Synthetic methods for the preparation of novel ARQ501 human metabolites

MEDI 320

Rui-Yang Yang, Darin Kizer, dkizer@arqule.com, Hui Wu, Erika Volckova, Xiusheng Miao, Khanh Nguyen, Syed Ali, Manish Tandon, Ron Savage, and Mark A. Ashwell. ArQule, Inc, 19 Presidential way, Woburn, MA 01801
The synthesis and characterization of novel metabolites of ARQ 501 (3,4-dihydro-2,2-dimethyl-2H-naptho[1,2-b]pyran-5,6-dione, beta-lapachone) are described.

ARQ 501 is an anti-cancer drug candidate currently in Phase 2 clinical trials. ARQ 501 elevates E2F-1 levels leading to the activation of the cell cycle checkpoint which results in the selective apoptotic cell death of cancer cells.

In this poster, we describe ARQ501 metabolites found in human blood. Structures of several major human blood metabolites were postulated based on high-resolution HPLC/MS/MS with 14C labeled and non-labeled ARQ501; postulated structures were synthesized and compared with metabolites through high resolution HPLC/ MS/MS. The structure of several metabolites, including novel ring contracted and ring opened structures, were confirmed.

 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007