Design and synthesis of pyrimidine-5-carbonitrile hybrids as COX-2 inhibitors: Anti-inflammatory activity, ulcerogenic liability, histopathological and docking studies was written by Alfayomy, Abdallah M.;Abdel-Aziz, Salah A.;Marzouk, Adel A.;Shaykoon, Montaser Sh. A.;Narumi, Atsushi;Konno, Hiroyuki;Abou-Seri, Sahar M.;Ragab, Fatma A. F.. And the article was included in Bioorganic Chemistry in 2021.Recommanded Product: 638-07-3 The following contents are mentioned in the article:
Two new series of 1,3,4-oxadiazole I [R = H, 4-F, 4-MeO, 4-Cl, 2,6-di-Cl; R1 = Me, MeO, Cl] and coumarin derivatives II [R2 = H, 4-F, 4-MeO, 4-Cl, 2,6-di-Cl; R3 = Me, MeO] and III [R4 = Cl, 4-methylpiperazin-1-yl] based on pyrimidine-5-carbonitrile scaffold were synthesized and evaluated for their COX-1/COX-2 inhibitory activity. Compounds I [R = 4-MeO, 2,6-di-Cl, R1 = Cl; R = 4-Cl, 4-MeO, 2,6-di-Cl, R1 = MeO], II [R2 = 2,6-di-Cl, R3 = Me; R2 = H, MeO, R3 = MeO] and III [R4 = 4-methylpiperazin-1-yl] were found to be the most potent and selective inhibitors of COX-2 (IC50 0.041-0.081μM, SI 139.74-321.95). Eight compounds were further investigated for their in-vivo anti-inflammatory activity. The most active derivatives I [R = 4-Cl, R1 = Cl; R = 2,6-di-Cl, R1 = MeO] and II [R2 = 2,6-di-Cl, R3 = Me] displayed superior in-vivo anti-inflammatory activity (% edema inhibition 39.3-48.3, 1 h; 58.4-60.5, 2 h; 70.8-83.2, 3 h; 78.9-89.5, 4 h) to the reference drug celecoxib (% edema inhibition 38.0, 1 h; 48.8, 2 h; 58.4, 3 h; 65.4, 4 h). These derivatives were also tested for their ulcerogenic liability, compound I [R = 2,6-di-Cl, R1 = MeO] showed better safety profile with reference to celecoxib while I [R = 4-Cl, R1 = Cl] and II [R2 = 2,6-di-Cl, R3 = Me] exhibited mild lesions. Mol. docking studies of I [R = 4-Cl, R1 = Cl; R = 2,6-di-Cl, R1 = MeO] and II [R2 = 2,6-di-Cl, R3 = Me] in the COX-2 active site revealed similar orientation and binding interactions as selective COX-2 inhibitors with a higher liability to access the selectivity side pocket. This study involved multiple reactions and reactants, such as Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3Recommanded Product: 638-07-3).
Ethyl 4-chloro-3-oxobutanoate (cas: 638-07-3) belongs to organic chlorides. An organic chloride is an organic compound containing at least one covalently bonded atom of chlorine. Their wide structural variety and divergent chemical properties lead to a broad range of names and applications. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Recommanded Product: 638-07-3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics