757251-59-5

Upstream product

• 123-30-8 4-amino-phenol 
• 220000-87-3 4-chloro-N-methylpicolinamide 
• 284462-37-9 4-(4-aminophenoxy)-N-methylpyridine-2-carboxamide 
• 24484-93-3 4-Chloro-pyridine-2-carboxylic acid methyl ester 
• 67-56-1 methanol 
• 1012058-77-3 4‐(4‐aminophenoxy)‐2‐pyridine carboxylic acid 

Downstream Products

• 573673-43-5 methyl 4‐(4‐(3‐(4‐chloro‐3‐(trifluoromethyl)phenyl)ureido)phenoxy)picolinate 
• 1610930-09-0 1-(4-(2-(2-(4-trifluoromethylphenylacetyl)hydrazinocarbonyl)pyridine-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-10-3 1-(4-(2-(2-(3-fluorophenylacetyl)hydrazinocarbonyl)pyridin-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-11-4 1-(4-(2-(2-(4-fluorophenylacetyl)hydrazinocarbonyl)pyridine-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-12-5 C₂₈H₁₉ClF₅N₅O₄ 
• 1610930-13-6 1-(4-(2-(2-(3-fluoro-4-bromophenylacetyl)hydrazinylcarbonyl)pyridinyl-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-14-7 1-(4-(2-(2-(2,3-difluorophenylacetyl)hydrazinocarbonyl)pyridine-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-15-8 1-(4-(2-(2-(3-chloro-4-hydroxyphenylacetyl)hydrazinocarbonyl)pyridine-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-16-9 1-(4-(2-(2-(2-methoxyphenylacetyl)hydrazinocarbonyl)pyridine-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-17-0 1-(4-(2-(2-(3,4-dimethoxyphenylacetyl)hydrazinocarbonyl)pyridine-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-18-1 1-(4-(2-(2-(4-ethoxyphenylacetyl)hydrazinocarbonyl)pyridine-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-19-2 1-(4-(2-(2-(naphthalen-2-ylacetyl)hydrazinocarbonyl)pyridin-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-20-5 1-(4-(2-(2-(4-phenylphenylacetyl)hydrazinocarbonyl)pyridine-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 
• 1610930-21-6 1-(4-(2-(2-(4-methylphenylacetyl)hydrazinocarbonyl)pyridine-4-yloxy)phenyl)-3-(4-chloro-3-trifluoromethylphenyl)urea 

Relevant academic research and scientific papers

Introduction of mercaptoethyl at sorafenib pyridine‐2‐amide motif as a potentially effective chain to further get sorafenib‐PEg‐DGL

The crystal structure of the sorafenib and B‐RAF complex indicates that the binding cavity occupied by the pyridine‐2‐carboxamide in sorafenib has a large variable space, making it a reasonable modification site. In order to identify novel compounds with anti‐cancer activity, better safety and polar groups for further application, five sorafenib analogs with new pyridine‐2‐amide side chains were designed and synthesized. Preliminary pharmacologic studies showed that these compounds displayed much lower toxicities than that of sorafenib. Among them, compound 10b bearing mercaptoethyl group kept relevant antiproliferation potency compared to sorafenib in Huh7 and Hela cell lines with values of IC50 58.79 and 63.67 μM, respectively. As a small molecule inhibitor targeting protein tyrosine kinases, thiol in compound 10b would be an active group to react with maleimide in a mild condition for forming nanoparticles Sorafenib‐PEG‐DGL, which could be developed as a delivery vehicle to improve the concentration of anti‐tumor therapeutic agents in the target cancer tissue and reduce side effects in the next study.

N' - aryl acetyl O-pyridine hydrazide derivative and its preparation and pharmaceutical composition and use thereof

The invention discloses N'-aryl acetyl o-pyridine hydrazide derivatives represented by the formula I and pharmaceutically acceptable salts and preparation methods thereof, a composition containing one or more of the compounds, and an application of the compounds in treatment of protein kinase related diseases, such as immune disorder and tumor disease.

Synthesis and anti-proliferative activity evaluation of sorafenib derivatives with a 3-arylacryloyl hydrazide unit

A series of sorafenib derivatives with a 3-arylacryloyl hydrazide unit were designed and synthesized, and their anti-proliferative activity against human cancer cell lines (ACHN, HCT116, MDA-MB-231) were evaluated by MTT assay. Most of the synthesized compounds showed superior or similar cytotoxicity against the selected cell lines to the control sorafenib. Among these derivatives, compounds 8a, 8h, 8l, 8m, 11a and 11b showed potent anti-proliferative activity. Compounds 8h and 8m were selected for further evaluation of biological activity against more cancer cell lines. And oral administration of sorafenib analogue 8h at the same dose of sorafenib (30 mg/kg) in the pancreatic cancer Capan2 and Mia-PaCa2 xenograft models in nude mice showed tumour growth inhibition of 60.98 and 54.59 %, respectively, which is similar to the positive control sorafenib.

Synthesis and in vitro cytotoxic activities of sorafenib derivatives

A series of novel sorafenib derivatives have been designed and synthesized. The cytotoxic activities of these compounds were tested in three tumor cell lines. Most of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 0-20 μmol/L. Some compounds demonstrated competitive antiproliferative activities to sorafenib against all three cancer cell lines. Among them, compound 5g demonstrated significant inhibitory activity against A549, ACHN and MDA-MB-231 cell lines with IC 50 values of 1.29, 1.99, 3.11 μmol/L, respectively.

RAF KINASE INHIBITORS CONTAINING A ZINC BINDING MOIETY

The present invention relates to Raf kinase inhibitors containing zinc-binding and their use in the treatment of Raf related diseases and disorders such as cancer. The said derivatives may further act as HDAC inhibitors.

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 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.