WO2006003923A1 - Composé du benzène substitué - Google Patents

Composé du benzène substitué Download PDF

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Publication number
WO2006003923A1
WO2006003923A1 PCT/JP2005/011928 JP2005011928W WO2006003923A1 WO 2006003923 A1 WO2006003923 A1 WO 2006003923A1 JP 2005011928 W JP2005011928 W JP 2005011928W WO 2006003923 A1 WO2006003923 A1 WO 2006003923A1
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Prior art keywords
group
alkyl
substituent
substituted
methyl
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PCT/JP2005/011928
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English (en)
Japanese (ja)
Inventor
Takahiro Yamaguchi
Masayuki Yoshida
Kazuhiko Tamaki
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Sankyo Company, Limited
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Publication of WO2006003923A1 publication Critical patent/WO2006003923A1/fr

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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
    • C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/24—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/25—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/24—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/26—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a saturated carbon skeleton containing rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/24—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
    • C07C233/27—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a carbon atom of an acyclic unsaturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C233/60—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/16—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C235/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/19—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and carboxyl groups, other than cyano groups, bound to the same saturated acyclic carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C275/32—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms
    • C07C275/34—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by singly-bound oxygen atoms having nitrogen atoms of urea groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
    • C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
    • C07C311/09—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton the carbon skeleton being further substituted by at least two halogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
    • C07C317/46—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/56—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring

Definitions

  • a direct risk factor for cardiovascular disease is arteriosclerosis with thickening of the arterial wall, which is caused by accumulation of acid-low density lipoprotein cholesterol (LDL-C) in the arterial wall.
  • LDL-C acid-low density lipoprotein cholesterol
  • LXR undergoes transcriptional regulation of oxidized sterols in the macrophage of the vascular wall, induces expression of ABCA1 (ATP Binding Cassette Transpoter-1) and ApoE (Apolipoprotein E), and a cholesterol arch from the vascular wall. I promotes the excision and reverse cholesterol transport to the liver (Lu, T. T "Repa, JJ, Mangelsdorf, D. J" J. Biol.
  • the present invention relates to a disease caused by administering a pharmacologically effective amount of a substituted benzene compound or a pharmacologically acceptable salt or ester thereof to a warm-blooded animal (particularly a human), preferably the above-mentioned
  • a method for treating or preventing a disease is provided.
  • Substituent Group a 1 to 3 groups selected from Substituent Group a), 5- to 10-membered aromatic heterocyclyl group, or substituted 5- to 10-membered aromatic heterocyclyl group (the substituents may be the same or different) And 1 to 3 groups selected from the substituent group ⁇ );
  • Chloalkyl (c-C alkyl) amino group, C-C cycloalkylamino group, C-C
  • R 12 represents a hydrogen atom, a C-C alkyl group, a substituted C-C alkyl group (the substituent is the same as
  • the substituents are the same or different and are 1 to 3 groups selected from the substituent group) 8), a furo (CC alkyl) group, a substituted furo (CC alkyl) group (the substituent
  • X 2 represents a C—C anoalkylene group
  • Z represents a group having the formula —CO—, —CS— or so. Indicates a group having
  • X 1 represents a single bond, a methylene group, or a substituted methylene group (the substituents are the same or different 1 to 2 C—C alkyl groups, and the two substituents are
  • trimethylene group may be formed.
  • Y is a phenyl group, a substituted phenyl group (the substituents are the same or different and are 1 to 3 groups selected from the substituent group ⁇ ), a 5- to 6-membered aromatic heterocyclyl group, or a substituted group.
  • a 5- to 6-membered aromatic heterocyclyl group (the substituents are the same or different and are 1 to 3 groups selected from the substituent group oc);
  • Substituent group ⁇ is a CC alkyl group, a halogeno CC alkyl group (the halogeno C
  • 1 4 1 4 1 C alkyl group represents a C C alkyl group substituted with 1 to 5 halogeno groups
  • the C—C alkoxy group is a C—C alkoxy group substituted with 1 to 5 halogeno groups.
  • Group may be the same or different), formyl group, (C C alkyl) carbonyl group, and
  • Substituent group j8 is a C C alkyl group, a halogeno C C alkyl group (the halogeno C
  • 1 4 1 4 1 C alkyl group represents a C C alkyl group substituted with 1 to 5 halogeno groups
  • the C—C alkoxy group is a C—C alkoxy group substituted with 1 to 5 halogeno groups.
  • Substituent group 0 includes a c C alkyl group, a halogeno C C alkyl group (the halogeno C
  • 1 4 1 4 1 C alkyl group represents a C C alkyl group substituted with 1 to 5 halogeno groups
  • the C—C alkoxy group is a C—C alkoxy group substituted with 1 to 5 halogeno groups.
  • Alkyl groups may be the same or different), carboxyl groups, (C C alkoxy) carbols
  • a group consisting of a group, a cyano group and a halogeno group is shown.
  • the present invention also relates to a pharmaceutical composition
  • a pharmaceutical composition comprising an effective amount of a pharmacological activity of the compound represented by the above general formula (I) or a pharmacologically acceptable salt or ester thereof, and a carrier or diluent.
  • the present invention provides the above-mentioned pharmaceutical composition for treatment or prevention in a warm-blooded animal, and the warm-blooded animal is a human disease that can be treated or prevented by regulating LXR function in the warm-blooded animal. It can be.
  • the pharmaceutical composition is for treatment or prevention in a warm-blooded animal, and the warm-blooded animal is atherosclerosis; atherosclerosis; arteriosclerosis caused by diabetes; hyperlipidemia ; High cholesterol Dysemia; lipid-related diseases; inflammatory diseases that are caused by bowel I by inflammatory site force-in; autoimmune diseases; cardiovascular diseases; cerebrovascular diseases; kidney diseases; diabetes; diabetes complications; Obesity; nephritis; hepatitis; cancer; and human being a disease selected from the group consisting of Alzheimer's disease.
  • the pharmaceutical composition is for treatment or prevention in a warm-blooded animal, and the warm-blooded animal is arteriosclerosis; atherosclerosis; arteriosclerosis caused by diabetes; hyperlipidemia Hypercholesterolemia; lipid-related diseases; inflammatory diseases that are caused by inflammatory cytokines; and humans that are diseases selected from the group of diabetics.
  • the pharmaceutical composition is for treatment or prevention in a warm-blooded animal, and the warm-blooded animal can be a human who has arteriosclerosis.
  • the present invention also provides a compound represented by the above general formula (I) or a pharmacologically acceptable salt or ester thereof for use as a medicament.
  • the present invention also relates to the use of one or more compounds represented by the above general formula (I) or a pharmacologically acceptable salt or ester thereof in the manufacture of a medicament for treatment or prevention in warm-blooded animals.
  • the warm-blooded animal can be a human being a disease that can be treated or prevented by modulation of LXR function in the warm-blooded animal.
  • the disease that can be treated or prevented by modulation of LXR function in warm-blooded animals is arteriosclerosis; atherosclerosis; arteriosclerosis caused by diabetes; hyperlipidemia; Lipid-related disease; inflammatory disease caused by inflammatory site force-in; autoimmune disease; cardiovascular disease; cerebrovascular disease; kidney disease; diabetes; diabetes complications; obesity; Cancer; and Alzheimer's disease group. More preferably, the disease is arteriosclerosis; atherosclerosis; arteriosclerosis caused by diabetes; hyperlipidemia; Lipid-related disease; inflammatory disease caused by inflammatory site force-in; autoimmune disease; cardiovascular disease; cerebrovascular disease; kidney disease; diabetes; diabetes complications; obesity; Cancer; and Alzheimer's disease group. More preferably, the disease is arteriosclerosis; atherosclerosis; arteriosclerosis caused by diabetes; hyperlipidemia; Lipid-related disease; inflammatory disease caused by inflammatory site force-in; autoimmune disease; cardiovascular disease; cerebrovascular disease; kidney disease; diabetes; diabetes complications; obesity; Cancer; and Alzheimer's disease group. More preferably
  • Arteriosclerosis atherosclerosis; arteriosclerosis caused by diabetes; hyperlipidemia; hypercholesterolemia; lipid-related disease; inflammatory disease that is caused by inflammatory site force-in; Selected from the group of diabetic power. Most preferably, the disease is arteriosclerosis.
  • the present invention also relates to a treatment or treatment for a warm-blooded animal by administering to the warm-blooded animal an effective amount of the compound represented by the above general formula (I) or a pharmacologically acceptable salt or ester thereof.
  • a preventive method and the warm-blooded animal is controlled by modulation of LXR function in the warm-blooded animal. It can be a human who is a disease that can be treated or prevented.
  • the disease that can be treated or prevented by modulation of LXR function in warm-blooded animals is arteriosclerosis; atherosclerosis; arteriosclerosis caused by diabetes; hyperlipidemia; Lipid-related diseases; inflammatory diseases caused by inflammatory site force-in; autoimmune diseases; cardiovascular diseases; cerebrovascular diseases; kidney diseases; diabetes; diabetes complications; obesity; Cancer; and Alzheimer's disease group. More preferably, the disease is arteriosclerosis; atherosclerosis; arteriosclerosis caused by diabetes; hyperlipidemia; Lipid-related diseases; inflammatory diseases caused by inflammatory site force-in; autoimmune diseases; cardiovascular diseases; cerebrovascular diseases; kidney diseases; diabetes; diabetes complications; obesity; Cancer; and Alzheimer's disease group. More preferably, the disease is arteriosclerosis; atherosclerosis; arteriosclerosis caused by diabetes; hyperlipidemia; Lipid-related diseases; inflammatory diseases caused by inflammatory site force-in; autoimmune diseases; cardiovascular diseases; cerebrovascular diseases; kidney diseases; diabetes; diabetes complications; obesity; Cancer; and Alzheimer's disease group. More preferably
  • Arteriosclerosis atherosclerosis; arteriosclerosis caused by diabetes; hyperlipidemia; hypercholesterolemia; lipid-related disease; inflammatory disease that is caused by inflammatory site force-in; Selected from the group of diabetic power. Most preferably, the disease is arteriosclerosis.
  • the present invention also provides a compound represented by the above general formula (I) or a pharmacologically acceptable salt or ester thereof; an HMG-CoA reductase inhibitor, an HMG-CoA synthase inhibitor, a plasma HDL-elevating agent.
  • CETP inhibitors Cholesterol biosynthesis inhibitors, squalene epoxidase inhibitors, squalene synthetase inhibitors, hypercholesterolemia treatments, acylchoenzyme A, cholesteryl ester transfer protein inhibitors (hereinafter referred to as CETP inhibitors), ACAT inhibitor, probucol, cholesterol absorption inhibitor, bile acid-adsorbing ion exchange resin, fibrates, nicotinic acid derivatives, niacinamide, LDL receptor inducer, vitamin B
  • Vitamin B Anti-acid vitamin, Angiotensin II inhibitor, Angiotensin converting enzyme
  • a pharmaceutical composition comprising an inhibitor, a beta blocker, a fibrinogen inhibitor, an aspirin, a diuretic, and a drug selected from the group consisting of combinations thereof; and a carrier or diluent.
  • R 9a is a C—C alkyl group, a C—C alkoxy group, (C
  • the halogeno C 1 -C alkoxy group is a C 1 -C alkyl substituted with 1 to 7 halogeno groups.
  • 1 6 1 6 represents a alkoxy group), c-c cycloalkyloxy group, (C—C alkyl) (c-c
  • alkyl groups are the same or different, and the two alkyl groups together with the nitrogen atom of the amino group are selected from 1 to 3 atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom.
  • Substituent group ⁇ 1 is methyl group, ethyl group, trifluoromethyl group, 2,2,2-trifluoroethyl group, pentafluoroethyl group, hydroxyl group, methoxy group, ethoxy group, trifluoromethoxy group, amino group
  • the compound described in (1) which represents a group consisting of a group, a methylamino group, an ethylamino group, a dimethylamino group, a jetylamino group, a formyl group, an acetyl group, a fluoro group, a black group, and a bromo group,
  • (3) is a compound of the formula 1 COR % [wherein R 9b represents a C—C alkoxy group or a halogeno C—C
  • ⁇ represents a C C alkoxy group).
  • a phenyl group or a substituted phenol group (the substituents are the same or different and are 1 to 3 groups selected from the substituent group a 2);
  • the substituent group a2 is described in (1), which represents a group consisting of a methyl group, an ethyl group, a trifluoromethyl group, a methoxy group, an ethoxy group, a trifluoromethoxy group, a fluoro group, and a black mouth group.
  • (4) is a group having the formula — COR 9e (wherein R 9e represents a C—C alkoxy group).
  • R 2 is a hydrogen atom, a trifluoromethyl group, a 2,2,2 trifluoroethyl group, a pentafluoroethyl group, a hydroxyl group, a fluoro group, or a black mouth group (1) to (5 )
  • R 3 is a CC alkyl group, a halogeno CC alkyl group (the halogeno CC
  • 1 4 1 4 1 4 alkyl group represents a C 1 C alkyl group substituted with 1 to 5 halogeno groups), (C
  • alkyl groups may be the same or different and
  • (1) to (8) which may be a fluoro group, a black mouth group, or a bromo group! , Any of the compounds listed in the
  • 1 4 1 4 1 4 alkyl group represents a C C alkyl group substituted with 1 to 5 halogeno groups
  • R 8 has the formula — N (R 1Qa ) ZR lla , — ZN (R 1Qa ) R 12a , — ZR 12a , — X 2 N (R 1Qa ) ZR lla , — X 2a ZN (R 1Qa ) R 12a or X 2a ZR 12a
  • R 1Qb represents a C—C alkyl group, a methoxymethyl group, a 2,2,2-trifluoroethyl group,
  • R 8 is the formula — N (R 1 ⁇ k ) ZR lle
  • Substituent group 03 is a methoxy group, a methylthio group, a methylamino group, or a dimethylamino group, and the compound according to any one of (1) to (15),
  • R 1M represents a methyl group or an ethyl group
  • Y is a phenyl group, a substituted phenyl group (the substituents are the same or different and are one or two groups selected from the substituent group ⁇ 1), a pyridyl group, or a substituted pyridyl group ( The substituents are the same or different, and are 1 to 2 groups selected from the substituent group ⁇ 1).
  • (23) ⁇ is a phenyl group, a substituted phenyl group (the substituent is one group selected from the substituent group ⁇ 3), or a pyridyl group,
  • Substituent group a 3 is a methoxy group, a methylamino group, a dimethylamino group, a fluoro group, and a compound as described in any one of (1) to (21),
  • R 2 which is selected from (9) to (11) forces the selected R 3, (12) to (13) forces the selected R 4 and R 5, (14 ) Through (15) force selected R 6 and R 7 , (16) through (19) force selected R 8 , (20) through (21) force selected X 1 , and (22) through ( 24) Strength
  • a compound obtained by arbitrarily combining selected Y or a pharmacologically acceptable salt or ester thereof is more preferable.
  • Such more preferred compounds are, for example,
  • R 1 is a formula —COR 9a [wherein R 9a is a C 1 -C alkyl group, a C—C alkoxy group, (
  • the halogeno C C alkoxy group is a C C alkyl substituted with 1 to 7 halogeno groups.
  • 1 6 1 6 represents a alkoxy group), c-c cycloalkyloxy group, (C—C alkyl)
  • the alkyl group is the same or different, and the two alkyl groups are selected from the group consisting of the nitrogen atom of the amino group, the nitrogen atom, the oxygen atom, and the sulfur atom).
  • a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms may be formed).
  • R 3 is a C—C alkyl group, a halogeno C—C alkyl group (the halogeno C—C alkyl group).
  • 1 4 1 4 1 4 group represents a C C alkyl group substituted with 1 to 5 halogeno groups), (C C
  • Chloalkyl (C—C alkyl) group, C—C cycloalkyl group, C—C alkell
  • 1 4 1 4 1 4 alkyl amino group (the alkyl group is the same or different, and the two alkyl groups together with the nitrogen atom of the amino group are composed of a nitrogen atom, an oxygen atom and a sulfur atom)
  • R 6 and R 7 are the same or different and are a hydrogen atom or a methyl group
  • R 8 has the formula N (R 1Qa ) ZR lla , 1 ZN (R 1Qa ) R 12a , 1 ZR 12a , 1 X 2 N (R 1Qa ) ZR lla , 1 X 2 3 ⁇ 4N (R 1Qa ) R 12a , or X 2a ZR 12a
  • R 1Qa represents a hydrogen atom, a CC alkyl group, a substituted CC alkyl group (the substituent
  • R is a hydrogen atom, a C 1 -C alkyl group, a substituted C 1 -C alkyl group (the substituent is
  • a substituted (5- to 7-membered heterocyclyl) (C—C alkyl) group substituted (5- to 7-membered heterocyclyl) (C—C alkyl) group (substituent of the heterocyclyl group)
  • R Ua is nag a hydrogen atom
  • R 12a is a hydrogen atom, a C—C alkyl group, a substituted C—C alkyl group (the substituent is
  • Group j8 is 1 to 2 groups selected from 1), a phenyl group, or a 5- to 7-membered heterocyclyl group, provided that in formulas —ZR 12a and —X 2a ZR 12a , Z is — When SO—
  • R 12a is not a hydrogen atom
  • X 2a represents a methylene group.
  • X 1 is a single bond or a methylene group
  • Y is a phenyl group, a substituted phenyl group (the substituents are the same or different and are one or two groups selected from the substituent group ⁇ 1), a pyridyl group, or a substituted pyridyl group (the substituent The groups are the same or different and are 1 to 2 groups selected from the substituent group ⁇ 1),
  • (26) is a compound of the formula 1 COR % [wherein R 9b is a C—C alkoxy group or a halogeno C—C
  • a phenyl group or a substituted phenol group (the substituents are the same or different and are 1 to 3 groups selected from the substituent group a 2);
  • R 2 is a hydrogen atom or a hydroxyl group
  • R 3 is a C—C alkyl group, a halogeno C—C alkyl group (the halogeno C—C alkyl group).
  • 1 4 1 4 1 4 group represents a C C alkyl group substituted with 1 to 5 halogeno groups), C C
  • Chloalkyl group C C alkell group, C C alkoxy group, fluoro group, or
  • R 4 and R 5 are hydrogen atoms
  • R 6 and R 7 are hydrogen atoms
  • R 8 is the formula — N (R 1 ⁇ ) b ) ZR llb or —ZN (R 1Qb ) R 12b
  • R 1Qb represents a C—C alkyl group, a methoxymethyl group, a 2,2,2-trifluoroethyl group,
  • R llb is a C—C alkyl group, a substituted C—C alkyl group (the substituent is a substituent group ⁇
  • R 12b is a C—C alkyl group, a substituted C—C alkyl group (the substituent is a substituent group j8
  • X 1 is a single bond
  • Y is a phenyl group, a substituted phenyl group (the substituent is one group selected from substituent group a 3), or a pyridyl group;
  • R 1 is a group having the formula — COR 9e (wherein R 9e represents a C—C alkoxy group)
  • R 2 is a hydrogen atom or a hydroxyl group
  • R 3 is a methyl group, an ethyl group, a 2-propyl group, a 2-methyl-2-propyl group, a trifluoromethyl group, a 2,2,2-trifluoroethyl group, a cyclopropyl group, or a bur group.
  • R 4 and R 5 are hydrogen atoms
  • R 6 and R 7 are hydrogen atoms
  • R 8 is the formula — N (R 1 ⁇ k ) ZR llc
  • R lfc represents a methyl group, an ethyl group, a 1-propyl group, or a 2-propyl group
  • R lle represents a C-C alkyl group, a substituted C-C alkyl group (the substituent is Substituent group ⁇
  • X 1 is a single bond
  • R 1 has the formula — COR 9d (wherein R 9d represents a 2-methyl-2 propoxy group). Is a group that
  • R 2 is a hydroxyl group
  • R 3 is a methyl group, an ethyl group, a 2-propyl group, a 2-methyl-2-propyl group, a trifluoromethyl group, a 2,2,2-trifluoroethyl group, a cyclopropyl group, or a bur group.
  • R 4 and R 5 are hydrogen atoms
  • R 6 and R 7 are hydrogen atoms
  • R 8 is the formula — N (R 1 ⁇ ) d ) COR lld , -N (R 10d ) CSR Ud , or N (R 1M ) SO R Ud
  • R 1M represents a methyl group or an ethyl group
  • R Ud represents a methyl group, an ethyl group, a 2-propyl group, a methoxymethyl group, a methylthiomethyl group, a cyclopropylmethyl group, or a cyclopropyl group.
  • (30) is the formula — COR 9b [wherein R 9b is a C—C alkoxy group or a halogeno C—C
  • R 3 is a C—C alkyl group, a halogeno C—C alkyl group (the halogeno C—C alkyl group).
  • 1 4 1 4 1 4 group represents a CC alkyl group substituted with 1 to 5 halogeno groups), CC A chloroalkyl group, a CC alkenyl group, a CC alkoxy group, a fluoro group, or a
  • R 4 and R 5 are hydrogen atoms
  • R 6 and R 7 are hydrogen atoms
  • R 8 is the formula — N (R 1 ⁇ k ) ZR llc
  • R lfc represents a methyl group, an ethyl group, a 1-propyl group, or a 2-propyl group
  • R lle represents a C-C alkyl group, a substituted C-C alkyl group (the substituent is Substituent group ⁇
  • X 1 is a single bond
  • ⁇ is a phenyl group, a substituted phenyl group (the substituent is one group selected from the substituent group a3), or a pyridyl group.
  • the present invention also provides:
  • a pharmaceutical composition comprising the compound according to any one of (1) to (30) or a pharmacologically acceptable salt or ester thereof as an active ingredient,
  • the pharmaceutical composition is a disease caused by arteriosclerosis, atherosclerosis, arteriosclerosis caused by diabetes, hyperlipidemia, hypercholesterolemia, lipid-related disease, inflammatory site force in A disease selected from the group consisting of an inflammatory disease, autoimmune disease, cardiovascular disease, cerebrovascular disease, kidney disease, diabetes, diabetic complications, obesity, nephritis, hepatitis, cancer, and Alzheimer's disease
  • a disease selected from the group consisting of an inflammatory disease, autoimmune disease, cardiovascular disease, cerebrovascular disease, kidney disease, diabetes, diabetic complications, obesity, nephritis, hepatitis, cancer, and Alzheimer's disease
  • the pharmaceutical composition according to (31) which is a pharmaceutical composition for the treatment or prevention of
  • composition in which the pharmaceutical composition is caused by arteriosclerosis, atherosclerosis, diabetes, arteriosclerosis, hyperlipidemia, hypercholesterolemia, lipid-related disease, inflammatory site force in
  • the pharmaceutical composition described in (31) which is a pharmaceutical composition for the treatment or prevention of a certain inflammatory disease and a disease selected from the group consisting of diabetes, or
  • a pharmaceutical composition for treating or preventing a disease selected from the group consisting of arteriosclerosis, atherosclerosis and arteriosclerosis caused by diabetes The pharmaceutical composition described in (31) is also provided.
  • the present invention provides:
  • the “C 1 -C 4 alkyl group” in R 9 of general formula (I) has 1 to 10 carbon atoms
  • 2-propyl group 1-butyl group, 2-butyl group, 2-methyl-1-propyl group, 2-methyl-2-propyl group, 1-pentyl group, 2-pentyl group, 3-pentyl group, 2-methyl-2-butyl group, 3-methyl- 2-butyl group, 1,1-dimethyl-1-propyl group, 1-hexyl group, 2-hexyl group, 3-hexyl group, 2-methyl-1-pentyl group, 3-methyl-3-pentyl group, 2-ethyl-1-butyl group, 2, 3 Dimethyl-1-butyl group,
  • the "C—C alkoxy group" in R 9 of the general formula (I) is the above CC alkyl group. Substituted hydroxyl groups such as methoxy, ethoxy, 1-propoxy, 2 propoxy,] _ butoxy, 2-butoxy, 2-methyl-1 propoxy, 2-methyl-2 propoxy, 1 Pentyloxy group, 2 pentyloxy group, 3 pentyloxy group, 2-methyl-2-butoxy group, 3-methyl-2-butoxy group, 2 methyl-2 butoxy group, 1-hexyloxy group, 2 hexyloxy group, 3 hexoxy group, 2 —Methyl-1 pentyloxy group, 3-methyl-3 pentyloxy group, 2-ethyl-1-butoxy group, 2, 3 dimethyl-1 butoxy group, 1-heptyloxy group, 3 1-heptyloxy group, 4-1-heptyloxy group, 3-methyl-3 —Hexyloxy, 3-ethyl-3-pentyloxy, 3-oc
  • Methyl 2-propoxy group or 2-methyl 2-butoxy group and most preferably 2-methylol-2-propoxy group.
  • a cyclic alkyl group having, for example, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group, and preferably a c-c cycloalkyl group
  • Group more preferably a C—C cycloalkyl group, most preferably cyclopropyl.
  • c-c alkyl group as well as the c-c alkyl moiety in each substituent, are 1 to
  • Linear or branched alkyl groups having 4 carbon atoms such as methyl, ethyl, 1 propyl, 2-propyl, 1-butyl, 2-butyl, 2-methyl-1 propyl Or a 2-methyl-2-propyl group, preferably a C—C group.
  • R 2 , R 4 , R 5 substituent group a, substituent group ⁇ , and “c-c alkoxy group” in substituent group y, and c in each substituent group -c alkoxy moiety or C
  • the “C—C alkoxy group” in the substituent group a, the substituent group ⁇ , and the substituent group y is preferably
  • ⁇ Xoxy group '' means the above c-c alkoxy substituted with one c-c cycloalkyl group
  • 3 6 1 4 groups for example, cyclopropylmethoxy group, cyclobutylmethoxy group, cyclopentylmethoxy group, cyclohexylmethoxy group, 1-cyclopropylethoxy group, 2-cyclopropylethoxy group, 1-cyclobutylethoxy group, 2-cyclobutylethoxy group, 1-cyclopentylethoxy group, 2-cyclopentylethoxy group, 1-cyclohexylethoxy group, 2-cyclohexylethoxy group, 1-cyclopropyl 1 propoxy group, 2-cyclopropyl 1 propoxy group, 3- Cyclopropyl 1 propoxy group, 1-cyclopropyl 2-propoxy group, 2-cyclopropyl 2-propoxy group, 1-cyclobutyl-1 propoxy group, 3 cyclobutyl-1 propoxy group, 3 cyclopentyl 1-propoxy group, 3 cyclohexyl group 1 Propoxy group, 1- Chlopropyl 1-butoxy group, 4-cycloprop
  • —C cycloalkyl) — (C—C alkyl) oxy group is preferably (C—C cycloalkyl) Alkyl) (c C alkyl) oxy group, more preferably (CC cycloalkyl).
  • a halogeno C 1 -C alkoxy group is a C 1 -C alcohol substituted with 1 to 5 halogeno groups.
  • the -C alkoxy group is a C 1 -C alkoxy group substituted with 1 to 5 halogeno groups.
  • it is a 1,1,1-trifluoro-2-propoxy group or a 2-trifluoromethyl 2-propoxy group.
  • “Ferru (C—C alkoxy) group” in R 9 of the general formula (I) means one phenol group.
  • it is a 1-phenyl 1-ethyl group or a 2-phenyl 2-propyl group.
  • C—C cycloalkyloxy group in R 9 and R 11 of the general formula (I) represents one of the above
  • a hydroxyl group substituted by a C-C cycloalkyl group for example cyclopropyl
  • Preferred is a C C cycloalkyloxy group, and most preferred is a cyclopropyloxy group.
  • the "C-C alkylamino group" in R 9 of the general formula (I) represents one CC alkyl group.
  • 1 10 is an amino group substituted with a group such as methylamino group, ethylamino group, 1-propoxy group, 2-propoxy group, 1-butoxy group, 2-butoxy group, 2-methyl-1- Propyl amino group, 2-methyl-2-propylamino group, 1 pentylamino group, 2-pentylamino group, 3 pentylamino group, 2-methyl-2-butylamino group, 3-methyl-2-butyl Ruamino group, 2-methyl-2-butylamino group, 1-hexylamino group, 2-hexylamino group, 3-hexylamino group, 2-methyl-1-pentylamino group, 3-methyl-3-pentylamino group, 2-ethyl-1-butylamino group, 2,3 Dimethyl-1-butylamino group, 1 Heptylamino group, 3 Heptylamino group, 4 Heptylamino group, 3-Methyl-3 Monohexylamino group, 1
  • C—C alkylamino group and even more preferably, C—C alkylamino group (especially
  • 2-propylamino group 2-methyl-2-propylamino group or 2-methyl-2-butylamino group
  • 2-methyl-2-propylamino group 2-methyl-2-butylamino group
  • 2-methyl-2-propylamino group 2-methyl-2-butylamino group
  • Tylethylamino group methylpropylamino group [for example, N- (1-propyl) -N-methylamino group, etc.], methylptylamino group [for example, N- (l-butyl) N-methylamino group, N-methyl-N — (2-Methyl-2-propyl) amino group, etc.], N-methyl-N— (2-methyl-2-butyl) amino group, N-methyl-N— (3-methyl-3-pentyl) amino group, N-methyl N- ( 3-Ethyl 3-pentyl) amino group, N-methyl N- (3-Ethyl 3-hexyl) amino group, N-Methyl-N- (4-Ethyl-4 monoheptyl) amino group, N-Methyl-N— [4 1- (1 propyl) -4 1-heptyl] amino group, jetylamino group, ethylpropylamino group [eg, N- (1-propy
  • N-methyl N— (2-methyl-2-propyl) amino group N-ethyl N— (2-methyl 2-propyl) amino group, N— (1-propyl) N— (2-methyl 2— Propyl) amino group, N- (1-butyl) -N- (2-methyl-2-propyl) amino group or di (2-methyl-2-propyl) amino group.
  • di (C—C alkyl) amino groups there are two “di (C—C alkyl) amino groups”.
  • This 5- to 7-membered saturated heterocyclyl group which may form , A pyrrolidyl group, a piperidyl group, a piperazyl group, a morpholinyl group, a thiomorpholinyl group, or a perhydroazepill group, and preferably selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom 1
  • the “CC aryl group” in R 1 of the general formula (I) has 6 to 10 carbon atoms.
  • An aromatic hydrocarbon group which may be, for example, a phenyl group or a naphthyl group, and is preferably a phenol group.
  • the "5- to 10-membered aromatic heterocyclyl group" in R 1 of the general formula (I) contains 1 to 4 atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur nuclear power 5
  • 10-membered aromatic heterocyclic group such as furyl group, chael group, pyrrolyl group, pyrazolyl group, imidazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, 1,2,3-oxadiazolyl group 1,2,3 thiadiazolyl group, triazolyl group, tetrazolyl group, viral group, pyridyl group, pyridazyl group, pyrimidyl group, pyrazyl group, azepyr group, azosyl group, azo-- Group, indolyl group, benzofural group, benzochel group, benzimidazolyl group, benzo
  • R 2 , R 4 , R 5 , the substituent group a, the substituent group ⁇ , and the “halogeno CC alkyl group” in the substituent group y are 1 to 5 of the following halogeno C substituted with a group
  • C alkyl group for example, fluoromethyl group, difluoromethyl group, dichloromethyl
  • a halogeno CC alkyl group (the halogeno CC alkyl group has 1 to 5
  • 1 4 1 4 is an amino group substituted by a group such as methylamino group, ethylamino group, propylamino group (eg 1-propylamino group, 2-propylamino group), 1-butylamino group, 2-butylamino group, It can be a 2-methyl-1-propylamino group or a 2-methyl-2-propylamino group, preferably a C 1 -C alkylamino group, more preferably methyl
  • Group is an amino group substituted with the same or different two C C alkyl groups.
  • dimethylamino group methylethylamino group, methylpropylamino group
  • a dimethylamino group More preferably, a dimethylamino group, a methylethylamino group, a methylpropylamino group, a jetylamino group, an ethylpropylamino group, or a dipropylamino group, and more preferably A dimethylamino group or a jetylamino group, and most preferably a dimethylamino group.
  • R 2 , R 3 , R 4 , R 5 , the substituent group a, the substituent group ⁇ , and the “norogeno group” in the substituent group y are a fluoro group, A chloro group, a bromo group, or a iodine group, preferably a fluor group, a chloro group, or a bromo group, more preferably a fluor group or a chloro group, and most preferably , A fluoro group.
  • the “C—C alkyl group” in R 3 , R 11 and R 12 in the general formula (I) is 1 to 6 carbon atoms.
  • Straight or branched alkyl group having an atom for example, methyl group, ethyl group, 1-propyl group, 2-propyl group, 1-butyl group, 2-butyl group, 2-methyl-1 propyl group, 2- Methyl-2-propyl group, 1-pentyl group, 2-pentyl group, 3-pentyl group, 2-methyl-2-butyl group, 3-methyl-2-butyl group, 1-hexyl group, 2-hexyl group, 3-hexyl group, 2-methyl- 1-pentyl group, 3-methyl-1-pentyl group, 2-ethyl-1-butyl group, 2,2-dimethyl-1-butyl group, or 2,3-dimethyl-1-butyl group, preferably C-C alkyl group And more preferably C
  • -C alkyl group (especially methyl group, ethyl group or propyl group), more preferably
  • the "nologeno CC alkyl group" in R 3 of the general formula (I) is a group having 1 to 7 halogeno atoms.
  • Fluoromethyl group dichloromethyl group, dibromomethyl group, trifluoromethyl group, trichloromethyl group, 2-fluoroethyl group, 2-bromoethyl group, 2-chloroethyl group, 2-chloroethyl group, 2,2-difluoroethyl group, 2,2,2-trifluoroethyl group, trichloroethyl group, pentafluoroethyl group, 3-fluoropropyl group, 3-chloropropyl group, 3,3,3-trifluoropropyl group, 4 fluorobutyl group 4,4,4 trifluorobutyl group, 5 fluoropentyl group, 5,5,5-trifluoropentyl group, 6-fluoro hexyl group, or 6,6,6-trifluoro hexyl group Yes, preferably a halogeno C—C alkyl
  • halogeno C C alkyl group is a C substituted with 1 to 5 halogeno groups
  • a halogeno C C alkyl group (the halogeno).
  • the C-C alkyl group is substituted with 1 to 5 fluoro, black or bromo groups
  • R 3 , R 11 and R 12 represent “(C—C cycloalkyl) — (C—C alkyl”.
  • group '' is a C C alkyl group substituted with one C C cycloalkyl group.
  • it is a (C C cycloalkyl) (C C alkyl) group, more preferably (C C C
  • -C cycloalkyl methyl group, most preferably a cyclopropylmethyl group.
  • a C C alkyl group substituted with a C C alkoxy group for example, methoxy
  • a methoxymethyl group or an ethoxymethyl group is suitable, and a methoxymethyl group is most preferred.
  • C-C alkylthio group in the substituent group y of the general formula (I), and C in R 3
  • C alkylthio moiety is a mercapto group substituted with one of the above C C alkyl groups
  • it may be a methylthio group, an ethylthio group, a 1 propylthio group, a 2-propylthio group, a 1-butylthio group, a 2-butylthio group, or a 2-methyl-2-propylthio group, and preferably a CC alkylthio group And more preferably a methylthio group.
  • thiolthio group and most preferably a methylthio group.
  • the C C alkyl group substituted with the C C alkylthio group for example,
  • the c-c alkyl sulfier moiety is substituted with one of the above c-c alkyl groups.
  • methyl sulfyl group ethyl sulfyl group, 1-propyl sulfiel group, 2-propyl sulfiel group, 1-butyl sulfinyl group, 2-butyl sulfiel group, Or a 2-methyl-2-propylsulfier group, preferably a C-C alkylsulfier group, more preferably methyl
  • a sulfiel group or an ethylsulfyl group, and a methylsulfur group is most preferred.
  • the "(C 1 -C alkylsulfier) (C 1 -C alkyl) group" in R 3 of the general formula (I) is A CC alkyl group substituted by one CC alkylsulfier group
  • Rufyl-methyl group most preferably methylsulfurmethyl group.
  • the c-c alkylsulfol moiety in this is substituted with one of the above c-c alkyl groups.
  • Sulfo group (SO-) for example, methane sulfo group, ethane sulfo group
  • methanesulfolmethyl group ethanesulfolmethyl group, (1 propanesulfol) methyl group, (2-propanesulfol) methyl group, (1 butanesulfol) methyl group, (2-butanesulfol group) ) Methyl group, (2-methyl-2-propanesulfol) methyl group, methanesulfolethyl group, ethanesulfolethyl group, (1-propanesulfol) ethyl group, (2-propanesulfol) ethyl group, (1 butanesulfo) ethyl group, (2 Butanesulfo) ethyl group, (2-methyl-2-propanesulfol) ethyl group, methanesulfol (1-propyl) group, ethanesulfol (1-propyl) group, (1-propanesulfonyl
  • the C C alkyl group substituted with the C C alkylamino group for example,
  • a methylaminomethyl group or an ethylaminomethyl group More preferably a methylaminomethyl group or an ethylaminomethyl group, and most preferably a methylaminomethyl group.
  • 1 4 1 4 group such as a dimethylaminomethyl group, a methylethylaminomethyl group, a methylpropylaminomethyl group [for example, [N (l propyl) -N-methylamino] methyl group, etc.], Methylbutylaminomethyl group [eg, [N- (l-butyl) -N-methylamino] methyl group, etc.], jetylaminomethyl group, ethylpropylaminomethyl group [eg, [N— (1— Propyl) —Nethylamino] methyl group], dipropylaminomethyl group [for example, di (1 propyl) Pyr) aminomethyl group, di (2-propyl) aminomethyl group, etc.], dibutylaminomethyl group [eg, di (1-butyl) aminomethyl group, di (2-butyl) aminomethyl group], di (2 —Methyl-1-propyl) aminomethyl group, di (2-methyl-2-prop
  • a dimethylaminomethyl group or a jetylaminomethyl group More preferably a dimethylaminomethyl group or a jetylaminomethyl group, and most preferably a dimethylaminomethyl group.
  • C—C alkenyl group in R 3 , R 11 and R 12 of the general formula (I) is 1 to 2 carbons.
  • alkenyl group having a carbon double bond and 2 to 6 carbon atoms for example, butyl group, 2-probe group, 2-buture group, 1,3 butadiene 1-yl group, 2-methyl-2-propyl group, 2-pentale group, 2-methyl-2-buture group, Alternatively, it can be a 2-hexyl group, preferably a C-C alkyl group, and more preferably
  • C—C alkell group C—C alkell group, and most preferably a bur group.
  • the "C-C alkyl group" in R 3 of the general formula (I) is a 1 to 2 carbon-carbon triplet.
  • alkynyl group having a bond and 2 to 6 carbon atoms for example, ethynyl group, 1 propyl group, 1-butyl group, 1,3 butadiyne 1-yl group, 1 pentyl group, or 1 may be a hexyl group, preferably a CC alkyl group, more
  • a C—C alkyl group is preferred, and an ethur group is most preferred.
  • C—C alkoxy group in R 3 and R 11 of the general formula (I) represents one C—C
  • alkyl group for example, methoxy group, ethoxy group, 1-propyloxy group, 2-propoxy group, 1-butoxy group, 2-butoxy group, 2-methyl-1 propoxy group Group, 2-methyl-2-propoxy group, 1 pentyloxy group, 2-pentyloxy group, 3 pentyloxy group, 2-methyl-2-butoxy group, 3-methyl-2-butoxy group, 1-hexyloxy group, 2 hexyloxy group, 3 Hexyloxy group, 2-methyl-1-pentyloxy group, 3-methyl-1-pentyloxy group, 2-ethyl-1-butoxy group, 2,2 dimethyl-1 butoxy group, or 2,3 dimethyl-1 butoxy group, preferably Is a C—C alkoxy group, more preferably a C—C alkoxy group
  • a methoxy group In particular, a methoxy group, an ethoxy group, or a propoxy group, more preferably a methoxy group or an ethoxy group, and most preferably a methoxy group.
  • Fluoromethoxy group dichloromethoxy group, dibromomethoxy group, trifluoromethoxy group, trichloromethoxy group, 2-fluoroethoxy group, 2-bromoethoxy group, 2-chloro ethoxy group, 2-iodoethoxy group, 2, 2-difur Fluoroethoxy group, 2,2,2-trifluoroethoxy group, 2,2,2 trichloro-epoxy group, pentafluoroethoxy group, 3, 3, 3 trifluoro-l-poxy group, 1, 1,1 trifluoro-2-propoxy group, 1,1,1 trichloro-2-propoxy group, 4,4,4 trifluoro-1 butoxy group, 4,4,4 trifluoro-2 butoxy group 2-trifluoromethyl-1 propoxy group, 2-trifluoromethyl-2-propoxy group, 5, 5, 5 trifluoro-1 pentyloxy group, 5, 5, 5 trifluoro-2 pentyloxy group, 1,1,1 Trifluoro-3 penty
  • a C C alkoxy group substituted with up to 5 halogeno groups and more preferably
  • a halogeno C 1 -C alkoxy group (the halogeno C 1 -C alkoxy group has 1 to 5
  • C 1 -C alkylthio group in R 3 of the general formula (I) represents one of the above C 1 -C alkyl
  • Mercapto groups substituted with 1 6 1 6 groups for example, methylthio group, ethylthio group, 1-propylthio group, 2-propylthio group, 1-butylthio group, 2-butylylthio group, 2-methyl-1-propylthio group, 2- Methyl-2-propylthio group, 1 pentylthio group, 2-pentylthio group, 3 pentylthio group, 2-methyl-2-butylthio group, 3-methyl-2-butylthio group, 1-hexylthio group, 2 hexylthio group, 3 hexylthio group, 2 -Methyl-1 pentylthio group, 3-methyl-1 pentylthio group, 2 ethyl-1-butylthio group, 2,2 dimethyl-1-butylthio group, or 2,3 dimethyl-1 butylthio group, preferably CC alkylthio group, More preferably, C
  • a methinoretio group or an ethinoretio group and most preferably a methylthio group.
  • the "C-C alkylsulfier group" in R 3 of the general formula (I) is one of the above-mentioned C-C A sulfiel group substituted with an alkyl group (one so-), for example, a methylsulfiel group, an ethylsulfyl group, a 1 propylsulfiel group, a 2-propylsulfiel group, a 1-butylsulfiel group, a 2- Butylsulfiel group, 2-methyl-1-propylsulfuryl group, 2-methyl-2-propylsulfuryl group, 1 pentylsulfuryl group, 2 pentylsulfuryl group, 3 pentylsulfuryl group, 2-methyl-2 buty Rusulfyl group, 3-methyl-2-butylsulfiel group, 1-hexylsulfenyl group, 2-hexylsulfiel group, 3-hexyls
  • a c-c alkylsulfier group especially methylsulfiyl group.
  • Nyl group ethylsulfyl group or propylsulfiel group
  • the “C—C alkylsulfol group” in R 3 of the general formula (I) represents one of the above C—C
  • 1 6 1 6 is a sulfol group substituted with an alkyl group (one so-), such as a methanesulfol group,
  • Ethanesulfol group 1-propanesulfol group, 2-propanepropane group, 1-butanesulfol group, 2-butanesulfol group, 2-methyl-1 propanesulfol group, 2-methyl- 2-Propanesulfol group, 1-Pentanesulfol group, 2-Pentanesulfol group, 3 Pentanesulfol group, 2-Methyl-2 Butanesulfol group, 3-Methyl-2-butanesulfol- Group, 1-hexanesulfol group, 2-hexanehexane group, 3 hexanesulfol group, 2-methyl-1 pentanesulfol group, 3 methyl-1-pentanesulfol group, 2-ethyl —1-butanesulfol group, 2,2-dimethyl-1-butanesulfol group, or 2,3 dimethyl-1-butanesulfol group, preferably a
  • a C—C alkylamino group especially a methylamino group, an ethylamino group.
  • a propylamino group more preferably a methylamino group or an ethylamino group, and most preferably a methylamino group.
  • methylethylamino group, methylpropylamino group [for example, N- (1-propyl) -N-methylamino group, etc.], methylptylamino group [for example, N- (l-ptyl) N-methylamino Group], jetylamino group, ethylpropylamino group [for example, N- (l propyl) -N ethylamino group, etc.], dipropylamino group [for example, di (1-propyl) amino group, di (2-propyl) amino Group], dibutylamino group [for example, di (1-ptyl) amino group, di (2-ptyl) amino group, etc.], di (2-methyl-1-propyl) amino group, dipentylamino group [for example, di ( 1 pentyl) amino group, di (2 pentyl) amino group, di (3 pentyl) amino group, etc.] or dihexylamino group
  • An amino group or a jetylamino group most preferably a dimethylamino group.
  • Di (C C alkyl) amino group means that the two alkyl groups are nitrogen atoms of the amino group.
  • the 7-membered saturated heterocyclyl group can be, for example, a pyrrolidinyl group, a piperidyl group, a piperazinyl group, a morpholinyl group, a thiomorpholinyl group, or a perhydroazepine group, and preferably a group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom
  • It is a diol group or an ethoxy carbo group, and most preferably a methoxy carbo group.
  • the "5- to 6-membered aromatic heterocyclyl group" in R 3 and Y of the general formula (I) contains 1 to 4 atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom 5 to 6-membered aromatic heterocyclic groups such as furyl, chael, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl Group, oxadiazolyl group, thiadiazolyl group, tetrazolyl group, biranyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, or pyrazyl group, preferably a chalcyl group, imidazolyl group, oxazolyl group, thiazolyl group, A triazolyl group or a pyrid
  • halogeno CC alkoxy group in R 4 , R 5 , substituent group a, substituent group ⁇ , and substituent group y in the general formula (I) is 1 to 5 of the above halogeno groups.
  • 1 4 1 4 Alkoxy group for example, fluoromethoxy group, difluoromethoxy group, dichloromethoxy group, dibromomethoxy group, trifluoromethoxy group, trichloromethoxy group, 2-fluoroethoxy group, 2-bromoethoxy group , 2-Chloro-ethoxy group, 2-Phodo-ethoxy group, 2,2-Difluoroethoxy group, 2,2,2-Trifluoroethoxy group, 2,2,2-Trichloro-ethoxy group, Pentafluoroethoxy 3, 3, 3 trifluoro-1 propoxy group, 1,1,1 trifluoro 1 2-propoxy group, 1,1, 1 trichloro 1 2 propoxy group, 4,4,4 trifluoro 1-butoxy group, 4 2,4,4 trifluoro 2 butoxy group, 2 trifluoromethyl-1-propoxy group, or 2-trifluoromethyl-2-propoxy group, preferably a halogeno C 1 -C alkoxy group
  • C-C alkyl group for R 6 and R 7 in the general formula (I) is a group having 1 to 3 carbon atoms.
  • a linear or branched alkyl group having, for example, a methyl group, an ethyl group, a 1-propyl group, or a 2-propyl group, preferably a methyl group or an ethyl group, most preferably Is a methyl group.
  • a C C alkyl group substituted with the above C C cycloalkyl group for example,
  • Fe-Lu (C—C alkyl) group in R 11 and R 12 of the general formula (I) is a group of one phenol.
  • a ferro (C—C alkyl) group (especially a benzyl group, a 1-ferroethyl group or 2
  • a benzyl group and most preferably a benzyl group.
  • “4- to 10-membered heterocyclyl group” in R 11 of general formula (I) and 4-to-10-membered heterocyclyl moiety in R 11 are selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur nuclear atom
  • a 4- to 10-membered heterocyclic group containing 1 to 4 atoms such as a furyl group, a phenyl group, a pyrrolyl group, a pyrazolyl group, an imidazolyl group, an oxazolyl group, an isoxazolinole group, a thiazolinole group, an isothiazolinole group 1,2,3-oxadiazolinol group, 1,2,3 thiadiazolyl group, triazolyl group, tetrazolyl group, biranyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, pyrajuryl group, azepin
  • 5- to 7-membered heterocycles containing 1 to 4 atoms selected from the group consisting of atoms, oxygen atoms and sulfur atoms More preferably, it is a 5- to 6-membered heterocyclyl group containing 1 to 2 atoms selected from the group consisting of a nitrogen atom, an oxygen atom and sulfur nuclear power, and more preferably imidazolyl.
  • Cryl group is a 5- to 7-membered heterocyclyl group containing 1 to 4 atoms selected from the group consisting of a nitrogen atom, an oxygen atom and sulfur nuclear power), and more preferably a 5 to 6-membered group.
  • Heterocyclyl (C—C alkyl) group (the heterocyclyl group is a nitrogen atom, oxygen
  • the “C—C alkoxy group” in R 11 of the general formula (I) represents one C—C alkenyl group.
  • Hydroxyl groups substituted with 3 6 3 6 groups for example, 2-probeoxy group, 2-buteroxy group, 2-methyl-2-proberoxy group, 2-penteroxy group , 2-methyl-2-butenyloxy group, or 2-hexenyl-oxy group, preferably C-C alkoxy group, and most preferably 2-probeoxy group or 2
  • chloroalkyl group such as cyclopropylamino group, cyclo It may be a butylamino group, a cyclopentylamino group, or a cyclohexylamino group, preferably a C—C cycloalkylamino group, more preferably a C—C cyclyl group.
  • 3 5 3 4 is an alkylamino group, most preferably a cyclopropylamino group.
  • C—C alkalamino group in R 11 of the general formula (I) is one C—C alkal group.
  • Amino groups substituted with 3 6 3 6 groups for example, 2-probelamino group, 2-butyramino group, 2-methyl-2-probelamino group, 2-penteramino group, 2-methyl- It can be a 2-butylamino group or a 2-hexene-lumino group, preferably a C-Calkene group.
  • -Luamino group most preferably 2-propenylamino group or 2-butenylamino group.
  • (C—C alkyl)] amino refers to one above C—C alkyl group and one above (C
  • N An amino group substituted with a —C cycloalkyl) — (C—C alkyl) group, for example, N
  • Group means one C CC alkyl group and one C C cycloalkyl group.
  • Substituted amino groups such as N-methyl-N cyclopropylamino, N ethyl N cyclopropylamino, N— (1-propyl) -N-cyclopropylamino, N— (2-propyl) -N-cyclopropylamino group, N— (1-butyl) -N-cyclopropylamino group, N— (l pentyl) one N cyclopropylamino group, N— (1-hexyl) —N cyclopropylamino group, N—Methyl N cyclobutylamino group, N ethyl-N cyclobutylamino group, N (l propyl) —N cyclobutylamino group, N— (2-propyl) -N-cyclobutylamino group, N— (1-butyl) -N-cyclobutylamino group, N- (1-pentyl) -N-
  • the "5- to 7-membered heterocyclyl group" in R 12 of the general formula (I) and the 5- to 7-membered heterocyclyl moiety in R 11 are selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur atom.
  • a 5- to 7-membered heterocyclic group containing 1 to 4 atoms such as furyl, phenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolinol, isothiazolinol, 1,2,3-oxadiazolinole group, 1,2,3 thiadiazolyl group, triazolyl group, tetrazolyl group, biranyl group, pyridyl group, pyridazinyl group, pyrimidyl group, birazinyl group, or azepi -Unsaturated heterocyclic group such as pyrrolidyl group, pyrrolidinyl group, pyrrolinyl group, imidazolidinyl group, imidazolinyl group, virazolidinyl group, virazolyl group, Such as lysyl group, piperazinyl group, morpholiny
  • a C C alkyl group substituted with 5 to 7 membered heterocyclyl groups for example
  • the “C—C alkylene group” in X 2 of the general formula (I) has 1 to 2 carbon atoms.
  • Alkylene groups such as methylene group, ethylene group [(CH 3) 2, methylmethylene
  • It may be a group [—CH (Me)], and is preferably a methylene group.
  • a carbo group substituted with a C C alkyl group (one CO 2), for example methyl
  • Boryl group (acetyl group), ethyl carbo yl group, 1 propyl carbo ol group, 2-propyl carbo yl group, 1 butyl carbo ol group, 2-butyl carbo yl group, or 2-methyl 2-propyl It can be a carbo group, preferably a (CC alkyl) carbo-
  • the "(CC alkoxy) carbol group" in the substituent group a of the general formula (I) is one A carbo group (one CO 2) substituted with a CC alkoxy group, for example, methoxy
  • Sicarbonyl group, ethoxycarbonyl group, 1-propoxycarbonyl group, 2-propoxycarbonyl group, 1-butoxycarbonyl group, 2-butoxycarbonyl group, or 2-methyl-2-propoxycarbonyl group Preferably a (C—C alkoxy) calcium
  • substitution position of X 1 is the 1-position
  • substitution position of R 8 is preferably the 3-position or the 4-position, and more preferably the 4-position.
  • the compound represented by the general formula (I) of the present invention or a pharmacologically acceptable ester force of the salt When having a basic group, it can be converted into a salt by reacting with an acid. When the compound represented by the formula (I) or a pharmacologically acceptable ester thereof has an acidic group, it can be converted into a salt by reacting with a base. If these salts are used in the treatment of disease, they must be pharmacologically acceptable.
  • the salt formed with the basic group of the compound represented by the general formula (I) of the present invention is preferably, for example, hydrochloride, hydrobromide, hydroiodide, etc.
  • Inorganic acid salts such as hydrohalides; nitrates; perchlorates; sulfates; or phosphates; substituted with fluorine atoms such as methanesulfonate, trifluoromethanesulfonate, ethanesulfonate, etc.
  • Salt with alkane sulfonic acid Salt with C C aryl sulfonic acid which may be substituted with C C alkyl such as benzene sulfonate, p-toluene sulfonate, etc .; Acetate; Apple
  • Acid salt acid salt
  • fumarate salt succinate salt
  • succinate salt tartrate salt
  • oxalate salt organic acid salt
  • organic acid salt such as maleate salt
  • glycine salt lysine salt
  • arginine salt ornithine salt
  • glutamine Amino acid salts such as acid salts and aspartates, and more preferably halogenated hydrates.
  • the salt formed with the acidic group of the compound represented by the general formula (I) of the present invention is preferably, for example, an alkali metal salt such as a sodium salt, a potassium salt or a lithium salt; a calcium salt, Aluminum salt; Iron salt; Zinc salt; Copper salt; Copper salt; Metal salt such as Conoret salt; Inorganic amine such as ammonium salt Salt; or t ota Tyramine salt, dibenzylamine salt, morpholine salt, darcosamine salt, phenylglycine alkyl ester salt, ethylene diamine salt, N-methyl darcamamine salt, guanidine salt, ditylamine salt, triethylamine salt, dicyclohexylamine salt, ⁇ , ⁇ '-dibenzyl ethylenediamine salt, black pro-in salt, pro-in salt, diethanolamine salt, ⁇ -benzylphenethylamine salt, piperazine salt, tetramethylammonium salt, tri
  • the compound represented by the general formula (I) of the present invention or a pharmacologically acceptable salt or ester thereof is hydrated by leaving it in the air or adsorbing water during recrystallization. These hydrates are also included in the present invention. Furthermore, the compounds of the present invention may incorporate other solvents to form solvates, which are also included in the present invention.
  • optical isomers including diastereomers
  • these isomers and mixtures thereof may be represented by a single formula (I) It is described by the following formula.
  • the present invention also encompasses deviations of each of these isomers and mixtures of them in any proportion (including racemates).
  • the present invention includes an ester of the compound represented by the general formula (I).
  • These esters are compounds in which the hydroxyl group or carboxyl group of the compound represented by the general formula (I) is modified with a protective group according to a method well known in the field (for example, “Prot ective Groups in Organic Synthesis, 3 ⁇ 4econa £ aitio ”, rheoaora W. Greene and Peter GM Wuts, 1991, John Wiley & Sons, Inc.).
  • the nature of the protecting group is not particularly limited. However, if this ester is used in the treatment of disease, it must be pharmacologically acceptable. For example, this protecting group is present when the compound is administered to a mammal in vivo. It must be able to be eliminated by metabolic processes (for example, hydrolysis) to produce a compound represented by the general formula (I) or a salt thereof. That is, a pharmacologically acceptable ester is a “prodrug” of the compound represented by the general formula (I) of the present invention. However, the compound represented by the general formula (I) of the present invention Ester potency of the compound When used for other than the treatment of disease (eg when used as an intermediate for the manufacture of other compounds), the ester need not be pharmacologically acceptable.
  • ester of the compound represented by the general formula (I) of the present invention is pharmacologically acceptable.
  • the compound is intravenously administered to an experimental animal such as a rat or mouse, and the blood or body fluid of the animal is examined to detect the compound represented by the general formula (I) of the present invention or a pharmacologically acceptable salt thereof.
  • the compound is determined to be a pharmacologically acceptable ester.
  • the compound represented by the general formula (I) of the present invention can be converted to an ester, and the ester can be, for example, a compound in which the hydroxyl group of the compound is esterified.
  • the ester residue may be a common protecting group when the esterified compound is used as an intermediate, and if the esterified compound is pharmacologically acceptable. In some cases, it may be a protecting group that can be removed by metabolic processes in vivo (for example, hydrolysis).
  • the general protecting group is an ester protecting group that can be removed under chemical conditions such as hydrolysis, hydrogenolysis, electrolysis, and photolysis.
  • These general protecting groups used for the preparation of the compounds of the general formula (I) in which the hydroxyl group has been modified may suitably be, for example:
  • An aliphatic acyl group such as an alkyl carbonyl group, a lower alkoxyalkyl carbonyl group having 1 to 25 carbon atoms, or an unsaturated alkyl carbonyl group having 1 to 25 carbon atoms;
  • aryl hydrocarbon group halogenoaryl carbonate group, lower alkyl aryl group carbonyl group, lower alkoxy aryl carbonate group, nitrated aryl carbonate group, lower alkoxy carbonate reel group, Or an aromatic acyl group such as an arylated carbonyl group;
  • Silyl groups such as (C C alkyl) silyl groups
  • Substituted ethyl groups such as 1 6 1 6 xyl) ethyl groups
  • —C one or more selected from the group consisting of alkoxy, nitro, halogeno and cyan
  • An aralkyl group such as a benzyl group, which may be substituted with a substituent
  • (X) an alkoxycarboxyl group having 3 to 6 carbon atoms
  • ester group that can be eliminated in a metabolic process (for example, hydrolysis) in a living body is eliminated in the metabolic process (for example, hydrolysis) when administered into the body of a mammal, and is represented by the general formula (I). It is an ester group which produces
  • protecting groups as ester residues may suitably be, for example:
  • Sodioxorenylmethyl group (the substituent is a C-C alkyl group and a C-C alkyl group)
  • a substituted carbo-alkylalkyl group such as 1 6 1 6 a group selected from the group of aryl groups that may be substituted with a kill or halogeno;
  • suitable compounds may be those shown in Tables 1 to 3 below. However, the compounds of the present invention are not limited to these compounds.

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Abstract

Il est exposé un excellent modulateur des LXR. Il est précisément exposé des composés représentés par la formule générale (I) suivante. (Dans la formule, R1 représente -COR9 (où R9 représente un alkyle, un alcoxy facultativement substitué ou un amino facultativement substitué ou similaire), un aryle facultativement substitué ou similaire ; R2 représente H, OH, un alcoxy ou similaire ; R3 représente H, un alkyle facultativement substitué, un alcényle, un alcoxy facultativement substitué, un amino facultativement substitué ou similaire ; R4 et R5 représentent respectivement H, un alkyle facultativement substitué, un halogéno ou similaire ; R6 et R7 représentent respectivement H, un alkyle ou similaire ; R8 représente -N(R10)ZR11, -ZN(R10)R12, -X2N(R10)ZR11 ou similaire (où R10 représente H, un alkyle facultativement substitué ou similaire, R11 représente H, un alkyle facultativement substitué, un cycloalkyle facultativement substitué, un alcényle facultativement substitué, un alcoxy facultativement substitué, un amino facultativement substitué, un phényle facultativement substitué ou similaire, R12 représente H, un alkyle facultativement substitué, un alcényle facultativement substitué ou similaire, X2 représente un alkylène et Z représente CO, CS ou SO2) ; X1 représente une liaison simple ou un méthylène facultativement substitué ; et Y représente un phényle facultativement substitué ou un hétérocyclyle facultativement substitué.)
PCT/JP2005/011928 2004-06-30 2005-06-29 Composé du benzène substitué WO2006003923A1 (fr)

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