Targacept, Inc.

Other

Jozef Klucik

Anatoly A Mazurov

Lan Miao

Craig Harrison Miller

Jeffrey Daniel Schmitt

Teresa Phillips

Angela S Seamans

Balwinder Singh Bhatti

Scott R Breining

Philip S Hammond

Yun-De Xiao

The present invention relates to pharmaceutical compositions incorporating compounds capable of affecting nicotinic acetylcholinergic receptors (nAChRs), for example, as modulators of specific nicotinic receptor subtypes (specifically, the &#x3b1;nAChR subtype). The present invention also relates to methods for treating a wide variety of conditions and disorders, particularly those associated with dysfunction of the central and autonomic nervous systems.

3-Substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof

The present invention relates to pharmaceutical compositions incorporating compounds capable of affecting nicotinic acetylcholinergic receptors (nAChRs), for example, as modulators of specific nicotinic receptor subtypes (specifically, the &#x3b1;7 nAChR subtype). The present invention also relates to methods for treating a wide variety of conditions and disorders, particularly those associated with dysfunction of the central and autonomic nervous systems.

3-substituted-2(arylalkyl)-1-azabicycloalkanes and methods of use thereof

The present invention relates to the pharmaceutical compositions incorporating compounds capable of affecting nicotinic acetylcholinergic receptors (nAChRs), for example, as modulators of specific nicotinic receptor subtypes (specifically, the &#x3b1;7 nAChR subtype). The present invention also relates to methods for treating a wide variety of conditions and disorders, particularly those associated with dysfunction of the central and autonomic nervous systems.

The present invention relates to 3-substituted-2-(arylalkyl)-1-azabicycloalkanes, methods of preparing the compounds, and methods of treatment using the compounds. The azabicycloalkanes generally are azabicycloheptanes, azabicyclooctanes, or azabicyclononanes. The compounds exhibit activity at nicotinic acetylcholine receptors (nAChRs), particularly the &#x3b1;7 nAChR subtype, and are useful towards modulating neurotransmission and the release of ligands involved in neurotransmission. Methods for preventing or treating conditions and disorders, including central nervous system (CNS) disorders, which are characterized by an alteration in normal neurotransmission, are also disclosed. Also disclosed are methods for treating inflammation, autoimmune disorders, pain and excess neovascularization, such as that associated with tumor growth.

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

The present invention relates to amide and urea derivatives of heteroaryl-substituted diazatricycloalkanes, pharmaceutical compositions including the compounds, methods of preparing the compounds, and methods of treatment using the compounds. More specifically, the methods of treatment involve modulating the activity of the &#x3b1;7 nAChR subtype by administering one or more of the compounds to treat or prevent disorders mediated by the &#x3b1;7 nAChR subtype. The diazatricycloalkanes typically consist of a 1-azabicyclooctane fused to pyrrolidine ring. The substitutent heteroaryl groups are 5- or 6-membered ring heteroaromatics, such as 3-pyridinyl and 5-pyrimidinyl moieties, which are attached directly to the diazatricycloalkane. The secondary nitrogen of the pyrrolidine moiety is substituted with an arylcarbonyl (amide type derivative) or an arylaminocarbonyl (N-arylcarbamoyl) (urea type derivative) group. The compounds are beneficial in therapeutic applications requiring a selective interaction at certain nAChR subtypes. That is, the compounds modulate the activity of certain nAChR subtypes, particularly the &#x3b1;7 nAChR subtype, and do not have appreciable activity toward muscarinic receptors. Radiolabeled versions of the compounds can be used in diagnostic methods.

Heteroaryl-substituted diazatricycloalkanes and methods of use thereof

The present invention relates to 3-substituted-2-(arylalkyl)-1-azabicycloalkanes, methods of preparing the compounds and methods of treatment using the compounds. The azabicycloalkanes generally are azabicycloheptanes, azabicyclooctanes, or azabicyclononanes. The aryl group in the arylalkyl moiety is a 5- or 6-membered ring heteroaromatic, preferably 3-pyridinyl and 5-pyrimidinyl moieties, and the alkyl group is typically a Calkyl. The substituent at the 3-position of the 1-azabicycloalkane is a carbonyl group-containing moiety, such as an amide, carbamate, urea, thioamide, thiocarbamate, thiourea or similar functionality. The compounds exhibit activity at nicotinic acetylcholine receptors (nAChRs), particularly the &#x3b1;7 nAChR subtype, and are useful towards modulating neurotransmission and the release of ligands involved in neurotransmission. Methods for preventing or treating conditions and disorders, including central nervous system (CNS) disorders, which are characterized by an alteration in normal neurotransmission, are also disclosed. Also disclosed are methods for treating inflammation, autoimmune disorders, pain and excess neovascularization, such as that associated with tumor growth.

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Marietta, GA, United States of America

Jozef Klucik