公开(公告)号：EP2284171B1

公开(公告)日：2012-02-15

申请号：EP10075738.4

申请日：2007-11-01

申请人： Targacept, Inc.

发明人： Mazurov, Anatoly ,  Miao, Lan ,  Xiao, Yun-de ,  Hammond, Philip S. ,  Miller, Craig H. ,  Akireddy, Srinivasa Rao ,  Murthy, V Srinivasa ,  Whitaker, Regina C. ,  Breining, Scott R. ,  Melvin, Matt S.

IPC分类号： C07D471/08 ,  A61P25/00 ,  A61K31/407 ,  C07D487/04

CPC分类号： C07D487/04 ,  C07D471/08

公开(公告)号：EP2284171A1

公开(公告)日：2011-02-16

申请号：EP10075738.4

申请日：2007-11-01

申请人： Targacept, Inc.

发明人： Mazurov, Anatoly ,  Miao, Lan ,  Xiao, Yun-de ,  Hammond, Philip S. ,  Miller, Craig H. ,  Akireddy, Srinivasa Rao ,  Murthy, V Srinivasa ,  Whitaker, Regina C. ,  Breining, Scott R. ,  Melvin, Matt S.

IPC分类号： C07D471/08 ,  A61P25/00 ,  A61K31/407 ,  C07D487/04

CPC分类号： C07D487/04 ,  C07D471/08

摘要： 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 heteroraryl carboxylic acids and certain diazabicycloalkanes. The 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, 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).
Formula I:

wherein n has the value of 0 or 1, and
Cy is a heteroaryl group chosen from the group of 2-furanyl, 3-furanyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 1,3,4-oxadiazol-2-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 1,3,4-thiadiazol-2-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl and 4-pyridinyl.

摘要翻译： 公开了化合物，包括该化合物的药物组合物，及其制备方法和用途。 这些化合物是可以由某些杂芳基羧酸和某些二氮杂双环烷烃制备的酰胺化合物。 该化合物对中枢神经系统（CNS）中a4ss2亚型的神经元烟碱受体表现出选择性并且以高亲和力结合。 化合物和组合物可用于治疗和/或预防多种病症或病症，特别是CNS疾病。 化合物可以：（i）改变患者脑部烟碱型胆碱能受体的数量，（ii）表现出神经保护作用，和（iii）当以有效量使用时，不会产生明显的不良副作用 因为血压和心率的显着增加，对胃肠道的显着的负面影响和对骨骼肌的显着影响）。 式I：其中n具有0或1的值，Cy是选自2-呋喃基，3-呋喃基，2-恶唑基，4-恶唑基，5-恶唑基，3-异恶唑基，4-恶唑基， 异恶唑基，5-异恶唑基，1,3,4-恶二唑-2-基，1,2,4-恶二唑-3-基，1,2,4-恶二唑-5-基，2-噻唑基，4-噻唑基， 5-噻唑基，3-异噻唑基，4-异噻唑基，5-异噻唑基，1,3,4-噻二唑-2-基，1,2,4-噻二唑-3-基，1,2,4-噻二唑-5-基， 吡啶基和4-吡啶基。

公开(公告)号：EP2357174A1

公开(公告)日：2011-08-17

申请号：EP11150475.9

申请日：2007-05-08

申请人： AstraZeneca AB ,  Targacept, Inc.

发明人： Bohlin, Martin Hans ,  Dull, Gary M. ,  Eriksson, Caroline ,  Miller, Craig H. ,  Munoz, Julio A. ,  Sebhatu, Tesfai

IPC分类号： C07D213/65 ,  A61K31/44 ,  A61P25/00

CPC分类号： C07D213/65

摘要： Phosphoric acid, edisylic acid (1,2-ethanedisulfonic acid), citric acid, orotic acid (uracil-6-carboxylic acid), R-mandelic acid, sulfuric acid, 1,5-naphthalenedisulfonic acid, D-aspartic acid, and lysine monohydrochloride salts of (2S)-(4E)-N-methyl-5-[3-(5-isopropoxypyridin)yl]-4-penten-2-amine, and methods for their preparation, pharmaceutical compositions comprising said salts, and use, are disclosed. The salts can be administered to patients susceptible to or suffering from conditions and disorders, such as central nervous system disorders, to treat and/or prevent such disorders.

摘要翻译： 磷酸，乙二酸（1,2-乙烷二磺酸），柠檬酸，乳清酸（尿嘧啶-6-羧酸），R-扁桃酸，硫酸，1,5-萘二磺酸，D-天冬氨酸和赖氨酸 （2S） - （4E）-N-甲基-5- [3-（5-异丙氧基吡啶）基] -4-戊烯-2-胺的单盐酸盐及其制备方法，包含所述盐的药物组合物和使用 ，被披露。 盐可以施用于易患或患有诸如中枢神经系统疾病的病症和障碍的患者，以治疗和/或预防这些疾病。

公开(公告)号：EP2078718A1

公开(公告)日：2009-07-15

申请号：EP09004359.7

申请日：2003-06-27

申请人： Targacept, Inc.

发明人： Bhatti, Balwinder S. ,  Miller, Craig H. ,  Schmitt, Jeffrey D.

IPC分类号： C07D453/02 ,  C07D487/20 ,  A61K31/409 ,  A61P29/00

CPC分类号： C07D487/20 ,  C07D453/02 ,  C07D471/10 ,  C07D471/20 ,  C07D487/10

摘要： Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are bridged analogues of N-heteroaryl diazaspirocyclic compounds, or prodrugs or metabolites of these compounds. The aryl group can be 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 in the brain of the patient, (ii) exhibit neuroprotective effects and (iii) when employed in effective amounts, not result in appreciable 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).

摘要翻译： 化合物，药物组合物，包括化合物，和制备方法以及它们的使用是游离缺失光盘。 这些化合物是桥连的N-杂环芳基化合物diazaspirocyclic或前药或合成化合物的代谢物的类似物。 所述芳基可以是一个五元或六元杂环（杂芳基）。 化合物和组合物可用于治疗和/或预防多种病症或障碍，特别是由烟碱性胆碱能神经传递功能障碍为特征的那些疾病，包括病症涉及神经递质释放的神经调节，：如多巴胺释放。 CNS障碍，其在正常神经递质释放上改变其特点，是紊乱的另一实施例也可以治疗和/或预防。 化合物和组合物因此可用于缓解疼痛。 化合物可以（ⅰ）改变烟碱性胆碱能受体的数目在患者的脑，（II）显示出神经保护作用和（iii）当以有效量使用，不会导致明显的副作用（例如副作用：如显著增加 率血压和心脏，对胃肠道显著的负面影响，以及对骨骼肌的显著效果）。