65141-04-0

Upstream product

• 1885-14-9 phenyl chloroformate 
• 371-40-4 4-fluoroaniline 
• 1195-45-5 para-fluorophenyl isocyanate 
• 108-95-2 phenol 
• 84882-85-9 N-(4-fluorophenyl)-1H-imidazole-1-carboxamide 

Downstream Products

• 153885-60-0 N-(4-fluorophenyl)hydrazinecarboxamide 
• 279241-45-1 [3-(acridin-9-yl)amino-5-amino]benzyl N-(4-fluorophenyl) carbamate 
• 1170321-68-2 N-(4-fluorophenyl)-3-endo-(phenylsulfonyl)-8-azabicyclo[3.2.1]octane-8-carboxamide 
• 1309469-91-7 4-[(10S)-dihydroartemisinin-10-oxycarbonyl]benzaldehyde N₄-(4-fluorophenyl)semicarbazone 
• 1350899-04-5 (E)-1-(4-hydroxy-3-methoxybenzylidene)-4-(4-fluorophenyl)semicarbazone 
• 1198565-08-0 N-(4-fluorophenyl)-1H-indole-1-carboxamide 
• 1596368-63-6 (E)-1-{[(7-dimethylamino)-2-oxo-2H-chromen-3-yl]methylidene}-4-(4-fluorophenyl)semicarbazone 

Relevant academic research and scientific papers

Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects

Inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapeutic approach in the treatment of inflammation. Driven by the in-house database product lead 1, a hybridization strategy was utilized for the design of a series of novel benzo [d]thiazol derivatives. To our delight, D016, a byproduct of compound 9, was obtained with an extraordinarily low IC50 value of 0.1 nM but poor physical and chemical properties. After removal of a non-essential urea moiety or replacement of the urea group by an amide group, compounds 15a, 17p, and 18d were identified as promising sEH inhibitors, and their molecular binding modes to sEH were constructed. Furthermore, compounds 15a and 18d exhibited more effective in vivo anti-inflammatory effect than t-AUCB in carrageenan-induced mouse paw edema. Compound 15a also showed moderate metabolic stability with a half-time of 34.7 min. Although 18d was unstable in rat liver microsomes, it might be a “prodrug”. In conclusion, this study could provide valuable insights into discovery of new sEH inhibitors, and compounds 15a and 18d were worthy of further development as potential drug candidates to treat inflammation.

Design, synthesis, and biological evaluation of sorafenib derivatives containing indole (ketone) semicarbazide analogs as antitumor agents

A series of new sorafenib derivatives was designed and synthesized. The antiproliferative activity of the synthesized compounds against human lung cancer cell (A549), human pancreatic cancer cell (PC-3), human leukemia cell (K562), and human hepatoma cell (SMMC-7721) was evaluated by MTT assay. The results revealed that several compounds displayed more significant antitumor activities than commercial anticancer agent sorafenib against SMMC-7721. In addition, compounds 7a, 7g, 7l, 7m, and 7p represented obvious growth inhibition with IC50 values of 1-9 μM against four cancer cell lines, demonstrating more predominant activities against cancer cells as compared to sorafenib. Furthermore, some structure-activity relationships have also been established. Compounds containing indole and benzene ring substituted by halogen showed better activity than sorafenib. Wound healing assay suggested that cells would be targeted on their migratory capacity by 7g, potentially affecting the migration activity of these tumors. The effects of A549 and PC-3 cell apoptosis induced by compound 7g were significantly increased compared with sorafenib. Importantly, the result of western blot assay showed that 7g inhibited cell growth by suppressing the activity of EGFR, especially the expression of p-EGFR (Tyr1068).

Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3

Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives. All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the “A” phenyl ring and “B” phenyl ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G1/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor.

Tyrosine kinase inhibitor and application thereof

The invention discloses a tyrosine kinase inhibitor. A chemical name of the tyrosine kinase inhibitor is 1-(2-chloro-4-((6,7-dimethoxyquinoline-4-yl)oxy)phenyl)-3-(4-fluorophenyl)carbamide and a structure is shown as a formula (I). Meanwhile, the inventio

Tyrosine kinase inhibitor and application thereof

The invention discloses a tyrosine kinase inhibitor. A chemical name of the tyrosine kinase inhibitor is 1-(2-chloro-4-((6,7-dimethoxyquinoline-4-yl)oxy)phenyl)-3-(4-fluorophenyl)carbamide and a structure is shown as a formula (I). Meanwhile, the inventio

Arylureas derived from colchicine: Enhancement of colchicine oncogene downregulation activity

Our efforts to get therapeutically useful colchicine derivatives for the treatment of cancer have led us to synthetize and biologically evaluate twenty-seven N,N′-disubstituted ureas containing a colchicine moiety and an aryl fragment. The cytotoxicity of

Highly Regioselective Carbamoylation of Electron-Deficient Nitrogen Heteroarenes with Hydrazinecarboxamides

The use of hydrazinecarboxamides as a new class of carbamoylating agents has been established through the dehydrazinative Minisci reaction of electron-deficient nitrogen heteroarenes. A wide range of electron-deficient nitrogen heteroarenes, including isoquinoline, quinoline, pyridine, phenanthridine, quinoxaline, and phthalazine, underwent copper/acid-catalyzed oxidative carbamoylation with hydrazinecarboxamide hydrochlorides to afford structurally diverse nitrogen-heteroaryl carboxamides as single regioisomers in moderate to excellent yields. The functional group tolerance was substantially demonstrated in the direct carbamoylation of quinine obviating multistep sequences involving protecting groups and prefunctionalization of the heterocycle.

Synthesis of N-aryl and N-arylcarbamoylamino derivatives of 1,3-diazinane-5-carboxamide and their activity against glioblastoma LN-229 cell line

Six structural motifs based on the initial (lead) structure of merbarone were designed, prepared, and tested against the glioblastoma LN-229 cell line. Three different structural moieties were modified in the search for optimal glioblastoma activity: the 1,3-diazinane moiety, the aryl moiety, and the heteroatom linker. Calculated molecular descriptors such as lipophilicity (C log P), acidic strength (calculated pKa), and polar surface area (PSA) were used to design a diverse structural library of these compounds. From six different structural motifs and 136 compounds, a handful of examples with moderate (100 μg/ml), good (10 μg/ml) and excellent (1 μg/ml) glioblastoma activity were elucidated.

TRPV1 modulators: Synthesis and in vitro evaluation of 1-heteroaryl piperidinecarboxamide and piperazinylurea derivatives

Abstract A series of new 1-heteroaryl piperidinecarboxamide and piperazinylurea derivatives was synthesized and evaluated as TRPV1 modulators in a Ca2+ channel assay in HEK-293 cells overexpressing the human recombinant TRPV1 channel. Structura

CARBAMATE COMPOUNDS AND METHODS OF USE IN DISEASES OF THE NERVOUS SYSTEM

In general, among other things, compounds of Formula I are provided: or a pharmaceutically acceptable salt thereof, in which R1-7 9-10 are each independently selected from the group consisting of hydrogen, hydroxy, alkoxy, and alkyl; and R8 is selected from the group consisting of fluoro, iodo, and tributyltin. Other compounds are also provided. Methods of treatment and diagnosis are also provided.