1346447-79-7

Upstream product

• 1493-27-2 ortho-nitrofluorobenzene 
• 761440-16-8 2-chloro-N-(2-(isopropylsulfonyl)phenyl)-5-methyl-pyrimidin-4-amine 
• 99-09-2 3-nitro-aniline 
• 70415-85-9 2-(isopropyl sulfanyl)nitrobenzene 
• 76697-50-2 1-amino-2-(isopropylsulphonyl)benzene 
• 70415-86-0 1-(isopropylsulfonyl)-2-nitrobenzene 
• 1632485-14-3 2,5-dichloro-N-[2-(propan-2-ylsulfanyl)phenyl]pyrimidin-4-amine 
• 6397-33-7 2-aminophenyl isopropyl sulphide 

Downstream Products

• 1346447-80-0 5-chloro-4-N-(2-isopropylsulfonylbenzene)-2-N-(3-aminophenyl)pyrimidine-2,4-diamine 
• 1346447-81-1 N-(3-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)phenyl)acrylamide 

Relevant academic research and scientific papers

Discovery of novel 2,4-diarylaminopyrimidine analogues (DAAPalogues) showing potent inhibitory activities against both wild-type and mutant ALK kinases

We have developed a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) bearing a flexible amino acid side chain, different from the majority of the literature reported ALK inhibitors that often possess a structurally constrained arylpiperazine fragment or its equivalents in the solvent-interaction region. Extensive structural elaboration led to compound 15 possessing IC50 values of 2.7 and 15.3 nM, respectively, in the ALK wild-type and gate-keeper mutant L1196M enzymatic assays. This compound not only showed high proliferative inhibition against ALK-addicted cells across different oncogenic forms but also effectively suppressed several ALK secondary mutant cells, including the gate-keeper L1196M and F1174L. Significant antitumor efficacy was achieved in the ALK-driven SUP-M2 xenograft model.

XHL11, a novel selective EGFR inhibitor, overcomes EGFRT790M-mediated resistance in non-small cell lung cancer

The first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib significantly improved the therapeutic effect in non–small cell lung cancer (NSCLC) patients with EGFR mutation. However, the EGFRT790M mutation occurs and results in acquired resistance. Consequently, mutant selective third-generation EGFR TKIs represented by AZD9291 (Osimertinib) have been developed to offer more effective therapeutic treatment, but the clinical application is limited by the acquired resistance and the high costs. A series of 5-chloropyrimidine-2,4-diamine derivatives were synthesized and screened for in vitro antitumor activity on H1975 and A431 cells. XHL11 showed the strongest antineoplastic activity. Compared to AZD9291, XHL11 suppressed cellular proliferation and colony formation and induced apoptosis in H1975 cells with EGFRL858R/T790M mutation. In addition, XHL11 caused expression changes in EGFR and apoptosis-related pathways. Moreover, oral administration of XHL11 suppressed tumor progression in vivo in a H1975 subcutaneous xenograft model. These data demonstrated that XHL11 might be developed as a promising EGFR TKI for the therapeutic use of NSCLC patients.

2, 4, 5-substituted pyrimidine compound and preparation method and application thereof

The invention relates to a preparation method of 2, 4-substituted pyrimidine compound and a preparation method and application thereof. The compound has a molecular structure shown as a formula I or pharmaceutically acceptable salt, solvate, stereoisomer or prodrug molecule thereof. The 2, 4, 5-substituted pyrimidine compound is low in cytotoxicity and has high selective inhibition on EGFR; the compound can inhibit the proliferation of EGFR drug-resistant mutant enzymes (such as T790M/L858R/C797S mutant enzymes) and cell strains thereof at a low concentration (such as nanomole concentration),so that the compound can be used for treating diseases caused by EGFR mutation, and is expected to be developed into a new generation of EGFR inhibitors.

The novel anti-tumor medicine synthetic method and a pharmaceutically acceptable salt thereof and solid preparation (by machine translation)

The invention discloses a method for synthesis of antineoplastic agent, the chemical name is 5 - chloro - N2 - (3 - amino-acetyl aminophenyl) - N4 - (2 - [...] phenyl) pyrimidine - 2, 4 - diamine. At the same time, its salt, crystalline form research, select and suitable for further development as a preparation of the maleate, tartrate and succinate and its corresponding crystalline form. The invention also provides a to the antineoplastic agent as the active ingredient of the solid preparation, wherein the supplemented with one or more solubilising. The invention solid preparation dissolution characteristic and excellent stability, with clinical application prospect. (by machine translation)

COMPOUNDS THAT MODULATE EGFR ACTIVITY AND METHODS FOR TREATING OR PREVENTING CONDITIONS THEREWITH

Provided are compounds and methods for treating or preventing kinase-mediated disorders therewith.