Bristol-myers Squibb Compnay

Christopher W Cianci

Nicholas A Meanwell

David R Langley

Annapurna Pendri

Yi Zhang

Samuel Gerritz

Bradley C Pearce

Kuo-Long Yu

Rita Civiello

Xiangdong Alan Wang

Guo Li

Shirong Zhu

Mark R Krystal

Weixu Zhai

Shuhao Shi

Keith D Combrink

Jan Willem Thuring

Richard J Colonno

Yaxiong Sun

Moira Hagen

Thomas D Chung

Sean Kim

A compound of Formula I is set forth, including pharmaceutically acceptable salts thereof: wherein Het is a 5 or 6-membered heterocycle with &#x2014;N, &#x2014;O, or &#x2014;S adjacent to the &#x2014;Ar substituent or adjacent to the point of attachment for the &#x2014;Ar substituent;Ar is aryl or heteroaryl;R is &#x2014;CH, &#x2014;CHF, or &#x2014;CH&#x2550;CH;W is &#x2014;NO, &#x2014;Cl, &#x2014;Br, &#x2014;CHO, &#x2014;CH&#x2550;CH, or &#x2014;CN;X is &#x2014;Cl, &#x2014;CH, or &#x2014;CN;Y is &#x2014;CH or &#x2014;N; andZ is C-Calkyl, C-Ccycloalkyl, substituted aryl, substituted heteroaryl, OR, or NHR, wherein Ris selected from the group of H, aryl, heteroaryl, C-Calkyl and C-Ccycloalkyl. This compound is useful in compositions for the prevention and treatment of influenza virus.

Piperazine analogs as broad-spectrum influenza antivirals

The present invention concerns antiviral compounds, their methods of preparation and their compositions, and use in the treatment of viral infections. More particularly, the invention provides heterocyclic substituted 2-methylbenzimidazole derivatives for the treatment of respiratory syncytial virus infection.

Substituted 2-methyl-benzimidazole respiratory syncytial virus antiviral agents

Novel capped oligonucleotides useful in treatment of influenza infection. A synthetically derived 67-nucleotide RNA substrate, containing a �.sup.32 P! labeled cap-1 structure was used to analyze parameters of influenza virus endonuclease activity. This substrate was specifically cleaved by the influenza virus polymerase to yield a single capped 11-nucleotide fragment capable of directly priming transcription. An analysis of systematic truncations of this RNA substrate in cleavage, elongation, and binding reactions demonstrated that the minimum chain length required for cleavage was one nucleotide past the cleavage site. In contrast, the minimum chain length required for priming activity was found to be 9 nucleotides, while a chain length of at least 4 nucleotides was required for efficient binding. Based on these chain length requirements, the present inventors show that a pool of capped oligonucleotides--too short to prime transcription but long enough to bind with high affinity to the viral polymerase--are potent inhibitors of cap-dependent in vitro transcription.

Capped nucleic acid oligomers that inhibit cap-dependent transcription

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Madison, CT, United States of America

Christopher W Cianci