Synthesis and antiviral activity of monobactams inhibiting the human cytomegalovirus protease

2-Azetidinone – A new profile of various pharmacological activities

“…49). A series of monobactam inhibitors of HCMV (No) protease bearing a heterocycle linked by a methylene group at C-4 was described by Ogilvie et al [80]. Inhibitors containing a heterocycle such as a 2-furyl, 2-thiophenyl, 4-methyl-2-tetrazole and 2-benzothiazole at the C-4 position of the b-lactam were found to be active in a plaque reduction assay; all had potencies between 0.7 and 7.1 mM.…”

Synthesis of New Tetrazole Derivatives of α,α‐Trehalose

“…[1,2] The development of the chemistry of tetrazoles has been largely associated with the wide use of these compounds in medicinal chemistry and in various materials science applications, including specialty explosives. [1,3,4] Various publications describe tetrazoles as inhibitors of monoamine oxidase, [5] antiviral activity, [6] antibacterial activity, [7] and as antagonists of cerebellum-specific GABA A receptors [8] and angiotensin II. [9] Some tetrazole derivatives have been prepared from carbohydrates and used as glycosidase inhibitors.…”

Recent strategies in the development of new human cytomegalovirus inhibitors

“…106 Moreover, some of the compounds in a smaller series bearing an aromatic ring linked by a methlylene group at C-4 compounds 60, 61, exhibited activity in a viral replication assay which suggested that these compounds were cell penetrable and could potentially be useful antiviral agents. 107,108 Directed mechanism-based screening, targeted to compounds that could afford a stable acylenzyme adduct of the active site serine, identi®ed a novel class of serine protease inhibitors, the spirocyclopropyl oxazolones represented by 62±64 as submicromolar inhibitors of HCMV protease, 109 and the known serine protease inhibitor class of 2-substituted benzoxazinones. 110,111 A series of 6-substituted 2-aminobenzoxazinone analogs (65±67) has been prepared that show potent inhibitory activity toward the target enzyme (IC 50 0.46±4 mM) and demonstrate antiviral activity in cell culture (IC 50 23 mM).…”