Synthesis and human β-adrenoceptor activity of 1-(3,5-diiodo-4- methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ol derivatives in vitro

Yali He, Victor I. Nikulin, Sandeep S. Vansal, Dennis R. Feller, Duane Miller

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Trimetoquinol (1, TMQ) is a potent nonselective β-adrenergic receptor (AR) agonist and a thromboxane A2/prostaglandin endoperoxide (TP) receptor antagonist, while 3',5'-diiodo-TMQ (2) exhibits β3-AR selectivity. In search of selective β3-AR agonists as potential drugs for the treatment of human obesity and type II diabetes mellitus, a series of 1-(3,5-diiodo-4- methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ols has been prepared and evaluated for their biological activities at human β1-, β2-, and β3-ARs expressed in Chinese hamster ovary (CHO) cells. The compounds have been synthesized by the Bischler-Napieralski cyclization of corresponding amides followed by NaBH4 reduction, and the halogens in the aromatic ring A were introduced by direct halogenation of protected compound 11. Whereas halogen substitution in ring A reduced either potency or intrinsic activity on β3- AR, the non-halogen-substituted compounds 8 and 10 were potent, selective, nearly full agonists for β3-AR.

Original languageEnglish (US)
Pages (from-to)591-598
Number of pages8
JournalJournal of Medicinal Chemistry
Volume43
Issue number4
DOIs
StatePublished - Mar 13 2000

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Tetrahydroisoquinolines
Adrenergic Agonists
Human Activities
Adrenergic Receptors
Halogens
Tretoquinol
Thromboxane Receptors
Thromboxane A2
Halogenation
Cyclization
Cricetulus
Amides
Type 2 Diabetes Mellitus
Ovary
Obesity
Pharmaceutical Preparations
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Synthesis and human β-adrenoceptor activity of 1-(3,5-diiodo-4- methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ol derivatives in vitro. / He, Yali; Nikulin, Victor I.; Vansal, Sandeep S.; Feller, Dennis R.; Miller, Duane.

In: Journal of Medicinal Chemistry, Vol. 43, No. 4, 13.03.2000, p. 591-598.

Research output: Contribution to journalArticle

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