title: Selecting against S1P3 enhances the acute cardiovascular tolerability of 3-(N-benzyl)aminopropylphosphonic acid S1P receptor agonists.
abstract: Structurally modified 3-(N-benzylamino)propylphosphonic acid S1P receptor agonists that maintain affinity for S1P1, and have decreased affinity for S1P3 are efficacious, but exhibit decreased acute cardiovascular toxicity in rodents than do nonselective agonists.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. jeffrey_hale@merck.com
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hale
authors.forename: George
authors.initials: G
authors.lastname: Doherty
authors.forename: Leslie
authors.initials: L
authors.lastname: Toth
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Richard
authors.initials: R
authors.lastname: Hajdu
authors.forename: Carol Ann
authors.initials: CA
authors.lastname: Keohane
authors.forename: Mark
authors.initials: M
authors.lastname: Rosenbach
authors.forename: James
authors.initials: J
authors.lastname: Milligan
authors.forename: Gan-Ju
authors.initials: GJ
authors.lastname: Shei
authors.forename: Gary
authors.initials: G
authors.lastname: Chrebet
authors.forename: James
authors.initials: J
authors.lastname: Bergstrom
authors.forename: Deborah
authors.initials: D
authors.lastname: Card
authors.forename: Michael
authors.initials: M
authors.lastname: Forrest
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Sun
authors.forename: Sarah
authors.initials: S
authors.lastname: West
authors.forename: Huijuan
authors.initials: H
authors.lastname: Xie
authors.forename: Naomi
authors.initials: N
authors.lastname: Nomura
authors.forename: Hugh
authors.initials: H
authors.lastname: Rosen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Mandala
mesh_terms: D000818:Animals; D001593:Benzyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D016466:CHO Cells; D002319:Cardiovascular System / Q000187:drug effects*; D006224:Cricetinae; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008246:Lysophospholipids / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology*; D010761:Phosphorus Radioisotopes; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
chemical_list: C495734:3-(N-benzyl)aminopropylphosphonic acid; D001593:Benzyl Compounds; D008246:Lysophospholipids; D009943:Organophosphorus Compounds; D010761:Phosphorus Radioisotopes; D043562:Receptors, G-Protein-Coupled; D049349:Receptors, Lysosphingolipid; D013110:Sphingosine