E.i. Dupont De Nemours and Company

The Dupont Merck Pharmaceutical Company

Engelbert Ciganek

Ashokkumar Bhikkappa Shenvi

Sang W Tam

Leonard Cook

Ann S Wright

Bet-key Wong

There are described novel (N-phthalimidoalkyl) piperidine compounds which exhibit selective sigma-receptor antagonism and therefore are useful in the treatment of physiological or drug induced psychosis and dyskinesia in a mammal. Also described are pharmaceutical compositions containing sigma selective compounds and methods of using these compositions for treating physiological or drug induced psychosis or dyskinesia in a mammal. Further provided are methods for preparing the compounds of this invention.

(N-phthalimidoalkyl)piperidines

There are provided novel nitrogen-containing bicyclic compounds which are useful in the treatment of physiological or drug induced psychosis or dyskinesia in a mammal. These novel compounds are selective sigma receptor antagonists and have a low potential for movement disorder side effects associated with typical antipsychotic agents.

Hydroisoindolines and hydroisoquinolines as psychotropic drugs

There is described novel (N-phthalimidoalkyl) piperidine compounds which exhibit selective sigma-receptor antagonism and therefore are useful in the treatment of physiological or drug induced psychosis and dyskinesia in a mammal. Also described are pharmaceutical compositions containing sigma selective compounds and methods of using these compositions for treating physiological or drug induced psychosis or dyskinesia in a mammal. Further provided are methods for preparing the compounds of this invention.

(N-phthalimidoalkyl) piperidines useful as treatments for psychosis

This invention relates to a novel process for the preparation of tertiary carbinamines by double addition of organolanthanide reagents, especially organocerium reagents, to nitriles. It further relates to the preparation of such amines by the addition of organolanthanide reagents to imines.

Process for the preparation of tertiary carbinamines

There are provided nitrogen-containing bicyclic compounds which are useful in the treatment of physiological or drug induced psychosis or dyskinesia in a mammal. These novel compounds are selective sigma receptor antagonists and have a low potential for movement disorder side effects associated with typical antipsychotic agents.

Hydroisoindolines and hydroisoquinolines as psychotropic

Known and novel 4-aryl-4-piperidinecarbinols and heterocyclic analogs are useful as analgesics. Also provided are novel pyrrolidinecarbinols and hexahydroazepine carbinols which are useful as analgesics, antidepressants and, in some cases, as anorectic agents.

4-aryl-4-piperidine (or pyrrolidine or hexahydroazepine) carbinols and

Known and novel 4-aryl-4-piperidinecarbinols and heterocyclic analogs are useful as analgesics. Also provided are novel pyrrolidinecarbinols and hexhydroazepine carbinols which are useful as analgesics, antidepressants and, in some cases, as anorectic agents.

Alkoxyalkyl and alkylmercaptoalkyl substituted bridged benzofuroisoquinolines have opioid antagonist, and/or appetite-controlling properties. Preferred compounds are kappa receptor selective antagonists. Examples of such preferred compounds are 5-Methoxymethyl-3-n-propyl- 1,2,3,4,5,6,7,7a-octahydro-4a,7-ethanobenzofuro[3,2-e]isoquinolin-9-ol and 3-Cyclopropylmethyl-5-methoxymethyl-1,2,3,4,5,6,7,7a-octahydro-4a,7-ethano benzofuro[3,2-e]isoquinoline-9-ol.

Alkoxyalkyl and alkylmercaptoalkyl substituted bridged

Imide intermediates for the preparation of analgesic and/or antagonist octahydrobenzofuro[3,2-e]-isoquinolines and octahydro-4a,7-ethano- and ethenobenzofuro[3,2-e]isoquinolines and processes for their preparation are provided. These imides have a formula selected from the group consisting of: ##STR1##

Imide intermediates for the preparation of analgesic and/or antagonist

Process for preparing analgesic and narcotic antagonistic isoquinolines comprising:

Intermediates for octahydrobenzofuro[3,2-e]isoquinolines

4-Aryl-4-piperidinecarbinols, for example, ##STR1## useful as antidepressants and, in some cases, as anorectic agents.

4-Aryl-4-piperidinecarbinols

Novel bridged benzofuroisoquinoline compounds having analgesic, narcotic antagonist and anorexigenic properties.

Octahydro-4A,7-ethano- and -etheno-benzofuro[3,2-e]isoquinoline

Certain tetrahydropyridine intermediates

Octahydro-1H-benzo[4,5]furo[3,2-e]isoquinoline compounds and processes for their manufacture are provided. The compounds correspond to the formula ##STR1## These compounds exhibit both analgesic and narcotic antagonistic properties, as well as low abuse liability. Novel intermediate compounds are also provided which have the formula ##STR2##

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Engelbert Ciganek