Your browser doesn't support javascript.
loading
4-Methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and Selective Agonist of S1P1.
Pennington, Lewis D; Sham, Kelvin K C; Pickrell, Alexander J; Harrington, Paul E; Frohn, Michael J; Lanman, Brian A; Reed, Anthony B; Croghan, Michael D; Lee, Matthew R; Xu, Han; McElvain, Michele; Xu, Yang; Zhang, Xuxia; Fiorino, Michael; Horner, Michelle; Morrison, Henry G; Arnett, Heather A; Fotsch, Christopher; Wong, Min; Cee, Victor J.
Afiliación
  • Pennington LD; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Sham KK; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Pickrell AJ; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Harrington PE; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Frohn MJ; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Lanman BA; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Reed AB; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Croghan MD; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Lee MR; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Xu H; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • McElvain M; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Xu Y; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Zhang X; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Fiorino M; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Horner M; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Morrison HG; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Arnett HA; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Fotsch C; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Wong M; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
  • Cee VJ; Medicinal Chemistry, Molecular Structure, HTS and Molecular Pharmacology, Inflammation Research, Pharmacokinetics and Drug Metabolism, Toxicology, and Pharmaceutics, Amgen , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
ACS Med Chem Lett ; 2(10): 752-7, 2011 Oct 13.
Article en En | MEDLINE | ID: mdl-24900263
ABSTRACT
The sphingosine-1-phosphate-1 receptor (S1P1) and its endogenous ligand sphingosine-1-phosphate (S1P) cooperatively regulate lymphocyte trafficking from the lymphatic system. Herein, we disclose 4-methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide (8), an uncommon example of a synthetic S1P1 agonist lacking a polar headgroup, which is shown to effect dramatic reduction of circulating lymphocytes (POC = -78%) in rat 24 h after a single oral dose (1 mg/kg). The excellent potency that 8 exhibits toward S1P1 (EC50 = 0.035 µM, 96% efficacy) and the >100-fold selectivity that it displays against receptor subtypes S1P2-5 suggest that it may serve as a valuable tool to understand the clinical relevance of selective S1P1 agonism.
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2011 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2011 Tipo del documento: Article