Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986)

Journal of Medicinal Chemistry

Volumn 59, Issue 20, 2016, Pages 9457-9472

  Doyle, Kevin ^a   Lönn, Hans ^b   Käck, Helena ^b   Van De Poël, Amanda ^a   Swallow, Steve ^c   Gardiner, Philip ^b   Connolly, Stephen ^b   Root, James ^b   Wikell, Cecilia ^b   Dahl, Göran ^b   Stenvall, Kristina ^b   Johannesson, Petra ^b  

^a Roche Welwyn   (United Kingdom)

^b ASTRAZENECA R AND D   (Sweden)

^c ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO N [1 CYANO 2 (4' CYANO [1,1' BIPHENYL] 4 YL)ETHYL]CYCLOPENTANECARBOXAMIDE; 2 AMINO N [1 CYANO 2 (4' CYANO[1,1' BIPHENYL] 4 YL)ETHYL]CYCLOHEPTANECARBOXAMIDE; 2 AMINO N [1 CYANO 2 (4' CYANO[1,1' BIPHENYL] 4 YL)ETHYL]CYCLOHEXANECARBOXAMIDE; DIPEPTIDYL PEPTIDASE I; DIPEPTIDYL PEPTIDASE IV INHIBITOR; N [1 CYANO 2 (4' CYANO[1,1' BIPHENYL] 4 YL)ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 (4' CYANO[1,1' BIPHENYL] 4 YL)ETHYL]AZEPANE 3 CARBOXAMIDE; N [1 CYANO 2 (4' CYANO[1,1' BIPHENYL] 4 YL)ETHYL]CYCLOHEXANECARBOXAMIDE; N [1 CYANO 2 (4' CYANO[1,1' BIPHENYL] 4 YL)ETHYL]MORPHOLINE 2 CARBOXAMIDE; N [1 CYANO 2 (4' CYANO[1,1' BIPHENYL] 4 YL)ETHYL]PIPERIDINE 3 CARBOXAMIDE; N [1 CYANO 2 [4 (1 METHYL 2 OXO 7 QUINOLYL)PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4 (3 ETHYL 2 OXO 1,3 BENZOXAZOL 5 YL)PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4 (3 METHYL 1,2 BENZOXAZOL 5 YL)PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4 (3 METHYL 2 OXO 1,3 BENZOTHIAZOL 5 YL)PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4 (3 METHYL 2 OXO 2,3 DIHYDROBENZO[D]OXAZOL 5 YL)PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4 (3,3 DIFLUORO 1 METHYL 2 OXOINDOLIN 6 YL)PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4 (3,7 DIMETHYL 2 OXO 2,3 DIHYDROBENZO[D]OXAZOL 5 YL)PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4 (4 METHYL 3 OXO 1,4 BENZOXAZIN 6 YL)PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4 (4 METHYL 3 OXO 3,4 DIHYDROQUINOXALIN 6 YL)PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4 [3 (2,2 DIFLUOROETHYL) 2 OXO 1,3 BENZOXAZOL 5 YL]PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4 [5 (TRIFLUOROMETHYL)PYRIMIDIN 2 YL]PHENYL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [1 CYANO 2 [4' (TRIFLUOROMETHYL)[1,1' BIPHENYL] 4 YL]ETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; N [2 [4 (1,3 BENZOTHIAZOL 5 YL)PHENYL] 1 CYANOETHYL] 1,4 OXAZEPANE 2 CARBOXAMIDE; POTASSIUM CHANNEL HERG; UNCLASSIFIED DRUG; BENZOXAZOLE DERIVATIVE; BRENSOCATIB; CTSC PROTEIN, HUMAN; OXAZEPINE DERIVATIVE; PROTEINASE INHIBITOR;

ANIMAL CELL; ANIMAL TISSUE; APPARENT PERMEABILITY; ARTICLE; BINDING KINETICS; CHRONIC OBSTRUCTIVE LUNG DISEASE; CONTROLLED STUDY; COVALENT BOND; DIASTEREOISOMER; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG PROTEIN BINDING; HUMAN; HUMAN CELL; IN VITRO STUDY; LIPOPHILICITY; MEAN RESIDENCE TIME; NONHUMAN; PHYSICAL CHEMISTRY; PKA; RAT; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DOG; DOSE RESPONSE; DRUG DEVELOPMENT; LEPORIDAE; METABOLISM; MOUSE; ORAL DRUG ADMINISTRATION; STRUCTURE ACTIVITY RELATION; U-937 CELL LINE;

ADMINISTRATION, ORAL; ANIMALS; BENZOXAZOLES; CATHEPSIN C; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; HUMANS; MICE; MOLECULAR STRUCTURE; OXAZEPINES; PROTEASE INHIBITORS; RABBITS; RATS; STRUCTURE-ACTIVITY RELATIONSHIP; U937 CELLS;

EID: 84994034513     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b01127     Document Type: Article

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