Literature DB >> 25516794

(7-Benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acids as S1P1 Functional Antagonists.

Daniel J Buzard1, Luis Lopez1, Jeanne Moody1, Andrew Kawasaki1, Thomas O Schrader1, Michelle Kasem1, Ben Johnson1, Xiuwen Zhu1, Lars Thoresen1, Sun Hee Kim1, Tawfik Gharbaoui1, Dipanjan Sengupta1, Lorene Calvano1, Ashwin Krishnan1, Yinghong Gao1, Graeme Semple1, Jeff Edwards1, Jeremy Barden1, Michael Morgan1, Khawja Usmani1, Chuan Chen1, Abu Sadeque1, Weichao Chen1, Ronald J Christopher1, Jayant Thatte1, Lixia Fu1, Michelle Solomon1, Kevin Whelan1, Hussien Al-Shamma1, Joel Gatlin1, Ibragim Gaidarov1, Todd Anthony1, Minh Le1, David J Unett1, Scott Stirn1, Anthony Blackburn1, Dominic P Behan1, Robert M Jones1.   

Abstract

S1P1 is a validated target for treatment of autoimmune disease, and functional antagonists with superior safety and pharmacokinetic properties are being sought as second generation therapeutics. We describe the discovery and optimization of (7-benzyloxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acids as potent, centrally available, direct acting S1P1 functional antagonists, with favorable pharmacokinetic and safety properties.

Entities:  

Keywords:  FTY720; Gilenya; S1P1 agonist; Sphingosine-1-phosphate; fingolimod

Year:  2014        PMID： 25516794      PMCID： PMC4265824          DOI： 10.1021/ml500422m

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  21 in total

1.  Synthesis, stereochemical determination and biochemical characterization of the enantiomeric phosphate esters of the novel immunosuppressive agent FTY720.

Authors:  Jeffrey J Hale; Lin Yan; William E Neway; Richard Hajdu; James D Bergstrom; James A Milligan; Gan-Ju Shei; Gary L Chrebet; Rosemary A Thornton; Deborah Card; Mark Rosenbach; Suzanne Mandala
Journal:  Bioorg Med Chem       Date:  2004-09-15       Impact factor: 3.641

Review 2.  Fingolimod for multiple sclerosis.

Authors:  Daniel Pelletier; David A Hafler
Journal:  N Engl J Med       Date:  2012-01-26       Impact factor: 91.245

3.  Fused tricyclic indoles as S1P₁ agonists with robust efficacy in animal models of autoimmune disease.

Authors:  Daniel J Buzard; Sangdon Han; Luis Lopez; Andrew Kawasaki; Jeanne Moody; Lars Thoresen; Brett Ullman; Juerg Lehmann; Imelda Calderon; Xiuwen Zhu; Tawfik Gharbaoui; Dipanjan Sengupta; Ashwin Krishnan; Yinghong Gao; Jeff Edwards; Jeremy Barden; Michael Morgan; Khawja Usmani; Chuan Chen; Abu Sadeque; Jayant Thatte; Michelle Solomon; Lixia Fu; Kevin Whelan; Ling Liu; Hussien Al-Shamma; Joel Gatlin; Minh Le; Charles Xing; Sheryll Espinola; Robert M Jones
Journal:  Bioorg Med Chem Lett       Date:  2012-05-07       Impact factor: 2.823

Review 4.  A mechanistically novel, first oral therapy for multiple sclerosis: the development of fingolimod (FTY720, Gilenya).

Authors:  Jerold Chun; Volker Brinkmann
Journal:  Discov Med       Date:  2011-09       Impact factor: 2.970

5.  Discovery of a brain-penetrant S1P₃-sparing direct agonist of the S1P₁ and S1P₅ receptors efficacious at low oral dose.

Authors:  Emmanuel H Demont; Sandra Arpino; Rino A Bit; Colin A Campbell; Nigel Deeks; Sapna Desai; Simon J Dowell; Pam Gaskin; James R J Gray; Lee A Harrison; Andrea Haynes; Tom D Heightman; Duncan S Holmes; Philip G Humphreys; Umesh Kumar; Mary A Morse; Greg J Osborne; Terry Panchal; Karen L Philpott; Simon Taylor; Robert Watson; Robert Willis; Jason Witherington
Journal:  J Med Chem       Date:  2011-09-09       Impact factor: 7.446

6.  Immunosuppressive and anti-angiogenic sphingosine 1-phosphate receptor-1 agonists induce ubiquitinylation and proteasomal degradation of the receptor.

Authors:  Myat Lin Oo; Shobha Thangada; Ming-Tao Wu; Catherine H Liu; Timothy L Macdonald; Kevin R Lynch; Chen-Yong Lin; Timothy Hla
Journal:  J Biol Chem       Date:  2007-01-21       Impact factor: 5.157

Review 7.  Th17 cell, the new player of neuroinflammatory process in multiple sclerosis.

Authors:  F Jadidi-Niaragh; A Mirshafiey
Journal:  Scand J Immunol       Date:  2011-07       Impact factor: 3.487

8.  Sphingosine 1-phosphate (S1P) receptor agonists mediate pro-fibrotic responses in normal human lung fibroblasts via S1P2 and S1P3 receptors and Smad-independent signaling.

Authors:  Katrin Sobel; Katalin Menyhart; Nina Killer; Bérengère Renault; Yasmina Bauer; Rolf Studer; Beat Steiner; Martin H Bolli; Oliver Nayler; John Gatfield
Journal:  J Biol Chem       Date:  2013-04-15       Impact factor: 5.157

Review 9.  Mechanism of action of oral fingolimod (FTY720) in multiple sclerosis.

Authors:  Jerold Chun; Hans-Peter Hartung
Journal:  Clin Neuropharmacol       Date:  2010 Mar-Apr       Impact factor: 1.592

10.  Sphingosine 1-phosphate receptor 5 mediates the immune quiescence of the human brain endothelial barrier.

Authors:  Ruben van Doorn; Melissa A Lopes Pinheiro; Gijs Kooij; Kim Lakeman; Bert van het Hof; Susanne M A van der Pol; Dirk Geerts; Jack van Horssen; Paul van der Valk; Elizabeth van der Kam; Eric Ronken; Arie Reijerkerk; Helga E de Vries
Journal:  J Neuroinflammation       Date:  2012-06-20       Impact factor: 8.322
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