公开(公告)号：US20160145309A1

公开(公告)日：2016-05-26

申请号：US14905338

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: C07K7/08 ,  A61K45/06 ,  A61K38/10 ,  C07K7/06 ,  A61K38/08

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.

Abstract translation: 本发明提供式I'的合成多肽：X1-RPR-X5-X6-X7-K-X9-P-X11-X12-X13或其酰胺，酯，盐或生物缀合物，其中X1，X5 ，X6，X7，X9，X11〜X13。 多肽和生物缀合物是APJ受体的激动剂。 本发明还涉及制备本发明的多肽或生物缀合物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 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：US20160108091A1

公开(公告)日：2016-04-21

申请号：US14963391

申请日：2015-12-09

Applicant: Frederic ZECRI ,  Philipp GROSCHE ,  Kayo YASOSHIMA ,  Hongjuan ZHAO ,  Jun YUAN ,  Aimee Richardson USERA ,  Changgang LOU ,  Aaron KANTER ,  Alexandra Marshall BRUCE ,  Carla GUIMARAES

Inventor： Frederic ZECRI ,  Philipp GROSCHE ,  Kayo YASOSHIMA ,  Hongjuan ZHAO ,  Jun YUAN ,  Aimee Richardson USERA ,  Changgang LOU ,  Aaron KANTER ,  Alexandra Marshall BRUCE ,  Carla GUIMARAES

IPC: C07K7/64 ,  C07K14/765

CPC classification number: C07K14/47 ,  A61K38/12 ,  A61K38/1709 ,  A61K45/06 ,  A61K47/542 ,  A61K47/60 ,  A61K47/643 ,  A61K47/6811 ,  C07K7/64 ,  C07K14/765 ,  C07K16/461 ,  C07K2319/30 ,  C07K2319/31

Abstract: The invention provides a cyclic polypeptide of Formula I (SEQ ID NO: 1): X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13  I or an amide, an ester or a salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, 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 or bioconjugates thereof, and their 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：US09266925B2

公开(公告)日：2016-02-23

申请号：US14336262

申请日：2014-07-21

Applicant: Frederic Zecri ,  Philipp Grosche ,  Kayo Yasoshima ,  Hongjuan Zhao ,  Jun Yuan ,  Aimee Richardson Usera ,  Changgang Lou ,  Aaron Kanter ,  Alexandra Marshall Bruce ,  Carla Giumaraes

Inventor： Frederic Zecri ,  Philipp Grosche ,  Kayo Yasoshima ,  Hongjuan Zhao ,  Jun Yuan ,  Aimee Richardson Usera ,  Changgang Lou ,  Aaron Kanter ,  Alexandra Marshall Bruce ,  Carla Giumaraes

IPC: C07K7/64 ,  C07K16/46 ,  A61K38/12 ,  A61K45/06 ,  C07K14/47

CPC classification number: C07K14/47 ,  A61K38/12 ,  A61K38/1709 ,  A61K45/06 ,  A61K47/542 ,  A61K47/60 ,  A61K47/643 ,  A61K47/6811 ,  C07K7/64 ,  C07K14/765 ,  C07K16/461 ,  C07K2319/30 ,  C07K2319/31

Abstract: The invention provides a cyclic polypeptide of Formula I (SEQ ID NO: 1): X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13  I or an amide, an ester or a salt thereof, or a bioconjugate thereof, wherein X1, X3, X4, 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 or bioconjugates thereof, and their 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）的环状多肽：X1-R-X3-X4-LS-X7-X8-X9-X10-X11-X12-X13I或酰胺，酯或盐 或其生物缀合物，其中X1，X3，X4，X7，X8，X9，X10，X11，X12和X13在本文中定义。 多肽是APJ受体的激动剂。 本发明还涉及制备本发明多肽或其生物缀合物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，心室 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，潴留，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：US08673848B2

公开(公告)日：2014-03-18

申请号：US13747621

申请日：2013-01-23

Applicant: Frédéric Zecri ,  Andrei Golosov ,  Philipp Grosche ,  Kayo Yasoshima ,  Hongjuan Zhao ,  Qi-Ying Hu ,  Hidetomo Imase ,  David Thomas Parker

Inventor： Frédéric Zecri ,  Andrei Golosov ,  Philipp Grosche ,  Kayo Yasoshima ,  Hongjuan Zhao ,  Qi-Ying Hu ,  Hidetomo Imase ,  David Thomas Parker

IPC: C07K7/08 ,  C07K7/60 ,  C07K7/56

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。

公开(公告)号：US20100029609A1

公开(公告)日：2010-02-04

申请号：US12440143

申请日：2007-09-06

Applicant: Frederic Berst ,  Philipp Grosche ,  Philipp Janser ,  Frederic Zecri ,  Birgit Bollbuck

Inventor： Frederic Berst ,  Philipp Grosche ,  Philipp Janser ,  Frederic Zecri ,  Birgit Bollbuck

IPC: A61K31/397 ,  C07D207/00 ,  A61K31/40 ,  C07D265/30 ,  A61K31/535 ,  C07D205/04 ,  A61P25/00

CPC classification number: C07C311/21 ,  C07C311/29 ,  C07D205/04 ,  C07D207/16 ,  C07D213/30 ,  C07D213/76 ,  C07D231/18 ,  C07D233/84 ,  C07D241/04 ,  C07D241/24 ,  C07D257/04 ,  C07D277/36 ,  C07D307/79 ,  C07D307/82 ,  C07D333/34 ,  C07D333/62

Abstract: A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof: wherein the groups R1-R5, R10 and X1-X7 are as defined in the specification.

Abstract translation: 式（I）化合物或其药学上可接受的盐或前药酯：其中R1-R5，R10和X1-X7基团如说明书中所定义。

公开(公告)号：US20090312304A1

公开(公告)日：2009-12-17

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 K. 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 K. Maibaum ,  Keiichi Masuya ,  Atsuko Nihonyanagi ,  Nils Ostermann ,  Masaki Suzuki ,  Atsushi Toyao ,  Fumiaki Yokokawa

IPC: A61K31/4545 ,  C07D211/00 ,  C07D401/10 ,  C07D413/12 ,  C07D417/12 ,  A61K31/445 ,  A61K31/536 ,  A61K31/5415

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，