USRE49481EActiveUtilityPatentIndex 62
Compounds for the treatment and prophylaxis of respiratory syncytial virus disease
Est. expiryAug 11, 2031(~5.1 yrs left)· nominal 20-yr term from priority
Inventors:CHEN LIFENG LICHUNFENG SONGGAO LUGUO TAOHUANG MENGWEILIANG CHUNGENLIU YONGFUWANG LISHAWONG JASON CHRISTOPHERWU JIM ZHENWU XIHANYUN HONGYINGZHENG XIUFANG
C07D 413/04C07D 409/14C07D 401/14C07D 401/04C07D 491/107C07D 487/04C07D 405/14C07D 498/04A61P 31/14A61P 11/00C07D 413/14C07D 417/04C07D 417/14C07D 471/04C07D 407/14A61P 31/12C07D 493/10
62
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0
Cited by
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References
59
Claims
Abstract
A compound of formula (I)as well as pharmaceutically acceptable salt thereof, wherein R1 to R10, A, Q, X and Y are as defined in the specification and claims, and their use as a pharmaceutical for the treatment or prophylaxis of respiratory syncytial virus disease.
Claims
exact text as granted — not AI-modifiedThe invention claimed is:
1. A compound of formula (I)
Wherein
R 1 is hydrogen, halogen, or C 1-6 alkyl;
R 2 is hydrogen, halogen, or C 1-6 alkyl;
R 3 is hydrogen, halogen, or C 1-6 alkyl;
R 4 is hydrogen, or C 1-6 alkyl;
R 5 is hydrogen, or halogen;
R 6 is hydrogen, halogen, hydroxy, C 1-6 alkoxy, carboxy, morpholinyl, or 4-C 0-6 alkylpiperazin-1-yl;
R 7 is hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylaminocarbonyl, diC 1-6 alkylaminocarbonyl, C 1-6 alkylsulfonyl, phenoxy, or hydroxy(CH 2 ) 2-6 —O—;
R 8 is hydrogen, halogen, or C 1-6 alkoxy;
R 9 is hydrogen, C 1-6 alkyl, or ═O;
R 10 is hydrogen, or ═O, provided that R 9 and R 10 are not ═O simultaneously;
A is nitrogen, or —C—R 11 , wherein R 11 is hydrogen, halogen, C 1-6 alkyl, cycloalkyl, C 1-6 alkoxy, trifluoromethyl, trifluoromethoxy, pyridinyloxy, C 1-6 alkoxy(CH 2 ) 1-6 —O—, difluoromethoxy, cyano, nitro, amino, vinyl, acetylenyl, aminocarbonyl, hydroxy(CH 2 ) 2-6 —O—, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, hydroxy(CH 2 ) 1-6 , deuteratedC 1-6 alkyl, carboxyl, C 1-6 alkoxycarbonyl, hydroxy, difluoromethyl, —CH(hydroxy) C 1-6 alkyl, or C 1-6 alkylsulfanyl;
X is —CH 2 —, —O—, —NH—, —CF 2 —, —C(C 1-6 alkyl)(OH)—, —S—, —C(═O)—, —C(═NOC 0-6 alkyl)-, —S(═O)—, —S(O 2 )— or —S(═O)(NH)—;
Y is —CH—, or nitrogen;
Q is hydrogen; halogen; C 1-6 alkyl, unsubstituted or once or twice substituted by amino or hydroxy, provided that di-substitution is not on the same carbon; amino(CH 2 ) 2-6 aminosulfonyl; 2-amino-4,5-dihydro-1,3-oxazol-4-yl(CH 2 ) 1-6 ; carboxy(CH 2 ) 1-6 ; phenylsulfonyl; piperidin-4-yl-carbonyl; 1H-pyrazol-3-yl; pyrrolidin-3-yloxy; piperidin-4-yloxy; amino(CH 2 ) 2-6 —O—; or NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen, C 1-6 alkyl, or hydroxy(CH 2 ) 2-6 , and the other one is {1-[amino(CH 2 ) 0-6 ]-3,3-difluorocyclobutyl}(CH 2 ) 1-6 ; guanidino(CH 2 ) 2-6 ; (S—C 1-6 alkylsulfonimidoyl)(CH 2 ) 2-6 ; 2-oxa-6-aza-spiro[3.4]oct-8-yl; {3-[amino(CH 2 ) 0-6 ]tetrahydrofuran-3-yl}(CH 2 ) 1-6 ; 3-aminomethyl-1,1-dioxidothietan-3-ylmethyl; 3-amino-1,1-dioxidothietan-3-ylmethyl; 3-(aminomethyl)thietan-3-ylmethyl;(1,1-dioxidothiomorpholin-4-yl)ethyl; C 0-6 alkyl(oxetanyl)N(CH 2 ) 2-6 ; 4,5-dihydro-1H-imidazol-2-yl; amino(CH 2 ) 2-6 —O—(CH 2 ) 2-6 ; amino(CH 2 ) 2-10 ; amino(CH 2 ) 1-6 difluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 difluoromethyldifluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 fluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 oxetanyl(CH 2 ) 0-6 ; amino(CH 2 ) 0-6 oxetanyl(CH 2 ) 1-6 ; amino(CH 2 ) 2-6 sulfanyl(CH 2 ) 2-6 ; amino(CH 2 ) 2-6 sulfonyl(CH 2 ) 2-6 ; amino(CH 2 ) 0-6 carbonyl(CH 2 ) 0-6 ; aminocycloalkyl(CH 2 ) 0-6 ; 2-aminodihydrooxazol-4-yl(CH 2 ) 1-6 ; 2-aminodihydrooxazol-5-yl(CH 2 ) 1-6 ; (2-amino-5-methyl-4,5-dihydro-1,3-oxazol-5-yl)methyl; aminophenyl; 4-aminotetrahydropyran-4-yl(CH 2 ) 1-6 ; azetidin-2-yl(CH 2 ) 1-6 ; azetidin-3-yl(CH 2 ) 0-6 ; azetidinylcarbonyl; C 1-6 alkoxy(CH 2 ) 2-6 ; C 1-6 alkoxy(CH 2 ) 2-6 amino(CH 2 ) 2-6 ; C 1-6 alkyl; C 1-6 alkylamino(CH 2 ) 2-6 ; C 1-6 alkylaminocarbonyl(CH 2 ) 0-6 ; C 1-6 alkylaminooxetanyl(CH 2 ) 1-6 ; C 1-6 alkylcarbonyl; C 1-6 alkylcarbonylamino(CH 2 ) 2-6 ; C 1-6 alkylcarbonylamino(CH 2 ) 1-6 oxetanyl(CH 2 ) 0-6 ; C 1-6 alkylsulfinyl(CH 2 ) 2-6 ; C 1-6 alkylsulfonyl; carboxy(CH 2 ) 1-6 ; cyano(CH 2 ) 1-6 ; diC 1-6 alkylamino(CH 2 ) 2-6 ;diC 1-6 alkylaminocarbonyl; difluoromethyl(CH 2 ) 1-6 amino(CH 2 ) 2-6 ; hydrogen; hydroxy(CH 2 ) 2-10 ; hydroxy(CH 2 ) 2-6 amino(CH 2 ) 2-6 ; hydroxy(CH 2 ) 1-6 carbonyl; hydroxy(CH 2 ) 0-6 oxetanyl(CH 2 ) 1-6 ; hydroxy(CH 2 ) 1-6 oxetanyl(CH 2 ) 0-6 ; hydroxycycloalkyl; isoxazolyl; morpholin-2-yl(CH 2 ) 1-6 ; morpholin-4-yl(CH 2 ) 2-6 ; oxetanyl(CH 2 ) 0-6 ; N-oxetanylpyrrolidin-3-yl; oxo-pyrrolidinylcarbonyl; phenylaminocarbonyl; phenyl(CH 2 ) 0-6 aminooxetanyl(CH 2 ) 1-6 ; phenylcarbonyl; piperazinyl(CH 2 ) 2-6 ; piperidin-1-yl(CH 2 ) 2-6 ; piperidin-2-yl(CH 2 ) 1-6 ; piperidin-3-yl(CH 2 ) 0-6 ; piperidin-4-yl(CH 2 ) 0-6 ; piperidinylcarbonyl; pyrazinylcarbonyl; pyrazol-3-yl; pyridazinylcarbonyl; pyridinyl(CH 2 ) 0-6 carbonyl; pyridinylamino(CH 2 ) 2-6 ; pyrrolidin-3-yl, unsubstituted or 4-substituted by halogen; pyrrolidin-4-yl, unsubstituted or 3-substituted by hydroxy or C 1-6 alkoxy; pyrrolidin-2-yl(CH 2 ) 1-6 ; pyrrolidinylcarbonyl; tetrahydrofuran-3-yl; tetrahydropyran-4-yl; tetrazolyl(CH 2 ) 2-6 ; trifluoromethylcarbonylamino(CH 2 ) 1-6 oxetanyl; trifluoromethylsulfonyl;
wherein R 14 is hydrogen, C 1-6 alkyl or hydroxy(CH 2 ) 1-6 ; R 15 is hydroxy, C 1-6 alkyl, hydroxy(CH 2 ) 1-6 or amino; and R 16 is C 1-6 alkyl, trifluoromethyl, hydroxy(CH 2 ) 1-6 , amino(CH 2 ) 1-6 , aminocarboxy or carboxy(CH 2 ) 1-6 ;
wherein R 17 is hydrogen, C 1-6 alkyl or hydroxy(CH 2 ) 1-6 ; R 18 is hydroxy(CH 2 ) 1-6 or C 1-6 alkyl; R 19 is hydroxy(CH 2 ) 1-6 , amino(CH 2 ) 1-6 , carboxy or aminocarboxy(CH 2 ) 0-6 ; or
wherein R 20 is hydrogen or C 1-6 alkyl; R 21 is C 1-6 alkyl; R 22 is C 1-6 alkoxy or amino;
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl, azetidinyl, diazepanyl or oxopyrrolidinyl ring; which may be unsubstituted, once or twice substituted by a group selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, gemdimethyl, amino, aminocarbonyl, hydroxy, oxetanylamino, C 1-6 alkylpiperazinyl, and amino(CH 2 ) 1-6 ;
R 12 and R 13 , with the nitrogen atom to which they are attached may form a bridge ring or a spiral ring selected from 2-oxa-6-aza-spiro[3.4]octan-6-yl, 2-oxa-5,7-diazaspiro[3.4]octan-6-one-5-yl, (4aS,7aR)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl, 4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d][1,3]oxazol-5-yl, 2-aza -bicyclo[2.1.1]hexan-2-yl, and 3-aza-bicyclo[3.1.0]hexan-3-yl; which may be unsubstituted or further substituted by amino;
and pharmaceutically acceptable salt and stereoisomers thereof.
2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen, halogen or C 1-6 alkyl;
R 2 is hydrogen, halogen or C 1-6 alkyl;
R 3 is hydrogen, halogen or C 1-6 alkyl;
R 4 is hydrogen or C 1-6 alkyl;
R 5 is hydrogen;
R 6 is hydrogen, halogen, hydroxy, C 1-6 alkoxy, morpholinyl or 4-C 0-6 alkylpiperazin-1-yl;
R 7 is hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, phenoxy or hydroxy(CH 2 ) 2-6 —O—;
R 8 is hydrogen, halogen or C 1-6 alkoxy;
R 9 is hydrogen or C 1-6 alkyl;
R 10 is hydrogen;
A is nitrogen or —C—R 11 , wherein R 11 is hydrogen, halogen, C 1-6 alkyl, cycloalkyl, C 1-6 alkoxy, trifluoromethyl, trifluoromethoxy, pyridinyloxy, C 1-6 alkoxy(CH 2 ) 1-6 —O—, difluoromethoxy, cyano, nitro, amino, vinyl, acetylenyl, aminocarbonyl, hydroxy(CH 2 ) 2-6 —O—, C 1-6 alkylsulfinyl, hydroxy(CH 2 ) 1-6 , deuteratedC 1-6 alkyl, carboxyl, alkoxycarbonyl, hydroxy, difluoromethyl, —CH(hydroxy)C 1-6 alkyl or C 1-6 alkylsulfanyl;
X is S, S═O, SO 2 or S(O)NH;
Y is —CH— or nitrogen;
Q is C 1-6 alkyl, unsubstituted or once substituted by amino; amino(CH 2 ) 2-6 aminosulfonyl; 2-amino-4,5-dihydro-1,3-oxazol-4-ylethyl; carboxy(CH 2 ) 1-6 ; phenylsulfonyl; piperidin-4-yl-carbonyl; 1H-pyrazol-3-yl; pyrrolidin-3-yloxy; piperidin-4-yloxy; amino(CH 2 ) 2-6 —O—; or
NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen, C 1-6 alkyl or hydroxy(CH 2 ) 2-6 , and the other one is {1-[amino(CH 2 ) 0-6 ]-3,3-difluorocyclobutyl}(CH 2 ) 1-6 ; (S—C 1-6 alkylsulfonimidoyl)(CH 2 ) 2-6 ; {3-[amino(CH 2 ) 0-6 ]tetrahydrofuran-3-yl}(CH 2 ) 1-6 ; (2-amino-5-methyl-4,5-dihydro-1,3-oxazol-5-yl)methyl; 3-aminomethyl-1,1-dioxidothietan-3-ylmethyl; 3-(aminomethyl)thietan-3-ylmethyl; (1,1-dioxidothiomorpholin-4-yl)ethyl; C 0-6 alkyl(oxetanyl)N(CH 2 ) 2-6 ; 4,5-dihydro-1H-imidazol-2-yl; amino(CH 2 ) 2-6 —O—(CH 2 ) 2-6 ; amino(CH 2 ) 2-10 ; amino(CH 2 ) 0-6 carbonyl(CH 2 ) 0-6 ; amino(CH 2 ) 1-6 difluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 difluoromethyldifluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 fluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 oxetanyl(CH 2 ) 0-6 ; amino(CH 2 ) 0-6 oxetanyl(CH 2 ) 1-6 ; amino(CH 2 ) 2-6 sulfanyl(CH 2 ) 2-6 ; amino(CH 2 ) 2-6 sulfonyl(CH 2 ) 2-6 ; 1-aminocyclobutylmethyl; 2-aminocyclohexyl; 3-aminocyclohexyl; 4-aminocyclohexyl; 1-aminocyclohexylmethyl; 2-aminocyclopentyl; 1-aminocyclopropylethyl; 1-aminocyclopropylmethyl; (2-amino-4,5-dihydro-oxazol-5-yl)(CH 2 ) 1-6 , (2-amino-4,5-dihydro-oxazol-4-yl)(CH 2 ) 1-6 ; aminophenyl; 4-aminotetrahydropyran-4-yl(CH 2 ) 1-6 ; azetidin-2-yl(CH 2 ) 1-6 ; azetidin-3-yl(CH 2 ) 0-6 ; azetidin-3-ylcarbonyl; C 1-6 alkoxy(CH 2 ) 2-6 ; C 1-6 alkoxy(CH 2 ) 2-6 amino(CH 2 ) 2-6 ; C 1-6 alkyl; C 1-6 alkylamino(CH 2 ) 2-6 ; C 1-6 alkylaminooxetanyl(CH 2 ) 1-6 ; C 1-6 alkylcarbonyl; C 1-6 alkylaminocarbonyl(CH 2 ) 0-6 ; C 1-6 alkylcarbonylamino(CH 2 ) 2-6 ; C 1-6 alkylcarbonylamino(CH 2 ) 1-6 oxetanyl(CH 2 ) 0-6 ; C 1-6 alkylsulfinyl(CH 2 ) 2-6 ; C 1-6 alkylsulfonyl; carboxy(CH 2 ) 1-6 ; cyano(CH 2 ) 1-6 ; diC 1-6 alkylamino(CH 2 ) 2-6 ; diC 1-6 alkylaminocarbonyl; difluoromethyl(CH 2 ) 1-6 amino(CH 2 ) 2-6 ; hydrogen; hydroxy(CH 2 ) 2-10 ; hydroxy(CH 2 ) 2-6 amino(CH 2 ) 2-6 ; hydroxy(CH 2 ) 1-6 carbonyl; hydroxy(CH 2 ) 1-6 oxetanyl(CH 2 ) 0-6 ; hydroxy(CH 2 ) 0-6 oxetanyl(CH 2 ) 1-6 ; 4-hydroxycyclohexyl; isoxazol-3-yl; morpholin-2-yl(CH 2 ) 1-6 ; morpholin-4-yl(CH 2 ) 2-6 ; 2-oxa-6-aza-spiro[3.4]oct-8-yl; oxetanyl(CH 2 ) 0-6 ; N-oxetanylpyrrolidin-3-yl; oxo-pyrrolidinylcarbonyl; phenylaminocarbonyl; phenyl(CH 2 ) 0-6 aminooxetanyl(CH 2 ) 1-6 ; phenylcarbonyl; piperazinyl(CH 2 ) 2-6 ; piperidin-1-yl(CH 2 ) 2-6 ; piperidin-2-yl(CH 2 ) 1-6 ; piperidin-3-yl(CH 2 ) 0-6 ; piperidin-4-yl(CH 2 ) 0-6 ; piperidinylcarbonyl; pyrazinylcarbonyl; pyrazol-3-yl; pyridazinylcarbonyl; pyridinyl(CH 2 ) 0-6 carbonyl; pyridinylamino(CH 2 ) 2-6 ; pyrrolidin-3-yl, unsubstituted or 4-substituted by halogen; pyrrolidin-4-yl, unsubstituted or 3-substituted by hydroxy or C 1-6 alkoxy; pyrrolidin-2-yl(CH 2 ) 1-6 ; pyrrolidinylcarbonyl; tetrahydrofuran-3-yl; tetrahydropyran-4-yl; tetrazolyl(CH 2 ) 2-6 ; trifluoromethylcarbonylamino(CH 2 ) 1-6 oxetanyl; trifluoromethylsulfonyl;
wherein R 14 is hydrogen or C 1-6 alkyl; R 15 is hydroxy, C 1-6 alkyl or amino; and R 16 is C 1-6 alkyl, trifluoromethyl, hydroxy(CH 2 ) 1-6 , amino(CH 2 ) 1-6 , aminocarbonyl or carboxy(CH 2 ) 1-6 ;
wherein R 17 is hydrogen, C 1-6 alkyl or hydroxy(CH 2 ) 1-6 ; R 18 is hydroxy(CH 2 ) 1-6 or C 1-6 alkyl; R 19 is hydroxy(CH 2 ) 1-6 , amino(CH 2 ) 1-6 , carboxy or aminocarbonyl(CH 2 ) 0-6 ; or
wherein R 20 is hydrogen or C 1-6 alkyl; R 21 is C 1-6 alkyl; R 22 is C 1-6 alkoxy or amino;
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl, azetidinyl, diazepanyl or oxopyrrolidinyl ring; which may be unsubstituted, once or twice substituted by a group selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, gemdimethyl, amino, aminocarbonyl, hydroxy, oxetanylamino, C 1-6 alkylpiperazinyl, and amino(CH 2 ) 1-6 ; or
R 12 and R 13 , with the nitrogen atom to which they are attached may form a bridge ring or a spiral ring selected from 2-oxa-6-aza-spiro[3.4]octan-6-yl, 2-oxa-5,7-diazaspiro[3.4]octan-6-one-5-yl, (4aS,7aR)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl, 4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d][1,3]oxazol-5-yl, 2-aza-bicyclo[2.1.1]hexan-2-yl and 3-aza-bicyclo[3.1.0]hexan-3-yl; which may be unsubstituted or further substituted by amino.
3. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 1 , R 2 or R 3 are hydrogen, fluoro, chloro or methyl;
R 4 is hydrogen or methyl;
R 5 is hydrogen;
R 6 is hydrogen, fluoro, hydroxy, methoxy, morpholinyl or 4-(propan-2-yl)piperazin-1-yl;
R 7 is hydrogen, fluoro, chloro, methyl, methoxy, ethoxy, hydroxyethoxy or phenoxy;
R 8 is hydrogen, fluoro or methoxy;
R 9 is hydrogen or methyl;
R 10 is hydrogen;
A is nitrogen or —C—R 11 , wherein R 11 is hydrogen, fluoro, chloro, bromo, methyl, ethyl, cyclopropyl, methoxy, trifluoromethyl, trifluoromethoxy, pyridinyloxy, methoxyethoxy, difluoromethoxy, cyano, nitro, amino, vinyl, acetylenyl, aminocarbonyl, hydroxyethoxy, methylsulfanyl, methylsulfinyl, hydroxymethyl, deuteratedmethyl, carboxyl, methoxycarbonyl, hydroxy, difluoromethyl, methylCH(hydroxy)- or methylsulfonyl;
X is S, S═O, SO 2 or S(O)NH;
Y is —CH— or nitrogen;
Q is 2-amino-4,5-dihydro-1,3-oxazol-4-ylethyl; aminoethoxy; aminoethylaminosulfonyl; aminopropyl; carboxyethyl; methyl; phenylsulfonyl; piperidin-4-yl-carbonyl; piperidin-4-yloxy; 1H-pyrazol-3-yl; pyrrolidin-3-yloxy; or NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen, methyl or hydroxyethyl, and the other one is aminobutyl; aminocarbonylethyl; aminocarbonylmethyl; 1-aminocyclobutylmethyl; 2-aminocyclohexyl; 3-aminocyclohexyl; 4-aminocyclohexyl; 1-aminocyclohexylmethyl; 2-aminocyclopentyl; 1-aminocyclopropylethyl; 1-aminocyclopropylmethyl; aminodecyl; (2-amino-4,5-dihydro-oxazol-5-yl)methyl; (2-amino-4,5-dihydro-oxazol-4-yl)methyl; aminoethoxyethyl; aminoethyl; aminoethylcarbonyl; aminoethylfluoromethylmethyl; aminoethylsulfanylethyl; aminoethylsulfonylethyl; aminoheptyl; aminohexyl; aminomethylcarbonyl; (1-aminomethyl-3,3-difluorocyclobutyl)methyl; aminomethyldifluoromethyldifluoromethylmethyl; aminomethyldifluoromethylmethyl; (2-amino-5-methyl-4,5-dihydro-1,3-oxazol-5-yl)methyl; 3-aminomethyl-1,1-dioxidothietan-3-ylmethyl; aminomethylfluoromethylethyl; aminomethylfluoromethylmethyl; aminomethyloxetanyl; aminomethyloxetanylmethyl; 3-(aminomethyl)thietan-3-ylmethyl; aminononyl; aminooctyl; aminooxetanylethyl; aminooxetanylmethyl; aminopentyl; aminophenyl; aminopropyl; 4-aminotetrahydropyran-4-ylmethyl; 3-aminotetrahydrofuran-3-ylmethyl;azetidin-3-yl; azetidin-3-ylcarbonyl; azetidin-2-ylmethyl; azetidin-3-ylmethyl; carboxyethyl; carboxymethyl; cyanoethyl; difluoromethylmethylaminoethyl; 4,5-dihydro-1H-imidazol-2-yl; dimethylaminocarbonyl; dimethylaminoethyl; (1,1-dioxidothiomorpholin-4-yl)ethyl; ethyl; ethylaminocarbonyl; ethylaminoethyl; ethylaminooxetanylmethyl; ethyl (oxetanyl)aminoethyl; hydrogen; 4-hydroxycyclohexyl; hydroxyethyl; hydroxyethylaminoethyl; hydroxyethyloxetanyl; hydroxymethylcarbonyl; hydroxymethyloxetanylmethyl; hydroxynonyl; hydroxypropyl; isoxazol-3-yl; methoxyethyl; methoxyethylaminoethyl; methyl; methylaminocarbonylmethyl; methylaminoethyl; methylcarbonyl; methylcarbonylaminoethyl; methylcarbonylaminomethyloxetanylmethyl; methylcarbonylaminopropyl; methylsulfinylethyl; 2-(S-methylsulfonimidoyl)ethyl; methylsulfonyl; morpholin-4-ylethyl; morpholin-2-ylmethyl; 2-oxa-6-aza-spiro[3.4]oct-8-yl; oxetanyl; oxetanylaminoethyl; oxetanylaminopropyl; oxetanylmethyl; N-oxetanylpyrrolidin-3-yl; oxo-pyrrolidin-4-ylcarbonyl; phenylaminocarbonyl; phenylcarbonyl; phenylmethylaminooxetanylmethyl; piperazin-1-ylethyl; piperidin-2-ylcarbonyl; piperidin-3-ylcarbonyl; piperidin-4-ylcarbonyl; piperidin-3-yl; piperidin-4-yl; piperidin-1-ylethyl; piperidin-2-ylmethyl; pyrazin-2-ylcarbonyl; pyrazol-3-yl; pyridazin-3-ylcarbonyl; pyridine-2-ylmethylcarbonyl; pyridine-2-ylaminoethyl; pyridine-2-ylcarbonyl; pyridine-3-ylcarbonyl; pyrrolidin-3-yl, unsubstituted or 4-substituted by fluoro; pyrrolidin-4-yl, unsubstituted or 3-substituted by hydroxy or methoxy; pyrrolidin-2-ylmethyl; pyrrolidin-2-ylcarbonyl; tetrahydrofuran-3-yl; tetrahydropyran-4-yl; tetrazolylethyl; trifluoromethylsulfonyl; trifluoromethylcarbonylaminomethyloxetanyl;
wherein R 14 is hydrogen or methyl; R 15 is hydroxy, methyl or amino; and R 16 is methyl, trifluoromethyl, hydroxymethyl, hydroxyethyl, aminomethyl, aminocarbonyl or carboxymethyl;
wherein R 17 is hydrogen, methyl or hydroxymethyl; R 18 is hydroxymethyl or methyl; R 19 is hydroxymethyl, aminomethyl, carboxy, aminocarbonyl or aminocarbonylmethyl; or
wherein R 20 is hydrogen or methyl; R 21 is methyl or ethyl; R 22 is methoxy or amino;
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl, azetidinyl, diazepanyl or oxopyrrolidinyl ring; which may be unsubstituted, once or twice substituted by a group selected from fluoro, methyl, methoxy, gemdimethyl, amino, aminocarbonyl, hydroxy, oxetanylamino, methylpiperazinyl and aminomethyl; or
R 12 and R 13 , with the nitrogen atom to which they are attached may form a bridge ring or a spiral ring selected from 2-oxa-6-aza-spiro[3.4]octan-6-yl, 2-oxa-5,7-diazaspiro[3.4]octan-6-one-5-yl, (4aS,7aR)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl, 4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d][1,3]oxazol-5-yl, 2-aza-bicyclo[2.1.1]hexan-2-yl or 3-aza-bicyclo[3.1.0]hexan-3-yl; which may be unsubstituted or further substituted by amino.
4. The compound according to any one of claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are hydrogen;
A is —C—R 11 , wherein R 11 is hydrogen, halogen or C 1-6 alkyl;
X is S;
Y is —CH— or nitrogen;
Q is NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen, and the other one is amino(CH 2 ) 2-6 ; amino(CH 2 ) 1-6 difluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 0-6 oxetanyl(CH 2 ) 1-6 or hydrogen; or
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl ring, which may be once substituted by amino.
5. The compound according to claim 4 or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are hydrogen;
A is —C—R 11 , wherein R 11 is hydrogen, chloro or methyl;
Q is NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen, and the other one is aminoethyl; aminomethyldifluoromethylmethyl; aminomethyloxetanylmethyl; aminooxetanylmethyl or hydrogen; or
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl ring, which may be once substituted by amino.
6. The compound according to any one of claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are hydrogen;
A is —C—R 11 , wherein R 11 is hydrogen, halogen, C 1-6 alkyl, hydroxy(CH 2 ) 1-6 , deuteratedmethyl or carboxyl;
X is S═O;
Y is —CH— or nitrogen;
Q is NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen; and the other one is amino(CH 2 ) 2-6 ; amino(CH 2 ) 1-6 difluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 fluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 oxetanyl; amino(CH 2 ) 1-6 oxetanyl(CH 2 ) 1-6 ; aminooxetanyl(CH 2 ) 1-6 ; hydroxy(CH 2 ) 2-10 ; phenyl(CH 2 ) 1-6 aminooxetanyl(CH 2 ) 1-6 ; pyrrolidin-3-yl, 4-substituted by halogen; or
wherein R 14 is hydrogen, R 15 is hydroxy, and R 16 is hydroxy(CH 2 ) 1-6 ; or
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl ring, which may be once or twice substituted by a group selected from halogen, amino and hydroxyl.
7. The compound according to claim 6 or a pharmaceutically acceptable salt thereof, wherein
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are hydrogen;
A is —C—R 11 , wherein R 11 is hydrogen, chloro, methyl, hydroxymethyl, deuteratedmethyl or carboxyl;
Q is NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen, and the other one is aminoethyl; aminomethyldifluoromethylmethyl; aminomethylfluoromethylmethyl; aminomethyloxetanyl; aminomethyloxetanylmethyl; aminooxetanylmethyl; aminopropyl; hydroxyethyl; phenylmethylaminooxetanylmethyl; pyrrolidin-3-yl, 4-substituted by fluoro; or
wherein R 14 is hydrogen, R 15 is hydroxy, and R 16 is hydroxymethyl; or
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl ring, which may be once or twice substituted by a group selected from fluoro, amino and hydroxyl.
8. The compound according to any one of claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 1 , R 2 , and R 3 are hydrogen, halogen or C 1-6 alkyl;
R 4 is hydrogen or C 1-6 alkyl;
R 5 is hydrogen;
R 6 is hydrogen, halogen, hydroxy, C 1-6 alkoxy, morpholinyl or 4-(propan-2-yl)piperazin-1-yl;
R 7 is hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, hydroxy(CH 2 ) 2-6 —O—, or phenoxy;
R 8 is hydrogen, halogen or C 1-6 alkoxy;
R 9 is hydrogen or C 1-6 alkyl;
R 10 is hydrogen;
A is nitrogen or —C—R 11 , wherein R 11 is hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, trifluoromethyl, trifluoromethoxy, pyridinyloxy, C 1-6 alkoxy(CH 2 ) 1-6 —O—, difluoromethoxy, nitro, cycloalkyl, cyano, amino, vinyl, acetylenyl, aminocarbonyl, hydroxy(CH 2 ) 2-6 —O—, C 1-6 alkylsulfanyl, C 1-6 alkylsulfinyl, hydroxy(CH 2 ) 1-6 , deuteratedmethyl, carboxyl, C 1-6 alkoxycarbonyl, hydroxy, difluoromethyl or methylCH(hydroxy)- ;
X is SO 2 ;
Y is —CH— or nitrogen;
Q is 2-amino-4,5-dihydro-1,3-oxazol-4-ylethyl; amino(CH 2 ) 2-6 —O—; amino(CH 2 ) 2-6 aminosulfonyl; C 1-6 alkyl, unsubstituted or once substituted by amino; carboxy(CH 2 ) 1-6 ; phenylsulfonyl; piperidin-4-yl-carbonyl; piperidin-4-yloxy; 1H-pyrazol-3-yl; pyrrolidin-3-yloxy; or
NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen, C 1-6 alkyl or hydroxy(CH 2 ) 2-6 ; and the other one is {1-[amino(CH 2 ) 0-6 ]-3,3 difluorocyclobutyl}(CH 2 ) 1-6 ; (S—C 1-6 alkylsulfonimidoyl)(CH 2 ) 2-6 ; 3-aminotetrahydrofuran-3-yl(CH 2 ) 1-6 ; (2-amino-5-methyl-4,5-dihydro-1,3-oxazol-5-yl)methyl; 3-aminomethyl-1,1-dioxidothietan-3-ylmethyl; 3-(aminomethyl)thietan-3-ylmethyl; (1,1-dioxidothiomorpholin-4-yl)ethyl; C 0-6 alkyl(oxetanyl)N(CH 2 ) 2-6 ; 4,5-dihydro-1H-imidazol-2-yl; amino(CH 2 ) 2-6 —O—(CH 2 ) 2-6 ; amino(CH 2 ) 2-10 ; amino(CH 2 ) 1-6 carbonyl; aminocarbonyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 difluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 difluoromethyldifluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 fluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 oxetanyl(CH 2 ) 0-6 ; amino(CH 2 ) 0-6 oxetanyl(CH 2 ) 1-6 ; amino(CH 2 ) 2-6 sulfanyl(CH 2 ) 2-6 ; amino(CH 2 ) 2-6 sulfonyl(CH 2 ) 2-6 ; 1-aminocyclobutylmethyl; 2-aminocyclohexyl; 3-aminocyclohexyl; 4-aminocyclohexyl; 1-aminocyclohexylmethyl; 2-aminocyclopentyl; 1-aminocyclopropylethyl; 1-aminocyclopropylmethyl; (2-amino-4,5-dihydro-oxazol-5-yl)(CH 2 ) 1-6 ; (2-amino-4,5-dihydro-oxazol-4-yl)(CH 2 ) 1-6 ; aminophenyl; 4-aminotetrahydropyran-4-yl(CH 2 ) 1-6 ; azetidin-2-yl(CH 2 ) 1-6 ; azetidin-3-yl(CH 2 ) 0-6 ; azetidin-3-ylcarbonyl; C 1-6 alkoxy(CH 2 ) 2-6 ; C 1-6 alkoxy(CH 2 ) 2-6 amino(CH 2 ) 2-6 ; C 1-6 alkyl; C 1-6 alkylamino(CH 2 ) 2-6 ; C 1-6 alkylaminooxetanyl(CH 2 ) 1-6 ; C 1-6 alkylcarbonyl; C 1-6 alkylcarbonylamino(CH 2 ) 2-6 ; C 1-6 alkylcarbonylamino(CH 2 ) 1-6 oxetanyl(CH 2 ) 0-6 ; C 1-6 alkylsulfinyl(CH 2 ) 2-6 ; C 1-6 alkylsulfonyl; carboxy(CH 2 ) 1-6 ; cyano(CH 2 ) 1-6 ; C 1-6 alkylaminocarbonyl(CH 2 ) 0-6 ; diC 1-6 alkylamino(CH 2 ) 2-6 ; diC 1-6 alkylaminocarbonyl; difluoromethyl(CH 2 ) 1-6 amino(CH 2 ) 2-6 ; hydrogen; hydroxy(CH 2 ) 2-10 ; hydroxy(CH 2 ) 2-6 amino(CH 2 ) 2-6 ; hydroxy(CH 2 ) 1-6 carbonyl; hydroxy(CH 2 ) 1-6 oxetanyl(CH 2 ) 0-6 ; 4-hydroxycyclohexyl; isoxazol-3-yl; morpholin-2-yl(CH 2 ) 1-6 ; morpholin-4-yl(CH 2 ) 2-6 ; 2-oxa-6-aza-spiro[3.4]oct-8-yl; oxetanyl(CH 2 ) 0-6 ; N-oxetanylpyrrolidin-3-yl; oxo-pyrrolidin-4-ylcarbonyl; phenylaminocarbonyl; phenyl(CH 2 ) 1-6 aminooxetanyl(CH 2 ) 1-6 ; phenylcarbonyl; piperazinyl(CH 2 ) 2-6 ; piperidin-1-yl(CH 2 ) 2-6 ; piperidin-2-yl(CH 2 ) 1-6 ; piperidin-3-yl(CH 2 ) 0-6 ; piperidin-4-yl(CH 2 ) 0-6 ; piperidin-2-ylcarbonyl; piperidin-3-ylcarbonyl; piperidin-4-ylcarbonyl; pyrazin-2-ylcarbonyl; pyrazol-3-yl; pyridazin-3-ylcarbonyl; pyridine-2-yl(CH 2 ) 0-6 carbonyl; pyridine-3-yl(CH 2 ) 0-6 carbonyl; pyridine-2-ylamino(CH 2 ) 2-6 ; pyrrolidin-3-yl, unsubstituted or 4-substituted by halogen; pyrrolidin-4-yl, unsubstituted or 3-substituted by hydroxy or C 1-6 alkoxy; pyrrolidin-2-yl(CH 2 ) 1-6 ; pyrrolidin-2-ylcarbonyl; tetrahydrofuran-3-yl; tetrahydropyran-4-yl; tetrazolyl(CH 2 ) 2-6 ; trifluoromethylcarbonylamino(CH 2 ) 1-6 oxetanyl; trifluoromethylsulfonyl;
wherein R 14 is hydrogen or C 1-6 alkyl; R 15 is hydroxy, C 1-6 alkyl or amino; and R 16 is C 1-6 alkyl, trifluoromethyl, hydroxy(CH 2 ) 1-6 , amino(CH 2 ) 1-6 , aminocarbonyl or carboxy(CH 2 ) 1-6 ;
wherein R 17 is hydrogen, C 1-6 alkyl or hydroxy(CH 2 ) 1-6 ; R 18 is hydroxy(CH 2 ) 1-6 or C 1-6 alkyl; R 19 is hydroxy(CH 2 ) 1-6 , amino(CH 2 ) 1-6 , carboxy or aminocarbonyl(CH 2 ) 0-6 ; or
wherein R 20 is hydrogen or C 1-6 alkyl; R 21 is C 1-6 alkyl; R 22 is C 1-6 alkoxy or amino;
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl, azetidinyl, diazepanyl or oxopyrrolidinyl ring; which may be unsubstituted, once or twice substituted by a group selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, gemdimethyl, amino, aminocarbonyl, hydroxy, oxetanylamino, C 1-6 alkylpiperazinyl and amino(CH 2 ) 1-6 ; or
R 12 and R 13 , with the nitrogen atom to which they are attached may form a bridge ring or a spiral ring selected from 2-oxa-6-aza-spiro[3.4]octan-6-yl, 2-oxa-5,7-diazaspiro[3.4]octan-6-one-5-yl, (4aS,7aR)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl, 4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d][1,3]oxazol-5-yl, 2-aza-bicyclo[2.1.1]hexan-2-yl or 3-aza-bicyclo[3.1.0]hexan-3-yl; which may be unsubstituted or further substituted by amino.
9. The compound according to claim 8 or a pharmaceutically acceptable salt thereof, wherein
R 1 , R 2 , and R 3 are hydrogen, fluoro, chloro or methyl;
R 4 is hydrogen or methyl;
R 5 is hydrogen;
R 6 is hydrogen, fluoro, hydroxy, methoxy, morpholinyl or 4-(propan-2-yl)piperazin-1-yl;
R 7 is hydrogen, fluoro, chloro, methyl, methoxy, hydroxyethoxy, or phenoxy;
R 8 is hydrogen, fluoro or methoxy;
R 9 is hydrogen or methyl;
R 10 is hydrogen;
A is nitrogen or —C—R 11 , wherein R 11 is hydrogen, fluoro, chloro, bromo, methyl, ethyl, methoxy, trifluoromethyl, trifluoromethoxy, pyridinyloxy, methoxyethoxy, difluoromethoxy, nitro, cyclopropyl, cyano, amino, vinyl, acetylenyl, aminocarbonyl, hydroxyethoxy, methylsulfanyl, methylsulfinyl, hydroxymethyl, deuteratedmethyl, carboxyl, methoxycarbonyl, hydroxy, difluoromethyl or methylCH(hydroxy)-;
Y is —CH— or nitrogen;
Q is 2-amino-4,5-dihydro-1,3-oxazol-4-ylethyl; aminoethoxy; aminoethylaminosulfonyl; aminopropyl; carboxyethyl; methyl; phenylsulfonyl; piperidin-4-yl-carbonyl; piperidin-4-yloxy; 1H-pyrazol-3-yl; pyrrolidin-3-yloxy; or
NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen, methyl or hydroxyethyl, and the other one is aminobutyl; aminocarbonylethyl; aminocarbonylmethyl; 1-aminocyclobutylmethyl; 2-aminocyclohexyl; 3-aminocyclohexyl; 4-aminocyclohexyl; 1-aminocyclohexylmethyl; 2-aminocyclopentyl; 1-aminocyclopropylethyl; 1-aminocyclopropylmethyl; aminodecyl; (2-amino-4,5-dihydro-oxazol-5-yl)methyl; (2-amino-4,5-dihydro-oxazol-4-yl)methyl; aminoethoxyethyl; aminoethyl; aminoethylcarbonyl; aminoethylfluoromethylmethyl; aminoethylsulfanylethyl; aminoethylsulfonylethyl; aminoheptyl; aminohexyl; aminomethylcarbonyl; (1-aminomethyl-3,3-difluorocyclobutyl)methyl; aminomethyldifluoromethyldifluoromethylmethyl; aminomethyldifluoromethylmethyl; (2-amino-5-methyl-4,5-dihydro-1,3-oxazol-5-yl)methyl; 3-aminomethyl-1,1-dioxidothietan-3-ylmethyl; aminomethylfluoromethylethyl; aminomethylfluoromethylmethyl; aminomethyloxetanyl; aminomethyloxetanylmethyl; 3-(aminomethyl)thietan-3-ylmethyl; aminononyl; aminooctyl; aminooxetanylethyl; aminooxetanylmethyl; aminopentyl; aminophenyl; aminopropyl; 4-aminotetrahydropyran-4-ylmethyl; 3-aminotetrahydrofuran-3-ylmethyl; azetidin-3-yl; azetidin-3-ylcarbonyl; azetidin-2-ylmethyl; azetidin-3-ylmethyl; carboxyethyl; carboxymethyl; cyanoethyl; difluoromethylmethylaminoethyl; 4,5-dihydro-1H-imidazol-2-yl; dimethylaminocarbonyl; dimethylaminoethyl; (1,1-dioxidothiomorpholin-4-yl)ethyl; ethyl; ethylaminocarbonyl; ethylaminoethyl; ethylaminooxetanylmethyl; ethyl (oxetanyl)aminoethyl; hydrogen; 4-hydroxycyclohexyl; hydroxyethyl; hydroxyethylaminoethyl; hydroxyethyloxetanyl; hydroxymethylcarbonyl; hydroxymethyloxetanylmethyl; hydroxynonyl; hydroxypropyl; isoxazol-3-yl; methoxyethyl; methoxyethylaminoethyl; methyl; methylaminocarbonylmethyl; methylaminoethyl; methylcarbonyl; methylcarbonylaminoethyl; methylcarbonylaminomethyloxetanylmethyl; methylcarbonylaminopropyl; methylsulfinylethyl; 2-(S-methylsulfonimidoyl)ethyl; methylsulfonyl; morpholin-4-ylethyl; morpholin-2-ylmethyl; 2-oxa-6-aza-spiro[3.4]oct-8-yl; oxetanyl; oxetanylaminoethyl; oxetanylaminopropyl; oxetanylmethyl; N-oxetanylpyrrolidin-3-yl; oxo-pyrrolidin-4-ylcarbonyl; phenylaminocarbonyl; phenylcarbonyl; phenylmethylaminooxetanylmethyl; piperazin-1-ylethyl; piperidin-2-ylcarbonyl; piperidin-3-ylcarbonyl; piperidin-4-ylcarbonyl; piperidine-3-yl; piperidine-4-yl; piperidin-1-ylethyl; piperidin-2-ylmethyl; pyrazin-2-ylcarbonyl; pyrazol-3-yl; pyridazin-3-ylcarbonyl; pyridine-2-ylmethylcarbonyl; pyridine-2-ylaminoethyl; pyridine-2-ylcarbonyl; pyridine-3-ylcarbonyl; pyrrolidin-3-yl, unsubstituted or 4-substituted by fluoro; pyrrolidin-4-yl, unsubstituted or 3-substituted by hydroxy or methoxy; pyrrolidin-2-ylmethyl; pyrrolidin-2-ylcarbonyl; tetrahydrofuran-3-yl; tetrahydropyran-4-yl; tetrazolylethyl; trifluoromethylsulfonyl; trifluoromethylcarbonylaminomethyloxetanyl;
wherein R 14 is hydrogen or methyl; R 15 is hydroxy, methyl or amino; and R 16 is methyl, trifluoromethyl, hydroxymethyl, hydroxyethyl, aminomethyl, aminocarbonyl or carboxymethyl;
wherein R 17 is hydrogen, methyl or hydroxymethyl; R 18 is hydroxymethyl or methyl; R 19 is hydroxymethyl, aminomethyl, carboxy, aminocarbonyl or aminocarbonylmethyl; or
wherein R 20 is hydrogen or methyl; R 21 is methyl or ethyl; R 22 is methoxy or amino;
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl, piperazinyl, piperidinyl, morpholinyl, azetidinyl, diazepanyl or oxopyrrolidinyl ring; which may be unsubstituted, once or twice substituted by a group selected from fluoro, methyl, methoxy, gemdimethyl, amino, aminocarbonyl, hydroxy, oxetanylamino, methylpiperazinyl and aminomethyl; or
R 12 and R 13 , with the nitrogen atom to which they are attached may form a bridge ring or a spiral ring selected from 2-oxa-6-aza-spiro[3.4]octan-6-yl, 2-oxa-5,7-diazaspiro[3.4]octan-6-one-5-yl, (4aS,7aR)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl, 4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d][1,3]oxazol-5-yl, 2-aza-bicyclo[2.1.1]hexan-2-yl or 3-aza-bicyclo[3.1.0]hexan-3-yl; which may be unsubstituted or further substituted by amino.
10. The compound according to any one of claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are hydrogen;
A is —C—R 11 , wherein R 11 is C 1-6 alkyl;
X is S(O)NH;
Y is —CH—;
Q is NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen; and the other one is amino(CH 2 ) 2-6 ; or
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl ring, which may be twice substituted by a group selected from amino and hydroxyl.
11. The compound according to claim 10 or a pharmaceutically acceptable salt thereof, wherein
R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are hydrogen;
A is —C—R 11 , wherein R 11 is methyl;
Q is NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen; and the other one is aminoethyl; or
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl ring, which may be twice substituted by a group selected from amino and hydroxyl.
12. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[(3-aminooxetan-3-yl)methyl]-2-(8-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(8-fluoro-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(7-fluoro-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(9-fluoro-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(7-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(8-chloro-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(7-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-[(3-aminotetrahydrofuran-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; and N-[(4-aminotetrahydro-2H-pyran-4-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine.
13. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[(3-aminooxetan-3-yl)methyl]-2-(8-methyl-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-(8-methyl-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(2-oxa-6-azaspiro[3.4]oct-8-yl)quinolin-4-amine; N-[2-(3-aminooxetan-3-yl)ethyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-(5-methyl-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(8-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-1,6-naphthyridin-4-amine; N-[(1-aminocyclohexyl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(8-fluoro-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; and N-{[3-(benzylamino)oxetan-3-yl]methyl}-6-chloro-2-(7-fluoro-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine.
14. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[(3-aminooxetan-3-yl)methyl]-6-chloro-2-(7-fluoro-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(7-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(7-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-{[3-({[2-(7-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}methyl)oxetan-3-yl]methyl}acetamide; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(8-methyl-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-6-methyl-2-(8-methyl-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; [3-({[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}methyl)oxetan-3-yl]methanol; (2S)-3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propane-1,2-diol; and (2R)-3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propane-1,2-diol.
15. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-{[1-(aminomethyl)-3,3-difluorocyclobutyl]methyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-6-chloro-2-(8-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-6-chloro-2-(8-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; trans-N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]cyclohexane-1,2-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]cyclohexane-1,3-diamine; (3R)-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4,4-dimethylpyrrolidin-3-ol; cis-N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]cyclohexane-1,4-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2,2-difluoropropane-1,3-diamine; N-[6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]-2,2-difluoropropane-1,3-diamine; and N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2-fluoropropane-1,3-diamine.
16. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[(3-aminooxetan-3-yl)methyl]-6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; [4-{[(3-aminooxetan-3-yl)methyl]amino}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-6-yl]methanol; N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-7-fluoro-6-methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-5-fluoro-6-methylquinolin-4-amine; N˜1˜-[6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]-2-methylpropane-1,2-diamine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(tetrahydro-2H-pyran-4-yl)quinolin-4-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-[2-(piperazin-1-yl)ethyl]quinolin-4-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(piperidin-4-ylmethyl)quinolin-4-amine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]heptane-1,7-diamine; and N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N′-methylethane-1,2-diamine.
17. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N′-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N,N-dimethylethane-1,2-diamine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N,6-dimethylquinolin-4-amine trifluoroacetate; (3S,4S)-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyrrolidine-3,4-diol; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(pyrrolidin-2-ylmethyl)quinolin-4-amine; 4-[4-(1,4-diazepan-1-yl)-6-methylquinolin-2-yl]-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N′-ethylethane-1,2-diamine; 2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}ethanol; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(piperidin-4-yl)quinolin-4-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(piperidin-3-yl)quinolin-4-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(piperidin-2-ylmethyl)quinolin-4-amine; and 2-[(2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}ethyl)amino]ethanol.
18. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2,2,3,3-tetrafluorobutane-1,4-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N′-(2-methoxyethyl)ethane-1,2-diamine; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-3-methylpyrrolidin-3-ol; N-[6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]ethane-1,2-diamine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(oxetan-3-yl)quinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-[(3R)-tetrahydrofuran-3-yl]quinolin-4-amine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; and N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine.
19. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(oxetan-3-ylmethyl)quinolin-4-amine; N-[(1-aminocyclobutyl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pentane-1,5-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]hexane-1,6-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-1,1,1-trifluoromethanesulfonamide hydrochloride; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyridazine-3-carboxamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]benzamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]acetamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]piperidine-3-carboxamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]piperidine-4-carboxamide; and 3-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-1,1-dimethylurea.
20. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(1,2-oxazol-3-yl)quinolin-4-amine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-(˜2˜H_3_)methylquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-6-chloro-2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-[6-chloro-2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]ethane-1,2-diamine; N-[(3-aminooxetan-3-yl)methyl]-2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; 1-[2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyrrolidin-3-amine; N-[2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]-2,2-difluoropropane-1,3-diamine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N-[2-(1,1-dioxidothiomorpholin-4-yl)ethyl]-6-methylquinolin-4-amine; N-[2-(2-aminoethoxy)ethyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N˜1˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2-methylpropane-1,2-diamine; and N˜1˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]-2-methylpropane-1,2-diamine.
21. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N˜1˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]propane-1,2-diamine; 4-[6-methyl-4-(4-methylpiperazin-1-yl)quinolin-2-yl]-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide; 1-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propan-2-ol; (2S)—N˜1˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]propane-1,2-diamine; (2R)—N˜1˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]propane-1,2-diamine; N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-7,8-difluoro-6-methylquinolin-4-amine; N-(2,2-difluoroethyl)-N′-[2-(1,1-dioxido-2,3-dihydro-1,4benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]ethane-1,2-diamine; 3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}oxetan-3-ethanol; N-{[3-(aminomethyl)thietan-3-yl]methyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; and N-{[3-(aminomethyl)-1,1-dioxidothietan-3-yl]methyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine.
22. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-(4,5-dihydro-1H-imidazol-2-yl)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; trans-4-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}cyclohexanol; (2S)-2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propan-1-ol; trans-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4-methoxypyrrolidin-3-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N-[trans-4-methoxypyrrolidin-3-yl]-6-methylquinolin-4-amine; 4-{4-[(4aS,7aR)-hexahydropyrrolo[3,4-b][1,4]oxazin-6(2H)-yl]-6-methylquinolin-2-yl}-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide; (3R,4R)-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4-(4-methylpiperazin-1-yl)pyrrolidin-3-ol; N-{2-[(2-aminoethyl)sulfanyl]ethyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; 1-{1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]piperidin-4-yl}methanamine; and 2-{[2-(8-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]amino}ethanol.
23. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]propane-1,3-diamine; 4-[6-methyl-4-(morpholin-4-yl)quinolin-2-yl]-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide; 3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propan-1-ol; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-[2-(piperidin-1-yl)ethyl]quinolin-4-amine; 1-amino-3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propan-2-ol; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]glycine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-fluoroquinolin-4-yl]ethane-1,2-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-ethylquinolin-4-yl]ethane-1,2-diamine; N-[7-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]propane-1,3-diamine; N-[8-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]propane-1,3-diamine; and N-[5-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]propane-1,3-diamine.
24. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2,2-dimethylpropane-1,3-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]ethane-1,2-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]ethane-1,2-diamine; N˜2˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2-methylpropane-1,2-diamine; N˜2˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]propane-1,2-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]butane-1,4-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-nitro quinolin-4-yl]ethane-1,2-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-5-fluoro-6-methylquinolin-4-yl]ethane-1,2-diamine; 2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-5-fluoro-6-methylquinolin-4-yl]amino}ethanol; 2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-7-fluoro-6-methylquinolin-4-yl]amino}ethanol; and N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-7-fluoro-6-methylquinolin-4-yl]ethane-1,2-diamine.
25. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-7,8-difluoro-6-methylquinolin-4-yl]ethane-1,2-diamine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N-(2-methoxyethyl)-6-methylquinolin-4-amine; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]piperidin-4-amine; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-1,6-naphthyridin-4-yl]pyrrolidin-3-amine; N-[6-(difluoromethyl)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]propane-1,3-diamine; 6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N-ethylquinolin-4-amine; 2-{[6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]amino}ethanol; N-[6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4 (5H)-yl)quinolin-4-yl]-N′-methylethane-1,2-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-(methylsulfanyl)quinolin-4-yl]propane-1,3-diamine; N-[6-bromo-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]propane-1,3-diamine; and {4-[(2-aminoethyl)amino]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-6-yl}methanol.
26. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propane-1,3-diol; 2,2′-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]imino}diethanol; 4-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4 (5H)-yl)-6-methylquinolin-4-yl]amino}-3-hydroxybutanoic acid; 1-amino-3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}-2-methylpropan-2-ol; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-[2-(morpholin-4-yl)ethyl]quinolin-4-amine; 2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-1,6-naphthyridin-4-yl]amino}ethanol; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-8-methylquinolin-4-yl]nonane-1,9-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-8-methylquinolin-4-yl]decane-1,10-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]octane-1,8-diamine; 9-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}nonan-1-ol; and N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-8-methylquinolin-4-yl]octane-1,8-diamine.
27. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
cis-4-amino-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyrrolidin-3-ol; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-L-alanine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-beta-alanine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]benzene-1,3-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]benzene-1,4-diamine; (3S)-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyrrolidin-3-ol; (3R)-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyrrolidin-3-ol; trans-N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]cyclopentane-1,2-diamine; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]piperidin-3-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N,N,6-trimethylquinolin-4-amine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-(trifluoromethoxy)quinolin-4-yl]propane-1,3-diamine; and N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-(trifluoromethyl)quinolin-4-yl]propane-1,3-diamine.
28. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[6-(difluoromethoxy)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]propane-1,3-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methoxyquinolin-4-yl]propane-1,3-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-8-methylquinolin-4-yl]propane-1,3-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-8-methylquinolin-4-yl]propane-1,3-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-7-methylquinolin-4-yl]propane-1,3-diamine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-fluoroquinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; (+)-N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-[1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl]quinolin-4-amine; (−)-N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-[1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl]quinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-6-chloro-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; and 2,2-difluoro-N-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]propane-1,3-diamine.
29. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[6-chloro-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]-2,2-difluoropropane-1,3-diamine; N-[6-chloro-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]ethane-1,2-diamine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-6-chloro-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]ethane-1,2-diamine; 2-{[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]amino}ethanol; trans-4-amino-1-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]pyrrolidin-3-ol; (1R,5S,6S)-3-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-3-azabicyclo[3.1.0]hexan-6-amine; trans-4-amino-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyrrolidin-3-ol; and 1-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]pyrrolidin-3-amine.
30. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
trans-1-[6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]-4-fluoropyrrolidin-3-amine; trans-4-amino-1-[6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]pyrrolidin-3-ol; trans-1-[6-chloro-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]-4-fluoropyrrolidin-3-amine; 2-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2-azabicyclo[2.1.1]hexan-5-amine; 2-(8-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; 2-(7-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[2-(1-aminocyclopropyl)ethyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(morpholin-2-ylmethyl)quinolin-4-amine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N-methylethane-1,2-diamine; and N-(azetidin-2-ylmethyl)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine.
31. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(pyrrolidin-3-yl)quinolin-4-amine; N-[(1-aminocyclopropyl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-(azetidin-3-yl)-6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; 6-[2-(1,1-dioxido-2,3dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2-oxa-6-azaspiro[3.4]octan-8-amine; trans-4-amino-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-1,6-naphthyridin-4-yl]pyrrolidin-3-ol; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyrrolidin-3-amine; N-(azetidin-3-yl)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]azetidin-3-amine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]prolinamide; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N-(trans-4-fluoropyrrolidin-3-yl)-6-methylquinolin-4-amine; and trans-4-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]amino}pyrrolidin-3-ol.
32. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
trans-4-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}pyrrolidin-3-ol; cis-4-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}pyrrolidin-3-ol; N-[trans-4-fluoropyrrolidin-3-yl]-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; 4-[(3-aminopropyl)amino]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-6-ol; 2-({4-[(3-aminopropyl)amino]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-6-yl}oxy)ethanol; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-(2-methoxyethoxy)quinolin-4-yl]propane-1,3-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-(pyridin-2-yloxy)quinolin-4-yl]propane-1,3-diamine; 3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propane-1,2-diol; 3-{[6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]amino}propane-1,2-diol; and 3-{[2-(8-chloro-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propane-1,2-diol.
33. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
3-{[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]amino}propane-1,2-diol; 3-{[6-methyl-2-(5-methyl-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]amino}propane-1,2-diol; N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-[7-(morpholin-4-yl)-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl]quinolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-2-{1,1-dioxido-7-[4-(propan-2-yl)piperazin-1-yl]-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl}-6-methylquinolin-4-amine; 3-{[4-(4-aminoquinolin-2-yl)-1,1-dioxido-2,3,4,5-tetrahydro-1,4-benzothiazepin-8-yl]oxy}propan-1-ol; N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-8-phenoxy-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N˜3˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-beta-alaninamide; 3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}butanamide; 3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}-2-methylpropanamide; and N˜2˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-L-alaninamide.
34. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N˜2˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]glycinamide; N˜2˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N-methylglycinamide; (2S)-2-amino-3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propan-1-ol; (2R)-2-amino-3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propan-1-ol; N-[(2-amino-4,5-dihydro-1,3-oxazol-5-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[(2-amino-5-methyl-4,5-dihydro-1,3-oxazol-5-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-{[(4R)-2-amino-4,5-dihydro-1,3-oxazol-4-yl]methyl}-2-(1,1-dioxido-2,3-dihydro-1,4benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-{[(4S)-2-amino-4,5-dihydro-1,3-oxazol-4-yl]methyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; and cis-5-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d][1,3]oxazol-2-amine.
35. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]glycinamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2-methylalaninamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]alaninamide; 2-amino-N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]butanamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2-methoxy-2-methylpropanamide; N˜1˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4,4,4-trifluorobutane-1,3-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-beta-alaninamide; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-N-{[3-(ethylamino)oxetan-3-yl]methyl}-6-methylquinolin-4-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-[1-(oxetan-3-yl)pyrrolidin-3-yl]quinolin-4-amine; and N′-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N-ethyl-N-(oxetan-3-yl)ethane-1,2-diamine.
36. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N′-(oxetan-3-yl)propane-1,3-diamine; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N-(oxetan-3-yl)pyrrolidin-3-amine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N′-(oxetan-3-yl)ethane-1,2-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-N′-(pyridin-2-yl)ethane-1,2-diamine; (4R)-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4-hydroxypyrrolidin-2-one; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-5-oxopyrrolidine-3-carboxamide; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(1H-pyrazol-3-yl)quinolin-4-amine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyridine-3-carboxamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]piperidine-2-carboxamide; and N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2-(pyridin-2-yl)acetamide.
37. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]methanesulfonamide trifluoroacetate; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyrazine-2-carboxamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2-hydroxyacetamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyridine-2-carboxamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]azetidine-2-carboxamide; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-3-phenylurea; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-3-ethylurea; N-[6-cyclopropyl-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]propane-1,3-diamine; 4-[(3-aminopropyl)amino]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinoline-6-carbonitrile; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-ethenylquinolin-4-yl]propane-1,3-diamine; and N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-ethynylquinolin-4-yl]propane-1,3-diamine.
38. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; N-{[3-(benzylamino)oxetan-3-yl]methyl}-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; 2-fluoro-N-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]propane-1,3-diamine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine; 2,2-difluoro-N-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]propane-1,3-diamine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]-2,2-difluoropropane-1,3-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]-2-fluoropropane-1,3-diamine; N-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]propane-1,3-diamine; N-[(3-aminooxetan-3-yl)methyl]-2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; and N-[(3-aminooxetan-3-yl)methyl]-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine.
39. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-6-chloro-2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-6-chloro-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; N-[(3-aminooxetan-3-yl)methyl]-6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; 2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]amino}ethanol; 2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine; N˜1˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]-2-methylpropane-1,2-diamine; N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine; N-[(1-aminocyclobutyl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine; and N-{[3-(aminomethyl)oxetan-3-yl]methyl}-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine.
40. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
(−)-N-{[3-(aminomethyl)oxetan-3-yl]methyl}-6-methyl-2-[1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl]quinazolin-4-amine; (+)-N-{[3-(aminomethyl)oxetan-3-yl]methyl}-6-methyl-2-[1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl]quinazolin-4-amine; N˜4˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]-2-fluorobutane-1,4-diamine; N˜1˜-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]-2-fluorobutane-1,4-diamine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine; trans-4-fluoro-1-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]pyrrolidin-3-amine; N-(Azetidin-3-yl)-6-methyl-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; N-(2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}ethyl)acetamide; N-{[3-({[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}methyl)oxetan-3-yl]methyl}acetamide; and N-(3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propyl)acetamide.
41. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]acetamide; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-3-methylpyrrolidin-3-amine; N-[(3-aminooxetan-3-yl)methyl]-2-(9-methoxy-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; 4-(4-{[(3-aminooxetan-3-yl)methyl]amino}-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepin-7-ol 1,1-dioxide; 3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}-2-methylpropane-1,2-diol; 4-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}butane-1,3-diol; N-[6-methyl-2-(2-methyl-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-yl]ethane-1,2-diamine; N-[(3-aminooxetan-3-yl)methyl]-6-methyl-2-(2-methyl-1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-4-amine; N-[(3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}oxetan-3-yl)methyl]-2,2,2-trifluoroacetamide; N-[3-(aminomethyl)oxetan-3-yl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; and 2-(aminomethyl)-2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propane-1,3-diol.
42. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
4-amino-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyrrolidin-2-one; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-[2-(methylsulfinyl)ethyl]quinolin-4-amine; N-{2-[(2-amino ethyl)sulfonyl]ethyl}-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-amine; N-[2-(1-imino-1-oxido-1,2,3,5-tetrahydro-4H-1lambda˜4˜,4-benzothiazepin-4-yl)-6-methylquinolin-4-yl]ethane-1,2-diamine; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-[2-(S-methylsulfonimidoyl)ethyl]quinolin-4-amine; trans-4-amino-1-[2-(1-imino-1-oxido-1,2,3,5-tetrahydro-4H-1lambda˜4˜,4-benzothiazepin-4-yl)-6-methylquinolin-4-yl]pyrrolidin-3-ol; trans-1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-4-fluoropyrrolidin-3-amine; 1-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]pyrrolidine-3-carboxamide; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-(methylsulfinyl)quinolin-4-yl]propane-1,3-diamine; 4-[(3-aminopropyl)amino]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinoline-6-carboxamide; and 1-{4-[(3-aminopropyl)amino]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-6-yl}ethanol.
43. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}propanenitrile; 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-[2-(1H-tetrazol-5-yl)ethyl]quinolin-4-amine; N˜4˜-(2-aminoethyl)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinoline-4,6-diamine; 5-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]-2-oxa-5,7-diazaspiro[3.4]octan-6-one; 3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]amino}propane-1,2-diol; 3-{[6-chloro-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]amino}propane-1,2-diol; N-[2-(2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]ethane-1,2-diamine; N-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]ethane-1,2-diamine; N-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-yl]ethane-1,2-diamine; and N-[3-(aminomethyl)oxetan-3-yl]-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine.
44. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-(trans-4-fluoropyrrolidin-3-yl)-6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; N-(trans-4-fluoropyrrolidin-3-yl)-6-methyl-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; 1-[6-methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-yl]pyrrolidin-3-amine; N-(azetidin-3-yl)-6-methyl-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; (4R)-4-{2-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]ethyl}-4,5-dihydro-1,3-oxazol-2-amine; 3-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-ethylquinolin-4-yl]propanoic acid; 3-[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]propan-1-amine; 2-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]oxy}ethanamine; 4-[6-methyl-4-(pyrrolidin-3-yloxy)quinolin-2-yl]-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide; 4-[6-methyl-4-(piperidin-4-yloxy)quinolin-2-yl]-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide; 4-(4,6-dimethylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide; and [2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl](piperidin-4-yl)methanone.
45. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
4-[6-methyl-4-(1H-pyrazol-3-yl)quinolin-2-yl]-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide; 4-[6-methyl-4-(phenylsulfonyl)quinolin-2-yl]-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide; N-(2-aminoethyl)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinoline-4-sulfonamide; methyl 4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinoline-6-carboxylate; 4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinoline-6-carboxylic acid; [4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinolin-6-yl]methanol; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-6-(˜2˜H_3_)methyl-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-4-amine; 4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazoline-6-carboxylic acid; 4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazoline-6-carboxylic acid; [4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1-oxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-6-yl]methanol; [4-({[3-(aminomethyl)oxetan-3-yl]methyl}amino)-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)quinazolin-6-yl]methanol; N-[(1-aminocyclopropyl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine; and 2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methyl-N-(pyrrolidin-3-yl)quinazolin-4-amine.
46. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen or halogen;
R 2 and R 4 are hydrogen;
R 3 is hydrogen or halogen;
R 5 is hydrogen or halogen;
R 6 is hydrogen, halogen, hydroxy, C 1-6 alkoxy or carboxy;
R 7 is hydrogen, halogen, C 1-6 alkoxy, C 1-6 alkylaminocarbonyl, diC 1-6 alkylaminocarbonyl or C 1-6 alkylsulfonyl;
R 8 is hydrogen or halogen;
R 9 is hydrogen or ═O;
R 10 is hydrogen or ═O, provided that R 9 and R 10 are not ═O simultaneously;
A is —C—R 11 , wherein R 11 is hydrogen, halogen, C 1-6 alkyl, C 1-6 alkoxy, trifluoromethyl, trifluoromethoxy, pyridinyloxy, difluoromethoxy or C 1-6 alkylsulfonyl;
X is —CH 2 —, —O—, —NH—, —CF 2 , —C(CH 3 )(OH)—, C═O, or —C(═N—C 1-6 alkoxy)-;
Y is —CH— or nitrogen;
Q is hydrogen; halogen; C 1-6 alkyl, once or twice substituted by hydroxy provided that disubstitution of hydroxy is not on the same carbon; amino(CH 2 ) 2-6 aminosulfonyl; 2-amino-4,5-dihydro-1,3-oxazol-4-ylethyl; or NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen, C 1-6 alkyl or hydroxy(CH 2 ) 2- , and the other one is guanidino(CH 2 ) 2-6 ; 3-aminomethyl-1,1-dioxidothietan-3-ylmethyl; 3-amino-1,1-dioxidothietan-3-ylmethyl; 3-(aminomethyl)thietan-3-ylmethyl; amino(CH 2 ) 2-6 —O—(CH 2 ) 2-6 ; amino(CH 2 ) 2-10 ; amino(CH 2 ) 1-6 carbonyl; amino(CH 2 ) 1-6 difluoromethyl(CH 2 ) 1-6 ; amino(CH 2 ) 1-6 oxetanyl(CH 2 ) 1-6 ; amino(CH 2 ) 2-6 sulfonyl(CH 2 ) 2-6 ; 3-aminocyclohexyl; 4-aminocyclohexyl; 2-amino-4,5-dihydro-oxazol-5-yl(CH 2 ) 1-6 ; aminooxetanyl(CH 2 ) 1-6 ; C 1-6 alkylamino(CH 2 ) 2-6 ; C 1-6 alkylaminocarbonyl; diC 1-6 alkylamino(CH 2 ) 2-6 ; hydroxy(CH 2 ) 2-6 ; piperazinyl(CH 2 ) 2-6 ; pyrrolidin-3-yl; or
wherein R 14 is hydrogen, C 1-6 alkyl or hydroxy(CH 2 ) 1-6 ; R 15 is hydroxy, hydroxy(CH 2 ) 1-6 or amino; and R 16 is C 1-6 alkyl, hydroxy(CH 2 ) 1-6 or amino(CH 2 ) 1-6 ; or
R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl, piperazinyl or diazepanyl ring; which may be unsubstituted, once or twice substituted by a group selected from C 1-6 alkyl, amino or hydroxy.
47. The compound according to claim 46 or a pharmaceutically acceptable salt thereof, wherein
R 1 is hydrogen or chloro;
R 2 and R 4 are hydrogen;
R 3 is hydrogen or chloro;
R 5 is hydrogen or fluoro;
R 6 is hydrogen, fluoro, hydroxy, methoxy, ethoxy or carboxy;
R 7 is hydrogen, fluoro, bromo, methoxy, dimethylaminocarbonyl, methylsulfonyl or ethylsulfonyl;
R 8 is hydrogen or chloro;
A is CR 11 , wherein R 11 is hydrogen, fluoro, chloro, bromo, methyl, methoxy, trifluoromethyl, trifluoromethoxy, pyridinyloxy, difluoromethoxy or methylsulfonyl;
Q is hydrogen; chloro; hydroxymethyl; hydroxymethyl(hydroxy)ethyl; aminoethylaminosulfonyl; 2-amino-4,5-dihydro-1,3-oxazol-4-ylethyl; or NR 12 R 13 , wherein one of R 12 and R 13 is hydrogen, methyl or hydroxyethyl; and the other one is aminobutyl; 3-aminocyclohexyl; 4-aminocyclohexyl; 2-amino-4,5-dihydro-oxazol-5-ylmethyl; 3-amino-1,1-dioxidothietan-3-ylmethyl; aminoethoxyethyl; aminoethyl; aminoethylsulfonylethyl; aminomethylcarbonyl; aminomethyldifluoromethylmethyl; 3-aminomethyl-1,1-dioxidothietan-3-ylmethyl; 3-(aminomethyl)thietan-3-ylmethyl; aminomethyloxetanylmethyl; aminooxetanylmethyl; aminopropyl; dimethylaminoethyl; ethylaminocarbonyl; guanidinoethyl; hydroxyethyl; hydroxypropyl; methylaminoethyl; piperazin-1-ylethyl; pyrrolidin-3-yl; or
wherein R 14 is hydrogen, methyl or hydroxymethyl; R 15 is hydroxy, hydroxymethyl or amino; and R 16 is methyl, hydroxymethyl or aminomethyl; or R 12 and R 13 , with the nitrogen atom to which they are attached, may form a pyrrolidinyl, piperazinyl or diazepanyl ring; which may be unsubstituted, once or twice substituted by a group selected from methyl, amino or hydroxy.
48. The compound according to claim 46 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[(3-amino oxetan-3-yl)methyl]-2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-amine; N-[2-(2-aminoethoxy)ethyl]-2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-amine; N-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]-N′-methylethane-1,2-diamine; 1-amino-3-{[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]amino}propan-2-ol; 3-{[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]amino}propane-1,2-diol; 3-{[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]amino}propan-1-ol; 2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methyl-N-[2-(piperazin-1-yl)ethyl]quinolin-4-amine; N˜1˜-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]propane-1,2-diamine; cis-N-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]cyclohexane-1,4-diamine; and 2-(9,9-difluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-yl)-6-methyl-N-(pyrrolidin-3-yl)quinolin-4-amine.
49. The compound according to claim 46 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
2,2′-{[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]imino}diethanol; N˜1˜-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]-2-methylpropane-1,2-diamine; 5,5-difluoro-2-[6-methyl-4-(4-methylpiperazin-1-yl)quinolin-2-yl]-2,3,4,5-tetrahydro-1H-2-benzazepine; 1-[2-(9,9-difluoro-6,7,8,9-tetrahydro-5H-benzo[7]annulen-6-yl)-6-methylquinolin-4-yl]-3-ethylurea; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-amine; 5,5-difluoro-2-[6-methyl-4-(piperazin-1-yl)quinolin-2-yl]-2,3,4,5-tetrahydro-1H-2-benzazepine; 2-[4-(1,4-diazepan-1-yl)-6-methylquinolin-2-yl]-5,5-difluoro-2,3,4,5-tetrahydro-1H-2-benzazepine; N-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]-N-methylethane-1,2-diamine; 1-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]pyrrolidin-3-amine; 2-{[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]amino}ethanol; and N-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]ethane-1,2-diamine.
50. The compound according to claim 46 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]cyclohexane-1,3-diamine; N′-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]-N,N-dimethylethane-1,2-diamine; N-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]propane-1,3-diamine; N-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]butane-1,4-diamine; trans-4-amino-1-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]pyrrolidin-3-ol; N-{[3-(aminomethyl)-1,1-dioxidothietan-3-yl]methyl}-2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-amine; N-{2-[(2-aminoethyl)sulfonyl]ethyl}-2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-amine; N-{[3-(aminomethyl)thietan-3-yl]methyl}-2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinazolin-4-amine; N-{[3-(aminomethyl)oxetan-3-yl]methyl}-2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinazolin-4-amine; and 2-(aminomethyl)-2-({[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinazolin-4-yl]amino}methyl)propane-1,3-diol.
51. The compound according to claim 46 , or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
2-(4-{[(3-aminooxetan-3-yl)methyl]amino}-6-methylquinazolin-2-yl)-5-methyl-2,3,4,5-tetrahydro-1H-2-benzazepin-5-ol; N-[(3-aminooxetan-3-yl)methyl]-2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinazolin-4-amine; N-[(3-amino-1,1-dioxidothietan-3-yl)methyl]-2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinazolin-4-amine; N-[2-(5,5-difluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinazolin-4-yl]-2,2-difluoropropane-1,3-diamine; N-[2-(7-bromo-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-chloroquinolin-4-yl]ethane-1,2-diamine; 2-{4-[(2-amino ethyl)amino]quinolin-2-yl}-2,3,4,5-tetrahydro-1H-2-benzazepin-8-ol; N-[6-methyl-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[2-(8-fluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]ethane-1,2-diamine; N-[6-chloro-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[6-chloro-2-(9-fluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[2-(8-fluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; and 1-amino-3-{[2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]amino}propan-2-ol trifluoroacetate.
52. The compound according to claim 46 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[6-bromo-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[6-methoxy-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[2-(6-chloro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[2-(7-fluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-methylquinolin-4-yl]ethane-1,2-diamine; N-methyl-N-[2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[2-(7-methoxy-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[2-(7-fluoro-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4yl]ethane-1,2-diamine; N-[2-(8-methoxy-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[6-(difluoromethoxy)-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-(trifluoromethyl)quinolin-4-yl]ethane-1,2-diamine; and N-[8-chloro-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine.
53. The compound according to claim 46 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[6-fluoro-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N,N-dimethyl-N′-[2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)-6-(trifluoromethoxy)quinolin-4-yl]ethane-1,2-diamine; N-[6-(methylsulfonyl)-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; 2-{4-[(2-amino ethyl)amino]quinolin-2-yl}-2,3,4,5-tetrahydro-1H-2-benzazepine-8-carboxylic acid; 2-(4-chloroquinolin-2-yl)-2,3,4,5-tetrahydro-1H-2-benzazepine; N-[5-chloro-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-{2-[7-(methylsulfonyl)-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl]quinolin-4yl}ethane-1,2-diamine; N-{2-[7-(ethylsulfonyl)-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl]quinolin-4-yl}ethane-1,2-diamine; N-[2-(8-ethoxy-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; N-[6-(pyridin-2-yloxy)-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethane-1,2-diamine; 2-{4-[(2-amino ethyl)amino]-6-chloroquinolin-2-yl}-N,N-dimethyl-2,3,4,5-tetrahydro-1H-2-benzazepine-7-carboxamide; 2-{4-[(2-aminoethyl)amino]quinolin-2-yl}-7-bromo-1,2,4,5-tetrahydro-3H-2-benzazepin-3-one; and 1-(2-{[2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]amino}ethyl)guanidine trifluoroacetate.
54. The compound according to claim 46 or a pharmaceutically acceptable salt thereof, selected from the group consisting of:
N-[(2-amino-4,5-dihydro-1,3-oxazol-5-yl)methyl]-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-amine trifluoroacetate; N-[(2-amino-4,5-dihydro-1,3-oxazol-5-yl)methyl]-6-chloro-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-amine; N-[2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]glycinamide; 3-[2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]propan-1-amine; [2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]methanol; 2-(6-chloroquinolin-2-yl)-2,3,4,5-tetrahydro-1H-2-benzazepine; 3-[6-chloro-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]propane-1,2-diol; (4S)-4-{2-[2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinolin-4-yl]ethyl}-4,5-dihydro-1,3-oxazol-2-amine; N-(2-aminoethyl)-2-(1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl)quinoline-4-sulfonamide trifluoroacetate; 4-{4-[(2-aminoethyl)amino]-6-methylquinolin-2-yl}-1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-one; N-[6-methyl-2-(1,2,3,5-tetrahydro-4H-1,4-benzodiazepin-4-yl)quinolin-4-yl]ethane-1,2-diamine; N-[2-(2,3-dihydro-1,4-benzoxazepin-4(5H)-yl)quinolin-4-yl]ethane-1,2-diamine; N-[(3-aminooxetan-3-yl)methyl]-2-[(5E)-5-(methoxyimino)-1,3,4,5-tetrahydro-2H-2-benzazepin-2-yl]-6-methylquinolin-4-amine and 2-(4-{[(3-aminooxetan-3-yl)methyl]amino}-6-methylquinazolin-2-yl)-1,2,3,4-tetrahydro-5H-2-benzazepin-5-one.
55. A pharmaceutical composition comprising a therapeutically effective amount of a compound in accordance with claim 1 and a pharmaceutically acceptable carrier.
56. A method for the treatment of respiratory syncytial virus infection, which method comprisis administering an effective amount of a compound of claim 1 .
57. A compound, wherein said compound is N-[(3-aminooxetan-3-yl)methyl]-2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinazolin-4-amine, or a pharmaceutically acceptable salt thereof.
58. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 57, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
59. A method for the treatment of respiratory syncytial virus infection, comprising the step of administering an effective amount of a compound according to claim 57, or a pharmaceutically acceptable salt thereof.Cited by (0)
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