Development of novel benzimidazole riboside compounds for treatment of cytomegalovirus disease.
Benzimidazole ribosides are a new class of compounds with novel mechanisms of action against CMV. One compound in this series, BDCRB, inhibits CMV DNA processing by the UL89 gene product (putative terminase), but rapid metabolism to an inactive compound makes it unsuitable for development as a medicine. Another benzimidazole analogue, 1263W94, has many characteristics that make it an attractive candidate for development, including high potency in vitro, selectivity, good oral bioavailability, and lower toxicity than therapies currently available for treatment of CMV disease. Initial clinical trials have provided encouraging results, including good tolerability and linear pharmacokinetics over a wide dose range. Ongoing and planned clinical trials that will study the safety and tolerability of repeated dosing and evaluate the in vivo antiviral activity and ocular penetration of 1263W94, will help to determine the potential of this drug as an improved therapy for CMV disease.
Chulay
J
J
GlaxoWellcome Incorporated, Research Triangle Park, North Carolina 27709, USA.
Biron
K
K
Wang
L
L
Underwood
M
M
Chamberlain
S
S
Frick
L
L
Good
S
S
Davis
M
M
Harvey
R
R
Townsend
L
L
Drach
J
J
Koszalka
G
G
D000998:Antiviral Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D015195:Drug Design; D006801:Humans; D012263:Ribonucleosides / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
D000998:Antiviral Agents; D001562:Benzimidazoles; D012263:Ribonucleosides; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole