Synthesis of substituted 1-norbornylamines with antiviral activity.
The reaction of (+/-)-camphor (7) with triflic anhydride (Tf2O) yields the bridgehead triflate 8. The Nametkin rearrangement of 8 to 3 was realized by treatment with triflic acid (TfOH). The solvolysis of the bridgehead triflates 3 and 8 in acetonitrile affords the N-acetyl-1-norbornylamines 4 and 9. The Pd(0)-catalyzed hydrogenation of 4 and 9 gives the amides 5 and 10. The corresponding 1-norbornylamines 2 and 13 and the N-ethyl derivatives 1, 6, 11, and 12 were obtained by basic hydrolysis or reduction with LiAlH4, respectively, of the amides 4, 5, 9, and 10. The antiviral activity of the hydrochlorides of some of the obtained 1-norbornylamines was evaluated against influenza A, herpes simplex 2, and African swine fever virus. Particularly noticeable is the activity of the hydrochlorides of 1 and 11 against influenza A virus (SI (selectivity index) = 1000).
D000358:African Swine Fever Virus / Q000187:drug effects; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002522:Chlorocebus aethiops; D009636:Norbornanes / Q000737:chemistry / Q000494:pharmacology*; D009975:Orthomyxoviridae / Q000187:drug effects; D018139:Simplexvirus / Q000187:drug effects; D014709:Vero Cells
D000998:Antiviral Agents; D009636:Norbornanes