425638-73-9

Usage

Chemical class

Quinazoline derivatives

Mechanism of action

Potent and selective inhibitor of cyclin-dependent kinases (CDKs) involved in cell cycle regulation

Potential use

Cancer therapy

Effects on cancer cells

Induces cell cycle arrest and apoptosis

Potential benefits

Overcoming drug resistance in cancer treatment

Upstream product

• 109-01-3 1-methyl-piperazine 
• 425638-74-0 2-(2-chloroquinazolin-4-yl)acetamide 
• 607-68-1 2,4-dichloroquinazoline 
• 86-96-4 1,2,3,4-tetrahydro-quinazoline-2,4-dione 

Downstream Products

• 425637-18-9 sotrastaurin 
• 908351-31-5 3-(1H-indol-3-yl)-4-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-1H-pyrrole-2,5-dione acetate 

Relevant academic research and scientific papers

INDOLYLMALEIMIDES AS SOFT PAN-PKC INHIBITORS

The present invention relates to new kinase inhibitors, more specifically soft PKC inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In particular, the present invention relates to new soft PKC inhibitors compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease. In addition, the invention relates to methods of treatment and use of said compounds in the manufacture of a medicament for the application to a number of therapeutic indications including autoimmune and inflammatory diseases.

NOVEL THIENOPYRROLE COMPOUNDS

The invention provides a compound of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treati

Structure-activity relationship and pharmacokinetic studies of sotrastaurin (aeb071), a promising novel medicine for prevention of graft rejection and treatment of psoriasis

Protein kinase C (PKC) isotypes have emerged as key targets for the blockade of early T-cell activation. Herein, we report on the structure-activity relationship and the detailed physicochemical and in vivo pharmacokinetic properties of sotrastaurin (AEB071, 1), a novel maleimide-based PKC inhibitor currently in phase II clinical trials. Most notably, the preferred uptake of sotrastaurin into lymphoid tissues is an important feature, which is likely to contribute to its in vivo efficacy.

Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4- yl]-pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes

A series of novel maleimide-based inhibitors of protein kinase C(PKC) were designed, synthesized, and evaluated. AEB071 (1) was found to be a potent, selective inhibitor of classical and novel PKC isotypes. 1 is a highly efficient immunomodulator, acting via inhibition of early T cell activation. The binding mode of maleimides to PKCs, proposed by molecular modeling, was confirmed by X-ray analysis of 1 bound in the active site of PKCα. 2009 American Chemical Society.

Indolylmaleimide derivatives

Indolylmaleimide derivatives comprising either a substituted phenyl, naphthyl, tetrahydronaphthyl, quinazolinyl, quinolyl, isoquinolyl or pyrimidinyl residue have interesting pharmaceutical properties, e.g. in the treatment and/or prevention of T-cell mediated acute or chronic inflammatory diseases or disorders, autoimmune diseases, graft rejection or cancer.