公开(公告)号：EP2139857A1

公开(公告)日：2010-01-06

申请号：EP08732913.2

申请日：2008-03-27

申请人： Targacept Inc.

发明人： HAMMOND, Philip, S. ,  MAZUROV, Anatoly, A. ,  XIAO, Yun-De ,  MURTHY, Srinivasa, V. ,  AKIREDDY, Srinivasa, Rao

IPC分类号： C07D209/52 ,  C07D221/22 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D405/06 ,  C07D405/12 ,  C07D413/06 ,  A61K31/403 ,  A61K31/439 ,  A61K31/4439 ,  A61K31/5355 ,  A61K31/541 ,  A61P25/00

CPC分类号： C07D209/52 ,  C07D221/22 ,  C07D401/06 ,  C07D401/12 ,  C07D403/06 ,  C07D405/06 ,  C07D405/12 ,  C07D413/06

摘要： 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 a4ß2 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).

公开(公告)号：EP1594869B9

公开(公告)日：2009-04-01

申请号：EP04713356.6

申请日：2004-02-20

申请人： Targacept, Inc.

发明人： MAZUROV, Anatoly, A. ,  KLUCIK, Jozef ,  MIAO, Lan ,  SEAMANS, Angela, S. ,  PHILLIPS, Teresa, Youngpeter ,  SCHMITT, Jeffrey, Daniel ,  MILLER, Craig, Harrison

IPC分类号： C07D453/00 ,  C07D453/02

CPC分类号： C07D471/08 ,  A61K51/0455 ,  C07D453/02 ,  C07D487/08

摘要： 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 C1-4 alkyl. 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 a7 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.

公开(公告)号：EP1594869B1

公开(公告)日：2007-12-19

申请号：EP04713356.6

申请日：2004-02-20

申请人： Targacept, Inc.

发明人： MAZUROV, Anatoly, A. ,  KLUCIK, Jozef ,  MIAO, Lan ,  SEAMANS, Angela, S. ,  PHILLIPS, Teresa, Youngpeter ,  SCHMITT, Jeffrey, Daniel ,  MILLER, Craig, Harrison

IPC分类号： C07D453/00 ,  C07D453/02

CPC分类号： C07D471/08 ,  A61K51/0455 ,  C07D453/02 ,  C07D487/08

摘要： 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 C1-4 alkyl. 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 a7 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.

公开(公告)号：EP1594869A2

公开(公告)日：2005-11-16

申请号：EP04713356.6

申请日：2004-02-20

申请人： Targacept, Inc.

发明人： MAZUROV, Anatoly, A. ,  KLUCIK, Jozef ,  MIAO, Lan ,  SEAMANS, Angela, S. ,  PHILLIPS, Teresa, Youngpeter ,  SCHMITT, Jeffrey, Daniel ,  MILLER, Craig, Harrison

IPC分类号： C07D453/00 ,  C07D453/02

CPC分类号： C07D471/08 ,  A61K51/0455 ,  C07D453/02 ,  C07D487/08

摘要： 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 C1-4 alkyl. 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 a7 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.