Non-anilinic derivatives of isothiazol-3(2h)-one 1,1-dioxides as liver x receptor modulatorsThe present invention relates to certain novel compounds of the formula (I) to processes for preparing such compounds, to their the utility in modulation of nuclear hormone receptors Liver X Receptor (LXR) a (NR1H3) and/or ss (NR1H2) and in treating and/or preventing clinical conditions including cardiovascular diseases such as atherosclerosis; inflammatory diseases, Alzheimer's disease, lipid disorders (dyslipidemias) whether or not associated with insulin resistance, type 2 diabetes and other manifestations of the metabolic syndrome, to methods for their therapeutic use and to pharmaceutical compositions containing them.General formula (i) compoundor its pharmacologically acceptable salt,whereinr 1representative optional by one or more x:f, oh, cn, nr that are independently selected from following group replacement ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr ac (o) r b, c (o) or a, oc (o) r b, so 2nr ar a, nr aso 2r b, nr ac (o) or b, oc (o) nr ar a, nr ac (o) nr ar aor it is optional by one or more c that are independently selected from following group replacement 1-c 4alkyl: f, oh, cn, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r bor nr ac (o) nr ar aor r 1be optional separately: f, oh, cn, nr by one or more cycloalkyl or heterocyclic radicals that are independently selected from following group replacement ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr ac (o) r b, c (o) or a, oc (o) r b, so 2nr ar a, nr aso 2r b, nr ac (o) or b, oc (o) nr ar a, nr ac (o) nr ar aor it is optional by one or more c that are independently selected from following group replacement 1-c 4alkyl: f, oh, cn, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr ac (o) r b, c (o) or a, oc (o) r b, so 2nr ar a, nr aso 2r b, nr ac (o) or b, oc (o) nr ar aor nr ac (o) nr ar aor r 1be optional separately: halogen (cl, f, i, br), oh, cn, no by one or more phenyl or heteroaryls that are independently selected from following group replacement 2, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr ac (o) r b, c (o) or a, oc (o) r b, so 2nr ar a, nr aso 2r b, nr ac (o) or b, oc (o) nr ar a, oso 2r b, r ac (o) nr ar a, so 2nhc (o) r bor it is optional by one or more c that are independently selected from following group replacement 1-c 4alkyl: f, oh, cn, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr ac (o) r b, c (o) or a, oc (o) r b, so 2nr ar a, nr aso 2r b, nr ac (o) or b, oc (o) nr ar aor nr ac (o) nr ar aor r 1be cycloalkyl y or heterocyclic radical y, wherein cycloalkyl or heterocyclic radical are optional separately is independently selected from following substituting group and replaces by one or more: f, oh, cn, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr ac (o) r b, c (o) or a, oc (o) r b, so 2nr ar a, nr aso 2r b, nr ac (o) or b, oc (o) nr ar a, nr ac (o) nr ar aor it is optional by one or more c that are independently selected from following group replacement 1-c 4alkyl: f, oh, cn, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr ac (o) r b, c (o) or a, oc (o) r b, so 2nr ar a, nr aso 2r b, nr ac (o) or b, oc (o) nr ar aor nr ac (o) nr ar aor r 1be phenyl y or heteroaryl y, wherein phenyl or heteroaryl are optional separately is independently selected from following substituting group and replaces by one or more: halogen (cl, f, i, br), oh, cn, no 2, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr ac (o) r b, c (o) or a, oc (o) r b, so 2nr ar a, nr aso 2r b, nr ac (o) or b, oc (o) nr ar a, oso 2r b, nr ac (o) nr ar a, so 2nhc (o) r bor it is optional by one or more c that are independently selected from following group replacement 1-c 4alkyl: f, oh, cn, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr cc (o) r b, c (o) or a, oc (o) r b, so 2nr ar a, nr aso 2r b, nr ac (o) or b, oc (o) nr ar aor nr ac (o) nr ar ar 2representative optional by one or more phenyl that are independently selected from following group replacement: halogen (cl, f, i, br), oh, cn, no 2, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr ac (o) r b, c (o) or a, oc (o) r b, so 2nr ar a, nr aso 2r b, nr ac (o) or b, c (o) nr ar a, oso 2r b, nr ac (o) nr ar a, so 2nhc (o) r bor it is optional by one or more c that are independently selected from following group replacement 1-c 4alkyl: f, oh, cn, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, c (o) nr ar a, nr ac (o) r b, c (o) or a, oc (o) r b, nr aso 2r b, so 2nr ar a, nr ac (o) or b, oc (o) nr ar aor nr ac (o) nr ar ar 3representative optional by one or more x:f, oh, cn, nr that are independently selected from following group replacement ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, nr ac (o) r b, c (o) nr ar a, oc (o) r b, c (o) or a, so 2nr ar a, nr aso 2r b, nr ac (o) or b, oc (o) nr ar a, nr ac (o) nr ar aor it is optional by one or more c that are independently selected from following group replacement 1-c 4alkyl: f, oh, cn, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r bor nr ac (o) nr ar aor r 3be mp or het 3p, wherein m and het 3choose wantonly separately on non-aromatic ring by one or more and be independently selected from following group and replace: f, oh, cn, nr ar a, or b, sr b, sir br br b, s (o) r b, so 2r b, c (o) r b, nr ac (o) r b, c (o) nr ar a, oc (o) r b, c (o) or a, so 2nr ar a, nr aso 2r b, oc (o)...
간 Ｘ 수용체 조절제로서 이소티아졸-3(2Ｈ)-온1,1-디옥사이드의 비-아닐린계 유도체 본 발명은 하기 특정한 신규 화학식 (I)의 화합물, 이러한 화합물의 제조 방법, 핵 호르몬 수용체인 간 X 수용체(LXR) α(NR1H3) 및/또는 β(NR1H2)의 조절시에, 그리고 죽상경화증과 같은 심혈관 질환, 염증 질환, 알츠하이머병, 인슐린 저항성과 관련되거나 관련이 없는 지질 이상(이상지혈증), 2형 당뇨병 및 대사 증후군의 기타 징후를 포함한 임상적 증상의 치료 및/또는 예방시에 상기 화합물의 용도, 치료에 상기 화합물을 이용하는 방법, 및 상기 화합물을 함유하는 약학 조성물에 관한 것이다.  (I) 하기 화학식(I)의 화합물, 또는 이것의 약학적으로 허용가능한 염: [이미지] (I) 상기 식 중, R1은 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRaC(O)Rb, C(O)ORa, OC(O)Rb, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa, NRaC(O)NRaRa, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환되는 X를 나타내거나; 또는 R1은 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRaC(O)Rb, C(O)ORa, OC(O)Rb, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa, NRaC(O)NRaRa, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRaC(O)Rb, C(O)ORa, OC(O)Rb, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 각각 치환되는 시클로알킬 또는 헤테로시클릴이거나; 또는 R1은 할로겐 (Cl, F, I, Br), OH, CN, NO2, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRaC(O)Rb, C(O)ORa, OC(O)Rb, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa, OSO2Rb, NRaC(O)NRaRa, SO2NHC(O)Rb, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRaC(O)Rb, C(O)ORa, OC(O)Rb, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 각각 치환되는 페닐 또는 헤테로아릴이거나; 또는 R1은 시클로알킬 또는 헤테로시클릴이 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRaC(O)Rb, C(O)ORa, OC(O)Rb, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa, NRaC(O)NRaRa, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRaC(O)Rb, C(O)ORa, OC(O)Rb, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 각각 치환되는 시클로알킬Y 또는 헤테로시클릴Y이거나; 또는 R1은 페닐 또는 헤테로아릴이 할로겐 (Cl, F, I, Br), OH, CN, NO2, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRaC(O)Rb, C(O)ORa, OC(O)Rb, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa, OSO2Rb, NRaC(O)NRaRa, SO2NHC(O)Rb, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRcC(O)Rb, C(O)ORa, OC(O)Rb, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 각각 치환되는 페닐Y 또는 헤테로아릴Y이고; R2는 할로겐 (Cl, F, I, Br), OH, CN, NO2, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRaC(O)Rb, C(O)ORa, OC(O)Rb, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa, OSO2Rb, NRaC(O)NRaRa, SO2NHC(O)Rb, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, C(O)NRaRa, NRaC(O)Rb, C(O)ORa, OC(O)Rb, NRaSO2Rb, SO2NRaRa, NRaC(O)ORb, OC(O)NRaRa 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환되는 페닐을 나타내며; R3은 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, NRaC(O)Rb, C(O)NRaRa, OC(O)Rb, C(O)ORa, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa, NRaC(O)NRaRa, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환되는 X를 나타내거나; 또는 R3은 M 및 Het3이 비방향족 고리 상에서 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, NRaC(O)Rb, C(O)NRaRa, OC(O)Rb, C(O)ORa, SO2NRaRa, NRaSO2Rb, OC(O)NRaRa, NRaC(O)ORb, NRaC(O)NRaRa, Q, QT, Het1, Het1T, R, RT, Het2, Het2T, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, NRaC(O)Rb, C(O)NRaRa, OC(O)Rb, C(O)ORa, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 각각 치환되며, 그리고 M 또는 Het3이 방향족 고리 상에서 할로겐 (Cl, F, Br, I), OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, NRaC(O)Rb, C(O)NRaRa, OC(O)Rb, C(O)ORa, SO2NRaRa, NRaSO2Rb, OC(O)NRaRa, NRaC(O)ORb, NRaC(O)NRaRa, OSO2Rb, SO2NRaC(O)Rb, Q, QT, Het1, Het1T, R, RT, Het2, Het2T, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, NRaC(O)Rb, C(O)NRaRa, OC(O)Rb, C(O)ORa, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 선택되는 것들 중 하나 이상에 의해 임의로 각각 치환되는 MP 또는 Het3P이거나; 또는 R3은 A 및 Het5가 할로겐 (F, Cl, Br, I), OH, CN, NO2, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, NRaC(O)Rb, C(O)NRaRa, OC(O)Rb, C(O)ORa, SO2NRaRa, NRaSO2Rb, OC(O)NRaRa, NRaC(O)ORb, OSO2Rb, SO2NRaC(O)Rb, NRaC(O)NRaRa, Q, QT, Het1, Het1T, R, RT, Het2, Het2T, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, NRaC(O)Rb, C(O)NRaRa, OC(O)Rb, C(O)ORa, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 각각 치환되는 AP 또는 Het5P이거나; 또는 R3은 비방향족 고리 상에서 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, NRaC(O)Rb, C(O)NRaRa, OC(O)Rb, C(O)ORa, SO2NRaRa, NRaSO2Rb, OC(O)NRaRa, NRaC(O)ORb, NRaC(O)NRaRa, Q, QZ, Het1, Het1Z, R, RZ, Het2, Het2Z, 또는 F, OH, CN, NRaRa, ORb, SRb, SiRbRbRb, S(O)Rb, SO2Rb, C(O)Rb, NRaC(O)Rb, C(O)NRaRa, OC(O)Rb, C(O)ORa, SO2NRaRa, NRaSO2Rb, NRaC(O)ORb, OC(O)NRaRa 또는 NRaC(O)NRaRa로부터 독립적으로 선택되는 것들 중 하나 이상에 의해 임의로 치환된 C1-C4알킬로부터 독립적으로 선택...