公开(公告)号：EP0341603A2

公开(公告)日：1989-11-15

申请号：EP89108140.8

申请日：1989-05-05

Applicant: ABBOTT LABORATORIES

Inventor： Rockway, Todd W. ,  Kiso, Yoshiaki ,  Davidsen, Steven K. ,  Lucas, Scott D. ,  Thomas, A. Mitchell ,  Von Geldern, Thomas W.

IPC: C07K7/08 ,  A61K37/02

CPC classification number: C07K14/582 ,  A61K38/00

Abstract: Atrial peptides comprising the amino acid sequence as follows: wherein R₁ is hydrogen, Ser, Cit, SerSer, Arg, Carbamoyl Ser, Guanido-Ser-Ser, Amcca, Guanido-Amcca, Lys, ArgArg, Ser-Arg, Ser-Lys, Acetyl-Ser-Ser, D-Ser-Ser, Ser-D-Ser, Guanido-Aocta, Aunda, Aocta, Ahexa, HSer, Apenta, Papaa, Abuta, Mamba, Orn, D-Orn or Acetyl-apenta, Acetyl-Ahexa, Guanido;
R₂ is Cys, D-Cys or Pen;
R₃ is L-Phe, D-Ala, L-Ala, D-Val, D-Cha, Sar, D-Phg, Aib, β-Ala or Gly;
R₄ is Phe, Trp, D-Tic, L-Tic, N-MePhe, D-Ala, Tyr, 2-Thi, DimeDOPA or DOPA;
R₅ is Gly-Gly, Ala-Gly, D-Ala-Gly, Gly-Ala, Amcca, Mapaa or Papaa;
R₆ is Arg, D-Arg or Cit;
R₇ is Ile, Leu, D-Leu or Met;
R₈ is Asp, Asn, β-methylAsp, cycloAsp, Gly or Ser;
R₉ is Arg, D-Arg or Ala;
R₁₀ is Ile, Leu or Phe;
R₁₁ is Cys, D-Cys, HCys, Cys-4-thiomethylproline, or trans-4-thiomethylproline;
R₁₂ is absent, Phe, D-Ala-Phe, D-Phe, Cha, Pro, D-Pro, 2-Thi, Aic, D-Tic, trans-4-FPro, L-Tic, Leu, Ile or β-NAl;
R₁₃ is OH, Arg, Arg-NH₂, D-Arg, Gln, Lys, HomoArg, or Gly; or pharmaceutically acceptable salts, esters or amides thereof.

Abstract translation: 包含如下氨基酸序列的心房肽：其中R1是氢，Ser，Cit，SerSer，Arg，氨基甲酰基Ser，Guanido-Ser-Ser，Amcca，Guanido-Amcca，Lys，ArgArg，Ser-Arg，Ser -Lys，乙酰基Ser-Ser，D-Ser-Ser，Ser-D-Ser，Guanido-Aocta，Aunda，Aocta，Ahexa，HSer，Apenta，Papaa，Abuta，Mamba，Orn，D-Orn或乙酰 - ，乙酰基 - 六甲胺，胍基; R2是Cys，D-Cys或Pen; R3是L-Phe，D-Ala，L-Ala，D-Val，D-Cha，Sar，D-Phg，Aib，β-Ala或Gly; R4是Phe，Trp，D-Tic，L-Tic，N-MePhe，D-Ala，Tyr，2-Thi，DimeDOPA或DOPA; R5是Gly-Gly，Ala-Gly，D-Ala-Gly，Gly-Ala，Amcca，Mapaa或Papaa; R6是Arg，D-Arg或Cit; R7是Ile，Leu，D-Leu或Met; R8是Asp，Asn，β-methylAsp，cycloAsp，Gly或Ser; R9是Arg，D-Arg或Ala; R10是Ile，Leu或Phe; R11是Cys，D-Cys，HCys，Cys-4-硫代甲基脯氨酸或反式-4-硫代甲基脯氨酸; R12不存在，Phe，D-Ala-Phe，D-Phe，Cha，Pro，D-Pro，2-Thi，Aic，D-Tic，反式-4-FPro，L-Tic，Leu，Ile或β- NAL; R13是OH，Arg，Arg-NH2，D-Arg，Gln，Lys，HomoArg或Gly; 或其药学上可接受的盐，酯或酰胺。

公开(公告)号：EP0475206A3

公开(公告)日：1992-08-05

申请号：EP91114542.3

申请日：1991-08-29

Applicant: ABBOTT LABORATORIES

Inventor： Winn, Martin ,  De, Biswanath ,  Zydowsky, Thomas M. ,  Kerkman, Daniel J. ,  De Bernardis, John F. ,  Rosenberg, Saul H. ,  Shiosaki, Kazumi ,  Basha, Fatima Z. ,  Tasker, Andrew S. ,  Von Geldern, Thomas W. ,  Kester, Jeffrey A. ,  Holleman, William H.

IPC: C07D403/12 ,  A61K31/44 ,  C07D401/12 ,  C07D239/42 ,  C07D257/04 ,  C07D405/14 ,  A61K31/495

CPC classification number: C07D239/42 ,  C07D257/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/14

Abstract: Novel pyrimidine, pyridine, pyridazine, pyrazine and triazine compounds are provided of the formula (I).
The compounds of the invention are useful for treating hypertension, edema, renal failure, congestive heart failure, psoriasis and glaucoma, and in the prevention and treatment of atherosclerosis or to treat gastrointestinal disorders associated with enhanced contractility and/or motility of intestinal smooth muscle or to treat contractile disorders of the uterus.

公开(公告)号：EP1609790A2

公开(公告)日：2005-12-28

申请号：EP05106190.1

申请日：1997-02-12

Applicant: ABBOTT LABORATORIES

Inventor： Winn, Martin ,  Henry, Kenneth J. Jr. ,  Liu, Gang ,  Wittenberger, Steven J. ,  King, Steven A. ,  Boyd, Steven A. ,  Hutchins, Charles W. ,  Jae, Hwan-Soo ,  Tasker, Andrew S. ,  Von Geldern, Thomas W. ,  Kester, Jeffrey A. ,  Sorensen, Bryan K. ,  Szczepankiewicz, Bruce G.

IPC: C07D405/04 ,  C07D405/12 ,  A61K31/40 ,  A61K31/41 ,  A61K31/435

CPC classification number: C07D401/04 ,  C07D207/16 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  Y02P20/55

Abstract: A compound of formula (I), or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

Abstract translation: 公开了式（I）化合物或其药学上可接受的盐，以及其制备方法和中间体，以及拮抗内皮素的方法。

公开(公告)号：EP1609790A3

公开(公告)日：2006-01-04

申请号：EP05106190.1

申请日：1997-02-12

Applicant: ABBOTT LABORATORIES

Inventor： Winn, Martin ,  Henry, Kenneth J. Jr. ,  Liu, Gang ,  Wittenberger, Steven J. ,  King, Steven A. ,  Boyd, Steven A. ,  Hutchins, Charles W. ,  Jae, Hwan-Soo ,  Tasker, Andrew S. ,  Von Geldern, Thomas W. ,  Kester, Jeffrey A. ,  Sorensen, Bryan K. ,  Szczepankiewicz, Bruce G.

IPC: C07D405/04 ,  C07D405/12 ,  A61K31/40 ,  A61K31/41 ,  A61K31/435

CPC classification number: C07D401/04 ,  C07D207/16 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  Y02P20/55

Abstract: A compound of formula (I), or a pharmaceutically acceptable salt thereof is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.

公开(公告)号：EP0475206A2

公开(公告)日：1992-03-18

申请号：EP91114542.3

申请日：1991-08-29

Applicant: ABBOTT LABORATORIES

Inventor： Winn, Martin ,  De, Biswanath ,  Zydowsky, Thomas M. ,  Kerkman, Daniel J. ,  De Bernardis, John F. ,  Rosenberg, Saul H. ,  Shiosaki, Kazumi ,  Basha, Fatima Z. ,  Tasker, Andrew S. ,  Von Geldern, Thomas W. ,  Kester, Jeffrey A. ,  Holleman, William H.

IPC: C07D403/12 ,  A61K31/44 ,  C07D401/12 ,  C07D239/42 ,  C07D257/04 ,  C07D405/14 ,  A61K31/495

CPC classification number: C07D239/42 ,  C07D257/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/14

Abstract: Novel pyrimidine, pyridine, pyridazine, pyrazine and triazine compounds are provided of the formula (I).

The compounds of the invention are useful for treating hypertension, edema, renal failure, congestive heart failure, psoriasis and glaucoma, and in the prevention and treatment of atherosclerosis or to treat gastrointestinal disorders associated with enhanced contractility and/or motility of intestinal smooth muscle or to treat contractile disorders of the uterus.

Abstract translation: 由式（I）提供新的嘧啶，吡啶，哒嗪，吡嗪和三嗪化合物。 本发明的化合物可用于治疗高血压，水肿，肾衰竭，充血性心力衰竭，牛皮癣和青光眼，以及预防和治疗动脉粥样硬化或治疗与增强的肠收缩力和/或运动性相关的胃肠道疾病 平滑肌或治疗子宫收缩性疾病。

公开(公告)号：EP0341603A3

公开(公告)日：1990-07-04

申请号：EP89108140.8

申请日：1989-05-05

Applicant: ABBOTT LABORATORIES

Inventor： Rockway, Todd W. ,  Kiso, Yoshiaki ,  Davidsen, Steven K. ,  Lucas, Scott D. ,  Thomas, A. Mitchell ,  Von Geldern, Thomas W.

IPC: C07K7/08 ,  A61K37/02

CPC classification number: C07K14/582 ,  A61K38/00

Abstract: Atrial peptides comprising the amino acid sequence as follows: wherein R₁ is hydrogen, Ser, Cit, SerSer, Arg, Carbamoyl Ser, Guanido-Ser-Ser, Amcca, Guanido-Amcca, Lys, ArgArg, Ser-Arg, Ser-Lys, Acetyl-Ser-Ser, D-Ser-Ser, Ser-D-Ser, Guanido-Aocta, Aunda, Aocta, Ahexa, HSer, Apenta, Papaa, Abuta, Mamba, Orn, D-Orn or Acetyl-apenta, Acetyl-Ahexa, Guanido;
R₂ is Cys, D-Cys or Pen;
R₃ is L-Phe, D-Ala, L-Ala, D-Val, D-Cha, Sar, D-Phg, Aib, β-Ala or Gly;
R₄ is Phe, Trp, D-Tic, L-Tic, N-MePhe, D-Ala, Tyr, 2-Thi, DimeDOPA or DOPA;
R₅ is Gly-Gly, Ala-Gly, D-Ala-Gly, Gly-Ala, Amcca, Mapaa or Papaa;
R₆ is Arg, D-Arg or Cit;
R₇ is Ile, Leu, D-Leu or Met;
R₈ is Asp, Asn, β-methylAsp, cycloAsp, Gly or Ser;
R₉ is Arg, D-Arg or Ala;
R₁₀ is Ile, Leu or Phe;
R₁₁ is Cys, D-Cys, HCys, Cys-4-thiomethylproline, or trans-4-thiomethylproline;
R₁₂ is absent, Phe, D-Ala-Phe, D-Phe, Cha, Pro, D-Pro, 2-Thi, Aic, D-Tic, trans-4-FPro, L-Tic, Leu, Ile or β-NAl;
R₁₃ is OH, Arg, Arg-NH₂, D-Arg, Gln, Lys, HomoArg, or Gly; or pharmaceutically acceptable salts, esters or amides thereof.

Abstract translation: 包含如下氨基酸序列的心房肽：其中R1是氢，Ser，Cit，SerSer，Arg，氨基甲酰基Ser，Guanido-Ser-Ser，Amcca，Guanido-Amcca，Lys，ArgArg，Ser-Arg，Ser -Lys，乙酰基Ser-Ser，D-Ser-Ser，Ser-D-Ser，Guanido-Aocta，Aunda，Aocta，Ahexa，HSer，Apenta，Papaa，Abuta，Mamba，Orn，D-Orn或乙酰 - ，乙酰基 - 六甲胺，胍基; R2是Cys，D-Cys或Pen; R3是L-Phe，D-Ala，L-Ala，D-Val，D-Cha，Sar，D-Phg，Aib，β-Ala或Gly; R4是Phe，Trp，D-Tic，L-Tic，N-MePhe，D-Ala，Tyr，2-Thi，DimeDOPA或DOPA; R5是Gly-Gly，Ala-Gly，D-Ala-Gly，Gly-Ala，Amcca，Mapaa或Papaa; R6是Arg，D-Arg或Cit; R7是Ile，Leu，D-Leu或Met; R8是Asp，Asn，β-methylAsp，cycloAsp，Gly或Ser; R9是Arg，D-Arg或Ala; R10是Ile，Leu或Phe; R11是Cys，D-Cys，HCys，Cys-4-硫代甲基脯氨酸或反式-4-硫代甲基脯氨酸; R12不存在，Phe，D-Ala-Phe，D-Phe，Cha，Pro，D-Pro，2-Thi，Aic，D-Tic，反式-4-FPro，L-Tic，Leu，Ile或β- NAL; R13是OH，Arg，Arg-NH2，D-Arg，Gln，Lys，HomoArg或Gly; 或其药学上可接受的盐，酯或酰胺。