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61. 发明专利

AU2012322698A1 8 - carbamoyl - 2 - (2,3- di substituted pyrid - 6 - yl) -1,2,3,4 -tetrahydroisoquinoline derivatives as apoptosis - inducing agents for the treatment of cancer and immune and autoimmune diseases 未知
公开(公告)号：AU2012322698A1
公开(公告)日：2014-04-17
申请号：AU2012322698
申请日：2012-10-11
申请人： ABBVIE INC
发明人： WANG LE , DOHERTY GEORGE , WANG XILU , TAO ZHI-FU , BRUNKO MILAN , KUNZER AARON R , WENDT MICHAEL D , SONG XIAOHONG , FREY ROBIN , HANSEN TODD M , SULLIVAN GERARD M , JUDD ANDREW , SOUERS ANDREW
IPC分类号： C07D417/14 , A61K31/4725 , A61P35/00 , C07D471/04 , C07D487/04 , C07D513/04
摘要： Disclosed are compounds of formula (I) which inhibit the activity of anti-apoptotic Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which Bcl-xL proteins are expressed, eg cancer. X is heteroaryl; Y

62. 发明专利

NZ593594A APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES 未知
公开(公告)号：NZ593594A
公开(公告)日：2013-08-30
申请号：NZ59359410
申请日：2010-01-15
申请人： ABBVIE INC
发明人： WANG XILU , PARK CHEOL-MIN , HEXAMER LAURA , WENDT MICHAEL D , KUNZER AARON R , ELMORE STEVEN W , SULLIVAN GERARD M , SOUERS ANDREW J , WANG GARY T
IPC分类号： C07C311/51 , A61K31/18 , A61P35/00 , C07D207/36 , C07D211/96 , C07D231/18 , C07D261/10 , C07D275/03 , C07D277/36 , C07D285/125 , C07D285/135 , C07D295/155
摘要： 593594 Disclosed are sulphonyl substituted benzylamides of formula (I) where the substituents are as disclosed in the specification. Examples of compounds of formula (I) are: 4-[4-(cyclohexylmethyl)-4-methoxypiperidin-1-yl]-N-{ [5-({ (1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl} amino)-4-nitrothien-2-yl]sulfonyl} benzamide; N-{ [5-({ (1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl} amino)-4-nitrothien-2-yl]sulfonyl} -4-[4-methoxy-4-(3-methylbenzyl)piperidin-1-yl]benzamide; N-{ [5-({ (1R)-3-(dimethylamino)-1-[(phenylthio)methyl]propyl} amino)-4-nitrothien-2-yl]sulfonyl} -4-[4-(3,3-diphenylprop-2-enyl)piperazin-1-yl]benzamide; and 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-({ 2-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-4-methyl-1,3-thiazol-5-yl} sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide. Further disclosed are the use of the compounds in the manufacture of a medicament for treating bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoid malignancy of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small cell lung cancer or spleen cancer in a patient.

63. 发明专利

UY34382A AGENTES INDUCTORES DE LA APOPTOSIS QUE PUEDEN USARSE PARA TRATAR EL CÁNCER Y LAS ENFERMEDADES INMUNES Y AUTOINMUNES 未知
公开(公告)号：UY34382A
公开(公告)日：2013-05-31
申请号：UY34382
申请日：2012-10-10
申请人： ABBVIE INC
发明人： GEORGE DOHERTY , KUNZER AARON R , XILU WANG , ZHI-FU TAO , LE WANG , MILAN BRUNKO , WENDT MICHAEL D , XIAOHONG SONG , ROBIN FREY , HANSEN TODD M , SULLIVAN GERARD M , ANDREW JUDD
IPC分类号： A61K31/345 , A61K31/44 , A61P35/00 , C07D401/02 , C07D401/04
摘要： Compuestos que inhiben la actividad de las proteínas antiapoptóticas Bcl-xL, composiciones que contienen dichos compuestos y métodos para tratar enfermedades en las que se expresan las proteínas antiapoptóticas Bcl-xL.

64. 发明专利

CL2012001421A1 Compuestos derivados de heterociclos, inductores de apoptosis, inhibidores de la actividad de la proteina bcl-2; usos de dichos compuestos y combinaciones que los comprenden, para el tratamiento del cancer y de enfermedades inmunes y autoinmunes. 未知
公开(公告)号：CL2012001421A1
公开(公告)日：2013-05-17
申请号：CL2012001421
申请日：2012-05-31
申请人： ABBVIE INC
发明人： WANG LE , WANG XILU , TAO ZHI-FU , WENDT MICHAEL D , SONG XIAOHONG , HANSEN TODD M , BRUNCKO MILAN , DING HONG , HASVOLD LISA , HEXAMER LAURA , KUNZER AARON , SOUERS ANDREW J , DAI YUJIA , DOHERTY GEORGE A , ELMORE STEVEN W , MANTEI ROBERT A , MCCLELLAN WILLIAM J , PARK CHANG H , PARK CHEOL-MIN , PETROS ANDREW M , SULLIVAN GERARD M , WANG GARY T
IPC分类号： C07D401/14 , A61K31/496 , A61P35/00 , A61P37/00 , C07D403/12
摘要： Compuesto derivado de heterociclos, inductores de apoptosis; composición farmacéutica que comprende dichos compuestos; y un método de tratamiento para el tratamiento de cáncer y enfermedades inmunes y autoinmunes.

65. 发明专利

AU2009322219B2 Sulfonamide derivatives as Bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases 未知
公开(公告)号：AU2009322219B2
公开(公告)日：2013-05-09
申请号：AU2009322219
申请日：2009-12-04
申请人： ABBVIE INC
发明人： BRUNCKO MILAN , DING HONG , DOHERTY GEORGE A , ELMORE STEVEN W , HASVOLD LISA , HEXAMER LAURA , KUNZER AARON R , MANTEI ROBERT A , MCCLELLAN WILLIAM J , PARK CHANG H , PARK CHEOL-MIN , PETROS ANDREW M , SONG XIAOHONG , SOUERS ANDREW J , SULLIVAN GERARD M , TAO ZHI-FU , WANG GARY T , WANG LE , WANG XILU , WENDT MICHAEL D
IPC分类号： C07D209/32 , A61K31/404 , A61P35/00 , C07D211/96 , C07D213/64 , C07D215/20 , C07D217/16 , C07D235/26 , C07D249/04 , C07D295/125 , C07D295/14 , C07D309/14 , C07D401/12 , C07D405/12
摘要： Disclosed are compounds of formula (I) which inhibit the activity of anti-apoptotic BcI -2 or BcI -xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti -aooptotic Bcl-2 protein.

66. 发明专利

CA2850976A1 APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES 未知
公开(公告)号：CA2850976A1
公开(公告)日：2013-04-18
申请号：CA2850976
申请日：2012-10-11
申请人： ABBVIE INC
发明人： WANG LE , DOHERTY GEORGE , WANG XILU , TAO ZHI-FU , BRUNKO MILAN , KUNZER AARON R , WENDT MICHAEL D , SONG XIAOHONG , FREY ROBIN , HANSEN TODD M , SULLIVAN GERARD M , JUDD ANDREW , SOUERS ANDREW
IPC分类号： C07D417/14
摘要： Disclosed are compounds having Formula (I) which inhibit the activity of anti-apoptotic Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-xL protein.

67. 发明专利

ZA201104672B APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES 未知
公开(公告)号：ZA201104672B
公开(公告)日：2012-03-28
申请号：ZA201104672
申请日：2011-06-23
申请人： ABBVIE INC
发明人： HEXAMER LAURA , ELMORE STEVEN W , SONG XIAOHONG , SULLIVAN GERARD M , WENDT MICHAEL D , DING HONG , KUNZER AARON R , SOUERS ANDREW J , TAO ZHI-FU
IPC分类号： A61K20060101 , A61P20060101 , C07D20060101

68. 发明专利

IL282594D0 Bcl xl inhibitory compounds having low cell permeability and antibody drug conjugates including the same 未知
公开(公告)号：IL282594D0
公开(公告)日：2021-06-30
申请号：IL28259421
申请日：2021-04-22
申请人： ABBVIE INC , TAO ZHI FU , DOHERTY GEORGE , WANG XILU , SONG XIAOHONG , SULLIVAN GERARD M , KUNZER AARON , WENDT MICHAEL , MARIN VIOLETA L , FREY ROBIN R , CULLEN STEVE C , WELCH DENNIE S , SHEN XIAOQIANG , BENNETT DAVID JONATHAN , HAIGHT ANTHONY R , ACKLER SCOTT L , BOGHAERT ERWIN R , SOUERS ANDREW J , JUDD ANDREW S
发明人： TAO ZHI-FU , DOHERTY GEORGE , WANG XILU , SONG XIAOHONG , SULLIVAN GERARD M , KUNZER AARON , WENDT MICHAEL , MARIN VIOLETA L , FREY ROBIN R , CULLEN STEVE C , WELCH DENNIE S , SHEN XIAOQIANG , BENNETT DAVID JONATHAN , HAIGHT ANTHONY R , ACKLER SCOTT L , BOGHAERT ERWIN R , SOUERS ANDREW J , JUDD ANDREW S
IPC分类号： A61K31/4709 , A61K31/4725 , A61K31/498 , A61K31/4985 , A61K31/538 , A61K45/06 , A61K47/68 , A61P35/00 , A61P35/02 , A61P43/00
摘要： The present disclosure concerns Bcl-xL inhibitors having low cell permeability, antibody drug conjugates (ADCs) comprising the inhibitors, synthons useful for synthesizing the ADCs, compositions comprising the inhibitors or ADCs, and various methods of using the inhibitors and ADCs.

69. 发明专利

SG10201911585XA BCL XL INHIBITORY COMPOUNDS HAVING LOW CELL PERMEABILITY AND ANTIBODY DRUG CONJUGATES INCLUDING THE SAME 未知
公开(公告)号：SG10201911585XA
公开(公告)日：2020-01-30
申请号：SG10201911585X
申请日：2015-12-09
申请人： ABBVIE INC
发明人： TAO ZHI-FU , DOHERTY GEORGE , WANG XILU , SULLIVAN GERARD M , SONG XIAOHONG , KUNZER AARON R , WENDT MICHAEL D , MARIN VIOLETA L , FREY ROBIN R , CULLEN STEVE C , WELCH DENNIE S , SHEN XIAOQIANG , BENNETT NATHAN B , HAIGHT ANTHONY R , ACKLER SCOTT L , BOGHAERT ERWIN R , SOUERS ANDREW J , JUDD ANDREW S
摘要： The present disclosure concerns Bcl-xL inhibitors having low cell permeability, antibody drug conjugates (ADCs) comprising the inhibitors, synthons useful for synthesizing the ADCs, compositions comprising the inhibitors or ADCs, and various methods of using the inhibitors and ADCs.

70. 发明专利

ES2699966T3 Agentes inductores de la apoptosis para el tratamiento del cáncer y enfermedades inmunes y autoinmunes 未知
公开(公告)号：ES2699966T3
公开(公告)日：2019-02-13
申请号：ES12778012
申请日：2012-10-11
申请人： ABBVIE INC
发明人： WANG LE , DOHERTY GEORGE , WANG XILU , TAO ZHI-FU , BRUNKO MILAN , KUNZER AARON R , WENDT MICHAEL D , SONG XIAOHONG , FREY ROBIN , HANSEN TODD M , SULLIVAN GERARD M , JUDD ANDREW , SOUERS ANDREW
IPC分类号： C07D417/14 , A61K31/428 , A61P35/00
摘要： Un compuesto o una sal terapéuticamente aceptable del mismo, en donde el compuesto se selecciona a partir del grupo que consiste en ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-bencil-1H-pirazol-4-il)piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(1-feniletil)-1H-pirazol-4-il]piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(3-clorobencil)-1H-pirazol-4-il]piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-bencil-3,5-dimetil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(3-metilbencil)-1H-pirazol-4-il]piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{3-[2-(dimetilamino)etoxi]bencil}-1Hpirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-bencil-3-metil-1H-pirazol-4-il)piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-bencil-5-metil-1H-pirazol-4-il)piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquino)in-2(1H)-il]-3-(20 1-{[6-(pirrolidin-1-il)piridin-2-il]metil}-1H- pirazol- 4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(2-clorobencil)-1H-pirazol-4-il]piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-bencil-3-(hidroximetil)-5-metil-1Hpirazol-4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(5-metil-1-{[6-(pirrolidin-1-il)piridin-2- il]metil}-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[3-(dimetilamino)bencil]-1H-pirazol-4- il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(2,3-dihidro-1H-inden-1-il)-1H-pirazol-4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{2-[2-(dimetilamino)etoxi]bencil}-1Hpirazol- 4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(2-fluorobencil)-5-metil-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(ciclohexilmetil)-1H-pirazol-4-il]piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(ciclohexilmetil)-5-metil-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{2-[3-(dimetilamino)propoxi]bencil}-1H- pirazol- 4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{2-[2-(dimetilamino)etoxi]bencil}-5-metil- 1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(2,3-difluorobencil)-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(3,5-difluorobencil)-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(2,5-difluorobencil)-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(2,6-difluorobencil)-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(tetrahidro-2H-piran-3-ilmetil)-1Hpirazol- 4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(2-nitrobencil)-1H-pirazol-4-il]piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(2-ciclohexiletil)-1H-pirazol-4-il]piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[3-(trifluorometil)bencil]-1H-pirazol-4- il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(ciclopentilmetil)-5-metil-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[5-metil-1-(tetrahidro-2H-piran-3-ilmetil)- 1H-pirazol-4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[(1-fenilciclohexil)metil]-1H-pirazol-4- il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(ciclohexilmetil)-5-ciclopropil-1H-pirazol- 4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[(4,4-difluorociclohexil)metil]-5-metil-1Hpirazol- 4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(trifluorometil)ciclohexil]metil}-1Hpirazol- 4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(difenilmetil)-1H-pirazol-4-il]piridin-2- carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[3-(morfolin-4-il)-1-fenilpropil]-1Hpirazol- 4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(5-metil-1-{2-[2-(morfolin-4-il)etoxi]bencil}- 1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[2-(dimetilamino)bencil]-1H-pirazol-4- il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(5-metil-1-{2-[3-(morfolin-4- il)propoxi]bencil}-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{5-metil-1-[(1-metilciclohexil)metil]-1Hpirazol- 4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(ciclohexilmetil)-5-etil-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[(1R,2R,5R)-6,6- dimetilbiciclo[3.1.1]hept-2-il]metil}-5-metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[(1S,2R,5S)-6,6- dimetilbiciclo[3.1.1]hept-2-il]metil}-5-metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(2-metilpropil)ciclohexil]metil}-1Hpirazol- 4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(2-metoxietil)ciclohexil]metil}-1Hpirazol- 4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[2-(2-metoxietoxi)bencil]-5-metil-1H pirazol-4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[(1R,2R,4R)-biciclo[2.2.1]hept-5-en-2- ilmetil]-5-metil-1H-pirazol-4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[(3,3-dimetilciclohexil)metil]-1H-pirazol- 4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(3-metoxi-1-fenilpropil)-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(4-metoxi-)1-fenilbutil)-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(2-metoxi-2-oxo-1-feniletil)-1H-pirazol- 4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(2-ciclohexil-1-feniletil)-1H-pirazol-4- il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(3-metoxipropil)ciclohexil]metil}-5- metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{2-[3-hidroxi-2-(hidroximetil)-2- metilpropoxi]bencil}-5-metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{5-metil-1-[2-(tetrahidro-2H-piran-4- ilmetoxi)bencil]-1H-pirazol-4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[2-(1,4-dioxan-2-il)metoxi)bencil)]-5-metil-1H-pirazol-4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(2-metoxietoxi)ciclohexil]metil}-5- metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(2-metoxietil)cicloheptil]metil}-5- metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(metoximetil)ciclohexil]metil}-5-metil- 1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[3,3-dimetil-1-(morfolin-4- il)ciclohexil]metil}-5-metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(2-metoxietil)-3,3- dimetilciclohexil]metil}-5-metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(3-metoxipropil)cicloheptil]metil}-5- metil-1H-pirazol-4-il)piridin-2-carboxílico; N-(1,3-benzotiazol-2-il)-2-{5-(1-{[1-(2-metoxietil)cicloheptil]metil}-5-metil-1H-pirazol-4-il)-6- [(metilsulfonil)carbamoil]piridin-2-il}-1,2,3,4-tetrahidroisoquinolin-8-carboxamida; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(tetrahidro-2H-piran-2-ilmetil)-1Hpirazol- 4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1R,2R,3R,5S)-2-(2-metoxietil)-6,6- dimetilbiciclo[3.1.1]hept-3-il]metil}-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(2-metoxietoxi)cicloheptil]metil}-5-metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[1-ciclohexil-3-(morfolin-4-il)propil]-5- metil-1H-pirazol-4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[5-metil-1-(tetrahidro-2H-piran-2-ilmetil)- 1H-pirazol-4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[5-metil-1-({1-[3-(morfolin-4- il)propoxi]cicloheptil}metil)-1H-pirazol-4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[(1-metoxi-3,3-dimetilciclohexil)metil]-5- metil-1H-pirazol-4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(5-metil-1-{[1-(morfolin-4- il)ciclohexil]metil}-1H-pirazol-4-il)piridin-2-carboxílico; N-(1,3-benzotiazol-2-il)-2-(5-{1-[(1-metoxi-3,3-dimetilciclohexil)metil]-5-metil-1H-pirazol-4-il}-6-[(metilsulfonil)carbamoil]piridin-2-il)-1,2,3,4-tetrahidroisoquinolin-8-carboxamida; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-1-metil-3,4-dihidroisoquinolin-2(1H)-il]-3-{5-metil-1-[(1-metilciclohexil)metil]- 1H-pirazol-4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-{1-[(1-metoxiciclohexil)metil]-5-metil-1Hpirazol-4-il}piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-({1-[2-(1,1-dioxidotiomorfolin-4- il)etoxi]ciclohexil}metil)-5-metil-1H-pirazol-4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(2-hidroxietoxi)ciclohexil]metil}-5- metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazo)-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(2,3- dimetoxipropoxi)cicloheptil]metil}-5-metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(1,4-dioxan-2- ilmetoxi)cicloheptil]metil}-5-metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[5-metil-)-({1-[2-(morfolin-4-il)-2- oxoetoxi]ciclohexil}metil)-1H-pirazol-4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(2,3- dihidroxipropoxi)cicloheptil]metil}-5-metil-1H-pirazol-4-il)piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-({3,3-dimetil-1-[2- (metilsulfonil)etoxi]ciclohexil}metil)-5-metil-1H-pirazol-4-il]piridin-2-carboxílico; ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-(1-{[1-(2-metoxietoxi)-3,3- dimetilciclohexil]metil}-5-metil-1H-pirazol-4-il)piridin-2-carboxílico; y ácido 6-[8-(1,3-benzotiazol-2-ilcarbamoil)-3,4-dihidroisoquinolin-2(1H)-il]-3-[1-(1-ciclohexil-3-metoxipropil)-5-metil-1Hpirazol- 4-il]piridin-2-carboxílico.

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