In a search for inhibitors of epinephrine biosynthesis as potential therapeutic agents, a series of 13 ring-chlorinated 1,2,3,4-tetrahydroisoquinolines was prepared. These compounds were tested initially for their ability to inhibit rabbit adrenal phenylethanolamine N-methyltransferase (PNMT) in vitro. Enzyme-inhibitor dissociation constants, determined for the six most potent members of the series, indicated the following order of decreasing potency: 7,8-Cl2 greater than 6,7,8-Cl3 greater than 7-Cl approximately 5,6,7,8-Cl4 greater than 5,7,8-Cl3. These compounds were subsequently examined for PNMT-inhibiting activity in intact rats and mice. 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline (13, SK&F 64139) was the most potent member of the series both in vitro and in vivo and is currently undergoing clinical investigation.

No abstract

Die Isochinoline (I) werden durch katalytische Hydrierung oder mit überschüssigem Diboran in Tetrahydrofuran zu den Tetrahydroisochinolinen (II) reduziert.

because the ortho aromatic protons of some compounds are found several cps (15-40) upfield with respect to the other (meta and para) protons.In fact, when the shielded ortho protons belong to 1,2disubstituted central ring-i.e., Table V: compounds 3-5the four central nuclear protons show the characteristic

Die aus den Aminoguanidinen (I) und Aceton (II) in Gegenwart von Natriumhydrid dargestellten Verbindungen (III) liefern mit den Isothiocyanaten (IV) die Isopropylidenamino‐amidino‐thioharnstoffe (V ), die sich durch Erhitzen mit Natronlauge oder Essigsäure zu den 1,2,4‐Triazolen (VI) cyclisieren lassen.