公开(公告)号：US20070299051A1

公开(公告)日：2007-12-27

申请号：US11667583

申请日：2005-11-08

申请人： Bansi Lal ,  Swati Bal-Tembe ,  Usha Ghosh ,  Arun Jain ,  Tulsidas More ,  Anil Ghate ,  Jacqueline Trivedi ,  Sapna Parikh

发明人： Bansi Lal ,  Swati Bal-Tembe ,  Usha Ghosh ,  Arun Jain ,  Tulsidas More ,  Anil Ghate ,  Jacqueline Trivedi ,  Sapna Parikh

IPC分类号： A61K31/554 ,  A61K31/39 ,  A61K31/496 ,  A61P9/00 ,  C07D267/16 ,  C07D411/02 ,  C07D413/02 ,  C07D327/00 ,  A61P9/10 ,  A61P39/00 ,  A61K31/5377

CPC分类号： C07D327/08

摘要： Guanidine derivatives having a condensed tricyclic ring of formula 1: are disclosed, wherein U is C(O), CRaRb, O, NRa or S(O)m; V is CRaRb or NRa; W is S(O)m; wherein Ra is H, alkyl, cycloalkyl, alkenyl or aralkyl; Rb is H, alkyl, OH, ORa or OCORa, and m is the integer 0, 1 or 2; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein with the proviso that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidino or guanidino carbonyl. These derivatives are sodium-proton exchange inhibitors and are useful as medicaments for the treatment of, for example, organ disorders associated with ischemia and reperfusion, cardiac arrhythmia, cardiac hypertrophy, hypertension, cell proliferative disorders and diabetes.

摘要翻译： 公开了具有式1的稠合三环的胍衍生物：其中U是C（O），CR 1，O，NR a， SUP>或S（O）m < V是R a，R b，O或NR a， W是S（O）m。 其中R a是H，烷基，环烷基，烯基或芳烷基; R b是H，烷基，OH，OR a或OCOR a a，m是整数0,1或2; R1，R2，R3，R4，R5，R6，R7和R8如本文所定义，条件是R 1，R 2，R 3，R 4，R 5，R 6，R 7或R 8中的至少一个是胍基或胍基羰基。 这些衍生物是钠 - 质子交换抑制剂，并且可用作治疗例如与缺血和再灌注相关的器官疾病，心律失常，心脏肥大，高血压，细胞增殖性疾病和糖尿病的药物。

公开(公告)号：US20100267690A1

公开(公告)日：2010-10-21

申请号：US12827277

申请日：2010-06-30

申请人： Bansi LAL ,  Swati Bal-Tembe ,  Usha Ghosh ,  Arun Kumar Jain ,  Tulsidas More ,  Anil Ghate ,  Jacqueline Trivedi ,  Sapna Parikh

发明人： Bansi LAL ,  Swati Bal-Tembe ,  Usha Ghosh ,  Arun Kumar Jain ,  Tulsidas More ,  Anil Ghate ,  Jacqueline Trivedi ,  Sapna Parikh

IPC分类号： A61K31/554 ,  A61K31/155 ,  A61K31/445 ,  A61K31/40 ,  A61K31/27 ,  A61K31/255 ,  A61K31/4965 ,  A61K31/5375 ,  A61K31/4174 ,  A61K31/34 ,  A61K31/381 ,  A61K31/497 ,  A61K31/5377 ,  A61K31/39 ,  A61P9/10 ,  A61P3/00 ,  A61P25/00

CPC分类号： C07D327/08

摘要： Guanidine derivatives having a condensed tricyclic ring of formula 1: are disclosed, wherein U is C(O), CRaRb, O, NRa or S(O)m; V is CRaRb or NRa; W is S(O)m; wherein Ra is H, alkyl, cycloalkyl, alkenyl or aralkyl; Rb is H, alkyl, OH, ORa or OCORa, and m is the integer 0, 1 or 2; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein with the proviso that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidino or guanidino carbonyl. These derivatives are sodium-proton exchange inhibitors and are useful as medicaments for the treatment of, for example, organ disorders associated with ischemia and reperfusion, cardiac arrhythmia, cardiac hypertrophy, hypertension, cell proliferative disorders and diabetes.

摘要翻译： 公开了具有式1的稠合三环的胍衍生物，其中U是C（O），CR a R b，O，NR a或S（O）m; V是CRaRb或NRa; W为S（O）m; 其中R a是H，烷基，环烷基，烯基或芳烷基; Rb是H，烷基，OH，ORa或OCORa，m是整数0,1或2; R1，R2，R3，R4，R5，R6，R7和R8如本文所定义，条件是R 1，R 2，R 3，R 4，R 5，R 6，R 7或R 8中的至少一个是胍基或胍基羰基。 这些衍生物是钠 - 质子交换抑制剂，并且可用作治疗例如与缺血和再灌注相关的器官疾病，心律失常，心脏肥大，高血压，细胞增殖性疾病和糖尿病的药物。

公开(公告)号：US08183234B2

公开(公告)日：2012-05-22

申请号：US12827277

申请日：2010-06-30

申请人： Bansi Lal ,  Swati Bal-Tembe ,  Usha Ghosh ,  Arun Kumar Jain ,  Tulsidas More ,  Anil Ghate ,  Jacqueline Trivedi ,  Sapna Parikh

发明人： Bansi Lal ,  Swati Bal-Tembe ,  Usha Ghosh ,  Arun Kumar Jain ,  Tulsidas More ,  Anil Ghate ,  Jacqueline Trivedi ,  Sapna Parikh

IPC分类号： A61P7/00 ,  A61P9/00

CPC分类号： C07D327/08

摘要： Guanidine derivatives having a condensed tricyclic ring of formula 1: are disclosed, wherein U is C(O), CRaRb, O, NRa or S(O)m; V is CRaRb or NRa; W is S(O)m; wherein Ra is H, alkyl, cycloalkyl, alkenyl or aralkyl; Rb is H, alkyl, OH, ORa or OCORa, and m is the integer 0, 1 or 2; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein with the proviso that at least one of R1, R2, R3, R4, R5, R6, R7 or R8 is guanidino or guanidinocarbonyl. These derivatives are sodium-proton exchange inhibitors and are useful as medicaments for the treatment of, for example, organ disorders associated with ischemia and reperfusion, cardiac arrhythmia, cardiac hypertrophy, hypertension, cell proliferative disorders and diabetes.

摘要翻译： 公开了具有式1的稠合三环的胍衍生物，其中U是C（O），CR a R b，O，NR a或S（O）m; V是CRaRb或NRa; W为S（O）m; 其中R a是H，烷基，环烷基，烯基或芳烷基; Rb是H，烷基，OH，ORa或OCORa，m是整数0,1或2; R1，R2，R3，R4，R5，R6，R7和R8如本文所定义，条件是R 1，R 2，R 3，R 4，R 5，R 6，R 7或R 8中的至少一个是胍基或胍基羰基。 这些衍生物是钠 - 质子交换抑制剂，并且可用作治疗例如与缺血和再灌注相关的器官疾病，心律失常，心脏肥大，高血压，细胞增殖性疾病和糖尿病的药物。

公开(公告)号：US07964631B2

公开(公告)日：2011-06-21

申请号：US12854745

申请日：2010-08-11

申请人： Bansi Lal ,  Somesh Sharma ,  Usha Ghosh ,  Swati Bal-Tembe ,  Tulsidas More ,  Pravin Gagare ,  Sunil Jadhav ,  Shashikant Patil ,  Asha Kulkarni-Almeida ,  Sapna Parikh ,  Radha Bhaskar Panicker ,  Anagha Damre ,  Ravindra Gupte

发明人： Bansi Lal ,  Somesh Sharma ,  Usha Ghosh ,  Swati Bal-Tembe ,  Tulsidas More ,  Pravin Gagare ,  Sunil Jadhav ,  Shashikant Patil ,  Asha Kulkarni-Almeida ,  Sapna Parikh ,  Radha Bhaskar Panicker ,  Anagha Damre ,  Ravindra Gupte

IPC分类号： A61K31/38

CPC分类号： C07D327/02

摘要： Compounds of formula 1: are disclosed, wherein V is CH2; W is S(O)m; m is the integer 0, 1 or 2; U is O, C(O), CR13R14 or NR15; where R13 is H, alkyl; R14 is H, OH, OR13 or OCOR13; R15 is H, alkyl, cycloalkyl, alkenyl, C(O)R13, C(O)OR13 or alkylaminocarbonyl; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein. These compounds are inhibitors of tumor necrosis factor-alpha (TNF-α) and are useful as medicaments for the treatment and prevention of disorders caused by increased TNF-α activity, in particular inflammations.

摘要翻译： 公开了式1化合物，其中V是CH 2; W为S（O）m; m是整数0,1或2; U是O，C（O），CR 13 R 14或NR 15; 其中R 13为H，烷基; R14是H，OH，OR13或OCOR13; R 15是H，烷基，环烷基，烯基，C（O）R 13，C（O）OR 13或烷基氨基羰基; R1，R2，R3，R4，R5，R6，R7和R8如本文所定义。 这些化合物是肿瘤坏死因子-α（TNF-α）的抑制剂，可用作治疗和预防由增加的TNF-α活性引起的疾病，特别是炎症的药物。

公开(公告)号：US20100305094A1

公开(公告)日：2010-12-02

申请号：US12854761

申请日：2010-08-11

申请人： Bansi Lal ,  Somesh Sharma ,  Usha Ghosh ,  Swati Bal-Tembe ,  Tulsidas More ,  Asha Kulkarni-Almeida ,  Sapna Parikh ,  Radha Panicker ,  Anagha Damre ,  Ravindra Gupte

发明人： Bansi Lal ,  Somesh Sharma ,  Usha Ghosh ,  Swati Bal-Tembe ,  Tulsidas More ,  Asha Kulkarni-Almeida ,  Sapna Parikh ,  Radha Panicker ,  Anagha Damre ,  Ravindra Gupte

IPC分类号： A61K31/554 ,  C07D281/14 ,  A61P29/00 ,  A61P19/02 ,  A61P9/10 ,  A61P9/00 ,  A61P31/18 ,  A61P37/00 ,  A61P11/06 ,  A61P35/00 ,  A61P3/10 ,  A61P19/10

CPC分类号： C07D327/02

摘要： Compounds of formula 1: are disclosed, wherein V is CH2; W is S(O)m; m is the integer 0, 1 or 2; U is O, C(O), CR13R14 or NR15; where R13 is H, alkyl; R14 is H, OH, OR13 or OCOR13; R15 is H, alkyl, cycloalkyl, alkenyl, C(O)R13, C(O)OR13 or alkylaminocarbonyl; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein. These compounds are inhibitors of tumor necrosis factor-alpha (TNF-α) and are useful as medicaments for the treatment and prevention of disorders caused by increased TNF-α activity, in particular inflammations.

摘要翻译： 公开了式1化合物，其中V是CH 2; W为S（O）m; m是整数0,1或2; U是O，C（O），CR 13 R 14或NR 15; 其中R 13为H，烷基; R14是H，OH，OR13或OCOR13; R 15是H，烷基，环烷基，烯基，C（O）R 13，C（O）OR 13或烷基氨基羰基; R1，R2，R3，R4，R5，R6，R7和R8如本文所定义。 这些化合物是肿瘤坏死因子-α（TNF-α）的抑制剂，可用作治疗和预防由增加的TNF-α活性引起的疾病，特别是炎症的药物。

公开(公告)号：US08163730B2

公开(公告)日：2012-04-24

申请号：US12854761

申请日：2010-08-11

申请人： Bansi Lal ,  Somesh Sharma ,  Usha Ghosh ,  Swati Bal-Tembe ,  Tulsidas More ,  Asha Kulkarni-Almeida ,  Sapna Parikh ,  Radha Bhaskar Panicker ,  Anagha Damre ,  Ravindra Gupte

发明人： Bansi Lal ,  Somesh Sharma ,  Usha Ghosh ,  Swati Bal-Tembe ,  Tulsidas More ,  Asha Kulkarni-Almeida ,  Sapna Parikh ,  Radha Bhaskar Panicker ,  Anagha Damre ,  Ravindra Gupte

IPC分类号： A61K31/554 ,  C07D281/16

CPC分类号： C07D327/02

摘要： Compounds of formula 1: are disclosed, wherein V is CH2; W is S(O)m; m is the integer 0, 1 or 2; U is O, C(O), CR13R14 or NR15; where R13 is H, alkyl; R14 is H, OH, OR13 or OCOR13; R15 is H, alkyl, cycloalkyl, alkenyl, C(O)R13, C(O)OR13 or alkylaminocarbonyl; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein. These compounds are inhibitors of tumor necrosis factor-alpha (TNF-α) and are useful as medicaments for the treatment and prevention of disorders caused by increased TNF-α activity, in particular inflammations.

摘要翻译： 公开了式1化合物，其中V是CH 2; W为S（O）m; m是整数0,1或2; U是O，C（O），CR 13 R 14或NR 15; 其中R 13为H，烷基; R14是H，OH，OR13或OCOR13; R 15是H，烷基，环烷基，烯基，C（O）R 13，C（O）OR 13或烷基氨基羰基; R1，R2，R3，R4，R5，R6，R7和R8如本文所定义。 这些化合物是肿瘤坏死因子-α（TNF-α）的抑制剂，可用作治疗和预防由增加的TNF-α活性引起的疾病，特别是炎症的药物。

公开(公告)号：US20100324026A1

公开(公告)日：2010-12-23

申请号：US12854745

申请日：2010-08-11

申请人： Bansi LAL ,  Somesh Sharma ,  Usha Ghosh ,  Swati Bal-Tembe ,  Tulsidas More ,  Pravin Gagare ,  Sunil Jadhav ,  Shashikant Patil ,  Asha Kulkarni-Almeida ,  Sapna Parikh ,  Radha Panicker ,  Anagha Damre ,  Ravindra Gupte

发明人： Bansi LAL ,  Somesh Sharma ,  Usha Ghosh ,  Swati Bal-Tembe ,  Tulsidas More ,  Pravin Gagare ,  Sunil Jadhav ,  Shashikant Patil ,  Asha Kulkarni-Almeida ,  Sapna Parikh ,  Radha Panicker ,  Anagha Damre ,  Ravindra Gupte

IPC分类号： A61K31/39 ,  A61K31/496 ,  A61K31/551 ,  A61K31/5377 ,  A61P1/00 ,  A61P29/00 ,  A61P19/02 ,  A61P19/10 ,  A61P9/10 ,  A61P31/18 ,  A61P33/06 ,  A61P35/00 ,  A61P3/10 ,  A61P25/28

CPC分类号： C07D327/02

摘要： Compounds of formula 1: are disclosed, wherein V is CH2; W is S(O)m; m is the integer 0, 1 or 2; U is O, C(O), CR13R14 or NR15; where R13 is H, alkyl; R14 is H, OH, OR13 or OCOR13; R15 is H, alkyl, cycloalkyl, alkenyl, C(O)R13, C(O)OR13 or alkylaminocarbonyl; R1, R2, R3, R4, R5, R6, R7 and R5 are as defined herein. These compounds are inhibitors of tumor necrosis factor-alpha (TNF-α) and are useful as medicaments for the treatment and prevention of disorders caused by increased TNF-α activity, in particular inflammations.

摘要翻译： 公开了式1化合物，其中V是CH 2; W为S（O）m; m是整数0,1或2; U是O，C（O），CR 13 R 14或NR 15; 其中R 13为H，烷基; R14是H，OH，OR13或OCOR13; R 15是H，烷基，环烷基，烯基，C（O）R 13，C（O）OR 13或烷基氨基羰基; R1，R2，R3，R4，R5，R6，R7和R5如本文所定义。 这些化合物是肿瘤坏死因子-α（TNF-α）的抑制剂，可用作治疗和预防由增加的TNF-α活性引起的疾病，特别是炎症的药物。

公开(公告)号：US20070299050A1

公开(公告)日：2007-12-27

申请号：US11667580

申请日：2005-11-08

申请人： Bansi Lal ,  Somesh Sharma ,  Usha Ghosh ,  Swati Bal-Tembe ,  Tulsidas More ,  Pravin Gagare ,  Sunil Jadhav ,  Shashikant Patil ,  Asha Kulkarni-Almeida ,  Sapna Parikh ,  Radha Panicker ,  Anagha Damre ,  Ravindra Gupte

发明人： Bansi Lal ,  Somesh Sharma ,  Usha Ghosh ,  Swati Bal-Tembe ,  Tulsidas More ,  Pravin Gagare ,  Sunil Jadhav ,  Shashikant Patil ,  Asha Kulkarni-Almeida ,  Sapna Parikh ,  Radha Panicker ,  Anagha Damre ,  Ravindra Gupte

IPC分类号： A61K31/39 ,  A61K31/38 ,  A61K31/496 ,  A61P1/00 ,  A61P19/00 ,  A61P25/00 ,  A61P37/00 ,  C07D281/12 ,  C07D327/00 ,  C07D411/02

CPC分类号： C07D327/02

摘要： Compounds of formula 1: are disclosed, wherein V is CH2; W is S(O)m; m is the integer 0, 1 or 2; U is O, C(O), CR13R14 or NR15; where R13 is H, alkyl; R14 is H, OH, OR13 or OCOR13; R15 is H, alkyl, cycloalkyl, alkenyl, C(O)R13, C(O)OR13 or alkylaminocarbonyl; R1, R2, R3, R4, R5, R6, R7 and R8 are as defined herein. These compounds are inhibitors of tumor necrosis factor-alpha (TNF-α) and are useful as medicaments for the treatment and prevention of disorders caused by increased TNF-α activity, in particular inflammations.

摘要翻译： 公开了式1的化合物，其中V是CH 2 2; W是S（O）m。 m是整数0,1或2; U是O，C（O），CR 13 R 14或NR 15; 其中R 13是H，烷基; R 14是H，OH，OR 13或OCOR 13; R 15是H，烷基，环烷基，烯基，C（O）R 13，C（O）OR 13或烷基氨基羰基; R 1，R 2，R 3，R 4，R 5， R 6，R 7和R 8是如本文所定义的。 这些化合物是肿瘤坏死因子-α（TNF-α）的抑制剂，可用作治疗和预防由增加的TNF-α活性引起的疾病，特别是炎症的药物。

公开(公告)号：US20110009396A1

公开(公告)日：2011-01-13

申请号：US12670701

申请日：2008-07-25

申请人： Dilip Narayanrao Bhedi ,  Ram Asrey Vishwakarma ,  Vaishali Deka ,  Dattatray Maruti More ,  Manivannan Ramalingam ,  Ashish Suthar ,  Rada Dalal ,  Sapna Parikh ,  Aditi Amol Tannu

发明人： Dilip Narayanrao Bhedi ,  Ram Asrey Vishwakarma ,  Vaishali Deka ,  Dattatray Maruti More ,  Manivannan Ramalingam ,  Ashish Suthar ,  Rada Dalal ,  Sapna Parikh ,  Aditi Amol Tannu

IPC分类号： A61K31/541 ,  C07D307/92 ,  C07D405/06 ,  C07D413/06 ,  C07D417/06 ,  A61K31/343 ,  A61K31/496 ,  A61K31/4525 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4025 ,  A61K31/5377 ,  A61P19/02 ,  A61P29/00 ,  A61P19/10 ,  A61P9/10 ,  A61P9/00 ,  A61P17/06 ,  A61P37/04 ,  A61P37/06 ,  A61P37/02 ,  A61P25/28 ,  A61P31/18 ,  A61P11/00 ,  A61P31/14 ,  A61P3/10 ,  A61P11/06 ,  A61P35/00

CPC分类号： C07D307/92 ,  C07D405/06 ,  C07D405/12 ,  C07D417/06 ,  C07H17/04

摘要： The present invention provides compounds represented by formula 1: wherein, R1 R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13 and X are as defined in the specification, in all its stereoisomeric and tautomeric forms and mixtures thereof in all ratios, and its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable polymorphs and prodrugs. These compounds are useful for treatment of inflammatory disorders including those caused by elevated levels of proinflammatory cytokines such as Tumor Necrosis Factor (TNF-α and/or interleukins (IL-1β, IL-6, IL-8). The invention also relates to processes for the manufacture of compounds of formula 1 and pharmaceutical compositions containing them.

摘要翻译： 本发明提供了由式1表示的化合物：其中R1 R2，R3，R4，R5，R6，R7，R8，R9，R10，R11，R12，R13和X如说明书中所定义，在其所有立体异构体和 互变异构形式及其混合物，以及其药学上可接受的盐，药学上可接受的溶剂化物，药学上可接受的多晶型物和前药。 这些化合物可用于治疗炎症性疾病，包括由升高的促炎细胞因子如肿瘤坏死因子（TNF-α和/或白细胞介素（IL-1和bgr，IL-6，IL-8））水平引起的疾病，本发明还涉及 制备式1化合物的方法和含有它们的药物组合物。

公开(公告)号：US08981131B2

公开(公告)日：2015-03-17

申请号：US12670701

申请日：2008-07-25

申请人： Dilip Narayanrao Bhedi ,  Ram Asrey Vishwakarma ,  Vaishali Deka ,  Dattatray Maruti More ,  Manivannan Ramalingam ,  Ashish Suthar ,  Roda Dalal ,  Sapna Parikh ,  Aditi Amol Tannu

发明人： Dilip Narayanrao Bhedi ,  Ram Asrey Vishwakarma ,  Vaishali Deka ,  Dattatray Maruti More ,  Manivannan Ramalingam ,  Ashish Suthar ,  Roda Dalal ,  Sapna Parikh ,  Aditi Amol Tannu

IPC分类号： A61K31/541 ,  C07D307/92 ,  C07D405/06 ,  C07D413/06 ,  C07D417/06 ,  A61K31/343 ,  A61K31/496 ,  A61K31/4525 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4025 ,  A61K31/5377 ,  A61P19/02 ,  A61P29/00 ,  A61P19/10 ,  A61P9/00 ,  A61P17/06 ,  A61P37/04 ,  A61P37/06 ,  A61P37/02 ,  A61P25/28 ,  A61P31/18 ,  A61P11/00 ,  A61P31/14 ,  A61P3/10 ,  A61P11/06 ,  A61P35/00 ,  C07D405/12 ,  C07H17/04

CPC分类号： C07D307/92 ,  C07D405/06 ,  C07D405/12 ,  C07D417/06 ,  C07H17/04

摘要： The present invention provides compounds represented by formula I: wherein, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13 and X are as defined in the specification, in all its stereoisomeric and tautomeric forms and mixtures thereof in all ratios, and its pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable polymorphs and prodrugs. These compounds are useful for treatment of inflammatory disorders including those caused by elevated levels of proinflammatory cytokines such as Tumor Necrosis Factor (TNF-α and/or interleukins (IL-1β, IL-6, IL-8). The invention also relates to processes for the manufacture of compounds of formula 1 and pharmaceutical compositions containing them.

摘要翻译： 本发明提供由式I表示的化合物：其中R1，R2，R3，R4，R5，R6，R7，R8，R9，R10，R11，R12，R13和X如说明书中所定义，在其所有立体异构体 和互变异构体形式及其各种比例的混合物，及其药学上可接受的盐，药学上可接受的溶剂合物，药学上可接受的多晶型物和前药。 这些化合物可用于治疗炎症性疾病，包括由升高的促炎细胞因子如肿瘤坏死因子（TNF-α和/或白细胞介素（IL-1和bgr，IL-6，IL-8））水平引起的疾病，本发明还涉及 制备式1化合物的方法和含有它们的药物组合物。