1078136-96-5

Upstream product

• 4284-50-8 N-(4-bromophenyl)methanesulfonamide 
• 1352244-85-9 N-(4-bromo-2-nitrophenyl)methanesulfonamide 
• 74-88-4 methyl iodide 

Downstream Products

• 1352244-20-2 N-[4-bromo-2-(2,5-dichloropyrimidin-4-ylamino)phenyl]-N-methylmethanesulfonamide 
• 1352244-22-4 N-[2-(2,5-dichloropyrimidin-4-ylamino)-4-vinylphenyl]-N-methylmethanesulfonamide 
• 1352244-34-8 N-(4-bromo-2-{5-chloro-2-[4-(4-methylpiperazin-1-yl)-3-vinylphenylamino]pyrimidin-4-ylamino}phenyl)-N-methylmethanesulfonamide 
• 1352244-37-1 N-(2-{2-[5-bromo-2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino]-5-chloropyrimidin-4-ylamino}-4-vinylphenyl)-N-methylmethanesulfonamide 
• 1078137-12-8 N-(2-amino-4-bromophenyl)-N-methylmethanesulfonamide 
• 1352244-14-4 N-(2-amino-4-vinylphenyl)-N-methylmethanesulfonamide 
• 1352244-86-0 N-methyl-N-(2-nitro-4-vinylphenyl)methanesulfonamide 

Relevant academic research and scientific papers

Design, synthesis, and anaplastic lymphoma kinase (ALK) inhibitory activity for a novel series of 2,4,8,22-tetraazatetracyclo[14.3.1.13,7.1 9,13]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene macrocycles

A novel set of 2,4,8,22-tetraazatetracyclo[14.3.1.13,7.1 9,13]docosa-1(20),3(22),4,6,9(21),10,12,16,18-nonaene macrocycles were prepared as potential anaplastic lymphoma kinase (ALK) inhibitors, designed to rigidly lock an energy-minimized bioactive conformation of the diaminopyrimidine (DAP) scaffold, a well-documented kinase platform. From 13 analogues prepared, macrocycle 2m showed the most promising in vitro ALK enzymatic (IC50 = 0.5 nM) and cellular (IC50 = 10 nM) activities. In addition, macrocycle 2m exhibited a favorable kinase selectivity preference for inhibition of ALK relative to the highly homologous insulin receptor (IR) kinase (IR/ALK ratio of 173). The inclusive in vitro biological results for this set of macrocycles validate this scaffold as a viable kinase template and further corroborate recent DAP/ALK solid state studies indicating that the inverted "U" shaped conformation of the acyclic DAPs is a preferred bioactive conformation.

MACROCYCLIC COMPOUNDS AS ALK, FAK AND JAK2 INHIBITORS

The present invention provides compounds of Formula I or a pharmaceutically acceptable salt forms thereof, wherein R1, R2, R3, R4, R5, A and X are as defined herein, methods of treatment and uses thereof.