网站主页>>>数据中心>>>工艺路线数据>>>Adagrasib CAS# 2326521-71-3 (2S)-4-[7-(8-氯-1-萘)-5,6,7,8-四氢-2-[[((2S)-1-甲基-2-吡咯烷基]甲氧基]吡啶基[3,4-d]嘧啶-4-基]-1-(2-氟-1-氧代-2-丙烯-1-基)-2-哌Chemicalbook嗪乙腈:2-((S)-4-(7-(8-氯萘-1-基)-2-((((S)-1-
Adagrasib CAS# 2326521-71-3 (2S)-4-[7-(8-氯-1-萘)-5,6,7,8-四氢-2-[[((2S)-1-甲基-2-吡咯烷基]甲氧基]吡啶基[3,4-d]嘧啶-4-基]-1-(2-氟-1-氧代-2-丙烯-1-基)-2-哌Chemicalbook嗪乙腈:2-((S)-4-(7-(8-氯萘-1-基)-2-((((S)-1-
Adagrasib (MRTX849) is a potent, selective, and irreversible inhibitor of KRAS^G12C^, a mutant form of the KRAS protein prevalent in various cancers. In preclinical studies, adagrasib demonstrated nanomolar potency with IC₅₀ values of 0.12–0.15 µM in KRAS^G12C^ mutant cell lines. It showed strong antitumor activity in xenograft models, with tumor regression observed at doses of 30–100 mg/kg. In the Phase 1/2 KRYSTAL-1 trial, adagrasib achieved an objective response rate (ORR) of 43% and disease control rate (DCR) of 80% in NSCLC patients with KRAS^G12C^ mutations. Its favorable pharmacokinetics include a long half-life (~24 hours), supporting twice-daily oral dosing.
📌 参考资料/链接：
Lu, Zhichao; Chen, Chengsheng; Paymode, Dinesh J. ; Gan, Yonghong; Scattolin, Thomas ; Roshandel, Sahar; Dong, Weitong; Yu, Stanley ; Lemeune, Stephane; Snead, David R. ; et alDOI: 10.1021/acs.oprd.4c00024Process optimization details are disclosed following the completion of process design for a second-generation manufacturing route of adagrasib. Key objectives for development included control of difficult-to-purge impurities in the key starting materials (KSMs), enhanced scalability of the KSM, improved pyrimidone formation of the core, increased robustness of oxidation, enhanced stability of the step 3 intermediate, removal of the halogenated solvent in the fourth step, and implementation of single crystallization of the final API. These improvements led to more efficient production of adagrasib and a further reduction in the cost of goods by approx. 50%.
Lu, Zhichao; Chen, Chengsheng; Paymode, Dinesh J. ; Gan, Yonghong; Scattolin, Thomas ; Roshandel, Sahar; Dong, Weitong; Yu, Stanley ; Lemeune, Stephane; Snead, David R. ; et alDOI: 10.1021/acs.oprd.4c00024Process optimization details are disclosed following the completion of process design for a second-generation manufacturing route of adagrasib. Key objectives for development included control of difficult-to-purge impurities in the key starting materials (KSMs), enhanced scalability of the KSM, improved pyrimidone formation of the core, increased robustness of oxidation, enhanced stability of the step 3 intermediate, removal of the halogenated solvent in the fourth step, and implementation of single crystallization of the final API. These improvements led to more efficient production of adagrasib and a further reduction in the cost of goods by approx. 50%.
📄 详细内容
CAS No. 2326521-71-3 (2S)-4-[7-(8-氯-1-萘)-5,6,7,8-四氢-2-[[((2S)-1-甲基-2-吡咯烷基]甲氧基]吡啶基[3,4-d]嘧啶-4-基]-1-(2-氟-1-氧代-2-丙烯-1-基)-2-哌Chemicalbook嗪乙腈:2-((S)-4-(7-(8-氯萘-1-基)-2-((((S)-1-Adagrasib synthetic routes
Lu, Zhichao; et al. Adagrasib's Second-Generation Synthesis: Transitioning from Route Scouting to Optimization. Organic Process Research & Development (2024), 28(8), 3128-3142
产品链接: CAS No. 2326521-71-3 ››
Lu, Zhichao; et al. Adagrasib's Second-Generation Synthesis: Transitioning from Route Scouting to Optimization. Organic Process Research & Development (2024), 28(8), 3128-3142
产品链接: CAS No. 2326521-71-3 ››