93256-31-6

Upstream product

• 99-61-6 3-nitro-benzaldehyde 
• 28144-70-9 anthranilic acid amide 
• 121-90-4 m-nitrobenzoic acid chloride 
• 118-92-3 anthranilic acid 
• 16063-03-9 2-(3-nitrophenyl)-4H-3,1-benzoxazin-4-one 
• 34637-85-9 2-(3-nitrophenyl)-(3H)-4-quinazolinone 

Downstream Products

• 911417-27-1 tert-butyl 5-(2-(3-nitrophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911417-38-4 (2R)-N-(3-(4-(1H-indazol-5-ylamino)quinazolin-2-yl)-phenyl)pyrrolidine-2-carboxamide 
• 911417-28-2 tert-butyl 5-(2-(3-aminophenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911417-56-6 tert-butyl 5-(2-(3-(3,3-dimethylureido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911417-34-0 tert-butyl 5-(2-(3-(2-methoxyacetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911417-47-5 tert-butyl 5-(2-(3-(2-chloroacetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911417-39-5 tert-butyl 5-(2-(3-(2-methoxy-2-oxoacetarnido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate 
• 911417-32-8 tert-butyl 5-(2-(3-(2-(dimethylamino)acetamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate 

Relevant academic research and scientific papers

Synthesis and biological investigation of 2,4-substituted quinazolines as highly potent inhibitors of breast cancer resistance protein (ABCG2)

Expression of ABCG2, a member of the ABC transporter superfamily, has been correlated to the clinical outcome of multiple cancers and is often associated with the occurrence of multidrug resistance (MDR) in chemotherapy. Inhibition of the transport protein by potent and selective inhibitors might be a way to treat cancer more efficiently and improve the therapy of cancer patients. Recently we reported the synthesis of new inhibitors based on a quinazoline scaffold. In the present study more structural variations were explored. Compounds with 3,4-dimethoxy groups and meta or para nitro substituents were found to be highly potent inhibitors of ABCG2. The most potent compound was more than five-fold more potent than Ko143, one of the best inhibitors of ABCG2. To determine the new compounds selectivity toward ABCG2 their inhibitory effects on ABCB1 and ABCC1 were also investigated identifying selective as well as broadspectrum inhibitors. Furthermore, intrinsic cytotoxicity and efficacy regarding the reversal of multidrug resistance toward SN-38 and mitoxantrone were explored. The most potent compounds were able to reverse the resistance toward the cytostatic agents with EC50 values below 20 nM. Additionally, the type of interaction between inhibitors and the ABCG2 substrate Hoechst 33342 was investigated yielding competitive and non-competitive interactions suggesting different modes of binding. Finally the effect of the derivatives on vanadate-sensitive ATPase activity of ABCG2 was determined. According to the different effects on ATPase activity we conclude the existence of different binding sites. This study provides the structural requirements for high potency inhibition and elucidates the interaction with ABCG2 setting the basis for further studies.

Design, Synthesis, and Pharmacological Characterization of N-(4-(2 (6,7-Dimethoxy-3,4-dihydroisoquinolin-2(1H)yl)ethyl)phenyl)quinazolin-4-amine Derivatives: Novel Inhibitors Reversing P-Glycoprotein-Mediated Multidrug Resistance

P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a principal obstacle for successful cancer chemotherapy. A novel P-gp inhibitor with a quinazoline scaffold, 12k, was considered to be the most promising for in-depth study. 12k possessed high potency (EC50 = 57.9 ± 3.5 nM), low cytotoxicity, and long duration of activity in reversing doxorubicin (DOX) resistance in K562/A02 cells. 12k also boosted the potency of other MDR-related cytotoxic agents with different structures, increased accumulation of DOX, blocked P-gp-mediated Rh123 efflux, and suppressed P-gp ATPase activity in K562/A02 MDR cells. However, 12k did not have any effects on CYP3A4 activity or P-gp expression. In particular, 12k had a good half-life and oral bioavailability and displayed no influence on DOX metabolism to obviate the side effects closely related to increased plasma concentrations of cytotoxic agents in vivo.

RHO KINASE INHIBITORS

The present invention relates to inhibitors of ROCK1 and ROCK2, which may be selective for ROCK2, and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCK1 and/or ROCK2. Also provided are treatments combining inhibitors of ROCK1 and/or ROCK2 with statins.

RHO KINASE INHIBITORS

The present invention relates to inhibitors of ROCKl and R0CK2, which may be selective for R0CK2, and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCKl and/or R0CK2. Also provided are treatments combining inhibitors of ROCKl and/or R0CK2 with statins.

PHARMACOKINETICALLY IMPROVED COMPOUNDS

The present invention relates to inhibitors of ROCKl and R0CK2 and methods of modulating the pharmacokinetic and/or pharmacodynamic properties of such compounds. Also provided are methods of inhibiting ROCKl and or R0CK2 that are useful for the treatment of disease.