The chlorine group at the 6-position of the heterocyclic ring is more reactive than the chlorine at the 2-position, hence it can be selectively replaced by an amino group, which was then converted to an amide using nitrous acid. Finally, the remaining chlorine was replaced by the amino group of aciclovir using ammonia in methanol. This synthesis and other methods for preparing the compound have been reviewed. History
Aciclovir was seen as the start of a new era in antiviral therapy, as it is extremely selective and low in cytotoxicity. Since discovery in mid 1970s, it has been used as an effective drug for the treatment of infections caused by most known species of the herpesvirus family, including herpes simplex and varicella zoster viruses. Nucleosides isolated from a Caribbean sponge, Cryptotethya crypta, were the basis for the synthesis of aciclovir. It was codiscovered by Howard Schaeffer following his work with Robert Vince, S. Bittner and S. Gurwara on the adenosine analog acycloadenosine which showed promising antiviral activity. Later, Schaeffer joined Burroughs Wellcome and continued the development of aciclovir with pharmacologist Gertrude B. Elion. A U.S. patent on aciclovir listing Schaeffer as inventor was issued in 1979. Vince later invented abacavir, an nRTI drug for HIV patients. Elion was awarded the 1988 Nobel Prize in Medicine, partly for the development of aciclovir. A related prodrug form, valaciclovir came into medical use in 1995.
It is converted to aciclovir in the body after absorption.In 2009, acyclovir in combination with hydrocortisone cream, marketed as Xerese, was approved in the United States for the early treatment of recurrent herpes labialis (cold sores) to reduce the likelihood of ulcerative cold sores and to shorten the lesion healing time in adults and children (six years of age and older). Society and culture
Names
Aciclovir is the international nonproprietary name (INN) and British Approved Name (BAN) while acyclovir is the United States Adopted Name (USAN) and former British Approved Name.It was originally marketed as Zovirax; patents expired in the 1990s and since then it is generic and is marketed under many brand names worldwide. Notes
References
Further reading
Hazra, S; Konrad, M; Lavie, A (2010). "The sugar ring of the nucleoside is required for productive substrate positioning in the active site of human deoxycytidine kinase (dCK): Implications for the development of dCK-activated acyclic guanine analogues". Journal of Medicinal Chemistry. 53 (15): 5792–800. doi:10.1021/jm1005379. PMC 2936711. PMID 20684612. Harvey Stewart C. in Remingtons Pharmaceutical Sciences 18th edition: (ed. Gennard, Alfonso R.)  Mack Publishing Company, 1990. ISBN 0-912734-04-3. Huovinen P., Valtonen V. in Kliininen Farmakologia (ed. Neuvonen et al.). Kandidaattikustannus Oy, 1994. ISBN 951-8951-09-8. Périgaud C.; Gosselin G.; Imbach J.-L. (1992). "Nucleoside analogues as chemotherapeutic agents: a review". Nucleosides and Nucleotides. 11 (2–4): 903–945. doi:10.1080/07328319208021748. Rang H.P., Dale M.M., Ritter J.M. : Pharmacology, 3rd edition. Pearson Professional Ltd, 1995. 2003 (5th) edition ISBN 0-443-07145-4; 2001 (4th) edition ISBN 0-443-06574-8; 1990 edition ISBN 0-443-03407-9. External links
"Acyclovir". Drug Information Portal.