Discovery of (R,E)-N-(7-chloro-1-(1-[4-(dimethylamino)but-2-enoyl]azepan-3-yl)-1H-benzo[d]imidazol-2-yl)-2-methylisonicotinamide (EGF816), a novel, potent, and WT sparing covalent inhibitor of oncogenic (L858R, ex19del) and resistant (T790M) EGFR mutants for the treatment of EGFR mutant non-small-cell lung cancers

Journal of Medicinal Chemistry

Volumn 59, Issue 14, 2016, Pages 6671-6689

  Lelais, Gérald ^a   Epple, Robert ^a   Marsilje, Thomas H ^a   Long, Yun O ^a   McNeill, Matthew ^a   Chen, Bei ^a   Lu, Wenshuo ^a   Anumolu, Jaganmohan ^b   Badiger, Sangamesh ^c   Bursulaya, Badry ^a   DiDonato, Michael ^a   Fong, Rina ^a,d   Juarez, Jose ^a   Li, Jie ^a   Manuia, Mari ^a   Mason, Daniel E ^a   Gordon, Perry ^a   Groessl, Todd ^a   Johnson, Kevin ^a   Jia, Yong ^a   Kasibhatla, Shailaja ^a   Li, Chun ^a   Isbell, John ^a   Spraggon, Glen ^a   Bender, Steven ^a   Michellys, Pierre Yves ^a   more..

^a GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

^b Pharmaceutical Development   (India)

^c Aurigene Discovery Technologies Limited   (India)

^d GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AFATINIB; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; NAZARTINIB; TERT BUTYL 3 [(2 CHLORO 6 NITROPHENYL)AMINO]AZEPANE 1 CARBOXYLATE; TERT BUTYL 3 [(2 METHYL 6 NITROPHENYL)AMINO]AZEPANE 1 CARBOXYLATE; TERT BUTYL 3 [(4 METHYL 2 NITROPHENYL)AMINO]AZEPANE 1 CARBOXYLATE; TERT BUTYL 3 [(4 METHYL 2 NITROPHENYL)AMINO]AZETIDINE 1 CARBOXYLATE; TERT BUTYL 3 [(4 METHYL 2 NITROPHENYL)AMINO]PIPERIDINE 1 CARBOXYLATE; TERT BUTYL 3 [(4 METHYL 2 NITROPHENYL)AMINO]PYRROLIDINE 1 CARBOXYLATE; TERT BUTYL 4 [(4 METHYL 2 NITROPHENYL)AMINO]AZEPANE 1 CARBOXYLATE; TERT BUTYL 4 [(4 METHYL 2 NITROPHENYL)AMINO]PIPERIDINE 1 CARBOXYLATE; TERT BUTYL CIS [2 [(4 METHYL 2 NITROPHENYL)AMINO]CYCLOHEXYL]CARBAMATE; TERT BUTYL CIS [3 [(4 METHYL 2 NITROPHENYL)AMINO]CYCLOHEXYL]CARBAMATE; TERT BUTYL CIS [4 [(4 METHYL 2 NITROPHENYL)AMINO]CYCLOHEXYL]CARBAMATE; TERT BUTYL METHYL[3 [(4 METHYL 2 NITROPHENYL)AMINO]PHENYL]CARBAMATE; TERT BUTYL TRANS [2 [(4 METHYL 2 NITROPHENYL)AMINO]CYCLOHEXYL]CARBAMATE; TERT BUTYL TRANS [3 [(4 METHYL 2 NITROPHENYL)AMINO]CYCLOHEXYL]CARBAMATE; TERT BUTYL TRANS [4 [(4 METHYL 2 NITROPHENYL)AMINO]CYCLOHEXYL]CARBAMATE; TERT BUTYL [2 [(4 METHYL 2 NITROPHENYL)AMINO]ETHYL]CARBAMATE; TERT BUTYL [2 [(4 METHYL 2 NITROPHENYL)AMINO]PHENYL]CARBAMATE; TERT BUTYL [3 [(4 METHYL 2 NITROPHENYL)AMINO]CYCLOPENTYL]CARBAMATE; TERT BUTYL [3 [(4 METHYL 2 NITROPHENYL)AMINO]PHENYL]CARBAMATE; TERT BUTYL [3 [(4 METHYL 2 NITROPHENYL)AMINO]PROPYL]CARBAMATE; TRANS 4 [(2 METHYL 2 NITROPHENYL)AMINO]CYCLOHEXAN 1 OL; TRANS 4 [(2 NITROPHENYL)AMINO]CYCLOHEXAN 1 OL; TRANS 4 [(3 METHYL 2 NITROPHENYL)AMINO]CYCLOHEXAN 1 OL; TRANS 4 [(4 METHYL 2 NITROPHENYL)AMINO]CYCLOHEXAN 1 OL; TRANS 4 [(5 METHYL 2 NITROPHENYL)AMINO]CYCLOHEXAN 1 OL; UNCLASSIFIED DRUG; UNINDEXED DRUG; (R,E)-N-(7-CHLORO-1-(1-(4-(DIMETHYLAMINO)BUT-2-ENOYL)AZEPAN-3-YL)-1H-BENZO(D)IMIDAZOL-2-YL)-2-METHYLISONICOTINAMIDE; ANTINEOPLASTIC AGENT; BENZIMIDAZOLE DERIVATIVE; NICOTINE; PROTEIN KINASE INHIBITOR;

ARTICLE; CANCER PATIENT; CONTROLLED STUDY; DRUG EFFICACY; DRUG SCREENING; DRUG TOLERABILITY; FEMALE; GENE MUTATION; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; IN VIVO STUDY; MALE; MOLECULAR DOCKING; MOUSE; NON SMALL CELL LUNG CANCER; NONHUMAN; RAT; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; CARCINOMA, NON-SMALL-CELL LUNG; CELL PROLIFERATION; CHEMISTRY; CONFORMATION; DOSE RESPONSE; DRUG DEVELOPMENT; DRUG EFFECTS; ENZYMOLOGY; GENETICS; LUNG NEOPLASMS; METABOLISM; MOLECULAR MODEL; MUTATION; NEOPLASMS, EXPERIMENTAL; NUDE MOUSE; PATHOLOGY; STRUCTURE ACTIVITY RELATION; SYNTHESIS; WISTAR RAT; X RAY CRYSTALLOGRAPHY;

ANIMALS; ANTINEOPLASTIC AGENTS; BENZIMIDAZOLES; CARCINOMA, NON-SMALL-CELL LUNG; CELL PROLIFERATION; CRYSTALLOGRAPHY, X-RAY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; LUNG NEOPLASMS; MALE; MICE; MICE, INBRED BALB C; MICE, NUDE; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MUTATION; NEOPLASMS, EXPERIMENTAL; NICOTINE; PROTEIN KINASE INHIBITORS; RATS; RATS, WISTAR; RECEPTOR, EPIDERMAL GROWTH FACTOR; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84979895476     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b01985     Document Type: Article

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