Importance of the aromatic ring in adrenergic amines. 8. 2-(Aminomethyl)-trans-2-decalols as inhibitors of norepinephrine N-methyltransferase

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Abstract
In an effort to determine the surface appearance of the hydrophobic ring binding region of the norepinephrine N-methyltransferase active site, some trans-decalin analog of 1-(aminomethyl)cycloundecanol (1), a potent NMT [norepinephrine N-methyltransferase] inhibitor were employed. These analog [axial and equatorial 2-(aminomethyl)-trans-2-decalol, 2 and 3] closely resemble a low energy crown conformation of 1. Both compounds were as potent as 1 at inhibiting bovine adrenal NMT (Ki [inhibition constant] = 3.6, 5.6 and 3.8 .mu.M for 1, 2, and 3, respectively), indicating that this conformation is most likely adopted within the active site in order to optimize contact with a flat hydrophobic area. None of the compounds showed significant substrate activity for NMT, a fact that is consistent with our proposed active site binding model.