Targacept, Inc.

Attenua, Inc.

Philip S Hammond

Scott R Breining

Yun-De Xiao

Anatoly A Mazurov

Balwinder Singh Bhatti

Craig Harrison Miller

Lan Miao

Srinivasa Rao Akireddy

Jozef Klucik

Matt S Melvin

Srinivasa V Murthy

Regina C Whitaker

Srinivisa Rao Akireddy

Gary Maurice Dull

Julio A Munoz

Daniel Yohannes

Yunde Xiao

John Genus

Timothy J Cuthbertson

Pieter Albert Otten

Nikolai Fedorov

Gregory J Gatto

Joesph Pike Mitchener, Jr

V Srinivasa Murthy

Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are amide compounds which can be prepared from certain heteroaryl carboxylic acids and certain diazabicycloalkanes. The compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the &#x3b1;4&#x3b2;2 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly CNS disorders. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g. side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle).

Nicotinic acetylcholine receptor sub-type selective amides of diazabicycloalkanes

The present invention relates to (R)-3-((E)-2-(pyrrolidin-3-yl)vinyl)-5-(tetrahydropyran-4-yloxy)pyridine, its salt forms, and to processes for the commercial-scale production of these compounds in sufficient purity and quality for use in pharmaceutical compositions.

Synthesis and novel salt forms of (R)-3-((E)-pyrrolidin-3-yl)vinyl)-5-tetrahydropyran-4-yloxy)pyridine

Sub-type selective amides of diazabicycloalkanes

Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are amide, ketone, and ester compounds prepared from certain azabicycloalkane carboxylic acids. The resulting compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the &#x3b1;4&#x3b2;2 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, such as those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and/or prevented. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g. side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle).

Sub-type selective azabicycloalkane derivatives

Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are N-aryl or heteroaryl azaspiroalkene/alkane compounds, prodrugs or metabolites of these compounds, or pharmaceutically acceptable salts thereof. The aryl group can be a phenyl ring or a five- or six-membered heterocyclic ring (heteroaryl). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and/or prevented. The compounds and compositions can also be used to alleviate pain. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).

N-aryl azaspiroalkene and azaspiroalkane compounds and methods of preparation and use thereof

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Pinnacle, NC, United States of America

Philip S Hammond