1,3-Diaminopropan-2-ol Sulfonamides as potent and selective inhibitors of the glycine transporter type 1

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 6, 2007, Pages 1741-1745

  Rahman, Shahzad S ^a   Coulton, Steven ^a   Herdon, Hugh J ^a   Joiner, Graham F ^a   Jin, Jian ^b   Porter, Roderick A ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

^b GLAXOSMITHKLINE   (United States)

Author keywords

1,3 Diaminopropan 2 ol; GlyT 1; NMDA; Schizophrenia; Transporter

Indexed keywords

1,3 DIAMINOPROPAN 2 OL SULFONAMIDE; GLYCINE TRANSPORTER 1; SULFONAMIDE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; NONHUMAN; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL LINE, TUMOR; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; COMPUTER SIMULATION; DRUG EVALUATION, PRECLINICAL; GLYCINE PLASMA MEMBRANE TRANSPORT PROTEINS; HUMANS; ISOMERISM; MOLECULAR CONFORMATION; RATS; SPECTROPHOTOMETRY, ULTRAVIOLET; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 33847063198     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.12.063     Document Type: Article

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14. -1, ambient temperature, detection was by UV absorbance at 290 nm.
15. 20 -9.5° (c 0.3% in MeOH).
16. 1 = 2,4-dimethyl pyrrolidin-1-yl) (800 mg; 4.65 mmol) in anhydrous dichloromethane (38 ml) was prepared, and aliquots (0.5 ml; 0.06 mmol) were added to solutions of 50 sulfonyl chlorides (0.075 mmol each) dissolved in anhydrous dichloromethane (1 ml each). Triethylamine (0.021 ml; 0.15 mmol) was added to each solution, which was shaken overnight at ambient temperature. The reaction mixtures were shaken with polymer-bound tris amine (∼45 mg) for 3 h, then filtered and purified by preparative HPLC to afford the sulfonamides (7) as the trifluoroacetate salts.
17. 0-inf 587 h ng/ml.