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1. 发明申请

US20050020588A1 Cysteine protease inhibitors 审中-公开
标题翻译：半胱氨酸蛋白酶抑制剂
公开(公告)号：US20050020588A1
公开(公告)日：2005-01-27
申请号：US10929133
申请日：2004-08-27
申请人： Martin Quibell , Steven Taylor , Urszula Grabowska , Magnus Nilsson , Veronique Morisson
发明人： Martin Quibell , Steven Taylor , Urszula Grabowska , Magnus Nilsson , Veronique Morisson
IPC分类号： C07D307/22 , C07D307/32 , C07D307/68 , C07D307/85 , C07D309/14 , C07D309/30 , C07D405/12 , C07D405/14 , C07D409/12 , C07D409/14 , A61K31/541 , A61K31/496 , A61K31/5377 , C07D413/02 , C07D417/02 , C07
CPC分类号： C07D307/32 , C07D307/22 , C07D307/68 , C07D307/85 , C07D309/14 , C07D309/30 , C07D405/12 , C07D405/14 , C07D409/12 , C07D409/14
摘要： Cathepsin S is a highly active cysteine protease belonging to the papain superfamily. It is found mainly in lymph nodes, spleen, and macrophages and this limited occurrence suggests the potential involvement of this enzyme in the pathogenesis of degenerative disease. The invention relates to novel protease inhibitors, particularly inhibitors of the cysteine proteases of the papain superfamily and more particularly to Cathepsin S. The inhibitors are Furanone derivatives of Formula (II) which have a characteristic non-hydrogen substituent R5. They are selective over other members of the family and in particular show selectivity over other members of the Cathepsin family such as L and K.
摘要翻译：组织蛋白酶S是属于木瓜蛋白酶超家族的高活性半胱氨酸蛋白酶。主要发现在淋巴结，脾脏和巨噬细胞中，这种有限的发生表明该酶潜在地参与退行性疾病的发病机制。本发明涉及新型蛋白酶抑制剂，特别是木瓜蛋白酶超家族的半胱氨酸蛋白酶的抑制剂，更具体地涉及组织蛋白酶S.抑制剂是具有特征非氢取代基R5的式（II）的呋喃酮衍生物。它们对家族的其他成员具有选择性，并且特别地显示出组织蛋白酶家族的其它成员如L和K的选择性。

2. 发明申请

US20050070598A1 Cysteine protease inhibitors 审中-公开
标题翻译：半胱氨酸蛋白酶抑制剂
公开(公告)号：US20050070598A1
公开(公告)日：2005-03-31
申请号：US10678947
申请日：2003-10-03
申请人： Martin Quibell , Steven Taylor , Urszula Grabowska , Magnus Nilsson , Veronique Morrison
发明人： Martin Quibell , Steven Taylor , Urszula Grabowska , Magnus Nilsson , Veronique Morrison
IPC分类号： C07D307/22 , C07D307/32 , C07D307/68 , C07D307/85 , C07D309/14 , C07D309/30 , C07D405/12 , C07D405/14 , C07D409/12 , C07D409/14 , A61K31/541 , A61K31/366 , A61K31/496 , A61K31/5377 , C07D413/02 , C07D417/02 , C07D45/02
CPC分类号： C07D405/12 , C07D307/22 , C07D307/32 , C07D307/68 , C07D307/85 , C07D309/14 , C07D309/30 , C07D405/14 , C07D409/12 , C07D409/14
摘要： of the formula (IV): where: R1=R′C(O), R′SO2, R′=a bicyclic, saturated or unsaturated, 8-12 membered ring system containing 0-4 hetero atoms selected from S, O and N, which is optionally substituted with up to four substituents independently selected from groups a), b) and c) below; or R′=a monocyclic, saturated or unsaturated, 5-7 membered ring containing 0-3 hetero atoms selected from S, O and N, which monocyclic ring bears at least one substituent selected from group a) and/or c) and which may optionally bear one or two further substituents selected from group b); R4=H, C1-7-alkyl, Ar—C1-7-alkyl, Ar, C3-7-cycloalkyl; C2-7alkenyl; R3=C1-7-alkyl, C2-C7 alkenyl, C2-C7 alkenyl, C3-7-cycloalkyl, Ar—C1-7-alkyl, Ar; R5=C1-7-alkyl, halogen, Ar—C1-7-alkyl, CO-3-alkyl-CONR3R4 or a bulky amine R6 is H, C1-7-alkyl, Ar—C1-7-alkyl, C1-3-alkyl-SO2-Rix, C1-3-alkyl-C(O)—NHRix or CH2XAr q is 0 or 1 have utility as inhibitors of cysteine proteases such as cathepsin K and falcipain.
摘要翻译：式（Ⅳ）：其中：R1 = R'C（O），R'SO2，R'=含有0-4个杂原子的双环饱和或不饱和的8-12元环系，其选自S，O和 N，其任选被至多四个独立地选自以下的基团a），b）和c）中的取代基取代; 或R'=含有0-3个选自S，O和N的杂原子的单环，饱和或不饱和的5-7元环，该单环具有至少一个选自a）和/或c）的取代基，并且其中可以任选地带有一个或两个其它选自组b）的取代基; R 4 = H，C 1-7 - 烷基，Ar-C 1-7 - 烷基，Ar，C 3-7 - 环烷基; C2-7烯基; R 3 = C 1-7 - 烷基，C 2 -C 7烯基，C 2 -C 7链烯基，C 3-7 - 环烷基，Ar-C 1-7 - 烷基，Ar; R 5 = C 1-7 - 烷基，卤素，Ar-C 1-7 - 烷基，CO-3-烷基-CONR 3 R 4或大体积的胺R 6是H，C 1-7 - 烷基，Ar-C 1-7 - 烷基，C 1-3 - 烷基-SO 2 -R 5，C 1-3 - 烷基-C（O）-NHR x或CH 2 XAr q为0或1可用作半胱氨酸蛋白酶如组织蛋白酶K和恶性蛋白酶的抑制剂。

3. 发明授权

US08853281B2 Cysteine protease inhibitors 有权
标题翻译：半胱氨酸蛋白酶抑制剂
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。

4. 发明授权

US08466158B2 Cysteine protease inhibitors 有权
标题翻译：半胱氨酸蛋白酶抑制剂
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。

5. 发明申请

US20120289519A1 PROTEASE INHIBITORS 有权
标题翻译： PROTEASE抑制剂
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。

6. 发明授权

US07893067B2 Cysteine protease inhibitors 有权
标题翻译：半胱氨酸蛋白酶抑制剂
公开(公告)号：US07893067B2
公开(公告)日：2011-02-22
申请号：US12145987
申请日：2008-06-25
申请人： Magnus Nilsson , Lourdes Oden , Pia Kahnberg , Urszula Grabowska
发明人： Magnus Nilsson , Lourdes Oden , Pia Kahnberg , Urszula Grabowska
IPC分类号： A61K31/407 , C07D491/04
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。

7. 发明申请

US20110039862A1 Protease Inhibitors 有权
标题翻译：蛋白酶抑制剂
公开(公告)号：US20110039862A1
公开(公告)日：2011-02-17
申请号：US12739489
申请日：2009-09-24
申请人： Lourdes Salvadore Odén , Magnus Nilsson , Pia Kahnberg , Bertil Samuelsson , Urszula Grabowska
发明人： Lourdes Salvadore Odén , Magnus Nilsson , Pia Kahnberg , Bertil Samuelsson , Urszula Grabowska
IPC分类号： A61K31/496 , C07D491/048 , A61P19/10 , A61P1/02 , A61P35/00 , A61P29/00 , A61P19/02 , A61P19/08 , A61P7/00
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 C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, 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R 1和R 2独立地是H，F或CH 3; 或R1形成乙炔基，R2是H或C3-C6环烷基，其任选地被一个或两个独立地选自甲基，CF 3，OMe或卤素的取代基取代; R 3是C 1 -C 3烷基或C 3 -C 6环烷基，当R 3是C 3 -C 6环烷基时，它们任选被一个或两个甲基和/或氟，三氟甲基或甲氧基取代，也可以被氟取代; R4是甲基或氟; m为0,1或2; E是任选被甲基或氟取代的键或噻唑基; A1是CH或N，A2是CR6R7或NR6，条件是A1和A2中的至少一个包括N; R6是H，C1-C4烷基，C1-C4卤代烷基，C1-C3烷基-O-C1-C3烷基，或当A2是C时，R6也可以是C1-C4烷氧基或F; R7是H，C1-C4烷基或F或其药学上可接受的盐，N-氧化物或其水合物，可用于治疗组织蛋白酶K不适当表达或活化的疾病，例如骨质疏松症，骨关节炎，类风湿性关节炎或骨骼转移。

8. 发明申请

US20080234260A1 Cysteine Protease inhibitors 有权
标题翻译：半胱氨酸蛋白酶抑制剂
公开(公告)号：US20080234260A1
公开(公告)日：2008-09-25
申请号：US10584930
申请日：2005-01-06
申请人： Magnus Nilsson , Xiao-Xiong Zhou , Lourdes Oden , Bjorn Classon , Rolf Noren , Urszula Grabowska , Philip Jackson , Philip Fallon , Andrew Carr , Mark Liley , Matt Tozer , Tony Johnson , Victor Diaz , Laia Crespo , Jussi Kangasmetsa , Thierry Bonnaud
发明人： Magnus Nilsson , Xiao-Xiong Zhou , Lourdes Oden , Bjorn Classon , Rolf Noren , Urszula Grabowska , Philip Jackson , Philip Fallon , Andrew Carr , Mark Liley , Matt Tozer , Tony Johnson , Victor Diaz , Laia Crespo , Jussi Kangasmetsa , Thierry Bonnaud
IPC分类号： A61K31/5377 , C07D491/048 , A61K31/407 , A61P19/00 , A61K31/496
CPC分类号： C07D491/04 , A61K31/407
摘要： A compound of the formula II wherein one of R1 and R2 is halo and the other is H or halo; R3 is C1-C4 straight or branched chain, optionally fluorinated, alkyl; R4 is H; or R3 together with R4 and the adjoining backbone carbon defines: a spiro-C5-C7 cycloalkyl, optionally substituted with 1 to 3 substituents selected from halo, hydroxyl, C1-C4 alkyl or C1-C4 haloalkyl; or optionally bridged with a methylene group; or a C4-C6 saturated heterocycle having a hetero atom selected from O, NRa, S, S(═O)2; where Ra is H, C1-C4 alkyl or CH3C(═O); R5 is independently selected from H or methyl; E is —C(═O)—, —S(═O)m—, —NR5S(═O)m—, —NR5C(═O)—, —OC(═O)—, R6 is a stable, optionally substituted, monocyclic or bicyclic, carbocycle or heterocycle; m is independently 0,1 or 2; are inhibitors of cathepsin K and useful in the treatment or prophylaxis of osteoporosis.
摘要翻译：式II的化合物，其中R 1和R 2中的一个为卤素，另一个为H或卤素; R 3是C 1 -C 4直链或支链，任选氟化的烷基; R 4是H; 或R 3连同R 4和邻位的主链碳定义：螺-C 5 -C 7 - 环烷基，任选被1至3个选自卤素，羟基，C 1 -C 4烷基或C 1 -C 4烷基的取代基取代。 4卤代烷基; 或任选地与亚甲基桥连; 或具有选自O，NRa，S，S（-O）2）的杂原子的C 4 -C 6 -C 6饱和杂环。其中R a是H，C 1 -C 4烷基或CH 3 C（-O）; R 5独立地选自H或甲基; E是-C（-O） - ， - S（-O）m - ， - NR 5 S（-O）m - ，-NR 5 C（-O） - ， - OC（-O） - ，R 6是稳定的，任选取代的单环或双环碳环或杂环; m独立地为0,1或2; 是组织蛋白酶K的抑制剂，可用于治疗或预防骨质疏松症。

9. 发明申请

US20120220602A1 CYSTEINE PROTEASE INHIBITORS 有权
标题翻译： CYSTEINE PROTEASE抑制剂
公开(公告)号：US20120220602A1
公开(公告)日：2012-08-30
申请号：US13468787
申请日：2012-05-10
申请人： Magnus Nilsson , Lourdes Oden , Pia Kahnberg , Urszula Grabowska
发明人： Magnus Nilsson , Lourdes Oden , Pia Kahnberg , Urszula Grabowska
IPC分类号： A61K31/496 , A61K31/407 , A61P1/02 , A61P29/00 , A61P35/00 , A61P3/00 , A61P19/02 , C07D491/048 , A61P19/08
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。

10. 发明授权

US08198283B2 Cysteine protease inhibitors 有权
标题翻译：半胱氨酸蛋白酶抑制剂
公开(公告)号：US08198283B2
公开(公告)日：2012-06-12
申请号：US12986830
申请日：2011-01-07
申请人： Magnus Nilsson , Lourdes Salvador Oden , Pia Kahnberg , Urszula Grabowska
发明人： Magnus Nilsson , Lourdes Salvador Oden , Pia Kahnberg , Urszula Grabowska
IPC分类号： A61K31/496 , A61K31/407 , C07D491/04
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。

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