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Synfacts 2011(10): 1047-1047  
DOI: 10.1055/s-0030-1261042
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of a PARP Inhibitor

Contributor(s): Philip Kocienski
D. J. Wallace et al.*
Merck Sharp and Dohme Research Laboratories, Hoddesdon, UK; Merck Research Laboratories, Rahway, USA; WuXi APPTec (Shanghai) Pharmaceutical Co. Ltd., Shanghai, P. R. of China
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Publication History

Publication Date:
20 September 2011 (online)

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Significance

Poly(ADP-ribose)polymerase (PARP) is a nuclear DNA repair enzyme that may play a role in the survival and proliferation of cancer cells. The target molecule is an orally active PARP1 inhibitor. A significant challenge in the large-scale synthesis depicted is the construction of the 2H-indazole ring at elevated temperatures via azide intermediate I derived from an SNAr reaction of nitroarene G by sodium azide. Extensive safety evaluations of this potentially hazardous reaction are described.