公开(公告)号：US20100197699A1

公开(公告)日：2010-08-05

申请号：US12524038

申请日：2008-01-30

申请人： Jonathan Bentley ,  Matteo Biagetti ,  Francesca Cardullo ,  Thorsten Genski ,  Silvia Rosalia Kopf ,  Colin Philip Leslie ,  Sergio Melotto ,  Mirco Meniconi ,  Giancarlo Merlo ,  Domenica Antonia Pizzi ,  Catia Seri

发明人： Jonathan Bentley ,  Matteo Biagetti ,  Francesca Cardullo ,  Thorsten Genski ,  Silvia Rosalia Kopf ,  Colin Philip Leslie ,  Sergio Melotto ,  Mirco Meniconi ,  Giancarlo Merlo ,  Domenica Antonia Pizzi ,  Catia Seri

IPC分类号： A61K31/423 ,  C07D498/10 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  A61K31/444 ,  A61K31/501 ,  A61K31/497 ,  A61K31/506 ,  A61P3/04 ,  A61P25/24

CPC分类号： C07D498/10 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： The present invention relates to novel compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R is an aryl or heteroaryl; which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; W is —CZ1 or nitrogen; Z1 is hydrogen, C1-C4 alkyl; A is a 5 membered heteroaryl, pyrazine, pyrimidine, or quinoline or quinazoline which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; B is hydrogen or a 5-10 membered aryl or heteroaryl which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; being A and B linked via any atom; provided that when W is —CZ1, compounds of formula (I) have a trans stereochemistry; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as NPY Y5 receptor antagonists and as agents for the treatment and/or prophylaxis of eating disorders such as a binge eating disorder.

摘要翻译： 本发明涉及新的式（I）化合物或其药学上可接受的盐或溶剂合物，其中R是芳基或杂芳基; 其可以被一个或多个取代：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基; W是-CZ1或氮; Z1是氢，C1-C4烷基; A是可被一个或多个卤素取代的5元杂芳基，吡嗪，嘧啶或喹啉或喹唑啉：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基; B是氢或可被一个或多个卤素取代的5-10元芳基或杂芳基：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基; 是通过任何原子连接的A和B; 条件是当W是-CZ1时，式（I）化合物具有反式立体化学; 它们的制备方法，这些方法中使用的中间体，含有它们的药物组合物及其在治疗中的用途，作为NPY Y5受体拮抗剂以及用于治疗和/或预防进食障碍如狂饮病症的药剂。

公开(公告)号：US20100286151A1

公开(公告)日：2010-11-11

申请号：US12524080

申请日：2008-01-30

申请人： Jonathan Bentley ,  Matteo Biagetti ,  Romano Di Fabio ,  Thorsten Genski ,  Sebastien Guery ,  Silvia Rosalia Kopf ,  Colin philip Leslie ,  Angelica Mazzali ,  Sergio Melotto ,  Domenica Antonia Pizzi ,  Fabio Maria Sabbatini ,  Catia Seri

发明人： Jonathan Bentley ,  Matteo Biagetti ,  Romano Di Fabio ,  Thorsten Genski ,  Sebastien Guery ,  Silvia Rosalia Kopf ,  Colin philip Leslie ,  Angelica Mazzali ,  Sergio Melotto ,  Domenica Antonia Pizzi ,  Fabio Maria Sabbatini ,  Catia Seri

IPC分类号： A61K31/423 ,  C07D417/14 ,  A61K31/4439 ,  A61K31/505 ,  C07D413/14 ,  A61K31/501 ,  A61K31/444 ,  A61K31/497 ,  A61K31/433 ,  C07D471/04 ,  A61K31/437 ,  C07D487/04 ,  A61K31/4985 ,  C07D413/12 ,  A61P3/04 ,  A61P3/00

CPC分类号： C07D413/14

摘要： The present invention relates to novel compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R is an aryl or heteroaryl; which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; Z1 is H, C1-C4 alkyl or F; Z is CH2, CH(C1-C4 alkyl), C(C1-C4 alkyl)2 or a bond; A is a 5 membered heteroaryl, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, Cl C4 haloalkoxy, cyano; B is hydrogen or is a 5-6 membered heteroaryl, or phenyl, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; being A and B linked via any atom; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as NPY Y5 receptor antagonists and as agents for the treatment and/or prophylaxis of eating disorders such as a binge eating disorder.

摘要翻译： 本发明涉及新的式（I）化合物或其药学上可接受的盐或溶剂合物，其中R是芳基或杂芳基; 其可以被一个或多个取代：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基; Z 1是H，C 1 -C 4烷基或F; Z是CH 2，CH（C 1 -C 4烷基），C（C 1 -C 4烷基）2或键; A是5元杂芳基，其可以被一个或多个取代：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基; B是氢或是5-6元杂芳基或苯基，其可以被一个或多个取代：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基; 是通过任何原子连接的A和B; 它们的制备方法，这些方法中使用的中间体，含有它们的药物组合物及其在治疗中的用途，作为NPY Y5受体拮抗剂以及用于治疗和/或预防进食障碍如狂饮病症的药剂。

公开(公告)号：US20100216821A1

公开(公告)日：2010-08-26

申请号：US12596931

申请日：2008-04-18

申请人： Nicholas Paul Barton ,  Benjamin Richard Bellenie ,  Jonathan Bentley ,  Matteo Biagetti ,  Thorsten Genski ,  Colin Philip Leslie ,  Angelica Mazzali ,  Domenica Antonia Pizzi ,  Fabio Maria Sabbatini ,  Catia Seri

发明人： Nicholas Paul Barton ,  Benjamin Richard Bellenie ,  Jonathan Bentley ,  Matteo Biagetti ,  Thorsten Genski ,  Colin Philip Leslie ,  Angelica Mazzali ,  Domenica Antonia Pizzi ,  Fabio Maria Sabbatini ,  Catia Seri

IPC分类号： A61K31/52 ,  A61P3/04 ,  A61P25/24 ,  C07D498/10 ,  A61K31/438 ,  C07D471/10 ,  C07D413/08 ,  A61K31/423 ,  C07D403/14 ,  A61K31/506

CPC分类号： C07D498/10 ,  C07D221/20 ,  C07D403/04 ,  C07D413/04 ,  C07D413/14 ,  C07D471/04

摘要： The present invention relates to compounds of formula (I), or a pharmaceutically acceptable salts, solvates, stereoisomers thereof, R1 may be C1-C4 alkyl, aryl or heteroaryl, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; R2 may be halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano, nitro; or aryl, heteroaryl or heterocycle, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; or R2 may correspond to —O—R3; R3 is a 6-membered aromatic carbocyclic ring which may contain 1 or 2 nitrogen X is carbon or oxygen; Z is carbon or nitrogen; G is a fused 6-membered aromatic carbocyclic ring which may contain 1 or 2 nitrogen; m may be 0 or an integer ranging from 1 to 4; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as NPY-Y5 receptor antagonists.

摘要翻译： 本发明涉及式（I）化合物或其药学上可接受的盐，溶剂化物，立体异构体，R 1可以是可被一个或多个取代的C 1 -C 4烷基，芳基或杂芳基：卤素，C 1 -C 4烷基 ，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基; R 2可以是卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基，硝基; 可以被一个或多个卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基取代的芳基，杂芳基或杂环; 或R 2可以对应于-O-R 3; R3是可以含有1或2个氮的6元芳族碳环，X是碳或氧; Z是碳或氮; G是稠合的6元芳族碳环，其可以含有1或2个氮; m可以是0或1至4的整数; 作为其制备方法，在这些方法中使用的中间体，含有它们的药物组合物及其在治疗中的用途，作为NPY-Y5受体拮抗剂。

公开(公告)号：US20090042897A1

公开(公告)日：2009-02-12

申请号：US12022327

申请日：2008-01-30

申请人： Jonathan Bentley ,  Matteo Biagetti ,  Thorsten Genski ,  Silvia Rosalia Kopf ,  Colin Philip Leslie ,  Sergio Melotto

发明人： Jonathan Bentley ,  Matteo Biagetti ,  Thorsten Genski ,  Silvia Rosalia Kopf ,  Colin Philip Leslie ,  Sergio Melotto

IPC分类号： C07D413/02 ,  A61K31/501 ,  A61K31/4439 ,  A61K31/423 ,  A61P3/00 ,  A61P25/00 ,  A61P25/24

CPC分类号： C07D413/14

摘要： The present invention relates to novel compounds or a pharmaceutically acceptable salt or solvate thereof, selected from a group consisting of: (trans)-8-({[1-(2-fluorophenyl)-1H-pyrazol-3-yl]amino}methyl)-3-(2-fluoro-3-pyridinyl)-1-oxa-3-azaspiro[4.5]decan-2-one; (trans)-8-({[1-(2-fluorophenyl)-1H-pyrazol-3-yl]amino}methyl)-3-(3-pyridazinyl)-1-oxa-3-azaspiro[4.5]decan-2-one; (trans)-8-({[1-(2-fluorophenyl)-1H-pyrazol-3-yl]amino}methyl)-3-(1-methyl-1H-pyrazol-3-yl)-1-oxa-3-azaspiro[4.5]decan-2-one; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as NPY Y5 receptor antagonists and as agents for the treatment and/or prophylaxis of eating disorders such as a binge eating disorder.

摘要翻译： 本发明涉及选自以下的新的化合物或其药学上可接受的盐或溶剂化物：（反）-8 - （{[1-（2-氟苯基）-1H-吡唑-3-基]氨基} 甲基）-3-（2-氟-3-吡啶基）-1-氧杂-3-氮杂螺[4.5]癸-2-酮; （反式）-8 - （{[1-（2-氟苯基）-1H-吡唑-3-基]氨基}甲基）-3-（3-哒嗪基）-1-氧杂-3-氮杂螺[4.5] 2-one; （反式）-8 - （{[1-（2-氟苯基）-1H-吡唑-3-基]氨基}甲基）-3-（1-甲基-1H-吡唑-3-基）-1-氧杂 - 3-氮杂螺[4.5]癸-2-酮; 它们的制备方法，这些方法中使用的中间体，含有它们的药物组合物及其在治疗中的用途，作为NPY Y5受体拮抗剂以及用于治疗和/或预防进食障碍如狂饮病症的药剂。

公开(公告)号：US20090203705A1

公开(公告)日：2009-08-13

申请号：US12360166

申请日：2009-01-27

申请人： Matteo Biagetti ,  Stefania Anna Contini ,  Thorsten Genski ,  Sebastien Guery ,  Colin Philip Leslie ,  Angelica Mazzali ,  Domenica Antonia Pizzi ,  Fabio Maria Sabbatini ,  Catia Seri

发明人： Matteo Biagetti ,  Stefania Anna Contini ,  Thorsten Genski ,  Sebastien Guery ,  Colin Philip Leslie ,  Angelica Mazzali ,  Domenica Antonia Pizzi ,  Fabio Maria Sabbatini ,  Catia Seri

IPC分类号： A61K31/501 ,  C07D413/14 ,  A61P3/04

CPC分类号： C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： The present invention relates to novel compounds of formula (I), or a pharmaceutically acceptable salt thereof, wherein R is an aryl or heteroaryl, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; Z1 is H, C1-C4 alkyl or F; Z is CH2, CH(C1-C4 alkyl), C(C1-C4 alkyl)2 or a bond; A is a 6-10 membered aryl or heteroaryl, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; or —C(═O)—X; or —O(CH2)0-1R1; B is hydrogen or is a 5-6 membered heteroaryl, or a 4-6 membered heterocycle, or phenyl, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, hydroxyl, cyano; A and B being linked via any atom; R1 is —(C1-C4)alkyl(C1-C4)alkoxy; or C3-C8 cycloalkyl; or R1 is an aryl or heteroaryl, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; or R1 is a 4-6 membered heterocycle, which may be substituted by one or more: halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, cyano; X is OR2 or NR3R4; R2 is C1-C4 alkyl; R3 is hydrogen or together with R4 and the nitrogen form a 5-6 saturated membered ring; R4 is C3-C8 cycloalkyl; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as NPY Y5 receptor antagonists and as agents for the treatment and/or prophylaxis of eating disorders such as a binge eating disorder.

摘要翻译： 本发明涉及新的式（I）化合物或其药学上可接受的盐，其中R是可被一个或多个取代的芳基或杂芳基：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C4卤代烷基，C1-C4卤代烷氧基，氰基; Z 1是H，C 1 -C 4烷基或F; Z是CH 2，CH（C 1 -C 4烷基），C（C 1 -C 4烷基）2或键; A是6-10元芳基或杂芳基，其可以被一个或多个取代：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基; 或-C（-O）-X; 或-O（CH 2）0-1R1; B是氢或是5-6元杂芳基或4-6元杂环，或苯基，其可被一个或多个取代：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C4卤代烷氧基，羟基，氰基; A和B通过任何原子相连; R1是 - （C1-C4）烷基（C1-C4）烷氧基; 或C 3 -C 8环烷基; 或者R 1是可被一个或多个卤素取代的芳基或杂芳基：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基; 或R 1是4-6元杂环，其可以被一个或多个取代：卤素，C 1 -C 4烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷基，C 1 -C 4卤代烷氧基，氰基; X为OR2或NR3R4; R2是C1-C4烷基; R3是氢或与R4一起形成5-6饱和的元环; R4是C3-C8环烷基; 它们的制备方法，这些方法中使用的中间体，含有它们的药物组合物及其在治疗中的用途，作为NPY Y5受体拮抗剂以及用于治疗和/或预防进食障碍如狂饮病症的药剂。

公开(公告)号：US20130035321A1

公开(公告)日：2013-02-07

申请号：US13512636

申请日：2010-12-01

申请人： Hakim Djaballah ,  Christophe Antczak ,  David H. Abramson ,  Horst-Dieter Ambrosi ,  Karsten Siems ,  Thorsten Genski

发明人： Hakim Djaballah ,  Christophe Antczak ,  David H. Abramson ,  Horst-Dieter Ambrosi ,  Karsten Siems ,  Thorsten Genski

IPC分类号： C07J71/00 ,  A61P35/00 ,  A61K31/585

CPC分类号： A61K31/44 ,  C07J19/00 ,  C07J19/005 ,  C07J71/0005 ,  C07J71/001

摘要： In one aspect, the instant invention provides novel compounds and pharmaceutical compositions useful for treating proliferative diseases such as cancer. In another aspect, the invention provides methods of using certain compounds in the treatment of proliferative diseases such as cancer. In particular, the instant invention provides methods of treating ocular cancer (e.g., retinoblastoma) using intraarterial infusion to administer inventive compounds locally to the eye of a subject with an ocular cancer.

摘要翻译： 一方面，本发明提供了用于治疗增殖性疾病例如癌症的新型化合物和药物组合物。 另一方面，本发明提供了使用某些化合物治疗增殖性疾病例如癌症的方法。 特别地，本发明提供了使用动脉内输注治疗眼癌（例如视网膜母细胞瘤）的方法，以将本发明化合物局部施用于患有眼部癌症的受试者的眼睛。