WO2008067709A1

WO2008067709A1 - Substituted cyclobutane compounds, preparation methods and pharmaceutical uses thereof

Info

Publication number: WO2008067709A1
Application number: PCT/CN2007/002768
Authority: WO
Inventors: Mingwei Wang; Na Li; Qing Liu; Lilin Lin; Yueyun Zhang; Jiayu Liao
Original assignee: Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences
Priority date: 2006-12-05
Filing date: 2007-09-19
Publication date: 2008-06-12
Also published as: CN101195612B; CN101195612A

Abstract

Substituted cyclobutane compounds represented by formula I or II. The preparation method of these compounds and uses thereof as glucagons like peptide-1 receptor(GLP-1R) regulators for preventing and/or treatment of metabolic disorders, which include but not limit to diabetes, insulin-resistance and obesity etc., cardiovascular diseases and neurodegenerative diseases such as Alzheimer's diseases etc..

Description

Compound with substituted cyclobutane structure, preparation method thereof and medical use thereof

The present invention relates to a compound having a substituted cyclobutane structure, a preparation method thereof, and a glucagon-like peptide

Glucagon like peptide-1 receptor (GLP-1R) modulators prevent and/or treat metabolic disorders (including but not limited to diabetes, insulin resistance and obesity, etc.), cardiovascular disease, neurodegenerative Medical use of diseases such as Alzheimer's disease.

Background technique

Disorders of glucose metabolism, especially diabetes, have become a major threat to human health and life in modern society. It is predicted that diabetes patients worldwide are increasing at a rate of 6% per year. By the end of 2006, there were 320 million patients (China's '60 million people, ranking second). Diabetes is a group of clinical syndromes caused by the interaction of genetic and environmental factors. It is mainly divided into type 1 and type 2. The basic pathophysiology of type 1 diabetes is absolute insulin secretion, and clinical treatment is mainly supplemented with insulin. It is also known as insulin-dependent diabetes. Type 2 diabetes accounts for more than 95% of the diseased population. Clinical studies have found that most patients with type 2 diabetes can synthesize normal or even excess insulin, but the sensitivity of target cells to insulin is reduced (also known as "insulin resistance"). Relatively insufficient insulin, also known as non-insulin dependent diabetes. Insulin resistance is a key factor in the development and progression of type 2 diabetes. Therapeutic drugs for type 2 diabetes include sulfonylureas, biguanides, other insulin sensitizers, and ancillary measures. After the sulfonylurea hypoglycemic agent binds to the receptor of the pancreatic β-cell membrane, the potassium ion channel is closed, and the potassium ion efflux is blocked, which leads to depolarization of the cell membrane, causing the Ca ²⁺ channel to be released, resulting in extracellular calcium influx. The increase in intracellular calcium concentration triggers the release of insulin. According to its advent, it was divided into two generations, the first generation such as toluene propyl propyl urea, the second generation including glibenclamide (glibenclamide), gliclazide (Damecon), glipizide (mepyrazin) ) and gliclazide (sugar leveling) and the like. The biguanide hypoglycemic agent can suppress appetite, increase the binding of insulin to the receptor, promote the anaerobic glycolysis of glucose, inhibit tissue respiration, and inhibit hepatic gluconeogenesis. Mainly there are metformin, phenformin and butyl bismuth. Other hypoglycemic agents mainly include Thiazolidinediones (such as troglitazone, rosiglitazone, pioglitazone, etc.), P 3-adrenergic receptor modulators, glucagon receptor antagonists, Fatty acid metabolism interfering drugs, α-glycosidase inhibitors (such as acarbose, voglibose, miglitol, etc.) and aldose reductase inhibitors.

Glucagon like peptide-1 receptor (GLP-1R) belongs to type B G protein-coupled receptor (GPCR). When the body ingests nutrients, the gutagonal peptide-1 (GLP-1) released by the enteroendocrine cells is activated by highly specific binding to GLP-1R. It stimulates insulin secretion, inhibits the production of glucagon, and lowers postprandial blood glucose and maintains it at a constant level. Under physiological conditions, the effect of GLP-1 on insulin secretion is dependent on blood glucose levels, and hypoglycemia does not occur due to continued secretion. GLP-1 also promotes proliferation and differentiation of sputum cells, as well as neuromodulation, delaying gastric emptying and reducing appetite. In vitro, GLP-1 promotes differentiation of embryonic stem cells into islets A secretory cell-like cell (J Endocrinol. 2005, 186: 343-52). GLP-1 acts on the central body to promote cell survival and reduce apoptosis, reduce the neurotoxicity of amyloid peptides, inhibit the progression of neurodegenerative diseases, and promote learning and memory. Therefore, it has recently been proposed to use GLP-1 for Alzheimer's. Treatment of the disease (Ann NY Acad Sci, 2004, 1035: 290-315; Nat Med, 2003, 9: 1173-1179; Curr Alzheimer Res, 2005, 2: 377-385; J Pharmacol Exp Ther, 2002, 302: 881 - 888). In addition, GLP-1 also plays an important role in the cardiovascular system. It has the effect of lowering blood pressure and dilating blood vessels. Acute injection of GLP-1 can improve left ventricular systolic function in cardiac hypertrophy experiments. It also reduces myocardial cell damage in the presence of myocardial ischemia and reperfusion (J. Hypertens, 2003, 21: 1125 - 1135; Am J Physiol Endocrinol Metab, 2004, 287: E1209 - E1215; Circulation, 2004, 110 : 955 - 961 ; Diabetes, 2005, 54 : 146 - 151). Due to the above-mentioned clear physiological effects, since the discovery of this target in the mid-1980s, the search for small molecule agonists of GLP-1R has been a research hotspot of many new drug development institutions in the world.

A number of internationally renowned multinational pharmaceutical companies are in the process of inventing GLP-1 innovative drugs, such as the GLP-1 derivative developed by Danovo Nordisk in Denmark (trade name Liraglutide; entering Phase III clinical trials) and Amylin Pharmaceuticals and Lilly in the United States. The company's joint development of the GLP-1 analogue Exendin-4 (trade name Exenatide; has been approved for listing in April last year, this year's sales are expected to exceed $1 billion). In addition to GLP-1 and its peptide analogs, there have been no reports of successful development of non-peptide small molecule GLP-1R agonists. Due to the inconvenient oral administration of peptide drugs, the search for non-peptide GLP-1R regulators and the development of new anti-diabetic drugs with independent intellectual property rights are the common concerns of many new drug research institutions.

Summary of the invention

It is an object of the present invention to provide a compound represented by the following formula I or hydrazine and a pharmaceutically acceptable object of the invention to provide a process for the preparation of a compound represented by the following formula I or hydrazine; A still further object of the invention is to provide a pharmaceutical composition comprising a compound represented by the following formula I or π; a further object of the present invention is to provide a compound represented by the following formula I or Π as a glucagon-like peptide- 1 Receptor modulators for medical use in the prevention and/or treatment of metabolic disorders, including but not limited to diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease.

The present invention provides a glucagon-like peptide-1 receptor modulator, which increases the prevention and/or treatment of metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases ( Members of drugs such as Alzheimer's disease. The present invention relates to a compound represented by the following formula I or II, or a pharmaceutically acceptable salt thereof:

And all of its stereo and optical isomers, or prodrugs having the same pharmacological effects, esters thereof, solvates thereof or metal complexes thereof.

Where X and Y are respectively (CH „, n is 0-2; 0; S or NH.

Wherein R _{2 is} each independently a substituent of any of the following: hydrogen; halogen; alkane; cycloalkyl hydrocarbon; hydroxyl group; nitro group; carboxyl group; aldehyde group; alkoxy group; amine group; amine group; amide group; Amido; thiol; sulfhydryl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Substituted thienyl; substituted or unsubstituted pyrrolyl;

R ₃ , ! ^ independently of any of the following substituents: hydrogen; anthracene; cycloalkane; alkoxy; amine; amine alkyl; amide; carboxamide; thiol; substituted or unsubstituted aryl; Substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

Preferably, the compounds of the above formulae I and II are characterized in that: X, Y are respectively (CH ₂ ) n, n is 0-2; 0; S or NH, R „ R ₂ are each independently:

Wherein R ₅ is any of the following substituents: H; - fluorenyl; - any one, two or three substituted C-containing groups including a halogen atom, a decyloxy group of d-C ₆ or a hydroxyl group, - a fluorenyl group of C ₆ ; a C ₂ - (: ₆ alkenyl group; any one, two or three substituted C ₂ -C ₆ alkenyl groups including a halogen atom, an alkoxy group of d- or a hydroxyl group C ₂ - (: ₆ alkynyl; any one, two or three substituted C ₂ -C ₆ alkynyl group including a halogen atom, C "C ₆ decyloxy group or hydroxyl group"; C ₃ - a C ₆ cycloalkyl group; any one, two or three substituted (: ₃ - C ₆ cycloalkyl) groups containing a halogen atom, C, -C ₆ alkoxy group or a hydroxyl group; Benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing fluorenyl group including a halogen atom, d-C ₄ , nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group Any one, two or three substituted aryl groups, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; a thiol group containing a halogen atom, (, _(: ₄ ) Any one, two or three substituted pyridyl groups, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; Any one, two or three of a halogen atom, a fluorenyl group of d-, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group a substituted furanyl group; containing a halogen atom, a ketone group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a thiol group, a methylthio group, an ethylthio group, etc. Any one, two or three substituted pyranyl groups; containing a ? _3⁄4 atom, (: ₄ alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, Any one, two or three substituted thienyl groups including an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, dc ₄ , a nitro group, a carboxyl group, or an aldehyde group Any one, two or three substituted pyrrolyl groups such as a nonyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; a cyanyl group of ₆ ; containing a halogen atom Any one, two or three substituted c, - C _B decanoyl groups, c, -^ alkoxy or hydroxy group; c ₂ - C ₆ enoyl group; containing a halogen atom, d- Any one, two or three substituted C ₂ -C ₆ alkenoyl groups such as a decyloxy group or a hydroxyl group; a C ₂ -C ₆ alkynyl group; containing a halogen atom, (^-(: ₆ oxime) Any one, two or three substituted c ₂ -c ₆ alkynyl groups, including a hydroxyl group; a c ₃ -c _B cyclodecanoyl group; a decyloxy group or a hydroxyl group containing a halogen atom, d-Ce Any one, two or three substituted c ₃ -c ₆ cyclodecanoyl groups; adamantyl formyl, substituted gold垸-formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; pyranoyl; X (CH, n is 0-2; 0; S or NH;

R ₃₎ R ₄ are:

Wherein R ₆ is any one of the following substituents: H; a fluorenyl group of d-C _e ; containing any one, two or three including a halogen atom, an alkoxy group or a hydroxyl group of (:, - (: ₆ ) Substituted (VC ₆ alkyl; C ₂ - (: ₆ alkenyl; containing any one, two or three substituted (including a halogen atom, C, -C ₆ decyloxy or hydroxy group): ₂ -(: ₆ alkenyl; (: ₂ -( ₆ alkynyl; containing any one, two or three substituted ^-C ₆ including a halogen atom, (alkoxy group of Ce or a hydroxyl group) alkynyl; C ₃ -C ₆ cycloalkyl group embankment; contain any halogen atoms include, d-Ce alkoxy or hydroxy the embankment, including one, two or three substituents of C ₃ - C ₆ cycloalkyl group of the embankment; Aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing alkyl group including a halogen atom, dC ₄ , nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group Any one, two or three substituted aryl groups, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substituted pyridyl groups, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; a halogen atom, (^ - (alkyl, nitro, carboxyl, aldehyde, alkoxy embankment, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including any one of _4, two Or three substituted furanyl groups; containing a halogen atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted pyranyl groups; containing a halogen atom, (^-(: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carbon) Any one, two or three substituted thienyl groups including an amide group, a fluorenyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, 0>, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group , amine, amide, carboxamide, sulfhydryl, a Any one, two or three substituted pyrrolyl groups including a thiol group; a decanoyl group; any one, two or three groups including a halogen atom, an alkoxy group of -G or a hydroxyl group Substituted C, -C ₆ decanoyl; c ₂ -c _e enoyl; any one, two or three substituted c ₂ -c containing a halogen atom, a decyloxy group or a hydroxyl group of dc _fi _fi enoyl; C ₂ - C ₆ alkynyl group; a halogen atom-containing optionally include, d- or hydroxyl group of the embankment, including one, two or three substituents of c ₂ -c ₆ alkynyl group; and c ₃ - c ₆ cycloalkanoyl; containing halogen Any one, two or three substituted c ₃ -cyclodecanoyl groups of an atom, d-alkoxy or hydroxy group; adamantyl formyl, substituted adamantyl formyl; aroyl; benzoyl; furan Acyl; pyranoyl; thiophene; pyrrolyl; (CH ₂ ), n is 0-2; 0; S or NH;

Or R ₃ , respectively:

Wherein R ₇ and R _s are each independently a substituent of any of the following: H; (^-(: ₆ fluorenyl; any one, two or three containing a halogen atom, an alkoxy group of CG or a hydroxyl group) Substituted (^-(: ₆ fluorenyl; (: ₂ -(: ₆ alkenyl; any one, two or three substituted C containing a halogen atom, a fluorenyloxy group or a hydroxy group) ₂ -alkenyl; C ₂ -C ₆ alkynyl; any one, two or three substituted C ₂ -C ₆ alkynyl group containing a halogen atom, a decyloxy group or a hydroxyl group of d-Ce ; C ₃ -C ₆ cycloalkyl group embankment; includes any halogen atom-containing, dC _e the embankment or a hydroxyl group, including one, two or three substituents of C ₃ -C ₆ cycloalkyl group embankment; an aryl group; Benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing a halogen atom, d- (: ₄ alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide Any one, two or three substituted aryl groups, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substitutions of 0, alkyl, nitro, carboxy, aldehyde, decyloxy, amino, amide, carboxamido, decyl, methylthio, ethylthio Pyridyl; containing a halogen atom, -(; ₄ fluorenyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted furanyl groups; containing a halogen atom, d- (: ₄ alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, Any one, two or three substituted pyranyl groups including a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, (a thiol group of a C4 group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group) Any one, two or three substituted thienyl groups including a amide group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and an alkyl group including a halogen atom, (:, -(: ₄ ), Nitro, carboxyl, aldehyde, decyloxy, amine, amide, Amide groups, mercapto, methylthio, ethylthio, including one, two or three substituents pyrrolyl; C, -C ₆ alkanoyl; include a halogen atom-containing, or hydroxyl group dC embankment ₆ of Any one, two or three substituted d-C ₆ alkanoyl groups; C ₂ -C _fi alkenoyl group; containing a halogen atom, (^-(: ₆ alkoxy group or hydroxyl group) Any one, two or three substituted c ₂ - c _fi enoyl groups; c ₂ - c ₆ alkynyl groups; any one containing a halogen atom, c, -c ₆ alkoxy group or a hydroxyl group, Two or three substituted c ₂ -c _e acetylene groups; c ₃ -c ₆ cyclodecanoyl group; any one, two or three containing a halogen atom, an alkoxy group of dc ₆ or a hydroxyl group Substituted (: ₃ -( ₆ cyclodecanoyl; adamantyl, substituted adamantyl; aroyl; benzyl; furanoyl; pyranoyl; thiophene; pyrroyl; X (CH ₂ ) _n , n is 0-2; 0; S or NH; X ₂ is (CH ₂ ) „, n is 0-2; 0; S or NH;

Or R ₃ , respectively -

Wherein R ₉ is any one of the following substituents: H; (:, -(: ₆ fluorenyl; any one, two or three substitutions including a halogen atom, d-(alkoxy group or hydroxy group) a fluorenyl group of d-Cs; (: ₂ -( ₆ alkenyl; any one, two or three substituted C ₂ - C ₆ containing a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group) Alkenyl; C ₂ -C ₆ alkynyl; any one, two or three substituted C ₂ -C _fi alkynyl group containing a halogen atom, C,-C ₆ decyloxy or hydroxy group; a C ₃ -C _fi cyclodecyl group; any one, two or three substituted C ₃ -C ₆ cyclodecyl groups containing a halogen atom, a C, or a C ₆ decyloxy group or a hydroxyl group; Benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, (^(alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide) group, any carbon amide group, a mercapto group, methylthio, ethylthio, including one, two or three aryl group substituents; include a halogen atom-containing, - (: ₄ Any one, two or three substituted pyridyl groups including a nitro group, a carboxy group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one or two including a halogen atom, an alkyl group of d-C ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and the like. Or three substituted furanyl groups; containing a halogen atom, a thiol group of d-C ₄ , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methyl group, Any one, two or three substituted pyranyl groups including an ethylthio group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxy group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carbon amide group Any one, two or three substituted thienyl groups including a thiol group, a thiol group, a methylthio group, an ethylthio group, a thiol group including a halogen atom, dC ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, Amine, amide, carboxamide, sulfhydryl, Any one, two or three substituted pyrrolyl groups such as a thio group or an ethylthio group; an alkanoyl group having a halogen atom, a decyloxy group having a halogen atom or d-Ce, or a hydroxyl group; Substituted C, -C ₆ decanoyl; c ₂ -c ₆ enoyl; any one, two or three substituted c ₂ - including a halogen atom, an alkoxy group of dc ₆ or a hydroxyl group An alkenoyl group of c ₆ ; an alkynyl group of c ₂ -c _{6 ;} an alkyne having any one, two or three substituted c ₂ -c ₆ groups including a halogen atom, a decyloxy group of d-c ₆ or a hydroxyl group; Acyl; c ₃ -c ₆ cyclodecanoyl; any one, two or three substituted c ₃ - c _fi cyclodecanoyl groups including a halogen atom, a d-c _fi decyloxy group or a hydroxyl group; Adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrroyl; X (CH ₂ ), n is 0-2; 0; Or NH;

Or R ₃ , respectively -

among them. , Ru each independently is any one of the following substituents: H; Ct- (: ₆ alkyl; any one, two or three substituted d including a halogen atom, d- alkoxy group or a hydroxyl group - fluorenyl; (: ₂ - (: ₆ alkenyl; any one, two or three substituted C ₂ - containing: a halogen atom, C, -C _e methoxy or hydroxy group (: ₆ alkenyl; ( _2- ( ₆ alkynyl; any one, two or three substituted C ₂ - (^ alkynyl group) including a halogen atom, a decyloxy group of CrC ₆ or a hydroxyl group; C a cycloalkyl group of ₃ -C _e ; any one, two or three substituted C:,-C ₆ cyclodecyl groups including a halogen atom, a C, or a C ₆ methoxy group or a hydroxyl group; Benzyl; furyl; pyranyl; thienyl; Pyrrolyl; pyridyl; containing halogen atom, thiol, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted aryl groups; containing a halogen atom, a sulfhydryl group, a nitro group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a group Any one, two or three substituted pyridyl groups including a thio group or an ethylthio group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carbon group Any one, two or three substituted furanyl groups including an amide group, a decyl group, a methylthio group, an ethylthio group; a fluorenyl group including a halogen atom, c, -c ₄ , a nitro group, a carboxyl group, an aldehyde group, Any one, two or three substituted pyranyl groups including a methoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; containing a halogen atom, (^-^) Sulfhydryl, nitro, carboxyl, aldehyde, decyloxy Any amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents thienyl; include a halogen atom-containing, (^ - ₍₄ embankment group, nitro Any one, two or three substituted pyrrolyl groups of a group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; Any one, two or three substituted decanoyl groups including a halogen atom, a decyloxy group or a hydroxyl group of dC ₆ ; an alkenoyl group of c ₂ -c _e ; containing a halogen atom, c, -c ₆ Any one, two or three substituted c ₂ -c ₆ enoyl groups such as alkoxy or hydroxy; c ₂ -c _e acetylenic group; alkoxy group containing a halogen atom, C, - c ₆ Or one, two or three substituted c ₂ -c ₆ alkynyl groups, or a c ₃ -c ₆ cyclodecanoyl group; or a hydroxy group including a halogen atom, dC ₆ or a hydroxyl group Any one, two or three substituted ( ₃ _(: ₆ cycloalkanoyl; adamantyl, Substituting adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X, (CH ₂ ), n 0-2; 0; S or NH; Is (CH ₂ ) _n , n is 0 - 2; 0; S or NH.

When R', R ₂ are each independently:

Wherein, R ₁₃ are each independently a substituent of any of the following: H; C "indenyl group of C ₆ ; any one or two of a fluorenyl group or a hydroxy group including a halogen atom, C, -C _fi or Three substituted (:, -(: ₆ alkyl); alkenyl; any one, two or three substituted ( ₂ -(:) containing a halogen atom, a decyloxy group or a hydroxyl group of d-: ₆ alkenyl; C ₂ - (: ₆ alkynyl group; a halogen atom includes contain any, or a hydroxyl group dC embankment ₆ of the inner one, two or three substituents of C ₂ - (alkynyl; C a cycloalkyl group; any one, two or three substituted C ₃ -C ₆ cycloalkyl groups including a halogen atom, a decyloxy group or a hydroxyl group of dC ₆ ; an aryl group; a benzyl group; a furyl group; Pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, -(: ₄ fluorenyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, Any one, two or three substituted aryl groups including a methylthio group and an ethylthio group; containing a halogen atom, Any one, two or three substituted pyridyl groups of an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; Containing a halogen atom, 0 (: ₄ fluorenyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, B Any one, two or three substituted furanyl groups including a thio group; containing a halogen atom, d-(indenyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide) Any one, two or three substituted pyranyl groups including a thiol group, a thiol group, an ethylthio group, a thiol group including a halogen atom, dc ₄ , a nitro group, a carboxy group, an aldehyde group, a decyloxy group Any one, two or three substituted thienyl groups, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, (:, _(: ₄ ) Any one, two or three substituted pyrrolyl groups including a nitro group, a carboxy group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; An alkanoyl group of -c _{6 ;} an alkanoyl group having any one, two or three substituted d-C ₆ groups including a halogen atom, a decyloxy group of dc ₆ or a hydroxyl group; a enoyl group of C ₂ - C _fi ; include a halogen atom-containing, d- (: any embankment ₆ alkoxy or hydroxy, including One, two or three substituents of C ₂ -C ₆ alkenyl group; a C ₂ - C ₆ alkynyl group; containing any one of a halogen atom include, CrC alkoxy or hydroxy embankment ₆ of the inner, two or three a substituted C ₂ -C ₆ alkynyl; a cycloalkanoyl; a cyclohexanoyl group containing any one, two or three substituents including a halogen atom, a decyloxy group or a hydroxyl group; Adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X CH , n is 0-2; 0; S or NH; ₂ is ((3⁄4)„, n is 0-2; 0; S or NH;

R ₃ , respectively:

Wherein R ₆ is any one of the following substituents: H; (: ₆ fluorenyl; or any one, two or three substituted dC ₆ including a halogen atom, ( ₆ alkoxy group or hydroxyl group) Alkyl; (: ₂ -(: ₆ alkenyl; any one, two or three substituted (including ₂ -( ₆ alkenyl; C) containing a halogen atom, a fluorenyloxy group or a hydroxy group ₂ - (: ₆ alkynyl; any one, two or three substituted C ₂ -C ₆ alkynyl groups containing a halogen atom, a C, a C ₆ decyloxy group or a hydroxyl group; C ₃ - a cyclic fluorenyl group of C ₆ ; a C ₂ -C _B cyclodecyl group containing a halogen atom, a decyloxy group or a hydroxyl group of a Ct-Cs; an aryl group; a benzyl group; furyl; tetrahydropyranyl; thienyl; pyrrolyl; pyridyl; include a halogen atom-containing, alkyl with ₄ dC, a nitro group, a carboxyl group, an aldehyde group, embankment group, an amine group, an amide group, a carbonamide group, a mercapto group Any one, two or three substituted aryl groups including a methylthio group and an ethylthio group; containing a halogen atom, a fluorenyl group, and a nitro group Any one, two or three substituted pyridyl groups including a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substituted alkyl, nitro, carboxy, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio a furan group; containing a halogen atom, d-(^, alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted pyranyl groups; containing a halogen atom, a fluorenyl group, a nitro group, a carboxy group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a group Any one, two or three substituted thienyl groups including a thio group and an ethylthio group; containing a halogen atom, d-(^, alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, Amido, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted pyrrolyl groups; alkanoyl group of d-Cs; any one, two or three substituted ds including a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group - C ₆垸 Acyl; C ₂ -C ₆ alkenoyl; any one, two or three substituted c ₂ -c ₆ alkenoyl group including a halogen atom, an alkoxy group of -G, or a hydroxyl group; c ₂ -c ₆ Alkynyl; a acetylenic group containing a halogen atom, (--: ₆ decyloxy or hydroxy group, any two, or three substituted c ₂ -c ₆ ; c ₃ -c ₆ ring; Any one, two or three substituted c ₃ -c ₆ cyclodecanoyl groups containing a halogen atom or a hydroxyl group including a halogen atom, C, - c ₆ ; adamantyl group, substituted adamantane Formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X ₂ is (CH ₂ ) _n , n is 0-2; 0; S or NH;

Or R ₃ , respectively -

Wherein R ₇ and R ₈ are each independently a substituent of any of the following: H; C "indenyl group of C _e ; any one or two of a decyloxy group or a hydroxyl group including a halogen atom, C, -C ₆ Or a three-substituted alkyl group; a C ₂ - (: ₆ alkenyl group; any one, two or three substituted groups including a halogen atom, an alkoxy group of d- or a hydroxyl group ( _2- ( ₆ ) alkenyl group; (: ₂ - (: ₆ alkynyl group; a halogen atom include containing, C, - one, two or three of any alkoxy or hydroxy-substituted C ₆ of the inner (: ₂ - (: ₆ Alkynyl; C ₃ -C _e cycloalkyl; any one, two or three substituted C ₃ -C ₆ cyclodecyl groups containing a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group; Aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing fluorenyl group including a halogen atom, dC ₄ , nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group Any one, two or three substituted aryl groups, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any sub, d- C ₄ alkyl with, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two, or a three-substituted pyridyl group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and the like Any one, two or three substituted furanyl groups; including a halogen atom, d-(indenyl, nitro, carboxyl, aldehyde, anthracene, amine, amide, carboxamide, sulfhydryl, Any one, two or three substituted pyranyl groups including a methylthio group and an ethylthio group; a mercapto group including a halogen atom, C, -C ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, Any one, two or three substituted thienyl groups including an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; and a halogen atom, a sulfhydryl group, a nitro group, Carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carbon amide Any one, two or three substituted pyrrolyl groups including a thiol group, a thiol group, a methylthio group, an ethylthio group; a decanoyl group of CrC _e; an arsenyl group containing a halogen atom, d-, or a hydroxyl group One, two or three substituted C,-C ₆ alkanoyl; C ₂ -C ₆ alkenoyl; any one or two containing a halogen atom, a decyloxy group or a hydroxyl group of d-Ce or three substituted C ₂ - C ₆ alkenyl group; a C ₂ -C ₆ alkyne group; a halogen atom include any containing, C, -C ₆ alkoxy or hydroxy, including one, two or three substituents Alkynyl group of c ₂ -c _e ; cycloalkanoyl group of c ₃ -c ₆ ; any one, two or three substituted groups including a halogen atom, an alkoxy group of d-CB or a hydroxyl group (: ₃ _(: ₆ cycloalkanoyl; adamantyl formyl, substituted adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrroyl; X, (CH ₂ ) „, n is 0- 2; 0; S or NH _; X ₂ is (CH ₂ ) „, n is 0_2; 0; S or NH; Or R ₃ , ^ are:

Wherein R ₉ is any one of the following substituents: H; C, -C ₆ fluorenyl; any one, two or three substituted d including a halogen atom, ( ₆ decyloxy or hydroxy group) - an alkyl group of c ₆ ; an alkenyl group of c ₂ -c ₆ ; any one, two or three substituted C ₂ - (: ₆ ) including a halogen atom, an alkoxy group of d-Ce or a hydroxyl group Alkenyl; C ₂ -alkynyl; any one, two or three substituted c ₂ -c ₆ alkynyl group containing a halogen atom, c,-c ₆ alkoxy group or hydroxyl group; C ₃ a cycloalkyl group of _C ₆ ; a mono-, two- or three-substituted c ₃ -c ₆ cyclodecyl group containing a halogen atom, a decyloxy group or a hydroxyl group of C-Ce; an aryl group; a benzyl group; Furanyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, (:, - (: ₄ alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, any carbon amide group, a mercapto group, methylthio, ethylthio, including one, two or three aryl group substituents; include a halogen atom-containing, alkyl with ₄ dC, nitro Any one, two or three substituted pyridyl groups including a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substitutions of d-(indolyl, nitro, carboxy, aldehyde, decyloxy, amino, amide, carboxamido, decyl, methylthio, ethylthio) a furan group; containing a halogen atom, (^-(: ₄ fluorenyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio) Any one, two or three substituted pyranyl groups; containing an alkyl group including a halogen atom, c, -c ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carbon Any one, two or three substituted thienyl groups including an amide group, a fluorenyl group, a methylthio group, an ethylthio group; an alkyl group including a halogen atom, c, -c ₄ , a nitro group, a carboxyl group, an aldehyde group, Alkoxy, amine, amide, carboxamide, sulfhydryl, methyl sulfide Any one, two or three substituted pyrrolyl groups including a thiol group; an alkanoyl group of d-; any one, two or three substitutions including a halogen atom, a hydroxyl group or a hydroxyl group Alkanoyl group of c, -c ₆ ; alkenoyl group of c ₂ -c ₆ ; any one, two or three substituted c ₂ - c ₆ containing an alkoxy group including a halogen atom, dC ₆ or a hydroxyl group; Alkenoyl; c ₂ -c ₆ alkynyl; acetylene group containing any one, two or three substituted c ₂ -c ₆ including a halogen atom, d- (: ₆ alkoxy group or hydroxyl group) a cycloalkanoyl group of c ₃ - c ₆ ; any one, two or three substituted c ₃ - c ₆ cycloalkanoyl groups including a halogen atom, a decyloxy group of d- or a hydroxyl group; Acyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X ₂ is (CH, n is 0-2; 0; S or NH;

Or R ₃ and R ₄ are:

Where R,. , Ru each independently is any one of the following substituents: H; a fluorenyl group of d-C ₆ ; any one, two or three substituted groups including a halogen atom, a C _C ₆ methoxy group or a hydroxyl group An alkyl group of C,-(; ₂ :( ₂ -alkenyl; an arbitrary one, two or three substituted C ₂ - containing a halogen atom, a C, a C _B group or a hydroxyl group) C _B alkenyl; C ₂ -C ₆ alkynyl; any one or two containing a halogen atom, an alkoxy group of dC _e or a hydroxyl group Three substituted c ₂ - (: ₆ alkynyl; c ₃ - c ₆ cycloalkyl; any one, two or three containing an alkoxy group including a halogen atom, c, -c ₆ or a hydroxyl group Substituted c ₃ -c _e cycloalkyl; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing fluorenyl group including halogen atom, CrC ₄ , nitro group, carboxyl group Any one, two or three substituted aryl groups including an aldehyde group, an oxime group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substitutions of -C ₄ thiol, nitro, carboxy, aldehyde, decyloxy, amine, amide, carboxamido, decyl, methylthio, ethylthio Pyridyl group; containing any of a halogen atom, an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and the like. One, two or three substituted furanyl groups; containing a halogen atom, d- (^ alkyl group, nitro group) Any one, two or three substituted pyranyl groups, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substitutions of an alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group or an ethylthio group of dC ₄ . a thiophenyl group; containing a halogen atom, a C "C ₄ alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a thiol group, a methylthio group, an ethylthio group, etc. Any one, two or three substituted pyrrolyl groups; C,-C _e decanoyl group; any one, two or three substituted C groups including a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group , -C ₆ decanoyl; C ₂ - C _e enoyl; containing any one, two or three substituted c ₂ - including a prime atom, (:, - ( methoxy or hydroxy group of ₆ ) c _e enoyl; C ₂ - C ₆ alkynyl group; a halogen atom-containing include, CrCe alkoxy or Group, including any one, two or three substituents of c -C ₆ alkynyl group of _2; c ₃ -c ₆ cycloalkyl group; a halogen atom-containing optionally include, dc embankment ₆ alkoxy or hydroxy, including One, two or three substituted c ₃ -c ₆ cyclodecanoyl; adamantyl formyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrole Formyl; X, is ((3⁄4)„,, n is 0-2; 0; S or NH; X ₂ is (CH ₂ ) „, n is 0-2; 0; S or NH.

Further preferably, when R _{2 is} each independently:

Wherein R ₁₄ is any one of the following substituents: H; (: "(: ₆ alkyl; containing any one, two or three including a halogen atom, (": ₆ alkoxy or hydroxy group Substituted (^-(: ₆ fluorenyl; (: ₂ - (: ₆ alkenyl; containing any one, two including a halogen atom, (:, - (: ₆ alkoxy or hydroxy) Or three substituted (: ₂ -(: ₆ alkenyl; C ₂ - ^ alkynyl; any one, two or three substituted C ₂ containing a halogen atom, an alkoxy group or a hydroxyl group) -C ₆ alkynyl; C ₃ -C ₆ cycloalkyl; any one, two or three substituted ( ₃ - C ₆ ring) containing a halogen atom, d-alkoxy or hydroxy group Alkyl; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, d-(^ thiol, nitro, carboxyl, aldehyde, alkoxy, Any one, two or three substituted aryl groups including an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three of an atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group. Substituted pyridyl; containing a halogen atom, d-(alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Arbitrarily One, two or three substituted furanyl groups; containing a halogen atom, an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group Any one, two or three substituted pyranyl groups including an ethylthio group; containing a halogen atom, (^-(: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group) Any one, two or three substituted thienyl groups, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; a halogen atom, a sulfhydryl group, a nitro group, a carboxy group Any one, two or three substituted pyrrolyl groups, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; a decanoyl group of d-C ₆ Any one, two or three substituted C,-decanoyl groups including a halogen atom, c, -c ₆ or a hydroxyl group; a c ₂ - c ₆ alkenoyl group; any c, -c embankment ₆ alkoxy or hydroxy, including one, two or three Generation c ₂ -c ₆ alkenyl group; a c ₂ -c ₆ alkynyl group; a halogen atom-containing optionally include, D- c embankment ₆ alkoxy or hydroxy, including one, two or three substituents _c-2 - alkynyl group of c ₆ ; cyclodecanoyl group of c ₃ - c _e ; ring of any one, two or three substituted C ₃ - C ₆ containing a halogen atom, a hydroxyl group of CC^ or a hydroxyl group Decanoyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; 乂₁ is 03⁄4) „, n is 0-2; 0; S or NH;

R ₃ , respectively:

Wherein R ₆ is any one of the following substituents: H; C, - (: ₆ fluorenyl; any one, two or three substituted including a halogen atom, a decyloxy group or a hydroxyl group of d- embankment group; C ₂ -C ₆ alkenyl group; a halogen atom include containing, C, - any C ₆ alkoxy or hydroxy embankment inner one, two or three substituents of C ₂ - C ₆ alkenyl group; C ₂ - (: ₆ alkynyl; any one, two or three substituted C ₂ -C ₆ alkynyl group including a halogen atom, a decyloxy group or a hydroxyl group; a C ₃ - C _e ring a fluorenyl group containing any one, two or three substituted c ₃ -c _e including a halogen atom, a decyloxy group or a hydroxyl group of a Ct-Ce; an aryl group; a benzyl group; a furyl group; a thiol group; a pyrenyl group; a pyrrolyl group; a pyridyl group; an alkyl group including a halogen atom, d-, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methyl group Any one, two or three substituted aryl groups including an ethylthio group; containing a halogen atom, a dc^alkyl group, a nitro group, a carboxyl group, Any one, two or three substituted pyridyl groups including an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, d- ( Any one, two or three substituted furans of thiol, nitro, carboxy, aldehyde, alkoxy, amine, amide, carboxamido, decyl, methylthio, ethylthio Any one containing an atom, a c c ₄ alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group, and the like. One, two or three substituted pyranyl groups; containing a halogen group including a halogen atom, c, -^, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, Any one, two or three substituted thienyl groups including a methylthio group, an ethylthio group; an alkyl group including a halogen atom, c, -c ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group Base, amide group, carboxamide group, sulfhydryl group, methylthio group, ethylthio group Any one, two or three substituents pyrrolyl; - (alkanoyl; containing optionally include a halogen atom, a hydroxyl group or a dc embankment ₆ of the inner one, two or three substituents _dc-6 alkanoyl ; a C ₂ -c ₆ enoyl group; containing any one, two or more including a halogen atom, (:, - (: ₆ decyloxy group or hydroxy group) Substituted by three C ₂ - C ₆ alkenyl group; a C ₂ -C ₆ alkynyl group; a halogen atom-containing optionally include, d- alkoxy or hydroxy group including one, two or three substituents of c _{a 2} - c ₆ alkynyl group; a c ₃ - c ₆ cyclodecanoyl group; any one, two or three substituted C ₃ -C ₆ groups including a halogen atom, a decyloxy group or a hydroxyl group of d- Cyclodecanoyl; adamantyl formyl, substituted adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X ₂ is (CH, n is 0-2; 0; S or NH;

Or R ₃ and R ₄ are:

Wherein R ₇ and R« are each independently a substituent of any of the following: H; d-alkyl; any one, two or three substituted groups including a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group. a fluorenyl group of d-; a C ₂ - (: ₆ alkenyl group; any one, two or three substituted groups including a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group (: ₂ - (: ₆ ) Alkenyl; C ₂ -C _fi alkynyl; any one, two or three substituted (including ₂ -(: ₆ alkynyl; C) containing a halogen atom, a decyloxy group or a hydroxyl group of d- _{a 3} -C ₆ cyclodecyl group; any one, two or three substituted C ₃ -C ₆ cyclodecyl groups containing a halogen atom, a C,-C ₆ decyloxy group or a hydroxyl group; an aryl group; Benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing arginyl, C, -C alkyl, nitro, carboxy, aldehyde, alkoxy, amine, amide Any one, two or three substituted aryl groups, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; ^ - (: any alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including _4, two or three a substituted pyridyl group; containing an alkyl group including a halogen atom, C, -C ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethyl sulfide Any one, two or three substituted furanyl groups including a halogen atom; a sulfhydryl group including a halogen atom, CC ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, Any one, two or three substituted pyranyl groups including a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxy group, an aldehyde group, a decyloxy group, Any one, two or three substituted thienyl groups including an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; and a halogen atom, (^-(: ₄ alkyl group), Nitro, carboxyl, aldehyde, decyloxy, amine, amide, carbonyl Any one, two or three substituted pyrrolyl groups including an amine group, a fluorenyl group, a methylthio group, an ethylthio group; -(: ₆ decanoyl group; a decyloxy group having a halogen atom, d- or a hydroxyl group; Any one, two or three substituted alkanoyl groups; a C ₂ -C ₆ alkenoyl group; any one or two containing a halogen atom, a C, a C ₆ -oxy group or a hydroxyl group or a three-substituted C ₂ -C ₆ alkenoyl group; a C ₂ -C ₆ alkynyl group; any one, two or three substituted alkyne containing a halogen atom, a decyloxy group or a hydroxyl group of dC ₆ An acyl group; a cycloalkanoyl group of C:,-C _e ; a C ₂ -CB cyclodecanoyl group containing a halogen atom, an alkoxy group of dc ₆ or a hydroxyl group; adamantane; Formyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X, (CH, n is 0-2; 0; S or NH _; Is ((3⁄4)„, n is 0-2; 0; S or NH;

Or R ₃ and R ₄ are:

Wherein R ₉ is any one of the following substituents: H; an fluorenyl group; any one, two or three substituted groups including a halogen atom, a -C methoxy group or a hydroxyl group (;-(: ₆垸) Any one, two or three substituted C ₂ - (: ₆ alkenyl; C ₂ -C alkynyl group containing a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group; Any one, two or three substituted C ₂ -C ₆ alkynyl groups including a halogen atom, an alkoxy group of C Ce or a hydroxyl group; a C ₃ -C ₆ cycloalkyl group; containing a halogen atom Any one, two or three substituted C ₃ -C ₆ cycloalkyl groups of d- alkoxy or hydroxy; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl a pyridyl group; a fluorenyl group containing a halogen atom, C _t - C ₄ , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted aryl groups; containing a halogen atom, C, - (: ₄ sulfhydryl, nitro, carboxyl Any one, two or three substituted pyridyl groups, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, d- Any one, two or three substituted furanyl groups including a fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, and an ethylthio group. Containing any one including a halogen atom, -(: ₄ alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group) , two or three substituted pyranyl groups; containing a halogen atom, -(: ₄ alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, fluorenyl group, A Any one, two or three substituted thienyl groups including a thio group or an ethylthio group; containing an alkyl group including a halogen atom, d-c ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, Amido, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted pyrrolyl groups; c, - c ₆ alkanoyl group; any one, two or three substitutions including a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group Alkanoyl group of d-; enoyl group of c ₂ -c ₆ ; enoyl group of any one, two or three substituted c ₂ -c ₆ containing a halogen atom, a decyloxy group or a hydroxyl group of d- a C ₂ -C ₆ alkynyl group; a acetylenic group having any one, two or three substituted c ₂ - c ₆ groups including a halogen atom, d- (: ₆ decyloxy group or hydroxyl group; c _{3 ;} a cyclodecanoyl group of -c ₆ ; any one, two or three substituted c ₃ - c ₆ cyclodecanoyl groups including a halogen atom or a hydroxyl group of c, - c ₆ ; Acyl, substituted adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; 乂₁ is (01 ₂ ) „, n is 0-2; Or NH;

Or R _3, respectively:

Wherein R _w , R „ each independently is any one of the following substituents: H; (: ₆ fluorenyl; any one, two or three containing a halogen atom, a decyloxy group or a hydroxyl group of d-Ce) Substituted C, -C ₆ fluorenyl; C ₂ -C _e alkenyl; any one, two or three substituted C ₂ containing a halogen atom, a C'-Ce alkoxy group or a hydroxyl group -C ₆ alkenyl; c ₂ -alkynyl; any one, two or three substituted c ₂ -c ₆ alkyne containing a halogen atom, c,-c _e or a hydroxyl group a c ring group of c ₃ -c ₆ ; an alkoxy group or a hydroxyl group including a halogen atom, c, - c _e Any one, two or three substituted c ₃ -c ₆ cyclodecyl; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, dc ₄ Any one, two or three substituted aryl groups including a fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Containing a halogen atom, (^-(: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group) Any one, two or three substituted pyridyl groups; containing an alkyl group including a halogen atom, dc ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methyl sulfide Any one, two or three substituted furanyl groups including a thiol group; a thiol group including a halogen atom, c, -c ₄ , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, Amide, carboxamide, sulfhydryl, methylthio, ethylthio Is intended one, two or three of the substituents pyranyl; comprising pigment containing atoms, C "c ₄ embankment group, a nitro group, a carboxyl group, an aldehyde group, embankment group, an amine group, an amide group, a carbonamide group, a mercapto group, Any one, two or three substituted thienyl groups including a methylthio group and an ethylthio group; containing a halogen atom, (: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, Any one, two or three substituted pyrrolyl groups such as an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group;

a decanoyl group of C, -C ₆ ; an alkanoyl group of any one, two or three substituted dcs including a halogen atom, an alkoxy group of CrCe or a hydroxyl group; an alkenoyl group of c ₂ -c ₆ ; a halogen atom, d- (: any embankment ₆ alkoxy or hydroxy, including one, two or three substituents of c ₂ -c ₆ alkenyl group; a c ₂ -c ₆ alkynyl group; a halogen atom-containing include, Any one, two or three substituted c ₂ -c ₆ alkynyl groups of c, -^ alkoxy or hydroxy; c ₃ -c ₆ cycloalkanoyl; containing an alkane including a halogen atom, C Any one, two or three substituted C ₃ - (; ₆ cyclodecanoyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyr Noryl; thiophene; pyrroyl; X, (CH ₂ ), n is 0-2; 0; S or NH _; (CH ' n is 0-2; 0; S or NH.

When R, R ₂ are each independently:

Wherein R ₁₅ , R _ie are each independently a substituent of any of the following: H; an fluorenyl group; any one, two or three substituted Cs including a halogen atom, a decyloxy group or a hydroxyl group of d-, An alkyl group of C ₆ ; a C ₂ -C ₆ alkenyl group; any one, two or three substituted C ₂ - ( ₆ alkenyl groups) containing a halogen atom, an alkoxy group of CrCe or a hydroxyl group; a C ₂ -C ₆ alkynyl group; any one, two or three substituted groups including a halogen atom, C "C ₆ alkoxy group or a hydroxyl group (: ₂ - (: ₆ alkynyl group; C ₃₎ a cycloalkyl group of C _fi ; a C ₂ -C ₆ cyclodecyl group containing a halogen atom, a decyloxy group or a hydroxyl group including d-; an aryl group; a benzyl group; Furanyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing fluorenyl group including a halogen atom, d-C ₄ , nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group Any one, two or three substituted aryl groups including a mercapto group, a methylthio group, an ethylthio group; Any one, two or three substituted alkyl groups of the alkyl group, the nitro group, the carboxyl group, the aldehyde group, the decyloxy group, the amine group, the amide group, the carboxamide group, the thiol group, the methylthio group and the ethylthio group. Pyridyl; containing a halogen atom, a fluorenyl group, a nitro group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, a Any one, two or three substituted furanyl groups including a thio group; a fluorenyl group including a halogen atom, C-C ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carbon group amide groups, mercapto, methylthio, ethylthio, including one, two or three of the substituents pyranyl; containing a halogen atom include, _ ₍₄ embankment group, a nitro group, a carboxyl group, an aldehyde group, embankment Any one, two or three substituted thienyl groups including an oxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; and a fluorene group including a halogen atom, d- (: ₄ ) Any one, two or three substituted pyrrolyl groups including a nitro group, a carboxy group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; a decanoyl group of -c _{6 ;} a decanoyl group having any one, two or three substituted d- groups including a halogen atom, c, -c _fi alkoxy group or a hydroxyl group; (C ₆ enoyl group; Any one or two containing a halogen atom, an alkoxy group or a hydroxyl group Or three substituted c ₂ - c ₆ enoyl groups; c _{2 -} c _e acetylene groups; containing any one, two or three substitutions including a halogen atom, a decyloxy group of d- or a hydroxyl group a acetylene group of c ₂ - c ₆ ; a cyclodecanoyl group of c ₃ -c ₆ ; a C ₃ -C ₆ containing any one, two or three substituents including a halogen atom, a decyloxy group or a hydroxyl group of Ce Cyclodecanoyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X, (CH ₂ ) _n , n 0-2; 0; S or NH; is (CH ₂ ) „, n is 0- 2; 0; S or NH,

R ₃ , respectively:

Wherein R6 is any of the following substituent groups: H; d- (group ₆ of the embankment; includes any containing a halogen atom, C "C ₆ alkoxy or hydroxy embankment inner one, two or three substituents of C, - (: ₆ alkyl; C ₂ - C _fi alkenyl group; or a hydroxyl group optionally having embankment include a halogen atom, the inner one, two or three substituents of C ₂ - C _fi alkenyl; C _{a 2-} _C6 alkynyl group; any one, two or three substituted c ₂ -c ₆ alkynyl groups including a halogen atom, a decyloxy group or a hydroxyl group; a C ₃ -C _e cyclodecyl group; Any one, two or three substituted ( ₃ -(: ₆ cyclodecyl; aryl; benzyl; furyl; pyranyl; thiophene) containing a halogen atom, a decyloxy group or a hydroxyl group; a pyrrolyl group; a pyridyl group; an alkyl group including a halogen atom, Cr C ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethyl sulfide Any one, two or three substituted aryl groups, including a halogen atom, a C, a fluorenyl group, a nitro group, a carboxyl group Any one, two or three substituted pyridyl groups including an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, d- ( Any one, two or three substituted furanyl groups including a fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, and an ethylthio group. Containing a halogen atom, (:, -(: ₄ alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group, etc.) Any one, two or three substituted pyranyl groups; containing an alkyl group including a halogen atom, C, -C ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group Any one, two or three substituted thienyl groups including a mercapto group, a methylthio group, an ethylthio group; a mercapto group including a halogen atom, dC ₄ , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group Base, amide group, carboxamide group, sulfhydryl group, methylthio group, B Group, including any one, two or three substituents pyrrolyl; dC ₆ alkanoyl; include a halogen atom-containing, dC _e embankment any group or hydroxyl group, including one, two or three substituents D- of 垸 An acyl group; an alkenoyl group of c ₂ -c _e ; an acyl group of any one, two or three substituted c ₂ - c ₆ containing an alkoxy group or a hydroxyl group including a halogen atom, c, -c ₆ ; ₂ -c ₆ alkynyl group; a halogen atom include any containing, c "c embankment ₆ alkoxy or hydroxy, including one, two or three substituents of c ₂ - ₆ alkynyl group c; c ₃ -c ₆ a cycloalkanoyl group; any one, two or three substituted c ₃ -c ₆ cycloalkanoyl groups including a halogen atom, a decyloxy group of d- or a hydroxyl group; an adamantyl formyl group, a substituted diamond rim Acyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (CH ₂ ) _n , n is 0- 2; 0; S or NH _;

Or R ₃ , respectively:

Wherein R ₇ and R ₈ are each independently a substituent of any of the following: H; a fluorenyl group of d-Ce; any one, two or three substituents including a halogen atom, a hydroxyl group of CC _e or a hydroxyl group; a d-C ₆ fluorenyl group; a C ₂ -C ₆ alkenyl group; any one, two or three substituted (including ₂ -(:) containing a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group; ₆ alkenyl; C ₂ -C ₆ alkynyl group; a halogen atom-containing optionally include, d- or hydroxyl group of the embankment, including one, two or three substituents of C ₂ -C ₆ alkynyl group; a C _{a 3-} C ₆ cycloalkyl group; a C ₂ -C _fi cyclodecyl group containing an alkoxy group or a hydroxyl group including a halogen atom, C, or C ₆ ; an aryl group; Benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, (:, -( ₄ fluorenyl, nitro, carboxyl, aldehyde, decyloxy, amine, Any one, two or three substituted aryl groups including an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; , C, - C ₄ alkyl with arbitrary, a nitro group, a carboxyl group, an aldehyde group, embankment group, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two, or a three-substituted pyridyl group; containing a halogen atom, -(: ₄ alkyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, mercapto group, methylthio group, ethyl sulfide Any one, two or three substituted furanyl groups including a halogen atom; a sulfhydryl group including a halogen atom, dC ₄ , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, Any one, two or three substituted pyranyl groups including a mercapto group, a methylthio group, an ethylthio group; a mercapto group including a halogen atom, d-C ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group Any one, two or three substituted thienyl groups, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; and an alkyl group including a halogen atom, (^-(; ₄ ) , nitro, carboxyl, aldehyde, alkoxy, amine, amide, carbon Any one, two or three substituted pyrrolyl groups such as an amide group, a fluorenyl group, a methylthio group or an ethylthio group; an alkanoyl group of d-Ce; a fluorenyl group containing a halogen atom, d- or a hydroxyl group Any one, two or three substituted d-Ce alkanoyl groups; c ₂ -c ₆ alkenoyl groups; any one or two containing a halogen atom, a Cr "C ₆ alkoxy group or a hydroxyl group Or three substituted c ₂ -c ₆ alkenoyl groups; c ₂ - c ₆ alkynyl groups; any one, two or three containing a halogen atom or a hydroxyl group including a halogen atom, c, -c ₆ Substituted c ₂ -c ₆ alkynyl; c ₃ -c ₆ cyclodecanoyl; any one, two or three substituted (including a halogen atom, an alkoxy group of d-Ce or a hydroxyl group): _3- (: ₆ cycloalkanoyl; adamantyl, substituted adamantyl form; aroyl; benzyl; furanoyl; pyranoyl; thiophene; pyrroyl; X, (CH, π is 0-2; 0; S or NH; is (CH, n is 0-2; 0; S or NH; Or R ₃ and R ₄ are:

Wherein R ₉ is any one of the following substituents: H; C, -C _fi fluorenyl; any one, two or three substituted C's including a halogen atom, a -oxy group or a hydroxyl group C ₆ fluorenyl; C ₂ -alkenyl; containing any one, two or three substituted C ₂ - (: ₆ olefins including a halogen atom, (": ₆ decyloxy or hydroxy group a C ₂ -C ₆ alkynyl group; any one, two or three substituted C ₂ -C _e alkynyl groups including a halogen atom, an alkoxy group of d- or a hydroxyl group; C ₃ -C embankment ₆ cycloalkyl group; a halogen atom-containing optionally include, d- alkoxy or hydroxy group including one, two or three substituents of (: ₃ - C ₆ cycloalkyl; aryl; benzyl; furan group; tetrahydropyranyl; thienyl; pyrrolyl; pyridyl; include a halogen atom-containing, (, - (alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide group ₄ , any mercapto, methylthio, ethylthio, including one, two or three aryl group substituents; include a halogen atom-containing, - ₍₄ embankment group, Any one, two or three substituted pyridyl groups including a carboxy group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three of d-(^ thiol, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio a substituted furanyl group; containing a halogen atom, a sulfhydryl group of c ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted pyranyl groups; containing a halogen atom, -( ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, fluorenyl group) , methylthio, ethylthio, including any one, two or three substituents thienyl; comprising pigment containing atoms, C, - (: ₄ alkyl, nitro, carboxyl, aldehyde, alkoxy , amine group, amide group, carboxamide group, sulfhydryl group, methylthio group, Any one, two or three substituted pyrrolyl groups including an ethylthio group; a decanoyl group of d-c ₆ ; any one, two or three containing a halogen atom, a decyloxy group or a hydroxyl group of d- a substituted alkanoyl group of c, -c ₆ ; an enoyl group of C ₂ -C ₆ ; any one, two or three substituted enoyl groups including a halogen atom, a decyloxy group of d-Ce or a hydroxyl group Alkynyl group of C ₂ _C ₆ ; acetylene group of any one, two or three substituted c ₂ -c _e containing a halogen atom, a decyloxy group or a hydroxyl group of d-Ce; c ₃ -c _B a cycloalkanoyl group; any one, two or three substituted c ₃ -c ₆ cyclodecanoyl groups including a halogen atom or a hydroxyl group of c, -c ₆ ; adamantyl formyl group, substituted Adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (CH ₂ ) _n , n is 0-2; 0; S or NH;

Or R ₃ , ^ are - K ^x i ^{Ri respectively} .

^X 2 ^R 11

Wherein R _in, Ru are each independently any of the following substituent groups: H; C, - alkyl; containing optionally include halogen atoms, C "C ₆ alkoxy or hydroxy, including one, two or three Substituted d-alkyl; C ₂ -(^ alkenyl; any one, two or three substituted C ₂ - C _s containing a halogen atom, a decyloxy group or a hydroxyl group of d- Alkenyl; C ₂ -C ₆ alkynyl group; a halogen atom include containing, C, - ^ alkoxy or hydroxy embankment any inner one, two or three substituents of c ₂ - C ₆ alkynyl group; a C a cycloalkyl group of ₃ - C ₆ ; any one, two or three substituted c ₃ -c ₆ cycloalkyl groups including a halogen atom, an alkoxy group of C- or a hydroxyl group; an aryl group; a benzyl group ; furanyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing fluorenyl group including a halogen atom, c, -c ₄ , nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carbon Any one, two or three substituted aryl groups including an amide group, a fluorenyl group, a methylthio group, an ethylthio group; a thiol group including a halogen atom, dc ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group Any one, two or three substituted pyridyl groups, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; a fluorenyl group containing a halogen atom, c, -c ₄ , Nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethyl sulphide Any one, two or three substituted furanyl groups; including halogen atom, alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, sulfhydryl group, methyl sulfide Any one, two or three substituted pyranyl groups including a thiol group; a fluorenyl group including a halogen atom, d-, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group , any carbon amide group, a mercapto group, methylthio, ethylthio, including one, two or three substituents thienyl; comprising pigment containing atoms, c "c ₄ alkyl with a nitro group, a carboxyl group, an aldehyde group Any one, two or three substituted pyrrolyl groups, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; an alkanoyl group of c, -c ₆ ; Any one, two or three substituted Cr"C ₆ decanoyl groups including a halogen atom, a dc ₆ alkoxy group or a hydroxyl group; a C ₂ -C ₆ enoyl group; containing a halogen atom, dC ₆ Any one, two or three of alkoxy or hydroxy a C ₂ -C ₆ alkenoyl group; a C ₂ -C ₆ alkynyl group; any one, two or three substituted c ₂ -c containing a halogen atom, a decyloxy group or a hydroxyl group of d- _fi alkynyl group; c ₃ -c ₆ cycloalkyl group embankment; includes any halogen atom-containing, C, -C ₆ alkoxy or hydroxy embankment inner one, two or three substituents of C ₃ - (: ₆ Cyclodecanoyl; adamantyl, substituted adamantyl; aroyl; benzyl; furanoyl; pyranoyl; thiophene; pyrrolyl; X, (CH, n 0-2 0; S or NH; X ₂ is (CH, n is 0-2; 0; S or NH.

Further preferably, the compound or a pharmaceutically acceptable salt thereof is provided in the form of a pharmaceutical composition, either alone or in combination with a pharmaceutically acceptable carrier or excipient. The invention also provides a medicament comprising the above compound for preventing and/or treating metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases (eg Alzheimer's) Ill).

In a further aspect, the invention relates to methods of preventing and/or treating metabolic disorders, including but not limited to diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease. The method comprises administering to a subject in need or willing to receive treatment or prevention an effective amount of a compound which selectively modulates the glucagon-like peptide-1 receptor or a pharmaceutically acceptable salt thereof for preventing or treating the above Disease or symptom. Preferably, the above metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases (such as Alzheimer's disease), etc., by administering an effective amount of the following Formula I or a compound represented by II or a pharmaceutically acceptable salt thereof for prevention or treatment:

Where X and Y are respectively (CH, n is 0-2; 0; S or .NH.

Wherein R, R ₂ are each independently one of the following substituents: hydrogen; halogen; anthracene; cyclohexane; hydroxy; nitro; carboxyl; aldehyde; alkoxy; amine; amidoxime; Carboxamide; mercapto; sulfonyl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

R ₃ , R ₄ are each independently any one of the following substituents: hydrogen; anthracene; cyclononene; anthracene; amine; amidoxime; amide; carboxamide; alkylthio; Substituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

In another aspect, the present invention relates to a combination preparation comprising a compound having a selective modulation of a glucagon-like peptide-1 receptor, particularly a function of activating the receptor, or a pharmaceutically acceptable salt thereof Or alone or in combination with a pharmaceutically acceptable carrier or excipient. This compound has the structure of the following formula I or II:

And all of its stereo and optical isomers, or prodrugs, esters, solvates or metal complexes thereof having the same pharmacological action.

Where X and Y are respectively (CH, n is 0-2; 0; S or NH.

Wherein R _{2 is} each independently any one of the following substituents: hydrogen; halogen; anthracene; a cyclic hydrocarbon; a hydroxyl group; a nitro group; a carboxyl group; an aldehyde group; an anthracene group; an amine group; an amine group; an amide group; Carboxamide; fluorenyl; sulfhydryl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

R ₃ , each independently of any of the following substituents: hydrogen; anthracene; cyclononene; alkoxy; amine; alkane Amide; carboxamide; alkylthio; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted a thienyl group; a substituted or unsubstituted pyrrolyl group.

The present invention provides a kit comprising the above combined preparation. The present invention further provides the use of the above combined preparations for the prevention and/or treatment of metabolic disorders including, but not limited to, diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases (eg Alzheimer's). Disease, etc., to achieve selective stimulation of the glucagon-like peptide-1 receptor, improve the patient's symptoms and quality of life.

In order to clarify the contents of the invention and not to be limited thereto, the invention will be described in detail in the following subsections.

A definition

The technical and scientific terms used in the present invention have the same meaning as the general understanding of the general art in the field to which the invention pertains, unless otherwise defined. All patents, applications, published applications and other publications and sequences derived from the Gene Bank and other databases referred to herein are referenced in full revenue. If the definitions set forth in this section are inconsistent with, or inconsistent with, all patents, applications, published applications, and other publications and sequences derived from the Gene Bank and other databases referenced in this patent, or inconsistent, The definition of clarification shall prevail.

As used herein, "a" or "an" refers to "at least one" or "one or more."

As used herein, "metabolic disorder" refers to a related symptom and/or disease caused by metabolic disorders such as sugar, fat or protein caused by various causes.

As used herein, "diabetes" refers to a multi-pathogenic metabolic disease characterized by chronic hyperglycemia accompanied by disorders of sugar, fat and protein metabolism caused by insulin secretion and/or dysfunction. As the time of diabetes is prolonged, the metabolic disorders in the body are not well controlled, leading to chronic complications of tissues such as the eyes, kidneys, nerves, blood vessels and heart, resulting in blindness, gangrene in the lower limbs, Uremic, stroke or myocardial infarction, even life-threatening.

As used herein, "insulin resistance" refers to a decrease in the sensitivity of tissues surrounding the body to insulin, and target tissues such as muscles and fats are resistant to insulin-induced glucose uptake. Insulin resistance is prevalent in type 2 diabetes, accounting for more than 90%, and is one of the main factors in the development of type 2 diabetes.

As used herein, "obesity" refers to an excess of body fat, a male weighing more than 25% of the ideal body weight, or a woman weighing more than 30% of the ideal body weight. Genetic factors, hypothalamic disease, endocrine disorders, overeating and too little activity are all causes of obesity.

As used herein, Alzheimer's disease (Alzheimer's disease, also known as Alzheimer's dementia) is a progressive degenerative disease of the nervous system, clinically characterized by chronic impairment of intelligence and memory. Chronic loss.

As used herein, "cardiovascular disease" includes heart disease, pulmonary heart disease, hypertension, and hyperlipidemia. It has the characteristics of "high incidence, high mortality, high disability rate, high recurrence rate" and "more complications".

As used herein, an "effective amount" of a compound used to treat a particular disease means sufficient improvement or to some extent Reduce the amount of symptoms associated with this disease. This dose can be administered in a single dose or in accordance with a therapeutic regimen. This dose cures the disease, but is typically administered to improve the condition. Repeated administration to improve symptoms may be desirable.

As used herein, "pharmaceutically acceptable salts, esters or other derivatives" include any salt, ester or derivative which is readily prepared by one skilled in the art using known methods. The compounds thus derived and produced can be administered to animals and humans without toxic effects. The compound is either pharmaceutically active or a prodrug.

As used herein, "treatment" means that the disease and symptoms are improved in any way, or other beneficial changes. Treatment also includes the use of the compounds of the invention in medicine.

As used herein, administration of a particular pharmaceutical composition to "improve" the symptoms of a particular disease means any reduction, whether permanent, temporary, prolonged, transient, can be attributed to or associated with the pharmaceutical composition. Relevant application.

As used herein, "substantially pure" means sufficiently uniform that no impurities can be detected by standard analytical methods used by those skilled in the art to evaluate purity, such as thin layer chromatography (TLC), gel electrophoresis, and High performance liquid chromatography (HPLC). Or sufficiently pure also means that even further purification does not alter the physicochemical properties detectable by the substance, such as enzymatic activity and biological activity. Methods for producing substantially chemically pure compounds for purification are well known to those skilled in the art. However, a substantially chemically pure compound can be a stereoisomer or a mixture of isomers. In this case, further purification may increase the specific activity of the compound.

As used herein, "prodrug" refers to a compound that is administered in vivo and which can be metabolized or converted into a biologically, pharmaceutically or therapeutically active form. To produce a prodrug, the pharmaceutically active compound will be modified to reproduce the active compound by metabolic processes. Prodrugs can be designed to alter their metabolic stability, or to transport precursors of properties, to mask their side effects or toxicity, to improve the taste of the drug, or to alter other properties. By virtue of pharmacokinetics and knowledge of the metabolism of the drug in the body, once the pharmaceutically active compound is known, one skilled in the art can design a prodrug of the compound. [See Medicinal Chemistry A Biochemical Approach, Oxford University Press, New York, 1985, pages 388-392].

The terms "substantially" are the same or are either hooked or similar, and the understanding of the relevant art may vary in the context, and is generally at least 70%, preferably at least 80%, more preferably at least 90%, The optimal is at least 95% identical.

As used herein, "composition" refers to any mixture. It may be a solution, suspension, liquid, powder, ointment, aqueous, non-aqueous or any combination thereof.

As used herein, "union" refers to any association between two or more.

The term "object" as used herein includes humans and animals, for example, dogs, cats, cows, pigs, rodents, and the like. Experienced practitioners should understand that the subject is suitable and willing to deal with metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular disease and neurodegenerative diseases (such as Alzheimer's disease). Treatment and prevention.

Any of the protective groups, abbreviations of amino acids and other compounds used herein, are consistent with their general, recognized abbreviations or the biochemical nomenclature issued by the IUPAC-IUB Commission, unless otherwise stated. B glucagon-like peptide-1 receptor modulator

The present invention provides a modulator of glucagon-like peptide-1 receptor function, which increases the prevention and/or treatment of metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases. Sexual diseases (such as

Member of the drug such as Alzheimer's disease. The present invention relates to a compound represented by the following formula I or II, or a pharmaceutically acceptable salt thereof:

Where X and Y are respectively (CH, n is 0-2; 0; S or NH.

Wherein R _t , R ₂ are each independently any one of the following substituents: hydrogen; halogen; anthracene; cyclohexane; hydroxy; nitro; carboxy; aldehyde; methoxy; amine; Carboxamide; mercapto; sulfonyl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

R ₃ , R ₄ are each independently any one of the following substituents: hydrogen; anthracene hydrocarbon; a cyclic anthracene: anthracenyloxy; an amine group; an amine group; an amide group; a carboxamide group; a thiol group; Substituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

The compound of the present invention may be a specific stereoisomer, such as the R- or S-configuration, or a mixture thereof, for example, a racemic mixture. The compounds contemplated herein include all classes of pharmaceutically active compounds, or solutions or mixtures thereof. Also included are hydration types thereof, such as aqueous solutions, hydrolysates or ionized products of these compounds; and these compounds may contain different amounts of bound water molecules.

The compounds of the invention may be prepared or synthesized according to any suitable method. Preferably, the compound is prepared by the synthetic method cited in Section F below.

Further preferably, the compound or a pharmaceutically acceptable salt thereof is provided in the form of a pharmaceutical composition, either alone or in combination with a pharmaceutically acceptable carrier or excipient.

The compounds of the invention may be prepared in the form of their pharmaceutically acceptable salts with any suitable acid. For example, inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, etc.; organic acids such as formic acid, acetic acid, propionic acid, benzoic acid, maleic acid, fumaric acid, succinic acid, tartaric acid, citric acid, etc.; Sulfonic acid such as methanesulfonic acid, ethylsulfonic acid, etc.; arylsulfonate An acid such as benzenesulfonic acid or p-toluenesulfonic acid can be used.

c treatment and prevention methods

The present invention relates to methods for preventing and/or treating metabolic disorders including, but not limited to, diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease. The method comprises administering to a subject in need or willingness to receive treatment or prevention an effective amount of a compound that selectively agonizes the glucagon-like peptide-1 receptor or a pharmaceutically acceptable salt thereof for treating or preventing the above-mentioned diseases. Or symptoms.

Preferably, the above disease is treated or prevented by administering an effective amount of a compound represented by the following formula I or II or a pharmaceutically acceptable salt thereof:

Wherein X and Y are respectively (CH ₂ ) „, n is 0-2; 0; S or NH.

Wherein R, R ₂ are each independently one of the following substituents: hydrogen; halogen; anthracene; cyclohexane; hydroxy; nitro; carboxy; aldehyde; alkoxy; amine; amidoxime; Carboxamide; mercapto; sulfonyl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

R ₃ , each independently of any of the following substituents: hydrogen; alkane; cycloalkylene; alkoxy; amine; amine alkyl; amide; carboxamide; thiol; substituted or unsubstituted aryl Substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

Any subject can be controlled by this method, preferably a mammal, more preferably a human.

The method can be used to control metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular diseases and neurodegenerative diseases (such as Alzheimer's disease). A preferred disease or condition is any disease or condition caused or accompanied by insulin secretion and/or dysfunction.

In the prevention and/or treatment of metabolic disorders, including but not limited to diabetes, insulin resistance and obesity, the invention may be used alone or in combination with other diabetes therapeutics, including insulin sensitizers that are already on the market or to be marketed. compound of. Any suitable metabolic disorder (including but not limited to diabetes, insulin resistance, and obesity) therapeutic agents can be used in combination with the compounds of the present invention. Among them, typical insulin sensitizers include rosiglitazone and pioglitazone.

In a preferred embodiment of the invention, the above insulin sensitizer is not administered when the compound of the invention is used. More preferred The compound of the present invention is used to treat or prevent a disease or symptom caused by the use of the above-mentioned diabetes treatment drugs (including insulin sensitizers) which have been marketed or will be marketed to cause drug resistance or side effects.

Administration of the compounds of the invention alone or in combination with other suitable diabetes therapeutics including insulin sensitizers can be by any suitable method. For example, it can be administered by intracavitary injection, subcutaneous injection, intravenous injection, intramuscular injection, intradermal injection, orally or topically, with a compound of the present invention, or with a pharmaceutically acceptable salt thereof.

In a specific embodiment, the method further comprises performing a diagnosis and prognosis assessment of the disease or condition of the subject to whom it is administered. Any suitable method can be used to diagnose and assess the associated disease or condition and its prognosis. Diagnosis and prognosis can be based on detecting and/or identifying any or all of the in vivo material, such as glycated hemoglobin, enzymes, antigens, antibodies, nucleic acids or other pathological and clinical markers, and related symptoms. For example, a diagnostic or prognostic method disclosed in International Patent No. WO 01/44815 and U.S. Patent No. 5,571,674 can be used.

D combined preparation, kit and method of combination

In another aspect, the invention also relates to a combination formulation comprising a compound that selectively modulates glucagon-like peptide-1 receptor function, or a pharmaceutically acceptable salt thereof, and one or more Therapeutic drugs for metabolic disorders include insulin sensitizers.

Preferably, such a combination comprises a compound of the present invention or a pharmaceutically acceptable salt thereof and a therapeutic agent for one or more metabolic disorders including an insulin sensitizer, which is represented by the following formula I or Π:

Wherein X and Y are each (CH ₂ ) _n and n is 0-2; 0; S or NH.

Wherein RR _{2 is} each independently one of the following substituents: hydrogen; halogen; anthracene; cycloalkyl; hydroxy; nitro; carboxy; aldehyde; alkoxy; amine; amine alkyl; Amido; thiol; sulfhydryl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Substituted thienyl; substituted or unsubstituted pyrrolyl.

R ₃ , R ₄ are each independently any of the following substituents: hydrogen; anthracene; cyclononene; anthracene; amine; amine sulfhydryl; amide; carbonamide; thiol; Substituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl. Any suitable therapeutic agent for diabetes, including insulin sensitizers, can be used in the combination formulations of the invention. In a specific embodiment, one or more of the above-described diabetes therapeutic agents including insulin sensitizers may be included in the combined preparation of the present invention.

In another specific embodiment, a method of treating or preventing a disease or condition caused or accompanied by insulin secretion and/or dysfunction is provided, the method comprising administering an effective amount to a subject in need and willing to receive treatment or prevention The above combined preparation, or a pharmaceutically acceptable salt thereof, thereby treating or preventing the above diseases or symptoms.

In another specific embodiment, there is provided a kit comprising a compound of the present invention or a pharmaceutically acceptable salt thereof, and the use of the above compound or a pharmaceutically acceptable salt thereof for controlling secretion and/or secretion by insulin Instructions for the use of a disease or condition caused by or associated with a dysfunction.

In still another embodiment, a kit is provided comprising the combination described above and instructions for using the combination to treat or prevent a disease or condition caused or accompanied by insulin secretion and/or dysfunction.

E formula and dosage

According to the invention, the compounds of the invention, alone or in combination with other agents, carriers or excipients, are formulated for any suitable route of administration, for example, intraluminal, subcutaneous, intravenous, intramuscular, intradermal Injection, oral or topical. The method can be administered by injection in a single dose in an ampoule, or in a multi-dose container with an added buffer. The formulations may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles. The formulations may contain formulating agents such as suspending, stabilizing and/or dispersing agents. In addition, the active ingredient may be in a powder form with a suitable vehicle, sterile non-pyrogenic water or other solvent before use. The topical medicament of the present invention may be a foam, a gel, an ointment, an ointment, a transdermal patch, or a paste.

Pharmaceutical compositions and methods for administration that may be used in the present invention include, but are not limited to, U.S. Patents 5,736,154, 6,197, 801 Bl, 5,741,511, 5, 886, 039 5, 941, 868, 6, 258, 374B1 and 5, 686, 102.

The size of the dose to be treated or prevented will vary depending on the severity of the condition and the route of administration. The dose and frequency of administration will vary with age, weight, health status, and individual patient response.

It should be pointed out that (the doctor should also know), according to toxicity and side effects, necessary measures must be taken to terminate, interrupt or reduce the therapeutic dose. Conversely, if the clinical response is not obvious (excluding toxicity and side effects), the doctor should adjust the treatment plan to increase the dose.

Any suitable route of administration can be employed. Dosage forms include tablets, lozenges, lenticular capsules, dispersing agents, suspending agents, solutions, capsules, films and the like.

In a practical application, the compound of the present invention, alone or in combination with other preparations, may be in accordance with a general pharmaceutical mixing technique with a pharmaceutical carrier or excipient such as β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. Finely mixed. Depending on the needs of the administration, a special carrier, a local or parenteral route, may be employed. For the preparation of parenteral dosage forms, such as compositions for intravenous injection or infusion, similar pharmaceutical vehicles can be employed, water, glycols, oils, buffers, sugars, preservatives, liposomes, etc., which are well known to those skilled in the art. . Examples of such parenteral compositions include, but are not limited to, 5% W/V Dextrose, saline or other solution. The total dose of the compound of the present invention, alone or in combination with other preparations, can be administered in vial vials in a volume of from about 1 ml to about 2000 ml. The amount of diluent will vary depending on the total dose administered.

The invention also provides a kit for achieving a therapeutic regimen. The kit comprises an effective amount of a compound of the invention in a pharmaceutically acceptable form, alone or in combination with other agents, in one or more containers. The preferred pharmaceutical form is in combination with sterile saline, dextrose solution, buffer solution, or other pharmaceutically acceptable sterile liquid. Alternatively, the composition may be lyophilized or dried; in this case, the kit optionally further comprises a pharmaceutically acceptable solution, preferably a sterile solution, in a container to reconstitute the complex A solution for injection purposes is formed. Typical pharmaceutically acceptable solutions are physiological saline and dextrose solutions.

In another embodiment, the kit of the present invention further comprises a needle or syringe and/or a packaged alcohol pad for injection of the composition, preferably in a sterile form. Instructions for use by a doctor or patient may optionally be included.

F preparation method

The raw materials (0601 - 0610) used in the present invention were synthesized in accordance with the synthesis method described in the Chinese patent (Application No.: 200310109331. 0). The invention is implemented by the following steps:

Compound 1 ( leq) and compound 2 ( leq) are dissolved in a suitable amount of dichloromethane, water, dichloroethane, DMS0, dioxane or a solvent mixture of the above solvents (or a catalytic amount of benzophenone is added) , the reaction temperature is controlled between 0 ° (: ~ 60 ° C, placed in a 150W high pressure mercury lamp or natural light for 1 day to 2 months, during the period by HPLC to detect the reaction. Freeze drying to remove the solvent, the residue with reversed-phase silica gel The product was isolated by column chromatography.

DRAWINGS

Figure 1. Reporter gene method to detect the agonistic effects of compounds on GLP-1R

detailed description

Experimental instruments and reagents

HP1100 HPLC system with binary gradient pump, online vacuum degasser, autosampler, column oven and photodiode array detector. The column is ZORBAX SB-C18 (2.11 x 150 mm, 3. 5 μηι), the mobile phase is acetonitrile/water 65: 35, the flow rate is 0. 2 ml/min, the detection wavelength is 254. The melting point is IA6304 type melting point. NMR was measured by Varian Mercury-300 and Varian Mercury Plus 400 NMR (solvent: CDCl _:i , CD ₃ 0D or DMSO-de); ESI-MS was measured by AB Mariner mass spectrometer, EI by Measured by a Finnigan MAT95 mass spectrometer. The materials used in the synthesis are commercially available products unless otherwise specified. The following specific examples are intended to further illustrate the invention but are not intended to limit the invention.

Example 1: Preparation of Compound GLP-A-1

NMR calibration: δ H 2.50 ppm (DMSO-d ₆ ).

Compound 0601 (1 g) was dissolved in an appropriate amount of DMSO, placed under a 150 W high-pressure mercury lamp for 3 days, 1 ml of water was added, and irradiation was continued for 25-30 days, during which time the reaction was followed by HPLC. After completion of the reaction, the solvent was removed by lyophilization, and the residue was separated by reversed silica gel column chromatography. The pale yellow powdery solid compound GLP-A-1 was obtained.

'Wake up R (300MHz, DMSO -d ₆ ) 10.118 (2H, br. s) , 8.615 (2H, br. s), 8.095 (2H, dd, =4.8 Hz, J ₂ =l.2 Hz), 8.027 (2H, dd, /, =3.9 Hz, / ₂ =1.5 Hz), 7.569 (4H, d, 8.4 Hz), 7.365 (4H, d, 8.7 Hz), 7.318 (2H, dd, Ji=3.9 Hz, / ₂ = 5.1 Hz), 7.280 (2H, m), 7.260 (2H, ra), 7.203 (2H, br. d, 8· 1 Hz), 4.981 (2H, s), 3.228 (6H, s), 2.015 ( 6H, s;).

Example 2: Preparation of Compound GLP-A-2

NMR calibration: δ H 2 · 50 ppm (DMSO-d ₆ ).

Compound 0602 (10 g) was dissolved in an appropriate amount of DMS0, placed under a 150 W high pressure mercury lamp for 3 days, 1 ml of water was added, and irradiation was continued for 25-30 days, during which time the reaction was followed by HPLC. After completion of the reaction, the solvent was removed by lyophilization, and the residue was separated by reversed silica gel column chromatography. The pale yellow powdery solid compound GLP-A-2 was obtained.

'Η匪R (300 MHz, DMSO-de) δ 8.770 (2Η, br. s), 8.090 (2H, d, J=5.1 Hz), 8.026 (2H, d, 7=3.9 Hz), 7.2-7.5 ( 18H, m), 5.011 (2H, s), 3.231 (6H, s).

Example 3: Preparation of Compound GLP-B-1

NMR calibration: δ H 2.50 ppm (DMSO-d ₆ ).

Compound 0603 (1.5 g) was dissolved in an appropriate amount of DMSO, placed under a 150 W high pressure mercury lamp for 3 days, 1 ml of water was added, and irradiation was continued for 25-30 days, during which time the reaction was followed by HPLC. After completion of the reaction, the solvent was removed by lyophilization, and the residue was separated by reversed silica gel column chromatography. A pale yellow powdery solid compound GLP-Bl was obtained.

NMR NMR (300 MHz, DMSO-d ₆ ) δ 9.532 (2H, br. s), 8.433 (2H, br. s), 7.534 (4H, m), 7.428 (4H, d, 8.7 Hz), 7.329 (4H , d, ^8.4 Hz), 7.234 (6H, m), 4.912 (2H, s), 1.453 (18H, s).

Example 4: Preparation of Compound GLP-B-2

NMR calibration: δ H 2.50 ppm (DMSO-d _e ).

Compound 0604 (2.7 g) was dissolved in an appropriate amount of DMS0, placed under a .150 W high pressure mercury lamp for 3 days, 1 ml of water was added, and the irradiation was continued for 20-25 days, during which time the reaction was followed by HPLC. After completion of the reaction, the solvent was removed by lyophilization, and the residue was separated by reversed silica gel column chromatography. A pale yellow powdery solid compound GLP-B-2 was obtained.

'Η NMR (300 MHz, DMS0_d ₆ ) δ 9.585 (2H, br. s), 8.451 (2H, br. s), 7.456 (4H, d, 8.7 Hz), 7.2-7.4 (12H, m), 7.1- 7.2 (8H, m), 6.854 (2H, d, 7.8 Hz), 4.926 (2H, s), 4.384 (4H, s), 1.463 (18H, s).

Example 5: Preparation of Compound GLP-B-3

NMR calibration: δ H 2.51 ppm (DMSO-d ₆ ).

Compound 0605 (1.4 g) was dissolved in an appropriate amount of DMSO, placed under a 150 W high-pressure mercury lamp for 3 days, and 1 ml of water was added thereto, and the irradiation was continued for 25-30 days, during which time the reaction was followed by HPLC. After completion of the reaction, the solvent was removed by lyophilization, and the residue was separated by reversed silica gel column chromatography. The pale yellow powdery solid compound GLP-B-3 was obtained.

NMR NMR (300 MHz, DMSO-d ₆ ) δ 9.554 (2H, br. s), 8.527 (2H, br. s), 7.420 (4H, d, 8.4 Hz), 7.283 (4H, d, 8.7 Hz), 7.215 (2H, br. s), 7.137 (2H, d, ^9.0 Hz), 7.092 (2H, d, J=8.1 Hz), 4.916 (2H, Br. s) , 3.229 (6H, s), 2.257 (6H, s), 1.450 (18H, s).

Example 6: Preparation of Compound GLP-B-4

Scaling NMR: δ H 2.50 ppm (DMSO- d 6).

Compound 0606 (2.2 g) was dissolved in an appropriate amount of DMSO, placed under a 150 W high pressure mercury lamp for 3 days, 1 ml of water was added, and irradiation was continued for 25-30 days, during which time the reaction was followed by HPLC. After completion of the reaction, the solvent was removed by lyophilization, and the residue was separated by reversed silica gel column chromatography. The pale yellow powdery solid compound GLP-B-4 was obtained.

lH NMR (300 MHz, DMS0-d ₆ ) δ 9.565 (2H, br. s), 8.215 (2H, br. s), 7.464 (8H, s), 7.436 (2H, m), 7.122 (2H, m) , 6.991 (2H, dd, Ji=4.5 Hz, J ₂ = 3.9 Hz), 5.055 (2H, s), 1.465 (18H, s).

Example 7: Preparation of Compound GLP-B-5

NMR calibration: δ H 2.50 ppm (DMSO-d ₆ ).

Compound 0607 (3.4 g) was dissolved in an appropriate amount of DMSO, placed under a 150 W high pressure mercury lamp for 3 days, and 1 ml of water was added thereto, and the irradiation was continued for 20-25 days, during which time the reaction was followed by HPLC. After completion of the reaction, the solvent was removed by lyophilization, and the residue was separated by reversed silica gel column chromatography. The pale yellow powdery solid compound GLP-B-5 was obtained. NMR NMR (300 MHz, DMSO-d ₆ ) δ 9.661 (2H, br. s), 8.220 (2H, m), 7.495 (4H, d, 8.4 Hz), 7.428 (4H, d, 8.7 Hz), 7.4- 7.6 (4H, m), 7.305 (4H, m), 5.875 (2H, s), 1.467 (18H, s).

Example 8: Preparation of Compound GLP-B-6

NMR calibration: δ H 2.50 ppm (DMSO-d ₆ ).

Compound 0608 (5 g) was dissolved in an appropriate amount of DMSO, placed under a 150 W high pressure mercury lamp for 3 days, 1 ml of water was added, and irradiation was continued for 25-30 days, during which time the reaction was followed by HPLC. After completion of the reaction, the solvent was removed by lyophilization, and the residue was separated by reversed silica gel column chromatography. The pale yellow powdery solid compound GLP-B-6 was obtained.

NMR NMR (300 MHz, DMS0-d ₆ ) δ 9.584 (2H, br. s), 8.927 (2H, br. s), 8.055 (2H, d, ^5.1 Hz), 7.977 (2H, d, J=2.7 Hz) , 7.631 (4H, d, ^8.4 Hz), 7.546 (4H, d, J=9.0 Hz), 7.489 (4H, d, 8.7 Hz), 7.275 (2H, dd, J,=4.5 Hz, J ₂ =3.9 Hz), 7.053 (4H, d, 8.7 Hz), 5.298 (2H, s), 1.481 (18H, s).

Example 9: Preparation of Compound GLP-B-7

NMR calibration: δ H 2.50 ppm (DMS0_d ₆ ).

Compound 0609 (2.6 g) was dissolved in an appropriate amount of DMS0, placed under a 150 W high pressure mercury lamp for 3 days, 1 ml of water was added, and irradiation was continued for 25-30 days, during which time the reaction was followed by HPLC. After completion of the reaction, the solvent was removed by lyophilization, and the residue was separated by reversed silica gel column chromatography. The pale yellow powdery solid compound GLP-B-7 was obtained.

NMR NMR (300 MHz, DMS0-d ₆ ) δ 9.542 (2Η, br.s), 8.306 (2Η, br. s), 7.2-7.5 (22H, m), 6.903 (4H, d, ^8.7 Hz), 5.066 (4H, s), 4.797 (2H, s), 1.462 (18H, s).

Example 10: Preparation of Compound GLP-C-1

NMR calibration: δ H 2.50 ppm (DMSO-d ₆ ).

Compound 0610 (4.5 g) was dissolved in an appropriate amount of DMSO, placed under a 150 W high pressure mercury lamp for 3 days, 1 ml of water was added, and the irradiation was continued for 25-30 days, during which time the reaction was followed by HPLC. After completion of the reaction, the solvent was removed by lyophilization, and the residue was separated by reversed silica gel column chromatography. The pale yellow powdery solid compound GLP-C-1 was obtained.

NMR NMR (300 MHz, DMS0-d ₆ ) δ 8.513 (2H, br.s), 7347 (4H, m), 7.267 (4H, d, 7· 8 Hz), 7.190 (4H, d, J=7.8 Hz ), 7.143 (2H, d, J^l.5 Hz), 7.042 (2H, d, J=l.5 Hz), 4.880 (2H, s), 2.292 (6H, s), 2.137 (6H, s) . Example 11: Preparation of compound GLP-D-1 NMR calibration: δ H 2. 50 ppm (DMSO-d ₆ ).

Example 12: Preparation of Compound GLP- D-2 calibration of NMR: δ H 2. 50 ppm (DMSO- d 6).

Example 13: Preparation of compound GLP-D-3 NMR calibration: δ H 2. 50 ppm (DMSO-d ₆ ).

Example 14: Preparation of Compound GLP-D-4

NMR calibration: δ H 2. 50 ppm (DMSO-d ₆ ).

Example 15: Preparation of compound GLP-D-5 NMR calibration: δ H 2. 50 ppm (DMS0-d _e ).

Example 16: Preparation of Compound GLP-D-6

NMR calibration: δ H 2. 50 ppm (DMSO-d ₆ ).

Example 17: Preparation of compound GLP-D-7 NMR calibration: δ H 2. 50 ppm (DMSO-d ₆ ).

Example 18: Preparation of Compound GLP-D-8

NMR calibration: δ H 2. 50 ppm (DMS0_d ₆ ).

Example 19: Preparation of Compound GLP-D-9

NMR calibration: δ H 2. 50 ppm (DMSO-d _e ).

Example 20: Preparation of compound GLP-D-10 NMR calibration: δ H 2. 50 ppm (DMSO-d ₆ ).

Example 21: Preparation of compound GLP-D-11 NMR calibration: δ H 2. 50 ppm (DMSO-d _e ).

Example 22: Preparation of Compound GLP-D-12

NMR calibration: δ H 2. 50 ppm (DMSO-d ₆ ).

Example 23: Preparation of Compound GLP-D-13

NMR calibration: δ H 2. 50 ppm (DMSO-d ₆ ).

Example 24: Preparation of compound GLP-D-14 NMR calibration: δ H 2. 50 ppra (DMS0-d ₆ ).

Example 25: Preparation of Compound GLP-D-15

NMR calibration: δ H 2. 50 ppm (DMSO-d ₆ ).

Example 26: Preparation of Compound GLP-D- R 16 bandit calibration: δ H 2. 50 ppm (DMSO- d 6).

Example 27: Biological Activity Test

Reporter gene expression detection

GLP-1R is a G protein-coupled receptor. When GLP-1R binds to an agonist, the G a subunit of the G protein is activated to stimulate adenylate cyclase, resulting in an increase in intracellular cAMP levels. Since the cAMP response element exists in the promoter region of the proinsulin gene, cAMP binds to the response element to initiate transcription of the pre-insulin gene, thereby stimulating insulin expression and secretion (Diabetes, 2000, Vol. 49: 1156-1164). In this experimental method, a human embryonic kidney cell strain (HEK 293) stably transfected with a GLP-1R receptor gene expression vector and a luciferase reporter gene expression vector regulated by a cAMP response element was used to detect its response to a test compound (Cell). Biology, 1992, Vol. 89: 8641-8645; Proc. Natl. Acad. Sci. USA 1987, Vol. 84: 3434-3438). A sample that induces expression of a luciferase reporter gene when screened for a compound is considered to have GLP-1R agonistic activity.

1. 1 Test materials and instruments

Cell line: HEK 293/GLP-lR+Luc cell line stably expressed by GLP-1R and luciferase (National New Drug Screening Center self-built)

Fetal bovine serum (GIBC0)

DMEM medium (GIBC0 company)

Steady-GloTM Luciferase Assay System (Promega)

GLP-1 standard (Sigma)

G418 (Invitrogen)

Forma Carbon Dioxide Incubator (Forma); Victor ² plate reader (Wallac);

Test compound: GLP-A-1, GLP-B-3, GLP-B-6, GLP-B-7

1. 2 Test methods

HEK293/GLP1R+Luc cells were inserted into 96-well culture plates at 20,000/100 μΐ/well, and cultured overnight at 37 ° C in DMEM medium containing 10% fetal calf serum and 500 μ _§ /πι 1 G418. The GLP-1 standard and the test compounds GLP-A-1, GLP-B-3, GLP-B-6, and GLP-B-7 were each diluted to a certain concentration gradient, and then added to the above 96 wells at 1 μM/well. In microplates. Incubate for 6 hours at 37° (:, 5% CO ₂ ). Luciferase activity was measured by the Steady-G1 ₀ ^TM Luciferase Assay System Kit, and the Victor ² reader was used for reading.

1. 3 test results

The results of the study showed that (Fig. 1, Table 1 and Table 2), the compounds GLP-AK GLP-B-3, GLP-B-6, and GLP-B-7 all showed certain agonistic activities. The luciferase activity induced by 10 nM of GLP-1 is 100%, and the highest reaction efficiencies of the above compounds are 48.8 %, 45.3%, 49.3% and 19.1%, respectively, of the compound EC _{5 of} GLP-A-1. The value is 318. 2 nM. EC ₅ of GLP-1 in the same test system. The value is 0. 11 nM.

Table 1. The agonistic activity of the reporter gene detection compounds GLP-B-3 and GLP-B-6

(% reaction, 100% reaction with 10 nM GLP-1)

Relative agonistic activity of GLP-1 (%)

Final concentration (nM)

GLP-B-3 GLP-B-6

200000 33. 0 49. 3

66667 45. 3 8. 9

22222 39. 2 3. 4

7407 16. 9 0. 2

2469 5. 9 -0. 2

823 1. 5 - 0. 4

274 0. 0 -0. 4

0 0. 0 0. 0 Table 2. Induction activity of reporter gene detection compounds GLP-B-7 and GLP-A-1

(% reaction, 100% reaction with 10 nM GLP-1)

GLP-B-7 GLP-A-1

300000 19. 7 48. 8

100000 13. 2 51. 1

33333 6. 4 58. 0 T't'

0·0 o'o 0

ε·ο- Zlf

ε ·ο_

0*19 ο·ο OL£

6f 9 ΐΐΐΐΐ

89.Z00/.00ZN3/X3d 60..90/800Ζ OAV

Claims

Claim

A compound having a substituted cyclobutane structure represented by the following formula I or II, or a pharmaceutically acceptable salt thereof, and all stereo and optical isomers thereof, or a prodrug having the same pharmacological action thereto , its ester, its solvate or its metal complex:

Where X and Y are respectively (C3⁄4)„, n is 0-2; 0; S or NH;

Wherein R, R ₂ are each independently any one of the following substituents: hydrogen; halogen; anthracene; cyclohexane; hydroxy; nitro; carboxy; aldehyde; methoxy; amine; amidoxime; Carboxamide; mercapto; sulfonyl; ether; thioether; substituted or unsubstituted aryl; substituted or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; Substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl;

R ₃ , ! ^ Each independently is any of the following substituents: hydrogen; alkane; cycloalkane; anthracene; amine; amidino; amide; carboxamide; sulfonyl; substituted or unsubstituted aryl; Or unsubstituted pyridyl; substituted or unsubstituted furyl; substituted or unsubstituted pyranyl; substituted or unsubstituted thienyl; substituted or unsubstituted pyrrolyl.

2. A compound having a substituted cyclobutane structure according to claim 1, wherein:

X and Y are respectively (CH ₂ ) _n , r is 0-2; 0; S or NH; R, and R ₂ are each independently:

Wherein R ₅ is any one of the following substituents: H; a fluorenyl group of d-; any one, two or three substituted groups including a halogen atom, a decyloxy group of d-C ₆ or a hydroxyl group (^- (: ₆ fluorenyl; C ₂ -C ₆ alkenyl; any one, two or three substituted (including ₂ - () containing a halogen atom, C, -C ₆ alkoxy group or hydroxyl group : ₆ alkenyl group; a C ₂ -C ₃ alkynyl group; a halogen atom contain any includes, C -Ce group or hydroxyl group of the embankment, including one, two or three substituents of c ₂ -c _e alkynyl a C ₃ -C ₆ cycloalkyl group; any one, two or three substituted (: ₃ -cyclodecyl) groups containing a halogen atom, a C, a C ₆ -oxy group or a hydroxyl group; group; a benzyl group; furyl; tetrahydropyranyl; thienyl; pyrrolyl; pyridyl; include a halogen atom-containing, C, -C ₄ alkyl with a nitro group, a carboxyl group, an aldehyde group, an amine group, amide groups, carboxamide, mercapto, methylthio, ethylthio, including one, two or three aryl group substituents; include a halogen atom-containing, C, _C ₄ embankment , Nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide group, a mercapto group, a methylthio group, B Any one, two or three substituted pyridyl groups including a thio group; an alkyl group including a halogen atom, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group Any one, two or three substituted furanyl groups including a methylthio group and an ethylthio group; containing a halogen atom, a fluorenyl group of dc ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, Any one, two or three substituted pyranyl groups including an amide group, a carboxamide group, a fluorenyl group, a methylthio group and an ethylthio group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxy group Any one, two or three substituted thienyl groups, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, d- Any one, two or three substitutions of ( ₄ ) thiol, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Pyrrolyl; d-c ₆ decanoyl; Any one, two or three substituted C,-C ₆ decanoyl groups such as a halogen atom, a d-Ce alkoxy group or a hydroxyl group; a c ₂ -c ₆ enoyl group; containing a halogen atom, d- Any one, two or three substituted c ₂ - C _e enoyl groups of a C 垸 oxy or hydroxy group; a C ₂ - C ₆ acetylene group; containing a halogen atom, d- (: ₆垸) Any one, two or three substituted c ₂ - c _e alkynyl groups such as an oxy group or a hydroxyl group; a c ₃ -c ₆ cycloalkanoyl group; a decyloxy group or a hydroxyl group containing a halogen atom, dc ₆ Any one, two or three substituted c ₃ -c ₆ cycloalkanoyl groups; adamantyl formyl, substituted adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; Acyl; pyrrolyl; pyranoyl; 乂₁ is (01, n is 0-2; 0; S or NH;

R ₃ and R ₄ are:

Wherein R ₆ is any one of the following substituents: H; d-C ₆ alkyl; or any one, two or three substituted including a halogen atom, d- (: ₆ alkoxy group or hydroxyl group) a thiol group of (:, -^; an alkenyl group of C ₂ -C ₃ ; any one, two or three substituted C ₂ -alkenyl groups including a halogen atom, a decyloxy group of d- or a hydroxyl group; Any one, two or three substituted C ₂ -C ₆ alkynyl groups including a halogen atom, a C-C decyloxy group or a hydroxyl group; a C ₃ -C ₆ ring enthalpy group; optionally include a halogen atom-containing, or hydroxyl group dC embankment ₆ of the inner one, two or three substituents (the embankment cycloalkyl group; an aryl group; a benzyl group; furyl; tetrahydropyranyl; thienyl; pyrrolyl; pyridyl; include halogen atoms contained, (:, - ₍₄ embankment, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide group, a mercapto group, a methylthio group, b thio, including any one, two or three aryl group substituents; include a halogen atom-containing, (:, - ₍₄ embankment group, a nitro group, Any one, two or three substituted pyridyl groups including an aldehyde group, an aldehyde group, an oxo group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; - any one, two or three substitutions of thiol, nitro, carboxy, aldehyde, alkoxy, amino, amido, carboxamido, decyl, methylthio, ethylthio a furanyl group; optionally containing a halogen atom, a thiol group of d-, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group One, two or three substituted pyranyl groups; containing a halogen atom, (:, -(: ₄ alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group) Any one, two or three substituted thienyl groups including a fluorenyl group, a methylthio group, an ethylthio group; a thiol group including a halogen atom, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, Amido, carboxamide, sulfhydryl, methylthio, ethanesulfide Including any one, two or three substituents pyrrolyl; (: - alkanoyl _(6; containing Any one, two or three substituted c, -c ₆ decanoyl groups including a halogen atom, a methoxy group or a hydroxyl group of G-; a C ₂ -C ₆ enoyl group; containing a halogen atom, d Any one, two or three substituted c ₂ -c ₆ enoyl groups such as a decyloxy group or a hydroxy group; a c ₂ -c ₆ alkynyl group; containing a halogen atom, c _r -c ₆ Any one, two or three substituted c ₂ - c ₆ alkynyl groups such as a decyloxy group or a hydroxyl group; a c ₃ - c _fi cycloalkanoyl group; a decyloxy group or a hydroxyl group including a halogen atom, dc ₆ Any one, two or three substituted c ₃ - c ₆ cyclodecanoyl groups; adamantyl, substituted adamantyl form; aroyl; benzyl; furanoyl; pyroyl; thiophene Formyl; pyrroyl group; (CH ₂ ) _n , n is 0-2; 0; S or NH;

Or R ₃ , respectively:

Wherein R ₇ and R ₈ are each independently a substituent of any of the following: H; d-alkyl; any one, two or three substitutions including a halogen atom, an alkoxy group of d-Ce or a hydroxyl group. D-alkyl; C ₂ - ( ₆ alkenyl; any one, two or three substituted C ₂ - (^ containing a halogen atom, C, -C6 oxime or hydroxyl group) Alkenyl; C ₂ - (: ₆ alkynyl; any one, two or three substituted C ₂ - ^ alkynyl groups containing a halogen atom, C, - c _fi alkoxy group or a hydroxyl group; a C ₃ _C ₆ cycloalkyl group; a cyclyl group of any one, two or three substituted c ₃ - c ₆ groups including a halogen atom, a decyloxy group or a hydroxyl group of d-Ce; an aryl group; a furanyl group; a pyrenyl group; a pyrenyl group; a pyrrolyl group; a pyridyl group; an alkyl group, a nitro group, a carboxy group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, methylthio, ethylthio, including any one, two or three aryl group substituents; containing a halogen atom include, dc ₄ alkyl, nitro, Any one, two or three substituted pyridyl groups including a aryl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; :, any one, two or three of -0< alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, ethylthio group a substituted furanyl group; containing a halogen atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and the like Any one, two or three substituted pyranyl groups; containing a halogen atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, Any one, two or three substituted thienyl groups including a methylthio group and an ethylthio group; containing a halogen atom, d- (: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine) Base, amide group, carboxamide group, sulfhydryl group, methylthio group, ethyl sulphide Any one, two or three substituted pyrrolyl groups; c a c ₆ alkanoyl group; any one or two containing a halogen atom or a hydroxyl group including a halogen atom, c, - c ₆ or Three substituted (:, -(: ₆ alkanoyl; c ₂ -c ₆ alkenoyl; any one, two or three containing an alkoxy group including a halogen atom, c, - c ₆ or a hydroxyl group) a substituted c ₂ - c ₆ alkenyl group; a C ₂ -C ₆ alkynyl group; optionally containing a halogen atom include, (alkoxy or hydroxy group including one, two or three substituents of c ₂ -c ₆ alkynyl group; c ₃ -c _fi cycloalkyl group; a halogen atom include containing, C, - any C ₆ alkoxy or hydroxy inner one, two or three substituents of ₍₃ - (: ₆ Cycloalkanoyl; adamantyl, substituted adamantyl; aroyl; benzyl; furanoyl; pyranoyl; thiophene; pyrroyl; X (CH ₂ ), n is 0- 2; 0; S or NH; X ₂ is (CH, n is 0-2; 0; S or NH;

Or R ₃ and R ₄ are:

Wherein any one of the following substituent groups: H; (: alkyl with _6; dC one, two or three substituents containing optionally include halogen, C "C ₆ alkoxy or hydroxy embankment of the inner embankment ₆ of ( _2- ( ₆ -alkenyl); an optionally, two or three-substituted C ₂ -C ₆ alkenyl group containing a halogen atom, a decyloxy group or a hydroxyl group of dC ₆ ; ( _2- (: ₆ alkynyl group; a halogen atom-containing optionally include, Cr "C ₆ alkoxy or hydroxy inner one, two or three substituents of C ₂ -C ₆ alkynyl group of; C ₃ -C ₆ of Any one, two or three substituted (including ₃ -(: ₆ cycloalkyl; aryl; benzyl; furanyl) containing a halogen atom, a decyloxy group or a hydroxyl group of d- ; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, (:, - (: ₄ fluorenyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide) Any one, two or three substituted aryl groups including a thiol group, a thiol group, an ethylthio group, and a halogen atom; Any one, two or three substituted pyridyl groups including a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three of an atom, d-(alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, thiol, methylthio, ethylthio) a substituted furanyl group; containing a halogen atom, a thiol group of a dC ₄ , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methyl group, an ethyl group, and an ethyl group Any one, two or three substituted pyranyl groups; containing a halogen atom, a C ₄ fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, Any one, two or three substituted thienyl groups including a methylthio group and an ethylthio group; containing a halogen atom, -(: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group) , amide group, carboxamide group, thiol group, methylthio group, Any of a group including two or three substituents pyrrolyl; D- alkanoyl; include a halogen atom-containing, C, -C ₆ alkoxy or hydroxy inner any one, two or three a substituted C ₆ decanoyl group; a C ₂ -C _e enoyl group; any one, two or three substituted C ₂ -C _fi containing a halogen atom, a decyloxy group or a hydroxyl group of dC ₆ Alkenoyl; C ₂ -C ₆ alkynyl; alkynyl group containing any one, two or three substituted c ₂ - c _fi including a halogen atom, d- (: ₆ decyloxy or hydroxy group; a cyclodecanoyl group of c ₃ -c ₆ ; any one, two or three substituted c ₃ -c ₆ cyclodecanoyl groups including a halogen atom, a decyloxy group or a hydroxyl group of d-; an adamantyl group , substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X^ (CH, n is 0-2; 0; S or NH;

Or R ₃ and R ₄ are:

Wherein R _{1( )} , Ru are each independently a substituent of any of the following: H; an fluorenyl group; any one, two or three substitutions including a halogen atom, a decyloxy group of Cr "C _e or a hydroxyl group (^-(: ₆垸 ;; ( ₂ - ( ₆ alkenyl; Any one, two or three substituted c ₂ - c ₆ alkenyl groups including a halogen atom, c, -c ₆ decyloxy group or a hydroxyl group; c ₂ -c ₆ alkynyl group; atom, any c "c embankment ₆ alkoxy or hydroxy, including one, two or three substituents of c -C ₆ alkynyl group of _2; C ₃ - C ₆ cycloalkyl group of embankment; include a halogen atom-containing, Any one, two or three substituted c ₃ -c ₆ cycloalkyl groups such as d-alkoxy or hydroxy; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; Pyridyl; containing any halogen atom, (alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio) One, two or three substituted aryl groups; containing a halogen atom, d- (: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, thiol group, methylthio, ethylthio, including any one, two or three substituted pyridyl; contains include halogen atoms, - (: ₄ Any one, two or three substituted furyl groups including a nitro group, a carboxy group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; optionally include a halogen atom, c, -c ₄ alkyl with a nitro group, a carboxyl group, an aldehyde group, embankment group, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, Two or three substituted pyranyl groups; containing an alkyl group including a halogen atom, d-, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methyl group, Any one, two or three substituted thienyl groups including an ethylthio group; including a halogen atom, a fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group Any one, two or three substituted pyrrolyl groups such as a methylthio group or an ethylthio group; an alkanoyl group of d-Ce; or an alkoxy group including a halogen atom, d- or a hydroxyl group; Two or three substituted c, -c ₆ decanoyl; c ₂ -c ₆ alkenyl group; a halogen atom-containing optionally include, d- or hydroxyl group of the embankment, including one, two or three substituents of c ₂ - c ₆ alkenyl group; a C ₂ -c ₆ alkynyl of Any one, two or three substituted c ₂ - c ₆ alkynyl groups containing a halogen atom, c, -c _fi alkoxy group or a hydroxyl group; c ₃ - c ₆ cycloalkanoyl group; Any one, two or three substituted C ₃ -C ₆ cyclodecanoyl groups including a halogen atom, a decyloxy group of d-Ce or a hydroxyl group; adamantyl, substituted adamantyl form; aroyl group Benzyl; furanoyl; pyranoyl; thiophene; pyrroyl; X, (CH, n is 0-2; 0; S or NH; (CH, n is 0-2; 0 ; S or NH;

When R', R ₂ are each independently:

Wherein R ₁₂ and R ₁₃ are each independently a substituent of any of the following: H: - anthracenyl; any one, two or three substituted ds including a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group; An alkyl group of C ₆ ; a C ₂ - C ₆ alkenyl group; any one, two or three substituted C ₂ - (containing a fluorenyloxy group or a hydroxyl group including a halogen atom, C, - C _B ) Alkenyl; C ₂ -C ₃ alkynyl; any one, two or three substituted C ₂ -C ₆ alkynyl group containing a halogen atom, d-alkoxy or hydroxy; C ₃ - a cycloalkyl group of C ₆ ; a mono-, two- or three-substituted c ₃ -c ₆ cyclodecyl group containing a halogen atom, a decyloxy group or a hydroxyl group of d-C _e ; an aryl group; a benzyl group ; furanyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, d- (indenyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide) Any one, two or three substituted aryl groups including a thiol group, a thiol group, a methylthio group, and an ethylthio group; Containing any one or two including a halogen atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Or three substituted pyridyl groups; containing a halogen group including a halogen atom, c, -c ₄ , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methyl group Any one, two or three substituted furanyl groups including an ethylthio group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carbon amide any group, a mercapto group, methylthio, ethylthio, including one, two or three of the substituents pyranyl; containing a halogen atom include, ^ - alkyl with, nitro, carboxyl, aldehyde, oxygen embankment ₄ Any one, two or three substituted thienyl groups including an amino group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and a halogen atom, (:, - (: ₄ ) Sulfhydryl, nitro, carboxyl, aldehyde, decyloxy, amine, Any one, two or three substituted pyrrolyl groups such as an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; a decanoyl group of dC ₆ ; an alkoxy group containing a halogen atom, C Ce or Any one, two or three substituted d-C ₆ decanoyl groups such as a hydroxyl group; a C ₂ - C _e enoyl group; any one containing a halogen atom, a C, a decyloxy group or a hydroxyl group , two or three substituted c ₂ -c ₆ enoyl groups; C ₂ -C ₆ alkynyl groups; containing any one, two or three substitutions including a halogen atom, a fluorenyloxy group or a hydroxyl group a c ₂ - c ₆ alkynyl group; a c ₃ - c ₆ cyclodecanoyl group; any one, two or three substituted groups including a halogen atom, c, -C _fi alkoxy group or a hydroxyl group ( Cyclodecanoyl c _e ; adamantyl formyl, substituted adamantyl formyl; aroyl; benzyl; furanoyl; pyranoyl; thiophene; pyrroyl; X, (CH ₂ ) _n , n is 0-2; 0; S or NH; is (CH, n is 0-2; 0; S or NH,

R ₃₎ are:

Wherein is any one of the following substituents: H; ("(: ₆ fluorenyl; containing any one, two or three substituted including a halogen atom, (:, - ( ₆ decyloxy or hydroxy) ₂₆ is alkenyl: containing optionally include a halogen atom, d- or hydroxyl group of the embankment, including one, two or three of the substituents (; C ₂ -C ₆ alkenyl group; a C ₆ alkyl with the - C, groups; C ₂ - ₍₆ alkynyl; include a halogen atom-containing, - or any embankment hydroxyl group including one, two or three substituents of c ₂ -c ₆ alkynyl group; C ₃ -C ₆ a cycloalkyl group; any one, two or three substituted C ₃ -C ₆ cycloalkyl groups including a halogen atom, a C, or an alkoxy group; a aryl group; a benzyl group; a pyranyl group; a pyrenyl group; a pyrrolyl group; a pyridyl group; a pyridyl group; a fluorenyl group, a fluorenyl group, a nitro group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group , methylthio, ethylthio, including any one, two or three aryl group substituents; containing a halogen atom include, dC alkyl with _4-nitro Any one, two or three substituted pyridyl groups including a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; Any one, two or three substitutions of ₄ : alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio a furanyl group; optionally containing a halogen atom, a thiol group of d-, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group One, two or three substituted pyranyl groups; containing an alkyl group, a C, a alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a group Any one, two or three substituted thienyl groups including a thio group or an ethylthio group; Any one or two containing a halogen atom, a -(^ thiol group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group) two or three substituents pyrrolyl; d-Ce acyl group of the embankment; containing optionally include a halogen atom, dc embankment ₆ alkoxy or hydroxy, including one, two or three substituents of C, -C ₆ acyl embankment An alkenoyl group of c ₂ -c _{6 ;} an enoyl group containing any one, two or three substituted c ₂ - C _e including a halogen atom, a decyloxy group of dc ₆ or a hydroxyl group; C ₂ - C ₆ Alkynyl; alkynyl group containing any one, two or three substituted c ₂ - c ₆ groups including a halogen atom, (:, - (: ₆ decyloxy group or hydroxy group); c ₃ -c ₆ Cyclodecanoyl; any one, two or three substituted c ₃ - c ₆ cyclodecanoyl groups including a halogen atom, a decyloxy group of d- or a hydroxy group; an adamantyl group, a substituted adamantyl group Aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; Is (CH ₂ )„, n is 0-2; 0; S or NH;

Or R ₃ and R ₄ are:

Wherein R ₇ and R ₈ are each independently a substituent of any of the following: H; ((: ₆ alkyl; one or two, including a halogen atom, C, -C ₆ alkoxy group or a hydroxyl group) Or an alkyl group of three substituted d-C ₆ ; (: ₂ - (: ₆ alkenyl; any one, two or three substituted including a halogen atom, an alkoxy group of d- or a hydroxyl group) C ₂ -C ₆ alkenyl; C ₂ -C ₆ alkynyl; any one, two or three substituted C ₂ - (: ₆ containing a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group; Alkynyl; C ₃ -C ₆ cycloalkyl; any one, two or three substituted C ₃ - C ₆ ring containing a halogen atom, C, -C ₆ decyloxy or hydroxy group Alkyl; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, (^-(: ₄ alkyl, nitro, carboxyl, aldehyde, alkoxy) Any one, two or three substituted aryl groups including an amino group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any prime atom, C, -C ₄ alkyl with a nitro group, a carboxyl group, an aldehyde group, embankment group, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two Or three substituted pyridyl groups; containing a halogen group including a halogen atom, C, -C ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methyl group Any one, two or three substituted furanyl groups including an ethylthio group; a mercapto group including a halogen atom, c, -c ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group Any one, two or three substituted pyranyl groups including a carbamide group, a fluorenyl group, a methylthio group, an ethylthio group, a thiol group including a halogen atom, a nitro group, a carboxy group, an aldehyde group, Any one, two or three substituted thienyl groups including an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; and a fluorene group including a halogen atom, -(: ₄ Base, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carbon Any one, two or three substituted pyrrolyl groups including an amide group, a fluorenyl group, a methylthio group, an ethylthio group; a decanoyl group of dC ₆ ; an alkoxy group or a hydroxyl group containing a halogen atom, d-c _fi within any one, two or three substituents of c, - c ₆ alkanoyl; C ₂ -c ₆ alkenyl group; a halogen atom-containing optionally include, d- c ₆ alkoxy or hydroxy, including a , two or three substituted c ₂ -c ₆ enoyl groups; C ₂ -C ₆ alkynyl groups; containing any one, two or three including a halogen atom, an alkoxy group of dC ₆ or a hydroxyl group Substituted c ₂ - c ₆ alkynyl; c ₃ - c ₆ cyclodecanoyl; any one, two or three substituted (including 3) including a halogen atom, a d-oxyl group or a hydroxyl group (: ₃ -(: ₆ of Cyclodecanoyl; adamantyl formyl, substituted adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; (01, n is 0-2; 0; S or NH; is (CH ₂ ) _n , n is 0-2; 0; S or NH;

Or R ₃ and R ₄ are:

Wherein R ₉ is any one of the following substituents: H; an alkyl group of d-C ₆ ; any one, two or three substituted groups including a halogen atom, a decyloxy group of d- or a hydroxyl group (^- (: alkyl with _6; C ₂ - ₍₆ alkenyl group; a halogen atom-containing optionally include, dC ₆ alkoxy or hydroxy, including one, two or three substituents of (: ₂ - _(6-ene (: ₂ -( ₆ alkynyl; alkynyl group containing any one, two or three substituted c ₂ -c ₆ including a halogen atom, (^-(: ₆ decyloxy or hydroxy group) a C ₃ -C _e cycloalkyl group; any one, two or three substituted C ₃ -C _fi cycloalkyl groups including a halogen atom, a C,-C ₆ decyloxy group or a hydroxyl group; Benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing alkyl group including a halogen atom, dC ₄ , nitro: carboxyl group, aldehyde group, decyloxy group, amine group, amide group Any one, two or three substituted aryl groups, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; a thiol group including a halogen atom, C, - Any one, two or three substituted pyridyl groups including a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one or two of an atom, a sulfhydryl group of a d-C ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, or a three-substituted furyl group; containing a halogen atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, Any one, two or three substituted pyranyl groups; containing an alkyl group including a halogen atom, dc ₄ , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group Any one, two or three substituted thienyl groups including a methylthio group and an ethylthio group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group , carboxamide, sulfhydryl, methylthio, Thio, including any one, two or three substituents pyrrolyl; d- c embankment ₆ acyl; include a halogen atom-containing, c, alkoxy or hydroxy -C ₆ including any one, two, Or three substituted c, - c ₆ decanoyl groups; c _{2 -} c ₆ enoyl groups; any one, two or three substituted c groups including a halogen atom, a decyloxy group or a hydroxyl group of d- ₂ -c ₆ enoyl; c ₂ -c ₆ alkynyl; any one, two or three substituted c ₂ - c ₆ alkyne containing a halogen atom, a decyloxy group or a hydroxyl group of d- acyl; c ₃ -c ₆ cycloalkyl group; a halogen atom includes contain any, or a hydroxyl group dC embankment ₆ of the inner one, two or three of c ₃ -c _fi substituted cycloalkyl group; an adamantyl embankment Formyl, substituted adamantyl formyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X, (CH, n is 0-2; 0; S or NH;

Or R ₃ , respectively:

Where R,. , Ru each independently is any one of the following substituents: H; C, - fluorenyl; any one, two or three substituted - alkyl groups including a halogen atom, a decyloxy group or a hydroxyl group of dG (: ₂ -(: ₆ alkenyl; any one, two or three substituted C ₂ -C ₆ alkenyl group including a halogen atom, a decyloxy group of dC ₆ or a hydroxyl group; C ₂ - (: ₆ alkynyl; any one, two or three substituted C ₂ - C _fi alkynyl group including a halogen atom, an alkoxy group of dC ₆ or a hydroxyl group; a C ₃ -C ₆ ring enthalpy Any one, two or three substituted C ₃ -C ₆ cyclodecyl groups containing a halogen atom, a C,-C ₆ decyloxy group or a hydroxyl group; an aryl group; a benzyl group; a furyl group; Pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, -(: ₄ alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, Any one, two or three substituted aryl groups including a methylthio group and an ethylthio group; a thiol group including a halogen atom, d-, Any one, two or three substituted pyridyl groups including a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one or two of atoms, -(: ₄ , nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio) three substituted furanyl; containing a halogen atom include, (^ - ₍₄ alkyl, nitro, carboxyl, aldehyde, embankment group, an amine group, an amide group, a carbonamide group, a mercapto group, a methylthio group, b Any one, two or three substituted pyranyl groups including a thio group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group , methylthio, ethylthio, including any one, two or three substituents thienyl; include a halogen atom-containing, ₍₄ ^ embankment group, a nitro group, a carboxyl group, an aldehyde group, an amine group , amide group, carboxamide group, sulfhydryl group, methylthio group Ethylthio, including any one, two or three substituents pyrrolyl; C, -C ₆ alkyl group; a halogen atom-containing optionally include, dC ₆ alkoxy or hydroxy, including one, two, or a three-substituted d-Ce decanoyl group; a C ₂ -C ₆ enoyl group; any one, two or three substituted c ₂ - including a halogen atom, a Ct-Ce decyloxy group or a hydroxyl group _; An alkenoyl group of c ₆ ; an alkynyl group of c ₂ -c ₆ ; any one, two or three substituted c ₂ -c ₆ containing a fluorenyloxy group or a hydroxyl group including a halogen atom, c, -c ₆ Alkynyl; c ₃ - c _fi cyclodecanoyl; any one, two or three substituted (: ₃ -(: ₆ cyclodecanoyl) containing a halogen atom, a C ₆ decyloxy group or a hydroxyl group ; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrroyl; X, (CH ₂ ) _n , n 0-2; 0; S or NH; is (CH, π is 0 - 2; 0; S or ΝΗ;

Further preferably, when RR _{2 is} each independently:

Wherein RH is any one of the following substituents: H; (:, -(: ₆ fluorenyl; any one, two or three substituted including a halogen atom, ( ₆ alkoxy group or hydroxyl group) dC ₆ alkyl; (: ₂ - (: ₆ alkenyl group; a halogen atom includes contain any, or a hydroxyl group dC embankment ₆ of the inner one, two or three substituents of (: ₂ - ( : ₆ alkenyl; (: ₂ -(: ₆ alkynyl; any one, two or three substituted C ₂ -C containing a halogen atom or a hydroxyl group including a halogen atom, C, - C ₆ ₆ alkynyl group; C ₃ - C ₆ cycloalkyl group of embankment; include a halogen atom-containing, C, - ^ alkoxy or hydroxy embankment any inner one, two or three substituents of ^ - cycloalkyl group embankment; Aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; Containing halogen atoms including, _ ^ (: alkyl with arbitrary _4, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including a , two or three substituted aryl groups; containing a halogen atom, (^-(: ₄ fluorenyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, Any one, two or three substituted pyridyl groups including a methylthio group and an ethylthio group; containing a halogen atom, (:, _(: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, alkoxy group) , any amine, amide, carboxamide group, an group, methylthio, ethylthio, including one, two or three substituents furanyl; containing pigment atoms include, dc embankment ₄ group, a nitro group, Any one, two or three substituted pyranyl groups including a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; (,-(: ₄ thiol, nitro, carboxyl, aldehyde, decyloxy, amine Groups, amide groups, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents thienyl; include halogen atoms contained, (: ₄ embankment group, a nitro group, a carboxyl group Any one, two or three substituted pyrrolyl groups, an aldehyde group, an oxime group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; a cyanyl group of d-c ₆ Any one, two or three substituted dC ₆ decanoyl groups including a halogen atom, a decyloxy group or a hydroxyl group; a c ₂ - C ₆ enoyl group; containing a halogen atom, d-Ce Any one, two or three substituted c ₂ -c _fi enoyl groups such as alkoxy or hydroxy; c ₂ -c ₆ alkynyl; containing a halogen atom, ( ₆ decyloxy or hydroxy group) Any one, two or three substituted c ₂ -c ₆ alkynyl groups; c ₃ -c ₆ cycloalkanoyl group; any one containing a halogen atom, a decyloxy group of CrCe or a hydroxyl group; two or three substituents of C ₃ -C ₆ cycloalkyl group embankment; adamantyl embankment formyl, substituted gold When S or NH,; formyl alkoxy; aroyl; a benzyl group; furoyl; formyl pyran; thenoyl; pyrroyl; X (CH, n is 0-2; 0

R ₃ and R ₄ are:

Wherein Re is any one of the following substituents: H; C, -C ₆ alkyl; or any one, two or three substituted including halogen atom, d- (: ₆ decyloxy or hydroxy group) C ₂ includes contain any halogen atoms, C "C ₆ alkoxy or hydroxy embankment inner one, two or three substituents of - (d- group of embankment;; C ₂ -C ₆ alkenyl group of: ₆ Alkenyl; (: "( ₆ : alkynyl; any one, two or three substituted C ₂ -C ₆ alkynyl group including a halogen atom, a decyloxy group or a hydroxyl group of Ci-Ce; C ₃ - C ₆ cycloalkyl group embankment; includes any containing a halogen atom, C "C _e is a hydroxyl group or embankment, including one, two or three substituents of C ₃ - C _fi cycloalkyl; aryl; Benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing a halogen atom, d-(^ alkyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, Any one, two or three substituted aryl groups including a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; and a fluorene including a halogen atom, C, - Any one, two or three substituted pyridyl groups, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; Any one, two or three of a halogen atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group. a substituted furanyl group; containing a halogen atom, (:, -(: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, fluorenyl group, methylthio group, Any one, two or three substituted pyranyl groups including an ethylthio group; an alkyl group including a halogen atom, d-, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, Amide groups, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents thienyl; containing a halogen atom include, ^ _ (: ₄ embankment group, a nitro group, a carboxyl group Any one, two or three substituted pyrrolyl groups, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; a decanoyl group of d-Ce; Any one, two or three substituted d-C ₆ decanoyl groups including a halogen atom, a decyloxy group or a hydroxyl group; a c ₂ -c ₆ alkenoyl group; containing a halogen atom, c, Any one, two or three substituted c ₂ -c ₆ alkenoyl groups of -c _fi alkoxy or hydroxy; C ₂ -C ₆ alkynyl; containing a halogen atom, d-c ₆ Any one, two or three substituted c ₂ - c ₆ alkynyl groups, alkoxy or hydroxy; c ₃ - c ₆ cyclodecanoyl; containing a halogen atom including a halogen atom, c, -c ₆ including a hydroxyl group or any one, two or three substituents of c ₃ -c ₆ cycloalkyl group embankment; adamantyl embankment formyl, taking Adamantane formyl embankment; aryl group; a benzyl group; furoyl; formyl pyran; thenoyl; pyrroyl; X ₂ is (CH ₂₎ _{n, n} is 0-2; 0; S, or NH;

Or R _3, respectively:

Wherein R ₇ and R _s are each independently a substituent of any of the following: H; (:, - (: ₆ alkyl; any one or two containing a halogen atom, a d-oxyl group or a hydroxyl group) Or a three-substituted fluorenyl group; a C ₂ - (: ₆ alkenyl group; any one, two or three substituted C ₂ -C ₆ containing a halogen atom, a decyloxy group or a hydroxyl group of d-Cs alkenyl; (: ₂ - (: ₆ alkynyl group; a halogen atom-containing include any, (the embankment of Ce alkoxy or hydroxy, including one, two or three substituents having ₂ to C ₆ alkynyl; _{C. 3} -C ₆ cycloalkyl; any one, two or three substituted C ₃ -C ₆ cycloalkyl groups including a halogen atom, a d-C ₆ decyloxy group or a hydroxyl group; an aryl group; ; furanyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing a halogen atom, C, - (: ₄ alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide Any one, two or three substituted aryl groups, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one or two of (^-(: ₄ alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio) Or a three-substituted pyridyl group; containing a halogen atom, an alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group Any one, two or three substituted furan groups; containing a halogen atom, a thiol group of dC ₄ , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, methylthio, ethylthio, including any one, two or three of the substituents pyranyl; include halogen atom-containing, ₍₄ embankment group, a nitro group, a carboxyl group, an aldehyde group, embankment group, an amine group, Any one, two or three substituted thienyl groups including an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, (^-(: ₄ fluorenyl group, nitro group, Carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carbonyl group Any group, a mercapto group, methylthio, ethylthio, including one, two or three substituents pyrrolyl; CrC embankment ₆ acyl; include a halogen atom-containing, C, -C ₆ alkoxy or hydroxy embankment in Any one, two or three substituted (-C ₆ decanoyl groups; C ₂ -C ₆ enoyl groups; containing any halogen atom, (^-( ₆ decyloxy group or hydroxy group) One, two or three substituted C ₂ -C ₆ enoyl groups; C ₂ -C ₆ alkynyl groups; any one or two containing an alkoxy group including a halogen atom, c, -c ₆ or a hydroxyl group c-three or a substituted alkynyl group of ₂ -c _6; c ₃ - _{c. 6} of the ring acyl embankment; Any one, two or three substituted C ₃ - (: ₆ cycloalkanoyl groups; adamantyl formyl, substituted adamantyl formyl group; aroyl group containing a halogen atom, a decyloxy group or a hydroxyl group of d- ; benzoyl; furoyl; pyranoyl; thiophene; pyrroyl; X (CH ₂ ), n is 0-2; 0; S or NH; X ₂ is (CH ₂ ) _n , n Is 0-2; 0; S or NH;

Or R _3, respectively:

Wherein R ₉ is any one of the following substituents: H; (, - (: ₆ fluorenyl; any one, two or three including a halogen atom, d- (: ₆ decyloxy or hydroxy group) Substituted (: "(: ₆ fluorenyl; C ₂ - C ₆ alkenyl; any one, two or three substituted C ₂ - including a halogen atom, an alkoxy group of dC ₆ or a hydroxyl group) An alkenyl group of C ₆ ; a C ₂ -C ₆ alkynyl group; an alkynyl group containing any one, two or three substituted c ₂ -c _fi groups including a halogen atom, a decyloxy group of -c, or a hydroxyl group; a C ₃ -C _e cycloalkyl group; any one, two or three substituted (: ₃ - C ₆ cyclodecyl) groups including a halogen atom, C, -C _fi alkoxy group or a hydroxyl group; Aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, d-( ₄ fluorenyl, nitro, carboxyl, aldehyde, decyloxy, amine, Any one, two or three substituted aryl groups including an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, an alkane Any one, two or three substituted pyridyl groups including a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group: Any one or two of a halogen atom, d- (: ₄ alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, fluorenyl group, methylthio group, ethylthio group) Or three substituted furanyl groups; containing a halogen atom, a fluorenyl group of dc ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethyl sulfide group, including any one, two or three of the substituents pyranyl; include halogen atom-containing, ₍₄ embankment group, a nitro group, a carboxyl group, an aldehyde group, embankment group, an amine group, an amide group, carbonamide group Any one, two or three substituted thienyl groups including a fluorenyl group, a methylthio group, an ethylthio group; containing a sulfhydryl group, a - (: ₄ fluorenyl group, a nitro group, a carboxyl group, an aldehyde group, an anthracene group) Base, amine group, amide group, carboxamide group, sulfhydryl group, methyl sulfide Any one, two or three substituted pyrrolyl groups including a thiol group; a decanoyl group of d-; any one, two or three containing a halogen atom, a decyloxy group of dc ₆ or a hydroxyl group a substituted alkanoyl group of d-c ₆ ; a C ₂ -C ₆ alkenoyl group; any one, two or three substituted c ₂ - c containing a halogen atom, a decyloxy group or a hydroxyl group of d- ₆ alkenoyl; C ₂ -C ₆ alkynyl group; a halogen-containing include any atom, D- (alkoxy or hydroxy embankment ₆ of the inner one, two or three substituents of c ₂ - C ₆ alkynyl group ; c ₃ -c ₆ cycloalkyl group; a halogen atom includes contain any, or a hydroxyl group dC embankment ₆ of the inner one, two or three substituents of c ₃ - c _e embankment cycloalkyl group; an adamantyl carboxylic embankment Acyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X, (CH ₂ ), n is 0-2; NH;

Or R ₃ , I ^ are: X2R11

Wherein R _{1 ( )} , Ru are each independently a substituent of any of the following: H; a fluorenyl group of C, -C ₆ ; any one or two containing a halogen atom, a decyloxy group or a hydroxyl group of d- or Three substituted (: ₆ fluorenyl; (: ₂ - (: ₆ alkenyl; any one, two or three substituted C ₂ containing a halogen atom, a d-oxyl group or a hydroxyl group) -C ₆ alkenyl; C ₂ - (: ₆ alkynyl; any one, two or three substituted C ₂ including a halogen atom, (:, - (: ₆ decyloxy or hydroxy group) -C ₆ alkynyl; C ₃ -C ₆ cyclodecyl; any one, two or three substituted C ₃ -C ₆ containing a sulfhydryl group or a hydroxyl group including a aryl group or d-Cs Cycloalkyl; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing halogen atom, (^-(: ₄ fluorenyl, nitro, carboxyl, aldehyde, hydrazine) Any one, two or three substituted aryl groups including an oxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; a single atom, (^-(: ₄ thiol, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio) Two or three substituted pyridyl groups; containing a halogen atom, (:, -(: ₄ alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, thiol group, Any one, two or three substituted furanyl groups including a methylthio group and an ethylthio group; containing a halogen atom, a C, a thiol group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group Any one, two or three substituted pyranyl groups including a amide group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and a halogen atom, (-, _4- , fluorenyl group, Any one, two or three substituted thienyl groups including a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; atoms, dC ₄ alkyl group, a nitro group, a carboxyl group, an aldehyde group, embankment group, amine Amide groups, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents pyrrolyl; Cr "C ₆ alkoxy group; a halogen atom include containing, C, -C ₆ Any one, two or three substituted d-C _e decanoyl groups such as alkoxy groups or hydroxyl groups; C ₂ -C ₆ enoyl groups; containing a fluorenyloxy group including a prime atom, d-C _e or Any one, two or three substituted C ₂ -C ₆ enoyl groups such as a hydroxyl group; a C ₂ -C _e alkynyl group; or an alkoxy group including a halogen atom, d-Cs or a hydroxyl group One, two or three substituted C ₂ -C ₆ alkynyl groups; C ₃ -C ₆ cyclodecanoyl group; any one, two or three containing a halogen atom, a decyloxy group or a hydroxyl group including dG Substituted (: ₃ -(: ₆ cycloalkanoyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrroyl; 乂₁ is (0, n is 0-2; 0; S or NH _; X ₂ is (CH, n is 0-2; 0; S or NH;

When RR _{2 is} independent of each other:

Wherein R, ₅ and R ₁₆ are each independently one of the following substituents: H; (:, -( ₆ fluorenyl; containing a halogen atom, C, -C ₆ decyloxy or hydroxy group, any one of , two or three substituted C, -0>fluorenyl; C ₂ - (alkenyl; Include a halogen atom-containing, C, - any C ₆ alkoxy or hydroxy inner one, two or three substituents of C ₂ - C ₆ alkenyl; C ₂ -C ₆ alkynyl group; comprising comprising! ¾ prime atom, a C _"6 alkoxy or hydroxy C embankment, including any of one, two or three substituents of c ₂ _c ₆ alkynyl group; a cycloalkyl group of c ₃ -c _e; include a halogen atom-containing, Any one, two or three substituted c ₃ -c ₆ cycloalkyl groups of c ₆ decyloxy or hydroxy; aryl; benzyl: furyl; pyranyl; thienyl; pyrrole Pyridyl; containing a halogen atom, (^-^, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted aryl groups; containing a halogen atom, (, - (: ₄ alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carbon amide) Any one, two or three substituted pyridyl groups including a thiol group, a thiol group, a methylthio group, and an ethylthio group; Arbitrary ₍₄ embankment group, a nitro group, a carboxyl group, an aldehyde group, embankment group, amine, amide, carboxamide, mercapto, methylthio, ethylthio, including one, two or three substituents of a furanyl group; a fluorenyl group including a halogen atom, c, -c ₄ , a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a thiol group, a methylthio group, an ethylthio group Any one, two or three substituted pyranyl groups; containing a halogen atom, - ( ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, fluorenyl group) Any one, two or three substituted thienyl groups including a methylthio group and an ethylthio group; containing a halogen atom, d-(alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group) Any one, two or three substituted pyrrolyl groups, an amide group, a carboxamide group, a decyl group, a methylthio group, an ethylthio group; a decanoyl group of d-; an alkoxy group containing a halogen atom, dC ₆ Any one, two or three substituted d-c ₆ a decanoyl group; an alkenoyl group of c ₂ -c _{6 ;} an enoyl group having any one, two or three substituted c ₂ - c _fi including a halogen atom, a decyloxy group or a hydroxyl group; c ₂ - c _fi Any one, two or three substituted c ₂ -c ₆ alkynyl groups containing a halogen atom or a hydroxyl group including a halogen atom, c, -c ₆ ; a c ₃ -c ₆ cyclodecanoyl group; Any one, two or three substituted C ₃ - (: ₆ cycloalkanoyl groups; adamantyl form, substituted adamantyl group, including a halogen atom, a decyloxy group of d-Ce or a hydroxyl group; Aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrroyl; X (CH ₂ ), n is 0-2; 0; S or NH; (CH, n is 0- 2; 0; S or NH,

R ₃₎ I ^ are:

Wherein R ₆ is any one of the following substituents: H; an alkyl group of d-C ₆ ; any one, two or three substituted groups including an alkoxy group including a halogen atom, C, -C ₆ or a hydroxyl group; Alkyl; C ₂ -C ₆ alkenyl; any one, two or three substituted C ₂ - (: ₆ alkenyl; C containing a halogen atom, a decyloxy group or a hydroxyl group of d-; ₂ - alkynyl; optionally include a halogen atom-containing, C, -C ₆ alkoxy or hydroxy embankment inner one, two or three substituents of C ₂ - C ₆ alkynyl group; C ₃ - cycloalkyl Any one, two or three substituted C ₃ -C ₆ cyclodecyl groups including a halogen atom, a decyloxy group or a hydroxyl group of dC ₆ ; an aryl group; a benzyl group; a furyl group; a pyranyl group; ; thienyl; pyrrolyl; pyridyl; containing fluorenyl group including a halogen atom, C, -C ₄ , nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, sulfhydryl group, methyl sulfide Any one, two or three substituted aryl groups including a thiol group, a thiol group containing a halogen atom, C "C ₄ ", a nitro group, a carboxy group Base, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, sulfhydryl group, methylthio group, B Any one, two or three substituted pyridyl groups including a thio group; a fluorenyl group including a halogen atom, d-, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group , any mercapto, methylthio, ethylthio, including one, two or three substituents furanyl; containing pigment include atoms, C _"4 alkyl with C, nitro, carboxyl, aldehyde, alkoxy Any one, two or three substituted pyranyl groups, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a halogen atom, (:, -(: ₄ ) Any one, two or three substituted thienyl groups of an alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one or two containing a halogen atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group. Or three substituted pyrrolyl; d-decanoyl; Any one, two or three substituted d-alkanoyl groups including a halogen atom, c- or C ₆ decyloxy group or a hydroxyl group; a C ₂ -C ₆ alkenoyl group; containing a halogen atom, d- Any one, two or three substituted c ₂ -c _e enoyl groups such as alkoxy groups or hydroxyl groups of Ce; c ₂ -c ₆ alkynyl groups; containing an oxygen atom including a halogen atom, d-c ₆ Any one, two or three substituted c ₂ - c ₆ alkynyl groups including a hydroxyl group; a c ₃ - c ₆ cyclodecanoyl group; and a halogen atom or a hydroxyl group including a halogen atom, d- Any one, two or three substituted c ₃ c ₆ cycloalkanoyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; Pyrrolyl; is ((3⁄4, n is 0- 2; 0; S or NH;

Or R ₃ and R ₄ are:

Wherein R ₇ and R ₈ are each independently a substituent of any of the following: H; a thiol group of -Ce; any one, two or three containing a fluorenyloxy group or a hydroxyl group including a halogen atom, C, -C ₆ a substituted decyl group of d-C _e ; C "C _fienyl ; any one, two or three substituted (including ₂ - ( ₆ olefins) including a halogen atom, a methoxy group or a hydroxyl group) a C ₂ -C _B alkynyl group; any one, two or three substituted C ₂ -C ₆ alkynyl groups including a halogen atom, an alkoxy group or a hydroxyl group; a C ₃ -C ₆ ring; Any one, two or three substituted C ₃ -C ₆ cyclodecyl groups including a halogen atom, a C ₆ alkoxy group or a hydroxyl group; an aryl group; a benzyl group; a furyl group; group; thienyl group; a pyrrolyl group; a pyridyl group; contains include halogen atoms, - (: ₄ embankment group, a nitro group, a carboxyl group, an aldehyde group, embankment group, an amine group, an amide group, a carbonamide group, a mercapto group, methylsulfanyl Any one, two or three substituted aryl groups including a thiol group, a halogen atom, a d- Any one, two or three substituted pyridyl groups including a carboxy group, a carboxy group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three substitutions of an alkyl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a decyl group, a methylthio group or an ethylthio group of dC ₄ . a furan group; containing a halogen atom, ((: ₄ thiol, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio) Any one, two or three substituted pyranyl groups; containing an alkyl group including a halogen atom, C, -C ₄ , a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group Any one, two or three substituted thienyl groups including a fluorenyl group, a methylthio group and an ethylthio group; containing a halogen atom, a fluorenyl group, a nitro group, a carboxy group, an aldehyde group, a decyloxy group, Amine, Any one, two or three substituted pyrrolyl groups such as an amide group, a carboxamide group, a decyl group, a methylthio group or an ethylthio group; a decanoyl group of dC ₆ ; a decyloxy group having a halogen atom, d- or Any one, two or three substituted d-C ₆ decanoyl groups such as a hydroxyl group; c ₂ -c ₆ enoyl group; any one containing a halogen atom, a decyloxy group of dc ₆ or a hydroxyl group; Two or three substituted c ₂ -c ₆ enoyl groups; c ₂ -c acetylene group; any one, two or three containing a halogen atom or a hydroxyl group including a halogen atom, c, -c _fi a substituted c ₂ -c _e acetylene group; C ₃ -(cyclodecanoyl; any one, two or three substituted C ₃ - ( ₆ ) containing a halogen atom, a methoxy group or a hydroxyl group Cycloalkanoyl; adamantyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; ((3⁄4) „, n is 0- 2; 0; S or NH; is (CH, n is 0-2; 0; S or NH;

Or R _3, respectively:

Wherein R ₉ is any one of the following substituents: H; d-alkyl; any one, two or three substituted (:, -() containing a halogen atom, a decyloxy group or a hydroxyl group of dC ₆ : alkyl with _6; C ₂ - (: ₆ alkenyl group; a halogen atom includes contain any, or a hydroxyl group, C ₆ embankment inner one, two or three substituents of c ₂ - alkenyl; C ₂ - ₍₆ alkynyl; optionally include a halogen atom-containing, Ct-Ce alkoxy or hydroxy group including one, two or three substituents of C ₂ -C _e alkynyl group; c ₃ - c ₆ of Any one, two or three substituted c ₃ -c ₆ cyclodecyl groups including a halogen atom, c "c ₆ decyloxy group or hydroxy group; aryl; benzyl; furanyl ; tetrahydropyranyl; thienyl; pyrrolyl; pyridyl; include a halogen atom-containing, d- embankment ₀₄ group, a nitro group, a carboxyl group, an aldehyde group, embankment group, an amine group, an amide group, a carbonamide group, a mercapto group Any one, two or three substituted aryl groups including a methylthio group and an ethylthio group; containing a halogen atom, a sulfhydryl group, and a nitrate Any one, two or three substituted pyridyl groups including a carboxyl group, an aldehyde group, a decyloxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; Any one, two or three of thiol, nitro, carboxy, aldehyde, decyloxy, amino, amide, carboxamide, sulfhydryl, methylthio, ethylthio Substituted furanyl; containing a halogen atom, - (: ₄ fluorenyl, nitro, carboxyl, aldehyde, decyloxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio Any one, two or three substituted pyranyl groups; containing a halogen atom, 0 (: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group) , any mercapto, methylthio, ethylthio, including one, two or three substituents thienyl; include a halogen atom-containing, c, - c ₄ embankment group, a nitro group, a carboxyl group, an aldehyde group, an oxygen embankment Base, amine group, amide group, carboxamide group, sulfhydryl group, methyl sulfide , Ethylthio, including any one, two or three substituents pyrrolyl; c, - c _fi alkanoyl: containing optionally include a halogen atom, dc embankment ₆ alkoxy or hydroxy, including one, two, Or a substituted alkanoyl group of c, -c ₆ ; an alkenoyl group of c ₂ -c ₆ ; any one, two or three substituted cs including a halogen atom, an alkoxy group of d- or a hydroxyl group alkenyl group of ₂ -c _6; C ₂ -c ₆ alkynyl group of; - c embankment any alkoxy or hydroxy _(6, including one, two or three substituents of ₂ - include a halogen atom-containing, C, c ₆ alkynyl group; c ₃ -c ₆ cycloalkyl group embankment; includes any halogen atom-containing, alkoxy or hydroxy CRCE including one, two or three substituents of C ₃ -C ₆ cycloalkyl group of the embankment; Gold Cycloalkanoyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrrolyl; X (CH ₂ ) _n , n 0-2; 0; Or NH;

Or R ₃ and R ₄ are:

Wherein R _{1 (>} , Ru are each independently a substituent of any of the following: H; a fluorenyl group of d-C ₆ ; any one of two, including a halogen atom, a C, a C ₆ -oxy group or a hydroxyl group; Or three substituted (:, -( ₆ fluorenyl; C ₂ -C ₆ alkenyl; any one, two or three substitutions including a halogen atom, a dC ₆ decyloxy group or a hydroxyl group) C ₂ - (: ₆ alkenyl; C ₂ -G^ alkynyl; any one, two or three substituted C ₂ containing a halogen atom or a hydroxyl group including a halogen atom, C, -C ₆ - an alkynyl group of C ₆ ; a C ₃ -C ₆ cyclodecyl group; any one, two or three substituted C ₃ - C containing a halogen atom or a hydroxyl group including a halogen atom, C, -C ₆ ₆ cyclyl; aryl; benzyl; furyl; pyranyl; thienyl; pyrrolyl; pyridyl; containing a halogen atom, a sulfhydryl group, a nitro group, a carboxyl group, an aldehyde group, a decyloxy group, an amine Any one, two or three substituted aryl groups including a amide group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group, and a halogen atom, dC ₄ Any one, two or three substituted pyridyl groups such as an alkyl group, a nitro group, a carboxyl group, an aldehyde group, an alkoxy group, an amine group, an amide group, a carboxamide group, a fluorenyl group, a methylthio group or an ethylthio group. Containing a halogen atom, (:, _ ( ₄ alkyl, nitro, carboxyl, aldehyde, alkoxy, amine, amide, carboxamide, sulfhydryl, methylthio, ethylthio) Any one, two or three substituted furanyl groups; including halogen atom, alkyl group, nitro group, carboxyl group, aldehyde group, decyloxy group, amine group, amide group, carboxamide group, thiol group, methylthio group, B Any one, two or three substituted pyranyl groups including a thio group; containing a halogen atom, (:, -(: ₄ fluorenyl group, nitro group, carboxyl group, aldehyde group, alkoxy group, amine group, Any one, two or three substituted thiopanyl groups including an amide group, a carboxamide group, a fluorenyl group, a methylthio group, an ethylthio group; containing a sulfonyl group, a (-, _4- (alkyl group, a nitro group) , carboxyl group, aldehyde group, alkoxy group, amine group, amide group, carboxamide group, Any one, two or three substituted pyrrolyl groups including a fluorenyl group, a methylthio group, an ethylthio group; a C,-C ₆ alkanoyl group; a decyloxy group or a hydroxyl group containing a halogen atom, C, -C _e Any one, two or three substituted c ₆ alkanoyl groups; c ₂ -c _e alkenoyl group; any one or two containing a halogen atom, a d-Ce alkoxy group or a hydroxyl group Or three substituted c ₂ -c ₆ enoyl groups; c ₂ -c ₆ alkynyl groups; any one, two or three substituted c groups including a halogen atom, a decyloxy group or a hydroxyl group of d- An alkynyl group of _{2 -} c _e ; a cyclodecanoyl group of c ₃ -c _{6 ;} a ring of any one, two or three substituted c ₃ - (including a halogen atom, a methoxy group or a hydroxyl group of c-) Decanoyl; adamantyl formyl, substituted adamantyl; aroyl; benzoyl; furoyl; pyranoyl; thiophene; pyrroyl; 乂₁ is ((3⁄4)„, n is 0- 2; 0; S or NH; is (CH, n is 0-2; 0; S or NH.

The compound having a substituted cyclobutane structure according to any one of claims 1 to 2, characterized in that, when geometric isomers are present in the molecule, the compounds are various individual geometric isomers or mixture.

4. A compound according to any one of claims 1 to 3, characterized in that when chiral carbon is present in the molecule, The compound is a racemate or an optically active body.

A method for producing a series of compounds having a substituted cyclobutane structure according to any one of claims 1 to 4, and a salt thereof, characterized in that the reactant is added to a solvent by ordinary light or under high-pressure mercury lamp illumination. .

A method for producing a compound having a substituted cyclobutyl fluorene structure according to claim 5, wherein the light-reactive solvent is methylene chloride, water, dichloroacetic acid, DMS0, dioxane or the above solvent. Mixed solvent.

The process for producing a compound having a substituted cyclobutane structure according to claim 5, wherein the reaction temperature is from 0 ° C to 60 ° C.

A process for the preparation of a compound having a substituted cyclobutane structure according to claim 5, characterized in that an appropriate amount of water is added during the reaction to complete the reaction.

A method of producing a compound having a substituted cyclobutyl fluorene structure according to claim 5, wherein the light used in the reaction is natural light, more preferably a high pressure mercury lamp.

A process for the preparation of a compound having a substituted cyclobutane structure according to claim 5, characterized in that a catalytic amount of benzophenone is added during the reaction to promote the reaction.

11. A compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, for use in the preparation of a prophylactic and/or therapeutic metabolic disorder (including but not limited to diabetes, insulin resistance and obesity), cardiovascular Uses of diseases and neurodegenerative diseases such as Alzheimer's disease.

12. A pharmaceutical composition for preventing and/or treating metabolic disorders including, but not limited to, diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease The composition contains, as an active ingredient, a compound according to any one of claims 1 to 4 and a therapeutically acceptable salt of such a compound and a linker with other molecules or carriers.

13. A pharmaceutical composition according to claim 12 further comprising a pharmaceutically acceptable carrier and excipient.

14. A pharmaceutical composition according to claim 12, characterized in that the disease or condition can be caused by resistance or toxic side effects to a therapeutic drug already marketed.

A combination preparation comprising a compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, and other therapeutic agents. .

A kit comprising the compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, and the use of the compound or a pharmaceutically acceptable salt thereof for prevention and/or prevention Descriptions for the treatment of metabolic disorders including, but not limited to, diabetes, insulin resistance and obesity, cardiovascular diseases and neurodegenerative diseases such as Alzheimer's disease.

17. A kit comprising the combination of claim 15 and using the combination to prevent and/or treat metabolic disorders (including but not limited to diabetes, insulin resistance and obesity), cardiovascular Description of diseases and neurodegenerative diseases (such as Alzheimer's disease).