1,3-diaminopropan-2-ol sulfonamides as potent and selective inhibitors of the glycine transporter type 1.
High throughput screening led to the discovery of a novel series of 1,3-diaminopropan-2-ol sulfonamides as selective GlyT-1 inhibitors. Structure-activity relationships of this novel series and optimisation of the initial hit that led to the identification of (2), a potent and selective GlyT-1 inhibitor, are also presented.
Rahman
Shahzad S
SS
Discovery Medicinal Chemistry, GlaxoSmithKline, Harlow, Essex CM19 5AW, UK. shahzad.rahman-1@gsk.com
Coulton
Steven
S
Herdon
Hugh J
HJ
Joiner
Graham F
GF
Jin
Jian
J
Porter
Roderick A
RA
D000818:Animals; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007536:Isomerism; D008968:Molecular Conformation; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
D050487:Glycine Plasma Membrane Transport Proteins; D013449:Sulfonamides