2. Academic Validation
  3. Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: design, synthesis, and X-ray cocrystal structure

Novel tricyclic poly(ADP-ribose) polymerase-1 inhibitors with potent anticancer chemopotentiating activity: design, synthesis, and X-ray cocrystal structure

  • J Med Chem. 2002 Nov 7;45(23):4961-74. doi: 10.1021/jm020259n.
Stacie S Canan Koch 1,  Lars H Thoresen,  Jayashree G Tikhe,  Karen A Maegley,  Robert J Almassy,  Jianke Li,  Xiao-Hong Yu,  Scott E Zook,  Robert A Kumpf,  Cathy Zhang,  Theodore J Boritzki,  Rena N Mansour,  Kanyin E Zhang,  Anne Ekker,  Chris R Calabrese,  Nicola J Curtin,  Suzanne Kyle,  Huw D Thomas,  Lan-Zhen Wang,  A Hilary Calvert,  Bernard T Golding,  Roger J Griffin,  David R Newell,  Stephen E Webber,  Zdenek Hostomsky
Affiliations

Affiliation

  • 1 Pfizer Global Research and Development, La Jolla/Agouron Pharmaceuticals, Inc., 10770 Science Center Drive, San Diego, California 92121, USA. stacie.canan@pfizer.com
PMID: 12408707 DOI: 10.1021/jm020259n
Abstract

A series of novel compounds have been designed that are potent inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1), and the activity and physical properties have been characterized. The new structural classes, 3,4,5,6-tetrahydro-1H-azepino[5,4,3-cd]indol-6-ones and 3,4-dihydropyrrolo[4,3,2-de]isoquinolin-5-(1H)-ones, have conformationally locked benzamide cores that specifically interact with the PARP-1 protein. The compounds have been evaluated with in vitro cellular assays that measure the ability of the PARP-1 inhibitors to enhance the effect of cytotoxic agents against Cancer cell lines.

Figures