities

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

2-Amino-4-benzyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridines : Novel selective β3-adrenoceptor agonists. / Zheng, Weiping; Nikulin, Victor I.; Konkar, Anish A.; Vansal, Sandeep S.; Shams, Gamal; Feller, Dennis R.; Miller, Duane.

In: Journal of Medicinal Chemistry, Vol. 42, No. 12, 17.06.1999, p. 2287-2294.

Research output: Contribution to journalArticle

Zheng, Weiping ; Nikulin, Victor I. ; Konkar, Anish A. ; Vansal, Sandeep S. ; Shams, Gamal ; Feller, Dennis R. ; Miller, Duane. / 2-Amino-4-benzyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridines : Novel selective β3-adrenoceptor agonists. In: Journal of Medicinal Chemistry. 1999 ; Vol. 42, No. 12. pp. 2287-2294.
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abstract = "Trimetoquinol (TMQ, 7) is a potent nonselective β-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 β1-, β2-, and β3-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 β3-AR, they exhibited a high degree of selective β3-AR agonist activity in functional assays. Moreover, the β3- 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 β3-AR activity.",
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AU - Feller, Dennis R.

AU - Miller, Duane

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N2 - Trimetoquinol (TMQ, 7) is a potent nonselective β-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 β1-, β2-, and β3-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 β3-AR, they exhibited a high degree of selective β3-AR agonist activity in functional assays. Moreover, the β3- 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 β3-AR activity.

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