Discovery and optimization of an azetidine chemical series as a free fatty acid receptor 2 (FFA2) antagonist: From hit to clinic

Journal of Medicinal Chemistry

Volumn 57, Issue 23, 2014, Pages 10044-10057

  Pizzonero, Mathieu ^a   Dupont, Sonia ^a   Babel, Marielle ^a   Beaumont, Stéphane ^a   Bienvenu, Natacha ^a   Blanqué, Roland ^a   Cherel, Laëtitia ^a   Christophe, Thierry ^b   Crescenzi, Benedetta ^a   De Lemos, Elsa ^a   Delerive, Philippe ^a   Deprez, Pierre ^a   De Vos, Steve ^b   Djata, Fatoumata ^a   Fletcher, Stephen ^a   Kopiejewski, Sabrina ^a   Lebraly, Christelle ^a   Lefrançois, Jean Michel ^a   Lavazais, Stéphanie ^a   Manioc, Murielle ^a   Nelles, Luc ^b   Oste, Line ^b   Polancec, Denis ^c   Quénéhen, Vanessa ^a   Soulas, Florilène ^a   Triballeau, Nicolas ^a   Van Der Aar, Ellen M ^b   Vandeghinste, Nick ^b   Wakselman, Emanuelle ^a   Brys, Reginald ^b   Saniere, Laurent ^a   more..

^a Galapagos   (France)

^b GALAPAGOS NV   (Belgium)

^c Fidelta Ltd   (Croatia)

Author keywords

[No Author keywords available]

Indexed keywords

1 (2 BENZOFURAN 3 YL ACETYL) 2 METHYL AZETIDINE 2 CARBOXYLIC ACID; 1 (2 BENZO[B]THIOPHEN 3 YL ACETYL) 2 METHYL AZETIDINE 2 CARBOXYLIC ACID; 1 (2 BENZO[B]THIOPHEN 3 YL ACETYL) 2 METHYL AZETIDINE 2 CARBOXYLIC ACID 4 CHLORO BENZYLAMIDE; 1 (2 BENZO[B]THIOPHEN 3 YL ACETYL) 2 METHYL AZETIDINE 2 CARBOXYLIC ACID(4 CHLORO BENZYL)(3 SULFAMOYL PROPYL)AMIDE; 1 (2 BENZO[B]THIOPHENE 3 CARBONYL) 2 METHYL AZETIDINE 2 CARBOXYLIC ACID; 1 (2 BIPHENYL 4 YL ACETYL) 2 METHYL AZETIDINE 2 CARBOXYLIC ACID(4 CHLORO BENZYL)METHYL AMIDE; 1 BENZYL 2 METHYL AZETIDINE 2 CARBOXYLIC ACID ETHYL ESTER; 1 [2 (3,5 DIMETHYL PHENYL)ACETYL] 2 METHYL AZETIDINE 2 CARBOXYLIC ACID; 1 [2 (3,5 DIMETHYL PHENYL)ACETYL] 2 METHYL AZETIDINE 2 CARBOXYLIC ACID(2 AMINO ETHYL) (4 CHLORO BENZYL)AMIDE; 1 [2 (3,5 DIMETHYL PHENYL)ACETYL] 2 METHYL AZETIDINE 2 CARBOXYLIC ACID(3 CARBAMOYL PROPYL)(4 CHLORO BENZYL)AMIDE; 1 [2 (3,5 DIMETHYL PHENYL)ACETYL] 2 METHYL AZETIDINE 2 CARBOXYLIC ACID(4 CHLORO BENZYL )METHYLCARBAMOYLMETHYL AMIDE; 1 [2 (3,5 DIMETHYL PHENYL)ACETYL] 2 METHYL AZETIDINE 2 CARBOXYLIC ACID(4 CHLORO BENZYL)(2 METHANESULFONYLAMINO ETHYL)AMIDE; 1 [2-(3,5 DIMETHYL PHENYL)ACETYL] 2 METHYL AZETIDINE 2 CARBOXYLIC ACID(4 CHLOROBENZYL)(4 MORPHOLIN 4 YL 4 OXO BUTYL)AMIDE; 2 BENZYLAMINO PROPIONIC ACID ETHYL ESTER; 2 METHYL AZETIDINE 1,2 DICARBOXYLIC ACID 1 TERT BUTYL ESTER 2 ETHYL ESTER; 2 [(4 CHLORO BENZYL)METHYL CARBAMOYL] 2 METHYL AZETIDINE 1 CARBOXYLIC ACID TERT BUTYL ESTER; 2 [BENZYL (2 CHLORO ETHYL)AMINO]PROPIONIC ACID ETHYL ESTER; 2 [BENZYL(2 CHLORO ETHYL)AMINO]PROPIONIC ACID ETHYL ESTER; 4 [1 (BENZO[B]THIOPHENE 3 CARBONYL) N (6 CHLOROPYRIDIN 3 YL) 2 METHYLAZETIDINE 2 METHYLAZETIDINE 2 CARBOXIMIDO]BUTANOIC ACID; 4 [[1 (BENZO[B]THIOPHENE 3 CARBONYL) 2 METHYL AZETIDINE 2 CARBONYL]BENZOFURAN 6 YLMETHYLAMINO]BUTYRIC ACID; ACETIC ACID; ANTIINFLAMMATORY AGENT; AZETIDINE; AZETIDINE DERIVATIVE; CARBOXYLIC ACID; FREE FATTY ACID RECEPTOR 2 ANTAGONIST; G PROTEIN COUPLED RECEPTOR; THIOPHENE; UNCLASSIFIED DRUG; UNINDEXED DRUG; [[1 (2 BENZO[B]THIOPHEN 3 YL ACETYL) 2 METHYL AZETIDINE 2 CARBONYL] (4 CHLORO BENZYL)AMINO]ACETIC ACID; 4-(((R)-1-(BENZO(B)THIOPHENE-3-CARBONYL)-2-METHYL-AZETIDINE-2-CARBONYL)-(3-CHLORO-BENZYL)-AMINO)-BUTYRIC ACID; BUTYRIC ACID DERIVATIVE; CELL SURFACE RECEPTOR; G-PROTEIN COUPLED RECEPTOR 43, HUMAN; NONSTEROID ANTIINFLAMMATORY AGENT; THIOPHENE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL MIGRATION; CONTROLLED STUDY; DRUG HALF LIFE; DRUG SOLUBILITY; DRUG STABILITY; DRUG STRUCTURE; EMBRYO; HUMAN; HUMAN CELL; HYDROGENOLYSIS; IC50; IN VITRO STUDY; MALE; NEUTROPHIL; NONHUMAN; PHARMACODYNAMICS; RAT; ANIMAL; ANTAGONISTS AND INHIBITORS; IMMUNOPATHOLOGY; LEUKOCYTE DISORDER; LIVER MICROSOME; METABOLISM; MOUSE; SPRAGUE DAWLEY RAT; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; AZETIDINES; BUTYRATES; HUMANS; IMMUNE SYSTEM DISEASES; INHIBITORY CONCENTRATION 50; LEUKOCYTE DISORDERS; MICE; MICROSOMES, LIVER; RATS, SPRAGUE-DAWLEY; RECEPTORS, CELL SURFACE; STRUCTURE-ACTIVITY RELATIONSHIP; THIOPHENES;

EID: 84918563561     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5012885     Document Type: Article

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