Substituted 2-mercaptoquinoline-3-carboxamides as kcnq2/3 modulatorsThe invention relates to substituted 2-mercaptoquinoline-3-carboxamides, methods for the production thereof, medicaments containing said compounds, and the use of said compounds for producing medicaments.The replacement 2-mercaptoquinoline-3-methane amide with general formula (1) of the salt form of compatible acid of free cpds or physiology or alkaliwhereinr 0represent c 1-10alkyl or c 2-10assorted alkyl, each self-saturation or unsaturated, branching or non-branching, do not replace or single-or polysubstituted; c 3-10naphthenic base or heterocyclic radical, each self-saturation or unsaturated, do not replace or single-or polysubstituted; aryl or heteroaryl, do not replace separately or single-or polysubstituted; c 1-8alkyl-or c 2-8the c of assorted alkyl-bridging 3-10naphthenic base or heterocyclic radical, each self-saturation or unsaturated, do not replace or single-or polysubstituted, wherein alkyl or assorted alkyl chain can be in each case branching or non-branching, saturated or unsaturated, replace, single-or polysubstituted; or c 1-8alkyl-or c 2-8the aryl or the heteroaryl of assorted alkyl-bridging do not replace or single-or polysubstituted separately, wherein alkyl or assorted alkyl chain can be in each case branching or non-branching, saturated or unsaturated, replace, single-or polysubstituted; r 1, r 2, r 3, r 4represent h separately independently of one another; f; cl; br; i; no 2cf 3cn; r 0c (=o) h; c (=o) r 0co 2h; c (=o) or 0conh 2c (=o) nhr 0c (=o) n (r 0) 2oh; or 0o-c (=o)-r 0o-c (=o)-o-r 0o-(c=o)-nh-r 0o-c (=o)-n (r 0) 2o-s (=o) 2-r 0o-s (=o) 2oh; o-s (=o) 2or 0o-s (=o) 2nh 2o-s (=o) 2nhr 0o-s (=o) 2n (r 0) 2nh 2nh-r 0n (r 0) 2nh-c (=o)-r 0nh-c (=o)-o-r 0nh-c (=o)-nh 2nh-c (=o)-nh-r 0nh-c (=o)-n (r 0) 2nr 0-c (=o)-r 0nr 0-c (=o)-o-r 0nr 0-c (=o)-nh 2nr 0-c (=o)-nh-r 0nr 0-c (=o)-n (r 0) 2nh-s (=o) 2oh; nh-s (=o) 2r 0nh-s (=o) 2or 0nh-s (=o) 2nh 2nh-s (=o) 2nhr 0nh-s (=o) 2n (r 0) 2nr 0-s (=o) 2oh; nr 0-s (=o) 2r 0nr 0-s (=o) 2or 0nr 0-s (=o) 2nh 2nr 0-s (=o) 2nhr 0nr 0-s (=o) 2n (r 0) 2sh; sr 0s (=o) r 0s (=o) 2r 0s (=o) 2oh; s (=o) 2or 0s (=o) 2nh 2s (=o) 2nhr 0or s (=o) 2n (r 0) 2r 6represent r 0, condition is if r 0be meant saturated or unsaturated, do not replace or single-or polysubstituted heterocyclic radical or do not replace or single-or polysubstituted heteroaryl, then the combination of this heteroaryl or heterocyclic radical realizes via the carbon atom of this heteroaryl or heterocyclic radical; r 7represent r 0, condition is if r 0be meant saturated or unsaturated, do not replace or single-or polysubstituted heterocyclic radical or do not replace or single-or polysubstituted heteroaryl, then the combination of this heteroaryl or heterocyclic radical realizes via the carbon atom of this heteroaryl or heterocyclic radical; wherein ' alkyl replacement ', ' assorted alkyl replaces ', the one or more wasserstoffatomss of ' heterocyclic radical replacement ' and ' cycloalkyl substituted ' representative are separately independently of one another by f; cl; br; i; cn; cf 3;=o;=nh;=c (nh 2) 2; no 2; r 0; c (=o) h; c (=o) r 0; co 2h; c (=o) or 0; conh 2; c (=o) nhr 0; c (=o) n (r 0) 2; oh; or 0;-o-(c 1-8alkyl)-o-; o-c (=o)-r 0; o-c (=o)-o-r 0; o-(c=o)-nh-r 0; o-c (=o)-n (r 0) 2; o-s (=o) 2-r 0; o-s (=o) 2oh; o-s (=o) 2or 0; o-s (=o) 2nh 2; o-s (=o) 2nhr 0; o-s (=o) 2n (r 0) 2; nh 2; nh-r 0; n (r 0) 2; nh-c (=o)-r 0; nh-c (=o)-o-r 0; nh-c (=o)-nh 2; nh-c (=o)-nh-r 0; nh-c (=o)-n (r 0) 2; nr 0-c (=o)-r 0; nr 0-c (=o)-o-r 0; nr 0-c (=o)-nh 2; nr 0-c (=o)-nh-r 0; nr 0-c (=o)-n (r 0) 2; nh-s (=o) 2oh; nh-s (=o) 2r 0; nh-s (=o) 2or 0; nh-s (=o) 2nh 2; nh-s (=o) 2nhr 0; nh-s (=o) 2n (r 0) 2; nr 0-s (=o) 2oh; nr 0-s (=o) 2r 0; nr 0-s (=o) 2or 0; nr 0-s (=o) 2nh 2; nr 0-s (=o) 2nhr 0; nr 0-s (=o) 2n (r 0) 2; sh; sr 0; s (=o) r 0; s (=o) 2r 0; s (=o) 2h; s (=o) 2oh; s (=o) 2or 0; s (=o) 2nh 2; s (=o) 2nhr 0; s (=o) 2n (r 0) 2replace; wherein the one or more wasserstoffatomss of ' aryl replacement ' and ' heteroaryl replacement ' representative are separately independently of one another by f; cl; br; i; no 2; cf 3; cn; r 0; c (=o) h; c (=o) r 0; co 2h; c (=o) or 0; conh 2; c (=o) nhr 0; c (=o) n (r 0) 2; oh; or 0;-o-(c 1-8alkyl)-o-; o-c (=o)-r 0; o-c (=o)-o-r 0; o-(c=o)-nh-r 0; o-c (=o)-n (r 0) 2; o-s (=o) 2-r 0; o-s (=o) 2oh; o-s (=o) 2or 0; o-s (=o) 2nh 2; o-s (=o) 2nhr 0; o-s (=o) 2n (r 0) 2; nh 2; nh-r 0; n (r 0) 2; nh-c (=o)-r 0; nh-c (=o)-o-r 0; nh-c (=o)-nh 2; nh-c (=o)-nh-r 0; nh-c (=o)-n (r 0) 2; nr 0-c (=o)-r 0; nr 0-c (=o)-o-r 0; nr 0-c (=o)-nh 2; nr 0-c (=o)-nh-r 0; nr 0-c (=o)-n (r 0) 2; nh-s (=o) 2oh; nh-s (=o) 2r 0; nh-s (=o) 2or 0; nh-s (=o) 2nh 2; nh-s (=o) 2nhr 0; nh-s (=o) 2n (r 0) 2; nr 0-s (=o) 2oh; nr 0-s (=o) 2r 0; nr 0-s (=o) 2or 0; nr 0-s (=o) 2nh 2; nr 0-s (=o) 2nhr 0; nr 0-s (=o) 2n (r 0) 2; sh; sr 0; s (=o) r 0; s (=o) 2r 0; s (=o) 2oh; s (=o) 2or 0; s (=o) 2nh 2; s (=o) 2nhr 0; s (=o) 2n (r 0) 2replace; except the following compounds:n-benzyl-2-(3-chloro-2-hydroxypropyl sulfenyl)-4-(2,4 dichloro benzene base) quinoline-3-methane amide.
ＫＣＮＱ２／３ 조절제로서의 치환된 ２-머캅토퀴놀린-３-카복스아미드본 발명은 치환된 2-머캅토퀴놀린-3-카복스아미드, 이의 제조방법, 상기 화합물을 함유하는 약제 및 약제를 제조하기 위한 상기 화합물의 용도에 관한 것이다. 화학식 1유리 화합물 또는 생리학적으로 상용성(compatibile)인 산 또는 염기의 염 형태의, 화학식 1의 치환된 2-머캅토퀴놀린-3-카복스아미드.화학식 1[이미지]위의 화학식 1에서, R0은 C1-10 알킬 또는 C2-10 헤테로알킬(이들은 각각 포화되거나 불포화되고, 측쇄 또는 직쇄이며, 치환되지 않거나 일치환 또는 다치환된다); C3-10 사이클로알킬 또는 헤테로사이클릴(이들은 각각 포화되거나 불포화되고, 치환되지 않거나 일치환 또는 다치환된다); 아릴 또는 헤테로아릴(이들은 각각 치환되지 않거나 일치환 또는 다치환된다); C1-8 알킬- 또는 C2-8 헤테로알킬-브릿징된 C3-10 사이클로알킬 또는 헤테로사이클릴(이들은 각각 포화되거나 불포화되고, 치환되지 않거나 일치환 또는 다치환되고, 여기서, 상기 알킬 또는 헤테로알킬 쇄는 각각의 경우 측쇄 또는 직쇄일 수있고, 포화되거나 불포화될 수 있으며, 치환되지 않거나 일치환 또는 다치환될 수 있다); 또는 C1-8 알킬- 또는 C2-8 헤테로알킬-브릿징된 아릴 또는 헤테로아릴(이들은 각각 치환되지 않거나 일치환 또는 다치환되고, 여기서, 상기 알킬 또는 헤테로알킬 쇄는 각각의 경우 측쇄 또는 직쇄일 수 있고, 포화되거나 불포화될 수 있으며, 치환되지 않거나 일치환 또는 다치환될 수 있다)을 나타내고;R1, R2, R3, R4는 각각 서로 독립적으로 H; F; Cl; Br; I; NO2; CF3; CN; R0; C(=O)H; C(=O)R0; CO2H; C(=O)OR0; CONH2; C(=O)NHR0; C(=O)N(R0)2; OH; OR0; O-C(=O)-R0; O-C(=O)-O-R0; O-(C=O)-NH-R0; O-C(=O)-N(R0)2; O-S(=O)2-R0; O-S(=O)2OH; O-S(=O)2OR0; O-S(=O)2NH2; O-S(=O)2NHR0; O-S(=O)2N(R0)2; NH2; NH-R0; N(R0)2; NH-C(=O)-R0; NH-C(=O)-O-R0; NH-C(=O)-NH2; NH-C(=O)-NH-R0; NH-C(=O)-N(R0)2; NR0-C(=O)-R0; NR0-C(=O)-O-R0; NR0-C(=O)-NH2; NR0-C(=O)-NH-R0; NR0-C(=O)-N(R0)2; NH-S(=O)2OH; NH-S(=O)2R0; NH-S(=O)2OR0; NH-S(=O)2NH2; NH-S(=O)2NHR0; NH-S(=O)2N(R0)2; NR0-S(=O)2OH; NR0-S(=O)2R0; NR0-S(=O)2OR0; NR0-S(=O)2NH2; NR0-S(=O)2NHR0; NR0-S(=O)2N(R0)2; SH; SR0; S(=O)R0; S(=O)2R0; S(=O)2OH; S(=O)2OR0;S(=O)2NH2; S(=O)2NHR0; 또는 S(=O)2N(R0)2를 나타내고; R5는 H; F; Cl; Br; I; NO2; CF3; CN; R0; C(=O)H; C(=O)R0; CO2H; C(=O)OR0; CONH2; C(=O)NHR0; C(=O)N(R0)2; OR0; O-C(=O)-R0; O-C(=O)-O-R0; O-(C=O)-NH-R0; O-C(=O)-N(R0)2; O-S(=O)2-R0; O-S(=O)2OH; O-S(=O)2OR0; O-S(=O)2NH2; O-S(=O)2NHR0; O-S(=O)2N(R0)2; NH2; NH-R0; N(R0)2; NH-C(=O)-R0; NH-C(=O)-O-R0; NH-C(=O)-NH2; NH-C(=O)-NH-R0; NH-C(=O)-N(R0)2; NR0-C(=O)-R0; NR0-C(=O)-O-R0; NR0-C(=O)-NH2; NR0-C(=O)-NH-R0; NR0-C(=O)-N(R0)2; NH-S(=O)2OH; NH-S(=O)2R0; NH-S(=O)2OR0; NH-S(=O)2NH2; NH-S(=O)2NHR0; NH-S(=O)2N(R0)2; NR0-S(=O)2OH; NR0-S(=O)2R0; NR0-S(=O)2OR0; NR0-S(=O)2NH2; NR0-S(=O)2NHR0; NR0-S(=O)2N(R0)2; SH; SR0; S(=O)R0; S(=O)2R0; S(=O)2OH; S(=O)2OR0;S(=O)2NH2; S(=O)2NHR0; 또는 S(=O)2N(R0)2를 나타내고; R6은 R0을 나타내고, 단 R0이 치환되지 않거나 일치환 또는 다치환된 포화 또는 불포화 헤테로사이클릴, 또는 치환되지 않거나 일치환 또는 다치환된 헤테로아릴인 경우, 상기 헤테로아릴 또는 헤테로사이클릴의 결합은 상기 헤테로아릴 또는 헤테로사이클릴의 탄소원자를 통해 이루어지며;R7은 R0을 나타내고, 단 R0이 치환되지 않거나 일치환 또는 다치환된 포화 또는 불포화 헤테로사이클릴, 또는 치환되지 않거나 일치환 또는 다치환된 헤테로아릴인 경우, 상기 헤테로아릴 또는 헤테로사이클릴의 결합은 상기 헤테로아릴 또는 헤테로사이클릴의 탄소원자를 통해 이루어지며; 여기서, "알킬 치환된", "헤테로알킬 치환된", "헤테로사이클릴 치환된" 및 "사이클로알킬 치환된"은 하나 이상의 수소원자가 각각 서로 독립적으로 F; Cl; Br; I; CN; CF3; =O; =NH; =C(NH2)2; NO2; R0; C(=O)H; C(=O)R0; CO2H; C(=O)OR0; CONH2; C(=O)NHR0; C(=O)N(R0)2; OH; OR0; -O-(C1-8 알킬)-O-; O-C(=O)-R0; O-C(=O)-O-R0; O-(C=O)-NH-R0; O-C(=O)-N(R0)2; O-S(=O)2-R0; O-S(=O)2OH; O-S(=O)2OR0; O-S(=O)2NH2; O-S(=O)2NHR0; O-S(=O)2N(R0)2; NH2; NH-R0; N(R0)2; NH-C(=O)-R0; NH-C(=O)-O-R0; NH-C(=O)-NH2; NH-C(=O)-NH-R0; NH-C(=O)-N(R0)2; NR0-C(=O)-R0; NR0-C(=O)-O-R0; NR0-C(=O)-NH2; NR0-C(=O)-NH-R0; NR0-C(=O)-N(R0)2; NH-S(=O)2OH; NH-S(=O)2R0; NH-S(=O)2OR0; NH-S(=O)2NH2; NH-S(=O)2NHR0; NH-S(=O)2N(R0)2; NR0-S(=O)2OH; NR0-S(=O)2R0; NR0-S(=O)2OR0; NR0-S(=O)2NH2; NR0-S(=O)2NHR0; NR0-S(=O)2N(R0)2; SH; SR0; S(=O)R0; S(=O)2R0; S(=O)2H;S(=O)2OH; S(=O)2OR0;S(=O)2NH2; S(=O)2NHR0; S(=O)2N(R0)2로 치환됨을 나타내고;"아릴 치환된" 및 "헤테로아릴 치환된"은 하나 이상의 수소원자가 각각 서로 독립적으로 F; Cl; Br; I; NO2; CF3; CN; R0; C(=O)H; C(=O)R0; CO2H; C(=O)OR0; CONH2; C(=O)NHR0; C(=O)N(R0)2; OH; OR0; -O-(C1-8 알킬)-O-; O-C(=O)-R0; O-C(=O)-O-R0; O-(C=O)-NH-R0; O-C(=O)-N(R0)2; O-S(=O)2-R0; O-S(=O)2OH; O-S(=O)2OR0; O-S(=O)2NH2; O-S(=O)2NHR0; O-S(=O)2N(R0)2; NH2; NH-R0; N(R0)2; NH-C(=O)-R0; NH-C(=O)-O-R0; NH-C(=O)-NH2; NH-C(=O)-NH-R0; NH-C(=O)-N(R0)2; NR0-C(=O)-R0; NR0-C(=O)-O-R0; NR0-C(=O)-NH2; NR0-C(=O)-NH-R0; NR0-C(=O)-N(R0)2; NH-S(=O)2OH; NH-S(=O)2R0; NH-S(=O)2OR0; NH-S(=O)2NH2; NH-S(=O)2NHR0; NH-S(=O)2N(R0)2; NR0-S(=O)2OH; NR0-S(=O)2R0; NR0-S(=O)2OR0; NR0-S(=O)2NH2; NR0-S(=O)2NHR0; NR0-S(=O)2N(R0)2; SH; SR0; S(=O)R0; S(=O)2R0; S(=O)2OH; S(=O)2OR0;S(=O)2NH2; S(=O)2NHR0; S(=O)2N(R0)2로 치환됨을 나타내고,N-벤질-2-(3-클로로-2-하이드록시프로필티오)-4-(2,4-디클로로페닐)퀴놀린-3-카복스아미드의 화합물은 제외된다.