Title:
HETEROCYCLIC COMPOUND FOR INDUCING DEGRADATION OF MUTANT KRAS PROTEIN
Document Type and Number:
WIPO Patent Application WO/2024/029613
Kind Code:
A1
Abstract:
Provided is a compound useful as an active ingredient in a pharmaceutical composition for treating pancreatic cancer. The present inventors carried out investigations with regard to compounds useful as an active ingredient in a pharmaceutical composition for treating pancreatic cancer and have found that a heterocyclic compound represented by formula (I) has an excellent action with regard to inducing the degradation of mutant KRAS protein and particularly with regard to inducing the degradation of G12V mutant, G12D mutant, and G12C mutant KRAS proteins, and has a mutant KRAS inhibitory activity and particularly G12V mutant, G12D mutant, and G12C mutant KRAS inhibitory activities. The present invention was achieved on the basis of these findings. The heterocyclic compound according to the present invention or a salt thereof can be used as a therapeutic agent for pancreatic cancer.
Inventors:
MORIKAWA TAKAHIRO (JP)
IMADA SUNAO (JP)
HAMAGUCHI HISAO (JP)
OKUMURA MITSUAKI (JP)
IMAIZUMI TOMOYOSHI (JP)
KOGANEMARU YOHEI (JP)
HONJO ERIKO (JP)
FUJIWARA YUTA (JP)
KAWAMINAMI EIJI (JP)
YOSHINARI TOMOHIRO (JP)
ISHIOKA HIROKI (JP)
KURAMOTO KAZUYUKI (JP)
NISHIZONO YOSHIHIRO (JP)
IMADA SUNAO (JP)
HAMAGUCHI HISAO (JP)
OKUMURA MITSUAKI (JP)
IMAIZUMI TOMOYOSHI (JP)
KOGANEMARU YOHEI (JP)
HONJO ERIKO (JP)
FUJIWARA YUTA (JP)
KAWAMINAMI EIJI (JP)
YOSHINARI TOMOHIRO (JP)
ISHIOKA HIROKI (JP)
KURAMOTO KAZUYUKI (JP)
NISHIZONO YOSHIHIRO (JP)
Application Number:
PCT/JP2023/028510
Publication Date:
February 08, 2024
Filing Date:
August 04, 2023
Export Citation:
Assignee:
ASTELLAS PHARMA INC (JP)
International Classes:
C07D401/14; A61K31/4709; A61K31/517; A61K31/5377; A61K38/05; A61P1/18; A61P35/00; A61P43/00; C07D403/14; C07D405/14; C07D413/14; C07D417/14
Domestic Patent References:
| WO2017172979A1 | 2017-10-05 | |||
| WO2018143315A1 | 2018-08-09 | |||
| WO2021041671A1 | 2021-03-04 | |||
| WO2022173032A1 | 2022-08-18 | |||
| WO2023120742A1 | 2023-06-29 |
Foreign References:
| JP2021521112A | 2021-08-26 |
Other References:
WANG HAO, CHI LINGLING, YU FUQIANG, DAI HONGLIN, GAO CHAO, SI XIAOJIE, WANG ZHENGJIE, LIU LIMIN, ZHENG JIAXIN, SHAN LIHONG, LIU HO: "Annual review of KRAS inhibitors in 2022", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 249, 1 March 2023 (2023-03-01), AMSTERDAM, NL , pages 115124, XP093135185, ISSN: 0223-5234, DOI: 10.1016/j.ejmech.2023.115124
BOND MICHAEL J., CHU LING, NALAWANSHA DHANUSHA A., LI KE, CREWS CRAIG M.: "Targeted Degradation of Oncogenic KRAS G12C by VHL-Recruiting PROTACs", ACS CENTRAL SCIENCE, vol. 6, no. 8, 26 August 2020 (2020-08-26), pages 1367 - 1375, XP055866207, ISSN: 2374-7943, DOI: 10.1021/acscentsci.0c00411
BOND MICHAEL J., CHU LING, NALAWANSHA DHANUSHA A., LI KE, CREWS CRAIG M.: "Targeted Degradation of Oncogenic KRAS G12C by VHL-Recruiting PROTACs", ACS CENTRAL SCIENCE, vol. 6, no. 8, 26 August 2020 (2020-08-26), pages 1367 - 1375, XP055866207, ISSN: 2374-7943, DOI: 10.1021/acscentsci.0c00411
Attorney, Agent or Firm:
YAMAMOTO, Osamu et al. (JP)
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