Discovery of ITX 4520: a highly potent orally bioavailable hepatitis C virus entry inhibitor.
The manuscript reports an identification of a highly potent, orally bioavailable hepatitis C virus entry inhibitor through optimization of a previously reported class of molecules (1) that were not stable in the rat plasma. Compound 39 (ITX 4520) exhibited an excellent PK profile in both rats and dogs with good oral exposure, half-life and oral bioavailability. The compound is also well-tolerated in the preliminary in vivo toxicity studies and has been selected as a pre-clinical candidate for our HCV clinical pipeline.
iTherX Pharmaceuticals, Inc., San Diego, CA 92191-0530, USA.
Gopi Kumar
GK
Mittapalli
Fang
F
Zhao
Andrew
A
Jackson
Hongfeng
H
Gao
Haekyung
H
Lee
Stephine
S
Chow
Maninder Pal
MP
Kaur
Natalie
N
Nguyen
Robert
R
Zamboni
Jeffrey
J
McKelvy
Flossie
F
Wong-Staal
James E
JE
Macdonald
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006207:Half-Life; D016174:Hepacivirus / Q000378:metabolism*; D006801:Humans; D008861:Microsomes / Q000378:metabolism; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship; D053586:Virus Internalization / Q000187:drug effects*
D000998:Antiviral Agents; D002227:Carbazoles; C576462:ITX 4520; D010069:Oxadiazoles