公开(公告)号：US20240252655A1

公开(公告)日：2024-08-01

申请号：US18288550

申请日：2022-04-29

申请人： Novartis AG ,  THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

发明人： Lydia Boike ,  Dustin Leard Dovala ,  Nathaniel James Henning ,  Matthew James Hesse ,  Gang Liu ,  Jeffrey M. McKenna ,  Daniel K. Nomura ,  Markus Eberhard Schirle ,  Jessica Nichole Spradlin ,  John A. Tallarico ,  Carl C. Ward ,  Melissa Pighetti

IPC分类号： A61K47/55 ,  C07D241/08 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D487/04

CPC分类号： A61K47/55 ,  C07D241/08 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D487/04

摘要： Described herein are bifunctional compounds, as well as pharmaceutically acceptable salts, hydrates, solvates, prodrugs, stereoisomers, or tautomers thereof, that function to recruit certain deubiquitinases to a target protein for modulation (e.g., stabilization) of the target protein, as well as methods of use thereof.

公开(公告)号：US10287266B2

公开(公告)日：2019-05-14

申请号：US15736925

申请日：2016-06-15

申请人： NOVARTIS AG

发明人： Zhuoliang Chen ,  Jorge Garcia Fortanet ,  Andriana Jouk ,  Rajesh Karki ,  Matthew J. LaMarche ,  Gang Liu ,  Mark G. Palermo ,  Lawrence Blas Perez ,  Patrick James Sarver ,  Michael David Shultz ,  Martin Sendzik ,  Bakary-Barry Toure ,  Bing Yu

IPC分类号： C07D401/14 ,  C07D401/04 ,  C07D471/10 ,  C07D491/107 ,  C07D498/10

摘要： The present invention relates to compounds of formula I: in which Y1, Y2, Y3, R1, R2, R4a, R4b, R5a, R5b, R6a and R6b are defined in the Summary of the Invention; capable of inhibiting the activity of SHP2. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds and compositions in the management of diseases or disorders associated with the aberrant activity of SHP2.

公开(公告)号：US12129246B1

公开(公告)日：2024-10-29

申请号：US18589841

申请日：2024-02-28

申请人： Novartis AG

发明人： Daniela Angst ,  Philippe Bolduc ,  Matthew William Carson ,  Atwood Kim Cheung ,  Véronique Darsigny ,  Xiang Gao ,  Viktor Hornak ,  Keith Jendza ,  Rajesh Karki ,  Ajay Kumar Lal ,  Gang Liu ,  Justin Yik Ching Mao ,  Jeffrey M. McKenna ,  Erik Meredith ,  Muneto Mogi ,  Vivek Rauniyar ,  Liansheng Su ,  Ritesh Tichkule ,  Shuangxi Wang ,  Chun Zhang ,  Liang Zhao ,  Rui Zheng

IPC分类号： C07D403/14 ,  A61K31/517 ,  A61K31/55 ,  A61K45/06 ,  C07D239/95 ,  C07D401/12 ,  C07D401/14

CPC分类号： C07D403/14 ,  A61K31/517 ,  A61K31/55 ,  A61K45/06 ,  C07D239/95 ,  C07D401/12 ,  C07D401/14

摘要： The disclosure relates to a compound of Formula (I):




or a pharmaceutically acceptable salt thereof wherein A, Ra to Rd, and R4 to R7, are as described herein, as well as compositions and methods of using such compounds.

公开(公告)号：US20240182464A1

公开(公告)日：2024-06-06

申请号：US18275379

申请日：2022-02-01

申请人： Les Laboratoirens Serviece ,  Novartis AG

发明人： András Herner ,  Piroska Markacz ,  Gang Liu ,  Katsumasa Nakajima ,  Tibor Novak ,  Georges-Alain Franzetti ,  Jérôme-Benoît Starck ,  Frédéric Colland ,  Patrice Desos ,  Attila Paczal ,  Bianka Szokol ,  Mátyás Pál Timari ,  Vilibald Kun ,  Matthew T. Burger ,  Joseph Anthony D'Alessio ,  Katherine Elizabeth Seiss ,  Rany Mathew Thomas ,  Liang Zhao

IPC分类号： C07D471/04 ,  A61P35/00 ,  C07D417/14

CPC分类号： C07D471/04 ,  A61P35/00 ,  C07D417/14

摘要： The present disclosure provides PROTAC compounds represented by Formula (A): D-L-DSM (A), or an enantiomer, a diastereoisomer, and/or a pharmaceutically acceptable salt of any one of the foregoing, wherein: DSM is a degradation signaling compound {e.g., an E3 ubiquitin ligase recruitment ligand, such as a CRBN ligand or a VHL ligand) covalently attached to a linker L; L is a linker that covalently attaches DSM to D; and D is a Bcl-xL inhibitor compound of Formula (I) or Formula (II) covalently attached to the linker L: (I); (II) wherein the definitions for the variables are described herein. Also provided are pharmaceutical compositions comprising the PROTAC compounds of the present disclosure and methods of use and methods of making thereof.

公开(公告)号：US10112931B2

公开(公告)日：2018-10-30

申请号：US15499824

申请日：2017-04-27

申请人： NOVARTIS AG

发明人： Thomas Raymond Caferro ,  Zhuoliang Chen ,  Young Shin Cho ,  Abran Q. Costales ,  Julian Roy Levell ,  Gang Liu ,  James R. Manning ,  Martin Sendzik ,  Cynthia Shafer ,  Michael David Shultz ,  James Clifford Sutton ,  Yaping Wang ,  Qian Zhao

IPC分类号： C07D413/14 ,  C07D413/04 ,  C07D417/14 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06

摘要： The invention is directed to a formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b and R3-R7 are herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formula (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

公开(公告)号：US09688672B2

公开(公告)日：2017-06-27

申请号：US15209731

申请日：2016-07-13

申请人： NOVARTIS AG

发明人： Thomas Raymond Caferro ,  Zhuoliang Chen ,  Young Shin Cho ,  Abran Q. Costales ,  Julian Roy Levell ,  Gang Liu ,  James R. Manning ,  Martin Sendzik ,  Cynthia Shafer ,  Michael David Shultz ,  James Clifford Sutton ,  Yaping Wang ,  Qian Zhao

IPC分类号： C07D413/14 ,  A61K31/506 ,  C07D413/04 ,  C07D417/14 ,  A61K31/5377

CPC分类号： C07D413/14 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D413/04 ,  C07D417/14

摘要： The invention is directed to a formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b and R3-R7 are herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formula (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

公开(公告)号：US20150152093A1

公开(公告)日：2015-06-04

申请号：US14408418

申请日：2014-03-12

申请人： NOVARTIS AG

发明人： Thomas Raymond Caferro ,  Zhuoliang Chen ,  Young Shin Cho ,  Abran Q. Costales ,  Julian Roy Levell ,  Gang Liu ,  James R. Manning ,  Martin Sendzik ,  Cynthia Shafer ,  Michael David Shultz ,  James Sutton ,  Yaping Wang ,  Qian Zhao

IPC分类号： C07D413/14 ,  C07D413/04 ,  A61K31/5377 ,  A61K31/506 ,  C07D417/14

CPC分类号： C07D413/14 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D413/04 ,  C07D417/14

摘要： The invention is directed to a formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b and R3-R7 are herein. The invention is also directed to compositions containing a compound of formula (I) and to the use of such compounds in the inhibition of mutant IDH proteins having a neomorphic activity. The invention is further directed to the use of a compound of formula (I) in the treatment of diseases or disorders associated with such mutant IDH proteins including, but not limited to, cell-proliferation disorders, such as cancer.

摘要翻译： 本发明涉及式（I）：或其药学上可接受的盐，其中R1，R2a，R2b和R3-R7为本文。 本发明还涉及含有式（I）化合物的组合物以及这些化合物在抑制具有新形态活性的突变体IDH蛋白质中的用途。 本发明还涉及式（I）化合物在治疗与这种突变体IDH蛋白相关的疾病或病症中的用途，包括但不限于细胞增殖病症如癌症。