Effect of fluorine substitution on the adrenergic properties of 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol

Adeboye Adejare, Jun Ying Nie, David Hebel, L. Ellen Brackett, Oksoon Choi, Fabian Gusovsky, William L. Padgett, John W. Daly, Cyrus R. Creveling, Kenneth L. Kirk

Research output: Contribution to journalArticle

Abstract

The 2- and 6-fluoro derivatives of the potent β-adrenergic agonist 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol were prepared and their adrenergic properties examined. The order of potency was as follows: β-adrenergic activity (simulation of cyclic AMP formation in C6 glioma cells), 2-F = parent ≫ 6-F; β1-activity (rate of contraction, guinea pig atria), parent > 2-F ≫ 6-F; β2-activity (relaxation of guinea pig tracheal strip), 2-F > parent ≫ 6-F. The affinity of the 2-fluoro analogue for β1-adrenergic receptors (inhibition of the specific binding of [3H]dihydroalprenolol, rat cerebral cortical membranes) was 2 times greater, while the 6-fluoro analogue was 1450 times less than the parent. These results suggest that the aromatic rings of phenoxypropanolamine adrenergic agonists and phenylethanolamine adrenergic agonists bind in similar fashion to the adrenergic receptor, and that if interactions between fluorine and the side-chain hydroxyl group are critical in defining β-adrenergic selectivity, the interactions are similar in both phenoxypropanolamines and phenylethanolamines.

Original languageEnglish (US)
Pages (from-to)1063-1068
Number of pages6
JournalJournal of Medicinal Chemistry
Volume34
Issue number3
StatePublished - 1991
Externally publishedYes

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Phenoxypropanolamines
Adrenergic Agonists
2-Propanol
Fluorine
Adrenergic Agents
Substitution reactions
Adrenergic Receptors
Guinea Pigs
Dihydroalprenolol
Glioma
Hydroxyl Radical
Cyclic AMP
Rats
Derivatives
Membranes

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Adejare, A., Nie, J. Y., Hebel, D., Brackett, L. E., Choi, O., Gusovsky, F., ... Kirk, K. L. (1991). Effect of fluorine substitution on the adrenergic properties of 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol. Journal of Medicinal Chemistry, 34(3), 1063-1068.

Effect of fluorine substitution on the adrenergic properties of 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol. / Adejare, Adeboye; Nie, Jun Ying; Hebel, David; Brackett, L. Ellen; Choi, Oksoon; Gusovsky, Fabian; Padgett, William L.; Daly, John W.; Creveling, Cyrus R.; Kirk, Kenneth L.

In: Journal of Medicinal Chemistry, Vol. 34, No. 3, 1991, p. 1063-1068.

Research output: Contribution to journalArticle

Adejare, A, Nie, JY, Hebel, D, Brackett, LE, Choi, O, Gusovsky, F, Padgett, WL, Daly, JW, Creveling, CR & Kirk, KL 1991, 'Effect of fluorine substitution on the adrenergic properties of 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol', Journal of Medicinal Chemistry, vol. 34, no. 3, pp. 1063-1068.
Adejare, Adeboye ; Nie, Jun Ying ; Hebel, David ; Brackett, L. Ellen ; Choi, Oksoon ; Gusovsky, Fabian ; Padgett, William L. ; Daly, John W. ; Creveling, Cyrus R. ; Kirk, Kenneth L. / Effect of fluorine substitution on the adrenergic properties of 3-(tert-butylamino)-1-(3,4-dihydroxyphenoxy)-2-propanol. In: Journal of Medicinal Chemistry. 1991 ; Vol. 34, No. 3. pp. 1063-1068.
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AU - Hebel, David

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AU - Choi, Oksoon

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AU - Padgett, William L.

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