Discovery and optimization of pyrrolo[1,2-a]pyrazinones leads to novel and selective inhibitors of PIM kinases

Bioorganic and Medicinal Chemistry

Volumn 21, Issue 23, 2013, Pages 7364-7380

  Casuscelli, Francesco ^a   Ardini, Elena ^a   Avanzi, Nilla ^a   Casale, Elena ^a   Cervi, Giovanni ^a   D'Anello, Matteo ^a   Donati, Daniele ^a   Faiardi, Daniela ^a   Ferguson, Ronald D ^a   Fogliatto, Gianpaolo ^a   Galvani, Arturo ^a   Marsiglio, Aurelio ^a   Mirizzi, Danilo G ^a   Montemartini, Marisa ^a   Orrenius, Christian ^a   Papeo, Gianluca ^a   Piutti, Claudia ^a   Salom, Barbara ^a   Felder, Eduard R ^a  

^a Nerviano Medical Sciences ^*  (Italy)

Author keywords

Anti cancer agents; Kinase selectivity; Natural product scaffold; PIM kinases; Pyrrolopyrazinone

Indexed keywords

1 OXO 7 [3 (TRIFLUOROMETHYL)PHENYL] 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL ACETIC ACID; 2 [1 OXO 7 [3 (TRIFLUOROMETHYL)PHENYL] 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL] N (TETRAHYDRO 2H PYRAN 4 YL)ACETAMIDE; 2 [7 (3 CHLOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL] N (FURAN 2 YLMETHYL)ACETAMIDE; 2 [7 (3,4 DIFLUOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL] N (FURAN 2 YLMETHYL)ACETAMIDE; 2 [7 (5 CHLORO 2 FLUOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL] N (FURAN 2 YLMETHYL)ACETAMIDE; 2 [7 (5 CHLORO 2 METHYLPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL] N (FURAN 2 YLMETHYL)ACETAMIDE; [7 (3 FLUOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETIC ACID; ETHYL 7 (3 TRIFLUOROMETHYLPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 CARBOXYLATE; ETHYL [7 (2 FLUOROPYRIDIN 4 YL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETATE; ETHYL [7 (3 CHLOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETATE; ETHYL [7 (3 TRIFLUOROMETHYLPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETATE; ETHYL [7 (3,4 DIFLUOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETATE; ETHYL [7 (5 CHLORO 2 FLUOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETATE; N (2,2 DIMETHYLPROPYL) 2 (1 OXO 7 PHENYL 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL)ACETAMIDE; N (2,2 DIMETHYLPROPYL) 2 [1 OXO 7 (PYRIDIN 4 YL) 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETAMIDE; N (2,2 DIMETHYLPROPYL) 2 [1 OXO 7 (THIOPHEN 3 YL) 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETAMIDE; N (2,2 DIMETHYLPROPYL) 2 [1 OXO 7 [3 (TRIFLUOROMETHYL)PHENYL] 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETAMIDE; N (2,2 DIMETHYLPROPYL) 2 [7 (2 FLUOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETAMIDE; N (2,2 DIMETHYLPROPYL) 2 [7 (3 FLUOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETAMIDE; N (2,2 DIMETHYLPROPYL) 2 [7 (4 FLUOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETAMIDE; N (3 FLUOROBENZYL) 2 [1 OXO 7 [3 (TRIFLUOROMETHYL)PHENYL] 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETAMIDE; N (CYCLOHEXYLMETHYL) 2 [7 (3 FLUOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETAMIDE; N (CYCLOHEXYLMETHYL) 2 [7 (3,4 DIFLUOROPHENYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETAMIDE; PHOSPHOTRANSFERASE; PHOSPHOTRANSFERASE INHIBITOR; PIM INHIBITOR; PROTEIN PIM; PYRROLO[1,2 A]PYRAZINONE DERIVATIVE; TERT BUTYL 4 [4 (2 ETHOXY 2 OXOETHYL) 1 OXO 1,2,3,4 TETRAHYDROPYRROLO[1,2 A]PYRAZIN 4 YL]ACETATE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG RESEARCH; DRUG SCREENING; DRUG SYNTHESIS; DRUG TARGETING; IC 50; PHARMACOKINETICS; PROCESS OPTIMIZATION; PROTEIN DOMAIN; PROTEIN FAMILY; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ANTI-CANCER AGENTS; KINASE SELECTIVITY; NATURAL PRODUCT SCAFFOLD; PIM KINASES; PYRROLOPYRAZINONE;

DRUG DISCOVERY; HUMANS; MOLECULAR DOCKING SIMULATION; PROTEIN KINASE INHIBITORS; PROTEIN STRUCTURE, TERTIARY; PROTO-ONCOGENE PROTEINS C-PIM-1; PYRAZINES;

EID: 84886953247     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2013.09.054     Document Type: Article

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