Document Detail

Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Large with Potent Proapoptotic Cell-Based Activity.
MedLine Citation:
PMID:  21366295     Owner:  NLM     Status:  Publisher    
ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-x(L) and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-x(L) that contain a heterocyclic alternative to the acylsulfonamide. These compounds exhibit submicromolar, mechanism-based activity in human small-cell lung carcinoma cell lines in the presence of 10% human serum. This comprises the first successful demonstration of a quinazoline sulfonamide core serving as an effective benzoylsulfonamide bioisostere. Additionally, these novel quinazolines comprise only the second known class of Bcl-2 family protein inhibitors to induce mechanism-based cell death.
Brad E Sleebs; Peter E Czabotar; Wayne J Fairbrother; W Douglas Fairlie; John A Flygare; David C S Huang; Wilhelmus J A Kersten; Michael F T Koehler; Guillaume Lessene; Kym Lowes; John P Parisot; Brian J Smith; Morey L Smith; Andrew J Souers; Ian P Street; Hong Yang; Jonathan B Baell
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-2
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  -     ISSN:  1520-4804     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
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