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公开(公告)号：US20160145309A1
公开(公告)日：2016-05-26
申请号：US14905338
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
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.
摘要翻译： 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。
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公开(公告)号：US20160108091A1
公开(公告)日：2016-04-21
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： C07K7/64 , 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.
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公开(公告)号：US09266925B2
公开(公告)日：2016-02-23
申请号：US14336262
申请日：2014-07-21
申请人： Frederic Zecri , Philipp Grosche , Kayo Yasoshima , Hongjuan Zhao , Jun Yuan , Aimee Richardson Usera , Changgang Lou , Aaron Kanter , Alexandra Marshall Bruce , Carla Giumaraes
发明人： Frederic Zecri , Philipp Grosche , Kayo Yasoshima , Hongjuan Zhao , Jun Yuan , Aimee Richardson Usera , Changgang Lou , Aaron Kanter , Alexandra Marshall Bruce , Carla Giumaraes
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.
摘要翻译： 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。
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公开(公告)号：US09067971B2
公开(公告)日：2015-06-30
申请号：US14165680
申请日：2014-01-28
申请人： Frederic Zecri , Andrei Golosov , Philippr Grosche , Hongjuan Zhao , Qi-Ying Hu , Hidetomo Imase
发明人： Frederic Zecri , Andrei Golosov , Philippr Grosche , Hongjuan Zhao , Qi-Ying Hu , Hidetomo Imase
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。
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公开(公告)号：US08673848B2
公开(公告)日：2014-03-18
申请号：US13747621
申请日：2013-01-23
申请人： Frédéric Zecri , Andrei Golosov , Philipp Grosche , Kayo Yasoshima , Hongjuan Zhao , Qi-Ying Hu , Hidetomo Imase , David Thomas Parker
发明人： Frédéric Zecri , Andrei Golosov , Philipp Grosche , Kayo Yasoshima , Hongjuan Zhao , Qi-Ying Hu , Hidetomo Imase , David Thomas Parker
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。
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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
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.
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公开(公告)号：US09340582B2
公开(公告)日：2016-05-17
申请号：US14336290
申请日：2014-07-21
申请人： Jun Yuan , Frederic Zecri , Philipp Grosche , Hongjuan Zhao , Eric Peters , Shari Lynn Caplan , Changgang Lou
发明人： Jun Yuan , Frederic Zecri , Philipp Grosche , Hongjuan Zhao , Eric Peters , Shari Lynn Caplan , Changgang Lou
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.
摘要翻译： 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。
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公开(公告)号：US20150031604A1
公开(公告)日：2015-01-29
申请号：US14336262
申请日：2014-07-21
申请人： Frederic ZECRI , Philipp GROSCHE , Kayo YASOSHIMA , Hongjuan ZHAO , Jun Yuan , Aimee Richardson USERA , Changgang LOU , Aaron KANTER , Alexandra Marshall BRUCE , Carla Giumaraes
发明人： Frederic ZECRI , Philipp GROSCHE , Kayo YASOSHIMA , Hongjuan ZHAO , Jun Yuan , Aimee Richardson USERA , Changgang LOU , Aaron KANTER , Alexandra Marshall BRUCE , Carla Giumaraes
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.
摘要翻译： 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。
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公开(公告)号：US20130196899A1
公开(公告)日：2013-08-01
申请号：US13747621
申请日：2013-01-23
申请人： Frédéric ZECRI , Andrei GOLOSOV , Philipp GROSCHE , Kayo YASOSHIMA , Hongjuan ZHAO , Qi-Ying HU , Hidetomo IMASE , David Thomas PARKER
发明人： Frédéric ZECRI , Andrei GOLOSOV , Philipp GROSCHE , Kayo YASOSHIMA , Hongjuan ZHAO , Qi-Ying HU , Hidetomo IMASE , David Thomas PARKER
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。
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公开(公告)号：US20100093842A1
公开(公告)日：2010-04-15
申请号：US12548002
申请日：2009-08-26
申请人： Brian M. Gallagher, JR. , Charles Johannes , Xiang-Yi Li , Marc Pesant , Hongjuan Zhao , Kozo Akasaka , Francis G. Fang
发明人： Brian M. Gallagher, JR. , Charles Johannes , Xiang-Yi Li , Marc Pesant , Hongjuan Zhao , Kozo Akasaka , Francis G. Fang
IPC分类号： A61K31/365 , C07D493/14 , C07D493/04 , C12N5/00 , A61P35/00
CPC分类号： C07D493/08
摘要： The present invention provides compounds having formula I: and pharmaceutically acceptable derivatives thereof, wherein R1-R10, q, t, X0, X1, A, B, D, E, G, J, K, L, M and Z are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of disorders associated with cellular hyperproliferation.
摘要翻译： 本发明提供具有式I化合物及其药学上可接受的衍生物，其中R1-R10，q，t，X0，X1，A，B，D，E，G，J，K，L， 通常和本文中的类别和亚类，并且另外提供其药物组合物，以及用于其用于治疗与细胞过度增殖相关的病症的方法。
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