Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy

Journal of Medicinal Chemistry

Volumn 58, Issue 17, 2015, Pages 6875-6898

  Papeo, Gianluca ^a   Posteri, Helena ^a   Borghi, Daniela ^a   Busel, Alina A ^b   Caprera, Francesco ^a   Casale, Elena ^a   Ciomei, Marina ^a   Cirla, Alessandra ^a   Corti, Emiliana ^a   D'Anello, Matteo ^a   Fasolini, Marina ^a   Forte, Barbara ^a,d   Galvani, Arturo ^a   Isacchi, Antonella ^a   Khvat, Alexander ^b   Krasavin, Mikhail Y ^b,e   Lupi, Rosita ^a   Orsini, Paolo ^a   Perego, Rita ^a   Pesenti, Enrico ^a   Pezzetta, Daniele ^c   Rainoldi, Sonia ^a   Riccardi Sirtori, Federico ^a   Scolaro, Alessandra ^a   Sola, Francesco ^a   Zuccotto, Fabio ^a   Felder, Eduard R ^a   Donati, Daniele ^a   Montagnoli, Alessia ^a   more..

^a NERVIANO MEDICAL SCIENCES   (Italy)

^b Chemical Diversity Research Institute   (Russian Federation)

^c Accelera   (Italy)

^d UNIVERSITY OF DUNDEE   (United Kingdom)

^e ST PETERSBURG STATE UNIVERSITY   (Russian Federation)

Author keywords

[No Author keywords available]

Indexed keywords

1 BENZYL N (FURAN 2 YLMETHYL)PIPERIDIN 4 AMINE; 2 (1 BENZYLPIPERIDIN 4 YL) 1 OXO 1,2,3,6,7,7A HEXAHYDRO 3A,6 EPOXYISOINDOLE 7 CARBOXYLIC ACID; 2 (1 BENZYLPIPERIDIN 4 YL) 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 (1 BENZYLPIPERIDIN 4 YL) 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXYLIC ACID; 2 (2 HYDROXYETHYL) 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 (2 METHOXYETHYL) 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 (3 METHOXYPROPYL) 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 BENZYL 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 [1 (4,4 DIFLUOROCYCLOHEXYL)PIPERIDIN 4 YL] 6 FLUORO 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 [2 (3,4 DIHYDROISOQUINOLIN 2(1H) YL)ETHYL] 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 [2 (3,4 DIHYDROQUINOLIN 1(2H) YL)ETHYL] 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 [2 (MORPHOLIN 4 YL)ETHYL] 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 [3 (1,4' BIPIPERIDIN 1' YL)PROPYL] 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE DIHYDROCHLORIDE; 2 [3 (2,6 DIMETHYLPIPERIDIN 1 YL)PROPYL] 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 [3 (4 BENZYLPIPERIDIN 1 YL)PROPYL] 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 [3 (MORPHOLIN 4 YL)PROPYL] 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 [[1 (3 METHYLBENZYL)PIPERIDIN 4 YL]METHYL] 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 2 [[1 (4 METHYLBENZYL)PIPERIDIN 4 YL]METHYL] 3 OXO 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 3 OXO 2 (2 PHENYLETHYL) 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 3 OXO 2 (3 PHENYLPROPYL) 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 3 OXO 2 (TETRAHYDROFURAN 2 YLMETHYL) 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 3 OXO 2 PROPYL 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 3 OXO 2 [2 (PYRIDIN 2 YL)ETHYL] 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; 3 OXO 2 [3 (PIPERIDIN 1 YL)PROPYL] 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE HYDROCHLORIDE; 3 OXO 2[2 (PIPERIDIN 1 YL)ETHYL] 2,3 DIHYDRO 1H ISOINDOLE 4 CARBOXAMIDE; ANTINEOPLASTIC AGENT; ISOINDOLE DERIVATIVE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; TEMOZOLOMIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG; DACARBAZINE; NMS-P118; PIPERIDINE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CONTROLLED STUDY; DEBENZYLATION; DIELS ALDER REACTION; DNA DAMAGE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; ENZYME ACTIVE SITE; FEMALE; HELA CELL LINE; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; HYDROGEN BOND; HYDROPHILIC INTERACTION CHROMATOGRAPHY; IC50; INTRINSIC CLEARANCE; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PLASMA PROTEIN BINDING; PROTON NUCLEAR MAGNETIC RESONANCE; TUMOR XENOGRAFT; ANALOGS AND DERIVATIVES; ANIMAL; BAGG ALBINO MOUSE; BIOAVAILABILITY; CANCER TRANSPLANTATION; CELL PROLIFERATION; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; DRUG SCREENING; LIVER MICROSOME; METABOLISM; NUDE MOUSE; ORAL DRUG ADMINISTRATION; PANCREATIC NEOPLASMS; PATHOLOGY; SPRAGUE DAWLEY RAT; STRUCTURE ACTIVITY RELATION; TRIPLE NEGATIVE BREAST CANCER; XENOGRAFT;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BIOLOGICAL AVAILABILITY; CELL PROLIFERATION; DACARBAZINE; DRUG SCREENING ASSAYS, ANTITUMOR; FEMALE; HETEROGRAFTS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; ISOINDOLES; MICE, INBRED BALB C; MICE, NUDE; MICROSOMES, LIVER; MODELS, MOLECULAR; NEOPLASM TRANSPLANTATION; PANCREATIC NEOPLASMS; PIPERIDINES; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; RATS, SPRAGUE-DAWLEY; STRUCTURE-ACTIVITY RELATIONSHIP; TRIPLE NEGATIVE BREAST NEOPLASMS;

EID: 84941551184     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b00680     Document Type: Article

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