148400-72-0

Upstream product

• 42772-85-0 2-hydroxyethyl 4-methylbenzenesulfonate 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 98-59-9 p-toluenesulfonyl chloride 
• 102229-10-7 2-(tert-butyldimethylsilyloxy)ethanol 

Downstream Products

• 133701-02-7 2,6-Bis-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-benzoic acid ethyl ester 
• 944127-26-8 25,27-bis{[2-(benzyloxy)ethyl]oxy}-26,28-bis{[2-(tert-butyldimethylsilyloxy)ethyl]oxy}calix[4]arene 
• 144127-73-1 C₃₆H₄₁NO₅SSi 
• 144127-89-9 C₃₄H₃₇NO₅Si 

Relevant academic research and scientific papers

Novel derivatives of anaplastic lymphoma kinase inhibitors: Synthesis, radiolabeling, and preliminary biological studies of fluoroethyl analogues of crizotinib, alectinib, and ceritinib

Anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase, is a therapeutic target in various cancers, including non-small cell lung cancer. Although several ALK inhibitors, including crizotinib, ceritinib, and alectinib, are approved for cancer treatment, their long-term benefit is often limited by the cancer's acquisition of resistance owing to secondary point mutations in ALK. Importantly, some ALK inhibitors cannot cross the blood-brain barrier (BBB) and thus have little or no efficacy against brain metastases. The introduction of a lipophilic moiety, such as a fluoroethyl group may improve the drug's BBB penetration. Herein, we report the synthesis of fluoroethyl analogues of crizotinib 1, alectinib 4, and ceritinib 9, and their radiolabeling with 18F for pharmacokinetic studies. The fluoroethyl derivatives and their radioactive analogues were obtained in good yields with high purity and good molar activity. A cytotoxicity screen in ALK-expressing H2228 lung cancer cells showed that the analogues had up to nanomolar potency and the addition of the fluorinated moiety had minimal impact overall on the potency of the original drugs. Positron emission tomography in healthy mice showed that the analogues had enhanced BBB penetration, suggesting that they have therapeutic potential against central nervous system metastases.

2-AZASPIRO[3.4]OCTANE DERIVATIVES AS M4 AGONISTS

Provided herein are compounds according to Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, and R7 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) as well as the use of such compounds as M4 receptor agonists.

COMPOUNDS AND USES THEREOF

The present invention features compounds useful in the treatment of BAF complex related disorders.