The discovery of antiviral agents: ten different compounds, ten different stories.
This review article, while autobiographical to some extent, describes the discovery of ten (classes of) antiviral compounds that have made (or just did not make) it to the market for the therapy of viral infections, but each in its own way influenced the landscape of our dealing with virus infections: (i) valaciclovir, (ii) BVDU, (iii) DHPA, (iv) cidofovir, (v) adefovir, (vi) tenofovir, (vii) stavudine, (viii) HEPT, (ix) TIBO, and (x) AMD3100. Successful drug development, as is certainly true for antiviral drugs and exemplified for the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir, requires patience and perseverance, and a close continuous and dedicated interaction between Chemistry, Biology/Medicine and Industry.
De Clercq
Erik
E
Katholieke Universiteit Leuven, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
D000212:Acyclovir / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001569:Benzodiazepines / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001596:Benzylamines; D000077404:Cidofovir; D000080027:Cyclams; D003596:Cytosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D009705:Nucleosides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000068698:Tenofovir; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014777:Virus Diseases / Q000188:drug therapy*
C476867:4,5,6,7-tetrahydroimidazo-(4,5,1- jk)(1,4)benzodiazepin-2 (1 H)-one; D000998:Antiviral Agents; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D007093:Imidazoles; D009705:Nucleosides; D063065:Organophosphonates; D001569:Benzodiazepines; C016391:9-(2,3-dihydroxypropyl)adenine; C053001:adefovir; D003596:Cytosine; D000068698:Tenofovir; D014633:Valine; D000225:Adenine; D000077404:Cidofovir; D000077483:Valacyclovir; C088327:plerixafor; D000212:Acyclovir