COMPOUNDS FOR INHIBITING C-MYC/MAX/DNA COMPLEX FORMATION

Abstract

Disclosed are novel compounds of specific chemical structures having inhibitory activity on c-Myc/Max/DNA complex formation or pharmaceutically acceptable salts thereof.

Claims

1. A compound of Formula 1a or 1b, or a pharmaceutically acceptable salt thereof: ##STR00118## in Formula 1a or 1 b, R.sub.1a to R.sub.1d are each independently hydrogen, a halogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.2-10 alkenyl, C.sub.2-10 haloalkenyl, C.sub.2-10 alkynyl, C.sub.2-10 haloalkynyl, a hydroxyl group, nitro, cyano, C.sub.1-6 alkoxycarbonyl, amino, C.sub.1-6 alkylamino, alkyl)amino, amino(C.sub.1-6)alkyl, (C.sub.1-6)alkylamino(C.sub.1-6)alkyl, C.sub.1-6 alkanoyl, C.sub.3-7 cycloalkyl, an aryl, a heterocycle, or a heteroaryl, wherein R.sub.1a to R.sub.1d are each independently unsubstituted or optionally substituted; R.sub.2 is hydrogen, C.sub.1-6 alkyl, (C.sub.1-6)alkoxy(C.sub.1-6)alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 hydroxyalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.2-10 alkenyl, C.sub.2-10 alkenyl carboxy, C.sub.2-10 haloalkenyl, C.sub.2-10 alkynyl, C.sub.2-10 haloalkynyl, a hydroxyl group, nitro, cyano, C.sub.1-6 alkoxycarbonyl, amino, C.sub.1-6 alkylamino, C.sub.1-6 cyanoalkyl, alkyl)amino, amino(C.sub.1-6)alkyl, (C.sub.1-6)alkylamino(C.sub.1-6)alkyl, C.sub.1-6 alkanoyl, C.sub.3-7 cycloalkyl, (C.sub.1-6)alkyl(C.sub.3-7)cycloalkyl, aryl, (C.sub.1-6)alkylaryl, (C.sub.1-6)haloalkylaryl, (C.sub.2-6)alkenylamide(C.sub.1-6)alkylalkoxy, a heterocycle, (C.sub.1-6)alkylheterocycle, a heteroaryl, or (C.sub.1-6)alkylheteroaryl, wherein R.sub.2 is unsubstituted or optionally substituted; R.sub.3 is C.sub.1-4 alkyl, isoalkyl, cycloalkyl, phenyl, or C.sub.1-4 haloalkyl; n is an integer from 0 to 2; and Y is hydrogen, an alkyl, a haloalkyl, C(O)alkyl, C(O)aryl, a sulfonylalkyl, a sulfonylaryl, an aryl, or an alkylaryl, wherein an alkyl has 1 to 10 carbon atoms, and an aryl is unsubstituted or optionally substituted.

2. The compound according to claim 1 having the structure of Formula 2a or 2b, or a pharmaceutically acceptable salt thereof: ##STR00119## in Formula 2a or 2b, R.sub.1a to R.sub.1d, R.sub.3, n and Y are as defined for Formula 1a or 1b in claim 1; m is an integer from 0 to 4; and R.sub.6 is phenyl, oxazole, pyrazole, pyrrole, imidazole, thiazole, thiophene, pyridine, pyrimidine, furan, indole, benzopyrazole, benzothiazole, benzooxazole, isoxazole, benzoimidazole, 1,2,5-oxadiazole, pyrrolo[2,3-b]pyridine, or benzothiophene, which is unsubstituted, or optionally substituted with one or more of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy, and a halogen, or is optionally substituted with one or more of hydrogen, phenyl, oxazole, pyrazole, pyrrole, imidazole, thiazole, thiophene, pyridine, pyrimidine, furan, indole, benzopyrazole, benzothiazole, benzooxazole, isoxazole, benzoimidazole, and benzothiophene, or is optionally substituted with unsubstituted phenyl.

3. The compound according to claim 2, wherein any one or more of R.sub.1a to R.sub.1d are halogens, R.sub.3 is C.sub.1-4 alkyl, isoalkyl, cycloalkyl, phenyl, or C.sub.1-4 haloalkyl, and m is 1 or 2.

4. The compound according to claim 1 having the structure of Formula 3a or 3b, or pharmaceutically acceptable salt thereof: ##STR00120## in Formula 3a or 3b, R.sub.1a to R.sub.1d, R.sub.3, and n are as defined for Formula 1a or 1 b in claim 1; R.sub.4a and R.sub.4b are each independently hydrogen, a halogen, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, or C.sub.1-4 alkyl in which one or more hydrogens are substituted with a substituent other than halogen; Ar is phenyl, a heteroaryl being 5-6-membered and having a heteroatom selected independently from N, S, and O, or a biheteroaryl being 8-12-membered and having a heteroatom selected independently from N, S, and O, wherein Ar is unsubstituted or optionally substituted with one or more of a halogen, C.sub.1-6 alkyl, C.sub.1-6 alkylthio, C.sub.1-6 haloalkyl, C.sub.1-6 haloalkylthio, alkoxy, haloalkoxy, C.sub.2-10 alkenyl, C.sub.2-10 haloalkenyl, C.sub.2-10 alkynyl, C.sub.2-10 haloalkynyl, a hydroxyl group, COOH, nitro, cyano, alkoxycarbonyl, amino, C.sub.1-6 alkylamino, alkyl)amino, amino(C.sub.1-6)alkyl, (C.sub.1-6)alkylamino(C.sub.1-6)alkyl, (C.sub.1-6)alkoxy(C.sub.1-6)alkylamino, (C.sub.1-6)alkylamino(C.sub.1-6) alkylamino, C.sub.1-6 alkanoyl, SF.sub.5, S(O)CF.sub.3, SCF.sub.3, NHC(O)CH.sub.3, C(O)NHCH.sub.3, NHSO2CH3, C.sub.3-7 cycloalkyl, an aryl, benzoyl, a heterocycle, a heteroaryl, phenyl, oxazole, pyrazole, pyrrole, imidazole, thiazole, thiophene, pyridine, pyrimidine, furan, indole, benzopyrazole, benzothiazole, benzooxazole, isoxazole, benzoimidazole, and benzothiophene, wherein the substituent of Ar is unsubstituted or optionally substituted with one or more of CF3, a halogen, (C.sub.1-3)alkyl, (C.sub.1-3)haloalkyl, hydrogen, COOH, nitro, cyano, amino, di(Cl-3 alkyl)amino, NHC(O)CH3, and C(O)NHCH3.

5. The compound according to claim 4, wherein any one or more of R.sub.1a to R.sub.1d are halogens, R.sub.3 is C.sub.1-4 alkyl, isoalkyl, cycloalkyl, phenyl, or C.sub.1-4 haloalkyl, and R.sub.4a and R.sub.4b are C.sub.1-4 alkyl, a halogen, or C.sub.1-4 cycloalkyl.

6. The compound according to claim 1 selected from the group consisting of: 3-acetyl-8-bromo-5-chloro-2-(methylsulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(methylthio)quinolin-4(1H)-one, 3-acetyl-2-(benzylthio)-8-bromo-5-chloroquinolin-4(1H)-one, 3-acetyl-2-(benzylsulfinyl)-8-bromo-5-chloroquinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-1-methyl-2-(methylthio)quinolin-4(1H)-one, 3-acetyl-5,8-dichloro-2-(methylsulfinyl)quinolin-4(1H)-one, 3-acetyl-6-fluoro-1-methyl-2-(methylthio)quinolin-4(1H)-one, 1-(6-fluoro-4-hydroxy-2-(methylthio)quinolin-3-yl)ethan-1-one, 3-acetyl-8-bromo-1-(4-bromobenzoyl)-5-chloro-2-(methylsulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((4-chlorobenzyl)thio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((4-chlorobenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(phenylthio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(phenylsulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((2-methoxyphenyl)thio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((2-methoxyphenyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-2-((4-bromophenyl)thio)-5-chloroquinolin-4(1H)-one, 3-acetyl-8-bromo-2-((4-bromophenyl)sulfinyl)-5-chloroquinolin-4(1H)-one, 1,1-(8-bromo-5-chloro-2-(methylthio)-4-oxoquinoline-1,3(4H)-diyl)bis(ethan-1-one), 1,1-(8-bromo-5-chloro-2-(methylsulfinyl)-4-oxoquinoline-1,3(4H)-diyl)bis(ethan-1-one), 3-acetyl-2-(benzylsulfinyl)-8-bromo-1-(4-bromobenzoyl)-5-chloroquinolin-4(1H)-one, 3-acetyl-8-bromo-1-(4-bromobenzoyl)-5-chloro-2-(methylsulfonyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-1-(3-chloro-4-fluorobenzyl)-2-(methylsulfinyl)quinolin-4(1H)-one, 3-acetyl-2-(benzylthio)-8-bromo-1-(4-bromobenzoyl)-5-chloroquinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(isopropylthio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(isopropylsulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((1-phenylethyl)sulfinyl)quinolin-4(1H)-one, 3-(((3-acetyl-8-bromo-5-chloro-4-oxo-1,4-dihydroquinolin-2-yl)thio)methyl)benzonitrile, 3-(((3-acetyl-8-bromo-5-chloro-4-oxo-1,4-dihydroquinolin-2-yl)sulfinyl)methyl)benzonitrile, 3-acetyl-8-bromo-5-chloro-2-((2,4-difluorobenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((3-chloro-4-fluorobenzyl)thio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((3-chloro-4-fluorobenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((4-nitrobenzyl)thio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((4-nitrobenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-2-(benzylsulfonyl)-8-bromo-5-chloroquinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-1-(methylsulfonyl)-2-(methylthio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(methylsulfinyl)-1-((trifluoromethyl)sulfonyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-1-((4-chlorophenyl)sulfonyl)-2-(methylthio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(methylthio)-1-((4-nitrophenyl)sulfonyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-1-(ethylsulfonyl)-2-(methylsulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-1-((4-(tert-butyl)phenyl)sulfonyl)-5-chloro-2-(methylthio)quinolin-4(1H)-one, 3-acetyl-8-bromo-1-((4-(tert-butyl)phenyl)sulfonyl)-5-chloro-2-(methylsulfonyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-1-((4-(tert-butyl)phenyl)sulfonyl)-5-chloro-2-(methylsulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((2,5-dichlorobenzyl)thio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((2,5-dichlorobenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((3,5-difluorobenzyl)thio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((3,5-difluorobenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((3-iodobenzyl)thio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((3-iodobenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((3-fluorobenzyl)thio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((3-fluorobenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(((5-methylisoxazol-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, 1-(2-(benzylthio)-8-bromo-5-chloro-4-hydroxyquinolin-3-yl)ethan-1-one, 1-(2-(benzylsulfinyl)-8-bromo-5-chloro-4-hydroxyquinolin-3-yl)ethan-1-one, 1-(2-(benzylsulfonyl)-8-bromo-5-chloro-4-hydroxyquinolin-3-yl)ethan-1-one, 3-acetyl-8-bromo-5-chloro-2-((3-methoxybenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((4-((trifluoromethyl)thio)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-5,8-dichloro-2-((4-nitrobenzyl)sulfinyl)quinolin-4(1H)-one, 2-(((3-acetyl-8-bromo-5-chloro-4-oxo-1,4-dihydroquinolin-2-yl)sulfinyl)methyl)benzonitrile, 3-acetyl-8-bromo-5-chloro-2-((3,5-dimethoxybenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-2-((4-(tert-butyl)benzyl)sulfinyl)-5-chloroquinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((methoxymethyl)thio)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-mercaptoquinolin-4(1H)-one, 3-acetyl-2-((4-benzoylbenzyl)sulfinyl)-8-bromo-5-chloroquinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((4-((trifluoromethyl)sulfinyl)benzyl)sulfinyl)quinolin-4(1H)-one, 2((3-acetyl-8-bromo-5-chloro-4-oxo-1,4-dihydroquinolin-2-yl)sulfinyl)acetonitrile, 2((3-acetyl-8-bromo-5-chloro-4-oxo-1,4-dihydroquinolin-2-yl)thio)acetonitrile, (Z)-3-((3-acetyl-8-bromo-5-chloro-4-oxo-1,4-dihydroquinolin-2-yl)thio)acrylic acid, 3-acetyl-8-bromo-5-chloro-2-((4-(pentafluoro-I6-sulfanyl)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((2-fluoro-4-(pentafluoro-I6-sulfanyl)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((4-(trifluoromethyl)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((4-(trifluoromethoxy)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(((5-(trifluoromethyl)furan-2-yl)methyl)sulfinyl)quinolin-4(1H)-one, 4-(((3-acetyl-8-bromo-5-chloro-4-oxo-1,4-dihydroquinolin-2-yl)sulfinyl)methyl)benzonitrile, 3-acetyl-8-bromo-5-chloro-2-((2-chloro-6-fluorobenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((2-m ethoxy-4-(pentafluoro-I6-sulfanyl)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((3-fluoro-5-(pentafluoro-I6-sulfanyl)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((3-(pentafluoro-I6-sulfanyl)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(((perfluorophenyl)methyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-5,8-dichloro-2-((4-((trifluoromethyl)thio)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-5,8-difluoro-2-((4-(pentafluoro-I6-sulfanyl)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-5,8-difluoro-2-(((5-(trifluoromethyl)furan-2-yl)methyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-5,8-difluoro-2-(((5-methylisoxazol-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-5,8-dichloro-2-((4-iodobenzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-((pyridin-3-ylmethyl)sulfinyl)quinolin-4(1H)-one, 5,8-difluoro-3-isobutyryl-2-((4-((trifluoromethyl)thio)benzyl)sulfinyl)quinolin-4(1H)-one, 5,8-dichloro-3-isobutyryl-2-(((5-methylisoxazol-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, 3-benzoyl-5,8-difluoro-2-((4-(pentafluoro-I6-sulfanyl)benzyl)sulfinyl)quinolin-4(1H)-one, 3-benzoyl-5,8-dichloro-2-(((5-methylisoxazol-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, methyl 5-(((3-acetyl-5,8-dichloro-4-oxo-1,4-dihydroquinolin-2-yl)sulfinyl)methyl)furan-2-carboxylate, 2-(((3-acetyl-5,8-dichloro-4-oxo-1,4-dihydroquinolin-2-yl)sulfinyl)methyl)isoindoline-1,3-dione, methyl 4-(((3-acetyl-5,8-dichloro-4-oxo-1,4-dihydroquinolin-2-yl)sulfinyl)methyl)benzoate, 3-acetyl-5-methoxy-2-((4-(pentafluoro-I6-sulfanyl)benzyl)thio)quinolin-4(1H)-one, 3-acetyl-5-methoxy-2-((4-(pentafluoro-I6-sulfanyl)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-5-methoxy-2-(((5-methylisoxazol-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, 8-bromo-5-chloro-3-isobutyryl-2-(((5-methylisoxazol-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, 8-bromo-5-chloro-3-(cyclopropanecarbonyl)-2-(((5-methylisoxazol-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, 5,8-dichloro-3-(cyclopropanecarbonyl)-2-(((5-methylisoxazol-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, 5-(((3-acetyl-8-bromo-5-chloro-4-oxo-1,4-dihydroquinolin-2-yl)sulfinyl)methyl)thiophene-2-carbonitrile, 2-(((6-(1H-pyrazol-1-yl)pyridin-3-yl)methyl)sulfinyl)-3-acetyl-8-bromo-5-chloroquinolin-4(1H)-one, 3-acetyl-2-(((6-aminopyridin-3-yl)methyl)sulfinyl)-8-bromo-5-chloroquinolin-4(1H)-one, 8-bromo-5-chloro-3-(cyclopropanecarbonyl)-2-((4-((trifluoromethyl)thio)benzyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, N-(4-(((3-acetyl-8-bromo-5-chloro-4-oxo-1,4-dihydroquinolin-2-yl)sulfinyl)methyl)phenyl)methanesulfonamide, 3-acetyl-8-bromo-5-chloro-2-(((6-chloropyridin-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(((6-((2-methoxyethyl)amino)pyridin-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, 3-acetyl-8-bromo-5-chloro-2-(((4-methyl-1,2,5-oxadiazol-3-yl)methyl)sulfinyl)quinolin-4(1H)-one, and 2-(((1H-pyrrolo[2,3-b]pyridin-5-yl)methyl)sulfinyl)-3-acetyl-8-bromo-5-chloroquinolin-4(1H)-one, or a pharmaceutically acceptable salt thereof.

7. A composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Description

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

[0130] Hereinafter, the present disclosure is described in detail with reference to the following examples. However, the examples according to the present disclosure can be modified into various other forms, and the scope of the present disclosure should not be construed as being limited to the following examples. The examples are provided to more fully explain the present disclosure to those skilled in the art to which the present disclosure pertains.

[0131] Preparation of Compounds of the Present Disclosure

[0132] The reagents and solvents used in the experiments described below can be purchased from Aldrich Chemical Co. (Milwaukee, Wis., USA). A .sup.1H-NMR spectrum was measured using a Varian Gemini 400 MHz NMR spectrometer.

Preparation of Compounds 3-acetyl-8-bromo-5-chloro-2-(methylthio)quinolin-4(1H)-one (4a), 3-acetyl-2-(benzylthio)-8-bromo-5-chloroquinolin-4(1H)-one (4b), 3-acetyl-8-bromo-5-chloro-2-(methylsulfinyl)quinolin-4(1H)-one (5a), and 3-acetyl-2-(benzylsulfinyl)-8-bromo-5-chloroquinolin-4(1H)-one (5b)

[0133] ##STR00117##

Synthesis of 2-Bromo-5-Chlorophenyl Isothiocyanate (2) (Isothiocyanate Formation)

[0134] 2-Bromo-5-chloroaniline (1) (10 g, 48.5 mmol) was dissolved in anhydrous dichloroethane (CH.sub.2Cl.sub.2, 250 mL) and sodium carbonate (Na.sub.2CO.sub.3, 11 g, 97 mmol) was added thereto. The solution was cooled to 5 C. with ice water under nitrogen gas, and thiophosgene (5.5 mL, 72.7 mmol) was added very slowly to the solution in that state. The reaction solution was stirred at room temperature for 12 hours and then filtered to remove inorganic matter. After removing the solvent by distillation under reduced pressure, nucleic acid (n-Hexane, 50 mL) was added to the resulting solid, and then the mixture was stirred for 10 minutes and subjected to filtering to quantitatively obtain a title compound as a yellow solid.

[0135] .sup.1H NMR (300 MHz, CDCl.sub.3) 7.51-7.49 (d, J=8.61 Hz, 1H), 7.26-7.25 (d, J=2.4 Hz, 1H), 7.13-7.09 (dd, J=2.46, 6.18 Hz, 1H).

[0136] LC/MS data: 249.52 g/mol

Synthesis of Ethyl (Z)-2-(((2-Bromo-5-Chlorophenyl)Amino)(Methylthio)Methylene)-3-Oxobutanoate, Compound 3a (CC Bond Formation)

[0137] Isothiothianate (2) (10 g, 40 mmol) synthesized in step 1 was dissolved in anhydrous DMF (20 mL), and the mixed solution was slowly added to a solution of ethyl oxobutanoate (5.2 g, 40 mmol) and K.sub.2CO.sub.3 (5.6 g, 40 mmol) dissolved in DMF (100 mL) at room temperature. The mixture was stirred for 12 hours at room temperature, and then iodomethane (5.7 g, 40 mmol) was slowly added thereto at room temperature. The solution was then stirred at room temperature for one day. After completion of the reaction was confirmed by TLC, water and ethyl acetate were added and the desired compound was extracted as an organic layer. Water was removed from the extracted organic layer using MgSO.sub.4, and the extracted organic layer was subjected to distillation under reduced pressure, and then purification was performed using a column to obtain title Compound 3a.

[0138] .sup.1H NMR (300 MHz, CDCl.sub.3) 12.90 (s, 1H), 7.45-7.42 (d, J=8.41 Hz, 1H), 6.90-6.86 (d, J=7.74 Hz, 1H), 6.68 (s, 1H), 4.36-4.29 (m, 2H), 2.54 (s, 3H), 2.04 (s, 3H), 1.37-1.33 (t, J=7.26 Hz, 3H).

[0139] LC/MS data: 393.69 g/mol

Synthesis of 3-acetyl-8-bromo-5-chloro-2-(methylthio)quinolin-4(1H)-one, Compound 4a (Cyclization)

[0140] Compound 3a synthesized in step 2 was dissolved in o-dichlorobenzene and stirred for 12 hours while heated at 180 C. After the reaction was completed, the reaction mixture was cooled to room temperature and was subjected to distillation under reduced pressure. A nucleic acid was added to the resulting solid, and the mixture was stirred for 10 minutes and was subjected to filtering to obtain Compound 4a.

[0141] .sup.1H NMR (300 MHz, CDCl.sub.3) 8.67 (s, 1H), 7.91-7.88 (d, J=8.19 Hz, 1H), 7.71-7.68 (d, J=8.49 Hz, 1H), 2.97 (s, 3H), 2.79 (s, 3H).

[0142] LC/MS data: 347.62 g/mol

Synthesis of 3-acetyl-8-bromo-5-chloro-2-(methylsulfinyl)quinolin-4(1H)-one, Compound 5a (Oxidation)

[0143] The quinolone compound 4a obtained in step 3 was oxidized with MCPBA (1.5 eq.) in anhydrous dichloroethane (CH.sub.2Cl.sub.2, 10 mL) to obtain title Compound 5a.

[0144] .sup.1H NMR (300 MHz, CDCl.sub.3) 11.13 (s, 1H), 7.82-7.79 (d, J=8.43 Hz, 1H), 7.38-7.36 (d, J=8.46 Hz, 1H), 3.02 (s, 3H), 2.78 (s, 3H).

[0145] LC/MS data: 363.62 g/mol

Synthesis of Ethyl (Z)-2-((Benzylthio)((2-Bromo-5-Chlorophenyl)Amino)Methylene)-3-Oxobutanoate, Compound 3b

[0146] Title Compound 3b was synthesized using benzyl bromide instead of MeI in a similar manner to the synthesis of Compound 3a.

[0147] .sup.1H NMR (300 MHz, CDCl.sub.3) 12.90 (s, 1H), 7.46-7.44 (m, 2H), 7.35-7.24 (m, 4H), 6.91-6.89 (d, J=7.95 Hz, 1H), 6.70 (s, 1H), 4.49-4.19 (m, 4H), 2.05 (s, 3H), 1.36-1.31(., J=7.11 Hz, 3H).

[0148] LC/MS data: 469.79 g/mol

Synthesis of 3-acetyl-2-(benzylthio)-8-bromo-5-chloroquinolin-4(1H)-one, Compound 4b

[0149] Title Compound 4b was synthesized in a similar manner to the synthesis of Compound 4a.

[0150] .sup.1H NMR (300 MHz, CDCl.sub.3) 8.59 (s, 1H), 7.93-7.90 (d, J=8.25 Hz, 1H), 7.52-7.47 (m, 2H), 7.42-7.21 (m, 4H), 4.80 (s, 2H), 2.93 (s, 3H).

[0151] LC/MS data: 423.72 g/mol

Synthesis of 3-acetyl-2-(benzylsulfinyl)-8-bromo-5-chloroquinolin-4(1H)-one, Compound 5b

[0152] Title Compound 5b was synthesized in a similar manner to the synthesis of Compound 5a.

[0153] Using the above-mentioned methods, the following compounds according to the present disclosure were synthesized by modifying reactants and/or starting materials appropriately. LC/MS and .sup.1H NMR measurement results are summarized in Table 4. In Table 4 below, MW refers to an average molecular weight, and MS is the value obtained by analyzing the actually prepared compounds.

TABLE-US-00004 TABLE 4 MW LC/ Compound (Molecular MS Number Formula Name Weight) data .sup.1H NMR 1 3-acetyl-8-bromo-5-chloro-2- 362.62 363 .sup.1H NMR (300 MHz, CDCl.sub.3) (methylsulfinyl)quinolin- 11.13 (br, 1H), 7.81 (d, J = 8.4 Hz, 1H), 4(1H)-one 7.37 (d, J = 8.4 Hz, 1H), 3.02 (s, 3H), 2.78 (s, 3H). 2 3-acetyl-8-bromo-5-chloro-2- 346.63 348 .sup.1H NMR (300 MHz, (methylthio)quinolin-4(1H)- CDCl.sub.3)8.67 (s, 1H), 7.91-7.88 (d, J = 8.19 Hz, one 1H), 7.71-7.68 (d, J = 8.49 Hz, 1H), 2.97 (s, 3H), 2.79 (s, 3H). 3 3-acetyl-2-(benzylthio)-8- 422.72 423 .sup.1H NMR (300 MHz, CDCl.sub.3)16.43 (s, bromo-5-chloroquinolin- 0.5H), 8.59 (br, 0.5H), 7.91 (d, J = 8.3 Hz, 4(1H)-one 1H), 7.62 (d, J = 8.4 Hz, 0.5H), 7.48-7.52 (m, 3H), 7.27-7.43 (m, 5H), 7.22 (d, J = 8.4 Hz, 0.5H), 4.80 (s, 2H), 4.32 (s, 1H), 2.93 (s, 3H), 2.69 (s, 1.5H). 4 3-acetyl-2-(benzylsulfinyl)-8- 438.72 439 .sup.1H NMR (300 MHz, CDCl.sub.3) bromo-5-chloroquinolin- 10.24 (br, 1H), 7.67 (d, J = 8.4 Hz, 1H), 4(1H)-one 7.29 (d, J = 8.4 Hz, 1H), 7.13-7.22 (m, 3H), 7.08-7.11 (m, 2H), 4.59-4.25 (m, 2H), 2.84 (s, 3H). 5 3-acetyl-8-bromo-5-chloro-1- 360.65 360 .sup.1H NMR (300 MHz, CDCl.sub.3) methyl-2- 7.92-7.89 (d, J = 8.22 Hz, 1H), 7.36-7.33 (d, (methylthio)quinolin-4(1H)- J = 8.13 Hz, 1H), 3.89 (s, 3H), 2.74 (s, one 3H), 2.65 (s, 3H). 6 3-acetyl-5,8-dichloro-2- 318.17 318 .sup.1H NMR (300 MHz, (methylsulfinyl)quinolin- CDCl.sub.3)11.07 (s, 1H), 4(1H)-one 7.67-7.64 (d, J = 8.46 Hz, 1H), 7.44-7.41 (d, J = 8.46 Hz, 1H), 3.02 (s, 3H), 2.78 (s, 3H). 7 3-acetyl-6-fluoro-1-methyl-2- 265.30 266 .sup.1H NMR (300 MHz, CDCl.sub.3) (methylthio)quinolin-4(1H)- 7.92-7.87 (q, J = 5.1, 3.99 Hz, 1H), one 7.69-7.65 (q, J = 2.88, 6.45 Hz, 1H), 7.48-7.39 (m, 1H), 4.53-4.46 (q, J = 7.14, 7.14 Hz, 2H), 4.08 (s, 3H), 3.66 (s, 3H), 1.48-1.44 (t, J = 7.14 Hz, 3H). 8 1-(6-fluoro-4-hydroxy-2- 251.28 252 .sup.1H NMR (300 MHz, CDCl.sub.3) (methylthio)quinolin-3- 7.83-7.78 (m, 2H), 7.49-7.42 (m, 1H), yl)ethan-1-one 4.59-4.52 (q, J = 7.14 Hz, 2H), 2.58 (s, 3H), 1.56-1.51 (t, J = 7.14 Hz, 3H). 9 3-acetyl-8-bromo-1-(4- 545.63 544 .sup.1H NMR (300 MHz, CDCl.sub.3) bromobenzoyl)-5-chloro-2- 8.09-8.07 (d, J = 5.73 Hz, 1H), 8.06-8.04 (d, (methylsulfinyl)quinolin- J = 6.15 Hz, 2H), 7.73-7.70 (d, J = 8.58 Hz, 4(1H)-one 2H), 7.56-7.54 (d, J = 8.22 Hz, 1H), 3.15 (s, 3H), 2.63 (s, 3H). 10 3-acetyl-8-bromo-5-chloro-2- 457.16 456 .sup.1H NMR (300 MHz, DMSO) ((4- 7.65-7.62 (d, J = 8.13 Hz, 1H), 7.45-7.42 (d, chlorobenzyl)thio)quinolin- J = 6.69 Hz, 2H), 7.29-7.26 (d, J = 8.34 Hz, 4(1H)-one 2H), 6.91-6.88 (d, J = 8.19 Hz, 1H), 4.44 (s, 2H), 2.40 (s, 3H). 11 3-acetyl-8-bromo-5-chloro-2- 473.16 472 .sup.1H NMR (300 MHz, ((4- CDCl.sub.3)10.21 (s, 1H), chlorobenzyl)sulfinyl)quinolin- 7.73-7.71 (d, J = 8.43 Hz, 1H), 7.33-7.31 (d, 4(1H)-one J = 8.37 Hz, 1H), 7.18-7.15 (d, J = 9 Hz, 2H), 7.05-7.03 (d, J = 8.25 Hz, 2H), 4.37 (s, 2H), 2.84 (s, 3H). 12 3-acetyl-8-bromo-5-chloro-2- 408.69 408 .sup.1H NMR (300 MHz, MeOD) (phenylthio)quinolin-4(1H)- 7.51-7.48 (m, 2H), 7.46-7.43 (d, J = 8.11 Hz, one 1H), 7.31-7.28 (d, J = 7.71 Hz, 3H), 6.81-6.78 (d, J = 8.19 Hz, 1H). 13 3-acetyl-8-bromo-5-chloro-2- 424.69 424 .sup.1H NMR (300 MHz, CDCl.sub.3) (phenylsulfinyl)quinolin- 7.84-7.75 (m, 2H), 7.68-7.64 (m, 2H), 4(1H)-one 7.52-7.50 (d, J = 8.43 Hz, 1H), 7.48-7.45 (m, 1H), 7.38-7.35 (d, J = 8.43 Hz, 1H), 2.78 (s, 3H). 14 3-acetyl-8-bromo-5-chloro-2- 438.72 438 .sup.1H NMR (300 MHz, ((2- CDCl.sub.3)8.55 (s, 1H), 7.709 (m, 1H), methoxyphenyl)thio)quinolin- 7.633 (m, 1H), 7.511 (d, 1H, J = 8.43 Hz), 4(1H)-one 7.158 (m, 3H), 3.861 (s, 3H), 2.781 (s, 3H). 15 3-acetyl-8-bromo-5-chloro-2- 454.72 454 .sup.1H NMR (300 MHz, CDCl.sub.3)7.84 (d, J = 8.4 Hz, ((2- 1H), 7.383 (d, J = 8.4 Hz, methoxyphenyl)sulfinyl)quinolin- 1H), 7.53 (m, 1H), 7.415 (m, 1H), 4(1H)-one 6.949 (s, 1H), 6.956 (s, 1H), 3.86 (s, 3H), 2.634 (s, 3H) 16 3-acetyl-8-bromo-2-((4- 487.59 486 .sup.1H NMR (300 MHz, bromophenyl)thio)-5- CDCl.sub.3)8.30 (s, 1H), 7.779 (d, J = 8.4 Hz, chloroquinolin-4(1H)-one 2H), 7.614 (d, J = 8.46 Hz, 2H), 7.541 (d, J = 8.4 Hz, 1H), 7.183 (d, J = 8.46 Hz, 1H), 2.77 (s, 3H). 17 3-acetyl-8-bromo-2-((4- 503.59 502 .sup.1H NMR (300 MHz, bromophenyl)sulfinyl)-5- CDCl.sub.3)11.37 (s, 1H), chloroquinolin-4(1H)-one 7.84-7.81 (d, J = 8.46 Hz, 1H), 7.73-7.70 (d, J = 8.73 Hz, 2H), 7.60-7.57 (d, J = 8.67 Hz, 2H), 7.39-7.38 (d, J = 8.43 Hz, 1H), 2.70 (s, 3H). 18 1,1-(8-bromo-5-chloro-2- 388.66 388 .sup.1H NMR (300 MHz, MeOD) 7.84 (d, (methylthio)-4-oxoquinoline- J = 8.25, 1H), 7.19 (d, J = 8.25, 1H), 1,3(4H)-diyl)bis(ethan-1-one) 2.72 (s, dH), 2.57 (s, 3H), 2.18 (s, 3H). 19 1,1-(8-bromo-5-chloro-2- 404.66 404 .sup.1H NMR (300 MHz, (methylsulfinyl)-4- CDCl.sub.3)8.07 (m, 1H), 7.60 (m, 1H), oxoquinoline-1,3(4H)- 3.03 (s, 3H), 3.02 (s, 3H), 2.78 (s, 3H). diyl)bis(ethan-1-one) 20 3-acetyl-2-(benzylsulfinyl)-8- 621.72 620 .sup.1H NMR (300 MHz, (CD.sub.3).sub.2CO) bromo-1-(4-bromobenzoyl)- 7.96-7.93 (d, J = 8.22 Hz, 1H), 7.73-7.60 (m, 5-chloroquinolin-4(1H)-one 7H), 7.45-7.42 (d, J = 8.25 Hz, 2H), 7.16-7.13 (d, J = 8.19 Hz, 1H), 2.86 (s, 3H). 21 3-acetyl-8-bromo-1-(4- 561.63 560 .sup.1H NMR (300 MHz, bromobenzoyl)-5-chloro-2- CDCl.sub.3)8.10 (d, J = 8.22 Hz, 1H), (methylsulfonyl)quinolin- 8.03-7.67 (dd, J = 8.61, 88.8 Hz, 4H), 4(1H)-one 7.60 (J = 8.22 Hz, 1H), 3.53 (s, 3H), 2.67 (s, 3H). 22 3-acetyl-8-bromo-5-chloro-1- 505.18 504 .sup.1H NMR (300 MHz, CDCl.sub.3) (3-chloro-4-fluorobenzyl)-2- 7.42-7.37 (m, 2H), (methylsulfinyl)quinolin- 7.24-7.09 (m, 3H), 4.49 (s, 2H), 3.44 (s, 3H), 4(1H)-one 2.14 (s, 3H). 23 3-acetyl-2-(benzylthio)-8- 605.73 604 .sup.1H NMR (300 MHz, CDCl.sub.3) bromo-1-(4-bromobenzoyl)- 8.06-8.03 (d, J = 8.28 Hz, 1H), 7.93-7.91 (d, 5-chloroquinolin-4(1H)-one J = 8.64 Hz, 2H), 7.71-7.68 (d, 8.64 Hz, 2H), 7.54-7.51 (d, J = 7.02 Hz, 2H), 7.49-7.46 (d, J = 8.25 Hz, 1H), 7.30-7.27 (d, J = 7.33 Hz, 2H), 6.97 (s, 1H), 4.71 (s, 2H). 24 3-acetyl-8-bromo-5-chloro-2- 374.68 374 .sup.1H NMR (300 MHz, (isopropylthio)quinolin- CDCl.sub.3)16.32 (s, 1H), 4(1H)-one 7.77-7.86 (d, J = 8.13 Hz, 1H), 7.26-7.23 (d, J = 8.61 HZ, 1H), 4.54-4.45 (m, 1H), 2.94 (s, 3H), 1.54-1.51 (m, 6H). 25 3-acetyl-8-bromo-5-chloro-2- 390.68 390 .sup.1H NMR (300 MHz, (isopropylsulfinyl)quinolin- CDCl.sub.3)10.99 (s, 1H), 4(1H)-one 7.80-7.77 (d, J = 8.37 Hz, 1H), 7.36-7.34 (d, J = 8.4 Hz, 1H), 3.61-3.51 (m, 1H), 2.77 (s, 3H), 1.63-1.61 (d, J = 7.12 Hz, 3H), 1.01-0.99 (d, J = 6.78 Hz, 3H). 26 3-acetyl-8-bromo-5-chloro-2- 452.75 452 .sup.1H NMR (300 MHz, ((1- CDCl.sub.3)11.06 (br, 1H), 7.82 (d, J = 8.4 Hz, phenylethyl)sulfinyl)quinolin- 1H), 7.60-7.65 (m, 2H), 4(1H)-one 7.41-7.50 (m, 3H), 7.38 (d, J = 8.5 Hz, 1H), 4.72 (q, J = 7.3 Hz, 1H), 2.84 (s, 3H), 1.42 (d, J = 7.1 Hz, 3H). 27 3-(((3-acetyl-8-bromo-5- 447.73 447 .sup.1H NMR (300 MHz, chloro-4-oxo-1,4- CDCl.sub.3)7.92 (d, J = 8.3 Hz, 1H), dihydroquinolin-2- 7.83 (s, 1H), 7.76 (d, J = 7.9 Hz, 1H), yl)thio)methyl)benzonitrile 7.55 (d, J = 7.7 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.32 (d, J = 8.3 Hz, 1H), 4.82 (s, 2H), 2.94 (s, 3H). 28 3-(((3-acetyl-8-bromo-5- 463.73 463 .sup.1H NMR (300 MHz, chloro-4-oxo-1,4- CDCl.sub.3)10.27 (br, 1H), 7.72 (d, J = 8.5 Hz, dihydroquinolin-2- 1H), 7.53-7.57 (m, 1H), yl)sulfinyl)methyl)benzonitrile 7.27-7.40 (m, 2H), 4.59-4.22 (m, 2H), 2.85 (s, 3H). 29 3-acetyl-8-bromo-5-chloro-2- 474.70 474 .sup.1H NMR (300 MHz, ((2,4- CDCl.sub.3)10.34 (br, 1H), 7.74 (d, J = 8.4 Hz, difluorobenzyl)sulfinyl)quinolin- 1H), 7.35 (d, J = 8.4 Hz, 1H), 4(1H)-one 7.20-7.28 (m, 1H), 6.81-6.87 (m, 1H), 6.60-6.75 (m, 1H), 4.53 (dd, J = 48.9, 13.2 Hz, 2H), 2.85 (s, 3H). 30 3-acetyl-8-bromo-5-chloro-2- 475.15 474 .sup.1H NMR (300 MHz, ((3-chloro-4- CDCl.sub.3)7.92 (d, J = 8.3 Hz, 1H), fluorobenzyl)thio)quinolin- 7.83 (s, 1H), 7.76 (d, J = 7.9 Hz, 1H), 4(1H)-one 7.55 (d, J = 7.7 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.32 (d, J = 8.3 Hz, 1H), 4.82 (s, 2H), 2.94 (s, 3H). 31 3-acetyl-8-bromo-5-chloro-2- 491.15 490 .sup.1H NMR (300 MHz, ((3-chloro-4- CDCl.sub.3)10.27 (br, 1H), 7.73 (d, J = 8.4 Hz, fluorobenzyl)sulfinyl)quinolin- 1H), 7.33 (d, J = 8.4 Hz, 1H), 4(1H)-one 7.22-7.24 (m, 1H), 6.95-6.98 (m, 2H), 4.33 (q, J = 12.8 Hz, 2H), 2.84 (s, 3H). 32 3-acetyl-8-bromo-5-chloro-2- 467.72 467 .sup.1H NMR (300 MHz, ((4-nitrobenzyl)thio)quinolin- CDCl.sub.3)8.16 (d, J = 8.6 Hz, 2H), 4(1H)-one 7.92 (d, J = 8.3 Hz, 1H), 7.69 (d, J = 8.6 Hz, 2H), 7.32 (d, J = 8.2 Hz, 1H), 4.90 (s, 2H), 2.94 (s, 3H). 33 3-acetyl-8-bromo-5-chloro-2- 483.72 483 .sup.1H NMR (300 MHz, ((4- CDCl.sub.3)10.23 (br, 1H), 8.08 (d, J = 8.7 Hz, nitrobenzyl)sulfinyl)quinolin- 2H), 7.70 (d, J = 8.4 Hz, 1H), 4(1H)-one 7.34 (dd, J = 8.5, 3.9 Hz, 3H), 4.49 (dd, J = 27.8, 12.6 Hz, 2H), 2.85 (s, 3H). 34 3-acetyl-2-(benzylsulfonyl)- 454.72 454 .sup.1H NMR (300 MHz, 8-bromo-5-chloroquinolin- CDCl.sub.3)10.25 (s, 1H), 7.66 (d, J = 8.46 Hz, 4(1H)-one 1H), 7.28 (d, J = 8.43 Hz, 1H), 7.20-7.08 (m, 5H), 4.41 (d, J = 3, 2H), 2.84 (s, 3H). 35 3-acetyl-8-bromo-5-chloro-1- 424.71 424 .sup.1H NMR (300 MHz, (methylsulfonyl)-2- CDCl.sub.3)7.96 (d, J = 8.25 Hz, 1H), (methylthio)quinolin-4(1H)- 7.42 (d, J = 8.28 Hz, 1H), 3.30 (s, 3H), one 2.76 (s, 3H), 2.73 (s, 3H). 36 3-acetyl-8-bromo-5-chloro-2- 494.68 494 .sup.1H NMR (300 MHz, CDCl.sub.3) (methylsulfinyl)-1- 8.08-8.05 (d, J = 8.22 Hz, 1H), 7.69-7.65 (d, ((trifluoromethyl)sulfonyl)quinolin- J = 8.25 Hz, 1H), 3.11 (s, 3H), 2.78 (s, 4(1H)-one 3H). 37 3-acetyl-8-bromo-5-chloro-1- 521.22 520 .sup.1H NMR (300 MHz, CDCl.sub.3) ((4-chlorophenyl)sulfonyl)-2- 7.93-7.91 (d, J = 8.22 Hz, 1H), 7.74-7.71 (d, (methylthio)quinolin-4(1H)- J = 8.7 Hz, 2H), 7.50-7.47 (d, J = 8.61 Hz, one 2H), 7.32-7.30 (d, J = 8.25 Hz, 1H), 2.71 (s, 3H), 2.62 (s, 3H). 38 3-acetyl-8-bromo-5-chloro-2- 531.78 531 .sup.1H NMR (300 MHz, CDCl.sub.3) (methylthio)-1-((4- 8.39-8.36 (d, J = 8.85 Hz, 2H), 8.03-8.00 (d, nitrophenyl)sulfonyl)quinolin- J = 8.85, 2H), 7.96-9.93 (d, J = 8.22 Hz, 4(1H)-one 1H), 7.35-7.32 (d, J = 8.22 Hz, 1H), 2.74 (s, 3H), 2.62 (s, 3H). 39 3-acetyl-8-bromo-5-chloro-1- 454.73 454 .sup.1H NMR (300 MHz, CDCl.sub.3) (ethylsulfonyl)-2- 7.96-7.93 (d, J = 8.23 Hz, 1H), 7.42-7.39 (d, (methylsulfinyl)quinolin- J = 8.16 Hz, 1H), 3.54-3.46 (q, J = 7.41, 4(1H)-one 7.5 Hz, 2H), 2.76 (s, 3H), 2.73 (s, 3H), 1.58-1.53 (t, J = 7.38, 7.44, 3H). 40 3-acetyl-8-bromo-1-((4-(tert- 542.89 542 .sup.1H NMR (300 MHz, CDCl.sub.3) butyl)phenyl)sulfonyl)-5- 7.88-7.85 (d, J = 8.16 Hz, 1H), 7.69-7.66 (d, chloro-2- J = 8.67 Hz, 2H), 7.47-7.44 (d, J = 8.7 Hz, (methylthio)quinolin-4(1H)- 2H), 7.25-7.23 (d, J = 8.13 Hz, one 1H), 2.71 (s, 3H), 2.63 (s, 3H), 1.33 (s, 9H). 41 3-acetyl-8-bromo-1-((4-(tert- 574.89 574 .sup.1H NMR (300 MHz, CDCl.sub.3) butyl)phenyl)sulfonyl)-5- 8.10-8.07 (d, J = 8.22 Hz, 1H), 7.80-7.78 (d, chloro-2- J = 8.64 Hz, 2H), 7.62-7.59 (d, J = 8.25 Hz, (methylsulfonyl)quinolin- 1H), 7.58-7.55 (d, J = 8.64 Hz, 4(1H)-one 2H), 3.48 (s, 3H), 2.71 (s, 3H), 1.37 (s, 9H). 42 3-acetyl-8-bromo-1-((4-(tert- 558.89 558 .sup.1H NMR (300 MHz, CDCl.sub.3) butyl)phenyl)sulfonyl)-5- 8.05-8.03 (d, J = 8.16 Hz, 1H), 7.71-7.68 (d, chloro-2- J = 8.64 Hz, 2H), 7.52-7.49 (d, J = 8.28 Hz, (methylsulfinyl)quinolin- 3H), 3.13 (s, 3H), 2.69 (s, 3H), 4(1H)-one 1.35 (s, 9H). 43 3-acetyl-8-bromo-5-chloro-2- 491.61 490 .sup.1H NMR (300 MHz, DMSO) ((2,5- 7.93-7.90 (d, J = 8.25 Hz, 1H), 7.84 (s, 1H), dichlorobenzyl)thio)quinolin- 7.52-7.49 (d, J = 8.52 Hz, 1H), 4(1H)-one 7.37-7.33 (m, 1H), 7.25-7.22 (d, J = 8.34 Hz, 1H), 4.65 (s, 2H). 44 3-acetyl-8-bromo-5-chloro-2- 507.60 506 .sup.1H NMR (300 MHz, ((2,5- CDCl.sub.3)10.35 (s, 1H), dichlorobenzyl)sulfinyl)quinolin- 7.73-7.72 (d, J = 10.86 Hz, 1H), 7.32 (s, 2H), 4(1H)-one 7.17 (s, 2H), 4.81-4.49 (dd, J = 13.33, 69.53 Hz, 2H), 2.81 (s, 3H). 45 3-acetyl-8-bromo-5-chloro-2- 458.70 458 .sup.1H NMR (300 MHz, CDCl.sub.3) ((3,5- 7.93-7.91 (d, J = 8.28 Hz, 1H), 7.33-7.30 (d, difluorobenzyl)thio)quinolin- J = 8.28 Hz, 1H), 7.06-7.04 (m, 3H), 4(1H)-one 4.78 (s, 2H), 2.94 (s, 3H). 46 3-acetyl-8-bromo-5-chloro-2- 474.70 474 .sup.1H NMR (300 MHz, ((3,5- CDCl.sub.3)10.43 (s, 1H), 7.75-7.72 (d, J = 8.4 Hz, difluorobenzyl)sulfinyl)quinolin- 1H), 7.35-7.32 (d, J = 8.46 Hz, 4(1H)-one 1H), 6.80-6.68 (m, 3H), 4.44-4.23 (q, J = 12.63, 36.84 Hz, 2H), 2.84 (s, 3H). 47 3-acetyl-8-bromo-5-chloro-2- 548.62 548 .sup.1H NMR (300 MHz, DMSO) ((3-iodobenzyl)thio)quinolin- 7.97-7.94 (d, J = 5.55 Hz, 1H), 7.89 (s, 1H), 4(1H)-one 7.61-7.58 (d, J = 8.16 Hz, 1H), 7.49-7.46 (d, J = 7.11 Hz, 1H), 7.31-7.29 (m, 1H), 7.13-7.80 (t, J = 7.76 Hz, 1H), 4.55 (s, 2H). 48 3-acetyl-8-bromo-5-chloro-2- 564.62 564 .sup.1H NMR (300 MHz, ((3- CDCl.sub.3)10.19 (s, 1H), iodobenzyl)sulfinyl)quinolin- 7.74-7.71 (d, J = 8.46 Hz, 1H), 7.56-7.54 (d, 4(1H)-one J = 8.07 Hz, 1H), 7.39 (s, 1H), 7.35-7.32 (d, J = 8.46 Hz, 1H), 7.09-7.07 (d, J = 8.01 Hz, 1H), 6.97-6.92 (t, J = 7.74 Hz, 1H), 4.40-4.30 (q, J = 12.71, 6.06 Hz, 2H), 2.87 (s, 3H). 49 3-acetyl-8-bromo-5-chloro-2- 440.71 440 .sup.1H NMR (300 MHz, CDCl.sub.3) ((3- 7.93-7.91 (d, J = 8.25 Hz, 1H), 7.32-7.30 (d, fluorobenzyl)thio)quinolin- J = 8.19 Hz, 2H), 7.28-7.27 (m, 2H), 4(1H)-one 6.97 (s, 1H), 4.79 (s, 2H), 2.94 (s, 3H). 50 3-acetyl-8-bromo-5-chloro-2- 456.71 456 .sup.1H NMR (300 MHz, ((3- CDCl.sub.3)10.30 (s, 1H), fluorobenzyl)sulfinyl)quinolin- 7.70-7.67 (d, J = 8.56 Hz, 1H), 7.30-7.27 (d, 4(1H)-one J = 8.43 Hz, 1H), 7.15-7.07 (m, 1H), 6.98-6.88 (m, 2H), 6.83-6.81 (d, J = 7.68 Hz, 1H), 4.42-4.32 (q, J = 12.66, 3.33 Hz, 2H), 2.82 (s, 3H). 51 3-acetyl-8-bromo-5-chloro-2- 443.70 442 .sup.1H NMR (300 MHz, (((5-methylisoxazol-3- CDCl.sub.3)10.50 (br, 1H), 7.77 (d, J = 8.4 Hz, yl)methyl)sulfinyl)quinolin- 1H), 7.36 (d, J = 8.4 Hz, 1H), 4(1H)-one 6.17 (s, 1H), 4.33-4.67 (m, 2H), 2.83 (s, 3H), 2.39 (s, 3H). 52 1-(2-(benzylthio)-8-bromo-5- 422.72 422 .sup.1H NMR (300 MHz, chloro-4-hydroxyquinolin-3- CDCl.sub.3)7.82 (d, J = 8.2 Hz, 1H), yl)ethan-1-one 7.53 (d, J = 6.8 Hz, 2H), 7.32-7.48 (m, 3H), 7.26 (d, J = 8.4 Hz, 1H), 6.77 (s, 2H), 5.24 (s, 3H). 53 1-(2-(benzylsulfinyl)-8- 438.72 438 .sup.1H NMR (300 MHz, bromo-5-chloro-4- CDCl.sub.3)7.99 (d, J = 8.2 Hz, 1H), hydroxyquinolin-3-yl)ethan- 7.60 (s, 1H), 7.54-7.57 (m, 2H), 7.51 (d, J = 8.2 Hz, 1-one 1H), 7.37-7.48 (m, 3H), 5.39 (s, 2H), 3.48 (s, 3H). 54 1-(2-(benzylsulfonyl)-8- 454.72 454 .sup.1H NMR (300 MHz, bromo-5-chloro-4- CDCl.sub.3)7.94 (d, J = 8.2 Hz, 1H), hydroxyquinolin-3-yl)ethan- 7.73 (s, 1H), 7.54-7.58 (m, 2H), 7.45 (d, J = 8.1 Hz, 1-one 2H), 7.38-7.41 (m, 2H), 5.42 (s, 2H), 3.01 (s, 3H). 55 3-acetyl-8-bromo-5-chloro-2- 468.75 468 .sup.1H NMR (300 MHz, ((3- CDCl.sub.3)10.32 (s, 1H), 7.71-7.69 (d, J = 8.4 Hz, methoxybenzyl)sulfinyl)quinolin- 1H), 7.33-7.30 (d, J = 8.43, 1H), 4(1H)-one 7.09-7.04 (t, J = 7.8 Hz, 1H), 6.76-6.70 (m, 2H), 6.65-6.63 (d, J = 7.47 Hz, 1H), 4.44-4.34 (q, J = 12.7, 4.86 Hz, 2H), 3.70 (s, 3H), 2.86 (s, 3H). 56 3-acetyl-8-bromo-5-chloro-2- 538.78 538 .sup.1H NMR (300 MHz, ((4- CDCl.sub.3)10.27 (s, 1H), ((trifluoromethyl)thio)benzyl)sulfinyl)quinolin- 7.69-7.66 (d, J = 8.40 Hz, 1H), 7.49-7.46 (d, 4(1H)-one J = 8.01 Hz, 2H), 7.31-7.28 (d, J = 8.40 Hz, 1H), 7.18-7.15 (d, J = 8.16 Hz, 2H), 4.52-4.37 (q, J = 12.7, 17.1 Hz, 2H), 2.84 (s, 3H). 57 3-acetyl-5,8-dichloro-2-((4- 439.26 439 .sup.1H NMR (300 MHz, MeOD) 9.95 (s, nitrobenzyl)sulfinyl)quinolin- 1H), 8.22-8.20 (d, J = 8.6 Hz, 2H), 4(1H)-one 7.73-7.70 (d, J = 8.31 Hz, 2H), 7.63-7.60 (d, J = 8.22 Hz, 1H), 7.29-7.26 (d, J = 8.13 Hz, 1H), 4.59-4.10 (q, J = 12.3, 122 Hz, 2H), 2.72 (s, 3H). 58 2-(((3-acetyl-8-bromo-5- 463.73 463 .sup.1H NMR (300 MHz, chloro-4-oxo-1,4- CDCl.sub.3)10.30 (br, 1H), 7.69 (d, J = 8.4 Hz, dihydroquinolin-2- 1H), 7.47-7.61 (m, 2H), yl)sulfinyl)methyl)benzonitrile 7.34-7.45 (m, 2H), 7.31 (d, J = 8.4 Hz, 1H), 4.71 (q, J = 13.1 Hz, 2H), 2.85 (s, 3H). 59 3-acetyl-8-bromo-5-chloro-2- 498.77 498 .sup.1H NMR (300 MHz, ((3,5- CDCl.sub.3)10.36 (s, 1H), 7.69 (d, J = 8.4 Hz, dimethoxybenzyl)sulfinyl)quinolin- 1H), 7.30 (d, J = 8.4 Hz, 1H), 6.23 (s, 4(1H)-one 3H), 4.25-4.39 (m, 2H), 3.62 (s, 6H), 2.83 (s, 3H). 60 3-acetyl-8-bromo-2-((4-(tert- 494.83 494 .sup.1H NMR (300 MHz, butyl)benzyl)sulfinyl)-5- CDCl.sub.3)10.15 (br, 1H), 7.62 (d, J = 8.4 Hz, chloroquinolin-4(1H)-one 1H), 7.25 (d, J = 8.4 Hz, 1H), 7.13 (d, J = 8.3 Hz, 2H), 6.96 (d, J = 8.3 Hz, 2H), 4.40 (dd, J = 53.3, 12.7 Hz, 2H),, 2.83 (s, 3H), 1.11 (s, 9H). 61 3-acetyl-8-bromo-5-chloro-2- 376.65 376 .sup.1H NMR (300 MHz, ((methoxymethyl)thio)quinolin- CDCl.sub.3)10.62 (br, 1H), 7.69 (d, J = 8.4 Hz, 4(1H)-one 1H), 7.24 (d, J = 8.4 Hz, 1H), 5.07 (s, 2H), 3.66 (s, 3H), 2.69 (s, 3H). 62 3-acetyl-8-bromo-5-chloro-2- 332.60 332 .sup.1H NMR (300 MHz, mercaptoquinolin-4(1H)-one CDCl.sub.3)10.11 (br, 1H), 7.74 (d, J = 8.5 Hz, 1H), 7.21 (d, J = 8.5 Hz, 1H), 3.15 (s, 3H). 63 3-acetyl-2-((4- 542.83 542 .sup.1H NMR (300 MHz, benzoylbenzyl)sulfinyl)-8- CDCl.sub.3)10.29 (br, 1H), 7.67 (d, J = 8.4 Hz, bromo-5-chloroquinolin- 1H), 7.61 (d, J = 8.2 Hz, 2H), 4(1H)-one 7.37-7.59 (m, 5H), 7.31 (d, J = 8.4 Hz, 1H), 7.23 (d, J = 8.2 Hz, 2H), 4.51 (q, J = 12.6 Hz, 2H), 2.85 (s, 3H). 64 3-acetyl-8-bromo-5-chloro-2- 554.78 554 .sup.1H NMR (300 MHz, CDCl.sub.3)10.30 (br ((4- s, 1H), 7.70-7.62 (m, 3H), 7.41-7.26 (m, ((trifluoromethyl)sulfinyl)benzyl)sulfinyl)quinolin- 3H), 4.55-4.45 (q, J = 16.3 Hz, 2H), 4(1H)- 2.84 (s, 3H). one 65 2-((3-acetyl-8-bromo-5- 387.63 387 .sup.1H NMR (300 MHz, chloro-4-oxo-1,4- CDCl.sub.3)10.97 (br, 1H), 7.87 (d, J = 8.4 Hz, dihydroquinolin-2- 1H), 7.43 (d, J = 8.5 Hz, 1H), yl)sulfinyl)acetonitrile 4.27 (q, J = 16.3 Hz, 2H), 2.84 (s, 3H). 66 2-((3-acetyl-8-bromo-5- 371.63 371 .sup.1H NMR (300 MHz, chloro-4-oxo-1,4- CDCl.sub.3)7.96 (d, J = 8.3 Hz, 1H), dihydroquinolin-2- 7.36 (d, J = 8.3 Hz, 1H), 4.30 (s, 2H), yl)thio)acetonitrile 2.94 (s, 3H). 67 (Z)-3-((3-acetyl-8-bromo-5- 402.64 402 .sup.1H NMR (300 MHz, MeOD) chloro-4-oxo-1,4- 9.03 (br, 0.5H), 8.84 (br, 1H), 7.97 (d, J = 8.2 Hz, dihydroquinolin-2- 1H), 7.91 (d, J = 8.3 Hz, 0.5H), yl)thio)acrylic acid 7.37 (d, J = 8.4 Hz, 1H), 7.31 (d, J = 8.3 Hz, 0.5H), 6.34 (d, J = 10.8 Hz, 0.5H), 6.22 (d, J = 10.3 Hz, 1H), 2.78 (s, 3H), 2.72 (s, 1.5H). 68 3-acetyl-8-bromo-5-chloro-2- 564.76 564 .sup.1H NMR (300 MHz, CDCl.sub.3)10.14 (s, ((4-(pentafluoro-l6- 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.57 (d, sulfanyl)benzyl)sulfinyl)quinolin- J = 8.7 Hz, 2H), 7.33 (d, J = 8.5 Hz, 4(1H)-one 1H), 7.20 (d, J = 8.3 Hz, 2H), 4.47 (dd, J = 30.2, 12.6 Hz, 2H), 2.87 (s, 3H). 69 3-acetyl-8-bromo-5-chloro-2- 582.75 582 .sup.1H NMR (300 MHz, ((2-fluoro-4-(pentafluoro-l6- CDCl.sub.3)10.19 (s, 1H), sulfanyl)benzyl)sulfinyl)quinolin- 7.71-7.68 (d, J = 8.43 Hz, 1H), 7.33-7.30 (d, 4(1H)-one J = 8.31 Hz, 1H), 4.73-4.40 (q, J = 13.0, 72.1 Hz, 2H), 2.83 (s, 3H). 70 3-acetyl-8-bromo-5-chloro-2- 506.72 506 .sup.1H NMR (300 MHz, CDCl.sub.3)10.16 (s, ((4- 1H), 7.71 (d, J = 8.4 Hz, 1H), 7.46 (d, (trifluoromethyl)benzyl)sulfinyl)quinolin- J = 8.1 Hz, 2H), 7.33 (d, J = 8.4 Hz, 4(1H)-one 1H), 7.25 (d, J = 8.0 Hz, 2H), 4.60-4.34 (m, 2H), 2.87 (s, 3H). 71 3-acetyl-8-bromo-5-chloro-2- 522.72 522 .sup.1H NMR (300 MHz, ((4- CDCl.sub.3)10.24 (br, 1H), 7.69 (d, J = 8.5 Hz, (trifluoromethoxy)benzyl)sulfinyl)quinolin- 1H), 7.30 (d, J = 8.4 Hz, 1H), 4(1H)-one 7.14 (d, J = 8.7 Hz, 2H), 7.04 (d, J = 8.1 Hz, 2H), 4.42 (q, J = 12.8 Hz, 2H), 2.84 (s, 3H). 72 3-acetyl-8-bromo-5-chloro-2- 496.68 496 .sup.1H NMR (300 MHz, CDCl.sub.3)10.34 (s, (((5-(trifluoromethyl)furan-2- 1H), 7.75 (d, J = 8.5 Hz, 1H), 7.36 (d, yl)methyl)sulfinyl)quinolin- J = 8.4 Hz, 1H), 6.71 (s, 1H), 6.59 (d, 4(1H)-one J = 3.1 Hz, 1H), 4.58 (dd, J = 71.0, 14.1 Hz, 2H), 2.87 (s, 3H). 73 4-(((3-acetyl-8-bromo-5- 463.73 463 .sup.1H NMR (300 MHz, CDCl.sub.3)10.21 (s, chloro-4-oxo-1,4- 1H), 775-7.72 (d, J = 8.4 Hz, 1H), dihydroquinolin-2- 7.52-7.50 (d, J = 8.04 Hz, 2H), 7.36-7.33 (d, yl)sulfinyl)methyl)benzonitrile J = 8.43 Hz, 1H), 7.27-7.25 (d, J = 8.1 Hz, 2H), 4.50-4.39 (q, J = 12.4, 6.33 Hz, 2H), 2.84 (s, 3H). 74 3-acetyl-8-bromo-5-chloro-2- 491.15 491 .sup.1H NMR (300 MHz, ((2-chloro-6- CDCl.sub.3)10.6 (s, 1H), 7.75-7.72 (d, J = 8.4 Hz, fluorobenzyl)sulfinyl)quinolin- 1H), 7.35-7.33 (d, J = 8.4 Hz, 1H), 4(1H)-one 7.31-7.28 (m, 1H), 7.24-7.18 (t, J = 8.8 Hz, 1H), 7.01-6.96 (t, J = 8.0 Hz, 1H), 5.08-5.05 (q, J = 1.9, 11, 120 Hz, 2H), 2.82 (s, 3H). 75 3-acetyl-8-bromo-5-chloro-2- 594.79 594 .sup.1H NMR (300 MHz, ((2-methoxy-4-(pentafluoro- CDCl.sub.3)10.26 (s, 1H), l6- 7.69-7.67 (d, J = 8.40 Hz, 1H), 7.31-7.28 (d, sulfanyl)benzyl)sulfinyl)quinolin- J = 8.43 Hz, 1H), 4.80-4.40 (q, J = 13.0, 4(1H)-one 95.7 Hz, 2H), 2.82 (s, 3H). 76 3-acetyl-8-bromo-5-chloro-2- 582.75 582 .sup.1H NMR (300 MHz, CDCl.sub.3)10.13 (s, ((3-fluoro-5-(pentafluoro-l6- 1H), 7.70 (d, J = 8.5 Hz, 1H), 7.38 (s, sulfanyl)benzyl)sulfinyl)quinolin- 1H), 7.33 (d, J = 8.6 Hz, 1H), 7.21 (d, 4(1H)-one J = 8.1 Hz, 1H), 7.09 (s, 1H), 4.44 (s, 2H), 2.84 (s, 3H). 77 3-acetyl-8-bromo-5-chloro-2- 564.76 564 .sup.1H NMR (300 MHz, CDCl.sub.3)10.06 (s, ((3-(pentafluoro-l6- 1H), 7.59-7.68 (m, 2H), sulfanyl)benzyl)sulfinyl)quinolin- 7.29-7.38 (m, 4H), 4.47 (q, J = 12.8 Hz, 2H), 4(1H)-one 2.85 (s, 3H). 78 3-acetyl-8-bromo-5-chloro-2- 528.67 528 .sup.1H NMR (300 MHz, (((perfluorophenyl)methyl)sulfinyl)quinolin- CDCl.sub.3)10.48 (s, 1H), 4(1H)-one 7.79-7.77 (d, J = 8.43 Hz, 1H), 7.38-7.36 (d, J = 8.31 Hz, 1H), 4.49-4.40 (q, J = 13.0, 128 Hz, 2H), 2.83 (s, 3H). 79 3-acetyl-5,8-dichloro-2-((4- 494.32 494 .sup.1H NMR (300 MHz, CDCl.sub.3)10.24 (br ((trifluoromethyl)thio)benzyl)sulfinyl)quinolin- s, 1H), 7.56-7.49 (m, 4H), 4(1H)-one 7.39-7.37 (d, J = 8.52 Hz, 2H), 7.21-7.18 (d, J = 7.68 Hz, 2H), 4.52-4.40 (q, J = 13.4 Hz, 2H), 2.87 (s, 3H). 80 3-acetyl-5,8-difluoro-2-((4- 487.40 487 .sup.1H NMR (300 MHz, CDCl.sub.3)9.78 (br (pentafluoro-l6- s, 1H), 7.59-7.58 (d, J = 8.49 Hz, 1H), sulfanyl)benzyl)sulfinyl)quinolin- 7.37-7.22 (m, 3H), 7.06-6.98 (m, 1H), 4(1H)-one 4.41 (s, 2H), 2.84 (s, 3H). 81 3-acetyl-5,8-difluoro-2-(((5- 419.32 419 .sup.1H NMR (300 MHz, CDCl.sub.3)9.93 (br (trifluoromethyl)furan-2- s, 1H), 7.41-7.33 (m, 1H), yl)methyl)sulfinyl)quinolin- 7.08-7.00 (m, 1H), 6.71-6.69 (m, 1H), 4(1H)-one 6.56-6.55 (m, 1H), 4.66 (d, J = 14.1 Hz, 1H), 4.48-4.44 (d, J = 14.07 Hz, 1H), 2.83 (s, 3H). 82 3-acetyl-5,8-difluoro-2-(((5- 366.34 366 .sup.1H NMR (300 MHz, CDCl.sub.3) 10.45 (br methylisoxazol-3- s, 1H), 7.61-7.59 (d, J = 8.49 Hz, 2H), yl)methyl)sulfinyl)quinolin- 7.41-7.38 (d, J = 8.46 Hz, 1H), 6.16 (s, 4(1H)-one 1H), 4.51-4.39 (q, J = 13.5, 21.8 Hz, 2H), 2.81 (s, 3H), 2.37 (s, 3H). 83 3-acetyl-5,8-dichloro-2-((4- 520.16 520 .sup.1H NMR (300 MHz, CDCl.sub.3)10.11 (br iodobenzyl)sulfinyl)quinolin- s, 1H), 7.60-7.57 (d, J = 8.46 Hz, 1H), 4(1H)-one 7.51-7.49 (d, J = 8.22 Hz, 2H), 7.40-7.37 (d, J = 8.43 Hz, 1H), 6.83-6.81 (d, J = 8.22 Hz, 2H), 4.32 (s, 2H), 2.83 (s, 3H). 84 3-acetyl-8-bromo-5-chloro-2- 439.71 439 .sup.1H NMR (300 MHz, DMSO) 8.41 (d, ((pyridin-3- J = 4.6 Hz, 1H), 8.21 (s, 1H), 7.99 (d, ylmethyl)sulfinyl)quinolin- J = 8.5 Hz, 1H), 7.52 (d, J = 7.9 Hz, 4(1H)-one 1H), 7.44 (d, J = 8.5 Hz, 1H), 7.25 (dd, J = 7.6, 4.6 Hz, 1H), 4.71 (d, J = 13.1 Hz, 1H), 4.37 (d, J = 13.0 Hz, 1H), 2.68 (s, 3H). 85 5,8-difluoro-3-isobutyryl-2- 489.48 489 .sup.1H NMR (300 MHz, ((4- CDCl.sub.3 + MeOD)7.60-6.92 (m, 6H), ((trifluoromethyl)thio)benzyl)sulfinyl)quinolin- 4.45-4.41 (m, 1H), 4.35-4.31 (m, 1H), 4(1H)-one 4.09-4.00 (m, 1H), 1.19-1.17 (d, J = 6 Hz, 3H), 1.11-1.08 (d, J = 7.17 Hz, 3H). 86 5,8-dichloro-3-isobutyryl-2- 427.30 427 .sup.1H NMR (300 MHz, CDCl.sub.3)10.43 (br (((5-methylisoxazol-3- s, 1H), 7.59-7.56 (d, J = 8.43 Hz, 1H), yl)methyl)sulfinyl)quinolin- 7.38-7.35 (d, J = 8.43 Hz, 1H), 6.13 (s, 4(1H)-one 1H), 4.50-4.39 (d, J = 8.54 Hz, 2H), 4.14-4.05 (m, 1H), 2.34 (s, 3H). 1.21-1.15 (dd, J = 6.8, 11.6 Hz, 6H). 87 3-benzoyl-5,8-difluoro-2-((4- 549.48 549 .sup.1H NMR (300 MHz, CDCl.sub.3) (pentafluoro-l6- 7.74-7.27 (m, 10H), 7.00-6.92 (m, 1H), sulfanyl)benzyl)sulfinyl)quinolin- 4.80-4.76 (d, J = 12.66 Hz, 1H), 4(1H)-one 4.53-4.49 (d, J = 12.6 Hz, 1H). 88 3-benzoyl-5,8-dichloro-2- 461.31 461 .sup.1H NMR (300 MHz, CDCl.sub.3) (((5-methylisoxazol-3- 7.77-7.75 (d, J = 6.75 Hz, 2H), 7.74-7.70 (d, yl)methyl)sulfinyl)quinolin- J = 8.28 Hz, 1H), 7.59-7.31 (m, 5H), 4(1H)-one 6.18 (s, 1H), 4.68 (s, 2H), 3.10 (s, 3H). 89 methyl 5-(((3-acetyl-5,8- 442.26 442 .sup.1H NMR (300 MHz, CDCl.sub.3)10.24 (s, dichloro-4-oxo-1,4- 1H), 7.56 (d, J = 8.5 Hz, 1H), 7.38 (d, dihydroquinolin-2- J = 8.5 Hz, 1H), 7.05 (d, J = 3.4 Hz, yl)sulfinyl)methyl)furan-2- 1H), 6.59 (d, J = 3.4 Hz, 1H), 4.65 (d, carboxylate J = 13.9 Hz, 1H), 4.44 (d, J = 13.9 Hz, 1H), 3.60 (s, 3H), 2.85 (s, 3H). 90 2-(((3-acetyl-5,8-dichloro-4- 463.29 463 .sup.1H NMR (300 MHz, CDCl.sub.3)10.52 (s, oxo-1,4-dihydroquinolin-2- 1H), 8.00-7.74 (m, 4H), 7.62 (d, J = 8.4 Hz, yl)sulfinyl)methyl)isoindoline- 1H), 7.43 (d, J = 8.5 Hz, 1H), 1,3-dione 5.74 (d, J = 12.6 Hz, 1H), 4.86 (d, J = 12.6 Hz, 1H), 2.87 (s, 3H). 91 methyl 4-(((3-acetyl-5,8- 452.30 452 .sup.1H NMR (300 MHz, CDCl.sub.3)10.23 (s, dichloro-4-oxo-1,4- 1H), 7.87 (d, J = 8.2 Hz, 2H), 7.52 (d, dihydroquinolin-2- J = 8.4 Hz, 1H), 7.36 (d, J = 8.4 Hz, yl)sulfinyl)methyl)benzoate 1H), 7.23 (d, J = 8.2 Hz, 2H), 4.44 (q, J = 12.5 Hz, 2H), 3.89 (d, J = 5.4 Hz, 3H), 2.85 (s, 3H). 92 3-acetyl-5-methoxy-2-((4- 465.45 465 .sup.1H NMR (300 MHz, CDCl.sub.3)8.18 (d, (pentafluoro-l6- J = 9.0 Hz, 1H), 7.71 (d, J = 8.7 Hz, sulfanyl)benzyl)thio)quinolin- 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.14 (d, 4(1H)-one J = 2.4 Hz, 1H), 7.08 (dd, J = 9.0, 2.5 Hz, 1H), 4.70 (s, 2H), 4.00 (s, 3H), 2.92 (s, 3H). 93 3-acetyl-5-methoxy-2-((4- 481.45 481 .sup.1H NMR (300 MHz, CDCl.sub.3)9.63 (s, (pentafluoro-l6- 1H), 8.28 (d, J = 9.0 Hz, 1H), 7.57 (d, sulfanyl)benzyl)sulfinyl)quinolin- J = 8.6 Hz, 2H), 7.23 (s, 1H), 7.04 (dd, 4(1H)-one J = 9.0, 2.2 Hz, 1H), 6.54 (d, J = 2.2 Hz, 1H), 4.39 (dd, J = 36.0, 12.5 Hz, 2H), 3.87 (d, J = 10.5 Hz, 3H), 2.87 (s, 3H). 94 3-acetyl-5-methoxy-2-(((5- 360.38 360 .sup.1H NMR (300 MHz, CDCl.sub.3)10.43 (s, methylisoxazol-3- 1H), 8.34 (d, J = 9.0 Hz, 1H), 7.08 (d, yl)methyl)sulfinyl)quinolin- J = 8.9 Hz, 1H), 6.93 (s, 1H), 6.08 (s, 4(1H)-one 1H), 4.45 (dd, J = 60.6, 13.3 Hz, 2H), 3.91 (s, 3H), 2.87 (s, 3H), 2.32 (s, 3H). 95 8-bromo-5-chloro-3- 471.75 471 .sup.1H NMR (300 MHz, CDCl.sub.3)10.49 (br isobutyryl-2-(((5- s, 1H), 7.75-7.72 (d, J = 8.43 Hz, 1H), methylisoxazol-3- 7.34-7.31 (d, J = 8.37 Hz, 1H), 6.13 (s, yl)methyl)sulfinyl)quinolin- 1H), 4.47 (s, 2H), 4.16-4.07 (m, 1H), 4(1H)-one 2.35 (s, 3H), 1.23-1.17 (dd, J = 6.7, 12.0 Hz, 6H). 96 8-bromo-5-chloro-3- 469.73 469 .sup.1H NMR (300 MHz, CDCl.sub.3)10.44 (br (cyclopropanecarbonyl)-2- s, 1H), 7.75-7.72 (d, J = 8.43 Hz, 1H), (((5-methylisoxazol-3- 7.34-7.31 (d, J = 8.4 Hz, 1H), 6.11 (s, yl)methyl)sulfinyl)quinolin- 1H), 4.48-4.37 (q, J = 10.5 Hz, 2H), 4(1H)-one 3.70-3.62 (m, 1H), 2.35 (s, 3H), 1.28-1.05 (m, 4H). 97 5,8-dichloro-3- 425.28 425 .sup.1H NMR (300 MHz, CDCl.sub.3)10.42 (br (cyclopropanecarbonyl)-2- s, 1H), 7.61-7.58 (d, J = 8.43 Hz, 1H), (((5-methylisoxazol-3- 7.41-7.38 (d, J = 8.43 Hz, 1H), 6.12 (s, yl)methyl)sulfinyl)quinolin- 1H), 4.49-4.37 (q, J = 11.7 Hz, 2H), 4(1H)-one 3.71-3.62 (m, 1H), 2.36 (s, 3H), 1.29-1.06 (m, 4H). 98 5-(((3-acetyl-8-bromo-5- 469.75 469 .sup.1H NMR (300 MHz, CDCl.sub.3)10.31 (br chloro-4-oxo-1,4- s, 1H), 7.79-7.77 (d, J = 8.43 Hz, 1H), dihydroquinolin-2- 7.42-7.36 (m, 2H), 6.91-6.86 (d, J = 3.84 Hz, yl)sulfinyl)methyl)thiophene- 1H), 4.77-4.72 (d, J = 13.74, 1H), 2-carbonitrile 4.63-4.59 (d, J = 13.71, 1H), 2.86 (s, 3H). 99 2-(((6-(1H-pyrazol-1- 505.77 505 .sup.1H NMR (300 MHz, DMSO- yl)pyridin-3- d.sub.6)10.00 (br s, 1H), 8.46-8.45 (s, 1H), yl)methyl)sulfinyl)-3-acetyl- 8.11 (s, 1H), 7.89-7.86 (d, J = 8.46 Hz, 8-bromo-5-chloroquinolin- 1H), 7.80 (s, 1H), 7.79-7.71 (m, 2H), 4(1H)-one 7.41-7.38 (d, J = 8.37 Hz, 1H), 6.55 (s, 1H), 4.79-4.75 (d, J = 12.99 Hz, 1H), 4.43-4.38 (d, J = 13.08 Hz, 1H), 2.70 (s, 3H). 100 3-acetyl-2-(((6-aminopyridin- 454.72 454 .sup.1H NMR (300 MHz, DMSO-d.sub.6) 3-yl)methyl)sulfinyl)-8- 8.22-7.65 (m, 4H), 7.09-7.06 (m, 1H), bromo-5-chloroquinolin- 4.36-4.32 (m, 1H), 4.14-4.11 (m, 1H), 2.88 (s, 4(1H)-one 3H). 101 8-bromo-5-chloro-3- 564.82 564 .sup.1H NMR (300 MHz, DMSO- (cyclopropanecarbonyl)-2- d.sub.6)10.11 (br s, 1H), ((4- 8.08-8.06 (d, J = 8.43 Hz, 1H), 7.55-7.52 (d, J = 7.71 Hz, ((trifluoromethyl)thio)benzyl)sulfinyl)quinolin- 2H), 7.45-7.43 (d, J = 8.37 Hz, 4(1H)-one 1H), 7.20-7.17 (d, J = 7.71 Hz, 2H), 4.65-4.61 (d, J = 12.66 Hz, 1H), 4.42-4.37 (d, J = 12.87 Hz, 1H), 3.55-3.47 (m, 1H), 1.28-1.02 (m, 4H). 102 3-acetyl-8-bromo-5-chloro-2- 521.73 521 .sup.1H NMR (300 MHz, DMSO- (((2-methyl-6- d.sub.6)10.32 (br s, 1H), 8.02-7.99 (d, (trifluoromethyl)pyridin-3- J = 8.46 Hz, 1H), 7.68-7.65 (d, J = 7.98 Hz, yl)methyl)sulfinyl)quinolin- 1H), 7.55-7.52 (d, J = 7.89 Hz, 1H), 4(1H)-one 7.45-7.42 (d, J = 8.49 Hz, 1H), 4.95-4.91 (d, J = 13.41 Hz, 1H), 4.51-4.46 (d, J = 13.08 Hz, 2H), 2.68 (s, 3H), 2.61 (s, 3H). 103 N-(4-(((3-acetyl-8-bromo-5- 531.82 531 .sup.1H NMR (300 MHz, DMSO- chloro-4-oxo-1,4- d.sub.6)10.25 (br s, 1H), 8.01 (m, 1H), dihydroquinolin-2- 7.67-7.64 (m, 1H), 7.41-6.98 (m, 6H), yl)sulfinyl)methyl)phenyl)methanesulfonamide 4.79-4.50 (m, 2H), 4.30-4.22 (m, 2H), 2.81 (s, 3H), 2.68 (s, 3H). 104 3-acetyl-8-bromo-5-chloro-2- 474.15 474 .sup.1H NMR (300 MHz, CDCl.sub.3)10.20 (s, (((6-chloropyridin-3- 1H), 8.10 (s, 1H), 7.76 (d, J = 8.4 Hz, yl)methyl)sulfinyl)quinolin- 1H), 7.51 (d, J = 7.8 Hz, 1H), 7.36 (d, 4(1H)-one J = 8.4 Hz, 1H), 7.24 (d, J = 8.1 Hz, 1H), 4.41 (dd, J = 26.8, 13.0 Hz, 2H), 2.86 (s, 3H). 105 3-acetyl-8-bromo-5-chloro-2- 512.80 512 .sup.1H NMR (300 MHz, CDCl.sub.3) (((6-((2- 12.59 (s, 1H), 7.75 (d, J = 8.2 Hz, 1H), 7.63 (d, methoxyethyl)amino)pyridin- J = 7.6 Hz, 1H), 7.04 (d, J = 8.2 Hz, 3- 2H), 6.11 (d, J = 7.6 Hz, 1H), yl)methyl)sulfinyl)quinolin- 4.61-4.53 (m, 1H), 3.90-3.84 (m, 1H), 4(1H)-one 3.71-3.65 (m, 2H), 3.64-3.55 (m, 2H), 3.41 (s, 3H), 3.33 (s, 3H). 106 3-acetyl-8-bromo-5-chloro-2- 444.68 444 .sup.1H NMR (300 MHz, DMSO-d.sub.6) (((4-methyl-1,2,5-oxadiazol- 7.76-7.73 (d, J = 8.5 Hz, 1H), 7.08-7.06 (d, 3- J = 8.5 Hz, 1H), 4.52-4.48 (d, J = 12.0 Hz, yl)methyl)sulfinyl)quinolin- 1H), 4.28-4.23 (d, J = 12.0 Hz, 4(1H)-one 1H), 2.50 (s, 3H), 2.44 (s, 3H). 107 2-(((1H-pyrrolo[2,3- 478.75 478 .sup.1H NMR (300 MHz, DMSO- b]pyridin-5- d.sub.6)11.62 (br s, 1H), 8.00-7.32 (m, yl)methyl)sulfinyl)-3-acetyl- 5H), 6.38 (s, 1H), 4.62-4.58 (m, 1H), 8-bromo-5-chloroquinolin- 4.20-4.10 (m, 1H), 2.60 (s, 3H). 4(1H)-one

[0154] Evaluation of Compounds of the Present Disclosure

[0155] Evaluation of Inhibitory Effect of Compounds on DNA Binding of c-Myc/Max

[0156] 1. Protein Assay

[0157] 1) Preparation of Recombinant c-Myc and Max Proteins Recombinant proteins were prepared as described in the following references: K. C. Jung et al., Fatty Acids, Inhibitors for the DNA Binding of c-Myc/Max Dimer, Suppress Proliferation and Induce Apoptosis of Differentiated HL-60 Human Leukemia Cell, Leukemia, 2006, 20(1), 122-7 or Kyung-Chae Jeong et al., Small-Molecule Inhibitors of c-Myc Transcriptional Factor Suppress Proliferation and Induce Apoptosis of Promyelocytic Leukemia Cell via Cell Cycle Arrest, Mol. BioSyst., 2010, 6, 1503-1509.

[0158] 2) Electrophoretic Mobility Shift Assay (EMSA)

[0159] The inhibitory activity of each candidate compound on DNA binding of recombinant c-Myc/Max was measured using an electrophoretic mobility shift assay (EMSA). The ratio of protein-DNA complexes in each sample was evaluated by measuring band intensity. The oligonucleotides (E-box) corresponding to the consensus binding site of Myc/Max were dimerized through an annealing process. The protein mixture was incubated at room temperature for 5 minutes, and a DMSO solution containing each candidate compound was added thereto. The mixture was further incubated for 5 minutes, and the biotinylated DNA was added. To achieve a state of equilibrium, the final mixture was incubated at room temperature for 10 minutes. The protein-DNA complexes were separated from unbound free DNA by pre-electrophoresis using 8% polyacrylamide gel and 1TBE buffer. After pre-electrophoresis, electrophoresis was performed at 120 V for 1 hour in 1TBE buffer. Each band was visualized using HRP-conjugated streptavidin and an ECL solution, and band intensity was measured using image analysis software.

[0160] 2. Cell Based Assay

[0161] Commercially available bladder cancer cell lines were treated with trypsin-EDTA and seeded in each well of a 96 well plate, followed by incubation for 24 hours. After incubation, candidate compounds were added to each well at a final concentration of 0 to 2 M. The compound-treated cells were further incubated for 72 hours. Cell viability was measured using an ATP detection method (CellTiter-Glo Luminescent Cell Viability Assay, Promega).

[0162] IC.sub.50 values calculated from an in vitro assay and a proliferation assay using compounds according to the present disclosure are summarized in Table 5 below.

TABLE-US-00005 TABLE 5 cell based assay Compound protein cell line 1 cell line 2 cell line 3 cell line 4 Number assay MBT-2 KU19-19 253J UM-UC-3 1 <1 M 1.19 M 1.94 M 1.35 M 1.51 M 2 <1 M >2 M >2 M >2 M >2 M 3 <1 M >2 M >2 M >2 M >2 M 4 <1 M 0.96 M 1.05 M 1.00 M 1.33 M 5 <1 M >2 M >2 M >2 M >2 M 6 <1 M 1.44 M >2 M 1.22 M 1.46 M 7 <1 M >2 M >2 M >2 M >2 M 8 <1 M >2 M >2 M >2 M >2 M 9 <1 M 1.20 M 1.97 M 1.10 M 1.18 M 10 <1 M >2 M >2 M >2 M >2 M 11 <1 M >2 M >2 M 1.41 M 1.49 M 12 <1 M >2 M >2 M >2 M >2 M 13 <1 M >2 M >2 M >2 M >2 M 14 <1 M >2 M >2 M >2 M >2 M 15 <1 M >2 M 1.91 M >2 M >2 M 16 <1 M >2 M >2 M >2 M >2 M 17 <1 M >2 M >2 M >2 M >2 M 18 <1 M >2 M >2 M >2 M >2 M 19 <1 M >2 M >2 M >2 M >2 M 20 <1 M >2 M >2 M >2 M >2 M 21 <1 M >2 M >2 M >2 M >2 M 22 <1 M >2 M >2 M >2 M >2 M 23 <1 M >2 M >2 M >2 M >2 M 24 <1 M >2 M >2 M >2 M >2 M 25 <1 M >2 M >2 M >2 M >2 M 26 <1 M >2 M >2 M >2 M >2 M 27 <1 M >2 M >2 M >2 M >2 M 28 <1 M 0.79 M 1.46 M 0.74 M 0.79 M 29 <1 M 1.20 M 1.68 M 0.96 M 1.13 M 30 <1 M >2 M >2 M >2 M >2 M 31 <1 M 1.28 M 1.45 M 0.89 M 1.02 M 32 <1 M >2 M >2 M >2 M >2 M 33 <1 M 0.90 M 1.42 M 1.39 M 1.11 M 34 <1 M >2 M >2 M >2 M >2 M 35 <1 M >2 M >2 M >2 M >2 M 36 <1 M 1.28 M >2 M >2 M >2 M 37 <1 M >2 M >2 M >2 M >2 M 38 <1 M >2 M >2 M >2 M >2 M 39 <1 M >2 M >2 M >2 M >2 M 40 <1 M >2 M >2 M >2 M >2 M 41 <1 M >2 M >2 M >2 M >2 M 42 <1 M >2 M >2 M >2 M 1.89 M 43 <1 M >2 M >2 M >2 M >2 M 44 <1 M 1.15 M 1.27 M 1.24 M 0.97 M 45 <1 M >2 M >2 M >2 M >2 M 46 <1 M 1.84 M 1.80 M 1.96 M 1.22 M 47 <1 M >2 M >2 M >2 M >2 M 48 <1 M >2 M >2 M >2 M 1.82 M 49 <1 M >2 M >2 M >2 M >2 M 50 <1 M 1.58 M 1.69 M 1.43 M 1.26 M 51 <1 M 0.76 M 1.26 M 1.13 M 0.63 M 52 <1 M >2 M >2 M >2 M >2 M 53 <1 M >2 M >2 M >2 M >2 M 54 <1 M >2 M >2 M >2 M >2 M 55 <1 M >2 M 1.38 M 1.33 M 1.58 M 56 <1 M 1.18 M 0.94 M 1.11 M 1.25 M 57 <1 M >2 M 1.83 M 1.92 M >2 M 58 <1 M 0.86 M 0.92 M 0.92 M 1.22 M 59 <1 M 1.30 M 1.23 M 1.14 M 1.37 M 60 <1 M >2 M 1.56 M 1.71 M >2 M 61 <1 M >2 M >2 M >2 M >2 M 62 <1 M >2 M >2 M >2 M >2 M 63 <1 M >2 M >2 M >2 M >2 M 64 <1 M 0.84 M 1.41 M 0.95 M 1.06 M 65 <1 M >2 M >2 M >2 M >2 M 66 <1 M >2 M >2 M >2 M >2 M 67 <1 M >2 M >2 M >2 M >2 M 68 <1 M 1.07 M 1.25 M 0.97 M 1.11 M 69 <1 M 1.26 M 1.50 M 1.08 M 1.20 M 70 <1 M 1.33 M 1.75 M 1.04 M 1.26 M 71 <1 M 1.47 M 1.60 M 1.11 M 1.61 M 72 <1 M 1.01 M 1.37 M 0.83 M 0.82 M 73 <1 M 1.00 M 2.00 M 1.34 M 1.62 M 74 <1 M 1.15 M 1.64 M 0.81 M 1.54 M 75 <1 M 1.05 M 1.21 M 0.86 M 1.01 M 76 <1 M 1.86 M 1.86 M 1.24 M 1.39 M 77 <1 M 1.45 M 1.38 M 0.90 M 1.18 M 78 <1 M 1.53 M >2 M 1.29 M 1.39 M 79 <1 M >2 M >2 M >2 M >2 M 80 <1 M >2 M >2 M >2 M >2 M 81 <1 M >2 M >2 M >2 M >2 M 82 <1 M >2 M >2 M >2 M >2 M 83 <1 M 1.35 M 1.60 M 1.42 M 1.31 M 84 <1 M 0.67 M 1.50 M 0.87 M 0.76 M 85 <1 M >2 M >2 M >2 M >2 M 86 <1 M 0.81 M 1.41 M 1.06 M 1.26 M 87 <1 M >2 M >2 M >2 M >2 M 88 <1 M >2 M >2 M >2 M >2 M 89 <1 M 1.27 M >2 M 1.84 M 1.47 M 90 <1 M >2 M >2 M >2 M >2 M 91 <1 M 1.37 M >2 M >2 M 1.56 M 92 <1 M >2 M >2 M >2 M >2 M 93 <1 M >2 M >2 M >2 M >2 M 94 <1 M 1.53 M >2 M >2 M >2 M 95 <1 M 0.80 M 1.29 M 0.77 M 1.06 M 96 <1 M 1.06 M >2 M 1.49 M 1.63 M 97 <1 M 0.81 M 1.62 M 1.20 M 1.27 M 98 <1 M 0.84 M 1.90 M 1.38 M 1.52 M 99 <1 M 0.47 M 1.12 M 0.80 M 0.77 M 100 <1 M >2 M >2 M >2 M >2 M 101 <1 M >2 M >2 M 1.82 M 1.93 M 102 <1 M 0.77 M 1.58 M 0.83 M 1.07 M 103 <1 M >2 M >2 M >2 M >2 M 104 <1 M 0.71 M 1.50 M 0.87 M 1.13 M 105 <1 M >2 M >2 M >2 M >2 M 106 <1 M >2 M >2 M >2 M >2 M 107 <1 M >2 M >2 M >2 M >2 M

[0163] As shown in Table 5, the compounds according to the present disclosure were highly effective in inhibiting c-Myc/Max/DNA complex formation, and were particularly effective in suppressing bladder cancer cell lines.

[0164] Evaluation of Selectivity of Compounds of the Present Disclosure

[0165] The selectivity of the compounds of the present disclosure to cancer cells was evaluated in the same manner as described in 2. Cell based assay. As a comparative example, KSI-3716 compound of Formula 4, which is a known compound, was used. Measurement results are summarized in Table 6 below.

TABLE-US-00006 TABLE 6 Compound Cytotoxicity (M) Compd. MBT-2 KU19-19 UM-UC-3 253J RT4 KSI-3716 1.0 0.4 0.9 1.2 1.5 Compound 4 1.0 1.1 1.5 1.1 >10 Compound 33 0.9 1.4 1.6 1.6 >10

[0166] 253J: human urinary tract transitional cell carcinoma

[0167] UM-UC-3: human urinary bladder transitional cell carcinoma

[0168] RT4: human urinary bladder transitional cell papilloma

[0169] As shown in Table 6, compound KSI-3716 causes nonselective cell death in both benign (RT4) and malignant (253J and UM-UC-3) bladder cancer cell lines, but the compounds of the present disclosure kill only malignant cancer cells with high selectivity.

[0170] The present disclosure provides novel compounds that can have various pharmacological activities by inhibiting c-Myc/Max/DNA complex formation. The compounds according to the present disclosure or pharmaceutically acceptable salts thereof are excellent in safety and has high selectivity in terms of inhibition of c-Myc/Max/DNA complex formation. Accordingly, various excellent effects can be exhibited.

[0171] All documents mentioned herein are incorporated herein by reference. When introducing elements of the present disclosure or the preferred embodiments thereof, the articles a, an, the and said are intended to mean that there are one or more of the elements. The terms comprising, including, and having are intended to be inclusive and mean that there may be additional elements other than the listed elements. Although the present disclosure is described with respect to particular aspects, it should not be construed as limiting the details of these aspects.