Organic compounds -- part of the class 532-570 series – Organic compounds – Nitriles
Patent
1988-03-14
1989-08-08
Brust, Joseph Paul
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitriles
558332, 558350, 564389, C07C12000, C07C12166
Patent
active
048554766
ABSTRACT:
The present invention relates to novel 5-fluoro- and 8-fluoro-trimetoquinol compounds of the general formula I wherein X.sub.1 =F, X.sub.2 =H or X.sub.1 =H, X.sub.2 =F ##STR1## The present invention also relates to a process for making the 5-fluoro- and 8-fluoro-trimetoquinol compounds by condensation of an appropriately substituted phenethylamine to afford an appropriately substituted phenlethylacetamide compound. The amides are cyclized to give appropriately substituted intermediate dihydroisoquinolines. Without isolation, the dihydroisoquinolines are reduced to give appropriately substituted tetrahydroisoquinolines. The hydrochloride salts of tetrahydroisoquinolines are prepared and subjected to hydrogenolysis, to give the fluorine substituted trimetoquinol compounds of the present invention. The present invention also encompasses the preparation of the phenethylamines by reducing appropriately substituted benzylcyanides and to the preparation of an intermediate benzylcyanide compound by converting a fluorine substituted methoxyphenol compound, under aminomethylation conditions into a N-N-dimethyl-4-hydroxy-3-methoxy-5-fluorobenzylamine. The benzylamine is converted to benzylnitrile and a functional group shuffle is carried out which yields the appropriately substituted benzylcyanide compound. In a composition aspect, the present invention encompasses novel pharmaceutical compositions comprising a compound of the formula I, together with a physiologically acceptable carrier or excipient, in an amount sufficient to increase .beta..sub.2 -adrenergic and antithrombotic activities while simultaneously decreasing the .beta..sub.1 -adrenergic activity in mammals, including humans. The compounds of the invention are useful in the treatment of pulmonary, cardiovascular or thromboembolic disorders.
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Adejare Adeboye
Clark Michael T.
Feller Dennis R.
Miller Duane D.
Romstedt Karl J.
Brust Joseph Paul
Ohio State University Research Foundation
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