The discovery of polo-like kinase 4 inhibitors: Design and optimization of spiro[cyclopropane-1,3′[3H]indol]-2′(1′H).ones as orally bioavailable antitumor agents

Journal of Medicinal Chemistry

Volumn 58, Issue 1, 2015, Pages 130-146

  Sampson, Peter B ^a   Liu, Yong ^a   Patel, Narendra Kumar ^a   Feher, Miklos ^a   Forrest, Bryan ^a   Li, Sze Wan ^a   Edwards, Louise ^a   Laufer, Radoslaw ^a   Lang, Yunhui ^a   Ban, Fuqiang ^a   Awrey, Donald E ^a   Mao, Guodong ^a   Plotnikova, Olga ^a   Leung, Genie ^a   Hodgson, Richard ^a   Mason, Jacqueline ^a   Wei, Xin ^a   Kiarash, Reza ^a   Green, Erin ^a   Qiu, Wei ^a   Chirgadze, Nickolay Y ^a,b   Mak, Tak W ^a   Pan, Guohua ^a   Pauls, Henry W ^a   more..

^a PRINCESS MARGARET HOSPITAL   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

2 (1 INDAZOL 6 YL)SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 (1H INDAZOL 6 YL)SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 (3 IODO 1H INDAZOL 6 YL) 5' METHOXYSPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 (3 IODO 1H INDAZOL 6 YL) 5' METHYLSPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 (3 IODO 1H INDAZOL 6 YL)SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 (3 VINYL 1H INDAZOL 6 YL)SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 [3 IODO 1 [[2 (TRIMETHYLSILYL)ETHOXY]METHYL 1H INDAZOL 6 YL]SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 [3 [2 (2,6 DIMETHYLPYRIDIN 3 YL)VINYL] 1H INDAZOL 6 YL]SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 [3 [2 (6 METHYLPYRIDIN 3 YL)VINYL] 1H INDAZOL 6 YL]SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 [3 [2 (PYRIDIN 3 YL)VINYL] 1H INDAZOL 6 YL] SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 [3 [2 (PYRIDIN 3 YL)VINYL] 1H INDAZOL 6 YL]SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 [3 [2 (PYRIDIN 4 YL)VINYL] 1H INDAZOL 6 YL]SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 [3 [2 [6 (PIPERIDIN 1 YLMETHYL)PYRIDIN 3 YL]VINYL] 1H INDAZOL 6 YL]SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 [3 [4 [(DIMETHYLAMINO)METHYL]STYRYL] 1H INDAZOL 6 YL] 5' METHOXYSPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 2 [3 [4 [(DIMETHYLAMINO)METHYL]STYRYL] 1H INDAZOL 6 YL]SPIROCYLOPROPANE 1,3' INDOLIN] 2' ONE; 4[2 [6 (2' OXOSPIRO[CYCLOPROPANE 1,3' INDOLINE] 2 YL) 1H INDAZOL 3 YL]VINYL]BENZALDEHYDE; 5 CHLORO 2 (3 IODO 1H INDAZOL 6 YL)SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 5' (DIFLUOROMETHOXY) 2 (3 IODO 1H INDAZOL 6 YL)SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 5' ETHYL 2 (3 IODO 1H INDAZOL 6 YL)SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 5' FLUORO 2 (3 IODO 1H INDAZOL 6 YL)SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 5' METHOXY 2 [3 [2 [6 (4 METHYLPIPERAZIN 1 YL)PYRIDIN 3 YL]VINYL] 1H INDAZOL 6 YL]SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; 5' METHOXY 2 [3 [2 [6 (PIPERIDIN 1 YLMETHYL)PYRIDIN 3 YL]VINYL] 1H INDAZOL 6 YL]SPIRO[CYCLOPROPANE 1,3' INDOLIN] 2' ONE; ANTINEOPLASTIC AGENT; CYCLOPROPANE DERIVATIVE; POLO LIKE KINASE 4; POLO LIKE KINASE 4 INHIBITOR; POLO LIKE KINASE INHIBITOR; SPIRO[CYCLOPROPANE 1,3'[3H]INDOL] 2'(1'H) ONE DERIVATIVE; TOZASERTIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; INDOLE DERIVATIVE; INDOLIN-2-ONE; PLK4 PROTEIN, HUMAN; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE; SPIRO COMPOUND;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; BINDING SITE; BREAST CANCER CELL LINE; CANCER INHIBITION; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG DESIGN; DRUG DISTRIBUTION; DRUG EFFECT; DRUG EFFICACY; DRUG EXCRETION; DRUG METABOLISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENANTIOMER; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; PLASMA PROTEIN BINDING; PROTEIN DOMAIN; RACEMIC MIXTURE; STRUCTURE ACTIVITY RELATION; TUMOR XENOGRAFT; X RAY CRYSTALLOGRAPHY; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOAVAILABILITY; CELL SURVIVAL; CHEMICAL MODEL; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG DEVELOPMENT; DRUG EFFECTS; DRUG SCREENING; HCT116 CELL LINE; MCF 7 CELL LINE; METABOLISM; NEOPLASMS; ORAL DRUG ADMINISTRATION; PATHOLOGY; RAT; TUMOR CELL LINE;

ADMINISTRATION, ORAL; ANIMALS; ANTINEOPLASTIC AGENTS; BIOLOGICAL AVAILABILITY; CELL LINE, TUMOR; CELL SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; DRUG DISCOVERY; DRUG SCREENING ASSAYS, ANTITUMOR; HCT116 CELLS; HUMANS; INDOLES; MCF-7 CELLS; MICE; MODELS, CHEMICAL; MOLECULAR STRUCTURE; NEOPLASMS; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; RATS; SPIRO COMPOUNDS; STRUCTURE-ACTIVITY RELATIONSHIP; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84984910848     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm500537u     Document Type: Article

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