公开(公告)号：US11578074B2

公开(公告)日：2023-02-14

申请号：US16643196

申请日：2018-08-31

Applicant: SHANGHAI PHARMACEUTICALS HOLDING CO., LTD.

Inventor： Guangxin Xia ,  Di Li ,  Jing Zhang ,  Lingjun Duan ,  Hongjian Zuo ,  Wenbo Xiao ,  Jia Xu ,  Yanjun Liu

IPC: C07D403/12 ,  C07D471/04 ,  C07D487/04 ,  A61P35/00

Abstract: A nitrogenous heterocyclic compound, a preparation method, an intermediate, a composition, and an application. The present invention provides a nitrogenous heterocyclic compound as represented by formula I, pharmaceutically acceptable salts thereof, enantiomers thereof, diastereoisomers thereof, tautomers thereof, solvates thereof, metabolites thereof, or prodrugs thereof. The compound has high inhibitory activity against ErbB2 tyrosine kinase, has good inhibitory activity against human breast cancer cells BT-474, human gastric cancer cells NCI-N87 and the like with high expression of ErbB2, and in addition has relatively weak inhibitory activity against EGFR kinase, that is, the compound is an EGFR/ErbB2 double target inhibitor that attenuates EGFR kinase inhibitory activity or a small-molecule inhibitor having selectivity for an ErbB2 target.

公开(公告)号：US10988476B2

公开(公告)日：2021-04-27

申请号：US16848942

申请日：2020-04-15

Applicant: SHANGHAI PHARMACEUTICALS HOLDING CO., LTD.

Inventor： Guangxin Xia ,  Qian Wang ,  Chen Shi ,  Xiong Zhai ,  Hui Ge ,  Xuemei Liao ,  Yu Mao ,  Zhixiong Xiang ,  Yanan Han ,  Guoyong Huo ,  Yanjun Liu

IPC: A61K31/506 ,  C07D239/30 ,  C07D471/04 ,  A61P35/00 ,  C07F5/02 ,  C07F7/08 ,  C07F9/6561 ,  C07F9/6584

Abstract: The present invention discloses a substituted pyridine compound represented by formula I, and a pharmaceutically acceptable salt, stereoisomer and tautomer thereof. The compounds of the present invention are useful in the treatment of cancers.

公开(公告)号：US10828305B2

公开(公告)日：2020-11-10

申请号：US16081558

申请日：2017-03-01

Applicant: SHANGHAI PHARMACEUTICALS HOLDING CO., LTD.

Inventor： Guangxin Xia ,  Di Li ,  Hongjian Zuo ,  Guangsheng Wu ,  Lingjun Duan ,  Jing Zhang ,  Yu Mao ,  Yanjun Liu

IPC: A61K31/519 ,  A61K31/5377 ,  C07D487/04 ,  A61P35/00 ,  A61K31/5355 ,  A61K31/541

Abstract: Disclosed are a nitrogenous heterocyclic compound, intermediates, a preparation method, a composition and use thereof. The nitrogenous heterocyclic compound in the present invention is as shown in formula I. The compound has a high inhibitory activity towards ErbB2 tyrosine kinase and a relatively good inhibitory activity towards human breast cancer BT-474 and human gastric cancer cell NCI-N87 which express ErbB2 at a high level, and at the same time has a relatively weak inhibitory activity towards EGFR kinase. Namely, the compound is a highly selective small-molecule inhibitor targeted at ErbB2, and hence it has a high degree of safety, and can effectively enlarge the safety window in the process of taking the drug.

公开(公告)号：US10662186B2

公开(公告)日：2020-05-26

申请号：US16067158

申请日：2016-12-30

Applicant: SHANGHAI PHARMACEUTICALS HOLDING CO., LTD.

Inventor： Guangxin Xia ,  Qian Wang ,  Chen Shi ,  Xiong Zhai ,  Hui Ge ,  Xuemei Liao ,  Yu Mao ,  Zhixiong Xiang ,  Yanan Han ,  Guoyong Huo ,  Yanjun Liu

IPC: A61K31/506 ,  C07D239/30 ,  C07D471/04 ,  A61P35/00 ,  C07F5/02 ,  C07F7/08 ,  C07F9/6561 ,  C07F9/6584

Abstract: The present invention discloses a nitrogen-containing fused heterocyclic compound, as well as a preparation method, intermediate, composition and application thereof. The nitrogen-containing fused heterocyclic compound of the present invention as represented by formula (I), as well as the pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, metabolite or drug precursor thereof, exhibit a high selectivity and a high inhibitory activity with respect to CDK4 and CDK6 at a molecular level, an excellent inhibitory activity with respect to breast cancer cells at a cellular level, and significant inhibition of tumor cell proliferation associated with cyclin-dependent kinase activity at an animal level. The invention also exhibits a good stability with respect to human or mouse liver microsomes without significant inhibition of metabolic enzymes, good in vivo absorption in mice and rats, a high bioavailability and good druggability.