1307812-49-2

Upstream product

• 1307812-08-3 6-Vinyl-3,4-dihydronaphthalen-1(2H)-one 
• 1307812-05-0 6-vinyl-3,4-dihydronaphthalen-1(2H)-one oxime 
• 1307812-10-7 methyl 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylate 
• 1236188-87-6 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylic acid 
• 1236188-86-5 ethyl 5-phenyl-4-(trifluoromethyl)isoxazole-3-carboxylate 
• 1236188-85-4 ethyl 4-iodo-5-phenylisoxazole-3-carboxylate 
• 144464-64-2 5-oxo-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate 
• 3470-50-6 6-Hydroxy-1-tetralone 
• 536-74-3 phenylacetylene 
• 7063-99-2 ethyl 5-phenylisoxazole-3-carboxylate 

Downstream Products

• 1307814-45-4 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde 
• 1307813-97-3 C₂₈H₂₆F₃N₃O₄ 
• 1307813-96-2 C₃₂H₃₂F₃N₃O₄ 
• 1307813-95-1 C₂₉H₂₈F₃N₃O₄ 
• 1307810-44-1 4-(((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)morpholino-3-yl)methanol 
• 1307810-42-9 3-(methyl((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)amino)propanamide 
• 1307810-40-7 2-((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methylamino)acetic acid 
• 1307810-39-4 (3S)-1-((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]-7-yl)methyl)piperidine-3-carboxylic acid 
• 1307810-38-3 3-((3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methylamino)propanoic acid 
• 1307811-63-7 C₃₀H₂₈F₃N₃O₅ 
• 1307811-62-6 C₃₀H₂₈F₃N₃O₅ 
• 1307809-76-2 2-((3R)-l-(2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)ethyl)piperidin-3-yl)acetic acid hydrochloride 
• 1307812-72-1 ethyl 2-((3R)-1-(2-hydroxy-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)ethyl)piperidin-3-yl)acetate 
• 1307811-61-5 C₂₉H₂₆F₃N₃O₅ 

Relevant academic research and scientific papers

Identification of Tricyclic Agonists of Sphingosine-1-phosphate Receptor 1 (S1P1) Employing Ligand-Based Drug Design

Fingolimod (1) is the first approved oral therapy for the treatment of relapsing remitting multiple sclerosis. While the phosphorylated metabolite of fingolimod was found to be a nonselective S1P receptor agonist, agonism specifically of S1P1 is responsible for the peripheral blood lymphopenia believed to be key to its efficacy. Identification of modulators that maintain activity on S1P1 while sparing activity on other S1P receptors could offer equivalent efficacy with reduced liabilities. We disclose in this paper a ligand-based drug design approach that led to the discovery of a series of potent tricyclic agonists of S1P1 with selectivity over S1P3 and were efficacious in a pharmacodynamic model of suppression of circulating lymphocytes. Compound 10 had the desired pharmacokinetic (PK) and pharmacodynamic (PD) profile and demonstrated maximal efficacy when administered orally in a rat adjuvant arthritis model.

TRICYCLIC HETEROCYCLIC COMPOUNDS

Disclosed are compounds of Formula (I) or stereoisomers or salts thereof, wherein: X1, X2, X3, W, Q1, Q2, and G2 are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.