83300-83-8

Upstream product

• 123-11-5 4-methoxy-benzaldehyde 
• 104-94-9 4-methoxy-aniline 
• 623-47-2 propynoic acid ethyl ester 

Downstream Products

• 83300-89-4 1,4-Bis-(4-methoxy-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid monoethyl ester 
• 83300-95-2 MC₂₇₃₇ 
• 83300-84-9 dimethyl 1,4-diphenyl-1,4-dihydropyridine-3,5-dicarboxylate 

Relevant academic research and scientific papers

Dually acting nonclassical 1,4-dihydropyridines promote the anti-tuberculosis (Tb) activities of clofazimine

The number of effective antituberculotic drugs is strongly limited to four first-line drugs in standard therapy. In case of resistances second-line antibiotics are used with a poor efficacy and tolerability. Therefore, novel antituberculotic drugs are urgently needed. We synthesized novel nonclassical 1,4-dihydropyridines and evaluated their antituberculotic properties depending on substituent effects. Preferred substituents could be identified. As related classical 1,4-dihydropyridines are known as inhibitors of the transmembrane efflux pump ABCB1 in cancer cells, we wondered whether a use of our compounds may be of favour to enhance the antituberculotic drug efficacy of the second-line antituberculotic drug clofazimine, which is a known substrate of ABCB1 by a suggested inhibition of a corresponding efflux pump in Mycobacterium tuberculosis (Mtb). For this, we determined the ABCB1 inhibiting properties of our compounds in a mouse T-lymphoma cell line model and then evaluated the drug-enhancing properties of selected compounds in a co-application with clofazimine in our Mtb strain. We identified novel enhancers of clofazimine toxicity which could prevent clofazimine resistance development mediated by an efflux pump activity.

Discovery of novel N-phenyl 1,4-dihydropyridines with a dual mode of antimycobacterial activity

There is an urgent need for novel drugs for the treatment of tuberculosis (TB) due to the increasing prevalence of antibiotic resistance among Mycobacterium tuberculosis (Mtb) strains against first-line and second-line therapeutics. We developed novel N-phenyl 1,4-dihydropyridines as potential antituberculotic agents. The observed activity depends on the substitution patterns of the aromatic residues. N-unsubstituted 1,4-dihydropyridines are known inhibitors of the cancer-relevant transmembrane efflux pump ABCB1. Based on the similarity of ABCB1 amino acids sequences relevant to 1,4-dihydropyridine binding and the MTb efflux pump Rv0194, we determined ABCB1-inhibitory properties of our compounds in a cell line model. We identified one compound, which substantially increased the activity of two antituberculotic drugs which are substrates of ABCB1. The data indicate that our N-phenyl 1,4-dihydropyridines represent a novel compound class which improves the efficacy of anti-TB drugs by interfering with transmembrane efflux pumps in Mtb.

EFFECT OF SUBSTITUENTS IN THE DIHYDROPYRIDINE RING ON THE REACTIVITY OF THE ESTER GROUP OF 3,5-DIALKOXYCARBONYL-1,4-DIHYDROPYRIDINES

The reactivity of the ester group of 3,5-dialkoxycarbonyl-1,4-dihydropyridines upon reaction with nucleophilic reagents increases when substituents are absent in the ortho positions relative to the ester group and also in the case of steric disruption of the coplanarity of the β-aminovinylcarbonyl system when substituents are introduced at the nitrogen atom in 2,6-dimethyl derivatives.Mono- and dicarboxylic acids were obtained by hydrolysis of such esters.Thus use of esters of propiolic acid esters and arylamines in the Hantzsch synthesis made it possible to obtain 1-aryl-2,6-unsubstituted derivatives of 1,4-dihydropyridine.