RASS-Enabled S/P−C and S−N Bond Formation for DEL Synthesis

DNA encoded libraries (DEL) have shown promise as a valuable technology for democratizing the hit discovery process. Although DEL provides relatively inexpensive access to libraries of unprecedented size, their production has been hampered by the idiosyncratic needs of the encoding DNA tag relegating DEL compatible chemistry to dilute aqueous environments. Recently reversible adsorption to solid support (RASS) has been demonstrated as a promising method to expand DEL reactivity using standard organic synthesis protocols. Here we demonstrate a suite of on-DNA chemistries to incorporate medicinally relevant and C−S, C−P and N−S linkages into DELs, which are underrepresented in the canonical methods.     

Preparation of Substituted Quinolinyl and Isoquinolinyl Sulfonyl Chlorides for the Synthesis of Novel Sulfonamides

Abstract

Novel sulfonyl chlorides of quinolines and isoquinolines have successfully been prepared. This enabled the preparation of the corresponding sulfonamides via reaction with an amine using the “resin-capture and release” methodology.     

Synthesis,antimicrobial activity and docking study of some novel 4-(4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino derivatives carrying biologically active sulfonamide moiety

A new series of 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(substituted)benzenesulfonamide 3–17, monosubstituted 2-((4-((4-aminophenyl)sulfonyl)phenyl)amino)methylene 18, and its disubstituted derivative 19 were synthesized from the starting material 2-((dimethylamino)methylene)-5,5-dimethylcyclohexane-1,3-dione 2. The crystal structures of compounds 2, 7 and 13 were reported by us through X-ray crystallography. All the prepared compounds were evaluated for their antibacterial activity against Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, Clostridium sporogenes), Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli), and antifungal activity against Aspergillus fumigatus, Penicillium chrysogenum, Fusarium oxysporum, Candida albicans. The synthesized compounds displayed interesting antimicrobial activity. Compounds 4 and 12 were the most potent in this study and displayed higher activity compared to the reference drugs, with MIC value of 3.9–31.3 μg/mL against a panel of Gram-positive, Gram-negative bacteria and fungi. Molecular modeling was performed inside the active site of dihydropteroate synthase. The synthesized compounds showed similar orientation and binding interactions to that of the co-crystallized ligand inside the binding pocket.     

Synthesis, anticancer, and anti-inflammatory activity evaluation of methanesulfonamide and amidine derivatives of 3,4-diaryl-2-imino-4-thiazolines

Condensation of 3,4-diaryl-2-imino-4-thiazoli-nes 1a–j with methanesulfonyl chloride gave methanesulfonamide derivatives 2a–j. Condensation of 2-cyanopyrazine, 4-cyanopyridine, and 2-cyanopyridine with 3,4-diaryl-2- imino-4-thiazolines 1h–m in the presence of sodium methoxide afforded amidine derivatives 3a–j. Compounds 2a–j and 3a–j were screened against various human cancer cell lines (COLO-205, HEP-2, A-549, IMR-32) and their percentage growth inhibition profile determined at 1 × 10⁻⁵M. The anti-inflammatory activity of these compounds was assessed using the carrageenan-induced paw edema model. Compound 2i exhibited 34.7% anti-inflammatory activity at 50 mg/kg p.o., which is comparable to standard care drug phenyl butazone (37% activity at 50 mg/kg p.o.)     

嘌呤磺胺衍生物的合成及抗肿瘤活性

合成了一系列结构全新的嘌呤磺胺类衍生物, 并应用溴化噻唑蓝四氮唑(MTT)法进行了初步体外抗肿瘤细胞增殖活性研究. 结果表明, 嘌呤环C2位、 N6位和N9位的取代对活性均有较大影响, C2位引入苯磺酰基哌嗪片段后有利于提高抗肿瘤活性. 化合物17d对3株肿瘤细胞PC-3, HCT116和K562 的增殖均有明显抑制作用, 且强度与阳性对照药Roscovitine相近.