公开(公告)号：US20210379056A1

公开(公告)日：2021-12-09

申请号：US17281567

申请日：2019-09-30

Applicant: Applied Pharmaceutical Science, Inc.

Inventor： Zhijian WANG ,  Jun ZHONG ,  Xuebing WANG

IPC: A61K31/496 ,  C07D471/04 ,  C07D519/00 ,  A61K31/4995 ,  A61K31/4545 ,  A61P35/00

Abstract: A compound is represented by the following formula I. The compound and stereoisomer, racemate, tautomer, isotope labelled derivative, nitrogen oxide, pharmaceutically acceptable salt or solvate thereof can be prepared and used in the preparation of a medicament for treating a RET kinase-mediated disease.

公开(公告)号：US20240174674A1

公开(公告)日：2024-05-30

申请号：US18264687

申请日：2022-01-24

Applicant: APPLIED PHARMACEUTICAL SCIENCE, INC.

Inventor： Jun ZHONG ,  Yongkuan ZHU ,  Yongbo LIU ,  Xiaohu CHEN ,  Libin LIU ,  Minchun CHEN ,  Hao WANG ,  Qin GAO

IPC: C07D471/14 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/501 ,  A61K31/5377 ,  A61K31/553 ,  C07D519/00

CPC classification number: C07D471/14 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/497 ,  A61K31/501 ,  A61K31/5377 ,  A61K31/553 ,  C07D519/00

Abstract: A nitrogen-containing polycyclic fused ring compound represented by formula I, a pharmaceutical composition thereof, a preparation method therefor, and a use thereof are provided. The compound has an inhibitory effect on RET gatekeeper residue mutant RET V804M mutation, RET solvent front residue mutant G810R, and other clinically relevant RET mutants and RET-wt. The compound can also significantly inhibit the growth of a TT cell line derived from thyroid cancer and Ba/F3 cells transformed by various RET mutants, and has a stronger inhibition effect than selective RET inhibitor LOXO-292. In addition, the compound can block cellular RET autophosphorylation and downstream pathways, and can significantly induce TT cell death.

公开(公告)号：US20220332731A1

公开(公告)日：2022-10-20

申请号：US17633137

申请日：2020-08-05

Applicant: APPLIED PHARMACEUTICAL SCIENCE, INC.

Inventor： Jun ZHONG ,  Yongbo LIU ,  Libin LIU ,  Xiaohu CHEN ,  Hao WANG ,  Ying LU

IPC: C07D519/00

Abstract: A nitrogen-containing polycyclic fused ring compound of formula I, a pharmaceutical composition thereof, a preparation method therefor and use thereof are related to the field of medicinal chemistry. The compound can be used as a selective and effective RET inhibitor. It has strong inhibitory effect on the RET gatekeeper residue mutant RET V804M, RET solvent-front residue mutant RET G810R and other clinically relevant RET mutants, as well as RET wt. The compound can also inhibit the growth of TT cell line derived from thyroid cancer and Ba/F3 cells transformed with various RET mutants, and induce the death of TT cells.

公开(公告)号：US09656951B2

公开(公告)日：2017-05-23

申请号：US14007925

申请日：2012-12-06

Applicant: Applied Pharmaceutical Science, Inc. ,  Zhijian Wang ,  Xiaohong Zhang

Inventor： Xiaohong Zhang ,  Lu Song ,  Wendong Sun ,  Kaiyang Liu ,  Chunlei Han

IPC: A61K31/277 ,  C07C255/47 ,  A61K31/56 ,  C07J63/00 ,  C07C253/34

CPC classification number: C07C255/47 ,  A61K31/277 ,  A61K31/56 ,  C07B2200/13 ,  C07C253/34 ,  C07J63/008

Abstract: The present invention relates to polymorphic forms of the compound of Formula I (i.e., ethyl 2-cyano-3,12-dioxoIeana-1,9(11)-dien-28-oate (CDDO ethyl ester)) and methods of using them for treating a variety of disease states such as cancer and condisitons associated with inflammation.

公开(公告)号：US20170355666A1

公开(公告)日：2017-12-14

申请号：US15601968

申请日：2017-05-22

Applicant: Applied Pharmaceutical Science Inc. ,  Zhijian Wang ,  Xiaohong Zhang

Inventor： Xiaohong Zhang ,  Lu Song ,  Wendong Sun ,  Kaiyang Liu ,  Chunlei Han

IPC: C07C255/47 ,  A61K31/277 ,  C07C253/34 ,  C07J63/00 ,  A61K31/56

CPC classification number: C07C255/47 ,  A61K31/277 ,  A61K31/56 ,  C07B2200/13 ,  C07C253/34 ,  C07J63/008

Abstract: The present invention relates to polymorphic forms of the compound of Formula I (i.e., ethyl 2-cyano-3,12-dioxokana-1,9(11)-dien-28-oate (CDDO ethyl ester)) and methods of using them for treating a variety of disease states such as cancer and conditions associated with inflammation.