Guilford Pharmaceuticals, Inc.

Scios Nova, Inc.

Marion Merrell Dow Inc.

Kenneth J Natalie, Jr

Waclaw J Rzeszotarski

Ronald H Erickson

Michael J Pontecorvo

Maria E Guzewska

Ciro J Spagnuolo

Daniel W McPherson

Sigma binding site agents having the formula ##STR1## wherein A.sup.1, A.sup.2, A.sup.3, B, y and 2 are defined in the specification, W is halogen, which are novel intermediates useful in preparing the presently binding site agents.

Intermediates for making sigma binding site agents

Sigma binding site agents having the formula ##STR1## which are useful to inhibit sigma binding site-induced activity, pharmaceutical compositions including these agents, and methods of using these agents to inhibit sigma binding site-induced activity in mammals. Also disclosed are novel intermediates useful in preparing the presently invented agents.

Sigma binding site agents

1-Phenyl-7-substituted-hept-5-yn-2-ones substituted with a C.sub.1 to C.sub.7 alkyl, C.sub.3 to C.sub.6 cycloalkyl, aryl, heteroaryl or heterocycloalkyl group at the 1-position and an amino, a dialkylamino, a piperidyl, a pyrrolidyl or a hexahydroazepinyl group at the 7-position are disclosed which may have one or two substituents in addition to the phenyl group at the 1-position and also may have a p-fluoro substituent on the phenyl group. The preferred compounds are, 1-cyclohexyl-1-phenyl-1-hydroxy-7-dimethylaminohept-5-yn-2-one, 1-cyclobutyl-1-phenyl-1-hydroxy-7-dimethylaminohept-5-yn-2-one and 1-cyclo-1-phenyl-1-hydroxy-7-ethylaminohept-5-yn-2-one. The compounds are highly specific M.sub.1 -AChR antagonists with relatively prolonged duration of activity. They are particularly useful in the treatment of neurogenic bladder disorders and may be administered orally or parenterally in conventional formulations containing optional conventional additives such as binders, surfactants, emulsifiers, flavorants, preservatives and the like.

1,7-substituted heptyn-2-ones and use

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Baltimore, MD, United States of America

Kenneth J Natalie, Jr