# US 9,428,495 B2 · Selectively substituted quinoline compounds

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- Number: US 9,428,495 B2
- Document ID: US9428495B2
- Status: Granted
- Kind: B2
- Application number: 14/513,556
- Filed: 2014-10-14
- Published: 2015-04-16
- Granted: 2016-08-30
- Earliest claimed: 2013-10-14
- Assignees: Eisai R&D Management Co., Ltd.
- Applicants: Eisai R&D Management Co., Ltd.
- Inventors: Eric Carlson; Hans Hansen; Lynn Hawkins; Sally Ishizaka; Matthew Mackey; Shawn Schiller; Chikako Ogawa; Heather Davis; Atsushi Endo
- Web page: https://patentgrep.com/patent/US9428495B2

## CPC

- C07D 417/14: containing three or more hetero rings
- C07D 215/48: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D 401/10: linked by a carbon chain containing aromatic rings
- C07D 401/14: containing three or more hetero rings
- C07D 403/14: containing three or more hetero rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 451/04: with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D 471/04: Ortho-condensed systems
- C07D 471/10: Spiro-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D 487/10: Spiro-condensed systems
- C07D 493/10: Spiro-condensed systems
- C12Q 1/6897: involving reporter genes operably linked to promoters
- G01N 33/5023: {on expression patterns}
- G01N 33/5047: {Cells of the immune system}
- C07B 2200/07: Optical isomers
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## 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.

## Claims

### Claim 1

A compound of formula (I) or pharmaceutically acceptable salt thereof:
wherein at least one of R1 and R2 is H, methyl, or ethyl, and the other is
—H; or the other is
C1-C6 alkyl that is optionally substituted with:
—OH, methoxy, ethoxy, —OCH(CH3)2, —O(CH2)2CH3, phenyl, furanyl, —O(CH2)2OH, phenoxy, methylthio, —F, —N(CH3)2, cyano, pyridinyloxy, fluorophenoxy, isochromanyl, phenol, benzylamino, —NHCH3, 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
C3-C7 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
R1 and R2, 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 R3 is —H or methyl.

### Claim 2 (depends on 1)

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):

### Claim 3 (depends on 1)

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-methylrnorpholine-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-fluoropyrrolid in-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.

### Claim 4 (depends on 3)

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.

### Claim 5

A compound of Formula (le) or pharmaceutically acceptable salt thereof, with relative stereochemistry indicated:

### Claim 6

A compound of Formula (II) or pharmaceutically acceptable salt thereof:
wherein
R4 is methyl;
R5 is C1-C5 alkyl that is saturated, partially saturated, or unsaturated, and that is optionally substituted with:
—H, —cl, —F, —OH, —NH2, oxo- , —N(CH2CH3)2, phenyl, cyclohexyl, phenyltriazolyl, cyclohexyltriazolyl, pyridinyl, pyrrolidinyl,
morpholinyl optionally substituted with methyl or hydroxymethyl, —O—, substituted with:
C1-C6 alkyl, methylphenyl, methylcyclohexyl, pyridinyl, diazinyl, or phenyl optionally substituted with —F or methyl, —NH—, substituted with:
C2-C7 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 R5 is
wherein n is 1-3, and wherein the cyclic amine is optionally substituted with
C1—C3 alkyl optionally substituted with
—OH, —F, phenyl, -—NH2, cyclohexyl, —N(CH3)2, —c(O)NH2, methylsulfonamidyl, benzenesulfonamidyl, methylbenzenesulfonamidyl, or
pyrrolidinyl optionally substituted with methyl or hydroxyl, or —NHC(O)R6, wherein R6 is
C1-C5 alkyl, phenyl, pyridinyl, fluorophenyl, methylsulfonyl, fluorobenzenesulfonyl, dimethyl pyrazole sulfonyl, or
pyrazolyl optionally substituted with methyl;
piperidinyl optionally substituted with —C(O)CH3, —C(O)CH2CH3, methyl, oxo-,
C(O)Ph, —NH2, —NH—C(O)CH3, or
piperazinyl optionally substituted with —C(O)OC(CH3)3, methyl, —C(O)CH3, —C(O)Ph, C(O)CH(CH3)2, —C(O)CH3, or methylsulfonyl; or
R5 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(CH3)2, amino, —CH2CH3, or
piperidinyl optionally substituted with methyl, —C(O)CH3, —C(O)CH(CH3)2, —C(O)Ph, or —C(O)OC(CH3)3, and
wherein R7 is —H, phenyl, —C(O)CH3, C1-C3 alkyl, —C(O)NH2, or —C(O)Ph; and
R8 is methoxy or cyano.

### Claim 7 (depends on 6)

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;
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-methylniorpholin-2-yl)methy)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-nnethylmorpholino)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)nnethyl)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,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;
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-1yl)methyl)morpholino) quinoline-8-carbonitrile;
5-((2R,6S)-2-methyl-6-((4-(piperidin-4-yl)piperazin-1yl)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-)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-4yl)-1,3-dimethyl-1H-pyrazole-4-sulfonamide;
N-(1-(((2S,6R)-4-(8-cyanoquinolin-5-yl)-6-methylmorpholin-2-yl)methypazetidin-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.

### Claim 8 (depends on 6)

The compound or pharmaceutically acceptable salt of claim 6, wherein said compound or 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.

### Claim 9

A compound of Formula (III) or pharmaceutically acceptable salt thereof:
wherein
R11 is H or methyl;
R10 is H or, when both R11 and R9 are H, is methyl-1,4′-bipiperidinyl;
R9 is —H or is —CH2- substituted by 1,4′-bipiperidinyl, oxo-, hydroxyl, methylpyridinyl, or piperidinyl optionally substituted with hydroxyl, —N(CH3)2, or piperidinyl.

### Claim 10 (depends on 9)

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.

### Claim 11 (depends on 1)

A method for treatment of lupus, comprising administering a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of claim 1.

### Claim 12 (depends on 11)

The method of claim 11, wherein said compound is administered as a pharmaceutically acceptable salt.

### Claim 13 (depends on 1)

A method for antagonizing TLR7, comprising administering a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of claim 1.

### Claim 14 (depends on 1)

A method for antagonizing TLR8, comprising administering a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of claim 1.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising at least one compound or pharmaceutically acceptable salt of claim 1 and at least one pharmaceutically acceptable carrier.

### Claim 16 (depends on 15)

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.

### Claim 17 (depends on 15)

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.

### Claim 18 (depends on 15)

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.

### Claim 19 (depends on 16)

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; (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.

### Claim 20 (depends on 1)

A method for treatment of a systematic lupus erythematosus, cutaneous lupus, or neuropsychiatric lupus, comprising administering a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt of claim 1.

### Claim 21 (depends on 20)

The method of claim 20, wherein said compound is administered as a pharmaceutically acceptable salt.

### Claim 22 (depends on 5)

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 hydrochloride.

### Claim 23 (depends on 22)

A method for treatment of lupus, comprising administering a pharmaceutically effective amount of the pharmaceutically acceptable salt of claim 22.

### Claim 24 (depends on 22)

A pharmaceutical composition comprising the pharmaceutically acceptable salt of claim 22 and at least one pharmaceutically acceptable carrier.

### Claim 25 (depends on 22)

A method for treatment of systematic lupus erythematosus, cutaneous lupus, or neutopsychiatric lupus, comprising administering a pharmaceutically effective amount of the pharmaceutically acceptable salt of claim 22.

### Claim 26 (depends on 22)

A method for antagonizing TLR7, comprising administering a pharmaceutically effective amount of the pharmaceutically acceptable salt of claim 22.

### Claim 27 (depends on 22)

A method for antagonizing TLR8, comprising administering a pharmaceutically effective amount of the pharmaceutically acceptable salt of claim 22.

### Claim 28 (depends on 5)

A method for treatment of lupus, comprising administering a pharmaceutically effective amount of the pharmaceutically acceptable salt of claim 5.

### Claim 29 (depends on 5)

A pharmaceutical composition comprising the pharmaceutically acceptable salt of claim 5 and at least one pharmaceutically acceptable carrier.

### Claim 30 (depends on 5)

A method for treatment of systematic lupus erythematosus, cutaneous lupus, or neutopsychiatric lupus, comprising administering a pharmaceutically effective amount of the pharmaceutically acceptable salt of claim 5.

### Claim 31 (depends on 5)

A method for antagonizing TLR7, comprising administering a pharmaceutically effective amount of the pharmaceutically acceptable salt of claim 5.

### Claim 32 (depends on 5)

A method for antagonizing TLR8, comprising administering a pharmaceutically effective amount of the pharmaceutically acceptable salt of claim 5.