1142004-97-4

Upstream product

• 75634-03-6 4-chloro-6-(2-methoxy-phenyl)-pyrimidine 
• 5305-59-9 4-amino-6-chloropyrimidine 
• 5720-06-9 2-Methoxyphenylboronic acid 

Downstream Products

• 1142005-67-1 [6-(2-methoxy-phenyl)-pyrimidin-4-yl]-carbamic acid ethyl ester 
• 1142005-74-0 {3-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-ureido}-acetic acid ethyl ester 
• 1142004-88-3 (3-{3-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-ureido}-phenyl)-acetic acid 
• 1142005-59-1 1-[6-(2-methoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-pyrrolidine-2-carboxylic acid methyl ester 
• 1142004-78-1 N-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-2,2-dimethyl-propionamide 
• 1142005-73-9 N-benzoyl-N-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-benzamide 
• 1142004-80-5 N-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-2-phenyl-acetamide 
• 1142004-86-1 1-(2-dimethylamino-ethyl)-3-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-urea 
• 1142004-83-8 (rac)-N-(6-(2-methoxyphenyl)pyrimidin-4-yl)-6-oxopiperidine-3-carboxamide 
• 1142005-78-4 2-{3-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-ureido}-2-methyl-propionic acid ethyl ester 
• 1142005-76-2 2-{3-[6-(2-methoxy-phenyl)-pyrimidin-4-yl]-ureido}-propionic acid ethyl ester 
• 1142005-46-6 3-[6-(2-methoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester 
• 1142005-03-5 (R)-benzyl 3-(6-(2-methoxyphenyl)pyrimidin-4-ylcarbamoyl)piperidine-1-carboxylate 
• 1142005-53-5 (S)-3-[6-(2-methoxy-phenyl)-pyrimidin-4-ylcarbamoyl]-piperidine-1-carboxylic acid benzyl ester 

Relevant academic research and scientific papers

Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity

Specific inhibition of CDK9 is considered a promising strategy for developing effective anticancer therapeutics. However, most of the reported CDK9 inhibitors are still at an early stage of development and lack selectivity against other CDKs. Herein, we discovered coumarin derivative 30i as a potent CDK9 inhibitor with high selectivity (8300-fold over CDK7). Binding mode analysis illustrated that the substituent coumarin moiety is a critical group for CDK9 selectivity by occupying a flexible hinge/αD region, which is sterically hindered in other CDKs. Compound 30i showed excellent cellular antiproliferative activity, moderate pharmacokinetic property and low hERG inhibition. Moreover, 30i significantly induced tumour growth inhibition in a dose-dependent manner without causing an obvious loss of body weight in an MV4-11 xenograft mice model. Altogether, these results suggest that 30i may serve as a potential acute myeloid leukaemia (AML) therapeutics by selectively targeting CDK9.

INHIBITORS OF PROTEIN KINASES

Compounds of general Formula I, wherein R1, R2, R3, x, A and Ra are as defined herein are inhibitors of cyclin-dependent kinases and are useful for preventing and/or treating any type of pain, inflammatory disorders, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases and neurodegenerative diseases.