1192471-59-2

Upstream product

• 15411-43-5 3-vinylaniline 
• 5750-76-5 2,4,5-trichloropyrimidine 

Downstream Products

• 1352244-26-8 N₂-(3-bromo-4-morpholin-4-ylphenyl)-5-chloro-N₄-3-vinylphenylpyrimidine-2,4-diamine 
• 1352244-27-9 N₂-[3-bromo-4-(2-pyrrolidin-1-ylethoxy)phenyl]-5-chloro-N₄-(3-vinylphenyl)pyrimidine-2,4-diamine 
• 1352244-28-0 N₂-[3-bromo-4-(4-methylpiperazin-1-yl)phenyl]-5-chloro-N₄-(3-vinylphenyl)pyrimidine-2,4-diamine 
• 1352244-35-9 N₂-[5-bromo-2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-5-chloro-N₄-(3-vinylphenyl)pyrimidine-2,4-diamine 

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.