Eli Lilly and Company

Shionogi Company Limited

William H Lunn

J Jeffry Howbert

Robert F Bruns, Jr

Donald R Gehlert

William J Wheeler

Paul Leslie Ornstein

David Kent Herron

Darryle D Schoepp

Robert Theodore Vasileff

Lawrence J Heinz

John Kevin Shadle

Bruce D Gitter

M Brian Arnold

Nancy K Augenstein

Dennis Michael Zimmerman

Wataru Nagata

Yoshio Hamashima

James Allen Monn

Teruji Tsuji

Edward V Mason

This invention discloses novel piperidine tetrazole compounds which are selective antagonists of EAA receptors particularly the NMDA receptors. The invention also provides formulations of the preferred compounds and for methods of using the compounds to treat various disorders associated with neuronal excitotoxicity.

NMDA receptor selective antagonists

The present invention provides novel compounds that affect excitatory amino acid receptors and are useful in the treatment of neurological disorders. This invention also provides synthetic methods for the preparation of the novel compounds.

Excitatory amino acid receptor antagonists

This invention provides novel decahydroisoquinoline compounds which are useful as excitatory amino acid receptor antagonists and in the treatment of neurological disorders. This invention also provides synthetic methods for preparing decahydroisoquinolines, as well as, novel intermediates in the synthesis thereof.

This invention provides methods for treating or preventing a condition associated with an excess of neuropeptide Y which methods comprise administration of one or more substituted benzofurans, benzothiophenes or indoles.

Heterocyclic neuropeptide Y receptor antagonists

A method of inhibiting the physiological disorder anxiety associated with an excess of neuropeptide Y or its symptoms comprising administering to a human in need thereof an effective amount of a compound having the formula ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

Method of treating anxiety by inhibiting physiological conditions

A method of inhibiting a physiological disorder associated with an excess of neuropeptide Y or its symptoms comprising administering to a human in need thereof an effective amount of a compound having the formula ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, --CH.sub.3, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

Methods of treating depression by inhibiting physiological conditions

A method of inhibiting obesity, a physiological disorder associated with an excess of neuropeptide Y, or its symptoms comprising administering to a human in need thereof an effective amount of a compound having the formula ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, --CH.sub.3, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

Methods of treating obesity by inhibiting physiological conditions

This invention provides substituted benzimidazoles which are useful in treating or preventing conditions associated with .beta.-amyloid peptide. Some such conditions associated with .beta.-amyloid peptide include Alzheimer's Disease, Down's Syndrome and amyloidosis of the Dutch type.

Methods for treating a physiological disorder associated with

A method of inhibiting a physiological condition associated with an excess of bradykinin comprising administering to a human in need thereof an effective amount of a compound having the formula ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, --CH.sub.3, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

Methods of inhibiting physiological conditions associated with an excess

This invention encompasses methods for the treatment or prevention of a physiological disorder associated with an excess of tachykinins, which method comprises administering to a mammal in need of said treatment an effective amount of a compound of Formula I ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamthylenemino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

Non-peptide tachykinin receptor antagonists to treat psycological

This invention provides methods of treating a physiological disorder associated with an excess of bradykinins in a mammal which comprises administering to a mammal in need of said treatment a compound selected from a series of substituted dihydronaphthalenes and naphthalenes.

Naphthyl bradykinin receptor antagonists

A method of inhibiting a physiological disorder associated with an excess of neuropeptide Y or its symptoms comprising administering to a human in need thereof an effective amount of a compound having the formula ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamethyleneamino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

Use of bengothiophenls to treat pain due to an excess of neuropeptide y

This invention encompasses methods for the treatment or prevention of a physiological disorder associated with an excess of tachykinins, said disorder being an allergy which method comprises administering to a mammal in need of said treatment an effective amount of a compound of Formula I ##STR1## wherein R.sup.1 and R.sup.3 are independently hydrogen, --CH.sub.3, ##STR2## wherein Ar is optionally substituted phenyl; R.sup.2 is selected from the group consisting of pyrrolidine, hexamthylenemino, and piperidino; or a pharmaceutically acceptable salt of solvate thereof.

Non-peptide tachykinin receptor antagonists to treat allergy

This invention provides methods of treating a physiological disorder associated with an excess of tachykinins in a mammal which comprises administering to a mammal in need of said treatment a compound selected from a series of substituted dihydronaphthalenes and naphthalenes.

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Indianapolis, IN, United States of America

William H Lunn