Synthesis and adrenergic properties of cyclic analogues of methoxamine: 2-amino-1-arylcyclohexanols and 2-amino-1,2,3,4-tetrahydro-1-naphthalenols

Abstract

The synthesis, conformational study, α-stimulant, and β-blocking activities of cis- and trans-2-amino-1-arylcyclohexanols 4–7 and cis- and trans-2-amino-1,2,3,4-tetrahydro-1-naphthalenols 8–11 are described. These compounds can be considered as conformationally restrained analogues of methoxamine, isopropylmethoxamine, and their demethoxylated derivatives. 1H NMR data indicate that, in the 2-amino-1-arylcyclohexanol series, Ar and NHR groups hold a gauche relationship, which could account for their lack of α-agonist and β-blocking properties. Among the 2-aminonaphthalenols, only cis- and trans- 10 showed α-agonist activities, although lower than that of methoxamine. These compounds were completely devoid of β-blocking properties. These results can be correlated with the conformation in solution found by 1H NMR for the above aminotetralols.