Synthesis and SAR of novel, potent and orally bioavailable benzimidazole inhibitors of poly(ADP-ribose) polymerase (PARP) with a quaternary methylene-amino substituent

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 14, 2008, Pages 3955-3958

  Zhu, Gui Dong ^a   Gandhi, Viraj B ^a   Gong, Jianchun ^a   Thomas, Sheela ^a   Luo, Yan ^a   Liu, Xuesong ^a   Shi, Yan ^a   Klinghofer, Vered ^a   Johnson, Eric F ^a   Frost, David ^a   Donawho, Cherrie ^a   Jarvis, Ken ^a   Bouska, Jennifer ^a   Marsh, Kennan C ^a   Rosenberg, Saul H ^a   Giranda, Vincent L ^a   Penning, Thomas D ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Anticancer; Benzimidazole; Inhibitor; PARP; Poly(ADP ribose) polymerase

Indexed keywords

AMIDE; AMINE; BENZIMIDAZOLE DERIVATIVE; CARBENE; CYCLOALKANE DERIVATIVE; CYCLOBUTANE DERIVATIVE; CYCLOPROPANE DERIVATIVE; CYTOTOXIC AGENT; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; TEMOZOLOMIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; AREA UNDER THE CURVE; ARTICLE; CELL FUNCTION; COMBINATION CHEMOTHERAPY; DISTRIBUTION VOLUME; DNA REPAIR; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG POTENTIATION; DRUG SYNTHESIS; DRUG TOLERABILITY; HYDROGEN BOND; IN VIVO STUDY; LOW DRUG DOSE; MELANOMA; MOLECULAR INTERACTION; MONOTHERAPY; MOUSE; NONHUMAN; RNA TRANSCRIPTION; STRUCTURE ACTIVITY RELATION; TUMOR MODEL;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZIMIDAZOLES; CELL LINE, TUMOR; CHEMISTRY, PHARMACEUTICAL; DNA; DNA REPAIR; DRUG DESIGN; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; KINETICS; MICE; NEOPLASM TRANSPLANTATION; POLY(ADP-RIBOSE) POLYMERASES; TRANSCRIPTION, GENETIC;

ANIMALIA; MURINAE;

EID: 47149087147     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.06.023     Document Type: Article

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20. 4 cells were mixed with 50% matrigel (BD Biosciences, Bedford, MA) and inoculated by sc injection into the flank of 6-8-week old female C57BL/6 mice, 20 g (Charles River Laboratories, Wilmington, MA), on day 1. Mice were injection-order allocated to treatment groups and PARP inhibitor therapy was initiated on days 6 (for 9b) and 5 (for 9k) following inoculation, with temozolomide treatment starting on days 6 and 5, respectively.