Yet another ten stories on antiviral drug discovery (part D): Paradigms, paradoxes, and paraductions

Abstract

This review article presents the fourth part (part D) in the series of stories on antiviral drug discovery. The stories told in part D focus on: (i) the cyclotriazadisulfonamide compounds; (ii) the {5-[(4-bromophenylmethyl]-2-phenyl-5H-imidazo[4,5-c]pyridine} compounds; (iii) (1H,3H-thiazolo[3,4-a]benzimidazole) derivatives; (iv) T-705 (6-fluoro-3-hydroxy-2-pyrazinecarboxamide) and (v) its structurally closely related analogue pyrazine 2-carboxamide (pyrazinamide); (vi) new strategies for the treatment of hemorrhagic fever virus infections, including, as the most imminent, (vii) dengue fever, (viii) the veterinary use of acyclic nucleoside phosphonates; (ix) the potential (off-label) use of cidofovir in the treatment of papillomatosis, particularly RRP (recurrent respiratory papillomatosis); and (x) finally, the prophylactic use of tenofovir to prevent HIV infections.

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

“…The incidence of CMV infections such as retinitis has recently dropped drastically thanks to the successful treatment of AIDS with the current anti-HIV drugs. Yet the broad anti-DNA virus activity of (S)-HPMPC, similar to that of (S)-HPMPA (71), makes the compound potentially useful for the treatment of various DNA virus infections, poxvirus infections (74), and papilloma and polyoma virus infections (75,76). (S)-HPMPC would be more effective than smallpox vaccination against a lethal monkeypox virus infection (77).…”

Mutations Conferring Resistance to Viral DNA Polymerase Inhibitors in Camelpox Virus Give Different Drug-Susceptibility Profiles in Vaccinia Virus

“…Pre-and posthydration, as well as probenecid, are required to manage its potential nephrotoxicity. (S)-HPMPC is also used off-label for the treatment of polyoma-, papilloma-, adeno-, herpes-, and poxvirus infections (20,22,23). The search for orally available ANPs led to the discovery of CMX001, a lipid conjugate of (S)-HPMPC.…”

Microwave-Assisted Synthesis of Bioactive Six-Membered Heterocycles and Their Fused Analogues

“…Pyrazine is a six membered hetero-aromatic ring usually found in the structure of numerous natural products and synthetic compounds, some of which are used in the food industry for their flavor properties [222][223][224]. Moreover, they are versatile synthetic intermediates [225], and many functionalized pyrazines possess pharmacological activities, such as antiviral [226,227] (242, 243), ATR kinase inhibitor [228] (244), antitumor [229], vascular endothelial growth factor inhibitory activity [230], or as epithelial sodium channel blockers [231] (Figure 15). Pyrazine is a six membered hetero-aromatic ring usually found in the structure of numerous natural products and synthetic compounds, some of which are used in the food industry for their flavor properties [222][223][224].…”

“…Moreover, they are versatile synthetic intermediates [225], and many functionalized pyrazines possess pharmacological activities, such as antiviral [226,227] (242, 243), ATR kinase inhibitor [228] (244), antitumor [229], vascular endothelial growth factor inhibitory activity [230], or as epithelial sodium channel blockers [231] (Figure 15). Original synthetic heterocycles, such as substituted dicyanopyrazines 247, 248, have been synthesized using a domestic MW oven [232].…”