Patent Watch

December 2, 2013

These cytomegalovirus inhibitors may overcome drug resistance. O. Lepage and co-inventors disclose 1,8-naphthyridin-2(1H)-one analogues represented by formula 1. These compounds inhibit human cytomegalovirus (HCMV) DNA polymerase and may be used for treating and preventing CMV infection or disease.

HCMV, also known as CMV or human herpes virus 5 (HHV-5), is a widespread β-herpes virus that infects people worldwide of either sex, any age group, or any ethnic background. HCMV infection is often unnoticed in healthy people, but it can be life-threatening for adults or children with immunocompromised systems. 

The approved drugs for treating HCMV include valganciclovir, ganciclovir, cidofovir, and foscarnet. Each of these therapies inhibits CMV DNA polymerase pUL54, an enzyme essential for virus replication. However, HCMV strains that are resistant to all of these drugs have emerged.

The compounds reported in this patent application have similar activities and may provide alternative treatments for HCMV infections. The inventors report structures and synthesis procedures for 231 analogues of formula 1. The three shown in the figure are representative examples.

The inventors evaluated the compounds with the HCMV polymerase scintillation proximity assay and the HCMV polymerase LANCE TR-FRET assay. In the LANCE TR-FRET assay, IC50 values in the range of 40 μM were reported for about 40 compounds. Examples 24 have some of the lower IC50 values (see table).

Example LANCE TR-FRET assay,
IC50 (nM)
2 50
3 30
4 22

(Boehringer Ingelheim International GMBH [Ingelheim am Rhein, Germany]. WIPO Publication 2013152063, Oct 10, 2013; Ahmed F. Abdel-Magid)

This patent was originally reviewed in ACS Medicinal Chemistry Letters.

View patent information from CAplus(SM) database.

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General formula and representative examples of HCMV inhibitors