Dihydropyrancarboxamides Related to Zanamivir:  A New Series of Inhibitors of Influenza Virus Sialidases. 1. Discovery, Synthesis, Biological Activity, and Structure−Activity Relationships of 4-Guanidino- and 4-Amino-4H-pyran-6-carboxamides

Abstract

4-Amino- and 4-guanidino-4H-pyran-6-carboxamides 4 and 5 related to zanamivir (GG167) are a new class of inhibitors of influenza virus sialidases. Structure--activity studies reveal that, in general, secondary amides are weak inhibitors of both influenza A and B viral sialidases. However, tertiary amides, which contain one or more small alkyl groups, show much greater inhibitory activity, particularly against the influenza A virus enzyme. The sialidase inhibitory activities of these compounds correlate well with their in vitro antiviral efficacy, and several of the most potent analogues displayed useful antiviral activity in vivo when evaluated in a mouse model of influenza A virus infection. Carboxamides which were highly active sialidase inhibitors in vitro also showed good antiviral activity in the mouse efficacy model of influenza A infection when administered intranasally but displayed modest activity when delivered by the intraperitoneal route.

Potent and Long-Acting Dimeric Inhibitors of Influenza Virus Neuraminidase Are Effective at a Once-Weekly Dosing Regimen

“…2, and the other dimers were prepared in an analogous manner (6,14). Thus, intermediate 3 (27) was converted into compound 9 in a four-step sequence: (i) carbonyl diimidazole in acetonitrile (CH 3 CN) (86% yield); (ii) 1,14-diisocyanatotetradecane, 4-dimethylaminopyridine, 4-Å sieves in dichloromethane (50% yield); (iii) CF 3 CO 2 H (82% yield); and (iv) triethyl in dichloromethane methanol, and H 2 O (40% yield). Compounds 4 to 12 were all purified by preparative high-pressure liquid chromatography and showed 1 H nuclear magnetic resonance and liquid chromatography (LC)-mass spectrometry (MS) parameters which were consistent with the expected structures.…”

An efficient approach to the synthesis of some novel heterocycles related to indoline moiety using [BMIm]Cl catalysis

“…In particular, they are used as antibacterial, antifungal, antiviral, antiphrastic and insecticidal agents [17][18][19][20][21][22][23]. Upon these salient aspects, incorporation of the two pharmacophoric, pyrazole and oxindole, motiffing into a single molecule via efficient and environmentally benign synthetic methods would be beneficial [24].…”

Microwave-assisted multicomponent reaction for the synthesis of 2-amino-4H-chromene derivatives using ilmenite (FeTiO3) as a magnetic catalyst under solvent-free conditions

“…2-Amino-4H-chromene derivatives are important class of heterocyclic compounds with an array of biological and pharmacological properties such as antimicrobial [12], antiviral [13,14], mutagenicity [15], antiproliferative [16], sex hormone [17], antitumour [18], cancer therapy [19,20], and central nervous system activities [20]. 2-Aminochromenes were also used as biodegradable agrochemicals and components of many natural products [21].…”