Novartis Ag

Philipp Grosche

Hongjuan Zhao

Jun Yuan

Frederic Zecri

Kayo Yasoshima

Andrei Alexandrovich Golosov

Fumiaki Yokokawa

Takanori Kanazawa

Kazuhide Konishi

Werner Breitenstein

Keiichi Masuya

Yuki Iwaki

Takeru Ehara

Nils Ostermann

Alec Nathanson Flyer

Lauren Gilchrist Monovich

Juergen Klaus Maibaum

Tajesh Jayprakash Patel

Masaki Suzuki

Changgang Lou

Eugene Yuejin Liu

Qi-Ying Hu

Claus Ehrhardt

Hidetomo Imase

Rui Zheng

Andreas Marzinzik

Aimee Richardson Usera

Frédéric Zecri

Aaron Kanter

Alexandra Marshall Bruce

Justin Yik Ching Mao

Shimpei Kawakami

Yuko Hitomi

Atsushi Toyao

Liansheng Su

Brian Addison Dechristopher

Lihua Yang

Karin Briner

Muneto Mogi

David Thomas Parker

Shari Lynn Caplan

Mohindra Seepersaud

Edgar Jacoby

Ian Lewis

Osamu Irie

Carla Guimaraes

Juerg Zimmermann

Atsuko Iwasaki

Carina Cristina Sanchez

Eric Peters

Carla Giumaraes

Claus Erhardt

Atsuko Nihonyanagi

Johannes Ottl

Patrick Crawford Reid

The disclosure relates to inhibitors of PCSK9 useful in the treatment of lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I):

Cyclic peptides as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for the treatment of metabolic disorders

The disclosure relates to inhibitors of PCSK9 useful in the treatment of cholesterol lipid metabolism, and other diseases in which PCSK9 plays a role, having the Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, N-oxide, or tautomer thereof, wherein R, R, R, R, R, R, R, R, R, X, X, and Xare described herein.

Cyclic tetramer compounds as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors for the treatment of metabolic disorders

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.

Synthetic linear apelin mimetics for the treatment of heart failure

The invention provides a synthetic polypeptide of Formula I': 

Synthetic apelin mimetics for the treatment of heart failure

The invention provides a synthetic polypeptide of Formula I (SEQ ID NO: 1):X1-R-X3-R-L-X6-X7-K-X9-P-X11-X12-X13&#x2003;&#x2003;I

Cyclic apelin derivatives for the treatment of heart failure

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&#x2003;&#x2003;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.

Cyclic polypeptides for the treatment of heart failure

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.

Disulfide cyclic polypeptides for the treatment of heart failure

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.

Bioconjugates of synthetic apelin polypeptides

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&#x2003;&#x2003;Ior 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.

The invention provides a synthetic polypeptide of Formula I' (SEQ ID NO: 1):X1-X2-X3-R&#x2014;X5-X6-X7-X8-X9-X10-X11-X12-X13&#x2003;&#x2003;I

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 3,4substituted 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), wherein the symbols have the meanings defined in the specification. 

Organic compounds

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. 

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 compounds have the formula I' wherein R1, R2, T, R3 and R4 are as defined in the specification.

Growing community of inventors

Inzlingen, Germany

Philipp Grosche