title: Novel glycine transporter type-2 reuptake inhibitors. Part 2: beta- and gamma-amino acid derivatives.
abstract: Several beta- and gamma-amino acid derivatives were prepared as glycine transport inhibitors and their ability to block the uptake of [(14)C]-glycine in COS7 cells transfected with human glycine transporter-2 (hGlyT-2) were evaluated. A range of lipophilic side chains were tolerated in the beta-amino acid series (i.e., Ph, CH(2)Ph, CH(CH(3))(2), and CH(2)CH(CH(3))(2)). In the gamma-amino acid series, minimal differences in potency were observed between the alpha,beta-unsaturated analogs and the corresponding saturated derivatives. In both series, a 4-biphenyl or 4-phenoxyphenyl substituent appended to the urea or cyanogunaidine moiety was necessary for in vitro activity.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USA. rwolin@prdus.jnj.com
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Wolin
authors.forename: Alejandro
authors.initials: A
authors.lastname: Santillán
authors.forename: Tristin
authors.initials: T
authors.lastname: Barclay
authors.forename: Liu
authors.initials: L
authors.lastname: Tang
authors.forename: Hariharan
authors.initials: H
authors.lastname: Venkatesan
authors.forename: Sandy
authors.initials: S
authors.lastname: Wilson
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Lee
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Lovenberg
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000037:antagonists & inhibitors* / Q000235:genetics; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D019556:COS Cells; D002522:Chlorocebus aethiops; D005998:Glycine / Q000378:metabolism; D050487:Glycine Plasma Membrane Transport Proteins; D006146:Guanidines / Q000737:chemistry; D014179:Neurotransmitter Uptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D000596:Amino Acids; D050487:Glycine Plasma Membrane Transport Proteins; D006146:Guanidines; D014179:Neurotransmitter Uptake Inhibitors; C004711:dicyandiamido; D005998:Glycine