WO2006109633A1 - Composé indole substitué - Google Patents

Composé indole substitué Download PDF

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Publication number
WO2006109633A1
WO2006109633A1 PCT/JP2006/307187 JP2006307187W WO2006109633A1 WO 2006109633 A1 WO2006109633 A1 WO 2006109633A1 JP 2006307187 W JP2006307187 W JP 2006307187W WO 2006109633 A1 WO2006109633 A1 WO 2006109633A1
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group
alkyl
substituted
amino
substituent
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Japanese (ja)
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Kazuhiko Tamaki
Takahiro Yamaguchi
Naoki Terasaka
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Sankyo Co Ltd
Daiichi Sankyo Co Ltd
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Sankyo Co Ltd
Daiichi Sankyo Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention regulates the action of Liver X receptors (LXR) to improve abnormal lipid metabolism or to control the production of inflammatory mediators, thereby improving the anti-atherosclerotic action and anti-inflammatory effect.
  • LXR Liver X receptors
  • the present invention relates to an indole compound or a pharmacologically acceptable salt or esterole that exhibits an action.
  • the present invention relates to an LXR modulator, an LXR antagonist, or an LXR antagonist, preferably an LXR modulator or an LXR enzyme, containing an odondolyl compound or a pharmacologically acceptable salt or ester thereof. It relates to a ghost, more preferably an LXR module.
  • the present invention relates to a pharmaceutical composition containing an odondolyl compound or a pharmacologically acceptable salt or ester thereof as an active ingredient, preferably arteriosclerosis, atherosclerosis, diabetes mellitus.
  • arteriosclerosis hyperlipidemia, hypercholesterolemia, lipid-related disease, inflammatory disease, autoimmune disease, arteriosclerotic heart disease, cardiovascular disease, coronary artery disease, cerebrovascular disease, kidney
  • arteriosclerosis for the treatment or prevention of arteriosclerosis, hyperlipidemia, hypercholesterolemia, lipid-related disease, inflammatory disease, arteriosclerotic heart disease, cardiovascular disease, coronary artery disease, or diabetes caused by Doctor More preferably, for the treatment or prevention of arteriosclerosis, atherosclerosis, arteriosclerosis caused
  • the present invention also relates to a pharmaceutical composition for inducing ABCA1 expression or promoting reverse cholesterol transfer comprising an indole compound or a pharmacologically acceptable salt or ester thereof as an active ingredient.
  • a pharmaceutical composition preferably an indole compound or a pharmacologically acceptable salt thereof for producing a pharmaceutical composition for treating or preventing the above-mentioned diseases. Relates to the use of esters.
  • the present invention relates to a disease caused by administering a pharmacologically effective amount of an indole compound or a pharmacologically acceptable salt or ester thereof to a warm-blooded animal (particularly a human), preferably Relates to a method for the treatment or prevention of the above diseases.
  • the present invention relates to a method for producing an odondolyl compound or a pharmacologically acceptable salt or ester thereof.
  • cardiovascular diseases for example, heart disease, cerebrovascular disease, renal disease, etc.
  • hypertension hyperlipidemia
  • hyperglycemia hyperglycemia
  • Antihypertensive drugs, antihyperlipidemic drugs, and antidiabetic drugs are used for the treatment of hypertension, hyperlipidemia, and hyperglycemia, respectively.
  • antihypertensive drugs include spleen and beta blockers, diuretics, calcium antagonists, ACE inhibitors, and A-II antagonists, and antihyperlipidemic drugs such as HMG-CoA reductase inhibitors.
  • Insulin exchange, succinic acid, nicotinic acid derivatives, probucol, and fibrates, and insulin, sulfonylureas, metformin, and glitazones are used as antidiabetic agents. These drugs contribute to the regulation of blood pressure and blood lipid or blood glucose levels. However, the mortality due to heart disease, cerebrovascular disease and kidney disease has not been greatly improved by the use of these drugs, and the development of better therapeutic agents for these diseases is desired.
  • 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 nuclear receptor
  • 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.
  • LXR induces expression of ABCA1 also in the small intestine, inhibit the absorption from the gastrointestinal tract of cholesterol from the diet (R epa, JJ, Turley, SD, Lobaccaro, JA, Medina, J. Li, L., Lustig, K., Shan, B., Heyman, RA, Dietschy, JM, Mange lsdorf, DJ, Science, 2002, 289, p. 1524-1529).
  • drugs that regulate LXR are arteriosclerosis, atherosclerosis, arteriosclerosis caused by diabetes, hyperlipidemia, lipid-related diseases. It is expected to be useful in the treatment or prevention of arteriosclerotic heart disease, cardiovascular disease, or coronary artery disease.
  • Atherosclerosis is also considered a chronic inflammatory disease (Ross, R., N. Engl. J. Med., 1986, 314, ⁇ .488- ⁇ 00).
  • LXR has been immunized by regulating the expression of inflammatory mediators such as nitric oxide synthase, cycloxygenase 2 (COX-2), and interleukin 6 (IL-6). It has been reported that it plays an important role in function control (Mangelsdorf, DJ, Tontonoz, P. et. Al., Nat. Med., 2003, Vol. 9, p.213-219). Therefore, LXR modulators are expected to suppress the development and progression of arteriosclerosis by anti-inflammatory action in addition to improving fat metabolism.
  • LXR modulators are expected to be useful for the treatment of various inflammatory diseases.
  • Patent Document 1 International Publication No. 03Z084544 Pamphlet
  • Patent Document 2 Pamphlet of International Publication No.98Z08818
  • Patent Document 3 International Publication No. 99Z43672 Pamphlet
  • the present invention regulates the action of the nuclear receptor LXR to improve abnormal lipid metabolism or to control the production of inflammatory mediators, thereby improving the anti-atherosclerotic action and anti-inflammatory action.
  • An indole compound or a pharmacologically acceptable salt or ester thereof is provided.
  • the present invention relates to an LXR modulator, an LXR antagonist, or an LXR antagonist, preferably an LXR modulator or an LXR antagonist, containing an odondolyl compound or a pharmacologically acceptable salt or ester thereof.
  • a ghost, more preferably an LXR module is provided.
  • the present invention provides a pharmaceutical composition containing an odondolyl compound or a pharmacologically acceptable salt or ester thereof as an active ingredient, preferably arteriosclerosis, atherosclerosis, diabetes mellitus.
  • arteriosclerosis hyperlipidemia, hypercholesterolemia, lipid-related disease, inflammatory disease, autoimmune disease, arteriosclerotic heart disease, cardiovascular disease, coronary artery disease, cerebrovascular disease, kidney Disease, diabetes, diabetic complications, obesity, nephritis, hepatitis
  • a pharmaceutical composition for the treatment or prevention of cancer, cancer, or Algno's disease more preferably, arteriosclerosis, atherosclerosis, arteriosclerosis caused by diabetes, hyperlipidemia, high
  • compositions for inducing ABCA1 expression or promoting reverse cholesterol transfer comprising a benzene compound having two or more substituents or a pharmacologically acceptable salt or ester thereof as an active ingredient.
  • the present invention provides a pharmaceutical composition, preferably an indole compound or a pharmacologically acceptable salt thereof for the production of a pharmaceutical composition for the treatment or prevention of the above diseases.
  • a pharmaceutical composition preferably an indole compound or a pharmacologically acceptable salt thereof for the production of a pharmaceutical composition for the treatment or prevention of the above diseases.
  • esters Provides the use of esters.
  • the present invention is directed to a disease caused by administering a pharmacologically effective amount of an odondolyl compound or a pharmacologically acceptable salt or ester thereof to a warm-blooded animal (particularly a human), preferably Provides a method for the treatment or prevention of the above diseases.
  • the present invention provides a method for producing an indole compound or a pharmacologically acceptable salt or ester thereof.
  • the present invention is a.
  • a halogeno C C alkyl group (the halogeno C C alkyl group comprises 1 to 7
  • halogeno C C alkoxy group (the halogeno C C alkoxy group is 1 to 7
  • Two such alkyl groups together with the nitrogen atom of the amino group, form a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur nuclear power. Which may be formed), a cyano group, a nitro group, a halogeno group or a phenenore group;
  • R 5 represents a hydrogen atom or a C 1 -C alkyl group
  • R 6 is the formula 1 COR 8 [wherein R 8 is a C—C alkoxy group, halogeno C—C alkoxy
  • a group (the halogeno C C alkoxy group is a C substituted with 1 to 7 halogeno groups;
  • C represents an alkoxy group), (C 1 -C cycloalkyl) — (C 1 -C alkyl) oxy group,
  • the groups are the same or different and are 1 to 3 groups selected from the substituent group ⁇ ), C C
  • alkyl groups may be the same or different and
  • a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atomic force. May be formed).
  • R 9 is a C—C alkyl group, a ferro (C—C alkyl) group,
  • a cyclyl- (C—C alkyl) group (the substituents may be the same or different,
  • R 7 is the formula —X 1Q
  • R 1Q is a formula — COR 11 [where R 11 is a hydroxyl group, a C—C alkoxy group, (C
  • the groups are the same or different, and the two alkyl groups together with the nitrogen atom of the amino group contain 1 to 3 atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur nuclear power 5 to 7-membered saturated heterocyclyl groups may be formed), di [(C—C
  • R 12 is a C—C alkyl group, (C—C cycloalkyl) — (C—C
  • the group together with the nitrogen atom of the amino group forms a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms selected from the group consisting of nitrogen, oxygen and sulfur atoms.
  • di [(C 1 -C cycloalkyl) (C 1 -C alkyl)] amino group di (C
  • R 13 is a hydrogen atom, a C-C alkyl group, (C-C cycloa
  • R 14 represents water
  • R 13 is as defined above, R 15 is a C—C alkyl group
  • X 2 represents a single bond, a C—C alkylene group, or a substituted C—C alkylene group (the substituted
  • the groups are the same or different and are 1 to 2 groups selected from the substituent group ⁇ , and the two substituents may be combined to form an ethylene group or a trimethylene group. .
  • X 1 represents a methylene group or a substituted methylene group (the substituent is 1 or 2 identical or different C 1 -C alkyl groups);
  • ⁇ 1 is a phenyl group, a substituted phenol group (the substituents are the same or different and are 1 to 3 groups selected from the substituent group ⁇ ), and a 5- to 6-membered aromatic heterocyclyl. Or a substituted 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 ex);
  • ⁇ 2 is a 6- to 10-membered aryl group, a substituted 6- to 10-membered aryl group (the substituents are the same or different and are 1 to 3 groups selected from the substituent group
  • the substituents are the same or different and are 1 to 3 groups selected from the substituent group (8)), 5 to 10-membered aromatic heterocyclyl groups, or substituted 5 to 10 membered heterocyclyl groups aromatic (said substituents may be the same or different, substituent group) is 1 to 3 groups selected from 8), 9 to the 10-membered unsaturated heterocyclyl group (provided that, Upsilon 1
  • the linking cyclic group
  • Substituent group ⁇ 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
  • Substituent group j8 includes C—C alkyl group, hydroxy (C 1 -C alkyl) group, carboxy (C
  • halogeno C C alkyl group is substituted with 1 to 7 halogeno groups.
  • the alkoxy group represents a C C alkoxy group substituted with 1 to 7 halogeno groups), C
  • 1 6 3 8 1 6 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)
  • a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom may be formed), N— (C 1 -C 6 cycloalkyl)
  • Substituent group 0 includes c-C alkyl group, hydroxy (c-c alkyl) group, (C-C alcohol)
  • alkyl groups may be the same or different,
  • Amino group (the alkyl group is the same or different, the two alkyl groups together with the nitrogen atom of the amino group together with the nitrogen atom, oxygen atom and sulfur nuclear power)
  • a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms selected may be formed), a di (C—C cycloalkyl) amino group, N— (C—C cycloalkyl) —N — (C
  • the present invention provides an LXR modulator, LXR agonist, or LXR antagonist containing a compound represented by the above general formula (I) or a pharmacologically acceptable salt or ester thereof, preferably Provides an LXR modulator or LXR agonist, more preferably an LX R modulator.
  • the present invention also includes a compound represented by the above general formula (I) or a pharmacologically acceptable salt or ester thereof showing an effective amount of pharmacological activity, and a carrier or diluent.
  • a pharmaceutical composition is provided.
  • the present invention provides the pharmaceutical composition for treating or preventing a disease in a warm-blooded animal, and the warm-blooded animal is an LXR machine in the warm-blooded animal. It can be a human suffering from a disease that can be treated or prevented by modulation of performance.
  • the disease may be a disease that can be treated or prevented by modulation of L XR function, preferably arteriosclerosis, atherosclerosis, arteriosclerosis caused by diabetes, hyperlipidemia, hypercholesterolemia.
  • the present invention provides a pharmaceutical composition for
  • 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 provides one or more compounds represented by the above general formula (I) or a pharmacologically acceptable salt thereof in the manufacture of a medicament for the treatment or prevention of a disease in a warm-blooded animal.
  • the warm-blooded animal can be a human suffering from a disease that can be treated or prevented by modulation of LXR function in the warm-blooded animal.
  • the disease can be similar to that shown above.
  • the present invention provides a method for treating a disease for a warm-blooded animal by administering an effective amount of the compound represented by the general formula (I) or a pharmacologically acceptable salt or ester thereof to the warm-blooded animal.
  • a method for treatment or prevention is provided, wherein the warm-blooded animal can be a human suffering from a disease that can be treated or prevented by modulation of LXR function in the warm-blooded animal.
  • the disease can be similar to that shown above.
  • 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 a drug selected from the group consisting of an inhibitor, ⁇ -blocker, fibrinogen inhibitor, aspirin, diuretic, or a combination thereof; and a carrier or diluent.
  • a halogeno C C alkyl group (the halogeno C C alkyl group is composed of 1 to 5 halogeno
  • a halogeno C 1 -C alkoxy group (the halogeno C 1 -C alkoxy group comprises 1 to 5
  • the compound described in (1) which is a uro group, a black mouth group, or a bromo group,
  • a trifluoromethyl group, a 2,2,2-trifluoroethyl group, a pentafluoroethyl group, a hydroxyl group, a methoxy group, an ethoxy group, a fluoro group, a black mouth group, or a bromo group (1 )
  • R 4 is the same or different and is a hydrogen atom, a fluoro group, or a black mouth group, the compound according to (1),
  • R 5 is a hydrogen atom or a CC alkyl group described in any one of (1) to (4)
  • R 6 has the formula —COR 8a [wherein R 8a is a C 1 -C alkoxy group, halogeno C 1 -C alcohol, Xoxy group (the halogeno CC alkoxy group is a C substituted with 1 to 7 halogeno groups)
  • the groups are the same or different and are 1 to 2 groups selected from the substituent group ⁇ 1), C C
  • a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms may be formed).
  • R 9a is a C—C alkyl group, a ferro (C—C alkyl) group,
  • An aryl 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 5- to 6-membered aromatic heterocyclyl group (the heterocyclyl group).
  • Group represents a chenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a triazolyl group, or a pyridyl group), or a substituted 5- to 6-membered aromatic heterocyclyl group (the heterocyclyl group includes a cetyl group, an imidazolyl group, An oxazolyl group, a thiazolyl group, a triazolyl group, or a pyridyl group, and the substituents are the same or different and are 1 to 2 groups selected from the substituent group a 1).
  • heterocyclyl group is Le
  • the heterocyclyl group represents a chenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a triazolyl group, or a pyridyl group, and the substituent is the same or different and is selected from 1 to 2 selected from the substituent group a 1 Group);
  • Substituent group ⁇ 1 is a methyl group, an ethyl group, a trifluoromethyl group, 2,2,2-trifluoro group.
  • R 6 has the formula —COR 8b [wherein R 8b is a C 1 -C alkoxy group, halogeno C 1 -C alcohol,
  • the substituent group a 2 is a group consisting of a methyl group, an ethyl group, a trifluoromethyl group, a methoxy group, an ethoxy group, a fluoro group, and a black mouth group, and any one of (1) to (6) Compound,
  • R 6 is formula 1 COR 8 wherein R & is a C—C alkoxy group or halogeno C—C
  • halogeno C—C alkoxy group is composed of 1 to 5 fluoro or chloro
  • R 6 is a group having the formula — COR 8d (where R 8d represents a C—C alkoxy group).
  • R 7 is the formula X 2a R 1Qa
  • R 1Qa is a formula — COR Ua [where R Ua is a hydroxyl group, a C—C alkoxy group, (C
  • the alkyl group together with the nitrogen atom of the amino group, forms a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur nuclear power.
  • a hydroxylamino group, or hydroxyl (C- c) represents an alkyl) amino group.
  • R 12a is a C 1 -C alkyl group, (C 1 -C cycloalkyl) — (C 1 -C 6
  • the alkyl group is the same or different, and the two alkyl groups together with the nitrogen atom of the amino group contain 1 to 3 atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom It may form a 5- to 7-membered saturated heterocyclyl group).
  • R 13a is a hydrogen atom, a C—C alkyl group, (C—C cyclo
  • R 14a is
  • X 2a is a single bond, a C 1 -C alkylene group, or a substituted C 1 -C alkylene group (the substituted
  • the groups are the same or different and are 1 to 2 groups selected from the substituent group ⁇ 1, and the two substituents may form an ethylene group or a trimethylene group together) Show.
  • Substituent group 01 includes methyl group, ethyl group, hydroxymethyl group, hydroxyethyl group, methoxymethyl group, methoxyethyl group, aminomethyl group, aminoethyl group, methylaminomethyl group, methylaminoethyl group, cyclopropyl Aminomethyl group, cyclopropylaminoethyl group, dimethylaminomethyl group, dimethylaminoethyl group, hydroxyl group, methoxy group, ethoxy group, amino group, methylamino group, ethylamino group, cyclopropylamino group, cyclopropylamino group, dimethylamino
  • (1) to (10) which is a group consisting of a group, a jetylamino group, a fluoro group, and a black mouth group,
  • R 7 is the formula — X 2b R 1Qb
  • R 1Qb is a formula — COR Ub [where R Ub is a hydroxyl group, C—C alkoxy group, (C — C cycloalkyl) — (C—C alkyl) oxy group, C—C cycloalkyloxy group
  • R 12b is a CC alkyl group, (CC cycloalkyl) (C
  • X 2b represents a single bond, a methylene group, an ethylene group, or a substituted methylene group or a substituted ethylene group (the substituents may be the same or different and are 1 to 2 groups selected from the substituent group ⁇ 2). And the two substituents together may form an ethylene group or a trimethylene group).
  • Substituent group 0 2 includes a methyl group, an ethyl group, a hydroxymethyl group, a methoxymethyl group, an aminomethyl group, a methylaminomethyl group, a dimethylaminomethyl group, a methoxy group, a methylamino group, a dimethylamino group, a fluoro group, and A compound described in any one of (1) to (10), which is also a group having a black mouth basic force,
  • R 7 is the formula — X 2 lfc
  • R 1Qc is a group having the formula — COR Uc (wherein R Uc represents a hydroxyl group, a methoxy group, or an ethoxy group), or
  • a group having the formula —SO 2 R 12e (wherein R 12e represents a methyl group or an ethyl group),
  • X 2e is a single bond, a methylene group, or a substituted methylene group (the substituent is two fluorine groups, and the two substituents may form an ethylene group together) Indicates. Or a compound according to any one of (1) to (10),
  • R 7 is the formula — X 2d R 1M
  • R 1M represents a group having the formula — COR Ud (wherein R Ud represents a hydroxyl group)
  • X 2d represents a methylene group or a substituted methylene group (the two substituents together form an ethylene group).
  • X 1 force A compound according to any one of (1) to (14), which is a methylene group, ( ⁇ ) ⁇ 1 is a phenyl group, a substituted phenol group (the substituents are the same or different and are 1 to 2 groups selected from the substituent group a 2), 5 to 6 members
  • An aromatic heterocyclyl group (which represents a pyrrolyl group, a furyl group, a chenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a pyridyl group, or a pyridazinyl group), or a substituted 5- to 6-membered aromatic Group heterocyclyl group (the heterocyclyl group represents a pyrrolyl group, a furyl group, a phenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a pyridyl group, or a pyrida
  • Y 1 is a phenyl group, a substituted phenol group (the substituent is one group selected from the substituent group ⁇ 3), a chael group, a pyridyl group, or A substituted chayl group or a substituted pyridyl group (the substituent is one group selected from the substituent group a 3); the substituent group a 3 includes a methyl group, a fluoro group, and a chloro group; (1) Nozomi (15) indicating a group consisting of mouth groups,
  • Y 2 force phenyl group, substituted phenol group (the substituents are the same or different and are 1 to 3 groups selected from the substituent group ⁇ 1), indanyl group or tetrahydronaphth methyl group (provided that a cyclic group bonded to Upsilon 1 is a benzene ring), location ⁇ Ndaniru group properly is substituted tetrahydronaphthyl group (provided that a cyclic group bonded to Upsilon 1 is a benzene ring, those wherein the substituents Are the same or different and are 1 to 3 groups selected from the substituent group ⁇ 8 1), a 5- to 6-membered aromatic heterocyclyl group (the heterocyclyl group is a pyrrolyl group, a furyl group, a enyl group, An imidazolyl group, an oxazolyl group, a thiazolyl group, a pyridyl group, or
  • a substituted 9- to 10-membered unsaturated heterocyclyl group (representing a chromanyl group)
  • the cyclic group bonded to Y 1 is an aromatic ring
  • the unsaturated heterocyclyl group is an indoline.
  • Substituent group j81 includes C—C alkyl group, hydroxy (C—C alkyl) group, carboxy (
  • 1 4 1 4 1 4 Lucoxy group represents a C C alkoxy group substituted with 1 to 5 halogeno groups
  • Aminocarbonyl group (the alkyl groups are the same or different, and the two alkyl groups together with the nitrogen atom of the amino group are selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom 1 A 5- to 7-membered saturated heterocyclyl group containing 3 atoms), a cyano group, a nitro group, a fluoro group, a black mouth group, and a bromo group (1) to (18)
  • Y 2 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 ⁇ 2), a chaer group , Thiazolyl group, pyridyl A substituted chael group, a substituted thiazolyl group or a substituted pyridyl group (the substituents are the same or different and are 1 to 2 groups selected from the substituent group
  • the group j8 2 includes C—C alkyl group, trifluoromethyl group, 2,2,2-trifluoro group.
  • Tyl group pentafluoroethyl group, C-C alkyl group, C-C alkyl group, C-C alkyl group, C
  • Ethanesulfol group amino group, methylamino group, ethylamino group, dimethylamino group, dimethylamino group, formyl group, methylcarbol group, ethylcarboro group, nitro group, fluoro group, and black mouth group
  • Y 2 is a phenyl group or a substituted phenol group (the substituent is one group selected from the substituent group j83);
  • Substituent group j83 is a C-C alkyl group, trifluoromethyl group, cyclopropyl group,
  • Xyl group, ethoxy group, methanesulfol group, ethanesulfol group, methylamino group, ethylamino group, dimethylamino group, jetylamino group, methylcarbol group, nitro group, fluoro group, and black mouth group A compound according to any one of (1) to (18), which is a group.
  • a halogeno C C alkyl group (wherein the halogeno C C alkyl group is 1 to 5 halo
  • halogeno C C alkoxy group (the halogeno C C alkoxy group has 1 to 5
  • R 5 is a hydrogen atom or a CC alkyl group
  • R 6 has the formula COR 8a [wherein R 8a is a C 1 -C alkoxy group, halogeno C 1 -C alkoxy
  • 1 6 1 c represents an alkoxy group), (c 1 -c cycloalkyl) (c 1 -c alkyl) oxy group, phenol
  • An aryloxy 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 C—C alkylamino group, a di (C—C
  • alkyl group is the same or different and the two alkyl groups together with the nitrogen atom of the amino group are selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom
  • a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms may be formed).
  • R 9a is a C—C alkyl group, a ferro (C—C alkyl) group,
  • An aryl 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 5- to 6-membered aromatic heterocyclyl group (the heterocyclyl group).
  • Group represents a chenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a triazolyl group, or a pyridyl group), or a substituted 5- to 6-membered aromatic heterocyclyl group (the heterocyclyl group includes a cetyl group, an imidazolyl group, An oxazolyl group, a thiazolyl group, a triazolyl group, or a pyridyl group, and the substituents are the same or different and are 1 to 2 groups selected from the substituent group a 1).
  • heterocyclyl group is Le
  • the heterocyclyl group represents a chenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a triazolyl group, or a pyridyl group, and the substituents are the same or different, and a is 1 to 2 groups selected from a 1);
  • R 7 is the formula — X 2a R 10a
  • R 1Qa is a formula — COR Ua [where R Ua is a hydroxyl group, a C—C alkoxy group, (C
  • the alkyl group together with the nitrogen atom of the amino group, forms a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur nuclear power. ), A hydroxylamino group, or hydroxyl (C-
  • R 12a is a C—C alkyl group, (C—C cycloalkyl) — (C—C
  • the alkyl group is the same or different, and the two alkyl groups together with the nitrogen atom of the amino group contain 1 to 3 atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom It may form a 5- to 7-membered saturated heterocyclyl group).
  • R 13a is a hydrogen atom, a C—C alkyl group, (C—C cyclo
  • R 14a is
  • X 2a is a single bond, a C 1 -C alkylene group, or a substituted C 1 -C alkylene group (the substituted
  • the groups are the same or different and are 1 to 2 groups selected from the substituent group ⁇ 1, and the two substituents may form an ethylene group or a trimethylene group together) Show.
  • a group having x 1 is a methylene group;
  • Y 1 is a phenyl group, a substituted phenol group (the substituents are the same or different and are 1 to 2 groups selected from the substituent group a 2), to a 5- to 6-membered aromatic Telocyclyl group (the heterocyclyl group represents pyrrolyl group, furyl group, chenyl group, imidazolyl group, oxazolyl group, thiazolyl group, pyridyl group or pyridazyl group), or substituted 5- to 6-membered aromatic heterocyclyl Group (the heterocyclyl group represents a pyrrolyl group, a furyl group, a chael group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a pyridyl group, or a pyridazinyl group, and the substituents may be the same or different; ⁇ 1 to 2 groups selected from 2);
  • Y 2 force phenyl group, substituted phenol group (the same or different substituents are 1 to 3 groups selected from substituent group ⁇ 1), indanyl group or tetrahydronaphthyl group (however, , cyclic group bonded to Upsilon 1 is a benzene ring), location ⁇ Ndaniru group or substitution tetrahydronaphthyl group (provided that a cyclic group bonded to Upsilon 1 is a benzene ring, those ⁇ substituent may be the same or different 5 to 6-membered aromatic heterocyclyl group (the heterocyclyl group is a pyrrolyl group, a furyl group, a phenyl group, an imidazolyl group, Oxazolyl group, thiazolyl group, pyridyl group, or pyrimidyl group), substituted 5- to 6-membered aromatic heterocyclyl group (the heterocyclyl group includes pyr
  • the cyclic group bonded to Y 1 is an aromatic ring, and the unsaturated heterocyclyl group includes indole group, dihydrobenzofuryl group, dihydrobenzozole group, tetrahydro group.
  • a quinolyl group or a chromal group) or a substituted 9 to 10-membered unsaturated heterocyclyl group (provided that the cyclic group bonded to Y 1 is an aromatic ring, and the unsaturated heterocyclyl group) Group represents an indole group, a dihydrobenzofuryl group, a dihydrobenzozoyl group, a tetrahydroquinolyl group, or a chromyl group, and the substituents may be the same or different, and the substituent group
  • the compounds described in 1 to a 3 groups) (1) is,
  • R 4 are the same or different and are a hydrogen atom or a C—C alkyl group.
  • R 5 is a hydrogen atom
  • R 6 has the formula 1 COR 8b [wherein R 8b is a C—C alkoxy group, halogeno C—C alkoxy
  • 1 4 2 6 represents a oxy group, a phenyl group, or a substituted phenoxy group (the substituents are the same or different and are one or two groups selected from the substituent group ⁇ 2). Or a group having
  • R 7 is the formula — X 2b R 10b
  • R 1Qb is a formula — COR Ub [where R Ub is a hydroxyl group, C—C alkoxy group, (C
  • R 12b is a CC alkyl group, (CC cycloalkyl) (C
  • X 2b represents a single bond, a methylene group, an ethylene group, or a substituted methylene group or a substituted ethylene group (the substituents may be the same or different and are 1 to 2 groups selected from the substituent group ⁇ 2). And the two substituents together may form an ethylene group or a trimethylene group).
  • X 1 is a methylene group
  • ⁇ 1 is a phenyl group, a substituted phenyl group (the substituent is one group selected from the substituent group a 3), a chael group, a pyridyl group, or a substituted chain. Or a substituted pyridyl group (the substituent is one group selected from the substituent group a 3); Y 2 force phenyl group, substituted phenol group (the substituents are the same or different and are one or two groups selected from the substituent group ⁇ 2), chael group, thiazolyl group, A pyridyl group, or a substituted chenyl group, a substituted thiazolyl group or a substituted pyridyl group (the substituents are the same or different and are one or two groups selected from the substituent group ⁇ 2) ( Compounds described in 1),
  • R 4 is the same or different and each represents a hydrogen atom, a fluoro group, or a group;
  • R 5 is a hydrogen atom
  • R 6 is a formula — COR 8e [where R & is a C—C alkoxy group or halogeno C—C
  • halogeno C—C alkoxy group is composed of 1 to 5 fluoro or
  • R 7 is the formula — X 2c R 10c
  • R 1Qc is a group having the formula — COR Uc (wherein R Uc represents a hydroxyl group, a methoxy group, or an ethoxy group), or
  • X 2e is a single bond, a methylene group, or a substituted methylene group (the substituent is two fluorine groups, and the two substituents may form an ethylene group together) Indicates.
  • X 1 is a methylene group
  • Y 1 is a phenol group
  • the compound according to (1) which is a Y 2 force phenol group or a substituted phenol group (the substituent is one group selected from the substituent group
  • R 4 is the same or different and each represents a hydrogen atom, a fluoro group, or a group;
  • R 5 is a hydrogen atom
  • R 6 is a group having the formula —COR 8d (wherein R 8d represents a C—C alkoxy group);
  • R 7 is the formula — X 2d R 1M
  • R 1M represents a group having the formula — COR Ud (wherein R 1 “represents a hydroxyl group)
  • X 2d represents a methylene group or a substituted methylene group (the two substituents together form an ethylene group).
  • X 1 is a methylene group
  • Y 1 is a phenol group
  • the compound according to (1) which is a Y 2 force phenol group or a substituted phenol group (the substituent is one group selected from the substituent group
  • R 5 is a hydrogen atom
  • R 6 is a formula — COR 8e [where R & is a C—C alkoxy group or halogeno C—C
  • halogeno C—C alkoxy group is composed of 1 to 5 fluoro or
  • R 7 is the formula — X 2c R 10c
  • R 1Qc is a group having the formula — COR Uc (wherein R Uc represents a hydroxyl group, a methoxy group, or an ethoxy group), or
  • X 2e is a single bond, a methylene group, or a substituted methylene group (the substituent is two fluorine groups, and the two substituents may form an ethylene group together) Indicates.
  • Y 1 is a phenol group
  • Y 2 force phenyl group, substituted phenol group (the substituents are the same or different and are one or two groups selected from the substituent group ⁇ 2), chael group, thiazolyl group, A pyridyl group, or a substituted chenyl group, a substituted thiazolyl group or a substituted pyridyl group (the substituents are the same or different and are one or two groups selected from the substituent group ⁇ 2) ( The compounds listed in 1) or
  • the present invention also provides:
  • a pharmaceutical composition comprising as an active ingredient the compound represented by the general formula (I) described in any one of (1) to (27) or a pharmacologically acceptable salt or ester thereof,
  • Arteriosclerosis Arteriosclerosis, atherosclerosis, arteriosclerosis caused by diabetes, hyperlipidemia, hypercholesterolemia, lipid-related disease, inflammatory disease, arteriosclerotic heart disease, cardiovascular disease, (28) a pharmaceutical composition for treating or preventing coronary artery disease or diabetes,
  • the present invention provides:
  • a compound represented by the general formula (I) described in any one of (1) to (27) or a pharmacologically acceptable salt or ester thereof; and an HMG-CoA reductase inhibitor, CE A pharmaceutical composition comprising, as an active ingredient, one or more pharmaceuticals selected from the group consisting of TP inhibitors and cholesterol absorption inhibitors,
  • HMG-CoA reductase inhibitor power Pharmaceutical composition described in (35), which is pravastatin, oral pastatin, sympastatin, flupastatin, cerivastatin, atorvastatin, pitapastatin, or rosuvastatin, or
  • the C C alkyl moiety is a straight or branched chain alkyl having 1 to 6 carbon atoms.
  • a methyl group or a propyl group more preferably a methyl group or an ethyl group, and most preferably a methyl group.
  • the “ru group” is the above-mentioned C C alkyl group substituted with 1 to 7 of the following halogeno groups,
  • fluoromethyl group difluoromethyl group, dichloromethyl group, dibromomethyl group
  • Trifluoromethyl group Trifluoromethyl group, trichloromethyl group, 2-fluoroethyl group, 2-bromoethyl group, 2-chloroethyl group, 2-iodoethyl group, 2,2-difluoroethyl group, 2,2,2-tri It may be a fluorethyl group, a trichlorodiethyl group, a pentafluoroethyl group, a 3-fluoropropyl group, a 3-chloropropyl group, a 4-fluorobutyl group, a 5-fluoropentyl group, or a 6-fluorohexyl group, Preferably, the halogeno CC alkyl group (the halo
  • Geno C C alkyl group is a C C alkyl group substituted with 1 to 5 halogeno groups
  • 1 4 1 4 Kill group is C 1 -C 4 alkyl substituted with 1 to 5 fluoro, black or bromo groups.
  • a hydroxyl group substituted with a C alkyl group for example, a methoxy group, an ethoxy group, 1
  • the “xy group” is the above-mentioned C C alkoxy group substituted with 1 to 7 of the following halogeno groups.
  • fluoromethoxy group difluoromethoxy group, dichloromethoxy group, dibromomethoxy group, trifluoromethoxy group, trichloromethoxy group, 2-fluoroethoxy group, 2-bromoethoxy group, 2-chloroethoxy group, 2 — Edoethoxy group, 2,2-Difluoroethoxy group, 2,2,2-Trifluoroethoxy group, Trichloro-epoxy group, Pentafluoroethoxy group, 3-Fluoropropoxy group, 3-Chloro-mouth It can be a propoxy group, a 4 fluorobutoxy group, a 5-fluoropentyloxy group, or a 6-fluorohexoxy group, A halogeno C 1 -C alkoxy group (the halogeno C 1 -C alkoxy group comprises 1 to 5
  • the halogeno C 1 -C alkoxy group is composed of 1 to 5 fluoro
  • ⁇ Group '' is a mercapto group substituted with the above C C alkyl group, for example, methylthio
  • thio group 14 is a thio group, more preferably a methylthio group or an ethylthio group, and most preferably a methylthio group.
  • Silicon group is a sulfiel group (one so-) substituted with the above-mentioned C C alkyl group
  • a tansulfiel group most preferably a methanesulfiel group.
  • methanesulfol group ethanesulfol group, 1 propanesulfol group, 2-propanesulfol 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-hexanesulfol group, 3-hexanesulfol group, 2-methyl-1-pentanesulfol group, 3-methyl-1-pentanesulfol group, 2-ethyl-1-butanes It can be a sulfonyl group, a 2,2-dimethyl 1-butanesulfol group, or a 2,3 di
  • a methanesulfol group or an ethanesulfol group is preferred, and a methanesulfol group is most preferred.
  • R 2 , R 3 , R 4 , R U , R 12 , substituent group ⁇ , and “c-c alkylamino group” in substituent group y were substituted with one of the above c-c alkyl groups
  • An amino group for example, a methylamino group, an ethylamino group, a propylamino group (for example, 1-propylamino group, 2-propylamino group), 1-butylamino group, 2-butylamino group, 2-methyl-1-propylamino group, 2 —Methyl-2-propylamino group, 1-pentylamino group, 2-pentylamino group, 3-pentylamino group, 2-methyl-2-butylamino group, 3-methyl-2-butylamino group, 1-hexylamino group, 2-hexylamino group, 3-hexylamino group Luamino group, 2-methyl-1 pentylamin
  • a c-c alkylamino group More preferred is a c-c alkylamino group, and more preferred is a methylamino group or
  • a tyramino group and most preferably a methylamino group.
  • Substituted amino groups such as a dimethylamino group, a methylethylamino group, a methylpropylamino group [eg, N— (lpropyl) N-methylamino group, etc.], a methylbutylamino group [eg, N (l— Butyl) -N-methylamino group, etc.], jetylamino group, ethylpropylamino group [eg, N- (1-propyl) -Nethylamino group, etc.], dipropylamino group [eg, di (1 propyl) amino group, di ( 2-propyl) amino group, etc.], di (1 butyl)
  • 3-methyl-2-pentyl) amino group di (4-methyl-2-pentyl) amino group, di (2,2-dimethyl-1-butyl) amino group, di (3,3 dimethyl-1-butyl) amino group, di (2,3 di Methyl (1-butyl) amino group or di (2-ethyl-1-butyl) amino group, preferably di (C—Calkyl) amino group (the alkyl groups are the same or different).
  • Ri more preferably, Jimechiruamino group, methyl E chill ⁇ amino group, methylpropylamino group, Jechiruamino group, E chill propylamino group, or a dipropylamino group, and more preferably, group other than R 11 Is a dimethylamino group or a jetylamino group, R 11 is a dimethylamino group or a methylethylamino group, and most preferably a dimethylamino group.
  • di (C—C alkyl) amino group means two alkyl groups
  • This 5- to 7-membered saturated heterocyclyl group includes, for example, azetidyl group, pyrrolidyl group, piperidyl group, piperazil group, morpholinyl group, thiomorpholinyl group
  • a perhydroazepine group preferably a 5- or 6-membered saturated heterocyclyl group containing 1 to 2 atoms selected from the group consisting of a nitrogen atom, an oxygen atom and sulfur nuclear power. More preferably, pyrrolidyl group, piperidyl group, morpholinyl group, Is a thiomorpholinyl group, more preferably a piperidyl group or a morpholinyl group.
  • R 2 , R 3 , R 4 , Substituent group a, Substituent group ⁇ , and “Halogeno group” in Substituent group y, and the halogeno moiety in each substituent include a fluoro group, a chloro group, It may be a bromo group or a iodine group, preferably a fluoro group, a black-or-mouth group or a bromine group, more preferably a fluoro group or a black-and-back group, and most preferably a fluoro group or is there.
  • the "C 1 -C alkoxy group" in R 8 of the general formula (I) is a C 1 -C alkyl group described below.
  • 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-octyloxy, 4-octyloxy, 3-ethyloxy group, 4-hexyloxy group, 4-noroxy
  • Alkoxy group (especially 2-propoxy group, 2-methyl-2-propoxy group or 2-methyl-2-butoxy group), most preferably 2-methyl-2-propoxy group .
  • R 8 of the general formula (I) is represented by 1 to 7 halo
  • a halogeno C—C alkoxy group is substituted with 1 to 5 fluoro, black or bromo groups.
  • a thioloxy group most preferably a cyclopropylmethyloxy group or Rumethyloxy group.
  • it is a benzyloxy group.
  • the ⁇ group '' is a hydroxyl group substituted with the following cC cycloalkyl group, for example,
  • It may be a chloropropyloxy group, a cyclobutyloxy group, a cyclopentyloxy group, a cyclohexyloxy group, a cycloheptyloxy group, or a cyclooctyloxy group, and preferably a C-C cycloalkyloxy group.
  • a xy group, more preferably C—C cycloalkyl It is a kiloxy group, and is most preferably a cyclopropyloxy group.
  • C—C alkoxy group in R 8 of the general formula (I) is 2 to 10 carbon atoms
  • a hydroxyl group substituted with a linear or branched alkenyl group (which may have one or more carbon-carbon double bonds) having, for example, a butoxy group, a 2-propyloxy group ( Aryloxy group), 2-butenyloxy group, 2-penteroxy group, 3-methyl-2-buturoxy group, 2-hexoxyloxy group, 3-methyl-2-penteroxy group, 2-heptuloxy group, 3-ethyl-2-penteroxy group, 2- Otaturoxy group, 3 ethyl-2-hexoxyloxy group, 2 non-oxyl group, or 2-deoxyloxy group, preferably CC alkyl group, more
  • Preferred is a C—C alkenyl group, and more preferred is a C—C alkenyl group.
  • C—C alkyloxy group in R 8 of the general formula (I) is 2 to 10 carbon atoms
  • a hydroxyl group substituted with a linear or branched alkynyl group (which may have one or more carbon-carbon triple bonds) having, for example, an ethuroxy group, a 2-propyloxy group, 2 —Butuloxy group, 2-pentyloxy group, 2-hexoxyloxy group, 2-heptyloxy group, 2-octyloxy group, 2-nonoxyloxy group, or 2-decyloxy group Possible, preferably a CC alkyl group, and more
  • Preferred is a C—C alkynyl group, and more preferred is a C—C alkynyl group.
  • the C C alkyl part of the “1 10 1 10 mino group” and the C C alkyl part of each substituent are 1
  • 1 10 1 is a linear or branched alkyl group having 10 to 10 carbon atoms, such as methyl, ethyl, 1 propyl, 2-propyl, 1 butyl, 2-butyl, 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, 3-heptyl group, 4 to 1-heptyl group, 3-methyl-3 Xyl, 3-ethyl 3-pentyl, 3-octyl, 4-octyl, 3-ethyl 3-hexyl, 4-n
  • C-C alkylamino group for R 8 in the general formula (I) represents one CC alkyl group.
  • amino group substituted with a 10 group for example, methylamino group, ethylamino group, 1 propylamino group, 2-propylamino group, 1-butylamino group, 2-butylamino 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-butylamino group, 2-methyl-2-butylamino group, 1 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 Ptylamino group, 3-heptylamino group, 4-heptylamino group, 3-
  • Preferred is a C—C alkylamino group, and even more preferred is a C—C alkylamino group.
  • Tylethylamino group methylpropylamino group [eg, N- (1-propyl) -N-methylamino group, etc.], methylptylamino group [eg, 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-tetraheptyl) amino group, N-methyl Tilu N— [4 (1 propyl) -4 monoheptyl] amino group, jetylamino group, ethyl propylamino group [for example, N— (1-propyl) —N eth
  • di (2-methyl 1-propyl) amino group di (2-methyl 2-propyl) amino group, N- (l-butyl) -N- (2-methyl-2-propyl) amino group, dipentyl Amino group [eg, di (1 pentyl) amino group, di (2 pentyl) amino group, di (3 pentyl) amino group, etc.], di (2-methyl-1-butyl) amino group, di (2-ethyl-1-propyl) ) Amino group, N— (1-pentyl) N— (2-methyl 2-propyl) amino group, dihexylamino group [eg, di (1 hexyl) amino group, di (2 hexyl) amino group Di (3-hexyl) amino group, etc.], di (2-methyl 1-pentyl) amino group, di (3-methyl 1-pentyl) amino group, di (4-methyl) -1 pentyl) amino group, di (2-methyl-2-pentyl) amino group
  • 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- (l-butyl) mono-N- (2-methyl-2-propyl) amino group, or di (2-methyl-2-propyl) amino group.
  • di (C—C alkyl) amino group is 2
  • the 5- to 7-membered saturated heterocyclyl group that may be formed can be, for example, a pyrrolidyl group, piperidyl group, piperazyl group, morpholinyl group, thiomorpholinyl group, or perhydroazepine group, Preferred is a 5- to 6-membered saturated heterocyclyl group containing 1 to 2 atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur nuclear atom, and more preferred are a pyrrolidinyl group and a piperidyl group.
  • a morpholinyl group or a thiomorpholinyl group more preferably a piperidyl group or a morpholinyl group.
  • the “ferro- (C—C alkyl) group” in R 6 and R 9 in the general formula (I) represents one phenol.
  • C alkyl group, more preferably a benzyl group or a 1-phenylethyl group.
  • the aromatic heterocyclyl moiety is a 5- to 6-membered aromatic heterocyclic group containing 1 to 4 atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, such as a furyl group or a chenyl group.
  • Pyrrolyl group pyrazolyl group, imidazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, triazolyl group, oxadiazolyl group, thiadiazolyl group, tetrazolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, or pyradyl group It can be.
  • the 5- to 6-membered aromatic heterocyclyl group in R 6 and R 9 is preferably a chenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a triazolyl group, or a pyridyl group, and more preferably a chenyl group. Or a pyridyl group, most preferably a pyridyl group.
  • the 5- to 6-membered aromatic heterocyclyl group in Y 1 is preferably a pyrrolyl group, a furyl group, a chenyl group, an imidazolyl group, an oxazolyl group, a thiazolyl group, a pyridyl group, or a pyridazyl group, and more preferably.
  • 16 groups such as furylmethyl group, cherylmethyl group, pyrrolylmethyl group, virazolylmethyl group, imidazolylmethyl group, imidazolylethyl group, imidazolylpropyl group, imidazolylbutyl group, oxazolylmethyl group, oxaxylmethyl group, Zolylethyl group, oxazolylpropyl group, isoxazolylmethyl group, thiazolylmethyl group, thiazolylethyl group, thiazolylpropyl group, isothiazolylmethyl group, 1,2,3 oxaziazolylmethyl group, 1,2,3 thiadiazolylmethyl group, triazolylmethyl group, triazolylethyl group, tetrazolylmethyl group, biarylmethyl group, pyridylmethyl group, pyridylethyl group, pyridylpropyl group, pyriyl Dibutyl group,
  • cyclopropylmethoxy group cyclobutylmethoxy group
  • cyclopentylmethoxy group cyclopropylmethoxy group
  • ⁇ 3 8 1 6 amino group '' means the above c -c alkyl substituted with one c -c cycloalkyl group below.
  • 3 8 1 6 amino group for example, cyclopropylmethylamino group, cyclobutylmethylamino group, cyclopentylmethylamino group, cyclohexylmethylamino group, cyclohexylmethylamino group, 1-cyclopropylene Tyramino group, 2-cyclopropylethylamino group, 2-cyclobutylethylamino group, 2-cyclopentylethylamino group, 2-cyclohexylethylamino group, 2 cycloheptylethylamino group Group, 3 cyclopropyl 1-propylamino group, 2-cyclopropyl 1-propylamino group, 2-cyclopropyl 1-propylamino group, 3 cyclobutyl 1-propylamino group, 3 cyclopentyl-1-propylamino group, 3 Cyclohexyl 1-propylamino group, 4 Cyclopropyl mono 1-Butylamino
  • ⁇ 3 8 alkylamino group '' is an amino group substituted with one of the following C C cycloalkyl groups,
  • it can be a cyclopropylamino group, a cyclobutylamino group, a cyclopentylamino group, a cyclohexylamino group, a cycloheptylamino group, or a cyclooctylamino group.
  • a C—C cycloalkylamino group Preferably a C—C cycloalkylamino group, and more preferably a C—C cycloalkyl group.
  • 3 6 3 4 is a killed amino group, most preferably a cyclopropylamino group.
  • Amino group is the same or different two (C—C cycloalkyl) one (C—C
  • 3 8 1 6 kill) group for example, di (cyclopropylmethyl) amino group, N-cyclopropylmethyl-N-cyclobutylmethylamino group, N-cyclopropylmethyl-N- Cyclopentylmethylamino group, N-cyclopropylmethyl-N-cyclohexylmethylamino group, N cyclopropylmethyl-N cycloheptylmethylamino group, N cyclopropylmethyl-N-cyclomethylmethylamino group, N-cyclopropylmethyl-N-cyclopropylethylamino group, N-cyclopropylmethyl N— (3-cyclopropyl-1-propyl) amino group, di (cyclobutylmethyl) amino group, di (cyclopentylmethyl) amino group Di (cyclohexylmethyl) amino group, di (cycloheptylmethyl) amino group, or di (cyclooctylmethyl) amino group
  • ⁇ 3 8 alkyl) amino group '' is substituted with the same or different two C C cycloalkyl groups described below.
  • dicyclopropylamino group ⁇ cyclopropyl ⁇ cyclobutylamino group, ⁇ cyclopropyl ⁇ cyclopentylamino group, ⁇ cyclopropyl- ⁇ -cyclohexylamino group, ⁇ -cyclopropyl- ⁇ -Cycloheptylamino Group, N cyclopropyl N cyclooctylamino group, dicyclobutylamino group, dicyclopentylamino group, dicyclohexylamino group, dicycloheptylamino group, or dicyclotylamino group, preferably Is a di (C 1 -C cycloalkyl) amino group
  • a di (C—C cycloalkyl) amino group More preferably a dicyclopropyl.
  • N cyclopropylmethyl-N-methylamino group N cyclopropylmethyl-N ethylamino group, N cyclopropylmethyl-N propylamino group, N cyclopropylmethyl N butylamino group, N cyclopropylmethyl N pentylamino group, N Cyclopropylmethyl N-hexylamino group, N-cyclopropylethyl-N-methylamino group, N (3 cyclopropyl-1-propyl) -N-methylamino group, N-cyclobutylmethyl N-methylamino group, N-cyclopentylmethyl N-methylamino group, N-cyclohexylmethyl-N-methylamino group, N-cycloheptylmethyl N-methylamino group, or N-cyclooctylmethyl-N-methylamino group, preferably N-[(C-C cycloalkyl) — (
  • N— (C—C alkyl) amino group more preferably N — [(C 1 -C cyclohexane
  • R u , R 12 , substituent group j8, and substituent group ⁇ are represented by “N— (C—C
  • N— (C—C cycloalkyl) amino refers to one (C—C cycloalkyl)
  • N— (C—C cycloalkyl) amino group more preferably N — [(C—C cycloalkyl)
  • Amino group or hydroxyl (ethyl) amino group most preferably a hydroxylmethylamino group.
  • C C alkyl group for example, cyclopropylmethyl group, cyclobutylmethyl group
  • cyclopropylmethyl group Even more preferred is a cyclopropylmethyl group or a cyclopropylethyl group, and most preferred is a cyclopropylmethyl group.
  • the ⁇ group '' is a cyclic alkyl group having 3 to 8 carbon atoms, and can be, for example, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, or a cyclooctyl group, Preferred is a C—C cycloalkyl group, and more preferred.
  • it is a c-c cycloalkyl group, more preferably, a c cycloalkyl group (
  • the "C—C alkylene group" in X 2 of the general formula (I) has 1 to 4 carbon atoms.
  • Alkylene groups such as methylene group, ethylene group [(CH 3) 2, methylmethylene
  • Suitable is a methylene group or ethylene group, and most preferred is a methylene group.
  • the "6- to 10-membered aryl group" in Y 2 of the general formula (I) is a 6- to 10-membered aromatic hydrocarbon group, for example, a phenyl group or a naphthyl group, Is a phenyl group.
  • the "9 to 10-membered unsaturated cyclic hydrocarbon group" in Y 2 of the general formula (I) is a group obtained by partially reducing a 9 to 10-membered aromatic hydrocarbon group, the hydrogen group a group a cyclic group bonded to Nag Upsilon 1 is a phenyl group.
  • the 9 to 10-membered unsaturated cyclic hydrocarbon group can be, for example, an indanyl group or a tetrahydronaphthyl group, and is preferably an indanyl group.
  • the "5- to 10-membered aromatic heterocyclyl group" in ⁇ 2 of the general formula (I) includes 1 to 4 atoms selected from the group consisting of a nitrogen atom, an oxygen atom, and a sulfur nuclear power.
  • 10-membered aromatic heterocyclic group for example, furyl group, chael group, pyrrolyl group, pyrazolyl group, imidazolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, triazolyl group, oxadiazolyl group, Thiadiazolyl group, tetrazolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, virazil group, azepiyl group, azosinyl group, azodiyl group, indolyl group, benzofuryl group, benzochel group, benzoimidazolyl Group, benzo
  • the "9 to 10-membered unsaturated heterocyclyl group" in ⁇ 2 of the general formula (I) is a group in which a 9 to 10-membered aromatic heterocyclyl group is partially reduced and is a saturated heterocyclyl group. Then, ⁇ 1 represents a group in which the cyclic group bonded to 1 is an aromatic ring group.
  • the 9 to 10-membered unsaturated heterocyclyl group can be, for example, an indole group, a dihydrobenzofuryl group, a dihydrobenzozoyl group, a tetrahydroquinolyl group, or a chromyl group, and preferably An indole group, a dihydrobenzofuryl group, or a dihydrobenzozo group.
  • the C C alkyl moiety is a straight or branched chain alkyl having 1 to 4 carbon atoms.
  • a c-c alkyl group more preferably a methyl group or
  • a til group most preferably a methyl group.
  • the "nologeno CC alkyl group" in the substituent group ⁇ of the general formula (I) represents 1 to 5 or more
  • a c C alkyl group substituted with a halogeno group such as a fluoromethyl group
  • Difluoromethyl group Difluoromethyl 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, 2,2,2 trichloroethyl group, pentafluoroethyl group, 3-fluoropropyl group, 3-chloropropyl group, 3, 3, 3-trifluoro group A propyl group, a 4 fluorobutyl group, or a 4,4,4 trifluorobutyl group, preferably a halogeno C 1 -C alkyl group (the halogeno
  • the C 1 -C alkyl group is a C 1 -C alkyl group substituted with 1 to 5 halogeno groups.
  • a trifluoromethyl group More preferably a trifluoromethyl group, 2,2,2-trifluoroethyl group, or a pentafluoroethyl group, and most preferably trifluoromethyl group. It is a group.
  • alkyl group for example, methoxy group, ethoxy group, 1-propyloxy group, 2-propoxy group, 1-butoxy group, 2-butoxy group, or 2-methyl-2 —A propoxy group, preferably a C—C alkoxy group, more preferably a methoxy group.
  • ⁇ 16 group '' is the above-mentioned C C alkyl group substituted with one hydroxyl group, for example,
  • a hydroxyethyl group or a hydroxypropyl group more preferably a hydroxymethyl group or a hydroxyethyl group, and most preferably a hydroxymethyl group.
  • the "carboxy (C 1 -C alkyl) group" in the substituent group ⁇ of the general formula (I) is a single carboxyl group.
  • methoxycarboromethyl group for example, methoxycarboromethyl group, ethoxycarboromethyl group, propoxycarboromethyl group, butoxycarboromethyl group, pentyloxyporomethyl group, hexyloxycarboromethyl group, It may be a methoxycarbolethyl group, a methoxycarbolpropyl group, a methoxycarbolbutyl group, a methoxycarbonylpentyl group, or a methoxycarboxyl group, and preferably
  • It is a chloromethyl group or a methoxycarboruethyl group, and most preferably a methoxycarboromethyl group.
  • the "C C alkylene group" in the substituent group j8 of the general formula (I) is a group of 2 to 7 carbon atoms.
  • a straight chain or branched chain alkenyl group (which may have one or more carbon-carbon double bonds) having, for example, a bur group, a 2-probe group (aryl group), 2 -Butul group, 2-pentyl group, 3-methyl-2 butyr group, 2 hexyl group, 3 methyl 2-pental group, 2 heptul group, or 3 ethyl 2-pentyl group, Preferred is a C—C alkenyl group, and more preferred is a C—C alkenyl group.
  • the “CC alkyl group” in the substituent group j8 of the general formula (I) is a group of 2 to 7 carbon atoms.
  • Straight chain or branched chain alkynyl group (which may have one or more carbon-carbon triple bonds), such as an ethur group, 2-propyl group, 2-butur group, 2- It can be a pentyl group, a 2-hexyl group, or a 2-heptyl group, preferably C
  • the carbon atom of the boramino group (one C0NH—) is substituted with one of the above C C alkyl groups.
  • methyl carbolumino group ethyl carbolumino group, (1 propyl) carbolumino group, (2-propyl) carbolumino group, (1-butyl) carboamino group, (2- Butyl) carbolamino group, (2-methyl-1-propyl) carboamino group, (2-methyl-2-propyl) carbolamino group, (1 pentyl) carbolamino group, or (1 hexyl) It can be a carbo-lumino group, preferably (C—C alkyl)
  • a carbolumino group more preferably a (C—C alkyl) carbolumino group.
  • methylcarbolumino group More preferred is a methylcarbolumino group or an ethylcarbolumino group, and most preferred is a methylcarbonylamino group.
  • C alkyl) amino group means that the —C alkyl) carbo-lumino group has a nitrogen atom of 1
  • C cycloalkyl) amino refers to the nitrogen atom of —C alkyl) carbo-lamino group above.
  • a group in which the child is substituted with one of the above C C cycloalkyl groups for example, N methyl
  • a methanesulfo-lamino group or an ethanesulfo-lamino group is preferably a methanesulfo-lumino group.
  • Amino group N-methanesulfurol-N ethylamine group, N-methanesulfurol-N N-pyramino group, N-methanesulfurol-N butyramino group, N-methanesulfurol-N N-pentylamino group, N-methanesulfol group 1 N-hexylamino group, N ethanesulfurol N-methylamino group, N-propanesulfurol group N-methylamino group, N-butansulfurol group N-methylamino group, N-pentanesulfurol group N-methylamino group, or May be an N-hexanesulfo-N-methylamino group, preferably N— (C 1 -C
  • amino group substituted with a C 1 -C cycloalkyl group for example, N-methanesulfol
  • the "(CC alkyl) carbol group" in the substituent group ⁇ of the general formula (I) represents one of the above
  • a carbo group substituted with a C C alkyl group (one CO 2), for example methyl
  • Methylaminocarbol group Methylaminocarbol group, ethylaminocarbol group, (1 propylamino) carbol group, (2-propylamino) carbonyl group, (1-butylamino) carbonyl group, (2-butylamino) carbole- Group, (2-methyl-1-propylamino) carbol group, (2-methyl-2-propylamino) carbol group, (1 pentylamino) carbol group, or (1 hexylamino) carbonyl group.
  • (CC cycloalkylamino) carbol group in the substituent group ⁇ of the general formula (I) is
  • a cyclopropylamino carbo yl group, a cyclo butyl amino carbo ol group, a cyclopentyl amino carbo ol group, a cyclohexyl amino carbo ol group, a cyclo heptyl amino carbo ol group, or can be a cyclooctylaminocarbol group, preferably
  • a C—C cycloalkylaminocarbo yl group more preferably a C—C cycloalkyl group.
  • 3 6 3 4 is a luminocarbo group, most preferably a cyclopropylamino carbo group.
  • dimethylaminocarbol group (N-methyl-Nethylamino) carbol group, (N-methylN-propylamino) carbol group [for example, [N- (1 propyl) N-methylamino] carbol Group], (N-methyl-N-butylamino) carbol group [for example, [N- (l-butyl) -N-methylamino] carbol group, etc.], (N-methyl-N-pentylamino) carbol Group, (N-methyl-N-hexylamino) carbol group, jetylaminocarbonyl group, dipropylaminocarbon group [for example, di (1-propyl) aminocarbonyl group, di (2-propyl) aminocarbol group, etc.
  • a di (C—C alkyl) aminocarbo group (the alkyl group is
  • the two alkyl groups are the same or different), more preferably a dimethylaminocarbonyl group or a dimethylaminocarbo ol group, and most preferably a dimethylaminocarbo ol group.
  • the di (C C alkyl) aminocarbo group the two alkyl groups are
  • the di (C—C alkyl) aminocarbol group is, for example, pyrrolidyl.
  • It may be a carbo yl group, a piperidyl carbo ol group, a piperazyl carbo ol group, a morpho carbonyl carbonyl group, or a thiomorpholinyl carbo yl group, preferably a pyrrolidyl- A rucarbonyl group, a piperidylcarbol group, or a morpholylcarbol group.
  • aminocarbol group refers to one N— (C—C cycloalkyl) N— (C—C
  • N cyclopropyl N-methylamino carbo ol group N cyclopropyl N ethylamino carbo ol group
  • N Cyclopropyl-N-propylaminocarbol group N cyclopropyl N butylamino carbo ol group
  • N cyclopropyl N pentylamino carbo ol group N cyclopropyl-N hexylamino carbo ol group
  • N-Cyclobutyl-N-methylaminocarbonyl group N-Cyclopentyl N-methylaminocarbole group
  • N-Cyclohexyl group N-Methylaminocarbol group
  • N cyclooctyl-N-methylaminocarbo ol group an N cyclooctyl-N-methylaminocarbo o
  • a sulfonyl group more preferably N— (C—C cycloalkyl) N— (C—C alkyl).
  • It is a tyraminocarbo group, and is most preferably an N cyclopropyl-N-methylaminocarbonyl group.
  • a C C alkyl group substituted with one C C alkoxy group for example
  • a (C—C alkoxy) (C—C alkyl) group is preferably a (C—C alkoxy) (C—C alkyl) group, more preferably a (C—C alkyl) group.
  • amino (C-C alkyl) group in the substituent group ⁇ of the general formula (I) is one amino group.
  • a substituted C C alkyl group such as an aminomethyl group, an aminoethyl group,
  • Amino (1-propyl) group Amino (2-propyl) group, Amino (1-butyl) group, Amino (2-butyl) Group), an amino (2-methyl 1-propyl) group, an amino (2-methyl 2-propyl) group, an amino (1 pentyl) group, or an amino (1 hexyl) group, preferably Amino (C -C
  • alkyl 14 alkyl group, more preferably an amino (c-c alkyl) group (especially an aminomethyl group,
  • aminoethyl group or an aminopropyl group more preferably an aminomethyl group or an aminoethyl group, and most preferably an aminomethyl group.
  • methylaminomethyl group ethylaminomethyl group, propylaminomethyl group, butyraminomethyl group, pentylaminomethyl group, hexylaminomethyl group, methylaminoethyl group, methylaminopropyl group, It can be a methylaminobutyl group, a methylaminopentyl group, or a methylaminohexyl group, preferably (C 1 -C alkylamino)-(C 1 -C
  • a methylaminomethyl group or a methylaminoethyl group More preferably a methylaminomethyl group or a methylaminoethyl group, and most preferably a methylaminomethyl group.
  • 3 8 16 groups such as cyclopropylaminomethyl group, cyclobutylaminomethyl group, cyclopentylaminomethyl group, cyclohexylaminomethyl group, cycloheptylaminomethyl group, It may be a cutylaminomethyl group, a cyclopropylaminoethyl group, a cyclopropylaminopropyl group, a cyclopropylaminobutyl group, a cyclopropylaminopentyl group, or a cyclopropylaminopentyl group, preferably (C — C cycloalkyl amino
  • ⁇ 1 6 1 6 group '' is a c -c alkyl group substituted by one di (c -c alkyl) amino group.
  • dimethylaminomethyl group (N-methyl-Nethylamino) methyl group, (N-methyl-N-propylamino) methyl group, (N-methyl-N-butylamino) methyl group, (N— Methyl N pentylamino) methyl group, (N methyl N hexylamino) methyl group, jetylaminomethyl group, dimethylaminoethyl group, dimethylaminopropyl group, dimethylaminobutyl group, dimethylaminopentyl group, or dimethylaminohexyl group
  • a di (C 1 -C alkyl) amino- (C 1 -C alkyl) group (the alkyl group).
  • alkyl groups are the same or different, more preferably a dimethylaminomethyl group or a dimethylaminoethyl group, and most preferably a dimethylaminomethyl group.
  • di (C—C alkyl) amino- (C—C alkyl) group is the di (C—C alkyl) amino- (C—C alkyl) group.
  • the alkyl group together with the nitrogen atom of the amino group, forms a 5- to 7-membered saturated heterocyclyl group containing 1 to 3 atoms selected from the group consisting of nitrogen atom, oxygen atom and sulfur nuclear power.
  • the di (C—C alkyl) aminocarbol group
  • a pyrrolidylmethyl group a piperidylmethyl group, a piperazylmethyl group, a morpholinylmethyl group, or a thiomorpholinylmethyl group, preferably a pyrrolidylmethyl group, a piperidylmethyl group, or a mole It is a folinylmethyl group.
  • 3 8 1 6 kill) group refers to a C—C alkyl substituted with one di (C—C cycloalkyl) amino group as described above.
  • 3 8 1 6 kill group for example, dicyclopropylaminomethyl group, ( ⁇ cyclopropyl- ⁇ cyclobutylamino) methyl group, ( ⁇ cyclopropyl ⁇ cyclopentylamino) methyl group, ( ⁇ cyclopropyl ⁇ cyclohexane) Xylamino) methyl group, ( ⁇ cyclopropyl-1-cycloheptylamino) methyl group, ( ⁇ cyclopropyl ⁇ cyclooctylamino) methyl group, dicyclobutylaminomethyl group, dicyclopentylaminomethyl group, dicyclohexene Xylaminomethyl group, dicycloheptylaminomethyl group, dicyclotylaminomethyl group, dicyclopropylaminoethyl group, dicyclopropylaminopropyl group, dicyclopropylaminobutyl group, dicyclopropylaminopentyl group, Alternatively, it can be
  • C 1 -C alkyl groups substituted with N- (C 1 -C alkyl) amino groups such as (N-cyclopropyl-N-methylamino) methyl group, (N cyclopropyl N ethylamino) methyl group, (N cyclo Propyl-N-propylamino) methyl group, (N-cyclopropyl-N-butylamino) methyl group, (N-cyclopropyl-N-pentylamino) methyl group, (N-cyclopropyl-N-hexylamino) methyl group, (N-cyclobutyl-N-methylamino) methyl group, (N cyclopentyl-N-methylamino) methyl group, (N cyclohexyl N-methylamino) methyl group, (N cycloheptyl N-methylamino) methyl group, (N -cyclooctyl-N-methylamino)

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Abstract

Il est exposé un excellent modulateur des récepteurs LXR. L'invention concerne un composé représenté par la formule générale (I) : (I) dans laquelle R1, R2, R3 et R4 sont chacun H, un alkyle qui peut être substitué, OH, un alcoxy qui peut être substitué, un amino qui peut être substitué, un halogéno, un phényle ou similaire ; R5 est H ou un alkyle ; R6 est -COR8 (où R8 est un alcoxy qui peut être substitué, un phényloxy qui peut être substitué, un amino qui peut être substitué ou similaire), -SO2R9 (où R9 est un alkyle qui peut être substitué, un phényle qui peut être substitué ou un groupe hétérocyclique qui peut être substitué) ou un alkyle qui peut être substitué ; R7 est -X2R10 [où R10 est -COR11 (où R11 est OH, un alcoxy qui peut être substitué ou un amino qui peut être substitué), -SO2R12 (où R12 est un alkyle qui peut être substitué ou un amino qui peut être substitué), -N(R13)COR14 (où R13 est H ou un alkyle qui peut être substitué ; R14 est H ou un alkyle qui peut être substitué), -N(R13)SO2R15 (où R13 est tel que défini ci-dessus ; R15 est un alkyle qui peut être substitué) ou un tétrazol-5-yle ; et X2 est une liaison simple ou un alkylène qui peut être substitué] ; X1 est un méthylène qui peut être substitué ; Y1 est un phényle qui peut être substitué ou un groupe hétérocyclique qui peut être substitué ; et Y2 est un aryle qui peut être substitué, un groupe hétérocyclique qui peut être substitué ou similaire.
PCT/JP2006/307187 2005-04-07 2006-04-05 Composé indole substitué Ceased WO2006109633A1 (fr)

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