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Antimicrobial Agents and Chemotherapy, September 2002, p. 2872-2877, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.2872-2877.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Antiviral Activities of MCC-478, a Novel and Specific Inhibitor of Hepatitis B Virus

Naohiro Kamiya,1* Atsushi Kubota,1 Yumiko Iwase,2 Kouichi Sekiya,1 Masaru Ubasawa,1 and Satoshi Yuasa1

Research Laboratory IV, Mitsubishi Pharma Corporation, Yokohama,1 Toxicology Laboratory, Mitsubishi Pharma Corporation, Kisarazu, Japan2

Received 10 January 2002/ Returned for modification 28 February 2002/ Accepted 17 June 2002

MCC-478 is a newly synthesized 2-amino-6-arylthio-9-phosphonomethoxyethylpurine bis(2,2,2-trifluoroethyl) ester derivative. MCC-478 showed a substantially higher (ca. 80-fold) anti-hepatitis B virus (HBV) activity than that of lamivudine, despite no significant anti-human immunodeficiency virus activity. Since the bis(2,2,2-trifluoroethyl) ester group was used to improve the oral bioavailability of the phosphonomethoxyethylpurine derivatives, two monoester derivatives and one phosphonic acid derivative were also evaluated. It was suggested that these hydrolyzed derivatives, which appeared in animals given MCC-478, have enough anti-HBV activity to contribute to efficacy in vivo. Furthermore, no apparent cytotoxic effects or reductions of mitochondrial DNA content by MCC-478 and its derivatives were observed. These results indicated that MCC-478 may be a new promising anti-HBV agent.

* Corresponding author. Mailing address: Research Laboratory IV, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. Phone: 81-45-963-3401. Fax: 81-45-963-3890. E-mail: Kamiya.Naohiro{at}mh.m-pharma.co.jp.

Antimicrobial Agents and Chemotherapy, September 2002, p. 2872-2877, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.2872-2877.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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