TRICYCLIC SULPHONAMIDE COMPOUNDS AND METHODS OF MAKING AND USING SAME

摘要

The invention provides tricyclic compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various tricyclic compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.

主权项

1. A compound selected from the group consisting of: (1aR,7bS)-5-[2-(2-diethylaminomethylcyclopropyl)-4-fluoro-benzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid, or enantiomers thereof; (1aR,7bS)-5-{4-fluoro-2-[2-(pyrrolidin-1-ylmethyl)cyclopropyl]-benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR,7bS)-5-[2-(3-diethylamino-2,2-dimethylpropyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopro-[c]chromene-4-carboxylic acid; (1aR,7bS)-5-[4-fluoro-2-((R)-pyrrolidin-3-ylmethyl)benzene-sulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5-[4-fluoro-2-((S)-pyrrolidin-3-ylmethyl)benzene-sulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa [c]chromene-4-carboxylic acid; (1aR,7bS)-5-{4-fluoro-2-[(R)-1-(2-hydroxy-2-methylpropyl)-pyrrolidin-3-ylmethyl]benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa [c]chromene-4-carboxylic acid; (1aR,7bS)-5-[2-(1-azabicyclo[2.2.2]oct-3-ylmethyl)-4-fluoro-benzenesulfonylamino]-1,1a,2,7b-tetrahydro cyclopropa-[c]chromene-4-carboxylic acid; (1aR,7bS)-5-[2-((Z)-1-azabicyclo[2.2.2]oct-3-ylidenemethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR,7bS)-5-[2-((E)-1-azabicyclo[2.2.2]oct-3-ylidenemethyl)-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR,7bS)-5-{2-[(E)-(1-ethylpiperidin-3-ylidene)methyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR,7bS)-5-{2-[(Z)-(1-ethylpiperidin-3-ylidene)methyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid, or enantiomers thereof; (1aR,7bS)-5-{2-[2-((S)-1-ethylpyrrolidin-2-yl)ethyl]-4-fluoro-benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR,7bS)-5-{4-fluoro-2-[(R)-1-(2-hydroxyethyl)pyrrolidin-3-ylmethyl]benzenesulfonylamino}-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5-[2-((endo)-8-ethyl-8-azabicyclo[3.2.1]oct-3-yl)methyl-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa [c]chromene-4-carboxylic acid; (1aR,7bS)-5-[2-((exo)-8-ethyl-8-azabicyclo[3.2.1]oct-3-yl)methyl-4-fluorobenzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa [c]chromene-4-carboxylic acid; (1aR,7bS)-5-{4-fluoro-2-[(Z)-3-(3-hydroxy-3-methylpyrrolidin-1-yl)prop-1-enyl]benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5{4-fluoro-2-[(Z)-3-(4-hydroxypiperidin-1-yl)prop-1-enyl]benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR,7bS)-5-{4-fluoro-2-[(Z)-3-(4-hydroxy-4-methylpiperidin-1-yl)prop-1-enyl]benzenesulfonylamino}-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5-[2-(3-ethyl-3-azabicyclo[3.1.0]hex-6-yl)-4-fluoro-benzenesulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1aR,7bS)-5-{4-fluoro-2-[(Z)-2-((S)-pyrrolidin-2-yl)ethenyl]-benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid; (1) enyl]benzenesulfonylamino}-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5-{4-fluoro-2-[(Z)-3-((R)-3-hydroxymethylpyrrolidin-1-yl)prop-1-enyl]benzenesulfonylamino}-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5-(4-fluoro-2-{(Z)-3-[(S)-3-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]prop-1-enyl}benzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5-(4-fluoro-2-{(Z)-3-[(R)-3-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]prop-1-enyl}benzenesulfonylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5-[4-fluoro-2-(hexahydro-1H-pyrrolizin-2-ylmethyl)benzenesulfonylamino]-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5-{2-[((S)-1-ethylpyrrolidin-3-ylcarbamoyl)methyl]-4-fluoro-benzenesulfonylamino}-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5-[2-((3R)-1-ethylpyrrolidin-3-ylmethyl)benzene-sulfonylamino]-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylic acid; (1aR,7bS)-5-{2-[((S)-1-ethylpyrrolidine-3-carbonyl)amino-methyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydro-cyclopropa[c]chromene-4-carboxylic acid-formic acid (1:1); (1aR,7bS)-5-{2-[2-((R)-1-ethylpyrrolidin-3-ylamino)ethyl]-4-fluorobenzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylic acid-formic acid (1:1) and pharmaceutically acceptable salts, stereoisomers, esters and prodrugs thereof.