Synthesis, SAR, and series evolution of novel oxadiazole-containing 5-lipoxygenase activating protein inhibitors: Discovery of 2-[4-(3-{(R)-1-[4-(2-amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]- N, N -dimethyl-acetamide (BI 665915)

Journal of Medicinal Chemistry

Volumn 58, Issue 4, 2015, Pages 1669-1690

  Takahashi, Hidenori ^a,d   Riether, Doris ^a   Bartolozzi, Alessandra ^a   Bosanac, Todd ^a   Berger, Valentina ^a   Binetti, Ralph ^a   Broadwater, John ^a   Chen, Zhidong ^a   Crux, Rebecca ^b   De Lombaert, Stéphane ^a,c   Dave, Rajvee ^a   Dines, Jonathon A ^b   Fadra Khan, Tazmeen ^a   Flegg, Adam ^b   Garrigou, Michael ^b   Hao, Ming Hong ^a   Huber, John ^a,e   Hutzler, J Matthew ^a,f   Kerr, Steven ^a   Kotey, Adrian ^b   Liu, Weimin ^a,g   Lo, Ho Yin ^a,h   Loke, Pui Leng ^b   Mahaney, Paige E ^a   Morwick, Tina M ^a   Napier, Spencer ^b   Olague, Alan ^a   Pack, Edward ^a   Padyana, Anil K ^a   Thomson, David S ^a,i   Tye, Heather ^b   Wu, Lifen ^a   Zindell, Renee M ^a   Abeywardane, Asitha ^a   Simpson, Thomas ^a   more..

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

^b EVOTEC UK LTD   (United Kingdom)

^c Karos Pharmaceuticals   (United States)

^d EISAI INC   (United States)

^e BRISTOL MYERS SQUIBB   (United States)

^f IQVIA   (United States)

^g Quintiles Bioanalytical and ADME Laboratories ^*  (China)

^h Synovel Laboratory Co Ltd   (United States)

ⁱ Biomanufacturing Research Institute and Technology Enterprise   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 BROMO PHENYL) CYCLOBUTANECARBONITRILE; 1 (4 BROMO PHENYL) N HYDROXY CYCLOBUTANECARBOXAMIDINE; 1 [4 (2 AMINO PYRIMIDIN 5 YL) PHENYL] N HYDROXY CYCLOBUTANECARBOXAMIDINE; 2 [4 [3 [1 [4 (2 AMINO PYRIMIDIN 5 YL) PHENYL] 1 CYCLOPROPYLETHYL] [ 1,2,4]OXADIAZOL 5 YL]PYRAZOL 1 YL] N,N DIMETHYL ACETAMIDE; 3 [1 (4 BROMO PHENYL) CYCLOBUTYL] 5 TRICHLOROMETHYL [1,2,4]OXADIAZOLE; 3 [1 (4 BROMO PHENYL) CYCLOBUTYL] [1,2,4]OXADIAZOL 5 YLAMINE; 3 [3 [1 [4 (2 AMINO PYRIMIDIN 5 YL) PHENYL] CYCLOBUTYL] [1,2,4]OXADIAZOL 5 YL] 1H PYRIMIDIN 2 ONE; 5 [4 [1 (5 AMINO [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 (5 ETHYLAMINO [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 (5 OXAZOL 4 YL [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 (5 PHENYL [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 (5 PYRAZIN 2 YL [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 (5 PYRIDAZIN 3 YL [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 (5 PYRIDAZIN 4 YL [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 (5 PYRIDIN 3 YL [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 (5 PYRIMIDIN 4 YL [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 (5 PYRIMIDIN 5 YL [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 (5 THIAZOL 4 YL [1,2,4]OXADIAZOL 3 YL) CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 [5 (1H IMIDAZOL 4 YL) [1,2,4]OXADIAZOL 3 YL] CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 [5 (1H PYRAZOL 3 YL) [1,2,4]OXADIAZOL 3 YL] CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 [5 (1H PYRAZOL 4 YL) [1,2,4]OXADIAZOL 3 YL] CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 [5 (1H [1,2,3]TRIAZOL 4 YL) [1,2,4]OXADIAZOL 3 YL] CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 [5 (1H [1,2,4]TRIAZOL 3 YL) [1,2,4]OXADIAZOL 3 YL] CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; 5 [4 [1 [5 (2 CHLORO PYRIDIN 3 YL) [1,2,4]OXADIAZOL 3 YL] CYCLOBUTYL] PHENYL] PYRIMIDIN 2 YLAMINE; ARACHIDONATE 5 LIPOXYGENASE ACTIVATING PROTEIN INHIBITOR; N [3 [1 (4 BROMO PHENYL) CYCLOBUTYL] [1,2,4]OXADIAZOL 5 YL] METHANESULFONAMIDE; N [3 [1 [4 (2 AMINO PYRIMIDIN 5 YL) PHENYL] CYCLOBUTYL] [1,2,4] OXADIAZOL 5 YL] METHANESULFONAMIDE; OXADIAZOLE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; [3 [1 (4 BROMO PHENYL) CYCLOBUTYL] [1,2,4]OXADIAZOL 5 YL] ETHYLAMINE; 2-(4-(3-(1-(4-(2-AMINOPYRIMIDIN-5-YL)PHENYL)-1-CYCLOPROPYLETHYL)-(1,2,4)OXADIAZOL-5-YL)PYRAZOL-1-YL)-N,N-DIMETHYLACETAMIDE; ACETAMIDE DERIVATIVE; ARACHIDONATE 5 LIPOXYGENASE; LIPOXYGENASE INHIBITOR;

ALKYLATION; ANIMAL EXPERIMENT; ARTICLE; ATHEROSCLEROSIS; BINDING AFFINITY; CHIRALITY; CRYSTAL STRUCTURE; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DESIGN; DRUG METABOLISM; DRUG POTENCY; DRUG SOLUBILITY; DRUG SYNTHESIS; ENANTIOMER; ENZYME LINKED IMMUNOSORBENT ASSAY; EX VIVO STUDY; EXPERIMENTAL DOG; HUMAN; IC50; LIPID BILAYER; LIPOPHILICITY; LIVER CELL; MACACA FASCICULARIS; MEAN RESIDENCE TIME; MEMBRANE PERMEABILITY; MOUSE; NONHUMAN; PHOSPHOLIPID BILAYER; PHYSICAL CHEMISTRY; PLASMA PROTEIN BINDING; STRUCTURAL HOMOLOGY; STRUCTURE ACTIVITY RELATION; VOLUME OF DISTRIBUTION; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; DOSE RESPONSE; DRUG DEVELOPMENT; METABOLISM; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ACETAMIDES; ARACHIDONATE 5-LIPOXYGENASE; CRYSTALLOGRAPHY, X-RAY; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; HUMANS; LIPOXYGENASE INHIBITORS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; OXADIAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84923914297     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm501185j     Document Type: Article

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