公开(公告)号：US08853281B2

公开(公告)日：2014-10-07

申请号：US13139962

申请日：2009-12-18

申请人： Susana Ayesa ,  Anna Karin Belfrage ,  Bjorn Classon ,  Urszula Grabowska ,  Ellen Hewitt ,  Vladimir Ivanov ,  Daniel Jönsson ,  Pia Kahnberg ,  Peter Lind ,  Magnus Nilsson ,  Lourdes Odén ,  Mikael Pelcman ,  Horst Wähling

发明人： Susana Ayesa ,  Anna Karin Belfrage ,  Bjorn Classon ,  Urszula Grabowska ,  Ellen Hewitt ,  Vladimir Ivanov ,  Daniel Jönsson ,  Pia Kahnberg ,  Peter Lind ,  Magnus Nilsson ,  Lourdes Odén ,  Mikael Pelcman ,  Horst Wähling

IPC分类号： A01N33/02 ,  A61K31/13 ,  A01N37/00 ,  A61K31/21 ,  A01N33/00 ,  A61K31/16 ,  A01N37/18 ,  A61K31/165 ,  A01N35/00 ,  A61K31/12 ,  A01N33/18 ,  A01N33/24 ,  A61K31/04 ,  A01N29/00 ,  A61K31/02 ,  A01N29/02 ,  C07D231/00 ,  C07D413/00 ,  C07D295/22 ,  C07D307/02 ,  C07C303/00 ,  C07C307/00 ,  C07C309/00 ,  C07C311/00 ,  C07C233/00 ,  C07C235/00 ,  C07C237/00 ,  C07C239/00 ,  C07C261/00 ,  C07C269/00 ,  C07C271/00 ,  C07D405/12 ,  C07D403/12 ,  C07C271/24 ,  C07D417/12 ,  C07C311/21 ,  C07D241/24 ,  C07D401/12 ,  C07D277/36 ,  C07D307/85 ,  C07D307/68 ,  C07D277/56 ,  C07D295/215 ,  C07C237/24 ,  C07D231/40 ,  C07D207/34 ,  C07D213/71 ,  C07D231/14 ,  C07D239/80 ,  C07D213/40

CPC分类号： C07C311/21 ,  C07C237/24 ,  C07C271/24 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/06 ,  C07C2601/08 ,  C07D207/34 ,  C07D213/40 ,  C07D213/71 ,  C07D231/14 ,  C07D231/40 ,  C07D239/80 ,  C07D241/24 ,  C07D277/36 ,  C07D277/56 ,  C07D295/215 ,  C07D307/68 ,  C07D307/85 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D417/12

摘要： Compounds of the formula I wherein R1a is H; and R1b is C1-C6 alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are H, halo, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy; or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a branched C5-C10alkyl chain, C2-C4haloalkyl or C3-C7cycloalkylmethyl, R4 is Het, Carbocyclyl, optionally substituted as defined in the specification and pharmaceutically acceptable salts, hydrates and N-oxides thereof; are inhibitors of cathepsin S and have utility in the treatment of psoriasis, autoimmune disorders and other disorders such as asthma, arteriosclerosis, COPD and chronic pain.

摘要翻译： 式Ⅰ化合物，其中R1a是H; 并且R 1b是C 1 -C 6烷基，碳环或Het; 或R 1a和R 1b一起限定具有3-6个环原子的饱和环胺; R2a和R2b是H，卤素，C1-C4烷基，C1-C4卤代烷基，C1-C4烷氧基; 或R 2a和R 2b与它们所连接的碳原子一起形成C 3 -C 6环烷基; R3是支链C 5 -C 10烷基链，C 2 -C 4卤代烷基或C 3 -C 7环烷基甲基，R 4是Het，碳环基，如说明书中所定义的任选取代，以及其药学上可接受的盐，水合物和N-氧化物; 是组织蛋白酶S的抑制剂，并且可用于治疗牛皮癣，自身免疫性疾病和其它疾病如哮喘，动脉硬化，COPD和慢性疼痛。

公开(公告)号：US20110312964A1

公开(公告)日：2011-12-22

申请号：US13139962

申请日：2009-12-18

申请人： Susana Ayesa ,  Anna Karin Belfrage ,  Björn Classon ,  Urszula Grabowska ,  Ellen Hewitt ,  Vladimir Ivanov ,  Daniel Jönsson ,  Pia Kahnberg ,  Peter Lind ,  Magnus Nilsson ,  Lourdes Odén ,  Mikael Pelcman ,  Horst Wähling

发明人： Susana Ayesa ,  Anna Karin Belfrage ,  Björn Classon ,  Urszula Grabowska ,  Ellen Hewitt ,  Vladimir Ivanov ,  Daniel Jönsson ,  Pia Kahnberg ,  Peter Lind ,  Magnus Nilsson ,  Lourdes Odén ,  Mikael Pelcman ,  Horst Wähling

IPC分类号： A61K31/5377 ,  C07D265/30 ,  C07D413/12 ,  C07D307/68 ,  C07D405/12 ,  C07C237/52 ,  C07C311/46 ,  C07C271/24 ,  A61K31/415 ,  A61K31/5375 ,  A61K31/341 ,  A61K31/18 ,  A61K31/166 ,  A61K31/4965 ,  A61P25/00 ,  A61P19/02 ,  A61P11/06 ,  A61P9/10 ,  A61P29/00 ,  A61P11/00 ,  A61P17/06 ,  C07D231/40

CPC分类号： C07C311/21 ,  C07C237/24 ,  C07C271/24 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/06 ,  C07C2601/08 ,  C07D207/34 ,  C07D213/40 ,  C07D213/71 ,  C07D231/14 ,  C07D231/40 ,  C07D239/80 ,  C07D241/24 ,  C07D277/36 ,  C07D277/56 ,  C07D295/215 ,  C07D307/68 ,  C07D307/85 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D417/12

摘要： Compounds of the formula I whereinR1a is H; and R1b is C1-C6 alkyl, Carbocyclyl or Het; orR1a and R1b together define a saturated cyclic amine with 3-6 ring atoms;R2a and R2b are H, halo, C1-C4alkyl, C1-C4haloalkyl, C1-C4alkoxy; orR2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl;R3 is a branched C5-C10alkyl chain, C2-C4haloalkyl or C3-C7cycloalkylmethyl,R4 is Het, Carbocyclyl,optionally substituted as defined in the specification and pharmaceutically acceptable salts,hydrates and N-oxides thereof; are inhibitors of cathepsin S and have utility in the treatment of psoriasis, autoimmune disorders and other disorders such as asthma, arteriosclerosis, COPD and chronic pain

摘要翻译： 式Ⅰ化合物，其中R1a是H; 并且R 1b是C 1 -C 6烷基，碳环或Het; 或R 1a和R 1b一起限定具有3-6个环原子的饱和环胺; R2a和R2b是H，卤素，C1-C4烷基，C1-C4卤代烷基，C1-C4烷氧基; 或R 2a和R 2b与它们所连接的碳原子一起形成C 3 -C 6环烷基; R3是支链C 5 -C 10烷基链，C 2 -C 4卤代烷基或C 3 -C 7环烷基甲基，R 4是Het，碳环基，如本说明书中所定义的任选取代，及其药学上可接受的盐，水合物和N-氧化物; 是组织蛋白酶S的抑制剂，并且可用于治疗牛皮癣，自身免疫性疾病和其它疾病如哮喘，动脉硬化，COPD和慢性疼痛

公开(公告)号：US20120309673A1

公开(公告)日：2012-12-06

申请号：US13514758

申请日：2010-12-10

申请人： Susana Ayesa ,  Karolina Ersmark ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jönsson ,  Pia Kahnberg ,  Björn Klasson ,  Peter Lind ,  Stina Lundgren ,  Lourdes Odén ,  Kevin Parkes ,  Daniel Wiktelius

发明人： Susana Ayesa ,  Karolina Ersmark ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jönsson ,  Pia Kahnberg ,  Björn Klasson ,  Peter Lind ,  Stina Lundgren ,  Lourdes Odén ,  Kevin Parkes ,  Daniel Wiktelius

IPC分类号： A61K38/05 ,  A61P19/02 ,  A61P25/00 ,  C07D241/04 ,  A61P9/00 ,  C07D233/48 ,  C07C271/20 ,  C07D261/14 ,  C07D231/40 ,  A61P11/06

CPC分类号： C07K5/06078 ,  A61K38/05 ,  C07C271/22 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D231/40 ,  C07D277/46 ,  C07D405/12 ,  C07K5/06034 ,  C07K5/0606 ,  C07K5/06139

摘要： Compounds of Formula II wherein R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a branched C5-C10 alkyl chain, C2-C4haloalkyl or —CH2C3-C7 cycloalkyl; R4′ is C1-C6alkyl, C1-C6haloalkyl or oxetany-3-yl. for use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

摘要翻译： 式II的化合物，其中R 1a是H; 并且R 1b是C 1 -C 6烷基，碳环或Het; 或R 1a和R 1b一起限定具有3-6个环原子的饱和环胺; R2a和R2b独立地为H，卤素，C1-C4烷基，C1-C4卤代烷基或C1-C4烷氧基，或R2a和R2b与它们所连接的碳原子一起形成C 3 -C 6环烷基; R3是支链C 5 -C 10烷基链，C 2 -C 4卤代烷基或-CH 2 C 3 -C 7环烷基; R 4'是C 1 -C 6烷基，C 1 -C 6卤代烷基或氧杂环丁烷-3-基。 用于预防或治疗以组织蛋白酶S不适当表达或活化为特征的病症。

公开(公告)号：US20120283305A1

公开(公告)日：2012-11-08

申请号：US13514760

申请日：2010-12-10

申请人： Susana Ayesa ,  Peter Carlqvist ,  Karolina Ersmark ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jönsson ,  Pia Kahnberg ,  Björn Klasson ,  Peter Lind ,  Lourdes Odén ,  Kevin Parkes ,  Daniel Wiktelius

发明人： Susana Ayesa ,  Peter Carlqvist ,  Karolina Ersmark ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jönsson ,  Pia Kahnberg ,  Björn Klasson ,  Peter Lind ,  Lourdes Odén ,  Kevin Parkes ,  Daniel Wiktelius

IPC分类号： A61K31/415 ,  C07C237/22 ,  A61K31/16 ,  A61P17/06 ,  A61P37/00 ,  A61P7/00 ,  A61P29/00 ,  A61P19/02 ,  A61P25/00 ,  A61P21/04 ,  A61P11/02 ,  A61P11/06 ,  A61P9/10 ,  A61P11/00 ,  C07D231/40

CPC分类号： C07K5/06078 ,  A61K38/05 ,  C07C271/22 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D231/40 ,  C07D277/46 ,  C07D405/12 ,  C07K5/06034 ,  C07K5/0606 ,  C07K5/06139

摘要： Compounds of the formula I wherein R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a branched C5-C10 alkyl chain, C2-C4haloalkyl or —CH2C3-C7 cycloalkyl; R4 is C1-C6alkyl, C1-C6haloalkyl, C1-C6alkylamino or C1-C6dialkylamino; for use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

摘要翻译： 式Ⅰ化合物，其中R1a是H; 并且R 1b是C 1 -C 6烷基，碳环或Het; 或R 1a和R 1b一起限定具有3-6个环原子的饱和环胺; R2a和R2b独立地为H，卤素，C1-C4烷基，C1-C4卤代烷基或C1-C4烷氧基，或R2a和R2b与它们所连接的碳原子一起形成C 3 -C 6环烷基; R3是支链C 5 -C 10烷基链，C 2 -C 4卤代烷基或-CH 2 C 3 -C 7环烷基; R 4是C 1 -C 6烷基，C 1 -C 6卤代烷基，C 1 -C 6烷基氨基或C 1 -C 6二烷基氨基; 用于预防或治疗以组织蛋白酶S不适当表达或活化为特征的病症。

公开(公告)号：US08815809B2

公开(公告)日：2014-08-26

申请号：US13514758

申请日：2010-12-10

申请人： Susana Ayesa ,  Karolina Ersmark ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jönsson ,  Pia Kahnberg ,  Björn Klasson ,  Peter Lind ,  Stina Lundgren ,  Lourdes Odèn ,  Kevin Parkes ,  Daniel Wiktelius

发明人： Susana Ayesa ,  Karolina Ersmark ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jönsson ,  Pia Kahnberg ,  Björn Klasson ,  Peter Lind ,  Stina Lundgren ,  Lourdes Odèn ,  Kevin Parkes ,  Daniel Wiktelius

IPC分类号： A61K38/00 ,  A61K38/05 ,  C07K5/065 ,  C07K5/078 ,  C07K5/062

CPC分类号： C07K5/06078 ,  A61K38/05 ,  C07C271/22 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D231/40 ,  C07D277/46 ,  C07D405/12 ,  C07K5/06034 ,  C07K5/0606 ,  C07K5/06139

摘要： Compounds of Formula II wherein R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a branched C5-C10 alkyl chain, C2-C4haloalkyl or —CH2C3-C7 cycloalkyl; R4′ is C1-C6alkyl, C1-C6haloalkyl or oxetany-3-yl. for use in the prophylaxis or treatment of a disorder characterized by inappropriate expression or activation of cathepsin S.

摘要翻译： 式II的化合物，其中R 1a是H; 并且R 1b是C 1 -C 6烷基，碳环或Het; 或R 1a和R 1b一起限定具有3-6个环原子的饱和环胺; R2a和R2b独立地为H，卤素，C1-C4烷基，C1-C4卤代烷基或C1-C4烷氧基，或R2a和R2b与它们所连接的碳原子一起形成C 3 -C 6环烷基; R3是支链C 5 -C 10烷基链，C 2 -C 4卤代烷基或-CH 2 C 3 -C 7环烷基; R 4'是C 1 -C 6烷基，C 1 -C 6卤代烷基或氧杂环丁烷-3-基。 用于预防或治疗以组织蛋白酶S不适当表达或活化为特征的病症。

公开(公告)号：US08859605B2

公开(公告)日：2014-10-14

申请号：US13514760

申请日：2010-12-10

申请人： Susana Ayesa ,  Peter Carlqvist ,  Karolina Ersmark ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jonsson ,  Pia Kahnberg ,  Bjorn Klasson ,  Peter Lind ,  Lourdes Oden ,  Kevin Parkes ,  Daniel Wiktelius

发明人： Susana Ayesa ,  Peter Carlqvist ,  Karolina Ersmark ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jonsson ,  Pia Kahnberg ,  Bjorn Klasson ,  Peter Lind ,  Lourdes Oden ,  Kevin Parkes ,  Daniel Wiktelius

IPC分类号： C07C271/22 ,  C07D405/12 ,  C07D231/40 ,  C07D277/46

CPC分类号： C07K5/06078 ,  A61K38/05 ,  C07C271/22 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D231/40 ,  C07D277/46 ,  C07D405/12 ,  C07K5/06034 ,  C07K5/0606 ,  C07K5/06139

摘要： Compounds of the formula I wherein R1a is H; and R1b is C1-C6alkyl, Carbocyclyl or Het; or R1a and R1b together define a saturated cyclic amine with 3-6 ring atoms; R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a branched C5-C10 alkyl chain, C2-C4haloalkyl or —CH2C3-C7 cycloalkyl; R4 is C1-C6alkyl, C1-C6haloalkyl, C1-C6alkylamino or C1-C6dialkylamino; for use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

摘要翻译： 式Ⅰ化合物，其中R1a是H; 并且R 1b是C 1 -C 6烷基，碳环或Het; 或R 1a和R 1b一起限定具有3-6个环原子的饱和环胺; R2a和R2b独立地为H，卤素，C1-C4烷基，C1-C4卤代烷基或C1-C4烷氧基，或R2a和R2b与它们所连接的碳原子一起形成C 3 -C 6环烷基; R3是支链C 5 -C 10烷基链，C 2 -C 4卤代烷基或-CH 2 C 3 -C 7环烷基; R 4是C 1 -C 6烷基，C 1 -C 6卤代烷基，C 1 -C 6烷基氨基或C 1 -C 6二烷基氨基; 用于预防或治疗以组织蛋白酶S不适当表达或活化为特征的病症。

公开(公告)号：US20130172232A1

公开(公告)日：2013-07-04

申请号：US13704441

申请日：2011-06-16

申请人： Susana Ayesa ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jonsson ,  Bjorn Klasson ,  Pia Kahnberg ,  Stina Lundgren ,  Jan Tejbrant ,  Daniel Wiktelius

发明人： Susana Ayesa ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jonsson ,  Bjorn Klasson ,  Pia Kahnberg ,  Stina Lundgren ,  Jan Tejbrant ,  Daniel Wiktelius

IPC分类号： C07K5/078 ,  C07K5/062 ,  C07K5/065

CPC分类号： C07D233/61 ,  A61K38/55 ,  C07C231/12 ,  C07C235/80 ,  C07C237/22 ,  C07C271/22 ,  C07C275/18 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D213/81 ,  C07D233/60 ,  C07D277/56 ,  C07D305/08 ,  C07K5/06034 ,  C07K5/0606 ,  C07K5/06078 ,  C07K5/06139

摘要： Compounds of the formula I wherein R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a C5-C10 alkyl, optionally substituted with 1-3 substituents independently selected from halo, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy; or R3 is a C2-C4alkyl chain with at least 2 chloro or 3 fluoro substituents; or R3 is C3-C7cycloalkylmethyl, optionally substituted with 1-3 substituents independently selected from C1-C4alkyl, halo, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy; R4 is C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylamino, C1-C6dialkylamino or; R4 is Het or Carbocyclyl, either of which is optionally substituted with 1-3 substituents R4 is Het, carbocyclyl, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy or C1-C6haloalkoxy; n is 1, 2 or 3; for the use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

公开(公告)号：US08859505B2

公开(公告)日：2014-10-14

申请号：US13704441

申请日：2011-06-16

申请人： Susana Ayesa ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jonsson ,  Bjorn Klasson ,  Pia Kahnberg ,  Stina Lundgren ,  Jan Tejbrant ,  Daniel Wiktelius

发明人： Susana Ayesa ,  Urszula Grabowska ,  Ellen Hewitt ,  Daniel Jonsson ,  Bjorn Klasson ,  Pia Kahnberg ,  Stina Lundgren ,  Jan Tejbrant ,  Daniel Wiktelius

IPC分类号： C07K14/81 ,  C07D233/60 ,  C07K5/065 ,  C07C271/22 ,  C07D277/56 ,  A61K38/55 ,  C07D305/08 ,  C07K5/062 ,  C07C275/18 ,  C07K5/078 ,  C07C237/22 ,  C07D213/81

CPC分类号： C07D233/61 ,  A61K38/55 ,  C07C231/12 ,  C07C235/80 ,  C07C237/22 ,  C07C271/22 ,  C07C275/18 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07D213/81 ,  C07D233/60 ,  C07D277/56 ,  C07D305/08 ,  C07K5/06034 ,  C07K5/0606 ,  C07K5/06078 ,  C07K5/06139

摘要： Compounds of the formula I wherein R2a and R2b are independently H, halo, C1-C4alkyl, C1-C4haloalkyl or C1-C4alkoxy, or R2a and R2b together with the carbon atom to which they are attached form a C3-C6cycloalkyl; R3 is a C5-C10 alkyl, optionally substituted with 1-3 substituents independently selected from halo, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy; or R3 is a C2-C4alkyl chain with at least 2 chloro or 3 fluoro substituents; or R3 is C3-C7cycloalkylmethyl, optionally substituted with 1-3 substituents independently selected from C1-C4alkyl, halo, C1-C4haloalkyl, C1-C4alkoxy, C1-C4haloalkoxy; R4 is C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, C1-C6haloalkoxy, C1-C6alkylamino, C1-C6dialkylamino or; R4 is Het or Carbocyclyl, either of which is optionally substituted with 1-3 substituents R4 is Het, carbocyclyl, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy or C1-C6haloalkoxy; n is 1, 2 or 3; for the use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

摘要翻译： 其中R 2a和R 2b独立地是H，卤素，C 1 -C 4烷基，C 1 -C 4卤代烷基或C 1 -C 4烷氧基或R 2a和R 2b与它们所连接的碳原子一起形成C 3 -C 6环烷基的式I化合物; R3是任选地被1-3个独立地选自卤素，C 1 -C 4卤代烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷氧基的取代基取代的C 5 -C 10烷基; 或R3是具有至少2个氯或3个氟取代基的C 2 -C 4烷基链; 或R3是C3-C7环烷基甲基，任选地被1-3个独立地选自C 1 -C 4烷基，卤素，C 1 -C 4卤代烷基，C 1 -C 4烷氧基，C 1 -C 4卤代烷氧基的取代基取代; R 4是C 1 -C 6烷基，C 1 -C 6卤代烷基，C 1 -C 6烷氧基，C 1 -C 6卤代烷氧基，C 1 -C 6烷基氨基，C 1 -C 6二烷基氨基或 R 4是Het或碳环基，其任一个任选被1-3个取代基取代，R 4是Het，碳环基，C 1 -C 6烷基，C 1 -C 6卤代烷基，C 1 -C 6烷氧基或C 1 -C 6卤代烷氧基; n为1,2或3; 用于预防或治疗以组织蛋白酶S的不适当表达或活化为特征的病症。

公开(公告)号：US08466158B2

公开(公告)日：2013-06-18

申请号：US13468787

申请日：2012-05-10

申请人： Magnus Nilsson ,  Lourdes Salvador Odén ,  Pia Kahnberg ,  Urszula Grabowska

发明人： Magnus Nilsson ,  Lourdes Salvador Odén ,  Pia Kahnberg ,  Urszula Grabowska

IPC分类号： A61K31/496

CPC分类号： C07D491/048

摘要： Compounds of the formula II: wherein R2 is the side chain of leucine, isoleucine, cyclohexylglycine, O-methyl threonine, 4-fluoroleucine or 3-methoxyvaline; R3 is H, methyl or F; Rq is trifluoromethyl and Rq′ is H or Rq and Rq′ define keto; Q is a p-(C1-C6alkylsulphonyl)phenyl- or an optionally substituted 4-(C1-C6alkyl)piperazin-1-yl-thiazol-4-yl-moiety have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

摘要翻译： 式II化合物：其中R2是亮氨酸的侧链，异亮氨酸，环己基甘氨酸，O-甲基苏氨酸，4-氟亮氨酸或3-甲氧基缬氨酸; R3是H，甲基或F; Rq是三氟甲基，Rq'是H或Rq，Rq'定义酮基; Q是对 - （C 1 -C 6烷基磺酰基）苯基 - 或任选取代的4-（C 1 -C 6烷基）哌嗪-1-基 - 噻唑-4-基 - 部分可用于治疗以不适当表达或活化为特征的疾病 组织蛋白酶K，例如骨质疏松症，骨关节炎，类风湿性关节炎或骨转移。

公开(公告)号：US20120289519A1

公开(公告)日：2012-11-15

申请号：US13541519

申请日：2012-07-03

申请人： Lourdes Salvador ODÉN ,  Magnus Nilsson ,  Pia Kahnberg ,  Bertil Samuelsson ,  Urszula Grabowska

发明人： Lourdes Salvador ODÉN ,  Magnus Nilsson ,  Pia Kahnberg ,  Bertil Samuelsson ,  Urszula Grabowska

IPC分类号： A61K31/496 ,  A61P19/02

CPC分类号： C07D277/40 ,  C07D491/048 ,  C07D495/04

摘要： Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or optionally substituted C3-C6 cycloalkyl; R3 is (optionally substituted) C1-C3 alkyl or C3-C6 cycloalkyl; R4 is methyl or fluoro; m is 0-2; E is optionally substituted thiazolyl; A1 and A2 together define an optionally substituted piperazine or piperidine ring have utility in the treatment of osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

摘要翻译： 式II化合物：其中R 1和R 2独立地是H，F或CH 3; 或R 1形成乙炔基，R 2为H或任选取代的C 3 -C 6环烷基; R3是（任选取代的）C 1 -C 3烷基或C 3 -C 6环烷基; R4是甲基或氟; m为0-2; E是任选取代的噻唑基; A1和A2一起限定任选取代的哌嗪或哌啶环可用于治疗骨质疏松症，骨关节炎，类风湿性关节炎或骨转移。