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：US20240216513A1

公开(公告)日：2024-07-04

申请号：US18281732

申请日：2022-03-10

申请人： Novartis AG

发明人： Claire Adcock ,  Valerie Broennimann ,  Jiashun Cheng ,  Rohit Kumar Duvadie ,  Tanzina Fazal ,  Jinhai Gao ,  Fengfeng Guo ,  Robert Martin Grotzfeld ,  Christina Hebach ,  Gregory John Hollingworth ,  Darryl Brynley Jones ,  Alexei Karpov ,  Jialiang Li ,  Julien Lorber ,  Chester A. Metcalf, III ,  Walter Michael ,  Mark Gabriel Palermo ,  Scott Vaughan Plummer ,  James Harold Roache ,  Martin Sendzik ,  Ranny Mathew Thomas ,  Aimee Richardson Usera ,  Anna Vulpetti ,  Frederic Zecri ,  Liang Zhao ,  Thomas Zoller

IPC分类号： A61K47/54 ,  A61K31/395 ,  A61K47/10 ,  A61P35/00

CPC分类号： A61K47/542 ,  A61K31/395 ,  A61K47/10 ,  A61P35/00

摘要： Described herein are fatty acid-bifunctional degrader compounds, their various targets, their preparation, pharmaceutical compositions comprising them, and their use in the treatment of conditions, diseases, and disorders mediated by various target proteins.

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.