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) or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1  and R 2  is H —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 or pharmaceutically acceptable salt of  claim 1 , wherein said compound or salt has a stereochemical configuration selected from one of those shown in the group consisting of Formula (Ia), Formula (Ib), Formula (1c), and Formula (1d): 
       
         
           
           
               
               
           
         
       
     
     
       3. The compound or pharmaceutically acceptable salt of  claim 1 , wherein said compound or salt 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-carboxannide; 
 (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-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-1carbonyl)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-methyl morpholine-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-methyl morpholine-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-methyl morpholine-2-carboxamide; 
 (2R,6R)-N-((1H-pyrazol-4-yl)methyl)-4-(8-cyanoquinolin-5-yl)-6-methyl morpholine-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-methyl morpholine-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-methyl morpholino)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-methyl morpholine-2-carboxamide hydrochloride; 
 (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((3S, 4R)-4-fluoropiperidin-3-yl)-6-methyl morpholine-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-carboxarnide; 
 5-((2R,6R)-2-(4-aminopiperidine-1-carbonyl)-6-methylmorpholino)quinoline-8-carbonitrile; 
 5-((2R,6R)-2-(4-amino-4-methylpiperidine-1carbonyl)-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-methyl morpholine-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-l-methylpiperidin-3-yl)-6-methylmorpholine-2-carboxamide hydrochloride. 
 
     
     
       4. The compound or pharmaceutically acceptable salt of  claim 3 , wherein said compound or salt 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. 
     
     
       5. A compound of Formula (1e) the following formula or pharmaceutically acceptable salt thereof, with relative stereochemistry indicated: 
       
         
           
           
               
               
           
         
       
     
     
       6. A compound of Formula (II) or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein 
         R 4  is methyl; 
         R 5  is C 1 -C 5  alkyl that is saturated, partially saturated, or unsaturated, and that is optionally substituted with:
 —H, —cl —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  —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. 
       
     
     
       7. The compound or pharmaceutically acceptable salt of  claim 6 , wherein said compound or salt is selected from the group consisting of:
 5-((2R,6S)-2,6-dimethylmorpholino)quinoline-8-carbonitrile; 
 (2R,6R)-methyl 4-(8-cyanoquinolin-5-yl)-6-methylmorpholine-2-carboxylate; 
 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-trifluoro-acetate); 
 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-dihydroxy-succinate; 
 5-((2S,6R)-2,6-dimethylmorpholino)quinoline-8-carbonitrile dimethanesulfonate; 
 N-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylniorpholinmethylmorpholin-2-yl)methymethyl)acetamide; 
 N-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl)pivalamide; 
 5-((2S,6S)-2,6-dimethylmorpholino)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; 
 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-nnethylmorpholinomethylmorpholino)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-nnethylmorpholino)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)nnethyl)-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)-6methylmorpholino)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)nnethylmethyl)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-methyl-morpholino)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; 
 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-methyl-morpholino)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-(hydroxyrnethyl)-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,6 S)-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; 
 tert-butyl 4-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methyl) piperidin-4-yl)piperazine-1-carboxylate; 
 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-1yl)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)ethyl)morpholino) quinoline-8-carbonitrile; 
 5-((2S,6R)-2-((3-(4-acetylpiperazin-1-yl)azetidin-1-yl)methyl)-6-methyl-morpholino)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-methyl-morpholino)quinoline-8-carbonitrile; 
 5-((2S,6R)-2-(4-(1-isobutyrylpiperidin-4-yl)piperazin-1-yl)methyl)-6-methyl-morpholino)quinoline-8-carbonitrile; 
 5-((2S,6R)-2-((4-(1-benzoylpiperidin-4-yl)piperazin-1-yl)methyl)-6-methyl-morpholino)quinoline-8-carbonitrile; 
 5-((2S,6R)-2-((3-(4-isobutyrylpiperazin-1-yl)azetidin-1-yl)methyl)-6-methyl-morpholino)quinoline-8-carbonitrile; 
 5-((2S,6R)-2-((4-(4-acetylpiperazin-1-yl)piperidin-1-yl)methyl)-6-methyl-morpholino)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-methyl-morpholino)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-methyl-quinoline-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-methyl-morpholino)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)methyppiperidin-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)methypazetidinmethyl)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)benzarnide; 
 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. 
 
     
     
       8. The compound or pharmaceutically acceptable salt of  claim 6 , wherein said A compound or pharmaceutically acceptable salt 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; 5-((2S,7R)-2([1,4′-bipiperidin]-1′-ylmethyl)-7-methyl-1,4-oxazepan-4-yl)quinoline-8-carbonitrile; 5-((2S,6R)-2-(((1,8-naphthyridin-2-yl)amino)methyl)-6-methylmorpholino) quinoline-8-carbonitrile; 5-((2R,6S)-2,6-diethylmorpholino)quinoline-8-carbonitrile; (2R,6S)-4-(8-chloro-1,7-naphthyridin-5-yl)-2,6-dimethylmorpholine; and 5-((2R,6R)-2-((benzyloxy)methyl-6-ethylmorpholino)quinoline-8-carbonitrile; 5-(3-methyl-5-((4-methylpiperazin-1-yl)methyl)phenyl)quinoline-8-carbonitrile; 5-(3-(chloromethyl)-5-methylphenyl)quinoline-8-carbonitrile; or a pharmaceutically acceptable salt thereof. 
     
     
       9. A compound of Formula (III) or pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein 
         R 11  is H or methyl; 
         R 10  is H or, when both R 11  and R 9  are H, is methyl-1,4′-bipiperidinyl; 
         R 9  is —H or is —CH 2 - substituted by 1,4′-bipiperidinyl, oxo-, hydroxyl, methylpyridinyl, or piperidinyl optionally substituted with hydroxyl, —N(CH 3 ) 2 , or piperidinyl. 
       
     
     
       10. The compound or pharmaceutically acceptable salt of  claim 9 , wherein said compound or salt is selected from the group consisting of:
 5-(3-([1,4′-bipiperidin]-1′-ylmethyl)pheny)quinoline-8-carbonitrile; 
 5-(4-([1,4′-bipiperidin]-1′-ylmethyl)pheny)quinoline-8-carbonitrile; 
 5-(3-formyl-5-methylphenyl)quinoline-8-carbonitrile; 
 5-(3-(hydroxymethyl)-5-methylphenyl)quinoline-8-carbonitrile; 
 5-(3-(chloromethyl)-5-methylphenyl)quinoline-8-carbonitrile; 
 5-(3-((4-hydroxypiperidin-1-yl)methyl)-5-methylphenyl)quinoline-8-carbonitrile; 
 5-(3-((4-(dimethylamino)piperidin-1-yl)methyl)-5-methylphenyl)quinoline-8-carbonitrile; 
 5-(3-methyl-5-((4-methylpiperazin-1-yl)methyl)phenyl)quinoline-8-carbonitrile; and 
 5-(3-([1,4′-bipiperidin]-1′-ylmethyl)-5-methylphenyl)quinoline-8-carbonitrile. 
 
     
     
       11. A method for treatment of lupus, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of  claim 1 . 
     
     
       12. The method of  claim 11 , wherein said compound is administered as a pharmaceutically acceptable salt. 
     
     
       13. A method for antagonizing TLR7, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of  claim 1 . 
     
     
       14. A method for antagonizing TLR8, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of  claim 1 . 
     
     
       15. A pharmaceutical composition comprising at least one compound or pharmaceutically acceptable salt of  claim 1  and at least one pharmaceutically acceptable carrier. 
     
     
       16. The pharmaceutical composition of  claim 15 , wherein said compound or pharmaceutically acceptable salt thereof has an IC50 less than or equal to 100 nM against human TLR7 receptors in a HEK-293 cell line. 
     
     
       17. The pharmaceutical composition of  claim 15 , wherein said compound or pharmaceutically acceptable salt thereof has an IC50 less than or equal to 20 nM against human TLR7 receptors expressed in a HEK-293 cell line. 
     
     
       18. The pharmaceutical composition of  claim 15 , wherein said compound or pharmaceutically acceptable salt thereof has an IC50 less than or equal to 5 nM against human TLR7 receptors expressed in a HEK-293 cell line. 
     
     
       19. The pharmaceutical composition of  claim 16 , 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 a 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 CO 2 ; (2) adding the compound or pharmaceutically acceptable salt thereof and incubating the cells for 30 minutes; (3) adding CL097 (InvivoGen) 2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-4-amine at 3 ug/ml and incubating the cells for approximately 20 hours; and (4) quantifying NF-kappaB dependent reporter activation by measuring luminescence. 
     
     
       20. A method for treatment of a systematic systemic lupus erythematosus, cutaneous lupus, or neuropsychiatric lupus, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of  claim 1 . 
     
     
       21. The method of  claim 20 , wherein said compound is administered as a pharmaceutically acceptable salt. 
     
     
       22. A pharmaceutically acceptable salt of  claim 5 , wherein the pharmaceutically acceptable salt, with relative stereochemistry indicated, is Rel-(2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((3S,4R)-4-fluoropyrrolidin-3-yl)-6-methylmorpholine-2- carboxamide (2R,6R)-4-(8-cyanoquinolin-5-yl)-N-((3S,4R)-4-fluoropyrrolidin-3-yl)-6-methylmorpholine-2-carboxamide hydrochloride. 
     
     
       23. A method for treatment of lupus, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of the pharmaceutically acceptable salt of  claim 22 . 
     
     
       24. A pharmaceutical composition comprising the pharmaceutically acceptable salt of  claim 22  and at least one pharmaceutically acceptable carrier. 
     
     
       25. A method for treatment of systematic systemic lupus erythematosus, cutaneous lupus, or neutopsychiatric lupus, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of the pharmaceutically acceptable salt of  claim 22 . 
     
     
       26. A method for antagonizing TLR7, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of the pharmaceutically acceptable salt of  claim 22 . 
     
     
       27. A method for antagonizing TLR8, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of the pharmaceutically acceptable salt of  claim 22 . 
     
     
       28. A method for treatment of lupus, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of the pharmaceutically acceptable salt of  claim 5 . 
     
     
       29. A pharmaceutical composition comprising the pharmaceutically acceptable salt of  claim 5  and at least one pharmaceutically acceptable carrier. 
     
     
       30. A method for treatment of systematic systemic lupus erythematosus, cutaneous lupus, or neutopsychiatric lupus, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of the pharmaceutically acceptable salt of  claim 5 . 
     
     
       31. A method for antagonizing TLR7, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of the pharmaceutically acceptable salt of  claim 5 . 
     
     
       32. A method for antagonizing TLR8, in a subject in need thereof, comprising administering to said subject a pharmaceutically effective amount of the pharmaceutically acceptable salt of  claim 5 .