WO2014190942A1 - Indole compound, and preparation method, pharmaceutical composition and use thereof - Google Patents

Abstract

Provided are an indole compound, and the preparation method, a pharmaceutical composition and a use thereof. In particular, the indole compound has a structure as shown in general formula (I), and can be used in the treatment of diseases associated with α₁-adrenoceptors, especially urinary diseases such as benign enlarged prostate, uroschesis, and bladder outlet obstruction.

Description

 A class of terpenoids, preparation methods thereof, pharmaceutical compositions and applications

The invention relates to the field of medicinal chemistry and chemotherapy. In particular, the present invention relates to a class of terpenoids of the formula (I), a process for the preparation thereof, a pharmaceutical composition thereof and a medicament for the treatment of a disease associated with the _αι -adrenergic receptor, in particular benign prostatic hyperplasia , urinary retention, bladder outlet obstruction and other urinary system diseases.

 Background technique

 Benign prostatic hyperplasia (BPH) is a common physiological disease in middle-aged and elderly men. With the inevitable population aging, the incidence of benign prostatic hyperplasia has been greatly improved compared with the previous one. It has become a middle-aged male in China. One of the most common geriatric diseases. Data show that the incidence of benign prostatic hyperplasia is very low before the age of 40, while about half of men over the age of 50 have benign prostatic hyperplasia, and nearly 90% of those aged 80 have the disease. Benign prostatic hyperplasia is a benign adenoma hyperplasia of cells in the peri-urethral region of the prostate. Progressive enlargement of the gland can cause stenosis of the prostatic urethra, causing obstruction of bladder urine outflow. The initial clinical manifestation is lower urinary tract system symptoms (LUTS). Can develop into urinary retention, bladder infections, bladder stones and kidney failure, and even endanger the lives of patients. Therefore, progenitor gland hyperplasia is one of the common diseases of domestic and foreign middle-aged men, which greatly reduces the quality of life of patients.

The pathogenesis of benign prostatic hyperplasia is complex and related to a variety of enzymes and receptors. At present, the main drugs for clinical treatment of BPH are: _αι -adrenergic receptor antagonist, 5α-reductase inhibitor, natural product preparation and the like. The two major drugs for the treatment of sputum, 5α-reductase inhibitors and α-receptor antagonists, are treated separately for the prostate volume and smooth muscle tone that cause symptoms of benign prostatic hyperplasia; in theory, the presence of hyperplasia is positive. It is dependent on these two important factors: static factors and kinetic factors, the two together affect the extent of the disease. Among them, on-adrenoceptor antagonists can quickly relieve symptoms, but can not significantly reduce the size of the prostate and early development of such drugs often have serious adverse reactions. 5α-reductase inhibitors can reduce the size of the prostate and fundamentally relieve symptoms, but have a poor effect on small-sized sputum and slower onset.

Adrenergic receptors (ARs) are classified into α-receptors and β-receptors, which are subdivided into several receptor subtypes. The alpha-adrenergic receptor is a family of 7 transmembrane G-protein coupled receptors (GPCRs) that are widely distributed in various organs, tissues and cells of the body. The α-adrenergic receptor (α-ARs) is divided into two types, _αι and α ₂ . Studies have shown that there are mainly type 0 receptors in the matrix components of the prostate and in the glandular epithelium. Molecular cloning methods have isolated and identified three on-receptor subtypes of α _1Α , α _1Β and a _1D , with a _1A -ARs accounting for approximately 70% of the total on-ARs in the human prostate and urinary tract system. In the reproductive, urinary system, alpha _1Α -receptors are mainly distributed in the prostate, urethra and bladder triangle, vas deferens, α _1Β -receptors are distributed in blood vessels, and a _1D -receptors are distributed in bladder detrusor and ureter smooth muscle.

In the pathological condition of BPH, the density of o-ARs increased significantly. In addition, the distribution characteristics of 0^- 1^ subtypes vary with age. The correlation between age and distribution is to understand and treat benign prostatic hyperplasia and lower urinary tract system symptoms, and develop on-adrenergic receptor antagonism. The agent is of great significance. The kinetics of BPH are dependent on the contraction of stromal smooth muscle, which is caused by on-adrenergic receptor-mediated sympathetic stimulation. The stimulation of _ai- ARs can cause contraction of the smooth muscle of the prostate, leading to a occlusive increase in urethral pressure, causing obstruction of the urine flow and symptoms of bladder irritation. The study found that 40% of urethral pressure in patients with benign prostatic hyperplasia comes from the regulation of _ai- ARs. Ligand binding assays have shown that _ai- ARs mediate smooth muscle contraction through a series of phosphatase C activation processes that produce second messenger-trisphosphate and diacylglycerol downstream, resulting in endogenous Ca ²⁺ Release to regulate gene expression.

Knowledge of the distribution and function of the _αι -adrenergic receptor subtype helps people determine benign prostatic hyperplasia The therapeutic target of birth. The α _1Α -adrenergic receptor is an ideal target for treatment, and its blockade has been shown to be effective in reducing the contraction frequency of prostate smooth muscle and improving bladder emptying. _Blockade of α _1Β -adrenergic receptors can lead to vascular smooth muscle relaxation, arteriovenous dilatation, and decreased peripheral resistance, which may cause side effects such as dizziness and hypotension in some patients. Activation of a _1D -adrenergic receptors can lead to hyperactivity of the detrusor, which can reduce the occurrence of emptying symptoms, which has been confirmed in animal experiments. In theory, a combination of a _1A and a _1D -adrenergic receptor inhibitors is a very effective drug for the control of benign prostatic hyperplasia. Because it contains the ability to reduce the frequency of contraction of the smooth muscle of the prostate and inhibit the detrusor dysfunction, in addition to avoid cardiovascular side effects caused by a _1B - adrenergic block.

The first generation of a receptor blockers that were developed and utilized to effectively alleviate the symptoms of benign prostatic hyperplasia were Phenoxybenzamine. An irreversible non-selective receptor blocker of phenoxybenzamine β-halohydrazine, which blocks alpha receptors in the prostate and relaxes fibrous tissue of the prostate. It is clinically used to treat non-mechanical urethra caused by prostate. Difficulties in urination caused by obstruction. The phenoxybenzamine structure contains a β-chloroethylamine structure, which is easily reacted with other enzymes in the body, so that toxicity and side effects are more. Moreover, as a non-selective alpha receptor blocker, it blocks the presynaptic alpha ₂ receptor while blocking the receptor, thus promoting the release of norepinephrine, which can cause heart rate and myocardial contractility. Increase, causing adverse reactions.

The use of non-selective 0^/01 ₂ receptor blockers is limited by their multiple side effects, including: syncope, orthostatic hypotension, reflex tachycardia, arrhythmia, etc. These side effects are mainly derived from alpha ₂ receptor blockade. In order to reduce these side effects, a second-generation _αι -adrenergic receptor antagonist with high selectivity for _αι receptor has emerged (eg, prazosin, terazosin, doxazosin, alfuzosin) . The on-adrenergic receptor relieves the contraction of the prostate and urethral smooth muscle caused by the sympathetic nerve, and reduces the symptoms of urethral obstruction in terms of kinetics. These drugs reduce the side effects caused by vasodilation while effectively relieving lower urinary tract symptoms. The oxazoazines have the structural nucleus of quinazoline and are currently commonly used in the clinical treatment of sputum and its lower urinary tract symptoms (LUTS).

However, due to the extensive distribution of 0^-adrenergic receptors and important physiological functions, side effects such as orthostatic hypotension, dizziness, and weakness are often _observed with _αι -adrenergic receptor antagonists. Our recent studies have shown that the _{steroids of the} general formula (I) have better α 1 _Α -adrenergic receptor antagonistic activity and can be developed as selective α 1 _Α -adrenergic receptor antagonists, thereby reducing side effects. , to provide useful help for the treatment of benign prostatic hyperplasia.

 The present invention provides a class of terpenoids, a preparation method thereof, a pharmaceutical composition thereof and a urinary system disease thereof for treating diseases associated with αΐ-adrenergic receptors, particularly benign prostatic hyperplasia, urinary retention, bladder outlet obstruction, and the like Applications.

 Summary of the invention

 One aspect of the present invention provides a quinone compound represented by the formula (I), and a pharmaceutically acceptable salt, a crystalline hydrate thereof, a solvate or a mixture thereof.

 Another aspect of the present invention provides a process for producing an intermediate of the compound of the formula (I), that is, a compound of the formula (II).

 Another aspect of the present invention provides a process for the preparation of a compound of the formula (III) which is another intermediate required for the preparation of the compound of the formula (I).

 Another aspect of the present invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula (I), a pharmaceutically acceptable salt thereof, a crystalline hydrate, and a solvate thereof. One or more; and one or more pharmaceutically acceptable carriers.

According to still another aspect of the present invention, there is provided a compound of the formula (I), and a pharmaceutically acceptable salt, a crystalline hydrate thereof, a solvate thereof or a mixture thereof for the preparation of a disease associated with on-adrenergic receptors. In medicine Application.

 Still another aspect of the present invention provides a method of treating a urinary system disease associated with an alpha-adrenergic receptor, particularly a benign prostatic hyperplasia, urinary retention, bladder outlet obstruction, comprising administering a therapeutically effective amount to a subject in need of such treatment. One or more selected from the group consisting of the compound of the formula (I), a pharmaceutically acceptable salt thereof, a crystalline hydrate and a solvate.

 According to one aspect of the present invention, there is provided an anthraquinone compound represented by the following formula (I), which is a pharmaceutically acceptable salt, a crystalline hydrate or

 General formula (I)

Wherein: R ₂ , R ₃ , R ₄ , R ₅ represent a substituent on the benzene ring, each independently selected from the group consisting of hydrogen, halogen, amino, carboxyl, cyano, nitro, hydroxy, unsubstituted or straight from C2-C6 A chain or branched alkenyl or halogen-substituted C1-C6 straight or branched fluorenyl group, a C1-C6 straight or branched decyloxy group unsubstituted or substituted by a C3-C6 cyclodecyl group or a halogen, C2-C12 straight or branched alkenyl group unsubstituted or substituted by halogen, C2-C12 straight or branched alkynyl group unsubstituted or substituted by halogen, C3-C6 unsubstituted or substituted by halogen Cyclodecyl, unsubstituted or substituted by halogen, C3-C6 cyclodecyloxy, unsubstituted or substituted by halogen C 1 -C 6 straight or branched mercaptocarbonyloxy, unsubstituted or substituted by halogen C 1 -C 6 Linear or branched fluorenylcarbonyl, unsubstituted or substituted by halogen, C1-C6 straight or branched fluorenyloxycarbonyl, unsubstituted or halogenated, C1-C6 straight or branched fluorenyl, C 1 -C6 linear or branched methoxy-substituted phenoxy group, unsubstituted or substituted by halogen, C1-C6 straight or branched fluorenyl group, C1-C6 straight or branched decyloxy group Benzyloxy, unsubstituted or by a C1-C6 linear or branched fluorenyl group and a C1-C6 linear or branched methoxy-substituted benzyloxycarbonyl group; preferably each independently selected from the group consisting of hydrogen, halogen, amino, hydroxy, unsubstituted or a C1-C6 straight or branched fluorenyl group substituted by a C2-C4 straight or branched alkenyl group or 1-3 halogens, unsubstituted or substituted by C3-C6 cyclodecyl or 1-3 halogen a C1-C6 linear or branched decyloxy group, a C3-C6 cyclodecyl group which is unsubstituted or substituted by 1-3 halogens, a C3-C6 cyclodecyloxy group which is unsubstituted or substituted by 1-3 halogens, a phenoxy group which is unsubstituted or substituted by a halogen, a C 1 -C6 linear or branched fluorenyl group, a C 1 -C 6 straight or branched fluorenyloxy group, and an unsubstituted or halogenated, C1-C6 linear chain Or branched fluorenyl or C 1 -C 6 linear or branched decyloxy substituted benzyloxy; more preferably each independently hydrogen, halogen, unsubstituted or substituted by vinyl or 1-3 halogen C1-C6 straight or branched fluorenyl, unsubstituted or substituted by C3-C6 cyclodecyl or 1-3 halogen, C1-C6 straight or branched decyloxy, unsubstituted or 1- 3 halogen-substituted C3-C6 cyclodecyl groups, and unsubstituted or taken from 1-3 halogens C3-C6 cyclodecyloxy; most preferably each independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, allyl, methoxy, ethoxy, cyclopropoxy, cyclopropyl Oxyl, tert-butoxy, neopentyloxy, trifluoromethoxy and 2,2,2-trifluoroethoxy;

Or the two adjacent substituents of Ri, R ₂ , R ₃ , R ₄ , and R ₅ together with the carbon atom to which the benzene ring is attached may form a hetero atom containing 1 to 3 selected from N, 0 and S. 5-6 membered heterocyclic ring; preferably forming a 5-6 membered heterocyclic ring containing 1 to 2 hetero atoms selected from 0 and S; more preferably forming a dioxole ring;

 n = 0, 1, or 2, preferably n = l;

R _{6 is} selected from hydrogen, unsubstituted or substituted by halogen, C 1 -C 6 straight or branched fluorenylcarbonyl, and unsubstituted or halogenated,

a C1-C6 linear or branched fluorenyl group, a C1-C6 linear or branched decyloxy-substituted benzoyl group; preferably selected from the group consisting of hydrogen,

a C1-C4 linear or branched fluorenyl group, and a C1-C4 straight or branched fluorenylcarbonyl group which is unsubstituted or substituted by 1-3 halogens; More preferably selected from the group consisting of hydrogen, methyl, acetyl and trifluoroacetyl;

R _{7 is} selected from the group consisting of hydrogen, a C1-C6 linear or branched fluorenyl group, and a C1-C6 linear or branched fluorenyloxy group; preferably a hydrazine group selected from hydrogen and a C1-C4 straight or branched chain; More preferably selected from the group consisting of hydrogen and methyl;

 * indicates chiral carbon.

 The anthraquinone compound represented by the formula (I) of the present invention may be a R-isomer, an S-isomer and a racemate, and is preferably a R-isomer.

 In a preferred embodiment,

 ! a C1-C6 straight or branched fluorenyl group selected from the group consisting of hydrogen, halogen, amino, carboxyl, cyano, nitro, hydroxy, unsubstituted or substituted by C2-C6 straight or branched alkenyl or halogen, a C1-C6 straight or branched decyloxy group which is unsubstituted or substituted by a C3-C6 cyclodecyl group or a halogen, a C2-C12 straight or branched alkenyl group which is unsubstituted or substituted by a halogen, unsubstituted or C2-C12 straight or branched alkynyl substituted by halogen, C3-C6 cyclodecyl unsubstituted or substituted by halogen, C3-C6 cyclodecyl unsubstituted or substituted by halogen, unsubstituted or Halogen-substituted C1-C6 straight or branched mercaptocarbonyloxy, unsubstituted or substituted by halogen, C1-C6 straight or branched mercaptocarbonyl, unsubstituted or substituted by halogen C1-C6 straight a benzyloxy group which is unsubstituted or substituted by a halogen, a C 1 -C 6 linear or branched fluorenyl group, a C 1 -C 6 straight or branched fluorenyloxy group, unsubstituted or Halogen, C1-C6 straight or branched fluorenyl, C1-C6 straight or branched decyloxy substituted benzyloxy, and unsubstituted or halogenated, C1-C6 straight or branched垸 base, C1-C6 straight Or branched methoxy-substituted benzyloxycarbonyl; preferably C1-C6 straight or branched chain selected from hydrogen, unsubstituted or substituted by C2-C4 straight or branched alkenyl or 1-3 halogen A fluorenyl group, an unsubstituted or C1-C6 linear or branched decyloxy group substituted by a C3-C6 cyclodecyl group or 1-3 halogens, an unsubstituted or C3-C6 substituted with 1-3 halogens Cyclodecyl, unsubstituted or substituted by 1-3 halogens, C3-C6 cyclodecyloxy, unsubstituted or halogenated, C1-C6 straight or branched fluorenyl, C1-C6 straight or branched a benzyloxy-substituted phenoxy group of the chain, and a benzyloxy group which is unsubstituted or substituted by a halogen, a C1-C6 linear or branched fluorenyl group, a C1-C6 linear or branched fluorenyloxy group; More preferably, a C1-C6 straight or branched fluorenyl group selected from hydrogen, unsubstituted or substituted by a vinyl group or 1-3 halogens, unsubstituted or substituted by a C3-C6 cyclodecyl group or 1-3 halogens a C1-C6 linear or branched decyloxy group, a C3-C6 cyclodecyl group which is unsubstituted or substituted by 1-3 halogens, and a C3-C6 cyclodecyloxy group which is unsubstituted or substituted by 1-3 halogens. Most preferably selected from the group consisting of methyl, ethyl, allyl, methoxy, Group, a cyclopropyloxy group, a cyclopropylmethoxy group, a tert-butoxy group, neopentyl group, trifluoromethoxy and 2,2,2-trifluoro-ethoxy.

R _{2 is} selected from hydrogen, halogen, unsubstituted or C1-C6 straight or branched fluorenyl substituted by C2-C6 straight or branched alkenyl or halogen; preferably selected from hydrogen, halogen and unsubstituted or a C2-C4 linear or branched alkenyl or halogen-substituted C1-C4 straight or branched fluorenyl group; more preferably selected from the group consisting of hydrogen, fluorine, chlorine, bromine and unsubstituted or substituted by 1-3 halogens a _{C 1 -C} 4 linear or branched fluorenyl group; most preferably selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl and ethyl;

R _{3 is} selected from hydrogen, halogen, unsubstituted or C1-C6 straight or branched fluorenyl substituted by C2-C6 straight or branched alkenyl or halogen, unsubstituted or substituted by 1-3 halogen C2-C12 linear or branched alkenyl; preferably selected from hydrogen, halogen and C1-C4 straight or branched fluorene unsubstituted or substituted by C2-C4 straight or branched alkenyl or halogen More preferably selected from the group consisting of hydrogen, fluorine, chlorine, bromine, and a C1-C4 straight or branched fluorenyl group which is unsubstituted or substituted by a vinyl group or 1-3 halogens; most preferably selected from the group consisting of hydrogen, methyl, and Base, allyl, fluorine, chlorine and bromine;

R _{4 is} selected from hydrogen, halogen, unsubstituted or C1-C6 straight or branched fluorenyl substituted by C2-C6 straight or branched alkenyl or halogen, and unsubstituted or substituted by 1-3 halogen C2-C12 straight or branched alkenyl; preferably selected from hydrogen, halogen and C1-C4 straight or branched, unsubstituted or substituted by C2-C4 straight or branched alkenyl or halogen Sulfhydryl; more preferably C1-C4 straight or branched fluorenyl, fluorine, chlorine and bromine selected from hydrogen, unsubstituted or substituted by vinyl or 1-3 halogen; more preferably selected from hydrogen, methyl, Ethyl, allyl, fluorine, chlorine and bromine;

Or R ₃ and may together with the carbon atom to which it is attached on the benzene ring constitutes 1 to 3 selected from 0 and S a 5- to 6-membered heterocyclic ring of a hetero atom; preferably a 5- to 6-membered heterocyclic ring having 1 to 2 hetero atoms selected from 0 and S; more preferably forming a dioxole ring;

R _{5 is} selected from the group consisting of hydrogen, halogen, amino, carboxy, cyano, nitro, hydroxy, unsubstituted or C1-C6 straight or branched fluorenyl substituted by C2-C6 straight or branched alkenyl or halogen a C1-C6 straight or branched decyloxy group which is unsubstituted or substituted by a C3-C6 cyclodecyl group or a halogen, a C2-C12 straight or branched alkenyl group which is unsubstituted or substituted by a halogen, unsubstituted Or a C2-C12 straight or branched alkynyl group substituted by halogen, a C3-C6 cyclodecyl group which is unsubstituted or substituted by halogen, a C3-C6 cyclodecyloxy group which is unsubstituted or substituted by halogen, unsubstituted or C1-C6 straight or branched mercaptocarbonyloxy substituted by halogen, C1-C6 straight or branched carbonyl unsubstituted or substituted by halogen, C1-C6 straight or branched unsubstituted or substituted by halogen a benzyloxy group, unsubstituted or substituted by a halogen, a C1-C6 straight or branched fluorenyl group or a C1-C6 straight or branched fluorenyloxy group, unsubstituted or by halogen, C1 -C6 straight or branched fluorenyl or C1-C6 straight or branched decyloxy substituted benzyloxy, and unsubstituted or halogenated, C1-C6 straight or branched fluorenyl or C1 -C6 linear or branched decyloxy group a benzyloxycarbonyl group; preferably a C 1 -C 6 straight or branched fluorenyl group unsubstituted or substituted by a C 2 -C 4 straight or branched alkenyl group or 1-3 halogens, unsubstituted or by C 3 -C6 cyclodecyl or 1-3 halogen-substituted C1-C6 straight or branched fluorenyloxy, unsubstituted or C3-C6 cyclodecyl substituted by 1-3 halogens, unsubstituted or by 1 a 3-halo-substituted C3-C6 cyclodecyloxy group, a phenoxy group which is unsubstituted or substituted by a halogen, a C1-C6 straight or branched fluorenyl group or a C1-C6 straight or branched decyloxy group, a benzyloxy group which is unsubstituted or substituted by a halogen, a C 1 -C 6 straight or branched fluorenyl group or a C 1 -C 6 straight or branched fluorenyloxy group; more preferably selected from unsubstituted or by vinyl or 1 - 3 halogen-substituted C 1 -C 6 straight or branched fluorenyl groups, unsubstituted or C 1 -C 6 linear or branched decyloxy groups substituted by C 3 -C 6 cyclodecyl or 1-3 halogens, C3-C6 cyclodecyl unsubstituted or substituted by 1-3 halogens, and C3-C6 cyclodecyloxy which is unsubstituted or substituted by 1-3 halogens; most preferably selected from methyl, ethyl, allylic , methoxy, ethoxy, cyclopropoxy, cyclopropylmethoxy, tert-butoxy, neopentyloxy , Trifluoromethoxy and 2,2,2-trifluoroethoxy.

R _{6 is} selected from hydrogen, unsubstituted or substituted by halogen, C 1 -C 6 straight or branched fluorenylcarbonyl, and unsubstituted or halogenated, C 1 -C 6 straight or branched fluorenyl, C 1 -C 6 straight a branched or branched methoxy-substituted benzoyl group; preferably selected from hydrogen and a C1-C4 straight or branched fluorenylcarbonyl group which is unsubstituted or substituted by 1-3 halogens; preferably selected from hydrogen, acetyl and Trifluoroacetyl group;

R _{7 is} selected from the group consisting of hydrogen, a C1-C6 linear or branched fluorenyl group, and a C1-C6 linear or branched fluorenyloxy group; preferably a hydrazine group selected from hydrogen and a C1-C4 straight or branched chain; More preferably selected from the group consisting of hydrogen and methyl; most preferably hydrogen;

 n = 0, 1 or 2, preferably n = 1.

 In the present invention, the pharmaceutically acceptable salt includes a non-toxic salt formed by reacting with a mineral acid or an organic acid, and the inorganic acid is not limitedly selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and amine sulfonate. Acid and phosphoric acid, the organic acid being selected, without limitation, from propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid and aspartic acid.

 In the present invention, the halogen is fluorine, chlorine, bromine or iodine.

In another preferred embodiment, Ri, R ₂ , R ₃ , R ₄ , R ₅ are each independently selected from the group consisting of hydrogen, halogen, unsubstituted or C2-C6 straight or branched alkenyl or halogen. Substituted C1-C6 linear or branched fluorenyl, unsubstituted or halogen-substituted C3-C6 cyclodecyloxy, unsubstituted or C1-C6 straight-chain substituted by C3-C6 cyclodecyl or halogen or Branched decyloxy;

Or the two adjacent substituents of Ri, R ₂ , R ₃ , R ₄ , and R ₅ together with the carbon atom to which the benzene ring is attached form a 5-6 containing 1 to 2 heteroatoms selected from 0 and S. A heterocyclic ring; more preferably a dioxolane ring.

In another preferred embodiment, R _{6 is} selected from hydrogen or a C 1 -C 6 straight or branched fluorenylcarbonyl group which is unsubstituted or substituted by halogen

(such as methylcarbonyl, ethylcarbonyl).

In another preferred embodiment, R _{7 is} selected from the group consisting of hydrogen. In another preferred embodiment, Ri, R ₂ , R ₃ , R ₄ , R ₅ are each independently selected from H, F, Cl, Br, unsubstituted or C2-C6 straight or branched alkenyl or halogen. Substituted C1-C6 straight or branched fluorenyl, methoxy, ethoxy, propoxy, cyclopropoxy, unsubstituted or C1-C6 straight chain substituted by C3-C6 cyclodecyl or halogen Or a branched alkoxy group (e.g., (CH ₃ ) ₃ CCH ₂ 0-, (CH ₃ ) ₃ CO-, (CF ₃ ) ₃ CO -).

In another preferred embodiment, at least one of Ri, R ₂ , R ₃ , R ₄ , R ₅ is a C1-C6 straight chain unsubstituted or substituted by a C2-C6 straight or branched alkenyl or halogen or Branched fluorenyl, C3-C6 cyclodecyloxy which is unsubstituted or substituted by halogen, C1-C6 straight or branched decyloxy which is unsubstituted or substituted by C3-C6 cyclodecyl or halogen.

In another preferred embodiment, at least one of Ri, R ₂ , R ₃ , R ₄ , R ₅ is selected from the group consisting of cyclopropoxy, methoxy, ethoxy, propoxy, (CH ₃ ) ₃ CCH ₂ 0-, (CH ₃ ) ₃ CO-, (CF ₃ ) ₃ CO-.

l-(3-羟基丙基) -5-[(2R)-2-[2-[5-氟

L-(3-hydroxypropyl)-5-[(2R)-2-[2-[5-fluoro

DC471824-2-Pentyloxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[5-fluoro

DC471825-2-(2,2,2-Trifluoroethoxy)phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro

DC471826 -2-ethoxy-phenoxy]ethylamino]propyl] - 吲哚-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro

DC471827-2-methoxy-phenoxy]ethylamino]propyl] - 吲哚-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro

DC471828-2-Cyclopropoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro

DC471829-2-Cyclopropoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro

DC471830-2-tert-butoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro

DC471831-2-Pentyloxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[5-A

DC471832 yl-2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]-indole-7-carboxamide L-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-

DC471833-yl-2-ethoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-

DC471834-based 2-methoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-

DC471835 Benzyl-2-cyclopropoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-

DC471836 base -2-cyclopropoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-

DC471837-yl-2-tert-butoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-

DC471838-yl-2-pivaloxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[5-chloro

DC471839 -2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-chloro

DC471840 -2-ethoxy-phenoxy]ethylamino]propyl] - 吲哚-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-chloro

DC471841-2-methoxy-phenoxy]ethylamino]propyl] - 吲哚-7-carboxamide

l-(3-羟基丙基) -5-[(2R)-2-[2-[4-録

L-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-record

DC471851 propyl -2-tert-butoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-[4-recorded

DC471852 propyl-2-pivaloxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-bromo-4-

DC471853 Fluoro-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-ethyl

DC471854 -Phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-2-[2-positive-propyl

DC471855 benzyl-phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(2-hydroxyethyl)-5-[(2R)-2-[2-[4-fluoro

DC471856-2-(2,2,2-Trifluoroethoxy)phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(4-hydroxybutyl)-5-[(2R)-2-[2-[4-fluoro

DC471857 -2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl]-indole-7-carboxamide

1-(2-hydroxyethyl)-5-[(2R)-2-[2-[5-fluoro

DC471858-2-(2,2,2-Trifluoroethoxy)phenoxy]ethylamino]propyl]-indole-7-carboxamide

 The compound of the present invention has a chiral center and may be an R-isomer, an S-isomer, and a racemate, and is preferably a R-isomer.

 The present invention provides a process for producing a compound represented by the formula (I). The preparation of the compound represented by the general formula (I) requires the preparation of the following two intermediates, an intermediate (Π) and an intermediate (III). Raw materials and reagents used in the present invention, such as commercial

( II) ( III)

(II) (III)

 Reaction route one

 Reaction route 1 includes the following reaction steps:

 Step la: nucleophilic substitution reaction of compound la with methyl bromoacetate to obtain compound lb; wherein the nucleophilic substitution reaction can be carried out in the presence of a base, such as potassium carbonate, cesium carbonate, potassium phosphate, Sodium hydroxide or potassium hydroxide, preferably potassium carbonate; the reaction solvent may be, for example, acetone, acetonitrile, tetrahydrofuran or hydrazine, hydrazine-dimethylformamide, preferably acetone;

 Step lb: Compound lb is subjected to amine transesterification with hydrazine, hydrazine-dimethylhydroxylamine hydrochloride to obtain compound lc; the amine transesterification reaction can be carried out in the presence of a catalyst such as trimethylaluminum, and the reaction solvent can be, for example, none. Dichloromethane;

 Step lc: The compound lc is subjected to a reduction reaction to obtain a compound Id; wherein the reduction reaction can be carried out using a reducing agent such as lithium aluminum hydride; the reaction solvent can be, for example, anhydrous tetrahydrofuran.

Reaction Scheme 2: Preparation of Intermediate (III):

反应路线二包括以下反应步骤：

Reaction route 2 includes the following reaction steps:

Step 3a _: Compound 3a is subjected to a nucleophilic substitution reaction with 2-bromo-1-ethanol or 3-bromo-1-propanol or 4-bromo-1-butanol to obtain compound 3b; wherein the nucleophilic substitution reaction can be carried out Reflowing in the presence of a base for 12-20 hours, the base may be, for example, potassium carbonate; the reaction solvent may be, for example, acetonitrile;

Step 3b _: Compound 3b is acylated with an acylating reagent to obtain compound 3c; wherein the acylation reaction can be carried out in the presence of a base, and the acylating agent can be, for example, an acid chloride, for example, a halogen, C1-C6 straight A chain or branched fluorenyl group, a C1-C6 linear or branched decyloxy substituted or unsubstituted benzoyl chloride or an unsubstituted or substituted 1-3 halogen substituted C1-C6 straight or branched fluorene The base may be, for example, triethylamine; the reaction solvent may be, for example, anhydrous dichloromethane;

 Step 3c: the compound 3c is subjected to a formylation reaction with hydrazine, hydrazine-dimethylformamide to obtain a compound 3d; wherein the formylation reaction can be carried out in the presence of a catalyst such as phosphorus oxychloride, for example, the reaction solvent can be It is anhydrous 1,2-one gas;

 Step 3d: The compound 3d is subjected to a condensation reaction with nitroacetamidine to obtain a compound 3e; wherein the condensation reaction can be carried out in the presence of a catalyst such as ammonium acetate; the reaction solvent can be, for example, a mixed solvent of acetic acid and nitroacetamidine. ;

Step 3e _: Compound 3e is subjected to a reduction reaction to obtain a compound 3f; wherein the reduction reaction can be used as an example a reducing agent such as sodium borohydride; the reaction solvent may be, for example, a mixed solvent of dichloromethane and methanol;

Step 3f _{: the} compound 3f is subjected to a formylation reaction with hydrazine and hydrazine-dimethylformamide to obtain a compound 2a; wherein the formylation reaction can be carried out in the presence of a catalyst such as phosphorus oxychloride, for example, the reaction solvent can be Is Ν, Ν-dimethylformamide;

Step 2a _: Compound 2a is subjected to an oxidation reaction to obtain a compound 2b; wherein, the oxidation reaction may use, for example, an oxidizing agent of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (abbreviated as DDQ); The reaction solvent may be, for example, ethyl acetate, dichloromethane or 1,4-dioxane;

Step 2b _: Compound 2b is subjected to a condensation reaction with hydroxylamine hydrochloride to obtain compound 2c; wherein the condensation reaction can be carried out in the presence of a base and a dehydrating agent, and the base can be, for example, pyridine; and the dehydrating agent can be, for example, acetic anhydride; The solvent may be, for example, anhydrous tetrahydrofuran;

Step 2c _: Compound 2c is subjected to a reduction reaction to obtain a compound 2d; wherein, the reduction reaction may use, for example, a reducing agent of 10% palladium carbon; and the reaction solvent may be, for example, methanol, tetrahydrofuran or a mixed solvent of methanol and tetrahydrofuran;

 Step 2d: Compound 2d is resolved to give compound 2e and compound 2f; the resolving agent may be, for example, L-(+)-tartaric acid or L-(-)-tartaric acid; and the reaction solvent may be, for example, acetone.

 Reaction route three

 Step 4a: The intermediate (II) and the intermediate (III) are subjected to a reductive amination reaction to obtain a compound 4a; wherein the reductive amination can be carried out, for example, in the presence of sodium borohydride or sodium cyanoborohydride, a reaction solvent For example, 1,2-dichloroethane;

Step 4b _: Compound 4a is subjected to a hydrolysis reaction to obtain a compound 4b; wherein the hydrolysis can be carried out, for example, in the presence of a base, which may be, for example, potassium hydroxide, sodium hydroxide or lithium hydroxide; the reaction solvent may be, for example, a mixed solvent of water and methanol;

 Step 4c: The compound 4b is subjected to a hydrolysis reaction to obtain a compound 4c; wherein the hydrolysis reaction can be carried out in the presence of a catalyst such as a base and hydrogen peroxide, the base being, for example, sodium hydroxide; and the reaction solvent being, for example, dimethyl Sulfoxide; or

Step 4d _: nucleophilic substitution reaction of compound 4a with benzyl bromide to obtain compound 4d; wherein, the nucleophilic substitution reaction can be carried out, for example, in the presence of a base, such as potassium carbonate; and the reaction solvent can be, for example, acetone. Step 4e: Compound 4d is subjected to a hydrolysis reaction to obtain a compound 4e; wherein, the hydrolysis reaction can be, for example, In the presence of a base, the base may be, for example, potassium hydroxide, sodium hydroxide, or lithium hydroxide; the reaction solvent may be, for example, a mixed solvent of water and methanol;

 Step 4f: The compound 4e is subjected to a hydrolysis reaction to obtain a compound 4f; wherein the hydrolysis reaction can be carried out in the presence of a catalyst such as a base and hydrogen peroxide, the base being, for example, sodium hydroxide; and the reaction solvent being, for example, dimethyl Sulfoxide

Step 4g _: compound 4f is acylated with an acylating reagent to obtain compound 4g; wherein the acylation reaction can be carried out in the presence of a base, and the acylating agent can be, for example, an acid chloride, for example, halogen, C1-C6 straight A chain or branched fluorenyl group, a C1-C6 straight or branched decyloxy substituted or unsubstituted benzoyl chloride, unsubstituted or substituted by a 1-3 halogen to a C1-C6 straight or branched decanoyl chloride The base may be, for example, triethylamine; the reaction solvent may be, for example, anhydrous dichloromethane;

 Step 4h: 4 g of the compound is subjected to hydrogenation debenzylation to obtain a compound 4h; wherein, the hydrodebenzylation reaction may use, for example, a reducing agent of 10% palladium carbon; and the reaction solvent may be, for example, methanol, tetrahydrofuran or a mixed solvent of methanol and tetrahydrofuran.

In Reaction Schemes 1, 2 and 3, the definition of Ri~R _{7 is} the same as defined above except that R _{6 is} not hydrogen. Further, the present inventors have found through experiments that the compound of the general formula (I) has excellent _{α 1} -adrenergic receptor antagonistic activity and selectivity, and thus the compound of the present invention can be used for preparing an experimental model tool related to on-adrenergic receptors. Or the preparation of a medicament for the treatment and prevention of diseases associated with on-adrenergic receptors, especially urinary system diseases such as benign prostatic hyperplasia, urinary retention, bladder outlet obstruction.

 The invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt, crystalline hydrate thereof, and solvate thereof, and one or more pharmaceutically acceptable Accepted carrier. The pharmaceutically acceptable salt thereof includes a non-toxic salt formed by reacting with an inorganic acid or an organic acid, and the inorganic acid includes hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, aminosulfonic acid, and phosphoric acid, and the organic acid includes propionic acid. , oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, aspartic acid. The pharmaceutical composition may further contain conventional additives such as odorants and flavoring agents.

 The pharmaceutical composition provided by the present invention preferably contains, in a weight ratio of 1 to 99%, one or more selected from the group consisting of a compound of the formula (I), a pharmaceutically acceptable salt thereof, a crystalline hydrate and a solvate thereof. The active ingredient, preferably, the active ingredient is from 65% to 99% by weight based on the total weight of the pharmaceutical composition, the remainder being a pharmaceutically acceptable carrier and/or conventional additives.

 The compounds and pharmaceutical compositions provided herein may be in a variety of forms, such as tablets, capsules, powders, syrups, solutions, suspensions, and aerosols, and may be presented in a suitable solid or liquid carrier or diluent. Neutralizes a suitable sterilizing device for injection or drip.

 Various dosage forms of the pharmaceutical compositions of the present invention can be prepared according to conventional methods of preparation in the pharmaceutical arts. The formulation of the formulation may comprise 0.05-200 mg, preferably 0.1 mg-100 mg of one or more selected from the group consisting of the compound of the formula (I), a pharmaceutically acceptable salt thereof, a crystalline hydrate and a solvate thereof. .

 The compounds and pharmaceutical compositions of this invention may be administered to mammals clinically, including humans and animals, and may be administered by the oral, nasal, dermal, pulmonary or gastrointestinal routes. The most preferred route of administration is oral.

Accordingly, the present invention also provides a method of treating a urinary system disease associated with an alpha-adrenergic receptor, particularly a benign prostatic hyperplasia, urinary retention, bladder outlet obstruction, including administration to a subject in need of such treatment. An effective amount is selected from one or more of the compounds of the formula (I) and pharmaceutically acceptable salts, crystalline hydrates and solvates thereof. It should be understood that within the scope of the present invention, the above various technical features of the present invention and the following (as in the embodiment) The various technical features specifically described in the description can be combined with one another to form a new or preferred technical solution. Due to space limitations, we will not repeat them here. detailed description

 The invention will be further illustrated in the following examples. These examples are for illustrative purposes only and are not intended to limit the invention in any way.

 The starting materials used in the present invention are commercially available unless otherwise specified.

 Example 1: 1-(3-Hydroxypropyl)-5-[(2R)-2-[2,6-dimethyl-phenoxy]ethylamino]propyl]-indole-7- Amide (DC371801) (as shown in Reaction Scheme 1 and Reaction Scheme 2, the corresponding two intermediates are prepared first, and then prepared by Reaction Scheme 3 shown in Reaction Scheme 3 (DC471801)

 1.1: 1-(3-hydroxypropyl)-indoline

50g (31.5ml) of indoline was dissolved in 600ml of acetonitrile, 47.5ml of 3-bromo-1-propanol was added, 120g of potassium carbonate was added, and refluxed for 12h. After the reaction solution was cooled, it was filtered by suction and purified by column chromatography. The oil was 64 g, and the yield was 86%. NMR (d-DMSO, 400 MHz): δ 7.95-8.06 (2 Η, m), 7.55 (IH, dd), 7.28 (IH, dd), 4.40-4.50 (2H, m), 3.48-3.60 (2H, m ), 3.3-3.4 (2H, m), 2.98-2.93 (2H, m), 2.36-2.50 (2H, m). ESI-MS m/z: 178 [M+H] ⁺ .

 1.2: l-(3-Benzoyloxypropyl)-indoline

The above-mentioned 1-(3-hydroxypropyl)-indoline 64 g was dissolved in 600 ml of anhydrous dichloromethane, and 56 ml of triethylamine was added thereto, and 43 ml of benzoyl chloride was slowly added dropwise under ice-cooling. The reaction was added for 10 h, then extracted with water three times (100 mL X 3 ), and then evaporated. 1H NMR (CDC1 ₃ , 400 MHz): δ 7.95-8.08 (m, 2H), 7.56-7.66 (m, IH), 7.31-7.50 (m, 6H), 4.4-4.5 (m, 2H), 3.79-4.0 (m, 2H) 3.5-3.6 (m, 2H), 3.31-3.40 (m, 2H), 2.38-2.5 (m, 2H). ESI-MS m/z: 282 [M+H]+.

 1.3: l-(3-Benzoyloxypropyl)-5-formyl-indoline

40 ml of hydrazine, hydrazine-dimethylformamide was dissolved in 500 ml of anhydrous 1,2-dichloroacetic acid, 64 ml of phosphorus oxychloride was slowly added dropwise under nitrogen and ice bath stirring, and the reaction was further completed for 1 h, then A solution of 1-(3-benzoyloxypropyl)-indoline (96.8 g) in anhydrous 1,2-dichloroacetamidine (300 ml) was added dropwise thereto, and the mixture was transferred to The reaction was carried out in an oil bath at 80 ° C for 2 h. After the reaction was completed, it was cooled to room temperature, and most of the solvent was removed by concentration. The residual phosphorus oxychloride was quenched with water and then extracted with ethyl acetate (300 ml X 3 ). Purification by column chromatography to give a yellow solid (yield: 82% ₎ (yield: 82% ₎ NMR (CDCI3, 400 MHz): δ 9.8 (s, IH), 8.0-8.12 (m, 2H), 7.42-7.63 (m: (5, H) J = 8.5 Hz), 2.01-2.2 (m, 2H). ESI-MS m/z: 310 [M+H]+.

 1.4: l-(3-Benzoyloxypropyl)-5-(2-nitropropenyl)-indoline

86 g of 1-(3-benzoyloxypropyl; )-5-formyl-indoline obtained in the previous step was dissolved in 250 ml of nitroacetamidine, 42 g of ammonium acetate was added, 120 ml of acetic acid was added, and the reaction was refluxed for 4 h. After that, the reaction mixture was concentrated, then EtOAc (3 mL), EtOAc (EtOAc) %. 1H NMR (CDC1 ₃ , 400 MHz): δ 8.05-8.1 (m, 3H), 7.55-7.65 (m, 1H), 7.42-7.5 (m, 2H), 7.2-7.3 (m, 2H), 6.40 (d , 1H, J = 8.4Hz), 4.41-4.49 (m, 2H), 3.5-3.6 (m, 2H), 3.3-3.4 (m, 2H), 3.0-3.1 (m, 2H), 2.48 (S, 3H ), 2.0-2.1 (m, 2H). ESI-MS m/z: 367 [M+H]+.

 1.5: l-(3-Benzoyloxypropyl)nitropropyl)-indoline

70 g of 1-(3-benzoyloxypropyl)nitropropenyl)-indoline obtained in the previous step was dissolved in a mixed solvent of 300 ml of dichloromethane and 600 ml of methanol, and stirred under ice bath. Slowly add sodium borohydride in batches until the reaction solution turns from red to colorless and clear and transparent (about 75 g of sodium borohydride). The reaction is detected by TLC. After the reaction is completed, the reaction solution is concentrated to remove most of the methanol, and then After adding 600 ml of ethyl acetate, a saturated aqueous solution of ammonium chloride was added thereto, and a large amount of a white solid was obtained, which was filtered, and the filtrate was washed three times with water (200 ml of EtOAc). g, yield 91%. 1H NMR (CDC1 ₃ , 400 MHz): δ 8.0-8.1 (m, 1H), 7.56-7.64 (m, 1H), 7.4-7.5 (m, 2H), 6.85 (s, 1H), 6.83 (d, 1H) , J=8.0Hz), 6.39 (d, 1H, J=8.0Hz), 6.53-6.51 (m, 1H), 4.65-4.75 (m, 1H), 4.4-4.5 (m, 2H), 3.3-3.4 ( m, 2H), 3.15-3.28 (m, 3H), 2.8-3.0 (m, 3H), 2.0-2.1 (m, 2H), 1.50 (d, 3H, J = 6.6Hz). ESI-MS m/z : 369 [M+H]+.

 1.6: l-(3-Benzoyloxypropyl)-7-formyl nitropropyl)-indoline

Under nitrogen protection and ice bath agitation, 40 ml of phosphorus oxychloride was slowly added dropwise to 120 ml of hydrazine, hydrazine-dimethylformamide, and the reaction was added for 1 h, and then one step was added dropwise to obtain 1-(3- Benzyloxypropyl)-5-(2-nitropropyl)-indoline (64.3g) in hydrazine, hydrazine-dimethylformamide solution (200ml), added, transferred to 80° C oil bath reaction for 2h, after the reaction is completed, cooled to room temperature, concentrated to remove most of the solvent, slowly added water to quench the residual phosphorus oxychloride, and then extracted with ethyl acetate (500ml X 3), the organic layer was combined, dried, column Purification by chromatography gave 60 g of a yellow solid, yield 86%. 1H NMR (CDC1 ₃ , 400 ΜΗζ): δ 9.94 (s, 1H), 8.0-8.1 (m, 2H), 7.5-7.6 (m,

1Η)7.4-7.5 (m, 2H), 7.22 (s, 1H), 6.93 (brs, 1H), 4.65-4.76 (m, 1H), 4.4-4.5 (m, 2H), 3.6-3.7 (m, 4H) ), 3.20 (dd, 1H, J=7.7, 14.2Hz), 3.0-3.1 (m, 2H), 2.93 (dd, 1H, J=6.4, 14.2Hz), 2.1-2.2 (m, 2H), 1.54 ( d, 3H, J = 6.6Hz). ESI-MS m/z: 397 [M+H]+.

 1.7: l-(3-Benzoyloxypropyl)-7-formyl nitropropyl)-oxime

60 g of 1-(3-benzoyloxypropyl)-7-formyl-5-(2-nitropropyl)-indoline obtained in the previous step was dissolved in 500 ml of ethyl acetate, and 2 was added. 5-dichloro-5,6-dicyano-1,4-benzoquinone 52g, the reaction was added for 12h, washed with saturated sodium bicarbonate three times (300ml X 3 ), the organic layer was concentrated to give a pale yellow oil 53.7g The yield was 90%. 1H NMR CCDC1 ₃ , 400 MHz): δ 10.04 (s, 1H), 8.02 (d, 2H), 7.67 (d, J = 1.3 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.49- 7.40 (m, 3H), 7.18 (d, J = 3.2 Hz, 1H), 6.52 (d, J = 3.2 Hz, 1H), 4.89-4.76 (m, 3H), 4.24 (t, J = 6.1 Hz, 2H ), 3.45 (dd, J = 14.2, 7.7 Hz, 1H), 3.16 (dd, J = 14.2, 6.5 Hz, 1H), 2.24-2.11 (m, 2H), 1.58 (d, J = 6.6 Hz, 3H) . ESI-MS m/z: 395 [M+H]+.

 1.8: l-(3-Benzoyloxypropyl)-7-cyano-5-(2-nitropropyl)-indole

53.7 g of 1-(3-benzoyloxypropyl)-7-formyl-5-(2-nitropropyl)-indole obtained in the previous step was dissolved in 450 ml of anhydrous tetrahydrofuran, and hydroxylamine hydrochloride 12 g was added. , add 50ml of pyridine, react at 50 ° C for 12h, then 52 ml of acetic anhydride was added in portions, and the mixture was warmed to reflux for 8h. The reaction mixture was evaporated, evaporated, evaporated, evaporated, evaporated. 87%. 1H NMR (CDC1 ₃ , 400 ΜΗζ): δ 8.0-8.1 (m, 2H), 7.5-7.6 (m, 1H), 7.4-7.5 (m, 2H), 7.16 (d, J = 3.2 Hz, 1H), 6.93 (brs, 1H), 6.89 (brs, 1H), 6.54 (d, J = 3.2 Hz, 1H), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 2H), 3.7-3.81 (m, 2H), 3.12 (dd, 1H, J=7.8, 14.2Hz), 2.86 (dd, 1H, J=6.2, 14.2Hz), 2.1-2.2 (m, 2H), 1.54 (d, 3H, J = 6.7Hz) ESI-MS m/z: 392 [M+H] ⁺ .

 1.9: l-(3-Benzoyloxypropyl)-7-cyanoaminopropyl)-oxime

The 1-(3-benzoyloxypropyl)-7-cyano-5-(2-nitropropyl)-indole (47 g) obtained in the previous step was dissolved in a mixed solvent of 400 ml of methanol and 400 ml of tetrahydrofuran. Adding 4.7 g of 10% palladium on carbon, reducing under a pressure of atmospheric pressure of hydrogen for 48 hours, after completion of the reaction, suction filtration, and concentration of the filtrate to obtain 41.2 g of product, yield Α Η NMR (CDC1 ₃ , 400 MHz): δ 8.02 (d , 2H), 7.67 (d, J = 1.3 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.49-7.40 (m, 3H), 7.15 (d, J = 3.2 Hz, 1H), 6.52 (d, J = 3.2 Hz, 1H), 4.89-4.76 (m, 3H), 4.24 (t, J = 6.1 Hz, 2H),

3.45- 3.52 (m, 3H), 3.16 (dd, J = 14.2, 6.5 Hz, 1H), 2.24-2.1 1 (m, 2H), 1.05 (d, J = 6.6 Hz, 3H). ESI-MS m/ z: 362 [M+H]+.

 1.10: l-(3-benzoyloxypropyl;)-7-cyano-5-[(2R)-2-aminopropyl]-indole

The 1-(3-benzoyloxypropyl)-7-cyano-5-(2-aminopropyl)-indole 5g obtained in the previous step was dissolved in acetone 30 ml, and added dropwise thereto under stirring. 1.2 g of L-(+)-tartaric acid aqueous solution (1.2 g of L-(+)-tartaric acid dissolved in 30 ml of water) was stirred for 12 h, and a large amount of solid was precipitated, and filtered to give the desired product, L-(+)-tartrate, 2.0 g. The obtained solid was dissolved in 80 ml of water, and the mixture was adjusted to pH 10 with a saturated aqueous solution of sodium carbonate, and extracted twice with ethyl acetate (100×2). The organic layer was combined, dried and concentrated to give a pale yellow oily solid 1.8 g. . 1H NMR (CDC1 ₃ , 400 MHz): δ 8.02 (d, 2H), 7.67 (d, J = 1.3 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.49-7.40 (m, 3H) , 7.18 (d, J = 3.2 Hz, 1H), 6.50 (d, J = 3.2 Hz, 1H), 4.89-4.76 (m, 3H), 4.24 (t, J = 6.1 Hz, 2H)

3.46- 3.54 (m, 3H), 3.16 (dd, J = 14.2, 6.5 Hz, 1H), 2.24-2.1 1 (m, 2H), 1.05 (d, J = 6.6 Hz, 3H). ESI-MS m/ z: 362 [M+H]+.

 1.1 1: l-(3-benzoyloxypropyl;)-7-cyano-5-[(2S)-2-aminopropyl]-fluorene

The 1-(3-benzoyloxypropyl)-7-cyano-5-(2-aminopropyl)-indole 5g obtained in the step 1.9 is dissolved in 30 ml of acetone, and added dropwise thereto under stirring. 1.2 g of L-(-)-tartaric acid aqueous solution (1.2 g of L-(-)-tartaric acid dissolved in 30 ml of water) was stirred for 12 hours, and a large amount of solid was precipitated, and filtered to give the desired product L-(-)-tartrate 2.0 g. The obtained solid was dissolved in 80 ml of water, and the mixture was adjusted to pH 10 with a saturated aqueous solution of sodium carbonate, and extracted twice with ethyl acetate (100×2). . 1H NMR (CDC1 ₃ , 400 MHz): δ 8.02 (d, 2H), 7.67 (d, J = 1.3 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.49-7.40 (m, 3H) , 7.08 (d, J = 3.2 Hz, 1H), 6.42 (d, J = 3.2 Hz, 1H), 4.89-4.76 (m, 3H), 4.24 (t, J = 6.1 Hz, 2H),

3.43-3.50 (m, 3H), 3.16 (dd, J = 14.2, 6.5 Hz, 1H), 2.24-2.1 1 (m, 2H), 1.05 (d, J = 6.6 Hz, 3H). ESI-MS m/ z: 362 [M+H]+.

 1.12: Methyl 2,6-dimethylphenoxyacetate

2,6-Dimethylphenol (4 g) was dissolved in acetone, 3.86 ml of methyl bromoacetate was added, and 9.12 g of potassium carbonate was added thereto, and the mixture was refluxed for 12 hours, filtered, and concentrated to give 6.2 g of pale yellow oil. %. 1H NMR (CDC1 ₃ , 400 MHz): δ 7.2-7.0 (m, 3H), 4.68 (s, 2H), 3.8 (s, 3H) 2.2 (s, 6H). ESI-MS m/z: 195 [M +H]+. 1.13: N-methyl-N-methoxy-2,6-dimethylphenoxyacetamide

6.2 g of N,0-dimethylhydroxylamine hydrochloride was dispersed in 200 ml of anhydrous dichloromethane, and 16 ml of a toluene solution of trimethylaluminum (2 mol/L) was added dropwise thereto under nitrogen atmosphere and ice bath stirring. Adding the reaction for 1 hour, then adding one step to obtain a solution of methyl 2,6-dimethylphenoxyacetate in anhydrous dichloromethane (50 ml), adding, reacting for 3 hours, and washing the reaction solution three times with water (150 ml X 3 ) The organic layer was dried and concentrated to give a pale yellow oil (yield: 7.0 g). 1H NMR (CDC1 ₃ , 400 MHz): δ 7.2 (s, IH), 7.16-7.08 (m, 2H), 4.70 (s, 2H), 4.0 (s, 3H), 3.7 (s, 3H), 2.2 ( s, 6H). ESI-MS m/z: 224 [M+H]+.

 1.14: 2,6-Dimethylphenoxyacetaldehyde

The N-methyl-N-methoxy-2,6-dimethylphenoxyacetamide (7.0 g) obtained in the previous step was dissolved in anhydrous tetrahydrofuran, and the mixture was slowly added in portions at -78 ° C. 1.2 g of lithium aluminum hydride was added, and the reaction was carried out for 3 hours. The reaction mixture was added dropwise with water to quench the residual lithium aluminum hydride. The filtrate was filtered and evaporated to give a white solid 4.6 g. 1H NMR (CDC1 ₃ , 400 MHz): δ 10.05 (s, IH), 7.16-7.1 (m, 3H), 4.70 (s, 2H), 2.23 (s, 6H). ESI-MS m/z:

163[MH] ⁺ .

 1.15: l-(3-Benzoyloxypropyl)-5-[(2R)-2-[2,4-dimethyl-phenoxy]ethylamino]propyl]-7-cyano -吲哚

1-(3-Benzoyloxypropyl;)-7-cyano-5-[(2R 2-aminopropyl]-indole 150 mg obtained in the step 1.10 was dissolved in 1,2-dichloroethane. In the crucible, 100 mg of 2,6-dimethylphenoxyacetaldehyde was added, and 125 mg of sodium borohydride hydride was added thereto, and the mixture was reacted for 12 h, and purified by column chromatography to yield 178 mg of pale yellow oil (yield: 83%) ESI-MS m/z: 510[M+H] ⁺ .

1.16: 1-(3-Hydroxypropyl)-5-[(2R)-2-[2,6-dimethyl-phenoxy]ethylamino]propyl]-7-cyano-indole The compound obtained in the previous step (178 mg) was dissolved in methanol, 525 μl of aqueous sodium hydroxide (concentration of 1 mol/L) was added, and the reaction was carried out for 6 hours, concentrated, and 20 ml of ethyl acetate and 20 ml of water layer were added, and the organic layer was dried and concentrated. Yellow oil 130 mg, yield 90%. ESI-MS m/z: 406 [M+H] ⁺ .

 1.17: 1-(3-hydroxypropyl;)-5-[(2R)-2-[2,6-dimethyl-phenoxy]ethylamino]propyl]-indole-7-carboxamide

( DC471801 )

The compound obtained in the previous step (130 mg) was dissolved in dimethyl sulfoxide, and 10 μl/L aqueous sodium hydroxide solution (110 μl) was added thereto, and a 30% aqueous hydrogen peroxide solution (aqueous solution) was added thereto. After reacting for 12 hours, 20 ml of water was added thereto, and the mixture was extracted three times with ethyl acetate. 20 ml of X 3 ), org. NMR (400 MHz, CDC1 ₃ ): δ 7.48 (s, IH), 7.16 (s, IH), 7.10 (d, J = 3.2 Hz, IH), 6.96 (s, IH), 6.92-6.87 (m,

3H), 6.87-6.80 (m, IH), 6.49 (d, J = 3.2 Hz, IH), 4.38 (m, 2H), 3.88 (m, 2H), 3.29 (t, J = 8.4 Hz, 2H), 3.17-2.94 (m, 3H), 2.83-2.70 (m, IH), 2.64-2.53 (m, IH), 2.15 (s, 6H), 1.67 (m, 2H), 1.1 1 (d, J = 6.0 Hz , 3H). ESI-MS m/z: 424 [M+H] ⁺ . Example 2: l-(3-Hydroxypropyl)-5-[(2R)-2-[2,4,6-trimethyl-phenoxy]ethylamino]propyl]-anthracene- 7-formamide (DC471802)

According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with 2,4,6-trimethylphenol. 1H NMR (400 MHz, CDC1 ₃ ): δ 7.44 (s, 1H), 7.14 (d, J = 3.2 Hz, 1H), 7.02 (s, 1H), 6.97 (s, 1H), 6.87 (d, J = 7.6 Hz, 1H), 6.80 (d, J = 7.6 Hz, 1H), 6.72 (s, 1H), 6.44 (d, J = 3.2 Hz, 1H), 3.88-3.76 (m, 2H), 3.68 (t, J = 5.6 Hz, 2H), 3.14 (t, J = 6.8 Hz, 2H), 3.05 (m, 1H),

3.00- 2.92 (t, J = 6.8 Hz, 2H), 2.69 (dd, J = 13.5, 6.7 Hz, 1H), 2.58 (dd, J = 13.5, 6.5 Hz, 1H), 2.19 (s, 3H), 2.16 (s, 3H), 2.11 (s, 3H), 1.79-1.70 (m, 2H), 1.09 (d, J = 6.3 Hz, 3H). ESI-MS m/z: 438 [M+H] ⁺ .

 Example 3: l-(3-Hydroxypropyl)-5-[(2R)-2-[2,3,6-trimethyl-phenoxy]ethylamino]propyl]-indole-7 - Formamide (DC471803)

 According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with 2,3,6-trimethylphenol. 1H NMR (400 MHz, CDCI3): δ 7.48 (s, 1H), 7.12 (d, J = 3.2 Hz, 1H), 7.02 (s, 1H),

7.01- 6.98 (m, 1H), 6.78 (s, 2H), 6.70 (s, 1H), 6.52 (d, J = 3.2 Hz, 1H), 3.90-3.80 (m, 2H), 3.68 (t, J = 5.6 Hz, 2H), 3.14 (t, J = 6.8 Hz, 2H), 3.07-3.02 (m, 1H), 2.92-2.96 (m, 2H), 2.71

(dd, J = 13.5, 6.7 Hz, 1H), 2.63-2.56 (m, 1H), 2.20 (s, 3H), 2.16 (s, 6H), 1.79-1.69 (m, 2H), 1.10 (d, J = 6.3 Hz, 3H). ESI-MS m/z: 438 [M+H] ⁺ .

 Example 4: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[5-ethyl-2-(2,2,2-trifluoroethoxy)phenoxy ]ethylamino]propyl]-indole-7-carboxamide (DC471804)

 According to the preparation method of Example 1, the 2,6-dimethylphenoxyacetaldehyde in the step 1.15 was replaced with 5-ethyl group.

 2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde, 5-ethyl-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde The preparation is as shown in the following Reaction Scheme 4. 1H NMR (400 MHz, CDCI3): δ 7.45 (s, 1H), 7.13 (d, J = 3.2 Hz, 1H), 6.98 (s, 2H), 6.86 (d, J = 8.0 Hz, 1H), 6.71 ( m, 2H), 6.62 (s, 1H), 6.55 (d, J = 3.2 Hz, 1H), 4.31-4.18 (m, 2H), 4.10 (t, J = 7.52 Hz, 2H), 3.68 (t, J = 5.5 Hz, 2H), 3.13 (m, 2H),

3.08-2.87 (m, 3H), 2.69 (dd, J = 13.5, 6.3 Hz, 1H), 2.62-2.46 (m, 3H), 1.82-1.67 (m, 2H), 1.20-1.14 (t, J = 7.7 Hz, 3H), 1.07 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 522 [M+H] ⁺ .

 4.1: 5-Ethyl-2-(2,2,2-trifluoroethoxy)-anisole

2.5 g of 2-methoxy-4-ethyl-phenol was dissolved in hydrazine, hydrazine-dimethylformamide, and 4.2 g of 2,2,2-trifluoroethyl-p-toluenesulfonate was added, and potassium carbonate was added. 7.0g, reacted at 100 ° C for 12h, added 200ml of water and 200ml of ethyl acetate layered, the organic layer was washed with water three times (200ml X 3 ), the organic layer was combined and purified by column chromatography to obtain 2.5g of pale yellow oil. The rate is 65%. 1H NMR (400 MHz, CDCI3): δ 6.85 (d, J = 2.2 Hz, 1H), 6.8 (d, J = 2.5 Hz, 1H), 6.74 (m, 1H), 4.31-4.18 (m, 2H), 3.8(s, 3H), 2.6(q, J = 6.8 Hz, 2H), 1.25(t, J = 6.8 Hz, 3H). ESI-MS m/z: 235 [M+H] X.

 4.2: 5-Ethyl-2-(2,2,2-trifluoroethoxy)-phenol

2.5 g of 5-ethyl-2-(2,2,2-trifluoroethoxy)-anisole obtained in the previous step was dissolved in anhydrous dichloromethane, and protected under nitrogen at -20 ° C. 2.0 ml of boron tribromide was slowly added dropwise thereto, and the reaction was further carried out for 2 hours. Then, water was added dropwise to the reaction liquid to quench the residual boron tribromide, and 200 ml of ethyl acetate and 200 ml of a water layer were added thereto, and the organic layer was dried and concentrated. A pale yellow oil of 2.35 g was obtained in a yield of 100%. NMR (400 MHz, CDC1 ₃ ) : δ 6.80 (d, J = 2.2 Hz, 1H), 6.78 (d, J = 2.5 Hz, 1H), 6.72 (m, 1H), 4.28-4.18 (m, 2H), 2.8 (q, J = 6.8 Hz, 2H), 1.25 (t, J = 6.8 Hz, 3H). ESI-MS m/z: 221 [M+H] ⁺ .

 4.3: Methyl 5-ethyl-2-(2,2,2-trifluoroethoxy)-phenoxyacetate

2.35 g of 5-ethyl-2-(2,2,2-trifluoroethoxy)-phenol obtained in the previous step was dissolved in acetone, 1.2 ml of methyl bromoacetate was added, and 3.0 g of potassium carbonate was added thereto, followed by reflux for 12 hours. , 抽, yield 99%. 1H NMR (400 MHz, CDC1 ₃ ) : δ 6.80 (d, J = 2.2 Hz, 1H), 6.78 (d, J = 2.5 Hz, 1H), 6.72 (m, 1H), 4.8 (s, 2H), 4.28 -4.18(m, 2H), 3.7(s, 3H), 2.8(q, J = 6.8 Hz, 2H), 1.25(t, J = 6.8 Hz, 3H). ESI-MS m/z: 293 [M+ H]+.

 4.4: N-methyl-N-methoxy-5-ethyl-2-(2,2,2-trifluoroethoxy)-phenoxyacetamide

 2.2 g of N,0-dimethylhydroxylamine hydrochloride was dispersed in 150 ml of anhydrous dichloromethane, and 8.2 ml of a toluene solution of trimethylaluminum (2 mol/L) was added dropwise thereto under nitrogen atmosphere and ice bath stirring. Adding the reaction for 1 hour, then adding one step to obtain a solution of methyl 5-ethyl-2-(2,2,2-trifluoroethoxy)-phenoxyacetate in anhydrous dichloromethane (30 ml). After the addition, the reaction was carried out for 3 h, and the reaction mixture was washed threetimes with water (150 ml EtOAc). 1H NMR (400 MHz, CDCI3): δ 6.83 (d, J = 2.2 Hz, 1H), 6.80 (d, J = 2.5 Hz, 1H), 6.74 (m, 1H), 4.78 (s, 2H), 4.22- 4.14(m, 2H), 3.8(s, 3H), 3.6(s, 3H), 2.77(q, J = 6.6 Hz, 2H), 1.26(t, J = 6.6 Hz, 3H). ESI-MS m/ z: 322 [M+H]+.

 4.5: 5-Ethyl-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde

The N-methyl-N-methoxy-5-ethyl-2-(2,2,2-trifluoroethoxy)-phenoxyacetamide (3.5 g) obtained in the previous step was dissolved in anhydrous tetrahydrofuran. 414mg of lithium tetrahydrogenate was added slowly to the batch at -78 °C, and the reaction was carried out for 3 hours. The reaction solution was added dropwise with water to quench the lithium tetrahydrogenate. The filtrate was dried and concentrated to give a white solid. g, yield 91%. ¹ MN MR (400 MHz, CDCl ₃ : 510.2 (s, 1H), 6.83-6.78 (m, 2H), 6.70 (m, 1H), 4.82 (s, 2H), 4.24-4.16 (m, 2H), 2.75 ( q, J = 6.6 Hz, 2H), 1.22 (t, J = 6.6 Hz, 3H). ESI-MS m/z: 261 [MH] ⁺ . Example 5: l-(3-hydroxypropyl) -5 -[(2R)-2-[2-[4-ethyl-2-ethoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide (DC471805)

 Prepared according to the preparation method of Example 1, replacing 2,6-dimethylphenoxyacetaldehyde in step 1.15 with 2-ethoxy-4-ethyl-phenoxyacetaldehyde, 2-ethoxy- The preparation of 4-ethyl-phenoxyacetaldehyde is shown in the following Reaction Scheme 5. iH NMR (400 MHz, CDCI3): δ 7.42 (s, 1H), 7.18 (d, J = 3.2 Hz, 1H), 6.98 (s, 2H), 6.88 (d, J = 8.0 Hz, 1H), 6.71 ( m, 2H), 6.62 (s, 1H), 6.56 (d, J = 3.2 Hz, 1H), 4.10 (t, J = 7.52 Hz, 2H), 3.8 (q, J = 6.8 Hz, 2H), 3.68 ( t, J = 5.5 Hz, 2H), 3.13 (m, 2H), 3.08-2.87 (m, 3H), 2.69 (dd, J = 13.5, 6.3 Hz, 1H), 2.62-2.46 (m, 3H), 1.82 -1.67 (m, 2H), 1.20-1.14 (m, 6H), 1.07 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 468[M+H]+.

Reaction Scheme 5: Preparation of 2-ethoxy-4-ethyl-phenoxyacetaldehyde

 5.1: 2-methoxy-4-ethyl-phenoxyacetic acid methyl ester

2.5 g of 2-methoxy-4-ethyl-phenol was dissolved in acetone, 1.68 ml of methyl bromoacetate was added, and 4.54 g of potassium carbonate was added thereto, and the mixture was refluxed for 12 hours, filtered with suction, and evaporated. The yield was 95%. 1H NMR (400MHz, CDC1 ₃ ): 56.83 (d, J = 7.8 Hz, IH), 6.80 (s, IH), 6.72 (d, J = 7.8 Hz, IH), 4.82 (s, 2H), 3.7 (s, 3H), 3.58(s, 3H), 2.65(q, J=7.2Hz, 2H), 1.2(t, J=7.2Hz, 3H). ESI-MS m/z: 225 [M+H]+.

 5.2: N-methyl-N-methoxy-2-methoxy-4-ethyl-phenoxyacetamide

Disperse 3.1 g of N,0-dimethylhydroxylamine hydrochloride in 150 ml of anhydrous dichloromethane, and add 1 1.5 ml of a toluene solution of trimethylaluminum (2 mol/L) under nitrogen atmosphere and ice bath stirring. After the addition reaction, lh, then add one step to obtain a solution of methyl 2-methoxy-4-ethyl-phenoxyacetate (3.5 g) in anhydrous dichloromethane (30 ml), add, and react for 3 h. The reaction solution was washed three times with water (150 ml EtOAc). ¹ H NMR (400 MHz, CDCI 3 ): δ 6.83-6.80 (m, 2H), 6.74 (d, J = 7.5 Hz, IH), 4.83 (s, 2H), 3.83 (s, 3H), 3.72 (s, 3H) , 3.56(s, 3H), 2.64 (q, J = 7.2 Hz, 2H), 1.22 (t, J = 7.2 Hz, 3H). ESI-MS m/z: 254 [M+H] ⁺ .

 5.3: N-methyl-N-methoxy-2-hydroxy-4-ethyl-phenoxyacetamide

The 3.6 g of N-methyl-N-methoxy-2-methoxy-4-ethyl-phenoxyacetamide obtained in the previous step was dissolved in anhydrous dichloromethane, and protected at -20 ° C under nitrogen. Next, 2.1 ml of boron tribromide was slowly added dropwise thereto, and the reaction was further carried out for 2 hours. Then, water was added dropwise to the reaction liquid to quench the residual boron tribromide, 200 ml of ethyl acetate and 200 ml of water layer were added, and the organic layer was dried. The mixture was concentrated to give a pale yellow oil (yield: 3.3 g). 1H NMR (400MHz, CDC1 ₃ ): δ 6.85-6.79 (m, 2H), 6.68 (d, J = 7.2 Hz, IH), 4.81 (s, 2H), 3.70 (s, 3H), 3.52 (s, 3H) , 2.65 (q, J = 7.82 Hz, 2H), 1.26 (t, J = 7.2 Hz, 3H). ESI-MS m/z: 240 [M+H] ⁺ .

 5.4: N-methyl-N-methoxy-2-ethoxy-4-ethyl-phenoxyacetamide

3.3 g of N-methyl-N-methoxy-2-hydroxy-4-ethyl-phenoxyacetamide obtained in the previous step was dissolved in N,N-dimethylformamide, and 1.2 ml of iodine was added. 9.0 g of cesium carbonate was reacted at 100 ° C for 12 h, then 200 ml of ethyl acetate and 200 ml of water were added to the reaction mixture, and the layers were separated. The organic layer was washed twice with water (150 ml X 2 ), dried and concentrated. Yellow oil 3.3 g, yield 89%. 1H NMR (400MHz, CDC1 ₃ ): 5 6.83 (d, J = 7.8 Hz, IH), 6.80 (s, IH), 6.72 (d, J = 7.8 Hz, IH), 4.81 (s, 2H), 3.8 (q) , J=7.5Hz, 2H), 3.70(s, 3H), 3.52(s, 3H), 2.65(q, J=7.82Hz, 2H), 1.26(t, J=7.2Hz, 3H), 1.21(t , J=7.5Hz, 3H). ESI-MS

m/z: 268 [M+H] ⁺ .

 5.5: 2-Ethoxy-4-ethyl-phenoxyacetaldehyde

3.3 g of N-methyl-N-methoxy-2-ethoxy-4-ethyl-phenoxyacetamide obtained in the previous step was dissolved in anhydrous tetrahydrofuran, and batched slowly at -78 °C. After adding 470 mg of lithium aluminum hydride, the reaction was carried out for 3 hours, and the reaction liquid was added dropwise with water to quench the lithium tetrahydrogenate. The filtrate was dried and concentrated to give a white solid (2.0 g, yield: 90%). iHNMR (400MHz, CDCI3): 510.1(s, IH), 6.82-6.76(m, 2H), 6.65(d, J=7.3Hz, IH), 4.78(s, 2H), 3.68 (q, J=7.4Hz , 2H), 2.65(q, J=7.4Hz, 2H), 1.28(t, J=7.3Hz, 3H), 1.23(t, J=7.3Hz, 3H). ESI-MS m/z: 207[MH ] ⁺ . Example 6: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-ethyl-2-methoxy-phenoxy]ethylamino]propyl] -吲哚-7-formamide (DC471806)

According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with 2-methoxy-4-ethyl-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.43 (s, 1H), 7.13 (d, J = 3.2 Hz, 1H), 7.07 (d, J = 5.6 Hz, 1H), 6.98 (s, 1H), 6.76 (d, J = 7.8 Hz, 1H), 6.71-6.65 (m, 2H), 6.55 (d, J = 17.6 Hz, 1H), 6.55 (d, J = 3.2 Hz, 1H), 4.14-4.00 (m, 2H), 3.76 (s, 3H), 3.69 (t, J = 4.6 Hz, 2H),

3.15 (t, J = 6.7 Hz, 2H), 3.10-2.88 (m, 3H), 2.70 (dd, J = 13.6, 6.5 Hz, 1H), 2.62-2.50 (m, 3H), 1.76 (dd, J = 11.9, 5.9 Hz, 2H), 1.19 (t, J = 7.6 Hz, 3H), 1.07 (d, J = 6.3 Hz, 3H).

ESI-MS m/z: 454[M+H]+.

 Example 7: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-ethyl-2-cyclopropoxy-phenoxy]ethylamino]propyl] -B 哚-7-formamide (DC471807)

 According to the preparation method of Example 5, the iodonium in the step 5.4 was replaced with bromocyclopropane. iH NMR (400 MHz, CDCI3): δ 7.46 (s, 1H), 7.16 (d, J = 3.2 Hz, 1H), 7.06 (d, J = 5.6 Hz, 1H), 6.98 (s, 1H), 6.74 ( d, J = 7.8 Hz, 1H), 6.70-6.63 (m, 2H), 6.54 (d, J = 17.6 Hz, 1H), 6.46 (d, J = 3.2 Hz, 1H), 4.14-4.00 (m, 2H) ), 3.70 (t, J = 4.6 Hz, 2H), 3.68 (m, 1H), 3.40-3.35 (m, 2H),

3.16 (t, J = 6.7 Hz, 2H), 3.10-2.90 (m, 3H), 2.70 (dd, J = 13.6, 6.5 Hz, 1H), 2.62-2.50 (m, 4H), 1.76 (dd, J = 11.9, 5.9 Hz, 2H), 1.19 (t, J = 7.6 Hz, 3H), l . l(d, J = 6.3 Hz, 3H), 0.73 (m, 1H), 0.56 (m, 2H). ESI- MS m/z: 454 [M+H]+.

 Example 8: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-ethyl-2-cyclopropoxy-phenoxy]ethylamino]propyl ] - 吲哚-7-carboxamide (DC471808)

 According to the preparation method of Example 5, the iodonium in the step 5.4 was replaced with bromomethylcyclopropane. iH NMR (400 MHz, CDCI3): δ 7.50 (d, j = 1.3 Hz, 1H), 7.14 (d, J = 1.4 Hz, 1H), 7.13 (d, J = 3.2 Hz, 1H), 6.94-6.83 ( m, 2H), 6.65 (s, 1H), 6.61 (d, J = 8.5 Hz, 1H), 6.46 (s, 1H), 6.42 (d, J = 3.2 Hz, 1H), 4.14-4.00 (m, 2H) ), 3.69 (t, J = 4.6 Hz, 2H), 3.56 (m, 2H), 3.18 (t, J = 6.7 Hz, 2H), 3.10-2.92 (m, 3H), 2.70 (dd, J = 13.6, 6.5 Hz, 1H), 2.62-2.50 (m, 3H), 1.76 (dd, J = 11.9, 5.9 Hz, 2H), 1.19 (t, J = 7.6 Hz, 3H), 1.09 (d, J = 6.3 Hz, 3H), 0.83 (m, 2H), 0.38 (m, 1H), 0.35 (m, 2H). ESI-MS m/z: 494[M+H]+.

 Example 9: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-ethyl-2-tert-butoxy-phenoxy]ethylamino]propyl] -B 哚-7-formamide (DC471809)

 According to the preparation method of Example 5, the iodonium in the step 5.4 was replaced with bromo-tert-butyl hydrazine. iH NMR

(400 MHz, CDCI3): δ 7.44 (d, J = 1.3 Hz, 1H), 7.10 (d, J = 1.3 Hz, 1H), 7.08 (d, J = 3.2 Hz, 1H), 6.93-6.82 (m, 2H), 6.62 (s, 1H), 6.62 (d, J = 8.5 Hz, 1H), 6.38 (s, 1H), 6.36 (d, J = 3.2 Hz, 1H), 4.14-4.00 (m, 2H), 3.68 (t, J = 4.6 Hz, 2H), 3.15 (t, J = 6.7 Hz, 2H), 3.10-2.90 (m, 3H), 2.70 (dd, J = 13.6, 6.5 Hz, 1H), 2.62-2.51 (m, 3H), 1.76 (dd, J = 11.9, 5.9 Hz, 2H), 1.45 (s, 9H), 1.19 (t, J = 7.6 Hz, 3H), 1.08 (d, J = 6.3 Hz, 3H) . ESI-MS m/z: 496[M+H]+.

 Example 10: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-ethyl-2-pivaloxy-phenoxy]ethylamino]propyl] - 吲哚-7-formamide (DC471810)

According to the preparation method of Example 5, the iodonium in the step 5.4 was replaced with 1-bromo-2,2-dimethylpropane. 1H NMR (400 MHz, CDCI3): δ 7.48 (d, J = 1.3 Hz, 1H), 7.15 (d, j = 1.3 Hz, 1H), 7.10 (d, J = 3.2 Hz, 1H), 6.99-6.87 ( m, 2H), 6.62 (s, 1H), 6.60 (d, J = 8.5 Hz, 1H), 6.49 (s, 1H), 6.45 (J = 3.2 Hz, 1H), 4.14-4.00 (m, 2H), 3.69 (t, J = 4.6 Hz, 2H), 3.52 (s, 2H), 3.15 (t, J = 6.7 Hz, 2H), 3.10-2.88 (m, 3H), 2.70 (dd, J = 13.6, 6.5 Hz , 1H), 2.62-2.50 (m, 3H), 1.76 (dd, J = 1 1.9, 5.9 Hz, 2H), 1.19 (t, J = 7.6 Hz, 3H), 1.07 (d, J = 6.3 Hz, 3H), 0.85(s, 9H). ESI-MS m/z: 510[M +H]+.

Example 11: l- ⁽³ - ^{hydroxypropyl) - 5 - [(2 R} ) - 2 - [2 - [5 - bromo - ² - ^{(2, 2, 2} - trifluoroethoxy) phenoxy ]ethylamino]propyl]-indole-7-carboxamide (DC471811)

According to the preparation method of Example 4, 2-methoxy-4-ethyl-phenol in Step 4.1 was replaced with 2-methoxy-4-bromo-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.48 (s, 1H), 7.12 (d, J = 3.2 Hz, 1H), 7.05-6.99 (m, 3H), 6.96 (s, 1H), 6.87-6.82 ( m, 1H), 6.69 (s, 1H), 6.50 (d, J = 3.2 Hz, 1H), 4.34-4.24 (m, 2H), 4.12-4.00 (m, 2H), 3.72 (t, J = 5.6 Hz 2, 2, 3, 3. 1H), 1.84-1.73 (m, 2H), 1.08 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 573 [M+H] ⁺ .

 Example 12: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-bromo-2-ethoxy-phenoxy]ethylamino]propyl]-hydrazine哚-7-carboxamide (DC471812)

According to the preparation method of Example 5, 2-methoxy-4-ethyl-phenol in Step 5.1 was replaced with 2-methoxy-4-bromo-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.48 (s, 1H), 7.12 (d, J = 3.2 Hz, 1H), 7.08-6.99 (m, 3H), 6.98 (s, 1H), 6.87-6.84 ( m, 1H), 6.69 (s, 1H), 6.53 (d, J = 3.2 Hz, 1H),

4.12-4.00 (m, 2H), 3.78 (q, J = 7.0 Hz, 2H), 3.75 (t, J = 5.6 Hz, 2H), 3.16 (t, J = 7.0 Hz, 2H), 3.12-2.94 (m , 3H), 2.67 (dd, J = 13.6, 6.6 Hz, 1H), 2.55 (dd, J = 13.4, 6.8 Hz, 1H), 1.84-1.75 (m, 2H), 1.2 (t, 3H), 1.07 ( d, J = 6.2 Hz, 3H). ESI-MS m/z: 518 : 520 = 1 : 1 [M+H] ⁺ .

 Example 13: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-bromo-2-methoxy-phenoxy]ethylamino]propyl]-hydrazine哚-7-formamide (DC471813)

 According to the preparation method of Example 1, 2,6-dimethylphenol in the step 1.12 was replaced with 2-methoxy-4-bromo-phenol. 1H NMR (400 MHz, CDC13): δ 7.49 (d, j = 1.3 Hz, 1H), 7.13 (d, j = 1.3 Hz, 1H), 7.09 (d, J = 3.2 Hz, 1H), 6.95-6.89 ( m, 2H), 6.65 (s, 1H), 6.60 (d, J = 8.5 Hz, 1H), 6.49 (s, 1H), 6.46 (d, J = 3.2 Hz, 1H), 4.33 (t, J = 7.1 Hz, 2H), 4.06-3.90 (m, 2H), 3.63 (s, 3H), 3.52-3.43 (m, 2H), 3.06-2.88 (m, 3H), 2.81-2.70 (m, 2H), 2.01- 1.88 (m, 2H), 1.08 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 504:506=1 : 1 [M+H]+.

 Example 14: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-bromo-2-cyclopropoxy-phenoxy]ethylamino]propyl] -吲哚-7-carboxamide (DC471814)

Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-bromo-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. It is made on behalf of the ring. NMR (400 MHz, CDC1 ₃ ) : δ 7.48 (s, 1H), 7.15 (d, J = 3.2 Hz, 1H), 7.05-6.98 (m, 3H), 6.97 (s, 1H), 6.87-6.84 (m , 1H), 6.71 (s, 1H), 6.56 (d, J = 3.2 Hz, 1H), 4.12-4.02 (m, 2H), 3.74 (t, J = 5.6 Hz, 2H), 3.69 (m, 1H) , 3.16 (t, J = 7.0 Hz, 2H), 3.14-2.95 (m, 4H), 2.68 (dd, J = 13.4, 6.5 Hz, 1H), 2.55 (dd, J = 13.6, 7.1Hz, 1H), 1.84-1.76 (m, 2H), 1.06 (d, J = 6.2 Hz, 3H), 0.75 (m, 1H), 0.58 (m, 2H). ESI-MS m/z:530:532=l: l [ M+H] ⁺ .

 Example 15: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-bromo-2-cyclopropoxy-phenoxy]ethylamino]propyl] - 吲哚-7-formamide (DC471815)

 Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-bromo-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. Made from methylcyclopropane. NMR (400 MHz,

CDCI3) : δ 7.44 (s, 1H), 7.12 (d, J = 3.2 Hz, 1H), 7.03-6.87 (m, 3H), 6.95 (s, 1H), 6.87-6.83 (m, 1H), 6.66 ( s, 1H), 6.53 (d, J = 3.2 Hz, 1H), 4.13-4.04 (m, 2H), 3.74 (t, J = 5.7 Hz, 2H), 3.55 (m, 2H), 3.18 (t, J = 7.2 Hz, 2H), 3.13-2.94 (m, 3H), 2.69 (dd, J = 13.4, 6.8Hz, 1H), 2.55 (dd, J = 13.8, 6.8 Hz, 1H), 1.84-1.76 (m, 2H), 1.07 (d, J = 6.4 Hz, 3H), 0.82 (m, 2H), 0.36 (m, 1H), 0.34 (m, 2H). ESI-MS m/z: 544:546 = l: l [M+H]+.

 Example 16: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-bromo-2-tert-butoxy-phenoxy]ethylamino]propyl] -吲哚-7-carboxamide (DC471816)

Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-bromo-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. Made by the uncle Ding Yu. NMR (400 MHz, CDC1 ₃ ) : δ 7.42 (s, 1H), 7.12 (d, J = 3.2 Hz, 1H), 7.08-6.95 (m, 3H), 6.94 (s, 1H), 6.87-6.82 (m , 1H), 6.69 (s, 1H), 6.48 (d, J = 3.2 Hz, 1H), 4.12-4.04 (m, 2H), 3.75 (t, J = 5.6 Hz, 2H), 3.16 (t, J = 7.5 Hz, 2H), 3.11-2.95 (m, 3H), 2.67 (dd, J = 13.6, 6.7 Hz, 1H), 2.53 (dd, J = 13.3, 6.8 Hz, 1H), 1.84-1.73 (m, 2H) ), 1.46 (s, 9H), 1.07 (d, J = 6.2 Hz, 3H). ESI-MS

m/z: 546:548 = l : l [M+H] ⁺ .

 Example 17: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-bromo-2-pivalyloxy-phenoxy]ethylamino]propyl] -吲哚-7-formamide (DC471817)

According to the preparation method of Example 5, the 2-methoxy-4-ethyl-phenol in the step 5.1 was replaced with 2-methoxy-4-bromo-phenol, and the iodonium in the step 5.4 was replaced with 1 -Bromo-2,2-dimethylpropanthine. NMR (400 MHz, CDC1 ₃ ) : δ 7.49 (s, 1H), 7.12 (d, J = 3.2 HzlH), 7.06-6.97 (m, 3H), 6.94 (s, 1H), 6.87-6.83 (m, 1H) ), 6.65 (s, 1H), 6.51 (d, J = 3.2 Hz, 1H), 4.12-4.01 (m, 2H), 3.75 (t, J = 5.6 Hz, 2H), 3.54 (s, 2H), 3.15 (t, J = 7.3 Hz, 2H), 3.12-2.93 (m, 3H), 2.68 (dd, J = 13.4, 6.7 Hz, 1H), 2.54 (dd, J = 13.2, 6.8 Hz, 1H), 1.84- 1.75 (m, 2H), 1.1 (d, J = 6.4 Hz, 3H), 0.86(s, 9H).

ESI-MS m/z: 560:562 = l: l [M+H] ⁺ .

 Example 18: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenoxy] Ethylamino]propyl]-indole-7-carboxamide (DC471818)

According to the preparation method of Example 4, 2-methoxy-4-ethyl-phenol in Step 4.1 was replaced with 2-methoxy-5-fluoro-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.52 (s, 1H), 7.10 (d, J = 3.2 Hz, 1H), 7.04-6.87 (m, 2H), 6.87-6.78 (m, 1H), 6.75- 6.64 (m, 3H), 6.44 (d, J = 3.2 Hz, 1H), 4.38-4.28 (m, 2H), 4.13-4.00 (m, 2H), 3.71 (t, J = 5.6 Hz, 2H), 3.17 (t, J = 6.9 Hz, 2H), 3.07-3.02 (m, 1H), 2.99-2.94 (m, 2H), 2.70 (dd, J = 13.6, 6.6 Hz, 1H), 2.54 (dd, J = 13.6) , 6.8 Hz, 1H), 1.83-1.74 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 512 [M+H] ⁺ .

 Example 19: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[5-fluoro-2-ethoxy-phenoxy]ethylamino]propyl]-hydrazine哚-7-carboxamide (DC471819)

According to the preparation method of Example 5, 2-methoxy-4-ethyl-phenol in Step 5.1 was replaced with 2-methoxy-5-fluoro-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.50 (s, 1H), 7.12 (d, J = 3.2 Hz, 1H), 7.05-6.89 (m, 2H), 6.88-6.75 (m, 1H), 6.78- 6.66 (m, 3H), 6.56 (d, J = 3.2 Hz, 1H), 4.14-4.02 (m, 2H), 3.76 (q, J = 7.1 Hz, 2H), 3.70 (t, J = 5.8 Hz, 2H ), 3.18 (t, J = 6.7 Hz, 2H), 3.09-3.02 (m, 1H), 2.99-2.93 (m, 2H), 2.71 (dd, J = 13.5, 6.7 Hz, 1H), 2.56 (dd, J = 13.6, 6.6 Hz, 1H), 1.83-1.77 (m, 2H), 1.22 (t, 3H), 1.08 (d, J = 6.3Hz, 3H). ESI-MS m/z: 458[M+H ]+.

 Example 20: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[5-fluoro-2-methoxy-phenoxy]ethylamino]propyl]-hydrazine哚-7-formamide (DC471820)

According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with 2-methoxy-5-fluoro-phenol. 1H NMR (400 MHz, CDC13): δ 7.52-7.44 (m, 1H), 7.13 (d, J = 1.4 Hz, 1H), 7.07 (t, J = 3.6 Hz, 1H), 6.79-6.66 (m, 2H) ), 6.63-6.51 (m, 3H), 6.45 (d, J = 3.2 Hz, 1H), 4.38-4.25 (m 2H), 4.05-3.90 (m, 2H), 3.60 (s, 3H), 3.47 (t , J = 5.8 Hz, 2H), 3.05-2.94 (m, 3H), 2.79-2.70 (m, 2H), 2.00-1.86 (m, 2H), 1.08 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 444 [M+H] +. Example 21: l-(3 -hydroxypropyl)-5-[(2R)-2-[2-[5-fluoro-2-cyclopropoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide ( DC471821 )

Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-5-fluoro-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. It is made on behalf of the ring. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.48 (s, 1H), 7.10 (d, J = 3.2 Hz, 1H), 7.07-6.89 (m, 2H), 6.86-6.77 (m, 1H), 6.74- 6.68 (m, 3H), 6.49 (d, J = 3.2 Hz, 1H), 4.15-4.04 (m, 2H), 3.72 (t, J = 5.8 Hz, 2H), 3.69 (m, 1H), 3.15 (t , J = 6.8 Hz, 2H), 3.07-3.05 (m, 2H), 2.98-2.91 (m, 2H), 2.70 (dd, J = 13.8, 6.5 Hz, 1H), 2.54 (dd, J = 13.8, 6.6 Hz, 1H), 1.83-1.76 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H), 0.78 (m, 1H), 0.59 (m, 2H). ESI-MS m/z: 470 [M +H]+.

 Example 22: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[5-fluoro-2-cyclopropoxy-phenoxy]ethylamino]propyl] - 吲哚-7-formamide (DC471822)

 Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-5-fluoro-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. Made from methylcyclopropane. NMR (400 MHz,

CDC1 ₃ ) : δ 7.46 (s, 1H), 7.13 (d, J = 3.2 Hz, 1H), 7.06-6.85 (m, 2H), 6.88-6.76 (m, 1H),

6.74- 6.63 (m, 3H), 6.54 (d, J = 3.2 Hz, 1H), 4.15-4.03 (m, 2H), 3.74 (t, J = 5.8 Hz, 2H), 3.61 (m, 2H), 3.16 (t, J = 6.6 Hz, 2H), 3.07-3.04 (m, 1H), 2.99-2.92 (m, 2H), 2.73 (dd, J = 13.8,

6.7 Hz, 1H), 2.54 (dd, J = 13.8, 6.8 Hz, 1H), 1.83-1.74 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H), 0.84 (m, 2H), 0.36 ( m, 1H), 0.35 (m, 2H). ESI-MS m/z: 484[M+H]+.

 Example 23: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[5-fluoro-2-tert-butoxy-phenoxy]ethylamino]propyl] -吲哚-7-carboxamide (DC471823)

Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-5-fluoro-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. Made by the uncle Ding Yu. NMR (400 MHz, CDC1 ₃ ) : δ 7.49 (s, 1H), 7.12 (d, J = 3.2 Hz, 1H), 7.02-6.86 (m, 2H), 6.84-6.77 (m, 1H), 6.78-6.63 (m, 3H), 6.55 (d, J = 3.2 Hz, 1H), 4.13-4.05 (m, 2H), 3.73 (t, J = 5.4 Hz, 2H), 3.15 (t, J = 6.9 Hz,

2H), 3.08-3.02 (m, 1H), 2.99-2.94 (m, 2H), 2.73 (dd, J = 13.8, 6.6 Hz, 1H), 2.54 (dd, J = 13.6)

6.8 Hz, 1H), 1.83-1.76 (m, 2H), 1.48(s, 9H), 1.07 (d, J = 6.2 Hz, 3H). ESI-MS

m/z: 486[M+H]+.

 Example 24: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[5-fluoro-2-pivalyloxy-phenoxy]ethylamino]propyl] -吲哚-7-formamide (DC471824)

 According to the preparation method of Example 5, the 2-methoxy-4-ethyl-phenol in the step 5.1 was replaced with 2-methoxy-5-fluoro-phenol, and the iodonium in the step 5.4 was replaced with 1 -Bromo-2,2-dimethylpropanthine. NMR (400 MHz, CDCI3): δ 7.44 (s, 1H), 7.12 (d, J = 3.2 Hz, 1H), 7.04-6.85 (m, 2H), 6.84-6.76 (m, 1H),

6.75- 6.65 (m, 3H), 6.47 (d, J = 3.2 Hz, 1H), 4.13-4.06 (m, 2H), 3.75 (t, J = 5.6 Hz, 2H), 3.59 (s, 2H), 3.19 (t, J = 6.8 Hz, 2H), 3.1-3.02 (m, 1H), 2.99-2.92 (m, 2H), 2.75 (dd, J = 13.7, 6.5

Hz, 1H), 2.54 (dd, J = 13.4, 6.9 Hz, 1H), 1.83-1.76 (m, 2H), 1.08 (d, J = 6.2 Hz, 3H), 0.85(s, 9H). ESI-MS m/z: 500 [M+H]+.

Example 2 ⁵ : l-( ³ -Hydroxypropyl) ^-5 -[( ² R)-2- ^2- [ ² -[ ⁵ -fluoro- ² -( ² , ² , ² -trifluoroethoxy)phenoxy Ethylamino]propyl]-indole-7-carboxamide (DC471825)

According to the preparation method of Example 4, 2-methoxy-4-ethyl-phenol in Step 4.1 was replaced with 2-methoxy-4-fluoro-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.94 (s, 1H), 7.52 (s, 1H), 7.40 (d, J = 1.2 Hz, 1H), 7.31 (d, J = 3.0 Hz, 1H), 7.02 (d, J = 1.2 Hz, 1H), 6.93-6.85 (m, 2H), 6.63 (td, J = 8.6, 3.2 Hz, 1H), 6.42 (dd, J = 7.8, 3.1 Hz, 1H), 4.38-4.27 (m, 2H), 4.15-4.10 (m, 2H), 3.73 (t: J = 5.5 Hz, 2H ), 3.16 (t, J = 6.8 Hz, 2H), 3.05-3.01 (m, 1H), 2.99-2.91 (m, 2H), 2.70 (dd, J = 13.6, 6.8 Hz, 1H), 2.52 (dd, J = 13.8, 6.6 Hz, 1H), 1.83-1.73 (m, 2H), 1.08 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 512 [M+H] ⁺ .

 Example 26: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro-2-ethoxy-phenoxy]ethylamino]propyl]-hydrazine哚

-7-carboxamide (DC471826)

According to the preparation method of Example 5, 2-methoxy-4-ethyl-phenol in Step 5.1 was replaced with 2-methoxy-4-fluoro-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.96 (s, 1H), 7.53 (s, 1H), 7.42 (d, J = 1.2 Hz, 1H), 7.30 (d, J = 3.3 Hz, 1H), 7.03 (d, J = 1.2 Hz, 1H), 6.93-6.82 (m, 2H), 6.64 (m, 1H), 6.40 (dd, J = 7.8, 3.1 Hz, 1H), 3.56 (q, J = 7.4 Hz, 2H), 3.72 (t, J = 5.6 Hz, 2H), 3.18 (t, J = 6.8 Hz, 2H), 3.11-3.04 (m, 1H), 2.98-2.94 (m, 4H), 2.75 (dd, J = 13.8, 6.6 Hz, 1H), 2.58 (dd, J = 13.6, 6.8 Hz, 1H), 1.83-1.79 (m, 2H), 1.25 (t, 3H), 1.09 (d, J = 6.3Hz, 3H) ESI-MS m/z: 458[M+H]+.

 Example 27: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro-2-methoxy-phenoxy]ethylamino]propyl]-hydrazine哚-7-carboxamide (DC471827)

 According to the preparation method of Example 1, 2,6-dimethylphenol in the step 1.12 was replaced with 2-methoxy-4-fluoro-phenol. 1H NMR (400 MHz, DMSO): δ 7.96 (s, 1H), 7.53 (s, 1H), 7.42 (d, J = 1.2 Hz, 1H), 7.30 (d, J = 3.1 Hz, 1H), 7.03 ( d, J = 1.2 Hz, 1H), 6.93-6.82 (m, 2H), 6.64 (td, J = 8.6, 3.0 Hz, 1H), 6.40 (dd, J = 7.8, 3.1 Hz, 1H), 4.32 (t , J = 6.9 Hz, 2H), 4.00-3.91 (m, 2H), 3.70 (s, 3H), 3.25 (t, J = 6.2 Hz, 2H), 2.99-2.89 (m, 3H), 2.88-2.81 ( m, 1H), 2.53 (dd, j = 11.3, 5.6 Hz, 1H), 1.77 (m, 2H), 0.96 (dd, J = 14.6, 6.4 Hz, 3H). ESI-MS m/z: 444 [M +H] +.

 Example 28: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro-2-cyclopropoxy-phenoxy]ethylamino]propyl] -吲哚-7-carboxamide (DC471828)

Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-fluoro-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. It is made on behalf of the ring. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.92 (s, 1H), 7.50 (s, 1H), 7.38 (d, J = 1.2 Hz, 1H), 7.33 (d, J = 3.0 Hz, 1H), 7.01 (d, J = 1.2 Hz, 1H), 6.96-6.84 (m, 2H), 6.63 (m, 1H), 6.43 (dd, J = 7.8, 3.1 Hz, 1H), 4.12-3.98 (m, 2H), 3.67(m, 1H), 3.68 (t, J = 8.6 Hz, 2H), 3.15 (t, J = 6.6 Hz, 2H), 3.07-2.99 (m, 2H), 2.98-2.87 (m, 2H), 2.68 (dd, J = 13.7, 6.6 Hz, 1H), 2.51 (dd, J = 13.8, 6.5 Hz, 1H), 1.84-1.68 (m, 2H), 1.07 (d, J = 6.2 Hz, 3H), 0.76 ( m, 1H), 0.60 (m, 2H). ESI-MS m/z: 470[M+H]+.

 Example 29: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro-2-cyclopropoxy-phenoxy]ethylamino]propyl] - 吲哚-7-carboxamide (DC471829)

 Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-fluoro-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. Made from methylcyclopropane. NMR (400 MHz,

CDCI3): δ 7.90 (s, 1H), 7.55 (s, 1H), 7.36 (d, J = 1.3 Hz, 1H), 7.31 (d, J = 3.1 Hz, 1H), 7.03 (m, 1H), 6.94 -6.85 (m, 2H), 6.68 (m, 1H), 6.44 (m, 1H), 4.09-3.96 (m, 2H), 3.67 (t, J = 8.5 Hz, 2H), 3.64 (t, J=7.4 Hz, 2H), 3.14 (t, J = 6.8 Hz, 2H), 3.03-2.98 (m, 1H), 2.99-2.88 (m, 2H), 2.66 (dd, J = 13.6, 6.5 Hz, 1H), 2.51 (dd, J = 13.6, 6.7 Hz, 1H), 1.81-1.68 (m, 2H), 1.05 (d, J = 6.2 Hz, 3H), 0.85 (m, 2H), 0.37 (m, 1H), 0.33 ( m, 2H). ESI-MS m/z: 484 [M+H]+.

 Example 30: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro-2-tert-butoxy-phenoxy]ethylamino]propyl] -吲哚-7-formamide (DC471830)

The 2-methoxy-4-ethyl-phenol in step 5.1 was replaced with 2-methoxy-4- as in the preparation method of Example 5. Fluoro-phenol, prepared by replacing iodonium in step 5.4 with bromo-t-butyl hydrazine. NMR (400 MHz, CDC1 ₃ ) : δ 7.92 (s, IH), 7.50 (s, IH), 7.44 (d, J = 1.2 Hz, IH), 7.31 (d, J = 3.1 Hz, IH), 7.03 ( d, J = 1.3 Hz, IH), 6.93-6.82 (m, 2H), 6.64 (td, J = 8.6, 3.0 Hz, IH), 6.43 (m, IH), 4.09-3.95 (m, 2H), 3.67 (t, J = 8.8 Hz, 2H), 3.16 (t, J = 6.7 Hz, 2H), 3.03-2.98 (m, IH), 2.99-2.88 (m, 2H), 2.66 (dd, J = 13.6, 6.5 Hz, IH), 2.51 (dd, J = 13.6, 6.7 Hz, IH), 1.81-1.68 (m, 2H), 1.44(s, 9H), 1.07 (d, J = 6.4 Hz, 3H). ESI-MS m/z: 486[M+H]+.

 Example 31: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-fluoro-2-pivalyloxy-phenoxy]ethylamino]propyl] -吲哚-7-carboxamide (DC471831)

According to the preparation method of Example 5, the 2-methoxy-4-ethyl-phenol in the step 5.1 was replaced with 2-methoxy-4-fluoro-phenol, and the iodonium in the step 5.4 was replaced with 1 -Bromo-2,2-dimethylpropanthine. NMR (400 MHz, CDC1 ₃ ) : δ 7.90 (s, IH), 7.50 (s, IH), 7.44 (m, IH), 7.31 (d, J = 3.1 Hz, IH), 7.05 (d, J = 1.2 Hz, IH), 6.94-6.82 (m, 2H), 6.64 (m, IH), 6.40 (dd, J = 7.8, 3.1 Hz, IH), 4.09-3.98 (m, 2H), 3.67 (t, J = 8.2Hz, 2H), 3.61 (s, 2H), 3.14 (t, J = 6.8 Hz, 2H), 3.03-2.98 (m, IH),

2.99-2.88 (m, 2H), 2.66 (dd, J = 13.4, 6.5 Hz, IH), 2.51 (dd, J = 13.6, 6.7 Hz, IH), 1.81-1.68 (m, 2H), 1.05 (d, J = 6.2 Hz, 3H), 0.86(s, 9H). ESI-MS m/z: 500[M+H]+.

 Example 32: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[5-methyl-2-(2,2,2-trifluoroethoxy)phenoxy ]ethylamino]propyl]-indole-7-carboxamide (DC471832)

According to the preparation method of Example 4, 2-methoxy-4-ethyl-phenol in Step 4.1 was replaced with 2-methoxy-4-methyl-phenol. NMR (400 MHz, CDC13): δ 7.49 (d, J = 1.3 Hz, IH), 7.12 (d, J = 1.3 Hz, IH), 7.07 (d, J = 3.2 Hz, IH), 6.82 (d, J = 8.6 Hz, IH), 6.68-6.63 (m, 2H), 6.58 (d, J = 2.9 Hz, 2H), 6.45 (d, J = 3.2 Hz, IH), 4.36-4.27 (m, 2H), 4.19 -3.97 (m, 4H), 3.47 (t, J = 5.7 Hz, 2H), 3.07-2.99 (m, 2H), 2.99-2.91 (m, IH), 2.81-2.75 (m, IH), 2.73-2.68 (m, IH), 2.25 (s _: 3H), 1.99-1.89 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 508[M+H]+.

 Example 33: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-methyl-2-ethoxy-phenoxy]ethylamino]propyl] -吲哚-7-carboxamide (DC471833)

According to the preparation method of Example 5, 2-methoxy-4-ethyl-phenol in Step 5.1 was replaced with 2-methoxy-4-methyl-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.49 (s, IH), 7.16 (d, J = 3.2 Hz, IH), 7.01 (s, IH), 6.96 (s, IH), 6.80 (d, J = 8.2 Hz, IH), 6.79 (s, IH), 6.72 (s, IH), 6.69-6.63 (m, IH), 6.50 (d, J = 3.2 Hz, IH), 4.11-4.02 (m, 2H), 3.84 (s, 3H), 3.65 (t, J = 5.8 Hz, 2H), 3.60 (q, J = 7.6 Hz, 2H), 3.15 (t, J = 6.9 Hz, 3H), 3.08-2.90 (m, 2H) ), 2.65 (dd, J = 13.8, 6.5 Hz, IH), 2.46 (dd, J = 13.8, 6.6 Hz, IH), 1.80-1.73 (m, 2H), 1.23 (t, 3H), 1.06 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 454 [M+H]+.

 Example 34: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-methyl-2-methoxy-phenoxy]ethylamino]propyl] -吲哚-7-formamide (DC471834)

 According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with 2-methoxy-4-methyl-phenol. 1H NMR (400 MHz, MeOD): δ 7.49 (d, J = 1.3 Hz, IH), 7.18 (d, J = 3.2 Hz, IH), 7.09 (m, IH), 6.90-6.83 (m, 2H), 6.74 (d, J = 8.0 Hz, IH), 6.52 (d, J = 3.2 Hz, IH), 4.25-4.10 (m, 2H), 3.84 (s, 3H), 3.65 (t, J = 6.3 Hz, 2H ), 3.42-3.36 (m, IH), 3.33-3.28 (m, 2H), 3.25 (t, J = 7.6 Hz, 2H), 3.04-2.93 (m, IH), 2.65 (dd, J = 13.3, 8.5 Hz, IH) , 2.31 (s, 3H), 1.86-1.76 (m, 2H), 1.24 (d, J = 6.4 Hz, 3H). ESI-MS m/z: 440[M+H]+.

Example 35: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-methyl-2-cyclopropoxy-phenoxy]ethylamino]propyl] - 吲哚-7-carboxamide (DC471835) Following the preparation of Example 5, the 2-methoxy-4-ethyl-phenol in step 5.1 was replaced with 2-methoxy-4-methyl-phenol, and the iodonium in step 5.4 was replaced with Made from bromocyclopropane. NMR (400 MHz,

MeOD) : δ 7.48 (d, J = 1.3 Hz, IH), 7.16 (d, J = 3.2 Hz, IH), 7.11 (d, J = 6.5 Hz, IH),

6.89- 6.83 (m, 2H), 6.76 (d, J = 8.2 Hz, IH), 6.51 (d, J = 3.2 Hz, IH), 4.25-4.13 (m, 2H), 3.84 (s, 3H), 3.69 (m, IH), 3.68 (t, J = 6.3 Hz, 2H), 3.42-3.37 (m, 2H), 3.33-3.28 (m, 2H), 3.25 (t,

J = 7.8 Hz, 2H), 3.07-2.99 (m, IH), 2.68 (dd, J= 13.5, 8.6 Hz, IH), 1.86-1.78 (m, 2H), 1.25 (d, J = 6.4 Hz, 3H ), 0.77 (m, IH), 0.62 (m, 2H). ESI-MS m/z: 466 [M+H]+.

Example 36: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-methyl-2-cyclopropoxy-phenoxy]ethylamino]propyl ] -吲哚_ ₇ _carboxamide (DC471836)

 Following the preparation of Example 5, the 2-methoxy-4-ethyl-phenol in step 5.1 was replaced with 2-methoxy-4-methyl-phenol, and the iodonium in step 5.4 was replaced with Made from bromomethylcyclopropane. 1H NMR (400 MHz, MeOD): δ 7.46 (d, J = 1.3 Hz, IH), 7.18 (d, J = 3.2 Hz, IH), 7.09 (d, J = 6.5 Hz, IH),

6.90- 6.83 (m, 2H), 6.74 (d, J = 8.0 Hz, IH), 6.52 (d, J = 3.2 Hz, IH), 4.25-4.10 (m, 2H), 3.65 (t, J = 6.3 Hz , 2H), 3.58(t, J=7.4Hz, 2H), 3.42-3.36 (m, 4H), 3.33-3.28 (m, 2H), 3.25 (t, J = 7.6 Hz, 2H), 3.04-2.93 ( m, IH), 2.65 (dd, J = 13.3, 8.5 Hz, IH), 1.86-1.76 (m, 2H), 1.24 (d, J = 6.4 Hz, 3H), 0.86 (m, 2H), 0.38 (m , IH), 0.36 (m, 2H). ESI-MS m/z: 480 [M+H]+.

 Example 37: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-methyl-2-tert-butoxy-phenoxy]ethylamino]propyl] - 吲哚-7-carboxamide (DC471837)

 Following the preparation of Example 5, the 2-methoxy-4-ethyl-phenol in step 5.1 was replaced with 2-methoxy-4-methyl-phenol, and the iodonium in step 5.4 was replaced with Made from bromo-tert-butyl hydrazine. NMR (400 MHz,

 MeOD) : 57.44 (d, J = 1.3 Hz, IH), 7.18 (d, J = 3.2 Hz, IH), 7.10 (d, J = 6.5 Hz, 2H),

6.91- 6.87 (m, IH), 6.76 (d, J = 8.3 Hz, IH), 6.50 (d, J = 3.2 Hz, IH), 4.26-4.13 (m, 2H), 3.85 (s, 3H), 3.67 (t, J = 6.7 Hz, 2H), 3.42-3.38 (m, IH), 3.34-3.26 (m, 2H), 3.25 (t, J = 7.7Hz, 2H), 3.05-2.96 (m, IH), 2.66 (dd, J = 13.5, 8.5 Hz, IH), 1.86-1.77 (m, 2H), 1.46(s, 9H), 1.22 (d, J = 6.4 Hz, 3H). ESI-MS m/z:482 [M+H] ⁺ .

 Example 38: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-methyl-2-pivaloxy-phenoxy]ethylamino]propyl] - 吲哚-7-carboxamide (DC471838)

 Following the preparation of Example 5, the 2-methoxy-4-ethyl-phenol in step 5.1 was replaced with 2-methoxy-4-methyl-phenol, and the iodonium in step 5.4 was replaced with 1-Bromo-2,2-dimethylpropanthine. 1H NMR (400 MHz MeOD): 57.45 (d, J = 1.3 Hz, IH), 7.12 (d, J = 3.2 Hz, IH), 7.08 (d, J = 6.4 Hz, IH),

6.92- 6.86(m, 2H), 6.73 (d, J = 8.1 Hz, IH), 6.49 (d, J = 3.2 Hz, IH), 4.23-4.10 (m, 2H), 3.85 (s, 3H), 3.62 (t, J = 6.5 Hz, 2H), 3.64 (s, 2H), 3.42-3.37 (m, IH), 3.35-3.29 (m, 2H), 3.23 (t, J = 7.6 Hz, 2H), 3.06- 2.94 (m, IH), 2.66 (dd, J = 13.4, 8.6 Hz, IH), 1.88-1.75 (m, 2H), 1.25 (d, J = 6.4 Hz, 3H), 0.88(s, 9H). ESI -MS m/z: 496[M+H]+.

Example 3 ⁹ : l-( ³ -Hydroxypropyl) - ⁵ -[( ² R)- ² -[ ² -[ ⁵ -chloro- ² -( ² , ² , ² -trifluoroethoxy)phenoxy Ethylamino]propyl]-indole-7-carboxamide (DC471839)

According to the preparation method of Example 4, 2-methoxy-4-ethyl-phenol in Step 4.1 was replaced with 2-methoxy-4-chloro-phenol. iH NMR (400 MHz, CDC13): δ 7.47 (t, J = 3.8 Hz, IH), 7.10 (t, J = 4.7 Hz, IH), 7.07 (d, J = 3.2 Hz, IH), 6.87-6.80 ( m, 3H), 6.63 (d, J = 18.6 Hz, 2H), 6.45 (d, j = 3.1 Hz, IH), 4.37-4.24 (m, 2H), 4.20-4.06 (m, 2H), 4.06-3.90 (m, 2H), 3.47 (t, J = 5.7 Hz, 2H), 3.03-2.92 (m, 3H), 2.81-2.75 (m, IH), 2.69 (dd, J = 13.6, 6.5 Hz, IH), 1.99-1.86 (m, 2H), 1.08 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 528:530 = 3: 1 [M+H] ⁺ . Example 40: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-chloro-2-ethoxy-phenoxy]ethylamino]propyl]-hydrazine哚-7-carboxamide (DC471840)

According to the preparation method of Example 5, 2-methoxy-4-ethyl-phenol in Step 5.1 was replaced with 2-methoxy-4-chloro-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.44 (t, J = 3.8 Hz, 1H), 7.12 (s, 1H), 7.07 (d, J = 3.2 Hz, 1H), 6.87-6.82 (m, 3H) , 6.65 (d, J = 18.6 Hz, 2H), 6.44 (d, J = 3.1 Hz, 1H), 4.12-3.98 (m, 2H), 3.70 (t, J = 5.4 Hz, 2H), 3.62 (q, J = 7.6 Hz, 2H), 3.21-3.12 (m, 2H), 3.09-3.10 (m, 1H), 3.05-2.89 (m, 2H), 2.69-2.64 (m, 1H), 2.52 (dd, J = 13.5, 6.8 Hz, 1H), 1.83-1.73 (m, 2H), 1.25 (t, 3H), 1.08 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 474:476=3 : 1 [M+H]+. Example 41: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-chloro-2-methoxy-phenoxy]ethylamine Propyl]-吲哚-7-carboxamide (DC341841)

 According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with 2-methoxy-4-chloro-benzenephenol. 1H NMR (400 MHz, CDC13): δ 7.46 (s, 1H), 7.11 (s, 1H), 7.05 (d, J = 3.1 Hz, 1H), 6.84 (s, 1H), 6.79-6.73 (m, 3H ), 6.63 (d, J = 9.1 Hz, 1H), 6.43 (d, J = 3.1 Hz, 1H), 4.29 (t, J = 7.1 Hz, 2H), 4.04-3.89 (m, 2H), 3.61 (s , 3H), 3.43 (t, J = 5.8 Hz, 2H), 3.02-2.93 (m, 2H), 2.93-2.84 (m, 1H), 2.79-2.63 (m, 2H), 1.89 (dq, J = 12.1 , 6.1 Hz, 2H), 1.04 (t, J = 10.6 Hz, 3H). ESI-MS m/z: 460:462=3 : 1 [M+H]+.

 Example 42: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-chloro-2-cyclopropoxy-phenoxy]ethylamino]propyl] -吲哚-7-carboxamide (DC471842)

Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-chloro-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. It is made on behalf of the ring. NMR (400 MHz, CDC1 ₃ ) : δ 7.48 (s, 1H), 7.10 (s, 1H), 7.08 (d, J = 3.1 Hz, 1H), 6.85 (s, 1H), 6.81-6.76 (m, 3H) ), 6.60 (d _: J = 9.1 Hz, 1H), 6.44 (d, J = 3.1 Hz, 1H), 4.08-3.98 (m, 2H), 3.65 (m, 1H), 3.68 (t, J = 5.5 Hz) , 2H), 3.16 (t, J = 7.0 Hz, 2H), 3.05-2.99 (m, 1H), 2.98-2.89 (m, 3H), 2.64 (dd, J = 13.8, 6.5 Hz, 1H), 2.51 ( Dd, J = 13.3, 6.5 Hz, 1H), 1.82-1.74 (m, 2H), 1.04 (d, J = 6.2 Hz, 3H), 0.79 (m, 1H), 0.64 (m, 2H). ESI-MS m/z: 486:488=3 : 1 [M+H]+.

 Example 43: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-chloro-2-cyclopropoxy-phenoxy]ethylamino]propyl] - 吲哚-7-formamide (DC471843)

 Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-chloro-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. Made from methylcyclopropane. NMR (400 MHz,

CDCI3) : δ 7.48 (s, 1H), 7.13 (s, 1H), 7.06 (d, j = 3.1 Hz, 1H), 6.83 (s, 1H), 6.79-6.72 (m, 3H), 6.66 (d, J = 9.1 Hz, 1H), 6.44 (d, J = 3.1 Hz, 1H), 4.10-3.95 (m, 2H), 3.68 (t, J = 5.8 Hz, 2H), 3.66 (t, J = 7.4 Hz, 2H), 3.14 (t, J = 6.9 Hz, 2H), 3.02-2.98 (m, 1H), 2.96-2.88 (m, 2H), 2.64 (dd, J = 13.5, 6.5 Hz, 1H), 2.50 (dd , J = 13.5, 6.6 Hz, 1H), 1.80-1.71 (m, 2H), 1.04 (d, J = 6.2 Hz, 3H), 0.85 (m, 2H), 0.39 (m, 1H), 0.37 (m, 2H). ESI-MS m/z: 500: 502 = 3: 1 [M+H]+. Example 44: l-(3-hydroxypropyl) -5-[(2R)-2-[2- [4-Chloro-2-tert-butoxy-phenoxy]ethylamino]propyl]-indole-7-carboxamide (DC471844)

Replace the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-chloro-phenol according to the preparation method of Example 5, and replace the iodonium in step 5.4 with bromine. Made by the uncle Ding Yu. NMR (400 MHz, CDC1 ₃ ) : δ 7.43 (s, 1H), 7.08 (s, 1H), 7.03 (d, J = 3.1 Hz, 1H), 6.82 (s, 1H), 6.78-6.72 (m, 3H) ), 6.65 (d, J = 9.1 Hz, 1H), 6.41 (d, J = 3.1 Hz, 1H), 4.09-3.95 (m, 2H), 3.68 (t, J = 5.8 Hz, 2H), 3.16 (t , J = 6.6 Hz, 2H), 3.08-2.99 (m, 1H), 2.97-2.89 (m, 2H), 2.63 (dd, J = 13.4, 6.6 Hz, 1H), 2.52 (dd, J = 13.8, 6.4 Hz, 1H), 1.82-1.71 (m, 2H), 1.44(s, 9H), 1.05 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 502:504=3:1 [M+H]10.

 Example 45: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-chloro-2-pivaloxy-phenoxy]ethylamino]propyl] -吲哚-7-carboxamide (DC471845)

According to the preparation method of Example 5, the 2-methoxy-4-ethyl-phenol in the step 5.1 was replaced with 2-methoxy-4-chloro-phenol, and the iodonium in the step 5.4 was replaced with 1 -Bromo-2,2-dimethylpropanthine. NMR (400 MHz, CDC1 ₃ ) : δ 7.49 (s, IH), 7.15 (s, IH), 7.08 (d, J = 3.1 Hz, IH), 6.82 (s, IH), 6.78-6.73 (m, 3H ), 6.54 (d, J = 9.1 Hz, IH), 6.41 (d, J = 3.1 Hz, IH), 4.09-3.99 (m, 2H), 3.65 (t, J= 5.5 Hz, 2H), 3.65 (s , 2H), 3.16 (t, J= 6.7 Hz, 2H), 3.04-2.99 (m, IH), 2.96-2.89 (m, 2H), 2.66 (dd, J = 13.3, 6.2 Hz, IH), 2.52 ( Dd, J = 13.6, 6.8 Hz, IH), 1.82-1.71 (m, 2H), 1.06 (d, J = 6.2 Hz, 3H), 0.86(s, 9H). ESI-MS m/z: 516:518 =3:1 [M+H]+.

 Example 46: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[5-allyl-2-(2,2,2-trifluoroethoxy)phenoxy Ethylamino]propyl]-indole-7-carboxamide (DC471846)

 According to the preparation method of Example 4, 2-methoxy-4-ethyl-phenol in Step 4.1 was replaced with 2-methoxy-4-allyl-phenol. iHNMR (400 MHz, CDCI3): δ 1H NMR (400 MHz, CDC13): δ 7.48 (s IH), 7.19-7.12 (m, IH), 7.09 (d, J = 3.2 Hz, IH), 6.88 (d, J = 5.4 Hz, IH), 6.82-6.73 (m, IH),

6.70 (dd, J = 8.4, 6.1 Hz, IH), 6.65 (m, IH), 6.49-6.37 (m, 2H), 6.15-6.03 (m, IH), 5.99-5.83 (m, IH), 5.09- 5.02 (m, IH), 4.31-4.23 (m, 2H), 4.16-4.05 (m, 2H), 3.75 (t, J = 5.6 Hz, 2H), 3.45-3.29 (m, IH), 3.26-3.17 ( m, IH), 3.08-2.89 (m, 2H), 2.72 (dd, J= 13.4, 6.6 Hz, IH), 2.58 (dd, J= 14.1, 6.3 Hz, IH), 1.86-1.69 (m, 2H) , 1.22 (t, 3H), 1.10 (d, J = 6.1 Hz, 3H). ESI-MS m/z: 534 [M+H] ⁺ .

 Example 47: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-allyl-2-ethoxy-phenoxy]ethylamino]propyl] - 吲哚-7-carboxamide (DC471847)

According to the preparation method of Example 5, 2-methoxy-4-ethyl-phenol in Step 5.1 was replaced with 2-methoxy-4-allyl-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ IH NMR (400 MHz, CDC13): δ 7.49 (s IH), 7.19-7.12 (m, IH), 7.09 (d, J = 3.2 Hz, IH), 6.86 ( d, J = 5.3 Hz, IH), 6.83-6.75 (m, IH),

6.71 (dd, J = 8.4, 6.1 Hz, IH), 6.68 (dd, J = 4.2, 2.4 Hz, IH), 6.49-6.36 (m, 2H), 6.14-6.01 (m _: IH), 5.98-5.85 ( m, IH), 5.09-5.01 (m, IH), 4.16-4.01 (m, 2H), 3.73 (t, J = 5.8 Hz, 2H), 3.60 (q, J = 7.6 Hz, 2H), 3.43-3.29 (m, 3H), 3.24-3.14 (m, 2H), 3.06-2.89 (m, 2H), 2.72 (dd, J = 13.6, 6.8 Hz, IH), 2.59 (dd, J= 14.1, 6.3 Hz, IH ), 1.84-1.69 (m, 2H), 1.24 (t, 3H), 1.11 (d, J = 6.1 Hz, 3H). ESI-MS m/z: 480 [M+H]+.

 Example 48: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-allyl-2-methoxy-phenoxy]ethylamino]propyl] - 吲哚-7-formamide (DC371848)

 According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with 2-methoxy-4-allyl-phenol. 1HNMR (400 MHz, CDC13): δ 7.44 (s, IH), 7.19-7.12 (m, IH), 7.1 (d, J = 3.2 Hz, IH), 6.89 (m, IH), 6.83-6.74 (m, IH), 6.66 (dd, J = 8.4, 6.1 Hz, IH), 6.63 (dd, J =

 4.2, 2.4 Hz, IH), 6.45-6.34 (m, 2H), 6.16-6.00 (m, IH), 5.96-5.83 (m, IH), 5.07-5.02 (m, IH), 4.34 (t, J = 7.0 Hz, 2H), 4.09-3.99 (m, 2H), 3.65 (s, 3H), 3.46 (t, J = 5.7 Hz, 2H), 3.34-3.26 (m, IH), 3.15-3.02 (m, 2H ), 3.02-2.92 (m, IH), 2.89-2.72 (m, 2H), 2.00-1.90 (m, 2H), 1.86-1.82 (m, IH), 1.13 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 466 [M+H]+.

 Example 49: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-allyl-2-cyclopropoxy-phenoxy]ethylamino]propyl ] - 吲哚-7-formamide (DC471849)

The 2-methoxy-4-ethyl-phenol in step 5.1 was replaced with 2-methoxy-4- as in the preparation method of Example 5. Allyl-phenol, prepared by replacing iodonium in step 5.4 with bromocyclopropane. NMR (400 MHz, CDC1 ₃ ): δ 1H NMR (400 MHz, CDC1 ₃ ) : δ 1H NMR (400 MHz, CDC13): δ 7.46 (s, 1H), 7.17-7.10 (m, 1H), 7.05 (d , J = 3.2 Hz, 1H), 6.85 (d, J = 5.4 Hz, 1H), 6.82-6.72 (m, 1H), 6.65 (dd, J = 8.4, 6.1 Hz, 1H), 6.62 (dd, J = 4.2, 2.4 Hz, 1H), 6.48-6.39 (m, 2H), 6.13-6.03 (m, 1H) 5.97-5.84 (m, 1H), 5.06-4.98 (m, 1H), 4.18-4.04 (m, 2H ), 3.72 (t, J = 5.6 Hz, 2H), 3.66 (m, 1H) 3.44-3.29 (m, 1H), 3.23-3.13 (m, 5H), 3.06-2.88 (m, 2H), 2.72 (dd , J = 13.6, 6.8 Hz, 1H) _: 2.59 (dd, J = 14.2, 6.2 Hz, 1H), 1.83-1.68 (m, 2H), 1.09 (d, J = 6.1 Hz, 3H), 0.78 (m, 1H), 0.66 (m, 2H). ESI-MS m/z: 492 [M+H]+.

 Example 50: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-allyl-2-cyclopropoxy-phenoxy]ethylamino]propyl -]-7-carboxamide (DC471850)

 Substituting the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-allyl-phenol according to the preparation method of Example 5, replacing the iodonium in step 5.4 Made from bromomethylcyclopropane. NMR (400 MHz, CDCI3): 1H NMR (400 MHz, CDC13): δ 7.47 (s, 1H), 7.18-7.13 (m, 1H), 7.08 (d, J = 3.2 Hz, 1H), 6.87 (d, J = 5.4 Hz, 1H), 6.83-6.74 (m, 1H), 6.69 (dd, J = 8.4, 6.1 Hz, 1H), 6.64 (dd, J = 4.2, 2.4 Hz, 1H), 6.49-6.38 (m , 2H), 6.14-6.01 (m, 1H), 5.98-5.85 (m, 1H), 5.09-5.01 (m, 1H), 4.19-4.03 (m, 2H), 3.74 (t, J = 5.6 Hz, 2H ), 3.68 (t, J=7.6Hz, 2H), 3.43-3.28 (m, 1H), 3.24-3.13 (m, 2H), 3.05-2.89 (m, 4H), 2.72 (dd, J = 13.3, 6.8 Hz, 1H), 2.56 (dd, J = 14.2, 6.5 Hz, 1H), 1.84-1.69 (m, 2H), 1.10 (d, J = 6.1 Hz, 3H), 0.85 (m, 2H), 0.38 (m , 1H), 0.37 (m, 2H). ESI-MS m/z: 506 [M+H]+.

 Example 51: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-allyl-2-tert-butoxy-phenoxy]ethylamino]propyl ] - 吲哚-7-carboxamide (DC471851)

 Substituting the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-allyl-phenol according to the preparation method of Example 5, replacing the iodonium in step 5.4 Made from bromo-tert-butyl hydrazine. NMR (400 MHz, CDCI3): 1H NMR (400 MHz, CDC13): δ 7.44 (s, 1H), 7.19-7.13 (m, 1H), 7.10 (d, J = 3.2 Hz, 1H), 6.88 (d, J = 5.4 Hz, 1H), 6.85-6.76 (m, 1H), 6.70 (dd, J = 8.4, 6.1 Hz, 1H), 6.65 (dd, J = 4.2, 2.4 Hz, 1H), 6.52-6.38 (m , 2H), 6.14-6.03 (m, 1H), 5.96-5.82 (m, 1H), 5.10-5.01 (m, 1H), 4.22-4.09 (m, 2H), 3.75 (t, J = 5.8 Hz, 2H ), 3.46-3.29 (m, 1H), 3.22-3.15 (m, 2H), 3.04-2.88 (m, 2H), 2.73 (m, 3H), 2.56 (dd, J = 14.0, 6.5 Hz, 1H), 1.82-1.69 (m, 2H), 1.46(s, 9H), 1.10 (d, J = 6.1 Hz, 3H). ESI-MS m/z: 508 [M+H]+.

 Example 52: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[4-allyl-2-pivaloxy-phenoxy]ethylamino]propyl ] - 吲哚-7-carboxamide (DC471852)

 Substituting the 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-allyl-phenol according to the preparation method of Example 5, replacing the iodonium in step 5.4 Made from 1-bromo-2,2-dimethylpropanthene. 1H NMR (400 MHz, CDCI3): 1H NMR (400 MHz, CDC13): δ 7.47 (s, 1H), 7.18-7.13 (m, 1H), 7.08 (d, J = 3.2 Hz, 1H), 6.87 (d , J = 5.4 Hz, 1H), 6.83-6.74 (m, 1H), 6.69 (dd, J = 8.4, 6.1 Hz, 1H), 6.64 (dd, J = 4.2, 2.4 Hz, 1H), 6.49-6.38 ( m, 2H), 6.14-6.01 (m, 1H), 5.98-5.85 (m, 1H), 5.09-5.01 (m, 1H), 4.15-4.03 (m, 2H), 3.74 (t, J = 5.4Hz, 2H), 3.68 (s, 2H), 3.43-3.27 (m, 1H), 3.23-3.14 (m, 2H), 3.06-2.89 (m, 4H), 2.72 (dd, J = 13.5, 6.7 Hz, 1H) , 2.59 (dd, J = 14.1 6.3 Hz, 1H), 1.83-1.69 (m, 2H), 1.10 (d, J = 6.1 Hz, 3H), 0.87(s, 9H). ESI-MS m/z:

522[M+H] ⁺ .

Example 53: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-bromo-4-fluoro-phenoxy]ethylamino]propyl]-indole-7- Amide (DC471853) According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with 2-bromo-4-fluoro-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.44 (m, IH), 7.17 (s, IH), 7.13 (d, J = 3.2 Hz, IH), 7.00 (s, IH), 6.99-6.88 (m, 2H), 6.78 (dd, J = 9.1, 4.8 Hz, 2H), 6.50 (d, J = 3.2 Hz, IH), 4.09-4.03 (m, IH), 4.03-3.95 (m, IH), 3.40-3.32 (m, 2H), 3.18-3.10 (m, 2H), 2.98-2.90 (m, 2H), 2.66-2.51 (m, 3H), 1.81-1.71 (m, 2H), 1.07 (d, J = 6.2 Hz , 3H). ESI-MS m/z:

492:494=1 : 1 [M+H] ⁺ .

 Example 54: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-ethyl-phenoxy]ethylamino]propyl]-indole-7-carboxamide (DC471854 )

According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with 2-ethyl-phenol. 1H NMR (400 MHz, CDCI3): δ 7.46 (s, IH), 7.16 (s, IH), 7.15 (d, J = 3.2 Hz, IH), 6.96 (s, IH), 6.92-6.89 (m, 2H) ), 6.87-6.80 (m, IH), 6.52 (d, J = 3.2 Hz, IH), 4.38 (m, 2H), 3.88 (m, 2H), 3.29 (t, J = 8.4 Hz, 2H), 3.17 -2.94 (m, 2H), 2.87 (t, J = 7.9 Hz, 2H), 2.83-2.70 (m, IH), 2.65 (q, j=7.3 Hz, 2H) 2.64-2.53 (m, IH), 1.67 (m, 2H), 1.11 (d, J = 6.0 Hz, 3H), 1.08 (t, j = 7.3, 3H). ESI-MS m/z: 424 [M+H] ⁺ .

 Example 55: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-n-propyl-phenoxy]ethylamino]propyl]-indole-7-carboxamide

(DC471855)

According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with 2-n-propyl-phenol. 1H NMR (400 MHz, CDC1 ₃ ): δ 7.48 (s, IH), 7.18 (s, IH), 7.18 (d, J = 3.2 Hz, IH), 6.96 (s, IH), 6.92-6.88 (m, 3H), 6.87-6.80 (m, IH), 6.55 (d, J = 3.2 Hz, IH), 4.38 (m, 2H), 3.88 (m, 2H), 3.29 (t, J = 8.4 Hz, 2H), 3.17-2.94 (m, 2H), 2.87 (t, J = 7.9 Hz, 2H), 2.83-2.70 (m, IH), 2.65 (t, J =7.0 Hz, 2H), 2.64-2.53 (m, IH) , 1.67 (m, 2H), 1.6 (m, 2H), 1.11 (d, J = 6.0 Hz, 3H), 0.91 (t, J = 6.6 Hz, 3H). ESI-MS m/z: 438[M+ H] ⁺ .

 Example 56: l-(2-Hydroxyethyl)-5-[(2R)-2-[2-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenoxy] Ethylamino]propyl]-indole-7-carboxamide (DC471856)

 According to the preparation method of Example 1, the 3-bromo-1-propanol in step 1.1 was replaced with 2-bromo-1-ethanol, and the steps were as follows.

The 2,6-dimethylphenoxyacetaldehyde in 1.15 is replaced by 4-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde, 4-fluoro-2-(2, 2,2-Trifluoroethoxy)-phenoxyacetaldehyde The 2-methoxy-4-ethyl-phenol in step 4.1 was replaced with 2-methoxy-5- as in the preparation method of Example 4. Fluorine-phenol produces 2, 2, 2. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.49 (s, IH), 7.16 (d, J = 3.2 Hz, IH), 7.13 (s, IH), 7.06-6.85 (m, IH), 6.89-6.76 ( m, IH), 6.77-6.63 (m, 3H), 6.51 (d, J = 3.2 Hz, IH), 4.35-4.29 (m, 2H), 4.13-4.04 (m, 2H), 3.74 (t, J = 5.8 Hz, 2H), 3.2 (t, J = 6.6 Hz, 2H), 3.08-3.02 (m, IH), 2.98-2.93 (m, 2H), 2.73 (dd, J = 13.6, 6.6 Hz, IH), 2.55 (dd, J = 13.4, 6.6 Hz, IH), 1.07 (d, J = 6.4 Hz, 3H). ESI-MS m/z: 498[M+H]+.

 Example 57: l-(4-Hydroxybutyl)-5-[(2R)-2-[2-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenoxy] Ethylamino]propyl]-indole-7-carboxamide (DC471857)

 Following the preparation of Example 1, the 3-bromo-1-propanol in step 1.1 was replaced with 4-bromo-1-butanol.

The 2,6-dimethylphenoxyacetaldehyde in 1.15 is replaced by 4-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde, 4-fluoro-2-(2, 2,2-Trifluoroethoxy)-phenoxyacetaldehyde The 2-methoxy-4-ethyl-phenol in step 4.1 was replaced with 2-methoxy-5- as in the preparation method of Example 4. Fluorine-phenol produces 2, 2, 2. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.49 (s, IH), 7.16 (d, J = 3.2 Hz, IH), 7.14 (s, IH), 7.06-6.86 (m, IH), 6.89-6.78 ( m, IH), 6.78-6.65 (m, 3H), 6.53 (d, J = 3.2 Hz, IH), 4.40-4.29 (m, 2H), 4.13-4.04 (m, 2H), 3.75 (t, J = 5.6 Hz, 2H), 3.15 (t, J = 6.6 Hz, 2H), 3.09-3.02 (m, IH), 2.96-2.92 (m, 2H), 2.74 (dd, J = 13.2, 6.8 Hz, IH), 2.55 (dd J = 13.7, 6.5 Hz, IH), 1.88-1.73 (m, 4H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 526 [M+H] ⁺ . Example 58: l-(2-Hydroxyethyl)-5-[(2R)-2-[2-[5-fluoro-2-(2,2,2-trifluoroethoxy)phenoxy] Ethylamino]propyl]-indole-7-carboxamide (DC471858)

According to the preparation method of Example 1, the 3-bromo-1-propanol in the step 1.1 was replaced with 2-bromo-1-ethanol, and the 2,6-dimethylphenoxyacetaldehyde in the step 1.15 was replaced with 5 -Fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde, 5-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde The preparation method of Example 4 was prepared by substituting 2-methoxy-4-ethyl-phenol in Step 4.1 with 2-methoxy-4-fluoro-phenol. 2,2,21H NMR (400 MHz, CDC1 ₃ ) : δ 7.46 (s, 1H), 7.15 (d, J = 3.2 Hz, 1H), 7.13 (s, 1H), 7.10 (s, 1H), 7.0- 6.87 (m, 1H), 6.88(s, 1H), 6.79-6.66 (m, 2H), 6.47 (d, J = 3.2 Hz, 1H), 4.39-4.25 (m, 2H), 4.17-4.12 (m, 2H), 3.72 (t, J = 5.6 Hz, 2H), 3.17 (t, J = 6.4 Hz, 2H), 3.06-3.01 (m, 1H), 2.98-2.90 (m, 2H), 2.72 (dd, J = 13.4, 6.6 Hz, 1H), 2.50 (dd, J = 13.8, 6.7 Hz, 1H), 1.07 (d, J = 6.3 Hz, 3H). ESI-MS m/z: 498[M+H]+.

Example 5 ^9: l- ⁽⁴ - ^{hydroxybutyl) - 5 - [(2 R} ) - 2 - [2 - [5 - fluoro - ² - ^{(2, 2, 2} - trifluoroethoxy) phenoxy Ethylamino]propyl]-indole-7-carboxamide (DC471859)

In the preparation method of Example 1, the 3-bromo-1-propanol in the step 1.1 was replaced with 4-bromo-1-butanol, and the 2,6-dimethylphenoxyacetaldehyde in the step 1.15 was replaced with 5-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde, 5-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde The preparation method of Example 4 was prepared by replacing 2-methoxy-4-ethyl-phenol in Step 4.1 with 2-methoxy-4-fluoro-phenol. 2,2,21H NMR (400 MHz, CDC1 ₃ ) : δ 7.48 (s, 1H), 7.18 (d, J = 3.2 Hz, 1H), 7.13 (s, 1H), 7.06 (s, 1H), 7.03- 6.89 (m, 1H), 6.84(s, 1H), 6.76-6.67 (m, 2H) 6.50 (d, J = 3.2 Hz, 1H), 4.35-4.24 (m, 2H), 4.16-4.11 (m, 2H) ), 3.75 (t, J = 5.5 Hz, 2H), 3.18 (t, J = 6.9 Hz, 2H), 3.07-3.01 (m, 1H), 2.99-2.90 (m, 2H), 2.72 (dd, J = 13.3, 6.9 Hz, 1H), 2.55 (dd, J = 13.4, 6.7 Hz, 1H), 1.86-1.70 (m, 4H), 1.08 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 526[M+H] ⁺ .

 Example 60: l-(3-Hydroxypropyl)-5-[2-[2-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino] Propyl] - 吲哚-7-carboxamide (DC471860)

According to the preparation method of Example 1, 1-(3-benzoyloxypropyl)-7-cyano-5-[(2R)-2-aminopropyl]-indole was replaced by 1 in the step 1.15. -(3-benzoyloxypropyl)-7-cyano-5-(2-aminopropyl)-indole, replacing 2,6-dimethylphenoxyacetaldehyde in step 1.15 with 4 -Fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde, 4-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde The preparation method of Example 4 was prepared by substituting 2-methoxy-4-ethyl-phenol in Step 4.1 with 2-methoxy-5-fluoro-phenol. 2,2,21H NMR (400 MHz, CDC1 ₃ ) : δ 7.46 (s, 1H), 7.16 (d, J = 3.2 Hz, 1H), 7.04-6.87 (m, 2H), 6.87-6.78 (m, 1H) ), 6.75-6.64 (m, 3H), 6.52 (d, J = 3.2 Hz, 1H), 4.38-4.28 (m, 2H), 4.13-4.00 (m, 2H), 3.71 (t, J = 5.6 Hz, 2H), 3.17 (t, J = 6.9 Hz, 2H), 3.07-3.02 (m, 1H), 2.99-2.93 (m, 2H), 2.70 (dd, J = 7.5, 6.6 Hz, 1H), 2.54 (dd , J = 7.5, 6.8 Hz, 1H), 1.83-1.74 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 512 [M+H] ⁺ .

Example 61: l- ⁽³ - ^{hydroxypropyl) _ 5 - [(2 S} ) - 2 - [2 _ [4 - fluoro - ² - ^{(2, 2, 2} - trifluoroethoxy) phenoxy ]ethylamino]propyl]-indole-7-carboxamide (DC471861)

According to the preparation method of Example 1, 1-(3-benzoyloxypropyl)-7-cyano-5-[(2R)-2-aminopropyl]-indole was replaced by 1 in the step 1.15. -(3-benzoyloxypropyl)-7-cyano-5-[(2S)-2-aminopropyl]-indole, 2,6-dimethylphenoxy b in step 1.15 The aldehyde is replaced by 4-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde, 4-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxy Acetaldehyde was prepared by the procedure of Example 4, replacing 2-methoxy-4-ethyl-phenol in Step 4.1 with 2-methoxy-5-fluoro-phenol. 2,2,2 ¹ :H NMR (400 MHz, CDCl ₃ ) : δ 7.43 (s, 1H), 7.15 (d, J = 3.2 Hz, 1H), 7.04-6.87 (m, 2H), 6.87-6.78 ( m, 1H), 6.75-6.64 (m, 3H), 6.53 (d, J = 3.2 Hz, 1H), 4.38-4.28 (m, 2H), 4.13-4.00 (m, 2H), 3.71 (t, J = 5.6 Hz, 2H), 3.17 (t, J = 6.9 Hz, 2H), 3.07-3.02 (m, 1H), 2.99-2.93 (m, 2H), 2.70 (dd, J = 13.6, 6.6 Hz, 1H), 2.54 (dd, J = 13.6, 6.8 Hz, IH), 1.83-1.74 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 512 [M+H] X. Example 62: l-(3- Hydroxypropyl) -5-[2-[2-[5-fluoro-2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino]propyl] - 吲哚-7- Formamide (DC471862)

In the preparation method of Example 1, 1-(3-benzoyloxypropyl)-7-cyano-5-[(2R)-2-aminopropyl]-indole was replaced by 1 in the step 1.15. -(3-benzoyloxypropyl)-7-cyano-5-(2-aminopropyl)-indole, replacing 2,6-dimethylphenoxyacetaldehyde in step 1.15 with 5 -Fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde, 5-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde The preparation method of Example 4 was prepared by substituting 2-methoxy-4-ethyl-phenol in Step 4.1 with 2-methoxy-4-fluoro-phenol. 2,2,21H NMR (400 MHz, CDC1 ₃ ) : δ 7.15 (s, IH), 7.16 (d, J = 3.2 Hz, IH), 7.08 (s, IH), 7.0-6.88 (m, IH), 6.85(s, IH), 6.78-6.69 (m, 3H), 6.54 (d, J = 3.2 Hz, IH), 4.38-4.27 (m, 2H), 4.15-4.10 (m, 2H), 3.73 (t, J = 5.5 Hz, 2H), 3.16 (t, J = 6.8 Hz, 2H), 3.05-3.01 (m, IH), 2.99-2.91 (m, 2H), 2.70 (dd, J = 7.2, 6.8 Hz, IH ), 2.52 (dd, J = 7.2, 6.6 Hz, IH), 1.83-1.73 (m, 2H), 1.08 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 512[M+H] ⁺ .

Example 6 ³ : l-( ³ -Hydroxypropyl) - ⁵ -[( ² S)- ² -[ ² -[ ⁵ -fluoro- ² -( ² , ² , ² -trifluoroethoxy)phenoxy Ethylamino]propyl]-indole-7-carboxamide (DC471863)

In the preparation method of Example 1, 1-(3-benzoyloxypropyl)-7-cyano-5-[(2R)-2-aminopropyl]-indole was replaced by 1 in the step 1.15. -(3-benzoyloxypropyl)-7-cyano-5-[(2S)-2-aminopropyl]-indole, 2,6-dimethylphenoxy b in step 1.15 The aldehyde is replaced by 5-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde, 5-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxy Acetaldehyde was prepared by the procedure of Example 4, replacing 2-methoxy-4-ethyl-phenol in Step 4.1 with 2-methoxy-4-fluoro-phenol. 2,2,2 ¹ :H NMR (400 MHz, CDCl ₃ ) : δ 7.45 (s, IH), 7.15 (d, J = 3.2 Hz, IH), 7.08 (s, IH), 7.0-6.88 (m, IH), 6.85(s, IH), 6.78-6.69 (m, 3H), 6.48 (d, J = 3.2 Hz, IH), 4.38-4.27 (m, 2H), 4.15-4.10 (m, 2H), 3.73 (t, J = 5.5 Hz, 2H), 3.16 (t, J = 6.8 Hz, 2H), 3.05-3.01 (m, IH), 2.99-2.91 (m, 2H), 2.70 (dd, J = 13.6, 6.8 Hz, IH), 2.52 (dd, J = 13.8, 6.6 Hz, IH), 1.83-1.73 (m, 2H), 1.08 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 512[M +H] ⁺ . Example 64: l-( ₃ -Hydroxypropyl)-5-[(2R)-2-[3,4-methyldioxy-phenoxy]ethylamino]propyl] -吲哚-7- formamide (DC471864)

 According to the preparation method of Example 1, the 2,6-dimethylphenol in the step 1.12 was replaced with sesame phenol.

NMR (400 MHz, CDC1 ₃ ) : δ 7.46 (s, IH), 7.15 (d, J = 3.2 Hz, IH), 7.00 (s, IH), 6.86 (s, IH), 6.65 (d, J = 8.5 Hz, IH), 6.56 (s, IH), 6.56 (d, J = 3.2 Hz, IH), 6.38 (d, J = 2.5 Hz, IH), 6.23 (dd, J = 8.5, 2.5 Hz, IH), 5.90-5.84 (m, 2H), 4.01-3.89 (m, 2H), 3.71 (t, J = 5.6 Hz, 2H), 3.17 (t, J = 6.8 Hz, 2H), 3.00-2.85 (m, 3H) , 2.64 (dd, J = 13.5, 6.9 Hz, IH), 2.55 (dd, J = 13.6 6.5 Hz, IH), 1.83-1.73 (m, 2H), 1.07 (d, J = 6.2 Hz, 3H). ESI -MS m/z: 440[M+H]+.

 Example 65: l-(3-Hydroxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino] Propyl] - 吲哚-7-carboxamide (DC471865)

According to the preparation method of Example 4, 2-methoxy-4-ethyl-phenol in Step 4.1 was replaced with 2-methoxyphenol. 1H NMR (400 MHz, CDC1 ₃ ): δ 7.49 (d, J = 1.3 Hz, IH), 7.13 (d, J = 1.3 Hz, IH), 7.07 (d, J = 3.2 Hz, IH), 7.01 -6.84 (m, 3H), 6.81 (dd, J = 8.0, 1.4 Hz, IH), 6.60 (d, J = 4.5 Hz, 2H), 6.45 (d, J = 3.2 Hz, IH), 4.31 (t, J = 7.3 Hz, 2H), 4.23-4.1 1 (m, 2H), 4.1 1 -3.97 (m, 2H), 3.46 (t, J = 5.8 Hz, 2H), 3.06-2.91 (m, 3H), 2.75 (m , 2H), 1.99-1.88 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 494[M+H]+.

Example _^66: l- ⁽³ - ^{acetoxypropyl) - 5 - [(2 R} ) - 2 - [2 - [2 - (2, 2, 2 - trifluoroethoxy) phenoxy] acetate Amino]propyl]-indole-7-carboxamide (DC471866)

 Preparation of 1-(3-acetoxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]B according to the above reaction formula Amino]propyl]-indole-7-carboxamide, the specific steps are as follows:

 66.1: 1-(3-Hydroxypropyl;)-indoline

50g (31.5ml) of indoline was dissolved in 600ml of acetonitrile, 47.5ml of 3-bromo-1-propanol was added, 120g of potassium carbonate was added, and refluxed for 12h. After the reaction solution was cooled, it was filtered by suction and purified by column chromatography. The oil was 64 g, and the yield was 86%. NMR (d-DMSO, 400 MHz): δ 7.95-8.06 (2 Η, m), 7.55 (IH, dd), 7.28 (IH, dd), 4.40-4.50 (2H, m), 3.48-3.60 (2H, m ), 3.3-3.4 (2H, m), 2.98-2.93 (2H, m), 2.36-2.50 (2H, m). ESI-MS m/z: 178 [M+H] ⁺ .

 66.2: l-(3-Benzoyloxypropyl;)-indoline

The above-mentioned 1-(3-hydroxypropyl)-indoline 64 g was dissolved in 600 ml of anhydrous dichloromethane, and 56 ml of triethylamine was added thereto, and 43 ml of benzoyl chloride was slowly added dropwise under ice-cooling. The reaction was added for 10 h, then extracted with water three times (100 mL X 3 ), and then evaporated. 1H NMR (CDC1 ₃ , 400 MHz): δ 7.95-8.08 (m, 2H), 7.56-7.66 (m, IH), 7.31-7.50 (m, 6H), 4.4-4.5 (m, 2H), 3.79-4.0 (m, 2H) 3.5-3.6 (m, 2H), 3.31-3.40 (m, 2H), 2.38-2.5 (m, 2H). ESI-MS m/z: 282 [M+H]+.

 66.3: l-(3-Benzoyloxypropyl)-5-formyl-indoline

40 ml of hydrazine, hydrazine-dimethylformamide was dissolved in 500 ml of anhydrous 1,2-dichloroacetic acid, 64 ml of phosphorus oxychloride was slowly added dropwise under nitrogen and ice bath stirring, and the reaction was further completed for 1 h, then A solution of 1-(3-benzoyloxypropyl)-indoline (96.8 g) in anhydrous 1,2-dichloroacetamidine (300 ml) was added dropwise thereto, and the mixture was transferred to The reaction was carried out in an oil bath at 80 ° C for 2 h. After the reaction was completed, it was cooled to room temperature, and most of the solvent was removed by concentration. The residual phosphorus oxychloride was quenched with water and then extracted with ethyl acetate (300 ml X 3 ). Purification by column chromatography to give a yellow solid (yield: 82% ₎ (yield: 82% ₎ (1H NMR (CDC1 ₃ , 400 MHz): δ 9.8 (s, IH), 8.0-8.12 (m, 2H), 7.42-7.63 (m: 5H) , 6.4(d, IH, J = 8Hz), 4.45 (t, 2H, J = 6.2Hz), 3.57-3.66(m, 2H), 3.36-3.45(m, 2H), 3.05 (t, 2H, J = 8.5 Hz), 2.01-2.2 (m, 2H). ESI-MS m/z: 310 [M+H]+.

66.4: l-(3-Benzoyloxypropyl)-5-(2-nitropropenyl)-indoline 86g of l-(3-benzoyloxypropyl; )-5-formyl-indoline obtained in the previous step was dissolved in 250 ml of nitroacetamidine, 42 g of ammonium acetate was added, 120 ml of acetic acid was added, and the reaction was refluxed for 4 h. After that, the reaction mixture was concentrated, then EtOAc (3 mL), EtOAc (EtOAc) %. 1H NMR (CDC1 ₃ , 400 MHz): δ 8.05-8.1 (m, 3H), 7.55-7.65 (m, 1H), 7.42-7.5 (m, 2H), 7.2-7.3 (m, 2H), 6.40 (d , 1H, J = 8.4Hz), 4.41-4.49 (m, 2H), 3.5-3.6 (m, 2H), 3.3-3.4 (m, 2H), 3.0-3.1 (m, 2H), 2.48 (S, 3H ), 2.0-2.1 (m, 2H). ESI-MS m/z: 367 [M+H]+.

 66.5: l-(3-Benzoyloxypropyl)-5-(2-nitropropyl)-indoline

70 g of 1-(3-benzoyloxypropyl)nitropropenyl)-indoline obtained in the previous step was dissolved in a mixed solvent of 300 ml of dichloromethane and 600 ml of methanol, and stirred under ice bath. Slowly add sodium borohydride in batches until the reaction solution turns from red to colorless and clear and transparent (about 75 g of sodium borohydride). The reaction is detected by TLC. After the reaction is completed, the reaction solution is concentrated to remove most of the methanol, and then After adding 600 ml of ethyl acetate, a saturated aqueous solution of ammonium chloride was added thereto, and a large amount of a white solid was obtained, which was filtered, and the filtrate was washed three times with water (200 ml of EtOAc). g, yield 91%. 1H NMR (CDC1 ₃ , 400 MHz): δ 8.0-8.1 (m, 1H), 7.56-7.64 (m, 1H), 7.4-7.5 (m, 2H), 6.85 (s, 1H), 6.83 (d, 1H) , J=8.0Hz), 6.39 (d, 1H, J=8.0Hz), 6.53-6.51 (m, 1H), 4.65-4.75 (m, 1H), 4.4-4.5 (m, 2H), 3.3-3.4 ( m, 2H), 3.15-3.28 (m, 3H), 2.8-3.0 (m, 3H), 2.0-2.1 (m, 2H), 1.50 (d, 3H, J = 6.6Hz). ESI-MS m/z : 369 [M+H]+.

 66.6: l-(3-Benzoyloxypropyl;)-7-formyl-5-P-nitropropyl;)-indoline

Under nitrogen protection and ice bath stirring, 40 ml of phosphorus oxychloride was slowly added dropwise to 120 ml of N, N-dimethylformamide, and the reaction was added for 1 h, and then one step was added dropwise to obtain 1-(3- Benzyloxypropyl)-5-(2-nitropropyl)-indoline (64.3g) in hydrazine, hydrazine-dimethylformamide solution (200ml), added, transferred to 80° C oil bath reaction for 2h, after the reaction is completed, cooled to room temperature, concentrated to remove most of the solvent, slowly added water to quench the residual phosphorus oxychloride, and then extracted with ethyl acetate (500ml X 3), the organic layer was combined, dried, column Purification by chromatography gave 60 g of a yellow solid, yield 86%. 1H NMR (CDC1 ₃ , 400 ΜΗζ): δ 9.94 (s, 1H), 8.0-8.1 (m, 2H), 7.5-7.6 (m,

 1Η)7.4-7.5 (m, 2H), 7.22 (s, 1H), 6.93 (brs, 1H), 4.65-4.76 (m, 1H), 4.4-4.5 (m, 2H), 3.6-3.7 (m, 4H) ), 3.20 (dd, 1H, J=7.7, 14.2Hz), 3.0-3.1 (m, 2H), 2.93 (dd, 1H, J=6.4, 14.2Hz), 2.1-2.2 (m, 2H), 1.54 ( d, 3H, J = 6.6Hz). ESI-MS m/z: 397 [M+H]+.

 66.7: l-(3-Benzoyloxypropyl;)-7-formyl-5-P-nitropropyl;) -吲哚

 Dissolving 1-(3-benzoyloxypropyl)-7-formyl-5-(2-nitropropyl)-indoline 60g obtained in the previous step

In 500 ml of ethyl acetate, add 52 g of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, add the reaction for 12 h, add 3 times with saturated sodium bicarbonate (300 ml X 3 ), organic The layer was concentrated to give a pale yellow oil (yield: 53.7 g). NMR CCDC1 ₃ , 400 MHz): δ 10.04 (s, 1Η), 8.02 (d, 2H), 7.67 (d, J = 1.3 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.49-7.40 (m, 3H), 7.18 (d, J = 3.2 Hz, 1H), 6.52 (d, J = 3.2 Hz, 1H), 4.89-4.76 (m, 3H), 4.24 (t, J = 6.1 Hz, 2H) , 3.45 (dd, J = 14.2, 7.7 Hz, 1H), 3.16 (dd, J = 14.2, 6.5 Hz, 1H), 2.24-2.11 (m, 2H), 1.58 (d, J = 6.6 Hz, 3H). ESI-MS m/z: 395 [M+H]+.

 66.8: l-(3-Benzoyloxypropyl)-7-cyano-5-(2-nitropropyl)-indole

53.7 g of 1-(3-benzoyloxypropyl)-7-formyl-5-(2-nitropropyl)-indole obtained in the previous step was dissolved in 450 ml of anhydrous tetrahydrofuran, and hydroxylamine hydrochloride 12 g was added. Add 50 ml of pyridine and react at 50 ° C for 12 h, then add 52 ml of acetic anhydride in portions, warm to reflux for 8 h, concentrate the reaction, add 500 ml of ethyl acetate, wash three times with water (200 ml X 3), and concentrate the organic layer. The solid was recrystallized from methanol to yield 47 g,yel. 1H NMR (CDC1 ₃ , 400 ΜΗζ): δ 8.0-8.1 (m, 2H), 7.5-7.6 (m, 1H), 7.4-7.5 (m, 2H), 7.16 (d, J = 3.2 Hz, 1H), 6.93 (brs, 1H), 6.89 (brs, 1H), 6.54 (d, J = 3.2 Hz, 1H), 4.6-4.7 (m, 1H), 4.4-4.5 (m, 2H), 3.7-3.81 (m, 2H), 3.12 (dd, 1H, J=7.8, 14.2Hz), 2.86 (dd, 1H, J=6.2, 14.2Hz), 2.1-2.2 (m, 2H), 1.54 (d, 3H, J = 6.7Hz). ESI-MS m/z: 392[M+H] ⁺ .

 66.9: l-(3-Benzoyloxypropyl)-7-cyano-5-(2-aminopropyl)-indole

The 1-(3-benzoyloxypropyl)-7-cyano-5-(2-nitropropyl)-indole (47 g) obtained in the previous step was dissolved in a mixed solvent of 400 ml of methanol and 400 ml of tetrahydrofuran. 4.7 g of 10% palladium carbon was added, and the mixture was reduced under a hydrogen atmosphere at atmospheric pressure for 48 hours. After completion of the reaction, the mixture was filtered under suction, and the filtrate was filtered, and the filtrate was concentrated to yield 41.2 g, yield 94%. iH NMR (CDC1 ₃ , 400 MHz): δ 8.02 (d, 2H), 7.67 (d, J = 1.3 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H),

7.49-7.40 (m, 3H), 7.15 (d, J = 3.2 Hz, 1H), 6.52 (d, J = 3.2 Hz, 1H), 4.89-4.76 (m, 3H), 4.24 (t, J = 6.1 Hz , 2H), 3.45-3.52 (m, 3H), 3.16 (dd, J = 14.2, 6.5 Hz, 1H), 2.24-2.11 (m, 2H), 1.05 (d, J = 6.6 Hz, 3H). ESI- MS m/z: 362 [M+H]+.

 66.10: l-(3-Benzoyloxypropyl;)-7-cyano-5-[(2R)-2-aminopropyl]-indole

The 1-(3-benzoyloxypropyl)-7-cyano-5-(2-aminopropyl)-indole 5g obtained in the previous step was dissolved in acetone 30 ml, and added dropwise thereto under stirring. 1.2 g of L-(+)-tartaric acid aqueous solution (1.2 g of L-(+)-tartaric acid dissolved in 30 ml of water) was stirred for 12 h, and a large amount of solid was precipitated, and filtered to give the desired product, L-(+)-tartrate, 2.0 g. The obtained solid was dissolved in 80 ml of water, and the mixture was adjusted to pH 10 with a saturated aqueous solution of sodium carbonate, and extracted twice with ethyl acetate (100×2). The organic layer was combined, dried and concentrated to give a pale yellow oily solid 1.8 g. . 1H NMR (CDC1 ₃ , 400 MHz): δ 8.02 (d, 2H), 7.67 (d, J = 1.3 Hz, 1H), 7.57 (t, J = 7.4 Hz, 1H), 7.49-7.40 (m, 3H) , 7.18 (d, J = 3.2 Hz, 1H), 6.50 (d, J = 3.2 Hz, 1H), 4.89-4.76 (m, 3H), 4.24 (t, J = 6.1 Hz, 2H) _: 3.46-3.54 ( m, 3H), 3.16 (dd, J = 14.2, 6.5 Hz, 1H), 2.24-2.1 1 (m, 2H), 1.05 (d, J = 6.6 Hz, 3H). ESI-MS m/z: 362 [ M+H]+.

 66.11: l-(3-Benzoyloxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamine Propyl] -7-cyano-oxime

The 1-(3-benzoyloxypropyl)-7-cyano-5-[(2R)-2-aminopropyl]-indole 400 mg obtained in the previous step was dissolved in 20 ml of 1,2-dichloroethane. In the crucible, 363 mg of 2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde was added, and 375 mg of sodium borohydride hydride was added thereto, and the reaction was carried out for 12 h. . ESI-MS m/z: 580 [M+H] ⁺ .

 66.12: 1-(3-Benzoyloxypropyl)-5-[(2R)-N-benzyl-N-2-[2-[2-(2,2,2-trifluoroethoxy) Phenoxy]ethyl-amino]propyl]-7-cyano-anthracene

1-(3-Benzoyloxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]] Ethylamino]propyl]-7-cyano-indole 480 mg was dissolved in 15 ml of acetone, and 156 mg of benzyl bromide was added thereto, and then 230 mg of potassium carbonate was added thereto, and refluxed for 12 hours, and column chromatography was carried out to obtain a white solid (yield: 500%). ESI-MS m/z: 670 [M+H] ⁺ .

 66.13: 1-(3-Hydroxypropyl)-5-[(2R)-N-benzyl-N-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy ]ethyl-amino]propyl]-7-cyano-anthracene

1-(3-Benzoyloxypropyl)-5-[(2R)-N-benzyl-N-2-[2-[2-(2,2,2-trifluoroethyl) obtained in the previous step Oxy)phenoxy]ethyl-amino]propyl]-7-cyano-indole 500mg is dissolved in 10ml of methanol, added with 1ml of 2mol/L NaOH aqueous solution, reacted for 4h, concentrated under reduced pressure to remove most of the methanol, 30 ml of ethyl acetate was added to the residue, and then 20 ml of water was added, and the mixture was evaporated. ESI-MS m/z: 566 [M+H] ⁺ .

 66.14: 1-(3-Hydroxypropyl)-5-[(2R)-N-benzyl-N-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy Ethyl-amino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-N-benzyl-N-2-[2-[2-(2,2,2-trifluoroethoxy)benzene obtained in the previous step Oxy]ethyl-amino]propyl]-7-cyano-indole 420 mg was dissolved in 5 ml of dimethyl sulfoxide, and then 5 mol/L of hydrogen and oxygen was added thereto. 500 μl of sodium sulphate solution, 300 μl of 30% aqueous hydrogen peroxide solution, and after 12 h of reaction, 20 ml of water was added, and the mixture was extracted with EtOAc (3 mL). The rate is 92%. ESI-MS m/z: 584 [M+H]+.

 66.15: 1-(3-acetoxypropyl)-5-[(2R)-N-benzyl-N-2-[2-[2-(2,2,2-trifluoroethoxy)benzene Oxy]ethyl-amino]propyl]-indole-7-carboxamide

1-(3-hydroxypropyl)-5-[(2R)-N-benzyl-N-2-[2-[2-(2,2,2-trifluoroethoxy)benzene obtained in the previous step 400 mg of oxy]ethyl-amino]propyl]-indole-7-carboxamide was dissolved in 25 ml of anhydrous dichloromethane, 145 μl of triethylamine was added, and then 54 μl of acetyl chloride was added, and the reaction was carried out for 10 hours. After adding 20 ml of dichloromethane, it was washed with water (20 ml of X 3 ), and the organic layer was concentrated to give a pale yellow oil, 410 mg, yield 96%. ESI-MS m/z: 626 [M+H] ⁺ .

 66.16. 1-(3-Acetoxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy]ethylamino] Propyl] - 吲哚-7-carboxamide

1-(3-acetoxypropyl)-5-[(2R)-N-benzyl-N-2-[2-[2-(2,2,2-trifluoroethoxy) obtained in the previous step 410 mg of phenoxy]ethyl-amino]propyl]-indol-7-carboxamide was dissolved in 20 ml of methanol, and 100 mg of 10% palladium carbon was added thereto, and it was reduced under a hydrogen atmosphere at atmospheric pressure for 24 hours. The filtrate was concentrated to give the product 330 mg, yield 94%. H NMR (400 MHz, CDC1 ₃ ): δ 7.52 (d, J = 1.3 Hz, 1H), 7.16 (d, J = 1.5 Hz, 1H), 7.05 (d, J = 3.4 Hz, 1H), 7.04-6.85 (m, 3H), 6.82 (dd, J = 8.2, 1.4 Hz, 1H), 6.63 (d, J = 4.6 Hz, 2H), 6.45-6.40 (m, 1H), 4.33 (t, J = 7.5 Hz, 2H), 4.24-4.13 (m, 2H), 4.1 1-3.95 (m, 2H), 3.48 (t, J = 5.6 Hz, 2H), 3.06-2.93 (m, 3H), 2.74 (m, 2H), 2.21(s, 3H), 1.99-1.86 (m, 2H), 1.08 (d, J = 6.3 Hz, 3H). ESI-MS m/z: 536 [M+H]+.

 Example 67: l-(3-Trifluoroacetoxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)phenoxy] Ethylamino]propyl]-indole-7-carboxamide (DC471867)

 Following the preparation of Example 66, the acetyl chloride in step 66.15 was replaced with trifluoroacetyl chloride. iH NMR OO MHz, CDCI3): δ 7.454 (d, J = 1.3 Hz, 1H), 7.16 (d, J = 1.3 Hz, 1H), 7.09 (d, J = 3.0 Hz, 1H), 7.05-6.85 (m , 3H), 6.82 (dd, J = 8.3, 1.4 Hz, 1H), 6.63 (d, J = 4.6 Hz, 2H), 6.47 (d, J = 3.3 Hz, 1H), 4.34 (t, J = 7.4 Hz , 2,,,,,,,,,,,,, , 2.03-1.97 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 590 [M+H]+.

 Example 68: l-(3-Acetoxypropyl)-2-methyl-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxy)benzene Oxy]ethylamino]propyl]-indole-7-carboxamide (DC471868)

 According to the preparation method of Example 66, the indoline in the step 66.1 was replaced with 2-methyl-indoline.

NMR (400 MHz, CDC1 ₃ ): δ 7.49 (d, J = 1.3 Hz, 1H), 7.14 (d, J = 1.4 Hz, 1H), 7.08 (d, J = 3.4 Hz, 1H), 7.06-6.84 ( m, 2H), 6.83 (dd, J = 8.3, 1.4 Hz, 1H), 6.65 (d, J = 4.5 Hz, 2H), 6.46-6.42 (m, 1H), 4.34 (t, J = 7.5 Hz, 2H ), 4.24-4.10 (m, 2H), 4.13-3.96 (m, 2H), 3.49 (t, J = 5.8 Hz, 2H), 3.09-2.95 (m, 3H), 2.76 (m, 2H), 2.22 ( s, 3H), 2.17(s, 3H), 2.05-1.90 (m, 2H), 1.06 (d, J = 6.5 Hz, 3H). ESI-MS m/z: 550 [M+H]+.

 Example 69: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[5-ethyl-2-(2,2,2-trifluoroethoxy) Phenoxy]ethylamino]propyl]-indole-7-carboxamide (DC471869)

According to the preparation method of Example 1, the dihydroanthracene in the step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in the step 1.15 was replaced with 5-B. Preparation of 5-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde (5-ethyl-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde The method is the same as in Example 4). 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.44 (s, 1H), 7.12 (d, J = 3.4 Hz, 1H), 6.95 (s, 2H), 6.83 (d, J = 8.1 Hz, 1H), 6.70 (m, 1H), 6.65 (s, 1H), 6.53 (d, J = 3.1 Hz, 1H), 4.30-4.15 (m, 2H), 4.12 (t, J = 7.5 Hz, 2H), 3.66 (t, J = 5.6 Hz, 2H), 3.14 (m, 2H), 3.06-2.89 (m, 3H), 2.71 (dd, J = 13.3, 6.4 Hz, 1H), 2.63-2.44 (m, 3H), 2.20(s, 3H ), 1.81-1.68 (m, 2H), 1.22-1.15 (t, J = 7.7 Hz, 3.2H), 1.08 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 536[M+H ] ⁺ .

 Example 70: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[4-ethyl-2-ethoxy-phenoxy]ethylamino ]propyl] -吲哚-7-carboxamide (DC471870)

According to the preparation method of Example 1, the indoline in step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in step 1.15 was replaced by 2-B. Oxy-4-ethyl-phenoxyacetaldehyde (2-ethoxy-4-ethyl-phenoxyacetaldehyde was prepared in the same manner as in Example 5). 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.45 (s, 1H), 7.17 (d, J = 3.2 Hz, 1H), 6.96 (s, 1H), 6.85 (d, J = 8.1 Hz, 1H), 6.74 (m, 2H), 6.63 (s, 1H), 6.57 (d, J = 3.1 Hz, 1H), 4.12 (t, J = 7.52 Hz, 2H), 3.83 (q, J = 6.7 Hz, 2H), 3.69 (t, J = 5.6 Hz, 2H), 3.15 (m, 2H), 3.12-2.90 (m, 3H), 2.66 (dd, J = 13.4, 6.5 Hz, 1H), 2.64-2.44 (m, 3H), 2.19(s, 3H), 1.80-1.69 (m, 2H), 1.21-1.13 (m, 6H), 1.05 (d, J = 6.2 Hz, 3H). ESI-MS m/z:

482[M+H] ⁺ .

 Example 71: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[5-bromo-2-(2,2,2-trifluoroethoxy) Phenoxy]ethylamino]propyl]-indole-7-carboxamide (DC471871)

 According to the preparation method of Example 1, the indoline in step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in step 1.15 was replaced with 5-bromo. Preparation method of -2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde (5-bromo-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde Example 4, replacing 2-methoxy-4-ethyl-phenol in 4.1 with 2-methoxy-4-bromo-phenol). 1H NMR (400 MHz, CDCI3): δ 7.46 (s, 1H), 7.13 (d, J = 3.0 Hz, 1H) 7.08-6.98 (m, 2H), 6.94 (s, 1H), 6.86-6.83 (m, 1H), 6.66 (s, 1H), 6.52 (d, J = 3.3 Hz, 1H), 4.34-4.25 (m, 2H), 4.12-4.02 (m, 2H), 3.74 (t, J = 5.7 Hz, 2H ), 3.15 (t, J = 7.1 Hz, 2H), 3.1 1-2.96 (m, 3H), 2.68 (dd, J = 13.7, 6.8 Hz, 1H), 2.55 (dd, J = 13.4, 6.8 Hz, 1H ), 2.19(s, 3H), 1.83-1.75 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 586:588=l : 1 [M+H]+ .

 Example 72: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[4-bromo-2-ethoxy-phenoxy]ethylamino] Propyl]-indole-7-carboxamide (DC471872)

According to the preparation method of Example 1, the indoline in step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in step 1.15 was replaced with 4-bromo. 2-ethoxy-phenoxyacetaldehyde (4-bromo-2-ethoxy-phenoxyacetaldehyde is prepared in the same manner as in Example 5, 2-methoxy-4-ethyl- in step 5.1 The phenol was replaced by 2-methoxy-4-bromo-benzene. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.44 (s, 1H), 7.11 (d, J = 3.2 Hz, 1H), 7.05-6.94 (m, 2H), 6.97 (s, 1H), 6.90-6.85 ( m, 1H), 6.62 (s, 1H), 6.55 (d, J = 3.5 Hz, 1H), 4.13-4.04 (m 2H), 3.79 (q, J = 7.1 Hz, 2H), 3.73 (t, J = 5.8 Hz, 2H), 3.17 (t, J = 7.3 Hz, 2H), 3.14-2.98 (m, 3H), 2.66 (dd, J = 13.5, 6.6 Hz, 1H), 2.54 (dd, J = 13.6, 6.8 Hz, 1H), 2.21(s, 3H), 1.84-1.78 (m, 2H), 1.21 (t, 3H), 1.04 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 532:534 =l : l [M+H] ⁺ .

Example 7 ³ : l-( ³ -Hydroxypropyl) _ ² _methyl _ ⁵ -[( ² R)- ² -[ ² _[ ⁴ -Fluoro ² -(2, ² , ² -Trifluoroethyl Oxy)phenoxy]ethylamino]propyl]-indole-7-carboxamide (DC471873)

According to the preparation method of Example 1, the dihydroanthracene in the step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in the step 1.15 was replaced with 4-fluorine. Preparation method of -2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde (4-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde Example 4, prepared by replacing 2-methoxy-4-ethyl-phenol in step 4.1 with 2-methoxy-5-fluoro-phenol). 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.50 (s, 1H), 7.12 (d, J = 3.0 Hz, 1H), 7.05-6.89 (m, 1H), 6.86-6.79 (m, 1H), 6.73- 6.63 (m, 3H), 6.43 (d, J = 3.3 Hz, 1H), 4.39-4.26 (m, 2H), 4.15-4.04 (m, 2H), 3.70 (t, J = 5.5 Hz, 2H), 3.16 (t, J = 6.8 Hz, 2H), 3.08-3.02 (m, 1H), 2.99-2.92 (m, 2H), 2.72 (dd, J = 13.5, 6.8 Hz, 1H), 2.53 (dd, J = 13.6) , 6.8 Hz, 1H), 2.22(s, 3H), 1.83-1.75 (m, 2H), 1.08 (d, J = 6.3 Hz, 3H). ESI-MS m/z: 526 [M+H] X. Example 74: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[5-fluoro-2-ethoxy-phenoxy]ethylamino]propyl ] -吲哚_ ₇ _carboxamide (DC471874)

According to the preparation method of Example 1, the dihydroanthracene in the step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in the step 1.15 was replaced with 5-fluorine. 2-ethoxy-phenoxyacetaldehyde (5-fluoro-2-ethoxy-phenoxyacetaldehyde is prepared in the same manner as in Example 5, 2-methoxy-4-ethyl- in step 5.1 The phenol was replaced by 2-methoxy-5-fluoro-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.51 (s, 1H), 7.13 (d, J = 3.1 Hz, 1H), 7.08-6.88 (m, 2H), 6.89-6.74 (m, 1H), 6.74- 6.62 (m, 2H), 6.58 (d, J = 3.1 Hz, 1H), 4.15-4.01 (m, 2H), 3.77 (q, J = 7.2 Hz, 2H), 3.72 (t, J = 5.8 Hz, 2H ), 3.15 (t, J = 6.8 Hz, 2H), 3.11-3.03 (m, 1H), 2.99-2.91 (m, 2H), 2.73 (dd, J = 13.6, 6.7 Hz, 1H), 2.55 (dd, J = 13.6, 6.6 Hz, 1H), 2.16(s, 3H), 1.85-1.75 (m, 2H), 1.23 (t, 3H), 1.07 (d, J = 6.3Hz, 3H). ESI-MS m/ z: 472 [M+H] ⁺ .

 Example 75: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[5-fluoro-2-(2,2,2-trifluoroethoxy) Phenoxy]ethylamino]propyl]-indole-7-carboxamide (DC471875)

According to the preparation method of Example 1, the dihydroanthracene in the step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in the step 1.15 was replaced with 5-fluorine. Preparation method of -2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde (5-fluoro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde Example 4, prepared by replacing 2-methoxy-4-ethyl-phenol in step 4.1 with 2-methoxy-4-fluoro-phenol). 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.96 (s, 1H), 7.53 (s, 1H) _: 7.41 (d, J = 1.4 Hz, 1H), 7.32 (d, J = 3.0 Hz, 1H), 7.03 (d, J = 1.2 Hz, 1H), 6.94-6.83 (m, 1H) 6.65 (td, J = 8.5, 3.2 Hz, 1H), 6.43 (dd, J = 7.9, 3.2 Hz, 1H), 4.37-4.26 (m, 2H), 4.16-4.10 (m 2H), 3.74 (t, J = 5.6 Hz, 2H), 3.18 (t, J = 6.7 Hz, 2H), 3.08-3.01 (m, 1H), 2.99-2.90 (m, 2H), 2.72 (dd, J = 13.7, 6.8 Hz, 1H), 2.54 (dd, J = 13.8, 6.8 Hz, 1H), 2.13(s, 3H), 1.85-1.75 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 526 [M+H] ⁺ .

 Example 76: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[4-fluoro-2-ethoxy-phenoxy]ethylamino] Propyl]-indole-7-carboxamide (DC471876)

 According to the preparation method of Example 1, the indoline in step 1.1 was replaced with 2-methyl-indoline, and the step was carried out.

The preparation method of 2,6-dimethylphenoxyacetaldehyde in 1.15 is replaced by 4-fluoro-2-ethoxy-phenoxyacetaldehyde (4-fluoro-2-ethoxy-phenoxyacetaldehyde) Example 5, prepared by replacing 2-methoxy-4-ethyl-phenol in step 5.1 with 2-methoxy-4-fluoro-phenol). 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.94 (s, 1H), 7.53 (s, 1H), 7.44 (d, J = 1.3 Hz, 1H), 7.33 (d, J = 3.3 Hz, 1H), 7.13 (d, J = 1.2 Hz, 1H), 6.96-6.87 (m, 1H), 6.66 (m, 1H), 6.43 (dd, J = 7.9, 3.3 Hz, 1H), 3.58 (q, J = 7.4 Hz, 2H), 3.74 (t, J = 5.8 Hz, 2H), 3.18 (t, J = 6.9 Hz, 2H), 3.13-3.04 (m, 1H), 2.98-2.92 (m, 4H), 2.76 (dd, J = 13.8, 6.6 Hz, 1H), 2.59 (dd, J = 13.6, 6.8 Hz, 1H), 2.19(s, 3H), 1.83-1.78 (m, 2H), 1.26 (t, 3H), 1.05 (d, J = 6.3Hz, 3H).

ESI-MS m/z: 472 [M+H] ⁺ .

 Example 77: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[5-methyl-2-(2,2,2-trifluoroethoxy) Phenoxy]ethylamino]propyl]-indole-7-carboxamide (DC471877)

 According to the preparation method of Example 1, the indoline in step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in step 1.15 was replaced with 5-a. Preparation of keto-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde (5-methyl-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde The same procedure as in Example 4 was carried out by replacing 2-methoxy-4-ethyl-phenol in step 4.1 with 2-methoxy-4-methyl-phenol. NMR (400 MHz, CDC13): δ 7.55 (d, J = 1.3 Hz, 1H), 7.16 (d, J = 1.2 Hz, 1H), 7.08 (d, J = 3.4 Hz, 1H), 6.86 (d, J = 8.8 Hz, 1H),

6.69-6.65 (m, 2H), 6.57 (d, J = 2.9 Hz, 1H), 6.47 (d, J = 3.1 Hz, 1H), 4.38-4.25 (m, 2H), 4.21-3.99 (m, 4H) , 3.48 (t, J = 5.9 Hz, 2H), 3.12-2.99 (m, 2H), 2.96-2.90 (m, 1H), 2.85-2.79 (m, 1H), 2.73-2.69 (m, 1H), 2.23 (s, 3H), 2.13(s, 3H), 1.99-1.88 (m, 2H), 1.07 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 522 [M+H] ⁺ .

Example 78: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[4-methyl-2-ethoxy-phenoxy]ethylamino ]propyl] -吲哚_ ₇ _carboxamide (DC471878)

 According to the preparation method of Example 1, the indoline in step 1.1 was replaced with 2-methyl-indoline, and the step was carried out.

Method for preparing 2,6-dimethylphenoxyacetaldehyde in 1.15 by replacing 4-methyl-2-ethoxy-phenoxyacetaldehyde (4-methyl-2-ethoxy-phenoxyacetaldehyde) In the same manner as in Example 5, 2-methoxy-4-ethyl-phenol in Step 5.1 was replaced with 2-methoxy-4-methyl-phenol. 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.52 (s, 1H), 7.18 (d, J = 3.2 Hz, 1H), 7.09 (s, 1H), 6.98 (s, 1H), 6.84 (d, J = 8.3 Hz, 1H), 6.82 (s, 1H), 6.72-6.62 (m, 1H), 6.53 (d, J = 3.0 Hz, 1H), 4.15-4.02 (m, 2H), 3.86 (s, 3H), 3.67 (t, J = 5.8 Hz, 2H), 3.63 (q, J = 7.6 Hz, 2H), 3.16 (t, J = 7.0 Hz, 3H), 3.12-2.93 (m, 2H), 2.68 (dd, J = 13.7, 6.4 Hz, 1H), 2.48 (dd, J = 13.8, 6.6 Hz, 1H), 2.21(s, 3H), 1.82-1.75 (m, 2H), 1.25 (t, 3H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 468 [M+H]+.

 Example 79: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[5-chloro-2-(2,2,2-trifluoroethoxy) Phenoxy]ethylamino]propyl]-indole-7-carboxamide (DC471879)

According to the preparation method of Example 1, the indoline in step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in step 1.15 was replaced with 5-chloro. Preparation method of -2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde (5-chloro-2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde Example 4, prepared by replacing 2-methoxy-4-ethyl-phenol in step 4.1 with 2-methoxy-4-chloro-phenol). NMR (400 MHz, CDC13): δ 7.55 (t, j = 3.8 Hz, 1H), 7.13 (t, J = 4.7 Hz, 1H), 7.08 (d, j = 3.2 Hz, 1H), 6.89-6.81 (m , 2H), 6.64 (d, J = 8.5 Hz, 2H), 6.47 (d, J = 3.3 Hz, 1H), 4.39-4.25 (m, 2H), 4.26-4.06 (m, 2H), 4.04-3.94 ( m, 2H), 3.45 (t, J = 5.8 Hz, 2H), 3.08-2.93 (m, 3H), 2.86-2.78 (m, 1H), 2.66 (dd, J = 13.7, 6.5 Hz, 1H), 2.20 (s, 3H), 1.98-1.87 (m, 2H), 1.09 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 542: 544=3: 1 [M+H] ⁺ .

 Example 80: l-(3-Hydroxypropyl)-2-methyl-5-[(2R)-2-[2-[4-chloro-2-ethoxy-phenoxy]ethylamino] Propyl]-indole-7-carboxamide (DC471880)

According to the preparation method of Example 1, the dihydroanthracene in the step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in the step 1.15 was replaced with 4-chloro. 2-ethoxy-phenoxyacetaldehyde (4-chloro-2-ethoxy-phenoxyacetaldehyde was prepared in the same manner as in Example 5, 2-methoxy-4-ethyl- in step 5.1 The phenol is replaced by 2-methoxy-4-chloro-phenol). 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.48 (t, J = 3.8 Hz, 1H), 7.14 (s, 1H), 7.08 (d, J = 3.3 Hz, 1H), 6.88-6.83 (m, 2H) , 6.67 (d, J = 8.5 Hz, 2H), 6.47 (d, j = 3.2 Hz, 1H),

 4.14-3.98 (m, 2H), 3.73 (t, J = 5.6 Hz, 2H), 3.63 (q, J = 7.8 Hz, 2H), 3.26-3.15 (m, 2H), 3.12-3.09O, 1H), 3.07-2.89 (m, 2H), 2.68-2.62 (m, 1H), 2.55 (dd, J = 13.5, 6.8 Hz, 1H), 2.13(s, 3H), 1.85-1.73 (m, 2H), 1.26 ( t, 3H), 1.06 (d, J = 6.2 Hz, 3H). ESI-MS m/z:

488:490=3 : 1 [M+H] ⁺ .

Example 81: l- ⁽³ _-hydroxypropyl) - ² - methyl ^{- 5 - [(2 R)} - 2 - [2 - [2 - (2, 2, 2 - trifluoroethoxy) phenoxy Ethylamino]propyl]-indole-7-carboxamide (DC471881)

According to the preparation method of Example 1, the dihydroanthracene in the step 1.1 was replaced with 2-methyl-indoline, and the 2,6-dimethylphenoxyacetaldehyde in the step 1.15 was replaced by 2-( 2,2,2-Trifluoroethoxy)-phenoxyacetaldehyde (wherein 2-(2,2,2-trifluoroethoxy)-phenoxyacetaldehyde is prepared according to the method of Example 4 The preparation method is prepared by replacing 2-methoxy-4-ethyl-phenol in step 4.1 with 2-methoxy-phenol. 1H NMR (400 MHz, CDC1 ₃ ): 5 7.48 (d, J = 1.3 Hz, 1H), 7.11 (d, J = 1.3 Hz, 1H), 7.06 (d, J = 3.3 Hz, 1H), 7.03-6.85 (m, 2H), 6.85 (dd, J = 8.1, 1.4 Hz, 1H), 6.62 (d, J = 4.5 Hz, 2H), 6.46 (d, J = 3.2 Hz, 1H), 4.32 (t, J = 7.4 Hz, 2H), 4.25-4.12 (m, 2H), 4.11-3.94 (m, 2H), 3.48 (t, J = 5.7 Hz, 2H), 3.08-2.90 (m, 3H), 2.76 (m, 2H), 2.14(s, 3H), 1.99-1.88 (m, 2H), 1.07 (d, J = 6.2 Hz, 3H). ESI-MS m/z: 508[M+H]+. Example 82: l-(3-hydroxypropyl -2-methyl-5-[(2R)-2-[2-[2-(ethoxy)phenoxy]ethylamino]propyl]-indole-7-carboxamide (DC471882)

 According to the preparation method of Example 1, the indoline in step 1.1 was replaced with 2-methyl-indoline, and the step was carried out.

The 2,6-dimethylphenoxyacetaldehyde in 1.15 is replaced by 2-ethoxy-phenoxyacetaldehyde (wherein the preparation method of 2-ethoxy-phenoxyacetaldehyde is as follows: Preparation according to Example 5 Method, the 2-methoxy-4-ethyl-phenol in step 5.1 is replaced by 2-methoxy-phenol). 1H NMR (400 MHz, CDC1 ₃ ) : δ 7.93 (s, 1H), 7.56 (s, 1H), 7.48 (d, J = 1.5 Hz, 1H), 7.39-7.32 (m, 1H), 7.14 (d, j = 1.4 Hz, 1H), 6.99-6.87 (m, 2H), 6.64 (m, 1H), 6.44 (dd, J = 7.8, 3.5 Hz, 1H), 3.59 (q, J = 7.5 Hz, 2H), 3.73 (t, J = 5.9 Hz, 2H), 3.17 (t, J = 6.8 Hz, 2H), 3.15-3.04 (m, 1H), 2.99-2.92 (m, 4H), 2.76 (dd, J = 13.6, 6.6 Hz, 1H), 2.59 (dd, J = 13.6, 6.8 Hz, 1H), 2.18(s, 3H), 1.86-1.79 (m, 2H), 1.25 (t, 3H), 1.06 (d, J = 6.3 Hz, 3H). ESI-MS m/z: [M+H]+.

 Example 83: Testing of Cellular Biological Activity

 experimental method:

HEK293 cells stably expressing α _1Α -adrenergic receptor (a _1A -AR) and G protein _Gal6 were seeded in 96-well plates, and after 24 hours of culture, the medium was removed, and 40 μί of 2 M Fluo- was added per well. 4 AM Hank Balanced Salt Solution (Hank Balanced Salt Solution: Contains 5.4 mM KCl, 0.3 mM Na ₂ HP0 ₄ , 0.4 mM KH ₂ PO ₄ , 4.2 mM NaHC0 ₃ , 1.3 mM CaCl ₂ , 0.5 mM MgCl ₂ , 0.6 mM MgSO ₄ , 137 mM NaCl, 5.6 mM D-glucose and 250 μM sulfinpyrazone, ρΗ 7.4) Incubate for 45 minutes in an incubator. Aspirate the dye and add 50 μL of HBSS containing the test compound or 1% DMS0 (negative control), incubate for 10 minutes at room temperature, and then read with a Flex Station 3 microplate reader. The detector automatically delivers 25 μL of agonist phenylephrine at the indicated time

 (Phenylephrine, final concentration 30 nM) was added to the reaction system, and the change of the fluorescence intensity of the dye caused by the change of intracellular calcium ion concentration was detected by excitation at 485 nm and at 525 nm.

 data analysis:

After incubation with different drugs, the response of cells to the a _1A -AR agonist Phenylephrine is calculated by the following formula:

 Reaction rate % = (D-B) / (S-B) * 100%;

 Where D is the peak of the calcium flow signal evoked by phenylephrine after incubation with the test drug; B is the peak of the calcium flow signal evoked by phenylephrine after incubation with the 10 μΜ positive control drug Tamsulosin; The peak of the calcium flow signal evoked by phenylephrine after incubation with the negative control 1% DMS0.

The response rate of different doses of the same drug was analyzed by GraphPad Prism software, and the dose response curve was obtained and the IC _5Q value was measured. Data are expressed as mean ± standard deviation and are the results of three independent experiments, each of which is three replicate wells.

 The results obtained are shown in the table below:

DC471804 6.83 DC471845 2.13

DC471804 6.83 DC471845 2.13

DC471808 4.62 DC471848 12.46

 DC471809 10.22 DC471853 13.02

 DC471813 2.50 DC471854 12.21

 DC471817 3.61 DC471855 2.13

 DC471820 0.21 DC471865 0.34

 DC471822 0.18 DC471829 0.45

DC471827 1.70 DC471832 2.01 As can be seen from the table, the compounds of the present invention are highly active in a _1A -AR antagonist, the IC ₅₀ of all compounds of lower than 20 nM, IC _5Q 6 compounds less than 1 nM. Such compounds have good application prospects against benign prostatic hyperplasia and thus have good commercial value.

Claims

A quinone compound represented by the formula (I), which is a pharmaceutically acceptable salt, a crystalline hydrate, a solvate or a mixture thereof,

 (I)  among them, Ri R ₂ , R ₃ , R ₄ , R ₅ represent a substituent on the phenyl ring, each independently selected from hydrogen, halogen, amino, carboxy, cyano, nitro, hydroxy, unsubstituted or straight chain by C2-C6 Or a branched alkenyl or halogen-substituted C1-C6 straight or branched fluorenyl group, a C1-C6 straight or branched fluorenyl group which is unsubstituted or substituted by a C3-C6 cyclodecyl group or a halogen, C2-C12 straight or branched alkenyl substituted or substituted by halogen, C2-C12 straight or branched alkynyl unsubstituted or substituted by halogen, unsubstituted or substituted by halogen C3-C6 cyclodecyl a C3-C6 cyclodecyloxy group which is unsubstituted or substituted by halogen, unsubstituted or substituted by a halogen to a C1-C6 straight or branched mercaptocarbonyloxy group, unsubstituted or substituted by a halogen to a C1-C6 straight or branched chain Mercaptocarbonyl, unsubstituted or substituted by halogen, C1-C6 straight or branched fluorenyloxycarbonyl, unsubstituted or halogenated, C1-C6 straight or branched fluorenyl, C1-C6 straight or branched a benzyloxy group substituted with a phenoxy group, unsubstituted or substituted by a halogen, a C1-C6 straight or branched fluorenyl group, a C1-C6 straight or branched fluorenyloxy group, unsubstituted or halogenated , C1-C6 a branched or branched fluorenyl group and a C1-C6 linear or branched decyloxy-substituted benzyloxycarbonyl group; preferably each independently selected from the group consisting of hydrogen, halogen, amino, hydroxy, unsubstituted or straight-chained by C2-C4 or Branched alkenyl or 1-3 halogen-substituted C1-C6 straight or branched fluorenyl, unsubstituted or C1-C6 straight or branched substituted by C3-C6 cyclodecyl or 1-3 halogen Alkyloxy of the chain, unsubstituted or substituted by 1-3 halogens, C3-C6 cyclodecyl, unsubstituted or substituted by 1-3 halogens, C3-C6 cyclodecyloxy, unsubstituted or by halogen, C1 -C6 straight or branched fluorenyl, C1-C6 linear or branched decyloxy substituted phenoxy, and unsubstituted or halogenated, C1-C6 straight or branched fluorenyl or C1- C6 straight or branched decyloxy substituted benzyloxy; more preferably C1-C6 straight or branched fluorene, each independently hydrogen, halogen, unsubstituted or substituted by vinyl or 1-3 halogen a C1-C6 straight or branched decyloxy group substituted with a C3-C6 cyclodecyl group or 1-3 halogens, a C3-C6 cyclodecyl group which is unsubstituted or substituted with 1-3 halogens. And C3-C6 cyclodecyloxy which is unsubstituted or substituted by 1-3 halogens Most preferably each independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, ethyl, allyl, methoxy, ethoxy, cyclopropoxy, cyclopropylmethoxy, tert-butoxy, new Pentyloxy, trifluoromethoxy and 2,2,2-trifluoroethoxy; Or the two adjacent substituents of Ri, R ₂ , R ₃ , R ₄ , and R ₅ together with the carbon atom to which the benzene ring is attached may form a hetero atom containing 1 to 3 selected from N, 0 and S. 5-6 membered heterocyclic ring; preferably forming a 5-6 membered heterocyclic ring containing 1 to 2 hetero atoms selected from 0 and S; more preferably forming a dioxole ring;  n = 0, 1, or 2, preferably n = l; R _{6 is} selected from hydrogen, unsubstituted or substituted by halogen, C1-C6 straight or branched fluorenylcarbonyl, and unsubstituted or halogenated, C1-C6 straight or branched fluorenyl, C1-C6 straight chain or Branched methoxy-substituted benzoyl; preferably selected from hydrogen, C1-C4 straight or branched fluorenyl, and C1-C4 straight or branched fluorene unsubstituted or substituted by 1-3 halogens More preferably selected from the group consisting of hydrogen, methyl, acetyl and trifluoroacetyl; R _{7 is} selected from the group consisting of hydrogen, a C1-C6 linear or branched fluorenyl group, and a C1-C6 linear or branched fluorenyloxy group; preferably a hydrazine group selected from hydrogen and a C1-C4 straight or branched chain; More preferably selected from the group consisting of hydrogen and methyl;  * indicates chiral carbon.  The quinone compound according to claim 1, which is a pharmaceutically acceptable salt, a crystalline hydrate, a solvate or a mixture thereof, wherein  ! a C1-C6 straight or branched fluorenyl group selected from the group consisting of hydrogen, halogen, amino, carboxyl, cyano, nitro, hydroxy, unsubstituted or substituted by C2-C6 straight or branched alkenyl or halogen, a C1-C6 straight or branched decyloxy group which is unsubstituted or substituted by a C3-C6 cyclodecyl group or a halogen, a C2-C12 straight or branched alkenyl group which is unsubstituted or substituted by a halogen, unsubstituted or C2-C12 straight or branched alkynyl substituted by halogen, C3-C6 cyclodecyl unsubstituted or substituted by halogen, C3-C6 cyclodecyl unsubstituted or substituted by halogen, unsubstituted or Halogen-substituted C1-C6 straight or branched mercaptocarbonyloxy, unsubstituted or substituted by halogen, C1-C6 straight or branched mercaptocarbonyl, unsubstituted or substituted by halogen C1-C6 straight a benzyloxy group which is unsubstituted or substituted by a halogen, a C 1 -C 6 linear or branched fluorenyl group, a C 1 -C 6 straight or branched fluorenyloxy group, unsubstituted or Halogen, C1-C6 straight or branched fluorenyl, C1-C6 straight or branched decyloxy substituted benzyloxy, and unsubstituted or halogenated, C1-C6 straight or branched垸 base, C1-C6 straight Or branched methoxy-substituted benzyloxycarbonyl; preferably C1-C6 straight or branched chain selected from hydrogen, unsubstituted or substituted by C2-C4 straight or branched alkenyl or 1-3 halogen A fluorenyl group, an unsubstituted or C1-C6 linear or branched decyloxy group substituted by a C3-C6 cyclodecyl group or 1-3 halogens, an unsubstituted or C3-C6 substituted with 1-3 halogens Cyclodecyl, unsubstituted or substituted by 1-3 halogens, C3-C6 cyclodecyloxy, unsubstituted or halogenated, C1-C6 straight or branched fluorenyl, C1-C6 straight or branched a benzyloxy-substituted phenoxy group of the chain, and a benzyloxy group which is unsubstituted or substituted by a halogen, a C1-C6 linear or branched fluorenyl group, a C1-C6 linear or branched fluorenyloxy group; More preferably, a C1-C6 straight or branched fluorenyl group selected from hydrogen, unsubstituted or substituted by a vinyl group or 1-3 halogens, unsubstituted or substituted by a C3-C6 cyclodecyl group or 1-3 halogens a C1-C6 linear or branched decyloxy group, a C3-C6 cyclodecyl group which is unsubstituted or substituted by 1-3 halogens, and a C3-C6 cyclodecyloxy group which is unsubstituted or substituted by 1-3 halogens. Most preferably selected from the group consisting of methyl, ethyl, allyl, methoxy, Group, a cyclopropyloxy group, a cyclopropylmethoxy group, a tert-butoxy group, neopentyl group, trifluoromethoxy and 2,2,2-trifluoro-ethoxy. R _{2 is} selected from hydrogen, halogen, unsubstituted or C1-C6 straight or branched fluorenyl substituted by C2-C6 straight or branched alkenyl or halogen; preferably selected from hydrogen, halogen and unsubstituted or a C2-C4 linear or branched alkenyl or halogen-substituted _{C 1 -C} 4 linear or branched fluorenyl group; more preferably selected from the group consisting of hydrogen, fluorine, chlorine, bromine and unsubstituted or 1-3 halogen Substituted _{C 1 -C} 4 linear or branched fluorenyl; most preferably selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl and ethyl; R _{3 is} selected from hydrogen, halogen, unsubstituted or C1-C6 straight or branched fluorenyl substituted by C2-C6 straight or branched alkenyl or halogen, unsubstituted or substituted by 1-3 halogen C2-C12 linear or branched alkenyl; preferably selected from hydrogen, halogen and C1-C4 straight or branched fluorene unsubstituted or substituted by C2-C4 straight or branched alkenyl or halogen More preferably selected from the group consisting of hydrogen, fluorine, chlorine, bromine, and a C1-C4 straight or branched fluorenyl group which is unsubstituted or substituted by a vinyl group or 1-3 halogens; most preferably selected from the group consisting of hydrogen, methyl, and Base, allyl, fluorine, chlorine and bromine;  a C1-C6 straight or branched fluorenyl group selected from hydrogen, halogen, unsubstituted or substituted by a C2-C6 straight or branched alkenyl or halogen, and C2 unsubstituted or substituted by 1-3 halogens a -C 12 straight or branched alkenyl group; preferably a C 1 -C 4 straight or branched fluorenyl group selected from the group consisting of hydrogen, halogen and unsubstituted or substituted by a C 2 -C 4 straight or branched alkenyl or halogen More preferably, C1-C4 straight or branched fluorenyl, fluorine, chlorine and bromine selected from hydrogen, unsubstituted or substituted by vinyl or 1-3 halogen; more preferably selected from hydrogen, methyl, ethyl , allyl, fluorine, chlorine and bromine; Or R ₃ and R ₄ may, together with the carbon atom to which they are attached, form a 5 to 6 membered heterocyclic ring having 1 to 3 hetero atoms selected from 0 and S; preferably 1 to 2 are selected from 0 And a 5-6 membered heterocyclic ring of a hetero atom of S; more preferably forming a dioxole ring; R _{5 is} selected from hydrogen, halogen, amino, carboxy, cyano, nitro, hydroxy, unsubstituted or C1-C6 straight or branched fluorenyl substituted by C2-C6 straight or branched alkenyl or halogen a C1-C6 straight or branched decyloxy group which is unsubstituted or substituted by a C3-C6 cyclodecyl group or a halogen, a C2-C12 straight or branched alkenyl group which is unsubstituted or substituted by a halogen, unsubstituted or C2-C12 straight or branched alkynyl substituted by halogen, C3-C6 cyclodecyl unsubstituted or substituted by halogen, C3-C6 cyclodecyl unsubstituted or substituted by halogen, unsubstituted or halogenated Substituted C1-C6 straight or branched mercaptocarbonyloxy, unsubstituted or C1-C6 straight or branched carbonyl substituted by halogen, unsubstituted or substituted by halogen, C1-C6 straight or branched oxime a carbonyl group, unsubstituted or substituted by a halogen, a C1-C6 straight or branched fluorenyl group or a C1-C6 straight or branched fluorenyloxy group, unsubstituted or halogenated, C1-C6 straight chain or Branched fluorenyl or C1-C6 linear or branched decyloxy substituted benzyloxy, and unsubstituted or halogenated, C1-C6 straight or branched fluorenyl or C1-C6 straight chain or branched Chain-substituted methoxy group Oxycarbonyl; preferably a C1-C6 straight or branched fluorenyl group unsubstituted or substituted by a C2-C4 straight or branched alkenyl group or 1-3 halogens, unsubstituted or by a C3-C6 ring enthalpy Or a 1-3 halogen-substituted C1-C6 straight or branched decyloxy group, unsubstituted or C3-C6 cyclodecyl substituted by 1-3 halogens, unsubstituted or substituted by 1-3 halogens C3-C6 cyclodecyloxy, unsubstituted or substituted by halogen, C1-C6 straight or branched fluorenyl or C1-C6 straight or branched decyloxy, phenoxy, unsubstituted or halogenated a C1-C6 linear or branched fluorenyl group or a C1-C6 linear or branched decyloxy-substituted benzyloxy group; more preferably a C1 group selected from unsubstituted or substituted by a vinyl group or 1-3 halogens -C6 straight or branched fluorenyl, unsubstituted or C1-C6 straight or branched decyloxy substituted by C3-C6 cyclodecyl or 1-3 halogen, unsubstituted or composed of 1-3 Halogen-substituted C3-C6 cyclodecyl, unsubstituted or C3-C6 cyclodecyloxy substituted by 1-3 halogens; most preferably selected from methyl, ethyl, allyl, methoxy, ethoxy , cyclopropyloxy, cyclopropylmethoxy, tert-butoxy, neopentyloxy, trifluoromethoxy And 2,2,2-trifluoroethoxy. R _{6 is} selected from hydrogen, unsubstituted or substituted by halogen, C1-C6 straight or branched fluorenylcarbonyl, and unsubstituted or halogenated, a C1-C6 linear or branched fluorenyl group, a C1-C6 linear or branched methoxy-substituted benzoyl group; preferably a C1-C4 straight selected from hydrogen and unsubstituted or substituted by 1-3 halogens a chain or branched fluorenylcarbonyl group; preferably selected from the group consisting of hydrogen, acetyl and trifluoroacetyl; R _{7 is} selected from the group consisting of hydrogen, a C1-C6 linear or branched fluorenyl group, and a C1-C6 linear or branched fluorenyloxy group; preferably a hydrogen group and a C1-C4 linear or branched fluorenyl group; Preferably selected from the group consisting of hydrogen and methyl; most preferably hydrogen;  n = 0, 1 or 2, preferably n = 1. The quinone compound according to claim 1, which is a pharmaceutically acceptable salt, a crystalline hydrate, a solvate or a mixture thereof, wherein each of Ri, R ₂ , R ₃ , R ₄ and R ₅ Independently selected from the group consisting of: hydrogen, halogen, unsubstituted or C1-C6 straight or branched fluorenyl substituted by C2-C6 straight or branched alkenyl or halogen, unsubstituted or substituted by halogen a C1-C6 cyclodecyloxy group, a C1-C6 straight or branched decyloxy group which is unsubstituted or substituted by a C3-C6 cyclodecyl group or a halogen; Or the two adjacent substituents of Ri, R ₂ , R ₃ , R ₄ , and R ₅ together with the carbon atom to which the benzene ring is attached form a 5-6 containing 1 to 2 heteroatoms selected from 0 and S. A heterocyclic ring; more preferably a dioxolane ring. The quinone compound according to claim 1, which is a pharmaceutically acceptable salt, a crystalline hydrate, a solvate or a mixture thereof, wherein R _{6 is} selected from hydrogen or C1 which is unsubstituted or substituted by halogen -C6 straight or branched fluorenylcarbonyl. The quinone compound according to claim 1, which is a pharmaceutically acceptable salt, a crystalline hydrate, a solvate or a mixture thereof, wherein Ri, R ₂ , R ₃ and R ₄ R ₅ are each independently § H, F, Cl, Br, unsubstituted or C1-C6 straight or branched fluorenyl, methoxy, ethoxy, substituted by C2-C6 straight or branched alkenyl or halogen Propyloxy, cyclopropoxy, unsubstituted or C1-C6 straight or branched decyloxy substituted by C3-C6 cyclodecyl or halogen (eg (CH ₃ ) ₃ CCH ₂ 0-, (CH ₃ ) ₃ CO-, (CF ₃ ) ₃ CO -). The quinone compound according to claim 1, which is a pharmaceutically acceptable salt, a crystalline hydrate, a solvent Or a mixture thereof, wherein at least one of Ri, R ₂ , R ₄ , R ₅ is a C1-C6 straight chain which is unsubstituted or substituted by a C2-C6 linear or branched alkenyl group or a halogen or Branched fluorenyl, C3-C6 cyclodecyloxy which is unsubstituted or substituted by halogen, C1-C6 straight or branched decyloxy which is unsubstituted or substituted by C3-C6 cyclodecyl or halogen. The quinone compound according to claim 6, which is a pharmaceutically acceptable salt, a crystalline hydrate, a solvate or a mixture thereof, wherein at least one of Ri, R ₂ , R ₃ and R ₄ R ₅ One selected from the group consisting of cyclopropoxy, methoxy, ethoxy, propoxy, (CH ₃ ) ₃ CCH ₂ 0-, (CH ₃ ) ₃ CO-, (CF ₃ ) ₃ CO-.  The quinone compound according to claim 1 or 2, which is a pharmaceutically acceptable salt, a crystalline hydrate, a solvate or a mixture thereof, wherein the quinone compound is selected from the group consisting of:

0868.0/M0ZN3/X3d

OS6 LO/nOZ D/13d Jf606lM0Z OAV The quinone compound according to any one of claims 1 to 8, which is a pharmaceutically acceptable salt, a crystalline hydrate, a solvate or a mixture thereof, wherein the quinone compound is an R type different The conformation, the S-isomer or the racemate are preferably the R-isomer. The quinone compound according to any one of claims 1 to 8, which is a pharmaceutically acceptable salt, a crystalline hydrate, a solvate or a mixture thereof, wherein the pharmaceutically acceptable salt And a non-toxic salt formed by reacting with an inorganic acid or an organic acid. Preferably, the inorganic acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, aminosulfonic acid and phosphoric acid, and the organic acid is selected from the group consisting of propionic acid, Oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid and aspartic acid. 1 1. A method for preparing a terpenoid according to claims 1 - 10, as shown in Reaction Scheme 3

 Reaction route three  Step 4a Intermediate (II) and intermediate (III) are subjected to reductive amination to give compound 4a;  Step 4b Compound 4a is subjected to a hydrolysis reaction to obtain a compound 4b;  Step 4c: Compound 4b is subjected to a hydrolysis reaction to obtain a compound 4c; or  Step 4d, compound 4a and benzyl bromide are subjected to nucleophilic substitution reaction to obtain compound 4d;  Step 4e compound 4d is subjected to a hydrolysis reaction to obtain a compound 4e;  Step 4f: Compound 4e is subjected to a hydrolysis reaction to obtain a compound 4f;  Step 4g of compound 4f and acylation reagent acylation reaction to obtain compound 4g;  Step 4h Compound 4g is subjected to hydrogenation debenzylation to give compound 4h; The definition of RR ₇ is the same as defined in the corresponding claims, except that R _{6 is} not hydrogen. The preparation method according to claim 11, wherein the preparation method of the intermediate (II) is as shown in Reaction Scheme 1, and includes:

 Reaction route one  Step la: nucleophilic substitution reaction of compound la with methyl bromoacetate to obtain compound lb;  Step lb: compound lb is transesterified with hydrazine, hydrazine-dimethylhydroxylamine hydrochloride to obtain compound lc; step lc: compound lc is subjected to reduction reaction to obtain compound Id;  In the middle

 Reaction route two Step 3a _: Compound 3a is subjected to nucleophilic substitution reaction with 2-bromo-1-ethanol or 3-bromo-1-propanol or 4-bromo-1-butanol to obtain compound 3b; Step 3b _: compound 3b is acylated with an acylating reagent to obtain compound 3c; Step 3c _: Compound 3c is subjected to a formylation reaction with hydrazine, hydrazine-dimethylformamide to obtain a compound 3d;  Step 3d: compound 3d is condensed with nitroacetamidine to obtain compound 3e;  Step 3e: Compound 3e is subjected to a reduction reaction to obtain a compound 3f;  Step 3f: Compound 3f is subjected to formylation with hydrazine, hydrazine-dimethylformamide to obtain compound 2a; Step 2a _: Compound 2a is subjected to an oxidation reaction to obtain a compound 2b; Step 2b _: compound 2b and hydroxylamine hydrochloride condensation reaction to obtain compound 2c;  Step 2c: Compound 2c is subjected to a reduction reaction to obtain a compound 2d;  Step 2d: Compound 2d is resolved to obtain compound 2e and compound 2f; Wherein, the definition of Ri~R ₇ is the same as defined in claim 6.  A pharmaceutical composition comprising a therapeutically effective amount of an anthraquinone compound according to any one of claims 1 to 10, and a pharmaceutically acceptable salt, a crystalline hydrate thereof, and a solvate thereof One or more, and one or more pharmaceutically acceptable carriers.  The steroid compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, a crystalline hydrate or a solvate thereof for the preparation of a medicament for treating a disease associated with αΐ-adrenergic receptor Use in.  The use according to claim 14, wherein the disease associated with the αΐ-adrenergic receptor is selected from the group consisting of a urinary system disease, particularly selected from the group consisting of benign prostatic hyperplasia, urinary retention, and bladder outlet obstruction.