630125-69-8

Upstream product

• 1124-33-0 4-nitraminopyridine N-oxide 
• 7677-24-9 trimethylsilyl cyanide 
• 123-30-8 4-amino-phenol 
• 19235-89-3 4-chloro-pyridine-2-carbonitrile 

Downstream Products

• 912471-76-2 4-{4-[(2-amino-6-chloropyrimidin-4-yl)amino]phenoxy}pyridine-2-carbonitrile 
• 940012-13-5 1-[5-tert-butyl-2-(3,5-difluoro-phenyl)-2H-pyrazol-3-yl]-3-[4-(2-cyano-pyridin-4-yloxy)-phenyl]-urea 

Relevant academic research and scientific papers

LEADOPT: An automatic tool for structure-based lead optimization, and its application in structural optimizations of VEGFR2 and SYK inhibitors

Lead optimization is one of the key steps in drug discovery, and currently it is carried out mostly based on experiences of medicinal chemists, which often suffers from low efficiency. In silico methods are thought to be useful in improving the efficiency of lead optimization. Here we describe a new in silico automatic tool for structure-based lead optimization, termed LEADOPT. The structural modifications in LEADOPT mainly include two operations: fragment growing and fragment replacing, which are restricted to carry out in the active pocket of target protein with the core scaffold structure of ligand kept unchanged. The bioactivity of the newly generated molecules is estimated by ligand efficiency rather than a commonly used scoring function. Twelve important pharmacokinetic and toxic properties are evaluated using SCADMET, a program for the prediction of pharmacokinetic and toxic properties. LEADOPT was first evaluated using two retrospective cases, in which it showed a very good performance. LEADOPT was then applied to the structural optimizations of the VEGFR2 inhibitor, sorafenib, and the SYK inhibitor, R406. Though just several compounds were synthesized, we have obtained some compounds that are more potent than sorafenib and R406 in enzymatic and functional assays. All of these have validated, at least to some extent, the effectiveness of LEADOPT.

Pyrimidine Derivatives

This invention relates to novel compounds (I) and processes for their preparation, methods of treating diseases, particularly cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly cancer.

PYRIMIDINE DERIVATIVES FOR TREATMENT OF HYPERPROLIFERATIVE DISORDERS

Pyrimidine derivatives of formula (I), pharmaceutical compositions containing these compounds, and methods of using these compounds in treatment of hyperproliferative diseases such as cancer are disclosed and claimed.

PYRIMIDINE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF CANCER

This invention relates to novel compounds (I) and processes for their preparation, methods of treating diseases, particularly cancer, comprising administering said compounds, and methods of making pharmaceutical compositions for the treatment or prevention of disorders, particularly cancer.

PYRIMIDINE DERIVATIVES FOR TREATMENT OF HYPERPROLIFERATIVE DISORDERS

Pyrimidine derivatives of formula (I) in which J and Y represent aromatic or heteroaromatic rings; R2, G, G', and G" represent substituent groups and R2a represents H or halogen; L represents a linking group; and M represents CH or N. Pharmaceutical compositions containing these compounds, and methods of using these compounds in treatment of hyperproliferative diseases such as cancer are also disclosed and claimed.

DIARYL UREA DERIVATIVES USEFUL FOR THE TREATMENT OF PROTEIN KINASE DEPENDENT DISEASES

The invention relates to the use of diaryl urea derivatives in the treatment of protein kinase dependent diseases or for the manufacture of pharmaceutical compositions for use in the treatment of said diseases, methods of use of diaryl urea derivatives in the treatment of said diseases, pharmaceutical preparations comprising diaryl urea derivatives for the treatment of said diseases, diaryl urea derivatives for use in the treatment of said diseases, novel diaryl urea derivatives, pharmaceutical preparations comprising these novel diaryl urea derivatives, processes for the manufacture of the novel diaryl urea derivatives, the use or methods of use of the novel diaryl urea derivatives as mentioned above, and/or these novel diaryl urea derivatives for use in the treatment of the animal or human body.