Miles Laboratories, Inc.

David L Leland

Michael P Kotick

Joseph O Polazzi

Robert N Schut

Disclosed are 7.beta.-arylalkyl substituted morphinan compounds characterized by the formula: ##STR1## In the above formula, R is H or methyl, R.sub.1 is methyl, cyclopropylmethyl or cyclobutylmethyl and n is 2 to 5.

7.beta.-Arylalkyl-6.alpha., 7 .alpha.-oxymethylene-3-methoxy or

Disclosed are 7.beta.-alkyl or arylalkyl-3-methoxy or hydroxy-4,5.alpha.-epoxy-6.beta.-hydroxy-7.alpha.-hydroxymethyl-17-methyl or cycloalkylmethylmorphinans of the formula: ##STR1## In the above formula, R is H or methyl, R.sub.1 is methyl, cyclopropylmethyl or cyclobutylmethyl, n is 2 to 4 and Y is H or phenyl. These compounds are useful as narcotic analgesics.

7.beta.-Arylalkyl-3-methoxy or

Disclosed are 7.beta.-arylalkyl-7.alpha.-methyl-6-oxo or 6.alpha.-hydroxy-3-methoxy or 3-hydroxy-4,5.alpha.-epoxy-17-methyl or 17-cycloalkylmethyl-morphinans of the formula: ##STR1## wherein R is H or methyl, X is oxo or .alpha.-hydroxy, n is 2 to 4 and R.sub.1 is methyl, cyclopropylmethyl or cyclobutylmethyl. These compounds are useful as strong analgesics.

7.beta.-Arylalkyl-7.alpha.-methyl-6-oxo or 6.alpha.-hydroxy-3-methoxy or

Disclosed are 7,7-dimethyl-4,5.alpha.-epoxy-morphinan-6-one compounds characterized by the formula: ##STR1## wherein R is H or CH.sub.3, R.sub.1 is H, CH.sub.3 or CH.sub.2 CH.sub.3 and R.sub.2 is cyclopropylmethyl or cyclobutylmethyl. Particular compounds circumscribed by the foregoing formula are useful as analgesics, narcotic antagonists or mixed analgesics/narcotic antagonists.

7,7-Ditosyloxymethyl-4,5.alpha.-epoxy-morphinan-6-ols

Disclosed are 7,8 and 7-8 substituted 4,5.alpha.-epoxymorphinan-6-one compounds characterized by the structural formula: ##STR1## In the foregoing formula R.sub.1 may be H or methyl, R.sub.2 is cyclopropylmethyl, cyclobutylmethyl, allyl or tetrahydrofurfuryl, R.sub.3 is H, .beta.-methyl, .beta.-ethyl or .alpha.-ethyl and R.sub.4 is H or .alpha.-methyl. Particular compounds corresponding to the foregoing description are useful as mixed analgesics/narcotic antagonists whereas others have been found to be pure narcotic antagonists.

7,8 and 7-8 Substituted 4,5.alpha.-epoxymorphinan-6-one compounds, and

Disclosed is a novel method for the introduction of a 7-methyl group into the morphinan nucleus to thereby provide precursors for the preparation of therapeutically useful 7-methyl-4,5.alpha.-epoxy morphinan and morphinan-6-one compounds. The method involves reacting thebaine, dihydrothebaine or the enol acetate of dihydrocodeinone with lithium dimethyl cuprate to form the corresponding 7-methyl-4,5.alpha.-epoxy cleaved product.

Method for the introduction of a methyl group into the 7 position of the

Disclosed are 7-methyl, 8.beta.-lower alkyl and 7 methyl-8-lower alkyl substituted B/C Cis or Trans morphinan-6-one compounds characterized by the structural formula: ##STR1## Specific compounds, included within the scope of the foregoing general formula wherein R.sub.1 is H or methyl, R.sub.2 is cyclopropylmethyl or cyclobutylmethyl, R.sub.3 is H, methyl, ethyl or n-propyl and R.sub.4 is H or methyl are useful as mixed analgesics/narcotic antagonists.

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Elkhart, IN, United States of America

David L Leland