23861-85-0

Upstream product

• 16153-81-4 4-(4-Methyl-piperazino)-anilin 
• 463-71-8 thiophosgene 
• 350-46-9 4-Fluoronitrobenzene 
• 109-01-3 1-methyl-piperazine 
• 16155-03-6 1-methyl-4-(4-nitrophenyl)piperazine 
• 6160-65-2 1,1'-Thiocarbonyldiimidazole 

Downstream Products

• 36070-72-1 2-methyl-thiomorpholine-4-carbothioic acid 4-(4-methyl-piperazin-1-yl)-anilide 
• 223784-70-1 AG12275 
• 443798-70-7 1-(2,6-difluorobenzoyl)-N₃-[4-(4-methyl-1-piperazinyl)phenyl]-1H-1,2,4-triazole-3,5-diamine 
• 1357271-78-3 N-((1r,1r)-4-(5-tert-butyl-1,3,4-oxadiazol-2-yl)cyclohexyl)-2-(4-(4-methylpiperazin-1-yl)phenylamino)-1H-benzo[d]imidazole-5-sulfonamide 
• 1392151-76-6 1-(5-((3,5-difluorophenyl)thio)-1H-pyrazolo[3,4-b]pyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)phenyl)thiourea 
• 1392151-78-8 1-(1-tert-butyl-5-(3,5-difluorophenylthio)-1H-pyrazolo[3,4-b]pyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)phenyl)urea 
• 1392151-77-7 1-(5-((3,5-difluorophenyl)thio)-1H-pyrazolo[3,4-b]pyridin-3-yl)-3-(4-(4-methylpiperazin-1-yl)phenyl)urea 

Relevant academic research and scientific papers

Discovery of benzo[d]oxazole derivatives as the potent type-I FLT3-ITD inhibitors

Fms-like tyrosine kinase 3 (FLT3) has been considered as a potential drug target for the treatment of acute myeloid leukemia (AML), because of its high and aberrant expression in AML patients, especially the patients with FLT3-ITD mutation. Initiating from a hit compound (IC50: 500 nM against FLT3-ITD), a series of compounds were designed and synthesized based on benzo[d]oxazole-2-amine scaffold to discover new potent FLT3-ITD inhibitors. During the medicinal chemistry works, flexible molecular docking was used to provide design rationale and study the binding modes of the target compounds. Through the mixed SAR exploration based on the enzymatic and cellular activities, compound T24 was identified with potent FLT3-ITD inhibitory (IC50: 0.41 nM) and anti-proliferative (IC50: 0.037 μM against MV4-11 cells) activities. And the binding mode of T24 with “DFG-in” FLT3 was simulated by a 20-ns molecular dynamics run, providing some insights into further medicinal chemistry efforts toward novel FLT3 inhibitors in AML therapy.

Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model

FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV4-11 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML.

Compounds and use thereof in anti-AML drugs

The present invention relates to the field of medicinal chemistry, discloses compounds and use thereof in anti-AML drugs, and specifically relates to imidazole ring-substituted thiophenic compounds, preparation method thereof, pharmaceutical compositions containing the compounds, and medical use of the compounds, particularly use of the compounds as an ITD mutant selective inhibitor of FMS-like tyrosine kinase 3.

2-thiazole cyclic substituted thiophen class PLK1 inhibitor and its use and its use

The invention relates to the field of medicinal chemistry, and in particular relates to 2-imidazole ring-substituted thiophene PLK1 (Polo-like kinase 1) inhibitors, a preparation method for the inhibitors, a medicinal composition containing the compounds, and medical applications for the compounds, and in particular an application for the compounds as Polo-like kinase 1 (PLK1) inhibitors.

THIAZOLE AND PYRAZOLE DERIVATIVES AS FLT-3 KINASE INHIBITORS

The invention relates to thiazole and pyrazole derivatives of formula (I) wherein Q is S and X is C, or Q is CH and X is N; R1 is unsubtituted or substituted phenyl; and R2 is unsubstituted or substituted aryl or heteroaryl; oa a salt of the said compounds, and to processes for the preparation thereof, to pharmaceutical compositions comprising such derivatives and to the use of such derivatives for the preparation of pharmaceutical compositions for the treatment especially of a proliferative disease, such as a tumour disease, in particular such diseases which respond to an inhibition of the FIt-3 kinase.

4-Aminothiazole derivatives, their preparation and their use as inhibitors of cyclin-dependent kinases

This invention is directed to aminothiazole compounds of formula (I) wherein R1 is a substituted or unsubstituted group selected from : C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; C1-6-alkoxyl; C1-6-alcohol; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; carbonyl; ether; (C1-6-alkyl)-carbonyl; (C1-6-alkyl)-aryl; (C1-6-alkyl)-cycloalkyl; (C1-6-alkyl)-(C1-6-alkoxyl); aryl-(C1-6-alkoxyl); thioether; thiol; and sulfonyl; wherein when R1 is substituted, each substituent independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol, thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; and R2 is a carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, ring structure having a substituent at the position adjacent to the point of attachment, which ring structure is optionally further substituted, where each substituent of R2 independently is a halogen; haloalkyl; C1-6-alkyl; C1-6-alkenyl; C1-6-alkynyl; hydroxyl; C1-6-alkoxyl; amino; nitro; thiol; thioether; imine; cyano; amido; phosphonato; phosphine; carboxyl; thiocarbonyl; sulfonyl; sulfonamide; ketone; aldehyde; ester; oxygen; carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, cycloalkyl; or carbocyclic or heterocyclic, monocyclic or fused or non-fused polycyclic, aryl; or a pharmaceutically acceptable salt of a compound of formula (I), or a prodrug or pharmaceutically active metabolite of a compound of formula (I) or pharmaceutically acceptable salt thereof, for inhibiting cyclin-dependent kinases (CDKs), such as CDK1, CDK2, CDK4, and CDK6. The invention is also directed to the therapeutic or prophylactic use of pharmaceutical compositions containing such compounds and to methods of treating malignancies and other disorders by administering effective amounts of such compounds.

Diaminothiazoles having antiproliferative activity

Disclosed are novel diaminothiazoles that are selective inhibitors of Cdk4. These compounds and their pharmaceutically acceptable salts and esters are anti-proliferative agents useful in the treatment or control of solid tumors, in particular breast, colon, lung and prostate tumors. Also disclosed are pharmaceutical compositions containing these compounds as well as intermediates useful in the preparation of the compounds.