PMID

Data

Article Title

Organization

Discovery of a Potent and Selective Sphingosine Kinase 1 Inhibitor through the Molecular Combination of Chemotype-Distinct Screening Hits.

Pfizer

Kinase-independent phosphoramidate S1P

Cardiff University

A benzo[b]thiophene-based selective type 4 S1P receptor agonist.

Harvard Medical School

Identification and Preclinical Pharmacology of BMS-986104: A Differentiated S1P1 Receptor Modulator in Clinical Trials.

Bristol-Myers Squibb

Novel S1P1 receptor agonists - Part 4: Alkylaminomethyl substituted aryl head groups.

Actelion Pharmaceuticals

Novel S1P1 receptor agonists - Part 5: From amino-to alkoxy-pyridines.

Actelion Pharmaceuticals

Potent and Selective Agonists of Sphingosine 1-Phosphate 1 (S1P1): Discovery and SAR of a Novel Isoxazole Based Series.

Bristol-Myers Squibb Research and Development

Identification and synthesis of potent and selective pyridyl-isoxazole based agonists of sphingosine-1-phosphate 1 (S1P1).

Bristol-Myers Squibb Research and Development

Synthesis, identification, and biological activity of metabolites of two novel selective S1P1 agonists.

Peking Union Medical College and Chinese Academy of Medical Sciences

Discovery of Tetrahydropyrazolopyridine as Sphingosine 1-Phosphate Receptor 3 (S1P3)-Sparing S1P1 Agonists Active at Low Oral Doses.

Glaxosmithkline

Discovery of novel S1P2 antagonists, part 3: Improving the oral bioavailability of a series of 1,3-bis(aryloxy)benzene derivatives.

Ono Pharmaceutical

Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

Boehringer Ingelheim Pharmaceuticals

Navigating CYP1A Induction and Arylhydrocarbon Receptor Agonism in Drug Discovery. A Case History with S1P1 Agonists.

Glaxosmithkline

Discovery of novel S1P2 antagonists. Part 2: Improving the profile of a series of 1,3-bis(aryloxy)benzene derivatives.

Ono Pharmaceutical

Identification and Optimization of Benzimidazole Sulfonamides as Orally Bioavailable Sphingosine 1-Phosphate Receptor 1 Antagonists with in Vivo Activity.

Astrazeneca

Novel Pyridyloxadiazole Agonists of Sphingosin-1-phosphate.

Dart Neuroscience

Discovery of heterocyclic sulfonamides as sphingosine 1-phosphate receptor 1 (S1P1) antagonists.

Astrazeneca

Discovery of novel S1P2 antagonists. Part 1: discovery of 1,3-bis(aryloxy)benzene derivatives.

Ono Pharmaceutical

Design and synthesis of new tricyclic indoles as potent modulators of the S1P1 receptor.

Arena Pharmaceuticals

Discovery of oxazole and triazole derivatives as potent and selective S1P(1) agonists through pharmacophore-guided design.

Peking Union Medical College and Chinese Academy of Medical Sciences

Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P1 agonists.

Daiichi Sankyo

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

Arena Pharmaceuticals

Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor.

Arena Pharmaceuticals

Optimization of sphingosine-1-phosphate-1 receptor agonists: effects of acidic, basic, and zwitterionic chemotypes on pharmacokinetic and pharmacodynamic profiles.

Glaxosmithkline

Piperazinyl-oxadiazoles as selective sphingosine-1-phosphate receptor agonists.

Boehringer Ingelheim Pharmaceuticals

Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator.

Genomics Institute of The Novartis Research Foundation

Exploring amino acids derivatives as potent, selective, and direct agonists of sphingosine-1-phosphate receptor subtype-1.

Praecis Pharmaceuticals Incorporated (Currently Glaxosmithkline)

Indole-propionic acid derivatives as potent, S1P3-sparing and EAE efficacious sphingosine-1-phosphate 1 (S1P1) receptor agonists.

Glaxosmithkline

Discovery of a novel class of zwitterionic, potent, selective and orally active S1P1 direct agonists.

RhôNe-Poulenc Rorer

An oral sphingosine 1-phosphate receptor 1 (S1P(1)) antagonist prodrug with efficacy in vivo: discovery, synthesis, and evaluation.

Novartis Pharma

A prospective cross-screening study on G-protein-coupled receptors: lessons learned in virtual compound library design.

Radboud University Nijmegen Medical Centre

Discovery of novel 1,2,4-thiadiazole derivatives as potent, orally active agonists of sphingosine 1-phosphate receptor subtype 1 (S1P(1)).

Glaxosmithkline

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

Arena Pharmaceuticals

Optimization of a Potent, Orally Active S1P1 Agonist Containing a Quinolinone Core.

TBA

Identification of benzoxazole analogs as novel, S1P(3) sparing S1P(1) agonists.

Glaxosmithkline

Synthesis and SAR of 1,3-thiazolyl thiophene and pyridine derivatives as potent, orally active and S1P3-sparing S1P1 agonists.

Daiichi Sankyo

Discovery of a novel class of potent and orally bioavailable sphingosine 1-phosphate receptor 1 antagonists.

Exelixis

4-Methoxy-N-[2-(trifluoromethyl)biphenyl-4-ylcarbamoyl]nicotinamide: A Potent and Selective Agonist of S1P1.

TBA

Discovery of thiadiazole amides as potent, S1P3-sparing agonists of sphingosine-1-phosphate 1 (S1P1) receptor.

Glaxosmithkline

Synthesis and SAR studies of a novel class of S1P1 receptor antagonists.

Sankyo

Constrained azacyclic analogues of the immunomodulatory agent FTY720 as molecular probes for sphingosine 1-phosphate receptors.

University of Montreal

Synthesis of 4(5)-phenylimidazole-based analogues of sphingosine-1-phosphate and FTY720: discovery of potent S1P1 receptor agonists.

University of Virginia

Synthesis of benzimidazole based analogues of sphingosine-1-phosphate: discovery of potent, subtype-selective S1P4 receptor agonists.

University of Virginia

Design and synthesis of conformationally constrained 3-(N-alkylamino)propylphosphonic acids as potent agonists of sphingosine-1-phosphate (S1P) receptors.

Merck Research Laboratories

The discovery of 3-(N-alkyl)aminopropylphosphonic acids as potent S1P receptor agonists.

Merck Research Laboratories

Synthesis of para-alkyl aryl amide analogues of sphingosine-1-phosphate: discovery of potent S1P receptor agonists.

University of Virginia

Synthesis and evaluation of CS-2100, a potent, orally active and S1P(3)- sparing S1P(1) agonist.

Daiichi Sankyo

Discovery of CS-2100, a potent, orally active and S1P3-sparing S1P1 agonist.

Daiichi Sankyo

Isoform-selective thiazolo[5,4-b]pyridine S1P1 agonists possessing acyclic amino carboxylate head-groups.

Amgen

Discovery of CS-0777: A Potent, Selective, and Orally Active S1P1 Agonist.

TBA

Quinolinone-based agonists of S1P¿?: use of a N-scan SAR strategy to optimize in vitro and in vivo activity.

Amgen

Novel 5- and 6-subtituted benzothiazoles with improved physicochemical properties: potent S1P¿? agonists with in vivo lymphocyte-depleting activity.

Amgen

Structure-activity relationship studies of S1P agonists with a dihydronaphthalene scaffold.

Ono Pharmaceutical

Novel immunomodulators based on an oxazolin-2-one-4-carboxamide scaffold.

Institute of Pharmacology & Toxicology

Discovery and characterization of potent and selective 4-oxo-4-(5-(5-phenyl-1,2,4-oxadiazol-3-yl)indolin-1-yl)butanoic acids as S1P¿? agonists.

Arena Pharmaceuticals

Discovery, synthesis and SAR analysis of novel selective small molecule S1P4-R agonists based on a (2Z,5Z)-5-((pyrrol-3-yl)methylene)-3-alkyl-2-(alkylimino)thiazolidin-4-one chemotype.

The Scripps Research Institute

Discovery of a brain-penetrant S1P3-sparing direct agonist of the S1P¿? and S1P5 receptors efficacious at low oral dose.

Glaxosmithkline

SAR analysis of innovative selective small molecule antagonists of sphingosine-1-phosphate 4 (S1P4) receptor.

The Scripps Research Institute

Discovery of S1P agonists with a dihydronaphthalene scaffold.

Ono Pharmaceutical

Discovery, design and synthesis of the first reported potent and selective sphingosine-1-phosphate 4 (S1P4) receptor antagonists.

The Scripps Research Institute

Structure-activity relationship studies of sphingosine-1-phosphate receptor agonists with N-cinnamyl-ß-alanine moiety.

Ono Pharmaceutical

Discovery of a Potent, S1P₃-Sparing Benzothiazole Agonist of Sphingosine-1-Phosphate Receptor 1 (S1P₁)

TBA

Discovery of AMG 369, a Thiazolo[5,4-b]pyridine Agonist of S1P₁ and S1P₅

TBA

Benzofuran Derivatives as Potent, Orally Active S1P₁ Receptor Agonists: A Preclinical Lead Molecule for MS

TBA

Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo.

The Scripps Research Institute

2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists.

Actelion Pharmaceuticals

Removal of sphingosine 1-phosphate receptor-3 (S1P(3)) agonism is essential, but inadequate to obtain immunomodulating 2-aminopropane-1,3-diol S1P(1) agonists with reduced effect on heart rate.

Mitsubishi Tanabe Pharma

Exploration of amino alcohol derivatives as novel, potent, and highly selective sphingosine-1-phosphate receptor subtype-1 agonists.

Praecis Pharmaceuticals

Stereochemistry-activity relationship of orally active tetralin S1P agonist prodrugs.

Biogen Idec

S1P receptor mediated activity of FTY720 phosphate mimics.

Novartis Institutes For Biomedical Research

Discovery of a novel series of potent S1P1 agonists.

Merck Serono

Pyrazole derived from (+)-3-carene; a novel potent, selective scaffold for sphingosine-1-phosphate (S1P(1)) receptor agonists.

Novartis Institutes For Biomedical Research

Synthesis and evaluation of arylalkoxy- and biarylalkoxy-phenylamide and phenylimidazoles as potent and selective sphingosine-1-phosphate receptor subtype-1 agonists.

Praecis Pharmaceuticals

Synthesis and evaluation of alkoxy-phenylamides and alkoxy-phenylimidazoles as potent sphingosine-1-phosphate receptor subtype-1 agonists.

Praecis Pharmaceuticals

Pharmacophore-based design of sphingosine 1-phosphate-3 receptor antagonists that include a 3,4-dialkoxybenzophenone scaffold.

Toa Eiyo

Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists.

University of Virginia

Discovery of 3-arylpropionic acids as potent agonists of sphingosine-1-phosphate receptor-1 (S1P1) with high selectivity against all other known S1P receptor subtypes.

Merck Research Laboratories

Highly selective and potent agonists of sphingosine-1-phosphate 1 (S1P1) receptor.

Merck

2-Aryl(pyrrolidin-4-yl)acetic acids are potent agonists of sphingosine-1-phosphate (S1P) receptors.

Merck Research Laboratories

2,5-Disubstituted pyrrolidine carboxylates as potent, orally active sphingosine-1-phosphate (S1P) receptor agonists.

Merck Research Laboratories

Discovery of Novel Sphingosine-1-Phosphate-1 Receptor Agonists for the Treatment of Multiple Sclerosis.

Korea Institute of Science & Technology (Kist)

The Repertoire of Small-Molecule PET Probes for Neuroinflammation Imaging: Challenges and Opportunities beyond TSPO.

Massachusetts General Hospital

Novel immunomodulator FTY720 is phosphorylated in rats and humans to form a single stereoisomer. Identification, chemical proof, and biological characterization of the biologically active species and its enantiomer.

Novartis Institutes For Biomedical Research

Synthesis and evaluation of highly selective quinazoline-2,4-dione ligands for sphingosine-1-phosphate receptor 2.

Washington University

Rational Design, Synthesis, and Biological Evaluation of Novel S1PR2 Antagonists for Reversing 5-FU-Resistance in Colorectal Cancer.

Ocean University of China

A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonists.

Merck Research Laboratories

Discovery and Optimization of Orally Bioavailable Phthalazone and Cinnolone Carboxylic Acid Derivatives as S1P2 Antagonists against Fibrotic Diseases.

Galapagos

Selecting against S1P3 enhances the acute cardiovascular tolerability of 3-(N-benzyl)aminopropylphosphonic acid S1P receptor agonists.

Merck Research Laboratories

Potent S1P receptor agonists replicate the pharmacologic actions of the novel immune modulator FTY720.

Merck Research Laboratories

Discovery of Potent Selective Nonzinc Binding Autotaxin Inhibitor BIO-32546.

Biogen

Identification and Preclinical Pharmacology of ((1 R,3 S)-1-Amino-3-(( S)-6-(2-methoxyphenethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986166): A Differentiated Sphingosine-1-phosphate Receptor 1 (S1P

Bristol-Myers Squibb Research and Development

Bicyclic Ligand-Biased Agonists of S1P

Bristol Myers Squibb Research & Early Development

Positional Analogue Scanning: An Effective Strategy for Multiparameter Optimization in Drug Design.

TBA

Novel Potent Selective Orally Active S1P5 Receptor Antagonists.

Biogen

Asymmetric Hydroboration Approach to the Scalable Synthesis of ((1R,3S)-1-Amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986104) as a Potent S1P

Bristol-Myers Squibb

Discovery of Soft-Drug Topical Tool Modulators of Sphingosine-1-phosphate Receptor 1 (S1PR1).

University of Dundee

Identification of Tricyclic Agonists of Sphingosine-1-phosphate Receptor 1 (S1P

Bristol-Myers Squibb

S1P

Peking Union Medical College and Chinese Academy of Medical Sciences

Small-molecule agents for the treatment of inflammatory bowel disease.

Gilead Sciences

Discovery and Structure-Activity Relationship (SAR) of a Series of Ethanolamine-Based Direct-Acting Agonists of Sphingosine-1-phosphate (S1P1).

Bristol-Myers Squibb

Design, synthesis, and in vitro bioactivity evaluation of fluorine-containing analogues for sphingosine-1-phosphate 2 receptor.

Washington University

An update on sphingosine-1-phosphate receptor 1 modulators.

The University of Arizona

Discovery of A-971432, An Orally Bioavailable Selective Sphingosine-1-Phosphate Receptor 5 (S1P5) Agonist for the Potential Treatment of Neurodegenerative Disorders.

Abbvie Bioresearch Center

Novel S1P(1) receptor agonists--part 3: from thiophenes to pyridines.

Actelion Pharmaceuticals

Novel S1P(1) receptor agonists--part 2: from bicyclo[3.1.0]hexane-fused thiophenes to isobutyl substituted thiophenes.

Actelion Pharmaceuticals

Discovery of Clinical Candidate GSK1842799 As a Selective S1P1 Receptor Agonist (Prodrug) for Multiple Sclerosis.

Praecis Pharmaceuticals

Sphingosine-1-phosphate (S1P) Receptor Modulators Provide Potential for Diverse Treatments.

Therachem Research Medilab (India)

Discovery, design and synthesis of a selective S1P(3) receptor allosteric agonist.

The Scripps Research Institute

Modulators of the Sphingosine 1-phosphate receptor 1.

The Scripps Research Institute

NBD-labeled derivatives of the immunomodulatory drug FTY720 as tools for metabolism and mode of action studies.

Novartis Institutes For Biomedical Research

Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1.

University of Dundee

Discovery of a 1-Methyl-3,4-dihydronaphthalene-Based Sphingosine-1-Phosphate (S1P) Receptor Agonist Ceralifimod (ONO-4641). A S1P

Ono Pharmaceutical

Modulators of Sphingosine-1-phosphate Pathway Biology: Recent Advances of Sphingosine-1-phosphate Receptor 1 (S1P

Bristol-Myers Squibb

Compounds for modulating S1P1 activity and methods of using the same

Trevena

Substituted bicyclic compounds

Bristol-Myers Squibb

Processes for the preparation of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[B]indol-3-yl)acetic acid and salts thereof

Arena Pharmaceuticals

Oxime ether compounds

Bristol-Myers Squibb

Alkylphenyl compounds

Bristol-Myers Squibb

Sphinogosine-1 -phosphate receptor modulators for treatment of cardiopulmonary disorders

The Scripps Research Institute

Spiro-cyclic amine derivatives as S1P modulators

Abbvie

Tetrahydronaphthalene derivative

Ono Pharmaceutical

Substituted bicyclic compounds

Bristol-Myers Squibb

Compositions for binding sphingosine-1-phosphate receptor 1 (S1P1), imaging of S1P1, and methods of use thereof

Washington University

Heterocyclic compounds for the treatment of disease

Oppilan Pharma

Modulators of sphingosine phosphate receptors

The Scripps Research Institute

Sphinogosine-1-phosphate receptor modulators for treatment of cardiopulmonary disorders

The Scripps Research Institute

Spiro-cyclic amine derivatives as S1P modulators

Abbvie

Pyridin-4-yl derivatives

Actelion Pharmaceuticals

Coumarin compounds as receptor modulators with therapeutic utility

Allergan

Aniline derivative, pharmaceutical composition containing same, and use thereof

Kissei Pharmaceutical

S1P receptors modulators and their use thereof

Akaal Pharma

Fused heterocyclic derivatives as S1P modulators

Abbvie

Substituted bicyclic compounds

Bristol-Myers Squibb

Heterocyclic group contained amino-methanol derivative, and salt, synthetic method and use thereof

Beijing Foreland Biopharma

Tricyclic heterocyclic compounds

Bristol-Myers Squibb

Substituted oxadiazole compounds

Bristol-Myers Squibb

S1P receptors modulators

Akaal Pharma

Processes for the preparation of (R)-2-(7-4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[B]indol-3-yl)acetic acid and salts thereof

Arena Pharmaceuticals

6-amino-pyrimidine-4-carboxamide derivatives and related compounds which bind to the sphingosine 1-phosphate (S1P) receptor for the treatment of multiple sclerosis

Merck Serono

Oxadiazole diaryl compounds

Merck Serono

Mandelamide heterocyclic compounds

Bristol-Myers Squibb

Substituted 3-phenyl-1,2,4-Oxadiazole compounds

Bristol-Myers Squibb

Pyrazole oxadiazole derivatives as S1P1 agonists

Merck Serono

Aryl benzylamine compounds

Novartis

Oxadiazole fused heterocyclic derivatives useful for the treatment of multiple sclerosis

Merck Serono

Heterocyclic compounds as S1P1 agonists for the treatment of autoimmune and vascular diseases

Bristol-Myers Squibb

Asymmetric synthesis and biological evaluation of the enantiomeric isomers of the immunosuppressive FTY720-phosphate.

Mitsubishi Pharma

SAR studies of 3-arylpropionic acids as potent and selective agonists of sphingosine-1-phosphate receptor-1 (S1P1) with enhanced pharmacokinetic properties.

Merck Research Laboratories

Discovery of potent 3,5-diphenyl-1,2,4-oxadiazole sphingosine-1-phosphate-1 (S1P1) receptor agonists with exceptional selectivity against S1P2 and S1P3.

Merck Research Laboratories