Discovery, Optimization, and in Vivo Evaluation of Benzimidazole Derivatives AM-8508 and AM-9635 as Potent and Selective PI3Kδ Inhibitors

Journal of Medicinal Chemistry

Volumn 59, Issue 1, 2016, Pages 431-447

  Shin, Youngsook ^a   Suchomel, Julia ^a   Cardozo, Mario ^a   Duquette, Jason ^a   He, Xiao ^a   Henne, Kirk ^a   Hu, Yi Ling ^b   Kelly, Ron C ^b   McCarter, John ^b   McGee, Lawrence R ^a   Medina, Julio C ^a   Metz, Daniela ^b   San Miguel, Tisha ^b   Mohn, Deanna ^b   Tran, Thuy ^a   Vissinga, Christine ^b   Wong, Simon ^a   Wannberg, Sharon ^b   Whittington, Douglas A ^b   Whoriskey, John ^b   Yu, Gang ^b   Zalameda, Leeanne ^b   Zhang, Xuxia ^b   Cushing, Timothy D ^a   more..

^a Department of Therapeutic Discovery ^*  (United States)

^b AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (6 FLUORO 1 PHENYL 1H BENZO[D]IMIDAZOL 2 YL)ETHANAMINE; 1 [1 (3,5 DIFLUOROPHENYL) 6 FLUORO 1H BENZO[D]IMIDAZOL 2 YL]ETHANAMINE; 1 [6 FLUORO 1 (4 FLUOROPHENYL) 1H BENZO[D]IMIDAZOL 2 YL]ETHANAMINE; 1 [6 FLUORO 1 (PYRIDIN 3 YL) 1H BENZO[D]IMIDAZOL 2 YL]ETHANAMINE; 1 [6 FLUORO 1 [2 (METHYLSULFONYL)PHENYL] 1H BENZO[D]IMIDAZOL 2 YL]ETHANAMINE; 1 [6 FLUORO 1 [3 (METHYLSULFONYL)PHENYL] 1H BENZO[D]IMIDAZOL 2 YL]ETHANAMINE; 4 AMINO 6 [1 (1 CYCLOPROPYL 6 FLUORO 1H BENZO[D]IMIDAZOL 2 YL]ETHYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 AMINO 6 [1 [1 (3,5 FLUOROPHENYL) 1H BENZO[D]IMIDAZOL 2 YL]ETHYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 AMINO 6 [1 [5 FLUORO 1 [3 (METHYLSULFONYL)PHENYL] 1H BENZO[D]IMIDAZOL 2 YL]ETHYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 AMINO 6 [1 [6 FLUORO 1 (3 FLUOROPHENYL) 1H BENZO[D]IMIDAZOL 2 YL]ETHYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 AMINO 6 [1 [6 FLUORO 1 (4 FLUOROPHENYL) 1H BENZO[D]IMIDAZOL 2 YL]ETHYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 AMINO 6 [1 [6 FLUORO 1 (5 FLUOROPYRIDIN 3 YL) 1H BENZO[D]IMIDAZOL 2 YL]ETHYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 AMINO 6 [1 [6 FLUORO 1 (METHYLSULFONYL)PHENYL] 1H BENZO[D]IMIDAZOL 2 YL]ETHYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 AMINO 6 [1 [6 FLUORO 1 (PYRIDIN 3 YL) 1H BENZO[D]IMIDAZOL 2 YL]ETHYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 AMINO 6 [1 [6 FLUORO 1 [2 (METHYLSULFONYL)PHENYL] 1H BENZO[D]IMIDAZOL 2 YL]ETHYLAMINO]PYRIMIDINE 5 CARBONITRILE; 4 AMINO 6 [1 [6 FLUORO 1 [3 (METHYLSULFONYL)PHENYL] 1H BENZO[D]IMIDAZOL 2 YL]ETHYLAMINO]PYRIMIDINE 5 CARBONITRILE; AM 8508; AM 9365; B LYMPHOCYTE RECEPTOR; BENZIMIDAZOLE DERIVATIVE; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; KEYHOLE LIMPET HEMOCYANIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE DELTA; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; TERT BUTYL 1 (1 CYCLOPROPYL 5 FLUORO 1H BENZO[D]IMIDAZOL 2 YL)ETHYLCARBAMATE; TERT BUTYL 1 (1 CYCLOPROPYL 6 FLUORO 1H BENZO[D]IMIDAZOL 2 YL)ETHYLCARBAMATE; TERT BUTYL 1 (6 FLUORO 1H BENZO[D]IMIDAZOL 2 YL)ETHYLCARBAMATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; AM-8508; AM-9635; HEMOCYANIN; KEYHOLE-LIMPET HEMOCYANIN; PROTEIN KINASE INHIBITOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DRUG CLEARANCE; DRUG POTENCY; DRUG SYNTHESIS; ENZYME ACTIVITY; FEMALE; HUMORAL IMMUNITY; IMMUNIZATION; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PHYSICAL CHEMISTRY; PLASMA PROTEIN BINDING; PROTEIN PHOSPHORYLATION; RAT; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; B LYMPHOCYTE; CHEMICAL STRUCTURE; DRUG EFFECTS; HUMAN; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ANIMALS; B-LYMPHOCYTES; BENZIMIDAZOLES; CRYSTALLOGRAPHY, X-RAY; HEMOCYANIN; HUMANS; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; MICE; MODELS, MOLECULAR; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84955053945     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.5b01651     Document Type: Article

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