tetano
Editor, Senior Moderator
Antivir Chem Chemother. 2012 Dec 7. doi: 10.3851/IMP2485. [Epub ahead of print]
Antiviral agents derived from novel 1-adamantyl singlet nitrenes.
[No authors listed]
Abstract
BACKGROUND:
Amantadine constitutes an interesting, diamond crystal lattice-shaped, antivirally active amine with inhibitory effect on influenza A viruses causing common "flu" in humans. Unfortunately, amantadine forfeited most of its therapeutic potential due to resistance development in recent influenza A virus isolates. The antiviral efficacy of amantadine congeners can be chemically modified, resulting in re-constitution, improvement and/or extension of antiviral activities mediated by amino-adamantyls.
METHODS:
Newly synthesized compounds were evaluated towards human immunodeficiency virus type 1 (HIV-1) replication in primary human lymphocytes. One N-phenacyl amantadine derivative was investigated for inhibiting the in vitro replication of respiratory viruses (influenza A viruses, influenza B virus, human parainfluenza virus type 3, SARS coronavirus).
RESULTS:
Two ketone-stabilized 1-adamantyl singlet nitrenes were discovered serendipitously. To our best knowledge these are the first persistently stable nitrenes to be reported. Their structure was proved by determining the X-ray single crystal structure of one hydrolytic elaboration product. This salt adduct revealed an incommensurately modulated crystal structure which was solved by extensive computational refinement. We could show that ketone-stabilized 1-adamantyl singlet nitrenes are versatile synthons for the synthesis of antiviral drug candidates. An amantadine‒folate conjugate was inhibitory on HIV-1 replication in primary human lymphocytes, and one N-phenacyl amantadine derivative was inhibitory towards low pathogenic avian influenza A virus (H5N1) replication in vitro.
CONCLUSIONS:
These results indicate that the aromatic-aliphatic ketone-stabilized 1-adamantyl singlet nitrenes, beyond being of fundamental interest in organic chemistry, represent versatile synthons for the synthesis of new amantadine-related potentially antiviral drugs.
PMID:
23234699
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23234699
Antiviral agents derived from novel 1-adamantyl singlet nitrenes.
[No authors listed]
Abstract
BACKGROUND:
Amantadine constitutes an interesting, diamond crystal lattice-shaped, antivirally active amine with inhibitory effect on influenza A viruses causing common "flu" in humans. Unfortunately, amantadine forfeited most of its therapeutic potential due to resistance development in recent influenza A virus isolates. The antiviral efficacy of amantadine congeners can be chemically modified, resulting in re-constitution, improvement and/or extension of antiviral activities mediated by amino-adamantyls.
METHODS:
Newly synthesized compounds were evaluated towards human immunodeficiency virus type 1 (HIV-1) replication in primary human lymphocytes. One N-phenacyl amantadine derivative was investigated for inhibiting the in vitro replication of respiratory viruses (influenza A viruses, influenza B virus, human parainfluenza virus type 3, SARS coronavirus).
RESULTS:
Two ketone-stabilized 1-adamantyl singlet nitrenes were discovered serendipitously. To our best knowledge these are the first persistently stable nitrenes to be reported. Their structure was proved by determining the X-ray single crystal structure of one hydrolytic elaboration product. This salt adduct revealed an incommensurately modulated crystal structure which was solved by extensive computational refinement. We could show that ketone-stabilized 1-adamantyl singlet nitrenes are versatile synthons for the synthesis of antiviral drug candidates. An amantadine‒folate conjugate was inhibitory on HIV-1 replication in primary human lymphocytes, and one N-phenacyl amantadine derivative was inhibitory towards low pathogenic avian influenza A virus (H5N1) replication in vitro.
CONCLUSIONS:
These results indicate that the aromatic-aliphatic ketone-stabilized 1-adamantyl singlet nitrenes, beyond being of fundamental interest in organic chemistry, represent versatile synthons for the synthesis of new amantadine-related potentially antiviral drugs.
PMID:
23234699
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23234699