Dihydropyridine Lactam Analogs Targeting BET Bromodomains was written by Jiang, Jiewei;Sigua, Logan H.;Chan, Alice;Kalra, Prakriti;Pomerantz, William C. K.;Schonbrunn, Ernst;Qi, Jun;Georg, Gunda I.. And the article was included in ChemMedChem in 2022.Computed Properties of C6H9ClO3 The following contents are mentioned in the article:
Inhibitors of Bromodomain and Extra Terminal (BET) proteins were investigated for various therapeutic indications, but selectivity for BRD2, BRD3, BRD4, BRDT and their resp. tandem bromodomains BD1 and BD2 remains suboptimal. Here, selectivity-focused structural modifications of previously reported dihydropyridine lactam to form 7-alkyl-1-ethyl-5-(p-tolyl)-5,7,8,9-tetrahydro-1H-pyrrolo[3′,4′:5,6]pyrido[2,3-d]pyrimidine-2,4,6(3H)-triones I [R = CH2Ph, CH2Bn, PhOCH2CH2, etc.] by changing linker length and linker type of the lactam side chain in efforts to engage the unique arginine 54 (R54) residue in BRDT-BD1 to achieve BRDT-selective affinity was reported. It was found that the analogs were highly selective for BET bromodomains and generally more selective for the first (BD1) and second (BD2) bromodomains of BRD4 rather than for those of BRDT. Based on AlphaScreen and BromoScan results and on crystallog. data for analog I [R = CH2CH(CH2CH2NCH2CH2)CH2(4-O2NC6H4)], we concluded that the lack of selectivity for BRDT is most likely due to the high flexibility of the protein and the unfavorable trajectory of the lactam side chain that do not allow interaction with R54. A 15-fold preference for BD2 over BD1 in BRDT was observed for analogs I [R = CH2CH(CH2CH2NCH2CH2)CH2C(O)Ph], I [R = CH2CH2(3-MeOC6H4)] which was supported by protein-based 19F NMR experiments with a BRDT tandem bromodomain protein construct. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Computed Properties of C6H9ClO3).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. Organic chlorides can be used in production of: PVC, pesticides, chloromethane, teflon, insulators. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Computed Properties of C6H9ClO3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics