公开(公告)号：US09683018B2

公开(公告)日：2017-06-20

申请号：US14905338

申请日：2014-07-21

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

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

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

CPC分类号： C07K7/08 ,  A61K38/08 ,  A61K38/10 ,  A61K45/06 ,  C07K7/06 ,  C07K14/47

摘要： 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

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

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

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

CPC分类号： C07K14/47 ,  A61K38/10 ,  A61K38/1709 ,  A61K45/06 ,  A61K47/643 ,  A61K47/6811

摘要： 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.

摘要翻译： 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

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

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

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

CPC分类号： C07K7/08 ,  A61K38/00 ,  A61K45/06 ,  C07K14/47

摘要： 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.

摘要翻译： 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

申请人： 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

发明人： 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分类号： A61K38/10 ,  A61K45/06 ,  C07K16/00 ,  C07K7/08 ,  C07K14/765 ,  A61K47/48

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

摘要： 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

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

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

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

CPC分类号： C07K14/765 ,  A61K38/385 ,  A61K45/06 ,  C07K14/47 ,  A61K38/1709 ,  A61K2300/00

摘要： 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.

摘要翻译： 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：US08759365B2

公开(公告)日：2014-06-24

申请号：US12745105

申请日：2008-12-01

申请人： Muneto Mogi ,  Toshio Kawanami ,  Ken Yamada ,  Kayo Yasoshima ,  Hidetomo Imase ,  Takahiro Miyake ,  Osamu Ohmori

发明人： Muneto Mogi ,  Toshio Kawanami ,  Ken Yamada ,  Kayo Yasoshima ,  Hidetomo Imase ,  Takahiro Miyake ,  Osamu Ohmori

IPC分类号： A61K31/5377 ,  A61K31/506 ,  A61K31/41 ,  A61K31/40 ,  C07D413/14 ,  C07D405/14 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D207/14

CPC分类号： C07D207/14 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14

摘要： The present invention provides a compound of formula (I): wherein the variants R1, R2, R3, R4, R6, R7 are as defined herein, and wherein said compound is an inhibitor of CETP, and thus can be employed for the treatment of a disorder or disease mediated by CETP or responsive to the inhibition of CETP.

摘要翻译： 本发明提供式（I）化合物：其中变体R1，R2，R3，R4，R6，R7如本文所定义，并且其中所述化合物是CETP的抑制剂，因此可用于治疗 由CETP介导的疾病或疾病或响应于CETP的抑制。

公开(公告)号：US20140155315A1

公开(公告)日：2014-06-05

申请号：US14082771

申请日：2013-11-18

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

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

IPC分类号： C07K7/08 ,  A61K38/10 ,  A61K45/06

CPC分类号： C07K7/08 ,  A61K38/00 ,  A61K45/06 ,  C07K14/47

摘要： 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.

摘要翻译： 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：US20140142022A1

公开(公告)日：2014-05-22

申请号：US14165680

申请日：2014-01-28

申请人： Frederic ZECRI ,  Andrei GOLOSOV ,  Philipp GROSCHE ,  Kayo YASOSHIMA ,  Hongjuan ZHAO ,  Qi-Ying HU ,  Hidetomo IMASE ,  David Thomas PARKER

发明人： Frederic ZECRI ,  Andrei GOLOSOV ,  Philipp GROSCHE ,  Kayo YASOSHIMA ,  Hongjuan ZHAO ,  Qi-Ying HU ,  Hidetomo IMASE ,  David Thomas PARKER

IPC分类号： C07K7/08

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

摘要： 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.

摘要翻译： 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：US20080045546A1

公开(公告)日：2008-02-21

申请号：US10575027

申请日：2004-10-02

申请人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pemerstorfer ,  Elke Reissmuller ,  Muneto Mogi ,  Takeshi Yura ,  Hiroshi Fujishima ,  Masanori Seki ,  Yuji Koriyama ,  Kayo Yasoshima ,  Keiko Misawa ,  Masaomi Tajimi ,  Noriyuki Yammoto ,  Klaus Urbahns ,  Fumihiko Hayashi ,  Yasuhiro Tsukimi ,  Jang Gupta

发明人： Axel Bouchon ,  Nicole Diedrichs ,  Achim Hermann ,  Klemens Lustig ,  Heinrich Meier ,  Josef Pemerstorfer ,  Elke Reissmuller ,  Muneto Mogi ,  Takeshi Yura ,  Hiroshi Fujishima ,  Masanori Seki ,  Yuji Koriyama ,  Kayo Yasoshima ,  Keiko Misawa ,  Masaomi Tajimi ,  Noriyuki Yammoto ,  Klaus Urbahns ,  Fumihiko Hayashi ,  Yasuhiro Tsukimi ,  Jang Gupta

IPC分类号： A61K31/519 ,  A61K31/44 ,  C07D211/68 ,  C07D213/06

CPC分类号： C07C275/32 ,  A61K31/167 ,  A61K31/17 ,  A61K31/357 ,  A61K31/42 ,  A61K31/433 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4412 ,  A61K31/455 ,  A61K31/4706 ,  A61K31/472 ,  A61K31/517 ,  A61K47/54 ,  C07C233/29 ,  C07C233/75 ,  C07C235/24 ,  C07C235/38 ,  C07C235/56 ,  C07C235/64 ,  C07C237/04 ,  C07C275/30 ,  C07C275/38 ,  C07C2602/08 ,  C07C2602/10 ,  C07D209/18 ,  C07D213/40 ,  C07D213/56 ,  C07D213/89 ,  C07D215/46 ,  C07D217/22 ,  C07D239/94 ,  C07D261/14 ,  C07D285/06 ,  C07D317/66

摘要： This invention relates to tetrahydro-naphthalene and urea derivatives and salts thereof which are useful as active ingredients of pharmaceutical preparations. The tetrahydro-naphthalene and urea derivatives of the present invention have vanilloid receptor (VR1) antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with VR1 activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor overactivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD).

摘要翻译： 本发明涉及四氢萘和脲衍生物及其盐，其可用作药物制剂的活性成分。 本发明的四氢萘和脲衍生物具有香草素受体（VR1）拮抗活性，可用于预防和治疗与VR1活性相关的疾病，特别是用于治疗泌尿系统疾病或病症，如逼尿肌 过度活动（膀胱过度活动），尿失禁，神经源性逼尿肌过度活动（逼尿肌hyperflexia），特发性逼尿肌过度活动（逼尿肌不稳定），良性前列腺增生和下尿路症状; 慢性疼痛，神经性疼痛，术后疼痛，类风湿性关节炎疼痛，神经痛，神经病，痛觉，神经损伤，局部缺血，神经变性，中风和炎性疾病如哮喘和慢性阻塞性肺（或气道）疾病（COPD）。

公开(公告)号：US09683019B2

公开(公告)日：2017-06-20

申请号：US14963391

申请日：2015-12-09

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

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

IPC分类号： A61K38/12 ,  C07K7/64 ,  C07K16/46 ,  A61K45/06 ,  C07K14/47 ,  A61K47/48 ,  C07K14/765

CPC分类号： 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

摘要： 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.