S(+)-4-(1-Phenylethylamino)quinazolines as Inhibitors of Human Immunoglobulin E Synthesis: Potency Is Dictated by Stereochemistry and Atomic Point Charges at N-1 was written by Berger, Michael;Albrecht, Bettina;Berces, Attila;Ettmayer, Peter;Neruda, Wolfgang;Woisetschlaeger, Maximilian. And the article was included in Journal of Medicinal Chemistry in 2001.HPLC of Formula: 175137-21-0 This article mentions the following:
The pathogenesis of allergic diseases is associated with elevated levels of IgE (IgE), a high throughput reporter gene assay in a human B-cell line to screen for low mol. weight IgE inhibitory compds was developed. Monitoring the IL-4 driven IgE-germline promoter activity (IgE-GLP), 4-(1-phenylethylamino)quinazolines was discovered as potent inhibitors of IgE-germline gene expression. Testing of the individual enantiomers revealed that only the S(+) enantiomer (I) was active. A cell viability assay done in the same cell line in parallel discriminated the dose-dependent inhibition from a general antiproliferative effect. The observed correlation of the inhibitory potencies found in the reporter gene assay with those measured by IgE-ELISA in primary human splenocytes provided evidence that the blockade of IgE synthesis is the direct consequence of IgE-germline gene inhibition, thereby validating the reporter gene assay. Parallel synthesis in solution rapidly provided a series of analogs of compound I with modifications in the phenethylamine side chain and the quinazoline core for SAR studies. Increasing the lipophilicity of the arylalkylamine moiety yielded S(+)-4-(1-(2-naphthyl)ethylamino)quinazoline (II) as the most potent inhibitor (IC50 of 14 nM) while the R(-) enantiomer was again found to be inactive. Within the set of S enantiomers, quantum mech. calculations revealed that the IgE inhibitory activity can be quant. described by the charge at N-1 of the heterocyclic core and to a lesser extent by the molar refractivity. These results demonstrate the importance of electron-deficient fused 4-aminopyrimidines and lipophilic side chains for biol. activity. The strong preference for the S configuration of the phenethylamine side chain is remarkable insofar as biol. activity for fused 4-(1-phenylethylamino)pyrimidines has been published for the R enantiomers only (EGFR tyrosine kinase inhibition). In the experiment, the researchers used many compounds, for example, 4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0HPLC of Formula: 175137-21-0).
4-Chloro-7-methylthieno[3,2-d]pyrimidine (cas: 175137-21-0) belongs to pyrimidine derivatives. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives. Pyrimidine derivatives have been used in a wide variety of pharmaceuticals including general anesthetics, anti-epilepsy medication, anti-malaria medication, drugs for treating high blood pressure, and HIV medication.HPLC of Formula: 175137-21-0
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia