1022958-40-2

Upstream product

• 95-54-5 1,2-diamino-benzene 
• 953048-66-3 N¹-(2,5-dichloropyrimidin-4-yl)benzene-1,2-diamine 
• 124-63-0 methanesulfonyl chloride 

Downstream Products

• 2244775-31-1 N-(2-((5-chloro-2-((2-methoxy-6-(4-methylpiperazin-1-yl)pyridin-3-yl)amino)pyrimidin-4-yl)amino)phenyl)methanesulfonamide 
• 1247914-91-5 N-(2-(2-(3-(2-aminoethoxy)phenylamino)-5-chloropyrimidin-4-ylamino)phenyl)methanesulfonamide 

Relevant academic research and scientific papers

Structure-based design of 2,4-diaminopyrimidine derivatives bearing a pyrrolyl group as ALK and ROS1 inhibitors

In order to develop potent ALK and ROS1 dual inhibitors, twenty-eight 2,4-diaminopyrimidine derivatives (9a-9n and 10a-10n) bearing a pyrrolyl moiety were designed and synthesized based on the co-crystal structure of ceritinib with ALKwt protein. Most compounds displayed considerable activity against ALK and ROS1 addicted cells; meanwhile, compound 10d showed excellent activity against Karpas299, H2228 and HCC78 with IC50 values of 0.01, 0.08 and 0.042 μM. Subsequently, seven compounds were selected for kinase studies in vitro, resulting in the discovery of 10d with IC50 values of 1.8, 4.3 and 3.6 nM against ALK, ALKL1196M and ROS1, respectively. Furthermore, the biological assays revealed that compound 10d induced cell apoptosis in a dose-dependent manner. Ultimately, molecular docking studies presented reasonable and optimal binding interactions with ALKwt and ROS1.

Discovery and antitumor activity of Benzo[d]imidazol-containing 2,4-diarylaminopyrimidine analogues as ALK inhibitors with mutation-combating effects

To address drug resistance caused by ALK kinase mutations, a series of novel 2,4-diarylaminopyrimidine (DAAP) analogues were designed by incorporating 1H-benzo[d]imidazol motif onto the maternal framework. All compounds were efficiently synthesized and an

Pyrroformyl-containing 2,4-diaminopyrimidine derivatives as a new optimization strategy of ALK inhibitors combating mutations

Aiming to identify new optimization strategy effective for ALK-mutations, two series of pyrroformyl-containing 2,4-diaminopyrimidine compounds (11a-o, 12a-o) were designed, synthesized and evaluated for their anti-proliferative activities against three ca

Design, synthesis and biological evaluation N2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives bearing acylamino or DBTD ‘head’ as potential ALK inhibitors

Aiming to develop promising ALK inhibitors, two series of N2-(2-alkyoxy-6-aliphatic aminopyridin-3-yl)-2,4-diaminepyrimidine derivatives (22a-x and 23a-d) were designed according to scaffold hopping and bioisosterism principles. All compounds were efficiently synthesized by concise reactions and anti-proliferative activities on ALK-addicted H2228, Karpas299 cells and EGFR-expressive A549 cell were evaluated by MTT assay. Several compounds exhibited potential cytotoxic activities with IC50 values below 0.10 μM. Five compounds (22g, 22h, 22l, 22s and 23a) were selected for further enzymatic determination, resulting in the discovery of 22l against ALK and ALKL1196M with IC50 values of 2.1 nM and 3.8 nM. Particularly, western blot and cell apoptosis assays identified 22l as a promising ALK inhibitor, which was capable of obviously inhibiting cellular ALK activity and inducing cell apoptosis. Eventually, molecular docking modes of 22l with ALK confirmed structural basis in accordance with the SARs analysis.

Aromatic heterocycle-containing 2, 4-diarylaminopyrimidine derivative as well as preparation and application of 2, 4-diarylaminopyrimidine derivative

The invention relates to an aromatic heterocycle-containing 2, 4-diarylaminopyrimidine derivative represented by a general formula I, an optical isomer, a pharmaceutically acceptable salt, a solvate or a prodrug thereof, preparation methods of the aromatic heterocycle-containing 2, 4-diarylaminopyrimidine derivative and the optical isomer, the pharmaceutically acceptable salt, the solvate or the prodrug, and a pharmaceutical composition using the compound represented by the general formula I as an active component, wherein substituents R1, R2, R3, R4, R5, R6, X, Y and Z have meanings given inthe specification. The invention also relates to the compound shown in the general formula I, which has strong ALK and ROS1 kinase inhibition effects, and also relates to application of the compound and the optical isomer and pharmaceutically acceptable salt thereof in preparation of drugs for treatment and/or prevention of diseases caused by ALK and ROS1 abnormal expression, and application of the compound in preparation of drugs for prevention of diseases caused by ALK and ROS1 abnormal expression. Use in particular in the preparation of a medicament for treatment and/or for preventing cancer

Dual potent ALK and ROS1 inhibitors combating drug-resistant mutants: Synthesis and biological evaluation of aminopyridine-containing diarylaminopyrimidine derivatives

To identify ALK and ROS1 dual inhibitors conferring resistance to ALK secondary mutations, especially ‘gatekeeper’ L1196 M and the most predominant ceritinib-resistant G1202R mutations, a series of novel 2,4-diarylaminopyrimidine analogues were designed and synthesized by incorporating 2-alkoxy-6-alicyclic aminopyridinyl motifs. The biological evaluations on cellular and enzymatic assays led to identification of compound F-1, which turned out to be effective against ALKWT, ROS1WT, ALKL1196M and ALKG1202R kinases with IC50 of 2.1 nM, 2.3 nM, 1.3 nM and 3.9 nM, respectively, superior to crizotinib and ceritinib. Moreover, F-1 exhibited significant cytotoxicity on ALK-addicted Karpas299, H2228, and Ba/F3 cell expressing G1202R mutant, as well as ROS1-positive HCC78 cell with IC50 values ranging from 10 nM to 43 nM. Notably, F-1 was capable of suppressing phospho-ALK and its relative downstream signaling pathways, and eventually, inducing cell apoptosis in a dose-dependent manner in Karpas-299 cell. Together, F-1 is validated as a promising ALK/ROS1 dual inhibitor great potential for G1202R ALK mutation cancers.

FLUORO SUBSTITUTED PYRIMIDINE COMPOUNDS AS JAK3 INHIBITORS

The invention relates to compounds of formula (I) wherein AA, R2 to R7 and X1 to X3 have the meaning as cited in the description and the claims. Said compounds are useful as selective inhibitors of JAK3 over JAK

ORTHO SUBSTITUTED PYRIMIDINE COMPOUNDS AS JAK INHIBITORS

The invention relates to compounds of formula (I) wherein X1 to X3, R, R2 to R7 and AA have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the treatment o

ORTHO SUBSTITUTED PYRIMIDINE COMPOUNDS AS JAK INHIBITORS

The present invention relates to compounds of formula (I), wherein X1 to X3, R, R2 to R7 and AA have the meaning as cited in the description and the claims. Said compounds are useful as JAK inhibitors for the tr

SULFONAMIDES AS ZAP-70 INHIBITORS

The invention relates to compounds of formula (I), wherein R1 to R9 and R4a have the meaning as cited in the description and the claims. Said compounds are useful as inhibitors of ZAP-70 for the treatment or prophylaxis of