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1. 发明申请

WO2013000924A1 1-ARYL-4-METHYL-[1,2,4]TRIAZOLO[4,3-a]QUINOXALINE DERIVATIVES 审中-公开
标题翻译： 1-芳基-4-甲基 - [1,2,4]三唑并[4,3-a]喹啉衍生物
公开(公告)号：WO2013000924A1
公开(公告)日：2013-01-03
申请号：PCT/EP2012/062381
申请日：2012-06-26
申请人： JANSSEN PHARMACEUTICA NV , ANDRÉS-GIL, José, Ignacio , ROMBOUTS, Frederik, Jan, Rita , TRABANCO-SUÁREZ, Andrés, Avelino , VANHOOF, Greta, Constantia, Peter , DE ANGELIS, Meri , BUIJNSTERS, Peter, Jacobus, Johannes, Antonius , GUILLEMONT, Jerôme, Emile, Georges , BORMANS, Guy, Maurits R. , CELEN, Sofie, Jeanne, Leopoldine , VLIEGEN, Maarten
发明人： ANDRÉS-GIL, José, Ignacio , ROMBOUTS, Frederik, Jan, Rita , TRABANCO-SUÁREZ, Andrés, Avelino , VANHOOF, Greta, Constantia, Peter , DE ANGELIS, Meri , BUIJNSTERS, Peter, Jacobus, Johannes, Antonius , GUILLEMONT, Jerôme, Emile, Georges , BORMANS, Guy, Maurits R. , CELEN, Sofie, Jeanne, Leopoldine , VLIEGEN, Maarten
IPC分类号： C07D487/04 , A61K31/4985 , A61P25/00
CPC分类号： C07D487/04 , A61K31/4985 , A61K45/06 , A61K51/0463 , G01N33/60
摘要： The present invention relates to novel l-aryl-4-methyl-[l,2,4]triazolo[4,3-a]- quinoxaline derivatives as inhibitors of phosphodiesterase 2 (PDE2) and to a lesser extent of phosphodiesterase 10 (PDE10) or as inhibitors of both, phosphodiesterases 2 and 10. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which PDE2 is involved, or disorders in which both PDE2 and PDE10 are involved, such as neurological and psychiatric disorders, and endocrinological or metabolic diseases. The present invention also relates to radiolabeled compounds which may be useful for imaging and quantifying the PDE2 enzyme in tissues, using positron- emission tomography (PET). The invention is also directed to compositions comprising such compounds, to processes for preparing such compounds and compositions, to the use of such compounds and compositions for imaging a tissue, cells or a host, in vitro or in vivo and to precursors of said compounds.
摘要翻译：本发明涉及新的1-芳基-4-甲基 - [1,2,4]三唑并[4,3-a] - 喹喔啉衍生物作为磷酸二酯酶2（PDE2）的抑制剂，而较少程度的磷酸二酯酶10（PDE10 ）或作为磷酸二酯酶2和10两者的抑制剂。本发明还涉及包含这些化合物的药物组合物，制备此类化合物和组合物的方法，以及用于预防和治疗疾病的化合物和组合物其中涉及PDE2，或PDE2和PDE10都涉及的疾病，如神经和精神疾病，以及内分泌或代谢疾病。本发明还涉及放射性标记的化合物，其可用于使用正电子发射断层摄影（PET）在组织中成像和定量PDE2酶。本发明还涉及包含这些化合物的组合物，用于制备此类化合物和组合物的方法，以使用这些化合物和组合物用于在体外或体内成像组织，细胞或宿主以及所述化合物的前体。

2. 发明申请

WO2007003525A2 CYCLIC ANILINO - PYRIDINOTRIAZINES 审中-公开
标题翻译： CYCLIC ANILINO - PYRIDINOTRIAZINES
公开(公告)号：WO2007003525A2
公开(公告)日：2007-01-11
申请号：PCT/EP2006/063555
申请日：2006-06-26
申请人： JANSSEN PHARMACEUTICA N.V. , ROMBOUTS, Frederik, Jan, Rita , LOVE, Christopher, John , VAN EMELEN, Kristof , VAN BRANDT, Sven, Franciscus, Anna , WU, Tongfei
发明人： ROMBOUTS, Frederik, Jan, Rita , LOVE, Christopher, John , VAN EMELEN, Kristof , VAN BRANDT, Sven, Franciscus, Anna , WU, Tongfei
CPC分类号： C07D487/18 , C07D251/16 , C07D401/04 , C07D471/18 , C07D471/22 , C07D487/08
摘要： The present invention concerns the compounds of formula (I), the N -oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein m represents 1, n represents 1, Z represents N or C, in particular N; -X 1 - represents C 1-4 alkyl, in particular methyl; -X 2 - represents -C 1-4 alkyl- or -C 1-4 alkyl-NR 7 -, in particular propyl, -ethyl-NR 7 - or -propyl-NR 7 -; -Y- represents-NR 2 -C 1-6 alkyl-CO-NR 4 -, -Het 1 -C 1-6 alkyl-CO-NR 5 - or -Het 2 -CO-NR 6 - and wherein the -C 1-6 alkyl- linker of -NR 2 -C 1-6 alkyl-CO-NR 4 - or -Het 1 -C 1-6 alkyl-CO-NR 5 - is optionally substituted with one or where possible two or more substituents selected from hydroxy, halo and phenyl; R 1 represents hydrogen, chloro, fluoro or bromo; R 2 represents -C 1-4 alkyl-, in particular ethyl or methyl; R 7 represents hydrogen; R 8 represents hydrogen; R 4 , R 5 and R 6 represent hydrogen; Het 1 is selected from piperazinyl or piperidinyl, in particular -piperazinyl; Het 2 selected from pyrrolidinyl or piperidinyl, in particular pyrrolidinyl wherein said pyrrolidinyl is optionally substituted with hydroxy.
摘要翻译：本发明涉及式（I）化合物，N-氧化物形式，其药学上可接受的加成盐和立体化学异构形式，其中m表示1，n表示1，Z表示N或C，特别是N; -X 1表示C 1-4烷基，特别是甲基; -X 2 - 表示-C 1-4烷基 - 或-C 1-4 - 烷基-NR 7 - - ，特别是丙基， - 乙基-NR 7 - 或 - 丙基-NR 7 - ; -Y-表示-NR 2 -C 1-6烷基-CO-NR 4 - ，-Het 1 SUP / > -C 1-6烷基-CO-NR 5 - 或-Het 2 -CO-NR 6 - - 并且其中-NR 2 -C 1-6烷基-CO-NR的-C 1-6烷基 - 连接基团， 4 - 或-Het 1 -C 1-6烷基-CO-NR 5 - 任选被一个或多个可能的两个或更多个选自羟基，卤素和苯基的取代基; R 1表示氢，氯，氟或溴; R 2表示-C 1-4 - 烷基 - ，特别是乙基或甲基; R 7表示氢; R 8表示氢; R 4，R 5和R 6表示氢; Het 1选自哌嗪基或哌啶基，特别是哌嗪基; Het 2选自吡咯烷基或哌啶基，特别是吡咯烷基，其中所述吡咯烷基任选被羟基取代。

3. 发明申请

WO2011154431A1 5,6-DIHYDRO-2H-[1,4]OXAZIN-3-YL-AMINE DERIVATIVES USEFUL AS INHIBITORS OF BETA-SECRETASE (BACE) 审中-公开
标题翻译：作为β-分泌酶（BACE）的抑制剂有用的5,6-二氢-2H- [1,4]氧杂-3-氨基胺衍生物
公开(公告)号：WO2011154431A1
公开(公告)日：2011-12-15
申请号：PCT/EP2011/059441
申请日：2011-06-08
申请人： JANSSEN PHARMACEUTICA NV , TRABANCO-SUÁREZ, Andrés, Avelino , ROMBOUTS, Frederik, Jan, Rita , TRESADERN, Gary, John , VAN GOOL, Michiel, Luc, Maria , MACDONALD, Gregor, James , MARTINEZ LAMENCA, Carolina , GIJSEN, Henricus, Jacobus, Maria
发明人： TRABANCO-SUÁREZ, Andrés, Avelino , ROMBOUTS, Frederik, Jan, Rita , TRESADERN, Gary, John , VAN GOOL, Michiel, Luc, Maria , MACDONALD, Gregor, James , MARTINEZ LAMENCA, Carolina , GIJSEN, Henricus, Jacobus, Maria
IPC分类号： C07D265/30 , C07D413/04 , A61K31/535 , A61K31/5355 , A61P25/28 , A61P25/16
CPC分类号： C07D265/30 , C07D413/04 , C07D413/10
摘要： The present invention relates to novel 5,6-dihydro-2H-[1,4]oxazin-3-ylamine derivatives as inhibitors of beta-secretase, also known as beta-site amyloid cleaving enzyme, BACE, BACE1, Asp2, or memapsin2. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which beta-secretase is involved, such as Alzheimer's disease (AD), mild cognitive impairment, senility, dementia, dementia with Lewy bodies, Down's syndrome, dementia associated with stroke, dementia associated with Parkinson's disease and dementia associated with beta- amyloid.
摘要翻译：本发明涉及作为β-分泌酶抑制剂的新的5,6-二氢-2H- [1,4]恶嗪-3-基胺衍生物，也称为β位点淀粉样蛋白切割酶，BACE，BACE1，Asp2或memapsin2 。本发明还涉及包含这种化合物的药物组合物，制备这些化合物和组合物的方法，以及这些化合物和组合物用于预防和治疗其中涉及β-分泌酶的疾病如阿尔茨海默病的用途（例如， AD），轻度认知障碍，衰老，痴呆，路易体痴呆，唐氏综合征，与中风相关的痴呆，与帕金森病相关的痴呆和与β-淀粉样蛋白相关的痴呆。

4. 发明申请

WO2007003525A3 CYCLIC ANILINO-PYRIDINOTRIAZINES AS GSK-3 INHIBITORS 审中-公开
标题翻译：作为GSK-3抑制剂的CYCLIC ANILINO-PYRIDINOTRIAZINES
公开(公告)号：WO2007003525A3
公开(公告)日：2008-04-10
申请号：PCT/EP2006063555
申请日：2006-06-26
申请人： JANSSEN PHARMACEUTICA NV , ROMBOUTS FREDERIK JAN RITA , LOVE CHRISTOPHER JOHN , EMELEN KRISTOF VAN , VAN BRANDT SVEN FRANCISCUS ANN , WU TONGFEI
发明人： ROMBOUTS FREDERIK JAN RITA , LOVE CHRISTOPHER JOHN , VAN EMELEN KRISTOF , VAN BRANDT SVEN FRANCISCUS ANN , WU TONGFEI
IPC分类号： C07D251/16 , A61K31/53 , C07D401/04 , C07D471/18 , C07D471/22 , C07D487/08 , C07D487/18
CPC分类号： C07D487/18 , C07D251/16 , C07D401/04 , C07D471/18 , C07D471/22 , C07D487/08
摘要： The present invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein m represents 1, n represents 1, Z represents N or C, in particular N; -X 1 - represents C 1-4 alkyl, in particular methyl; -X 2 - represents -C 1-4 alkyl- or -C 1-4 alkyl-NR 7 -, in particular propyl, -ethyl-NR 7 - or -propyl-NR 7 -; -Y- represents-NR 2 -C 1-6 alkyl-CO-NR 4 -, -Het 1 -C 1-6 alkyl-CO-NR 5 - or -Het 2 -CO-NR 6 - and wherein the -C 1-6 alkyl- linker of -NR 2 -C 1-6 alkyl-CO-NR 4 - or -Het 1 -C 1-6 alkyl-CO-NR 5 - is optionally substituted with one or where possible two or more substituents selected from hydroxy, halo and phenyl; R 1 represents hydrogen, chloro, fluoro or bromo; R 2 represents -C 1-4 alkyl-, in particular ethyl or methyl; R 7 represents hydrogen; R 8 represents hydrogen; R 4 , R 5 and R 6 represent hydrogen; Het 1 is selected from piperazinyl or piperidinyl, in particular -piperazinyl; Het 2 selected from pyrrolidinyl or piperidinyl, in particular pyrrolidinyl wherein said pyrrolidinyl is optionally substituted with hydroxy.
摘要翻译：本发明涉及式（I）化合物，N-氧化物形式，其药学上可接受的加成盐和立体化学异构形式，其中m表示1，n表示1，Z表示N或C，特别是N; -X 1表示C 1-4烷基，特别是甲基; -X 2 - 表示-C 1-4烷基 - 或-C 1-4 - 烷基-NR 7 - - ，特别是丙基， - 乙基 - NR 7 - 或 - 丙基-NR 7 - 。 -Y-表示-NR 2 -C 1-6烷基-CO-NR 4 - ，-Het 1 SUP / > -C 1-6烷基-CO-NR 5 - 或-Het 2 -CO-NR 6 - - 并且其中-NR 2 -C 1-6烷基-CO-NR的-C 1-6烷基 - 连接基团， 4 - 或-Het 1 -C 1-6烷基-CO-NR 5 - 任选被一个或多个可能的两个或更多个选自羟基，卤素和苯基的取代基; R 1表示氢，氯，氟或溴; R 2表示-C 1-4烷基 - ，特别是乙基或甲基; R 7表示氢; R 8表示氢; R 4，R 5和R 6表示氢; Het 1选自哌嗪基或哌啶基，特别是哌嗪基; Het 2选自吡咯烷基或哌啶基，特别是吡咯烷基，其中所述吡咯烷基任选被羟基取代。

5. 发明申请

WO2011006903A1 SUBSTITUTED TRIAZOLE AND IMIDAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS 审中-公开
标题翻译：取代三唑和咪唑衍生物作为GAMMA秘密调节剂
公开(公告)号：WO2011006903A1
公开(公告)日：2011-01-20
申请号：PCT/EP2010/060083
申请日：2010-07-13
申请人： ORTHO-MCNEIL-JANSSEN PHARMACEUTICALS, INC , WU, Tongfei , GIJSEN, Henricus, Jacobus, Maria , ROMBOUTS, Frederik, Jan, Rita , BISCHOFF, François, Paul , BERTHELOT, Didier, Jean-Claude , OEHLRICH, Daniel , DE CLEYN, Michel, Anna, Jozef , PIETERS, Serge, Maria, Aloysius , MINNE, Garrett, Berlond , VELTER, Adriana, Ingrid , VAN BRANDT, Sven, Franciscus, Anna , SURKYN, Michel
发明人： WU, Tongfei , GIJSEN, Henricus, Jacobus, Maria , ROMBOUTS, Frederik, Jan, Rita , BISCHOFF, François, Paul , BERTHELOT, Didier, Jean-Claude , OEHLRICH, Daniel , DE CLEYN, Michel, Anna, Jozef , PIETERS, Serge, Maria, Aloysius , MINNE, Garrett, Berlond , VELTER, Adriana, Ingrid , VAN BRANDT, Sven, Franciscus, Anna , SURKYN, Michel
IPC分类号： C07D233/60 , C07D401/14 , C07D403/10 , C07D487/04 , A61K31/4178 , A61K31/4196 , A61K31/4439 , A61P25/28 , C07D405/14 , C07D471/04 , C07D498/04
CPC分类号： C07D233/60 , C07D401/14 , C07D403/10 , C07D405/14 , C07D471/04 , C07D487/04 , C07D498/04
摘要： The present invention is concerned with novel substituted triazole and imidazole derivatives of Formula (I) wherein R 1 , R 2 , A 1 , A 2 , A 3 , A 4 , X, and Het 1 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.
摘要翻译：本发明涉及式（I）的新型取代的三唑和咪唑衍生物，其中R1，R2，A1，A2，A3，A4，X和Het1具有权利要求中限定的含义。根据本发明的化合物可用作γ-分泌酶调节剂。本发明还涉及制备这种新化合物的方法，包含所述化合物作为活性成分的药物组合物以及所述化合物作为药物的用途。

6. 发明申请

WO2006061415A1 2,4 (4,6) PYRIMIDINE DERIVATIVES 审中-公开
标题翻译： 2,4（4,6）吡嗪衍生物
公开(公告)号：WO2006061415A1
公开(公告)日：2006-06-15
申请号：PCT/EP2005/056606
申请日：2005-12-08
申请人： JANSSEN PHARMACEUTICA N.V. , FREYNE, Eddy, Jean, Edgard , WILLEMS, Marc , EMBRECHTS, Werner, Constant , Johan , VAN EMELEN, Kristof , VAN BRANDT, Sven, Franciscus, Anna , ROMBOUTS, Frederik, Jan, Rita
发明人： FREYNE, Eddy, Jean, Edgard , WILLEMS, Marc , EMBRECHTS, Werner, Constant , Johan , VAN EMELEN, Kristof , VAN BRANDT, Sven, Franciscus, Anna , ROMBOUTS, Frederik, Jan, Rita
IPC分类号： C07D487/08 , C07D487/22 , C07D498/18 , A61K31/505 , A61P35/00 , C07D259/00 , C07D239/00 , C07D241/00 , C07D209/00 , C07D273/00 , C07D221/00
CPC分类号： C07D487/18 , C07D487/08 , C07D487/22 , C07D498/08 , C07D498/18
摘要： The present invention concerns the compounds of formula (I), the N -oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z 1 and Z 2 represent NH; Y represents -C 3-9 alkyl-, -C 3-9 alkenyl-, -C 1-5 alkyl-NR 6 -C 1-5 alkyl-, -C 1-5 alkyl-NR 7 -CO-C 1 -5 alkyl-, -C 1-6 alkyl-CO-NH-, -C 1-6 alkyl-NH-CO-, -C 1-2 alkyl-CO-Het 10 -CO-, -C 1-3 alkyl-NH-CO-Het 3 -, -Het 4 -C 1-3 alkyl-CO-NH-C 1-3 alkyl-, -C 1-2 alkyl-NH-CO-L 1 -NH-, -NH-CO-L 2 -NH-, -C 1-2 alkyl-CO-NH-L 3 -CO-, -C 1-2 alkyl-NH-CO-L 1 -NH-CO-C 1-3 alkyl-, -C 1-2 alkyl-CO-NH-L 3 -CO-NH-C 1-3 alkyl-, -C 1-2 alkyl-NR 11 -CH 2 -CO-NH-C 1-3 alkyl-, Het 5 -CO-C 1-2 alkyl-, -C 1-5 alkyl-CO-NH-C 1-3 alkyl-CO-NH-, -C 1-5 alkyl-NR 13 -CO-C 1-3 alkyl-NH-, -C 1-3 alkyl-NH-CO-Het 27 -CO-, or -C 1-3 alkyl-CO-Het 28 -CO-NH-; X 1 represents a direct bond, O, -O-C 1-2 alkyl-, -CO-C 1-2 alkyl-, -NR 16 -C 1-2 alkyl-, -CO-NR 17 -, Het 23 -C 1-2 alkyl- or C 1-2 alkyl; X 2 represents a direct bond, O, -O-C 1-2 alkyl-, -CO-C 1-2 alkyl-, -NR 18 -C 1-2 alkyl-, -CO-NR 19 -, Het 24 -C 1-2 alkyl- or C 1-2 alkyl; R 1 and R 5 each independently represent hydrogen, halo, C 1-6 alkyloxy- or C 1-6 alkyloxy- substituted with Het 1 or C 1-4 alkyloxy-; R 2 and R 4 each independently represent hydrogen or halo; R 3 represents hydrogen or cyano; R 6 , R 7 , R 13 , R 17 and R 19 represent hydrogen; R 11 represents hydrogen or C 1-4 alkyl; R 16 and R 18 represent hydrogen, C 1-4 alkyl or Het 17 -C 1-4 alkyl-; L 1 , L 2 and L 3 each independently represents C 1-8 alkyl optionally substituted with one or where possible two or more substituents selected from phenyl, methylsulfide, cyano, polyhaloC 1-4 alkyl-phenyl-, C 1-4 alkyloxy, pyridinyl, mono- or di(C 1-4 alkyl)-amino- or C 3-6 cycloalkyl; Het 1 , Het 2 , Het 17 each independently represent morpholinyl, oxazolyl, isoxazolyl, or piperazinyl; Het 3 , Het 4 , Het 5 each independently represent morpholinyl, piperazinyl, piperidinyl or pyrrolidinyl; Het 10 represents piperazinyl, piperidinyl, pyrrolidinyl or azetidinyl; Het 22 represents morpholinyl, oxazolyl, isoxazolyl or piperazinyl wherein said Het 22 is optionally substituted with C 1-4 alkyl; Het 23 and Het 24 each independently represent a heterocycle selected from pyrrolidinyl, piperazinyl or piperidinyl wherein said Het 23 or Het 24 are optionally substituted with Het 22 -carbonyl; Het 27 and Het 28 each independently represent a heterocycle selected from morpholinyl, piperazinyl, piperidinyl or pyrrolidinyl.
摘要翻译：本发明涉及式（I）化合物，N-氧化物形式，其药学上可接受的加成盐和立体化学异构形式，其中Z 1和Z 2，代表NH; Y表示-C 3-9 - 烷基 - ， - C 3-9 - 烯基 - ， - C 1-5烷基-NH- C 1-6烷基 - ， - C 1-5 - 烷基-NR 7 -CO-C 1 -C 6 - 1〜5个烷基 - ， - C 1-6 - 烷基-CO-NH - ， - C 1-6烷基-NH- CO - ， - C 烷基-CO-Het 10 -CO-，-C 1-3烷基-NH-CO-Het 3 H-4-C 1-3烷基-CO-NH-C 1-3烷基 - ， - C 烷基-NH-CO-L 1 -NH-，-NH-CO-L 2 -NH-，-C 烷基-CO-NH-L 3 -CO-，-C 1-12烷基-NH-CO-L， 1-NH-CO-C 1-3烷基 - ， - C 1-12烷基-CO-NH-L 3 -CO-NH-C 1-3烷基 - ， - C 1-12烷基-NR 11 -CH 2 - -CO-NH-C 1-3烷基 - ，Het 5 -CO-C 1-2烷基 - ， - C 烷基-CO-NH-C 1-3烷基-CO-NH - ， - C 1-5烷基-NH- 叔-C 1-3烷基-NH-，-C 1-3烷基-NH-CO-Het 27， -CO-或-C 1-3烷基-CO-Het 28 -CO-NH-; X 1表示直接键合，O，-OC 1-2烷基 - ， - CO-C 1-12 - 烷基 - ， - NR C 1-12烷基 - ， - CO-NR 17 - ，Het 23 -C _{1-2个烷基 - 或C 1-12烷基; O 2代表直接键合，O，-OC 1-2烷基 - ， - CO-C 1-2烷基 - ， - NR C 1-12烷基 - ， - CO-NR 19 - ，Het 24 -C _{1-2个烷基 - 或C 1-12烷基; R 1和R 2各自独立地表示氢，卤素，C 1-6烷氧基或C 1-6 >由Het 1或C 1-4烷氧基取代的烷氧基取代; R 2和R 4各自独立地表示氢或卤素; R 3表示氢或氰基; R 6，R 7，R 13，R 17和R 19代表氢; R 11表示氢或C 1-4烷基; R 16和R 18代表氢，C 1-4烷基或Het 17 -C 1 -4 烷基 - ; L 1，L 2和L 3各自独立地表示任选被一个或多个取代基取代的C 1-8烷基可能的两个或更多个选自苯基，甲基硫基，氰基，多卤代1-4烷基 - 苯基 - ，C 1-4烷基氧基，吡啶基，单 - 或二（C C 1-4烷基） - 氨基 - 或C 3-6环烷基; Het 2，Het 2，Het 17各自独立地表示吗啉基，恶唑基，异恶唑基或哌嗪基; Het 4，Het 4，Het 5 H 3各自独立地表示吗啉基，哌嗪基，哌啶基或吡咯烷基; Het 10表示哌嗪基，哌啶基，吡咯烷基或氮杂环丁烷基; Het 22代表吗啉基，恶唑基，异恶唑基或哌嗪基，其中所述Het 22任选被C 1-4烷基取代; Het 23和Het 24各自独立地表示选自吡咯烷基，哌嗪基或哌啶基的杂环，其中所述Het 23或Het 24， SUP>任选被Het 22-羰基取代; Het 27和Het 28各自独立地表示选自吗啉基，哌嗪基，哌啶基或吡咯烷基的杂环。}}

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