Selectively substituted quinoline compounds

Abstract

Embodiments of the disclosure relate to selectively substituted quinoline compounds that act as antagonists or inhibitors for Toll-like receptors 7 and/or 8, and their use in pharmaceutical compositions effective for treatment of systemic lupus erythematosus (SLE) and lupus nephritis.

We claim: 
     
         1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1  and R 2  is —H, methyl, or ethyl, and the other is
 —H; or the other is 
 C 1 -C 6  alkyl that is optionally substituted with:
 —OH, methoxy, ethoxy, —OCH(CH 3 ) 2 , —O(CH 2 ) 2 CH 3 , phenyl, furanyl, —O(CH 2 ) 2 OH, phenoxy, methylthio, —F, —N(CH 3 ) 2 , cyano, pyridinyloxy, fluorophenoxy, isochromanyl, phenol, benzylamino, —NHCH 3 , oxo-, amino, carboxyl, 7-member spiroaminyl, a three to six member cycloalkyl, saturated or unsaturated and optionally including one or more heteroatoms selected from O and N, and optionally substituted at one or more C or N atoms by methyl, cyano, fluoro, methylamino, or trifluoromethyl; or the other is 
 
 C 3 -C 7  cycloalkane, saturated or unsaturated, optionally bridged, optionally including one or more heteroatoms selected from O, S, and N, and optionally substituted at one or more C or N atoms by methyl, ethyl, pyridinyl, azetidinyl, acetamidyl, carboxamidyl, cyano, fluoro, methylamino, or trifluoromethyl; or 
 
       R 1  and R 2 , together with the nitrogen atom to which they are attached, form an 8 to 11 member spirodiamine, an 8 member bicyclodiamine, a 7 member spiroxamine, a piperidinyl optionally substituted with ethyl, or a four to six member cycloalkyl, optionally substituted with at least one of carboxamidyl, aminomethyl, methyl, (ethylamino)methyl, (dimethylamino)methyl, dimethylamino, (methylamino)methyl, and amino; and wherein 
       R 3  is —H or methyl. 
     
     
         2 . The compound of  claim 1 , wherein said compound is selected from the group consisting of:
 5-((2R,6R)-2-formyl-6-methylmorpholino)quinoline-8-carbonitrile;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-ethyl-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-isopropyl-6-methylmorpholine-2-carboxamide;   5-((2R,6R)-2-formyl-6-methylmorpholino)quinoline-8-carbonitrile;   (2R,6R)-methyl 4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxylate;   (6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   5-((2R,6R)-2-((S)-3-ethylpiperazine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(3,4-difluorobenzyl)-6-methylmorpholine-2-carboxamide;   5-((2R,6R)-2-((S)-3-aminopyrrolidine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(azetidine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-([1,4′-bipiperidine]-1′-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-cyclopropyl-6-methylmorpholine-2-carboxamide;   5-((2R,6R)-2-(3-aminoazetidine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-hydroxyethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-methoxyethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((R)-2-hydroxypropyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((S)-1-hydroxypropan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((R)-1-hydroxypropan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((S)-1-hydroxybutan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((S)-1-hydroxy-3-methylbutan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((S)-2-hydroxy-1-phenylethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((R)-2-hydroxy-1-phenylethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-hydroxybutyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-ethoxyethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((R)-1-hydroxybutan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(1,3-dihydroxypropan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2,3-dihydroxypropyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—(((R)-tetrahydrofuran-2-yl)methyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-((tetrahydrofuran-2-yl)methyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(2-propoxyethyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((R)-1-hydroxypentan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-isopropoxyethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(1-methoxybutan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-(2-fluorophenyl)-2-hydroxyethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((R)-1-hydroxy-3-methylbutan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2,2-dimethoxyethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-(2-hydroxyethoxy)ethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((1S,2S)-2-hydroxycyclohexyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-hydroxycyclohexyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(1-hydroxyhexan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((S)-1-hydroxy-3,3-dimethylbutan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((S)-1-hydroxyhexan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((2S,3S)-1-hydroxy-3-methylpentan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((S)-1-hydroxy-4-methylpentan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((R)-1-hydroxy-4-methylpentan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-((4-methylmorpholin-2-yl)methyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((S)-1-hydroxy-4-(methylthio)butan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(2-phenoxyethyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((S)-1-hydroxy-3-phenylpropan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(2-phenoxypropyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-hydroxy-3-phenylpropyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(2-(pyridin-3-yloxy)propyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-(4-fluorophenoxy)ethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-(3-fluorophenyl)-2-hydroxyethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N—((S)-1-cyclohexyl-3-hydroxypropan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(isochroman-1-ylmethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-hydroxy-3-phenoxypropyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((1S,2R)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((1S)-1,3-dihydroxy-1-phenylpropan-2-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-hydroxy-3-(piperazin-1-yl)propyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)—N-(azetidin-3-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((S)-pyrrolidin-3-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((R)-pyrrolidin-3-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((S)-piperidin-3-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((R)-piperidin-3-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((S)-pyrrolidin-2-ylmethyl)morpholine-2-carboxamide;   (2R,6R)—N-(2-(benzylamino)ethyl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(pyridin-2-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(6-methylpyridin-2-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(5-methylisoxazol-3-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(2,2,2-trifluoroethyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2,2-difluoroethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(3,3,3-trifluoropropyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-(dimethylamino)-2-methylpropyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((S)-morpholin-2-ylmethyl)morpholine-2-carboxamide hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—(((S)-4-methylmorpholin-2-yl)methyl)morpholine-2-carboxamide acetic acetate;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-fluoroethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(3-fluoropropyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((S)-1,1,1-trifluoropropan-2-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((R)-1,1,1-trifluoropropan-2-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(1,3-dimethyl-1H-pyrazol-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(1-methyl-1H-pyrazol-5-yl)morpholine-2-carboxamide;   (2R,6R)—N-(cyanomethyl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)—N-(1-cyanocyclopropyl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(1,2,4-thiadiazol-5-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(3-methyl-1,2,4-thiadiazol-5-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(piperidin-4-yl)morpholine-2-carboxamide;   5-((2R,6R)-2-methyl-6-(2,6-diazaspiro[3.4]octane-2-carbonyl)morpholino)quinoline-8-carbonitrile hydrochloride;   5-((2R,6R)-2-methyl-6-(3-((methylamino)methyl)azetidine-1-carbonyl)morpholino)quinoline-8-carbonitrile hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((4-fluoropiperidin-4-yl)methyl)-6-methylmorpholine-2-carboxamide hydrochloride;   (2R,6R)—N-(azetidin-3-ylmethyl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   5-((2R,6R)-2-methyl-6-(2,6-diazaspiro[3.5]nonane-2-carbonyl)morpholino)quinoline-8-carbonitrile hydrochloride;   5-((2R,6R)-2-methyl-6-(1,6-diazaspiro[3.4]octane-1-carbonyl)morpholino)quinoline-8-carbonitrile hydrochloride;   5-((2R,6R)-2-methyl-6-(1,7-diazaspiro[4.4]nonane-7-carbonyl)morpholino)quinoline-8-carbonitrile hydrochloride;   (2R,6R)—N-(3-carbamoyl-1-methyl-1H-pyrazol-4-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(oxetan-3-ylmethyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(tetrahydro-2H-pyran-4-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(tetrahydrofuran-3-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-((3-methyloxetan-3-yl)methyl)morpholine-2-carboxamide;   5-((2R,6R)-2-methyl-6-(2-oxa-6-azaspiro[3.3]heptane-6-carbonyl)morpholino)quinoline-8-carbonitrile;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(oxetan-3-yl)morpholine-2-carboxamide;   (2R,6R)—N-((3-(aminomethyl)oxetan-3-yl)methyl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(oxetan-2-ylmethyl)morpholine-2-carboxamide;   5-((2R,6R)-2-methyl-6-(piperazine-1-carbonyl)morpholino)quinoline-8-carbonitrile hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(2-(methylamino)ethyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((S)-3,3,3-trifluoro-2-hydroxypropyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((R)-3,3,3-trifluoro-2-hydroxypropyl)morpholine-2-carboxamide;   methyl 2-((2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamido)acetate;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(2-(dimethylamino)ethyl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((S)-4,4,4-trifluoro-3-hydroxybutyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((R)-4,4,4-trifluoro-3-hydroxybutyl)morpholine-2-carboxamide;   (2R,6R)—N-(3-amino-4,4,4-trifluorobutyl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   2-((2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamido)acetic acid;   1-((2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carbonyl)azetidine-3-carboxamide;   5-((2R,6R)-2-methyl-6-(2,7-diazaspiro[4.4]nonane-2-carbonyl)morpholino)quinoline-8-carbonitrile hydrochloride;   5-((2R,6R)-2-methyl-6-(3,9-diazaspiro[5.5]undecane-3-carbonyl)morpholino)quinoline-8-carbonitrile hydrochloride;   (2R,6R)—N-(3-carbamoylpyridin-4-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((R)-morpholin-2-ylmethyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(pyridin-4-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(pyridin-3-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)morpholine-2-carboxamide hydrochloride;   (2R,6R)—N-(1-(azetidin-3-yl)-1H-pyrazol-4-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   (2R,6R)—N-((1H-pyrazol-5-yl)methyl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)—N-((1H-pyrazol-4-yl)methyl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-((3-(trifluoromethyl)pyridin-2-yl)methyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(1-(pyridin-2-yl)ethyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(pyridin-2-ylmethyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-((6-methylpyridin-2-yl)methyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-((1-methylpiperidin-2-yl)methyl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-((3-methylpyridin-2-yl)methyl)morpholine-2-carboxamide;   (2R,6R)—N-(4-cyano-1H-pyrazol-3-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((3S,4R)-4-fluoro-1-methylpyrrolidin-3-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((3S,4R)-4-fluoropiperidin-3-yl)-N,6-dimethylmorpholine-2-carboxamide hydrochloride;   5-((2R,6R)-2-(3-(aminomethyl)azetidine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(3-((ethylamino)methyl)azetidine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(3-((dimethylamino)methyl)azetidine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(1-methylazepan-4-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(((2R,6R)-6-methylmorpholin-2-yl)methyl)morpholine-2-carboxamide;   5-((2R,6R)-2-methyl-6-(octahydropyrrolo[3,4-c]pyrrole-2-carbonyl)morpholino)quinoline-8-carbonitrile;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((R)-pyrrolidin-2-ylmethyl)morpholine-2-carboxamide hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((S)-piperidin-2-ylmethyl)morpholine-2-carboxamide hydrochloride;   (2R,6R)—N-((1R,3R,5S)-8-azabicyclo[3.2.1]octan-3-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   (2R,6R)—N-(azepan-4-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   (2R,6R)—N-((1R,5S,6S)-3-azabicyclo[3.1.0]hexan-6-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-6-dimethylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(((2S,6R)-4,6-dimethylmorpholin-2-yl)methyl)-6-methylmorpholine-2-carboxamide;   5-((2R,6R)-2-(4-(dimethylamino)piperidine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(1-methylpiperidin-4-yl)morpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((3S,4R)-4-fluoropyrrolidin-3-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((3S,4R)-4-fluoropiperidin-3-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(2-azaspiro[3.3]heptan-6-yl)morpholine-2-carboxamide hydrochloride;   (2R,6R)—N-(1-(2-amino-2-oxoethyl)piperidin-4-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   5-((2R,6R)-2-(4-aminopiperidine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(4-amino-4-methylpiperidine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N,6-dimethyl-N—((R)-piperidin-3-yl)morpholine-2-carboxamide hydrochloride;   (2R,6R)—N-(2-carbamoylpyridin-4-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-6-dimethyl-N—((S)-piperidin-3-yl)morpholine-2-carboxamide hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(1-ethylpiperidin-4-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(1-ethylpiperidin-3-yl)-6-methylmorpholine-2-carboxamide;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N—((R)-1-methylpiperidin-3-yl)morpholine-2-carboxamide hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(4-methylpiperidin-4-yl)morpholine-2-carboxamide;   (2R,6R)—N-(2-amino-2-methylpropyl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide;   rel-(2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((3R,4S)-4-fluoropyrrolidin-3-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   rel-(2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((3S,4R)-4-fluoropyrrolidin-3-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   (2R,6R)—N-(azepan-3-yl)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxamide hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(1-methylazepan-3-yl)morpholine-2-carboxamide hydrochloride;   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(1,4-dimethylpiperidin-4-yl)-6-methylmorpholine-2-carboxamide; and   (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-(4-fluoro-1-methylpiperidin-3-yl)-6-methylmorpholine-2-carboxamide hydrochloride.   
     
     
         3 . The compound of  claim 2 , wherein said compound is selected from the group consisting of rel-(2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((3R,4S)-4-fluoropyrrolidin-3-yl)-6-methylmorpholine-2-carboxamide hydrochloride and (2R,6R)-4-(8-cyanoquinolin-5-yl)-6-methyl-N-(1-methylpiperidin-4-yl)morpholine-2-carboxamide. 
     
     
         4 . A compound of Formula (Ie), with relative stereochemistry indicated: 
       
         
           
           
               
               
           
         
       
     
     
         5 . A compound of Formula (II): 
       
         
           
           
               
               
           
         
       
       wherein 
       R 4  is —H or methyl; 
       R 5  is C 1 -C 5  alkyl that is saturated, partially saturated, or unsaturated, and that is optionally substituted with:
 —H, —Cl, —F, —OH, —NH 2 , oxo-, —N(CH 2 CH 3 ) 2 , phenyl, cyclohexyl, phenyltriazolyl, cyclohexyltriazolyl, pyridinyl, pyrrolidinyl, 
 morpholinyl optionally substituted with methyl or hydroxymethyl, 
 —O—, substituted with:
 C 1 -C 6  alkyl, methylphenyl, methylcyclohexyl, pyridinyl, diazinyl, or phenyl optionally substituted with —F or methyl, 
 
 —NH—, substituted with:
 C 2 -C 7  alkyl that is linear, branched, or cyclic, saturated or unsaturated, and optionally substituted with oxo-, phenyl, methyl, or —OH, 
 pyridinyl optionally substituted with methyl, methoxy, phenyl, or amino, 
 diazinyl optionally substituted with ethyl, 
 benzoimidazolyl, methylphenyl, phenylpyrazolyl, naphthyridyl, 
 phenyl optionally substituted with —F, methyl, ethyl, or ethoxy, 
 imidazolidinyl optionally substituted with methyl 
 
 
       or R 5  is 
       
         
           
           
               
               
           
         
       
       wherein n is 1-3, and wherein the cyclic amine is optionally substituted with
 C 1 -C 3  alkyl optionally substituted with
 —OH, —F, phenyl, —NH 2 , cyclohexyl, —N(CH 3 ) 2 , —C(O)NH 2 , methylsulfonamidyl, benzenesulfonamidyl, methylbenzenesulfonamidyl, or 
 pyrrolidinyl optionally substituted with methyl or hydroxyl, or 
 
 —NHC(O)R 6 , wherein R 6  is
 C 1 -C 5  alkyl, phenyl, pyridinyl, fluorophenyl, methylsulfonyl, fluorobenzenesulfonyl, dimethyl pyrazole sulfonyl, or 
 pyrazolyl optionally substituted with methyl; 
 
 piperidinyl optionally substituted with —C(O)CH 3 , —C(O)CH 2 CH 3 , methyl, oxo-, C(O)Ph, —NH 2 , —NH—C(O)CH 3 , or 
 
       
         
           
           
               
               
           
         
         piperazinyl optionally substituted with —C(O)OC(CH 3 ) 3 , methyl, —C(O)CH 3 , —C(O)Ph, C(O)CH(CH 3 ) 2 , —C(O)CH 3 , or methylsulfonyl; or 
       
       R 5  is 
       
         
           
           
               
               
           
         
       
       where n is 1 or 2, and wherein the cyclic diamine is optionally substituted on at least one carbon atom with
 methyl, oxo-, —N(CH 3 ) 2 , amino, —CH 2 CH 3 , or 
 piperidinyl optionally substituted with methyl, —C(O)CH 3 , —C(O)CH(CH 3 ) 2 , —C(O)Ph, or —C(O)OC(CH 3 ) 3 , and 
 wherein R 7  is —H, phenyl, —C(O)CH 3 , C 1 -C 3  alkyl, —C(O)NH 2 , or —C(O)Ph; and 
 R 8  is methoxy or cyano. 
 
     
     
         6 . The compound of  claim 2 , wherein said compound is selected from the group consisting of:
 5-((2R,6S)-2,6-dimethylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2,6-dimethylmorpholino)quinoline-8-carbonitrile dihydrochloride;   5-((2R,6S)-2,6-dimethylmorpholino)quinoline-8-carbonitrile methanesulfonate;   5-((2R,6S)-2,6-dimethylmorpholino)quinoline-8-carbonitrile bis(2,2,2-trifluoroacetate);   5-((2R,6S)-2,6-dimethylmorpholino)quinoline-8-carbonitrile bis(sulfonate);   5-((2R,6S)-2,6-dimethylmorpholino)quinoline-8-carbonitrile sulfonate;   5-((2S,6R)-2,6-dimethylmorpholino)quinoline-8-carbonitrile 2,3-dihydroxysuccinate;   5-((2S,6R)-2,6-dimethylmorpholino)quinoline-8-carbonitrile dimethanesulfonate;   5-(2-(chloromethyl)morpholino)quinoline-8-carbonitrile;   (S)-5-(2-(chloromethyl)morpholino)quinoline-8-carbonitrile;   N-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)acetamide;   N-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)pivalamide;   5-(2-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6S)-2,6-dimethylmorpholino)quinoline-8-carbonitrile;   5-(2-ethylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(aminomethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-(2-(hydroxymethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   (2R,6S)-4-(8-methoxyquinolin-5-yl)-2,6-dimethylmorpholine;   5-((2R,6S)-2,6-dimethylmorpholino)quinoline-8-carboxamide;   (R)-5-(2-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(hydroxymethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(methoxymethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((benzyloxy)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(fluoromethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(ethoxymethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(isopropoxymethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(isobutoxymethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(chloromethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((hexyloxy)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((cyclohexylmethoxy)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-propylmorpholino)quinoline-8-carbonitrile;   5-((2S,6S)-2-(fluoromethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6S)-2-(chloromethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((2,6-dimethylphenoxy)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2,6-diethylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-pentylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-formyl-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((benzyloxy)methyl)-6-ethylmorpholino)quinoline-8-carbonitrile;   N-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)-2-phenylpropanamide;   5-((2R,6R)-2-(1-hydroxyallyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((S)-1-hydroxyallyl)-6-methylmorpholino)quinoline-8-carbonitrile;   N-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)-1-phenylcyclobutanecarboxamide;   5-((2R,6R)-2-((R)-1-hydroxyallyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(pyrrolidin-1-ylmethyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((diethylamino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((benzylamino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-(phenoxymethyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((m-tolyloxy)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((p-tolyloxy)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(1-hydroxypropyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((R)-1-hydroxypentyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((S)-1-hydroxypentyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(((R)-cyclohexyl(hydroxy)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((S)-cyclohexyl(hydroxy)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   N-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)-2-phenylacetamide;   5-((2R,6R)-2-((R)-1-hydroxy-2-phenylethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((S)-1-hydroxy-2-phenylethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((R)-1-hydroxy-3-phenylpropyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((S)-1-hydroxy-3-phenylpropyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((phenylamino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((m-tolylamino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((o-tolylamino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((p-tolylamino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((3,4-difluorophenoxy)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((3-fluorophenoxy)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((1,2-dimethyl-1H-benzo[d]imidazol-5-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((1-ethyl-2-methyl-1H-benzo[d]imidazol-5-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((cyclohexylamino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((2-fluorophenoxy)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-propionylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-(cyclohexanecarbonyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-(3-phenylpropanoyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((o-tolyloxy)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((pyrimidin-2-ylamino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((pyridin-2-ylamino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((6-methylpyridin-2-yl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((5-methylpyridin-2-yl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((R)-2-(hydroxymethyl)pyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((2,2-dimethylpyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((2-isopropylpyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((S)-2-methylpyrrolidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((S)-3-phenylpyrrolidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((R)-3-methylpyrrolidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((S)-3-hydroxypyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((4-methylpyridin-2-yl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((3-phenylpyrrolidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((6-methoxypyridin-3-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((R)-2-methylpyrrolidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((2,5-dimethylpyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((4-methoxypyridin-2-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((6-methoxypyridin-2-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((1-phenyl-1H-pyrazol-5-yl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((S)-2-(hydroxymethyl)pyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((R)-3-hydroxypyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((S)-3-methylpyrrolidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((3,3-dimethylpyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((R)-3-phenyl-1-(pyrrolidin-1-yl)propyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((S)-3-phenyl-1-(pyrrolidin-1-yl)propyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((3-methoxypyridin-2-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((R)-3-hydroxypiperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((2R,6S)-2,6-dimethylpiperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((S)-3-hydroxypiperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-hydroxypiperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((2-(hydroxymethyl)piperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((2-methylpiperidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((2-ethylpiperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((2,3-dimethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((pyridin-3-ylamino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((pyridin-4-ylamino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((S)-2-(trifluoromethyl)pyrrolidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-methylpiperidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4,4-difluoropiperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-phenylpiperidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-fluoropiperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((cyclopentylamino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((3-methylcyclohexyl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((3-methylpyridin-2-yl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-ethyl-6-(hydroxymethyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((4-phenylpyridin-2-yl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(piperazin-1-ylmethyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-phenylpiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((6-aminopyridin-2-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((2,5-dimethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-acetylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((2S,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((R)-2-methylpiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((R)-3-methylpiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((S)-3-methylpiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((2R,5R)-2,5-dimethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((2R,5S)-2,5-dimethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((4-methylcyclohexyl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((cyclobutylamino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((cycloheptylamino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((4-hydroxycyclohexyl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((2-hydroxycyclopentyl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((2-methylcyclohexyl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((5-phenylpyridin-2-yl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((3-phenylpyridin-2-yl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((((1S,3R)-3-hydroxycyclopentyl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((3-ethoxypyridin-2-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((2-phenylpyridin-4-yl)amino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((6-phenylpyridin-2-yl)amino)methyl)morpholino)quinoline-8-carbonitrile;   (S)-5-(2-((pyridin-2-ylamino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((2-methyl-5-oxopiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-methylpiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-propylpiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-(dimethylamino)piperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-([1,4′-bipiperidin]-1′-ylmethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-([1,4′-bipiperidin]-1′-ylmethyl)-6-methylmorpholino)quinoline-8-carbonitrile dihydrochloride;   5-((2S,6R)-2-(((R)-3-aminopiperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   (2R,6S)-4-(8-chloro-1,7-naphthyridin-5-yl)-2,6-dimethylmorpholine;   5-((2S,6R)-2-((4-aminopiperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((5-fluoropyrimidin-2-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(piperidin-1-ylmethyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(morpholinomethyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((2S,6R)-2,6-dimethylmorpholino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((2R,6R)-2-(hydroxymethyl)-6-methylmorpholino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-(pyridin-2-yl)piperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-(pyridin-4-yl)piperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)acetamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)acetamide hydrochloride;   5-((2S,6R)-2-(((1,8-naphthyridin-2-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidine-4-carboxamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)benzamide;   5-((2S,6R)-2-((4-isopropylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   4-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperazine-1-carboxamide;   5-((2S,6R)-2-((4-cyclohexylpiperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-(pyrrolidin-1-yl)piperidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-((4-cyclohexyl-1H-1,2,3-triazol-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((2-oxo-[1,4′-bipiperidin]-1′-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((5-ethylpyrimidin-2-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((6-amino-3,5-dimethylpyridin-2-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((pyrazin-2-ylamino)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((1,3-dimethyl-1H-pyrazol-5-yl)amino)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,7R)-2-(hydroxymethyl)-7-methyl-1,4-oxazepan-4-yl)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-ethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((3-(pyrrolidin-1-yl)azetidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((3-(piperidin-1-yl)azetidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((R)-2,4-dimethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-(hydroxymethyl)piperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((R)-[1,3′-bipyrrolidin]-1′-ylmethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((R)-3-(piperidin-1-yl)pyrrolidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-methyl-1,4-diazepan-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-benzoylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)nicotinamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)isonicotinamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)picolinamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)hexanamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)isobutyramide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)isobutyramide hydrochloride;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)pivalamide;   5-((2S,7R)-2-([1,4′-bipiperidin]-1′-ylmethyl)-7-methyl-1,4-oxazepan-4-yl)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-morpholinopiperidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   1 tert-butyl 4-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)piperazine-1-carboxylate;   1 tert-butyl 4-(4-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperazin-1-yl)piperidine-1-carboxylate;   5-((2R,6S)-2-methyl-6-((4-(piperazin-1-yl)piperidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-(piperidin-4-yl)piperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((3-(4-methylpiperazin-1-yl)azetidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-([4,4′-bipiperidin]-1-ylmethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((1′-acetyl-[4,4′-bipiperidin]-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((1′-methyl-[4,4′-bipiperidin]-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((3-(piperazin-1-yl)azetidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((3-(4-acetylpiperazin-1-yl)azetidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((1′-isobutyryl-[4,4′-bipiperidin]-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((3-(4-benzoylpiperazin-1-yl)azetidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((1′-benzoyl-[4,4′-bipiperidin]-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-(1-methylpiperidin-4-yl)piperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-(1-acetylpiperidin-4-yl)piperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-(1-isobutyrylpiperidin-4-yl)piperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-(1-benzoylpiperidin-4-yl)piperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((3-(4-isobutyrylpiperazin-1-yl)azetidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-(4-acetylpiperazin-1-yl)piperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-(4-isobutyrylpiperazin-1-yl)piperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-(4-benzoylpiperazin-1-yl)piperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-(4-methylpiperazin-1-yl)piperidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((4-(4-methylpiperazin-1-yl)piperidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile trihydrochloride;   5-((2S,6R)-2-([1,4′-bipiperidin]-1′-ylmethyl)-6-methylmorpholino)-2-methylquinoline-8-carbonitrile;   N—((R)-1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)pyrrolidin-3-yl)acetamide;   N—((R)-1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)pyrrolidin-3-yl)isobutyramide;   5-((2R,6S)-2-methyl-6-(((S)-3-(piperidin-1-yl)pyrrolidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((S)-3-(piperidin-1-yl)pyrrolidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile dihydrochloride;   5-((2R,6S)-2-methyl-6-((3-morpholinoazetidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((3-((S)-2-methylpyrrolidin-1-yl)azetidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((S)-2-methylpiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((S)-2,4-dimethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((R)-3,4-dimethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((S)-3,4-dimethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((S)-3-ethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-(((S)-3-ethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile dihydrochloride;   5-((2S,6R)-2-(((S)-3-ethyl-4-methylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((4-(azepan-1-yl)piperidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((S)-[1,3′-bipyrrolidin]-1′-ylmethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((3-(4-aminopiperidin-1-yl)azetidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   N-(1-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)azetidin-3-yl)piperidin-4-yl)acetamide;   5-((2R,6S)-2-methyl-6-((3-(4-(methylsulfonyl)piperazin-1-yl)azetidin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2S,6R)-2-((3-((S)-3-hydroxypyrrolidin-1-yl)azetidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)-1,3-dimethyl-1H-pyrazole-4-carboxamide;   N-(1-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)azetidin-3-yl)piperidin-4-yl)-1,3-dimethyl-1H-pyrazole-4-carboxamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)methanesulfonamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)benzenesulfonamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)-4-fluorobenzenesulfonamide;   5-((2S,6R)-2-((3-aminoazetidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)azetidin-3-yl)acetamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)azetidin-3-yl)-4-fluorobenzamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)azetidin-3-yl)methanesulfonamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)azetidin-3-yl)-4-fluorobenzenesulfonamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)azetidin-3-yl)-1,3-dimethyl-1H-pyrazole-4-sulfonamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)piperidin-4-yl)-1,3-dimethyl-1H-pyrazole-4-sulfonamide;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)azetidin-3-yl)isobutyramide;   5-((2R,6S)-2-methyl-6-(((S)-2-methyl-5-oxopiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((R)-2-methyl-5-oxopiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((R)-2-methyl-3-oxopiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-(((S)-2-methyl-3-oxopiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((2,4,5-trimethylpiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6S)-2-methyl-6-((2,3,4-trimethylpiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile;   N—((R)-1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)pyrrolidin-3-yl)benzamide;   5-((2S,6R)-2-(((R)-3-(dimethylamino)pyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   N—((S)-1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)pyrrolidin-3-yl)acetamide;   N—((S)-1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)pyrrolidin-3-yl)isobutyramide;   N—((S)-1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)pyrrolidin-3-yl)benzamide;   5-((2S,6R)-2-(((S)-3-(dimethylamino)pyrrolidin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((pyrazin-2-yloxy)methyl)morpholino)quinoline-8-carbonitrile;   N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)azetidin-3-yl)benzamide;   5-((2S,6R)-2-((3,3-dimethylpiperazin-1-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile dihydrochloride;   5-((2R,6S)-2-methyl-6-((3,3,4-trimethylpiperazin-1-yl)methyl)morpholino)quinoline-8-carbonitrile dihydrochloride;   5-((2R,6R)-2-((R)-1-hydroxyethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)-N-ethylpiperidine-4-carboxamide;   1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)-N-ethylpiperidine-4-carboxamide hydrochloride;   5-((2R,6R)-2-((S)-1-hydroxyethyl)-6-methylmorpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((pyridin-2-yloxy)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((pyrimidin-2-yloxy)methyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((R)-1-(pyrimidin-2-yloxy)ethyl)morpholino)quinoline-8-carbonitrile;   5-((2R,6R)-2-methyl-6-((S)-1-(pyrimidin-2-yloxy)ethyl)morpholino)quinoline-8-carbonitrile; and   5-((2R,6R)-2-((S)-hydroxy(pyridin-2-yl)methyl)-6-methylmorpholino)quinoline-8-carbonitrile.   
     
     
         7 . The compound of  claim 5 , wherein said compound is selected from the group consisting of 5-((2S,6R)-2-([1,4′-bipiperidin]-1′-ylmethyl)-6-methylmorpholino)quinoline-8-carbonitrile and 5-((2R,7R)-2-(hydroxymethyl)-7-methyl-1,4-oxazepan-4-yl)quinoline-8-carbonitrile. 
     
     
         8 . A method for treatment of systemic lupus erythematosus or lupus, comprising administering a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of  claim 1 . 
     
     
         9 . The method of  claim 8 , wherein said compound is administered as a pharmaceutically acceptable salt. 
     
     
         10 . A method for antagonizing TLR7, comprising administering a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of  claim 1 . 
     
     
         11 . A method for antagonizing TLR8, comprising administering a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of  claim 1 . 
     
     
         12 . A pharmaceutical composition comprising at least one compound or pharmaceutically acceptable salt of  claim 1  and at least one pharmaceutically acceptable carrier. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein said compound or pharmaceutically effective salt thereof has an IC50 less than or equal to 100 nM against human TLR7 receptors in a HEK-293 cell line. 
     
     
         14 . The pharmaceutical composition of  claim 12 , wherein said compound or pharmaceutically effective salt thereof has an IC50 less than or equal to 20 nM against human TLR7 receptors expressed in a HEK-293 cell line. 
     
     
         15 . The pharmaceutical composition of  claim 12 , wherein said compound or pharmaceutically effective salt thereof has an IC50 less than or equal to 5 nM against human TLR7 receptors expressed in a HEK-293 cell line. 
     
     
         16 . The pharmaceutical composition of  claim 13 , wherein the IC50 against human TLR7 receptors expressed in a HEK-293 cell line is measured by (1) plating cells of the HEK-293 cell line stably expressing TLR7 in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum at a density of 2.22×105 cells/ml into a 384-well plate and incubating for 2 days at 37° C., 5% CO2; (2) adding the compound or pharmaceutically acceptable salt thereof and incubating the cells for 30 minutes; (3) adding CL097 (InvivoGen) at 3 ug/ml and incubating the cells for approximately 20 hours; and (4) quantifying NF-kappaB dependent reporter activation by measuring luminescence. 
     
     
         17 . A method for treatment of a systematic lupus erythematosus, cutaneous lupus, neuropsychiatric lupus, or lupus, comprising administering a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of  claim 1 . 
     
     
         18 . The method of  claim 17 , wherein said compound is administered as a pharmaceutically acceptable salt.