公开(公告)号：US20150030594A1

公开(公告)日：2015-01-29

申请号：US14336290

申请日：2014-07-21

Applicant: Jun YUAN ,  Frederic ZECRI ,  Philipp GROSCHE ,  Hongjuan ZHAO ,  Andrei GOLOSOV ,  Kayo YASOSHIMA ,  David Thomas PARKER ,  Eric PETERS ,  Aimee Richardson USERA ,  Shari Lynn CAPLAN ,  Aaron KANTER ,  Changgang LOU ,  Carla Guimaraes

Inventor： Jun YUAN ,  Frederic ZECRI ,  Philipp GROSCHE ,  Hongjuan ZHAO ,  Andrei GOLOSOV ,  Kayo YASOSHIMA ,  David Thomas PARKER ,  Eric PETERS ,  Aimee Richardson USERA ,  Shari Lynn CAPLAN ,  Aaron KANTER ,  Changgang LOU ,  Carla Guimaraes

IPC: C07K7/08 ,  A61K45/06 ,  C07K14/47 ,  C07K16/00 ,  A61K39/395 ,  A61K47/48 ,  A61K38/10

CPC classification number: A61K38/10 ,  A61K38/00 ,  A61K45/06 ,  A61K47/542 ,  A61K47/643 ,  A61K47/68 ,  A61K47/6811 ,  C07K14/47 ,  C07K14/765 ,  C07K2319/30 ,  C07K2319/31

Abstract: The invention provides a bioconjugates comprising a synthetic polypeptide of Formula I′ (SEQ ID NO: 1): or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein and a half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the bioconjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract translation: 本发明提供包含式I'（SEQ ID NO：1）的合成多肽的生物缀合物或其酰胺，其酯或其盐，其中X 1，X 2，X 3，X 4，X 5，X 6，X 7，X 8，X 9 ，X10，X11，X12和X13在本文中定义并且半衰期延长部分，其中肽和半衰期延长部分任选地经由连接体共价连接或融合。 多肽是APJ受体的激动剂。 本发明还涉及本发明的生物缀合物的制备方法及其治疗用途，例如治疗或预防急性失代偿性心力衰竭（ADHF），慢性心力衰竭，肺动脉高压，心房颤动，布鲁加达综合征，室性心动过速，动脉粥样硬化 ，高血压，再狭窄，缺血性心血管疾病，心肌病，心脏纤维化，心律失常，保水，糖尿病（包括妊娠糖尿病），肥胖，外周动脉疾病，脑血管意外，短暂性脑缺血发作，创伤性脑损伤，肌萎缩性侧索硬化，烧伤（ 包括晒伤）和先兆子痫。 本发明还提供药理活性剂和药物组合物的组合。

公开(公告)号：US08163773B2

公开(公告)日：2012-04-24

申请号：US11995484

申请日：2006-07-10

Applicant: Werner Breitenstein ,  Claus Erhardt ,  Juergen Klaus Maibaum ,  Nils Ostermann ,  Juerg Zimmermann ,  Keiichi Masuya ,  Kazuhide Konishi ,  Fumiaki Yokokawa ,  Takanori Kanazawa ,  Edgar Jacoby ,  Andreas Marzinzik ,  Philipp Grosche ,  Shimpei Kawakami

Inventor： Werner Breitenstein ,  Claus Erhardt ,  Juergen Klaus Maibaum ,  Nils Ostermann ,  Juerg Zimmermann ,  Keiichi Masuya ,  Kazuhide Konishi ,  Fumiaki Yokokawa ,  Takanori Kanazawa ,  Edgar Jacoby ,  Andreas Marzinzik ,  Philipp Grosche ,  Shimpei Kawakami

IPC: A61K31/445 ,  C07D401/00

CPC classification number: C07D403/14 ,  C07D211/56 ,  C07D403/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: The invention relates to 3,5-substituted piperidine compounds, these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (=disorder) that depends on activity of renin; the use of a compound of that class for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; pharmaceutical formulations comprising a 3,5-substituted piperidine compound, and/or a method of treatment comprising administering a 3,5-substituted piperidine compound, a method for the manufacture of a 3,5-substituted piperidine compound, and novel intermediates and partial steps for its synthesis. The preferred compounds (which can also be present as salts) have the formula I wherein R1, R2, T, R3 and R4 are as defined in the specification.

Abstract translation: 本发明涉及3,5-取代的哌啶化合物，这些化合物用于诊断和治疗温血动物，特别是用于治疗依赖于肾素活性的疾病（=病症）; 使用该类化合物制备用于治疗依赖于肾素活性的疾病的药物制剂; 使用该类化合物治疗依赖于肾素活性的疾病; 包含3,5-取代的哌啶化合物的药物制剂和/或治疗方法，包括给予3,5-取代的哌啶化合物，制备3,5-取代的哌啶化合物的方法，以及新的中间体和部分 其合成步骤。 优选的化合物（其也可以盐形式存在）具有式I，其中R 1，R 2，T，R 3和R 4如说明书中所定义。

公开(公告)号：US08084450B2

公开(公告)日：2011-12-27

申请号：US11719762

申请日：2005-12-28

Applicant: Werner Breitenstein ,  Takeru Ehara ,  Claus Ehrhardt ,  Philipp Grosche ,  Yuko Hitomi ,  Yuki Iwaki ,  Takanori Kanazawa ,  Kazuhide Konishi ,  Juergen Klaus Maibaum ,  Keiichi Masuya ,  Atsuko Nihonyanagi ,  Nils Ostermann ,  Masaki Suzuki ,  Atsushi Toyao ,  Fumiaki Yokokawa

Inventor： Werner Breitenstein ,  Takeru Ehara ,  Claus Ehrhardt ,  Philipp Grosche ,  Yuko Hitomi ,  Yuki Iwaki ,  Takanori Kanazawa ,  Kazuhide Konishi ,  Juergen Klaus Maibaum ,  Keiichi Masuya ,  Atsuko Nihonyanagi ,  Nils Ostermann ,  Masaki Suzuki ,  Atsushi Toyao ,  Fumiaki Yokokawa

IPC: A61K31/536 ,  A61K31/451 ,  C07D265/36 ,  C07D211/60

CPC classification number: C07D471/04 ,  C07D211/60 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D409/10 ,  C07D409/12 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: 3,4-substituted piperidine compounds, these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (=disorder) that depends on activity of renin; the use of a compound of that class for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; pharmaceutical formulations comprising a 3,4-substituted piperidine compound, and/or a method of treatment comprising administering a 3,4-substituted piperidine compound, a method for the manufacture of a 3,4-substituted piperidine compound, and novel intermediates and partial steps for their synthesis are disclosed. The 3,4-disubstituted piperidine compounds have the formula I,

Abstract translation: 3,4-取代的哌啶化合物，这些化合物用于诊断和治疗温血动物，特别是用于治疗依赖于肾素活性的疾病（=病症）; 使用该类化合物制备用于治疗依赖于肾素活性的疾病的药物制剂; 使用该类化合物治疗依赖于肾素活性的疾病; 包括3,4-取代的哌啶化合物的药物制剂和/或包括给药3,4-取代的哌啶化合物的方法，制备3,4-取代的哌啶化合物的方法和新的中间体和部分 公开了它们合成的步骤。 3,4-二取代的哌啶化合物具有式I，

公开(公告)号：US20090233920A1

公开(公告)日：2009-09-17

申请号：US11995484

申请日：2006-07-10

Applicant: Werner Breitenstein ,  Claus Erhardt ,  Juergen Klaus Maibaum ,  Nils Ostermann ,  Juerg Zimmermann ,  Keiichi Masuya ,  Kazuhide Konishi ,  Fumiaki Yokokawa ,  Takanori Kanazawa ,  Edgar Jacoby ,  Andreas Marzinzik ,  Philipp Grosche ,  Shimpei Kawakami

Inventor： Werner Breitenstein ,  Claus Erhardt ,  Juergen Klaus Maibaum ,  Nils Ostermann ,  Juerg Zimmermann ,  Keiichi Masuya ,  Kazuhide Konishi ,  Fumiaki Yokokawa ,  Takanori Kanazawa ,  Edgar Jacoby ,  Andreas Marzinzik ,  Philipp Grosche ,  Shimpei Kawakami

IPC: A61K31/538 ,  C07D265/36 ,  A61P9/12

CPC classification number: C07D403/14 ,  C07D211/56 ,  C07D403/12 ,  C07D409/12 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: The invention relates to 3,5-substituted piperidine compounds, these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (=disorder) that depends on activity of renin; the use of a compound of that class for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; pharmaceutical formulations comprising a 3,5-substituted piperidine compound, and/or a method of treatment comprising administering a 3,5-substituted piperidine compound, a method for the manufacture of a 3,5-substituted piperidine compound, and novel intermediates and partial steps for its synthesis. The preferred compounds (which can also be present as salts) have the formula I wherein R1, R2, T, R3 and R4 are as defined in the specification.

Abstract translation: 本发明涉及3,5-取代的哌啶化合物，这些化合物用于诊断和治疗温血动物，特别是用于治疗依赖于肾素活性的疾病（=病症）; 使用该类化合物制备用于治疗依赖于肾素活性的疾病的药物制剂; 使用该类化合物治疗依赖于肾素活性的疾病; 包含3,5-取代的哌啶化合物的药物制剂和/或治疗方法，包括给予3,5-取代的哌啶化合物，制备3,5-取代的哌啶化合物的方法，以及新的中间体和部分 其合成步骤。 优选的化合物（其也可以盐形式存在）具有式I，其中R 1，R 2，T，R 3和R 4如说明书中所定义。

公开(公告)号：US09683018B2

公开(公告)日：2017-06-20

申请号：US14905338

申请日：2014-07-21

Applicant: Frederic Zecri ,  Philipp Grosche ,  Kayo Yasoshima ,  Hongjuan Zhao ,  Jun Yuan

Inventor： Frederic Zecri ,  Philipp Grosche ,  Kayo Yasoshima ,  Hongjuan Zhao ,  Jun Yuan

IPC: A61K38/12 ,  C07K7/50 ,  A61K38/10 ,  C07K7/04 ,  C07K7/08 ,  C07K14/47 ,  A61K38/08 ,  A61K45/06 ,  C07K7/06

CPC classification number: C07K7/08 ,  A61K38/08 ,  A61K38/10 ,  A61K45/06 ,  C07K7/06 ,  C07K14/47

Abstract: The invention provides a synthetic polypeptide of Formula I′: X1-R-P-R-X5-X6-X7-K-X9-P-X11-X12-X13 or an amide, an ester, a salt or a bioconjugate thereof, wherein X1, X5, X6, X7, X9 and X11 to X13 are defined herein. The polypeptides and bioconjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides or bioconjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

公开(公告)号：US20160159871A1

公开(公告)日：2016-06-09

申请号：US14905333

申请日：2014-07-21

Applicant: Frédéric ZECRI ,  Philipp GROSCHE ,  Kayo YASOSHIMA ,  Hongjuan ZHAO ,  Jun YUAN

Inventor： Frederic ZECRI ,  Philipp GROSCHE ,  Kayo YASOSHIMA ,  Hongjuan ZHAO ,  Jun YUAN

IPC: C07K14/47 ,  A61K38/17 ,  A61K47/48 ,  A61K45/06

CPC classification number: C07K14/47 ,  A61K38/10 ,  A61K38/1709 ,  A61K45/06 ,  A61K47/643 ,  A61K47/6811

Abstract: The invention provides a synthetic polypeptide of Formula I′: X1-R-X3-R-L-X6-X7-K-X9-P-X11-X12-X13 or an amide, an ester, a salt thereof, or a bioconjugate thereof, wherein X1, X3, X6, X7, X9, X11, X12 and X13 are defined herein. The polypeptides and bioconjugates are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides and bioconjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract translation: 本发明提供式I'的合成多肽：X1-R-X3-RL-X6-X7-K-X9-P-X11-X12-X13或其酰胺，酯，其盐或其生物缀合物， 其中X1，X3，X6，X7，X9，X11，X12和X13在本文中定义。 多肽和生物缀合物是APJ受体的激动剂。 本发明还涉及本发明的多肽和生物缀合物的制备方法及其治疗用途，例如治疗或预防急性失代偿性心力衰竭（ADHF），慢性心力衰竭，肺动脉高压，心房颤动，Brugada综合征，室性心动过速 ，动脉粥样硬化，高血压，再狭窄，缺血性心血管疾病，心肌病，心脏纤维化，心律失常，保水，糖尿病（包括妊娠糖尿病），肥胖，外周动脉疾病，脑血管意外，短暂性脑缺血发作，创伤性脑损伤，肌萎缩性侧索硬化，烧伤 受伤（包括晒伤）和先兆子痫。 本发明还提供药理活性剂和药物组合物的组合。

公开(公告)号：US08921307B2

公开(公告)日：2014-12-30

申请号：US14082771

申请日：2013-11-18

Applicant: Frédéric Zecri ,  Kayo Yasoshima ,  Philipp Grosche ,  Jun Yuan ,  Hongjuan Zhao

Inventor： Frédéric Zecri ,  Kayo Yasoshima ,  Philipp Grosche ,  Jun Yuan ,  Hongjuan Zhao

IPC: C07K7/08 ,  C07K7/60 ,  C07K7/56 ,  A61K45/06 ,  C07K14/47 ,  A61K38/00

CPC classification number: C07K7/08 ,  A61K38/00 ,  A61K45/06 ,  C07K14/47

Abstract: The invention provides a synthetic polypeptide of Formula I′ (SEQ ID NO: 1): X1-X2-X3-R—X5-X6-X7-X8-X9-X10-X11-X12-X13  I or an amide, an ester or a salt thereof, wherein X1, X2, X3, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract translation: 本发明提供式I'（SEQ ID NO：1）的合成多肽：X1-X2-X3-R-X5-X6-X7-X8-X9-X10-X11-X12-X13I或酰胺，酯 或其盐，其中X 1，X 2，X 3，X 5，X 6，X 7，X 8，X 9，X 10，X 11，X 12和X 13如本文所定义。 多肽是APJ受体的激动剂。 本发明还涉及制备本发明多肽的方法及其治疗用途，例如治疗或预防急性失代偿性心力衰竭（ADHF），慢性心力衰竭，肺动脉高压，心房颤动，Brugada综合征，室性心动过速，动脉粥样硬化 ，高血压，再狭窄，缺血性心血管疾病，心肌病，心脏纤维化，心律失常，保水，糖尿病（包括妊娠糖尿病），肥胖，外周动脉疾病，脑血管意外，短暂性脑缺血发作，创伤性脑损伤，肌萎缩性侧索硬化，烧伤（ 包括晒伤）和先兆子痫。 本发明还提供药理活性剂和药物组合物的组合。

公开(公告)号：US20160166634A1

公开(公告)日：2016-06-16

申请号：US15053316

申请日：2016-02-25

Applicant: Shari Lynn CAPLAN ,  Andrei GOLOSOV ,  Philipp GROSCHE ,  Carla GUIMARAES ,  Aaron KANTER ,  Changgang LOU ,  David Thomas PARKER ,  Eric C. Peters ,  Aimee Richardson USERA ,  Kayo YASOSHIMA ,  Jun YUAN ,  Federic ZECRI ,  Hongjuan ZHAO

Inventor： Shari Lynn CAPLAN ,  Andrei GOLOSOV ,  Philipp GROSCHE ,  Carla GUIMARAES ,  Aaron KANTER ,  Changgang LOU ,  David Thomas PARKER ,  Eric C. Peters ,  Aimee Richardson USERA ,  Kayo YASOSHIMA ,  Jun YUAN ,  Federic ZECRI ,  Hongjuan ZHAO

IPC: A61K38/10 ,  A61K45/06 ,  C07K16/00 ,  C07K7/08 ,  C07K14/765 ,  A61K47/48

CPC classification number: A61K38/10 ,  A61K38/00 ,  A61K45/06 ,  A61K47/542 ,  A61K47/643 ,  A61K47/68 ,  A61K47/6811 ,  C07K14/47 ,  C07K14/765 ,  C07K2319/30 ,  C07K2319/31

Abstract: The invention provides a bioconjugates comprising a synthetic polypeptide of Formula I′ (SEQ ID NO: 1): or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein and a half-life extending moiety wherein the peptide and the half-life extending moiety are covalently linked or fuse, optionally via a linker. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the bioconjugates of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

公开(公告)号：US20150284446A1

公开(公告)日：2015-10-08

申请号：US14440198

申请日：2013-11-19

Applicant: Frédéric ZECRI ,  Kayo YASOSHIMA ,  Philipp GROSCHE ,  Jun YUAN ,  Hongjuan ZHAO

Inventor： Frederic Zecri ,  Kayo Yasoshima ,  Philipp Grosche ,  Jun Yuan ,  Hongjuan Zhao

IPC: C07K14/765 ,  A61K45/06 ,  A61K38/38

CPC classification number: C07K14/765 ,  A61K38/385 ,  A61K45/06 ,  C07K14/47 ,  A61K38/1709 ,  A61K2300/00

Abstract: The invention relates to novel compositions comprising modified apelin-13 peptide sequences designed to treat cardiovascular disease in subjects to whom they are administered, and which exhibit greater resistance to degradation, and equivalent or greater bioactivity than their wild type counterparts. The invention also relates to methods of making said compositions and using said compositions as pharmaceutically active agents to treat cardiovascular disease.

Abstract translation: 本发明涉及包含修饰的apelin-13肽序列的新型组合物，其设计用于治疗其给药对象的心血管疾病，并且其表现出比其野生型对应物更大的降解抗性和等同或更大的生物活性。 本发明还涉及制备所述组合物并使用所述组合物作为药物活性剂治疗心血管疾病的方法。

公开(公告)号：US20150252076A1

公开(公告)日：2015-09-10

申请号：US14714914

申请日：2015-05-18

Applicant: Frederic ZECRI ,  Andrei GOLOSOV ,  Philipp GROSCHE ,  Hongjuan ZHAO ,  Qi-Ying HU ,  Hidetomo IMASE

Inventor： Frederic ZECRI ,  Andrei GOLOSOV ,  Philipp GROSCHE ,  Hongjuan ZHAO ,  Qi-Ying HU ,  Hidetomo IMASE

IPC: C07K7/08 ,  A61K38/10

CPC classification number: A61M16/0816 ,  A61K38/00 ,  A61K38/10 ,  A61M16/0066 ,  A61M16/201 ,  A61M2016/0027 ,  A61M2016/003 ,  A61M2205/35 ,  A61M2205/502 ,  C07K7/08 ,  C07K7/56 ,  C07K7/60

Abstract: The invention provides a synthetic polypeptide of Formula I′: or an amide, an ester or a salt thereof, wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 are defined herein. The polypeptides are agonist of the APJ receptor. The invention also relates to a method for manufacturing the polypeptides of the invention, and its therapeutic uses such as treatment or prevention of acute decompensated heart failure (ADHF), chronic heart failure, pulmonary hypertension, atrial fibrillation, Brugada syndrome, ventricular tachycardia, atherosclerosis, hypertension, restenosis, ischemic cardiovascular diseases, cardiomyopathy, cardiac fibrosis, arrhythmia, water retention, diabetes (including gestational diabetes), obesity, peripheral arterial disease, cerebrovascular accidents, transient ischemic attacks, traumatic brain injuries, amyotrophic lateral sclerosis, burn injuries (including sunburn) and preeclampsia. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

Abstract translation: 本发明提供式I'的合成多肽：或其酰胺，酯或其盐，其中X1，X2，X3，X4，X5，X6，X7，X8，X9，X10，X11，X12和X13被定义 这里。 多肽是APJ受体的激动剂。 本发明还涉及制备本发明多肽的方法及其治疗用途，例如治疗或预防急性失代偿性心力衰竭（ADHF），慢性心力衰竭，肺动脉高压，心房颤动，Brugada综合征，室性心动过速，动脉粥样硬化 ，高血压，再狭窄，缺血性心血管疾病，心肌病，心脏纤维化，心律失常，保水，糖尿病（包括妊娠糖尿病），肥胖，外周动脉疾病，脑血管意外，短暂性脑缺血发作，创伤性脑损伤，肌萎缩性侧索硬化，烧伤（ 包括晒伤）和先兆子痫。 本发明还提供药理活性剂和药物组合物的组合。