Use of small-molecule crystal structures to address solubility in a novel series of g protein coupled receptor 119 agonists: Optimization of a lead and in vivo evaluation

Journal of Medicinal Chemistry

Volumn 55, Issue 11, 2012, Pages 5361-5379

  Scott, James S ^a   Birch, Alan M ^a   Brocklehurst, Katy J ^a   Broo, Anders ^b   Brown, Hayley S ^a   Butlin, Roger J ^a   Clarke, David S ^a   Davidsson, Öjvind ^b   Ertan, Anne ^c   Goldberg, Kristin ^a   Groombridge, Sam D ^a   Hudson, Julian A ^a   Laber, David ^a   Leach, Andrew G ^a   MacFaul, Philip A ^a   McKerrecher, Darren ^a   Pickup, Adrian ^a   Schofield, Paul ^a   Svensson, Per H ^c   Sörme, Pernilla ^a   Teague, Joanne ^a   more..

^a ASTRAZENECA   (United Kingdom)

^b ASTRAZENECA R AND D   (Sweden)

^c ASTRAZENECA R AND D   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

4 [[2 [2 METHYL 4 [5 (1 METHYLETHYL) 1,2,4 OXADIAZOL 3 YL]PIPERAZIN 1 YL]PYRIMIDIN 5 YL)OXY]METHYL]PYRIDINE 3 CARBONITRILE; ANTIDIABETIC AGENT; G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR 119; G PROTEIN COUPLED RECEPTOR 119 AGONIST; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE; PYRIDINE DERIVATIVE; SITAGLIPTIN; SULFONE DERIVATIVE; TERT BUTYL 4 [5 [[4 (METHYLSULFONYL)BENZYL]OXY]PYRIMIDIN 2 YL]PIPERAZINE 1 CARBOXYLATE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; DISTRIBUTION VOLUME; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG HALF LIFE; DRUG POTENCY; DRUG SCREENING; DRUG SOLUBILITY; DRUG SYNTHESIS; GLUCOSE BLOOD LEVEL; HIGH THROUGHPUT SCREENING; HUMAN; IN VIVO STUDY; KNOCKOUT MOUSE; METABOLIC SYNDROME X; MOLECULAR INTERACTION; MOUSE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; ORAL GLUCOSE TOLERANCE TEST; STRUCTURE ACTIVITY RELATION; WILD TYPE;

ANIMALS; BIOLOGICAL AVAILABILITY; CARBAMATES; CRYSTALLOGRAPHY, X-RAY; DOGS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MODELS, MOLECULAR; MOLECULAR STRUCTURE; OXADIAZOLES; PIPERIDINES; PYRIDINES; RATS; RATS, WISTAR; RECEPTORS, G-PROTEIN-COUPLED; SMALL MOLECULE LIBRARIES; SOLUBILITY; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONES;

EID: 84862303554     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm300310c     Document Type: Article

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