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.

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.