CN107098846A

CN107098846A - N- acyl sulfonamides class FBPase inhibitor, its preparation method, pharmaceutical composition and purposes

Info

Publication number: CN107098846A
Application number: CN201610105864.9A
Authority: CN
Inventors: 徐柏玲; 申竹芳; 别建波; 穆永钊; 陈华龙; 刘率男; 周洁; 李彩娜; 曹冉; 环奕; 孙淑娟
Original assignee: Institute of Materia Medica of CAMS
Current assignee: Institute of Materia Medica of CAMS
Priority date: 2016-02-26
Filing date: 2016-02-26
Publication date: 2017-08-29
Anticipated expiration: 2036-02-26
Also published as: CN107098846B

Abstract

The invention discloses the N- acyl sulfonamides class FBPase inhibitor and its preparation method and pharmaceutical composition and purposes of new construction.Specifically; the present invention relates to the N- acyl sulfonamides class FBPase inhibitor shown in formula I; its officinal salt; and preparation method thereof; composition containing such one or more compound; with purposes of such compound in preparing FBPase inhibitor or treating the relevant disease medicaments of FBPase, and the purposes in prevention and/or treatment diabetes medicament is prepared.

Description

N- acyl sulfonamides class FBPase inhibitor, its preparation method, pharmaceutical composition and Purposes

Technical field

The present invention relates to the N- acyl sulfonamides class FBPase inhibitor of the new construction shown in Formulas I, its officinal salt, and its Preparation method, the composition containing such one or more compound, and such compound are suppressing FBPase and treatment Disease relevant FBPase, and the purposes in preparing, preventing and/or treat diabetes medicament.

Background technology

Diabetes are a kind of chronic metabolic diseases of polygenes regulation and control, are mainly shown as lasting hyperglycaemia and glycosuria. Lasting hyperglycaemia can cause the generation of many complication, such as retina, kidney, nervous system lesion and vascular complication. The diabetes mellitus in China incidence of disease is increased rapidly, it is predicted that diabetes mellitus in China patient has exceeded 92,000,000, there are about 1.48 hundred million people is sugar Sick High risk group (New.Engl.J.Med., 2010,362 of urine:1090-1101).

Diabetes are divided into two types, insulin-dependent (I types) and non-insulin-depending type (II types), wherein II types sugar Urine patient accounts for the 90%~95% of diabetic's sum.Biological study shows, leads diabetogenic main pathological basis It is hypoinsulinism, insulin resistance and Hepatic glucose production increase.The medicine clinically applied at present mainly has two classes： One is to be directed to hypoinsulinism, such as：Sulfonylureas and meglitinide Drugs Promoting Insulin Secretion；Two be to improve insulin resistance, Such as：Study of Thiazolidinedione derivatives as Insulin Sensitizer.Up to the present, the antidiabetic of endogenous glucose generation is not reduced also Thing is applied to clinic.Melbine can reduce the output of hepatic glucose, but the molecular target of effect is not clear.

There are some researches show endogenous glucose generation increase is to cause the elevated main original of diabetic's fasting blood-glucose Cause.Endogenous glucose is mainly derived from liver.Hepatic glucose production has two kinds of approach, and one kind is to be endogenously synthesized grape Sugar, i.e. gluconeogenesis (gluconeogenesis)；Another is hepatic glycogenolytic (glycogenolysis).Therefore, pass through Regulate and control gluconeogenesis approach, reduce the generation of endogenous glucose, be the new of potential exploitation novel mechanism antidiabetic medicine Strategy.

Gluconeogenesis is, by the carbon precursor of lactic acid, glycine and glycerine etc. three, under the catalytic action of a variety of enzymes, to convert For the process of glucose.During gluconeogenesis, ester of Harden Young enzyme (Fructose-1,6-bisphosphatase, FBPase) catalysis fructose-1,6-diphosphate is converted into fructose-6-phosphate salt, and discharges a molecule phosphoric acid.The catalytic reaction It is one of ratedeterming step of endogenous glucose generation, suppresses FBPase activity, the generation of endogenous glucose can be reduced, drops Low blood glucose level.Therefore, FBPase inhibitor is likely to become the antidiabetic medicine of novel mechanism, especially empty in reduction In terms of abdomen blood sugar level, with significantly more meaning.

Up to the present, many researchers have carried out the research of FBPase inhibitor, it was recently reported that various structures type FBPase inhibitor.2003, Pfizer drugmakers obtained indol-carbocylic acids compound by high flux screening, right FBPase inhibitory activity IC₅₀Value is in micromolar levels (Bioorg.Med.Chem.Lett., 2003,13:2055-2058).2006 Year, von Geldern et al. report benzoxazole -2- benzenesulfonamides, to FBPase inhibitory activity IC₅₀Value exists 10^-6-10^-7Mol level (Bioorg.Med.Chem.Lett., 2006,16:1811-1815).2010, Roche pharmacy was public Department reports the sulfonylurea FBPase inhibitor that the thiazole found by high flux screening replaces, its inhibitory activity IC₅₀Value exists 10^-7-10^-8Mol level (Bioorg.Med.Chem.Lett., 2010,20:594-599).2007-2010, Metbasis Drugmaker reports finds AMP analogs using structure-based SARS drug design strategy, finds FBPase inhibitor, warp After constantly structure optimization, they have obtained benzimidazole FBPase inhibitor (J.Am.Chem.Soc., 2007,129: 15480-15490；J.Med.Chem.,2010,53:441-451) and thiazoles FBPase inhibitor (J.Am.Chem.Soc., 2007,129:15491-15502；J.Med.Chem.,2011,54:153-165), MB07803 is the phosphoric acid of thiazole compound Diamides prodrug, is currently under II phases clinical research (US, 225259 A1 [P] .2007-09-27.).

It is reported in spite of the FBPase inhibitor of various structures type, but up to the present, only Metabasis systems FBPase the inhibitor Cs S-917 and MB07803 of medicine company research and development enter II phase clinical researches.But the two candidate agents contain There is phosphonyl group, be to enter clinical research with phosphonic acids diamides prodrug forms, to overcome its phosphonic acids active compound (MB05032) orally raw The problem of thing availability low (4%).Due to the internal metabolic process that aforementioned prodrugs are complicated, cause its clinical research prospect more difficult To expect.Therefore, FBPase inhibitor of the medicine for good properties is found as the antidiabetic medicine of new mechanism with very heavy The clinical meaning wanted.

Present invention design has synthesized the N- acyl sulfonamides class FBPase inhibitor of new construction, does not contain phosphonic acids or phosphate Group, to obtain there is medicine to have established architecture basics for well-behaved, Orally-administrable FBPase inhibitor.It is contemplated that seeking Look for that anti-diabetic activity is strong, medicine is for property is preferable, orally active antidiabetic thing.

The content of the invention

Present invention solves the technical problem that be provide Formulas I shown in N- acyl sulfonamides analog derivative and can physiologically connect The salt received, its preparation method, pharmaceutical composition and its preparing FBPase inhibitor and its potential medicinal usage, preparing Purposes in antidiabetic medicine.

To solve the technical problem of the present invention, the invention provides following technical scheme：

The first aspect of technical solution of the present invention there is provided N- acyl sulfonamides analog derivative as shown in formula I and its Physiologically acceptable salt：

In Formulas I,

A is selected from NR₁、O、S、Se、CR₈R₉, C=O, wherein R₁、R₈And R₉Independently selected from hydrogen, substituted or non-substituted C1-6 Straight or branched alkyl, substituted or non-substituted C2-6 straight or branched alkenyl or alkynyls, wherein substituent be selected from F, Cl, Br, CN、ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, cyclopropyl, ring third Methylene, cyclobutyl, oxetanylmethoxy, cyclopenta, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、 Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl；

B is selected from CR₃, N, wherein R₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, acetenyl, third Alkynyl, cyclopropyl, the methylene of ring third, F, Cl, Br, substitution C1-3 straight or branched alkyls, wherein substituent be selected from F, Cl, Br、CN、ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, methyl, ethyl；

D is selected from CR₄、N；E is selected from CR₅、N；F is selected from CR₆、N；G is selected from CR₇、N；D, E, F, G can be individually for N, two it is same When be N and/or three while being N；R₄And R₇It is asynchronously hydrogen；

R₄And R₇Following atom or group or structure fragment are independently selected from, including

(1)H、F、Cl、Br、CN、NO₂、CONRc₁Rd₁、COORc₂、SO₂Rc₃、SO₂NRc₄Rd₂, wherein described Rc₁、Rd₁、 Rc₂、Rc₃、Rc₄、Rd₂Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；

(2) substituted or non-substituted C1-8 straight or branched alkyls, substituted or non-substituted C2-8 straight or branched alkenyls Or alkynyl, wherein described substituent is selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、 NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、 Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；

(3) substituted or non-substituted C3-7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, substitution or The azacycloalkyl of non-substituted 3-8 yuan of rings, wherein described substituent be selected from C1-5 straight or branched alkyls, F, Cl, Br, CN、ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkane Base, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；It can contain 1 in the oxacycloalkyl and azacycloalkyl of 3-8 yuan of rings Individual hetero atom, multiple hetero atoms can also be contained simultaneously；

(4) substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、 Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched Alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, can in five yuan of heteroaromatics To be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five First heteroaromatic can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected from 1,2,3；Its Described in halogen include F, Cl, Br；

(5)ORe₁、NRe₂Rf₁、SRe₃、NRe₄CORf₂、NRe₅COORf₃、NRe₆SO₂Rf₄, wherein described Re₁、Re₂、 Rf₁、Re₃、Re₄、Rf₂、Re₅、Rf₃、Re₆、Rf₄Independently selected from H, substituted or non-substituted C1-8 straight or branched alkyls, substitution Or non-substituted C2-8 straight or brancheds alkenyl, substituted or non-substituted C2-8 straight or branched alkynyls, wherein described substitution Base is selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、 NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；

Described Re₁、Re₂、Rf₁、Re₃、Re₄、Rf₂、Re₅、Rf₃、Re₆、Rf₄Also can be independently selected from substituted or non-substituted C3-7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, the azacyclo- of substituted or non-substituted 3-8 yuan of rings Alkyl, wherein described substituent is selected from C1-5 straight or branched alkyls, F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、 COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、 Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, Cyclobutyl, cyclopenta；Can also simultaneously it contain containing 1 hetero atom in the oxacycloalkyl and azacycloalkyl of 3-8 yuan of rings There are multiple hetero atoms；

(6)OAr_a1、NRg₁Ar_a2、SAr_a3、CH₂Ar_a4、COAr_a5、NRg₂COAr_a6、NRg₃COOAr_a7、NRg₄SO₂Ar_a8, its Described in Rg₁、Rg₂、Rg₃、Rg₄Selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, ring penta Base；Described Ar_a1、Ar_a2、Ar_a3、Ar_a4、Ar_a5、Ar_a6、Ar_a7、Ar_a8Selected from substituted or non-substituted phenyl, substitution or non-take The nitrogenous hexa-atomic heteroaromatic in generation, five yuan of substituted or non-substituted heteroaromatics, wherein substituent be selected from C1-4 straight or branched alkyls, The C1-4 straight or branched alkyls of halogen substitution, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、 COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂) nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb ′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, ring penta Base；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, in five yuan of heteroaromatics can be monosubstituted or polysubstituted；Hexa-atomic virtue is miscellaneous Ring can also contain multiple nitrogen-atoms containing 1 N atom；Five yuan of heteroaromatics be able to can also contain containing a hetero atom There are multiple hetero atoms, hetero atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br；

(7)OCH₂Ar_a9、NHCH₂Ar_a10、SCH₂Ar_a11、CH₂CH₂Ar_a12, described Ar_a9、Ar_a10、Ar_a11、Ar_a12It is selected from Substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, five yuan of substituted or non-substituted heteroaromatics, wherein Substituent is selected from C1-4 straight or branched alkyls, F, Cl, Br, NO that C1-4 straight or branched alkyls, halogen replace₂, CN, methylene Two epoxides, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、Ra′₅、Rb′₂、 Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched alkyl, ring third Base, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, in five yuan of heteroaromatics can singly take Generation or it is polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five yuan of heteroaromatics It can also contain multiple hetero atoms containing a hetero atom, hetero atom is selected from O, N, S；N is selected from 1,2,3；It is wherein described Halogen includes F, Cl, Br；

R₅And R₆Following atom or group or structure fragment are independently selected from, including

(1)H、F、Cl、Br、CN、NO₂、CONRh₁Ri₁、COORh₂、SO₂Rh₃、SO₂NRh₄Ri₂, wherein described Rh₁、Ri₁、 Rh₂、Rh₃、Rh₄、Ri₂Independently selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third, cyclobutyl；

(2) substituted or non-substituted C1-4 straight or branched alkyls, substituted or non-substituted C2-4 straight or brancheds alkenyl, Substituted or non-substituted C2-4 alkynyls, wherein substituent are selected from F, Cl, Br, CN, NO₂、CONRh₁Ri₁、COORh₂、SO₂Rh₃、 SO₂NRh₄Ri₂, wherein described Rh₁、Ri₁、Rh₂、Rh₃、Rh₄、Ri₂Independently selected from H, methyl, ethyl, propyl group, isopropyl, ring Propyl group, the methylene of ring third, cyclobutyl；

(3) substituted or non-substituted C3-6 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-6 yuan of rings, substitution or The azacycloalkyl of non-substituted 3-6 yuan of rings, wherein substituent are selected from methyl, ethyl, propyl group, isopropyl, CF₃、CH₂CF₃、 CHF₂、F、Cl、Br、CN、CONRh₁Ri₁、COORh₂、SO₂Rh₃、SO₂NRh₄Ri₂、ORh₅、SRh₆、NRh₇Ri₃、NRh₈CORi₄、 NRh₉COORi₅, wherein described Rh₁、Ri₁、Rh₂、Rh₃、Rh₄、Ri₂、Rh₅、Rh₆、Rh₇、Ri₃、Rh₈、Ri₄、Rh₉、Ri₅Independently Selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third, cyclobutyl；The oxacycloalkyl or 3-6 of 3-6 yuan of rings It can also can simultaneously contain multiple hetero atoms containing 1 hetero atom in the azacycloalkyl of yuan of rings；

(4)ORj₁、NRj₂Rk₁、SRj₃、NRj₄CORk₂、NRj₅COORk₃、NRj₆SO₂Rk₄, wherein described Rj₁、Rj₂、 Rk₁、Rj₃、Rj₄、Rk₂、Rj₅、Rk₃、Rj₆、Rk₄Independently selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third Base, cyclobutyl, CF₃, CH₂CF₃, CHF₂；

R is selected from following group or structure fragment：

(1) substituted or non-substituted C1-10 straight or branched alkyls, substituted or non-substituted C2-10 straight or branched alkene Base, substituted or non-substituted C2-10 straight or branched alkynyls, wherein described substituent is selected from F, Cl, Br, CN, ORx₁、SRx₂、 NRx₃Ry₁、NRx₄CORy₂、COORx₅、CONRx₆Ry₃、NRx₇COORy₄、SO₂NRx₈Ry₅, described Rx₁、Rx₂、Rx₃、Ry₁、Rx₄、 Ry₂、Rx₅、Rx₆、Ry₃、Rx₇、Ry₄、Rx₈、Ry₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, Cyclobutyl, cyclopenta；

(2) substituted or non-substituted C3-7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, substitution or The azacycloalkyl of non-substituted 3-8 yuan of rings, wherein described substituent be selected from C1-5 straight or branched alkyls, F, Cl, Br, CN、ORx₁、SRx₂、NRx₃Ry₁、NRx₄CORy₂、COORx₅、CONRx₆Ry₃、NRx₇COORy₄、SO₂NRx₈Ry₅, described Rx₁、 Rx₂、Rx₃、Ry₁、Rx₄、Ry₂、Rx₅、Rx₆、Ry₃、Rx₇、Ry₄、Rx₈、Ry₅Independently selected from H, C1-4 straight or branched alkyl, ring Propyl group, the methylene of ring third, cyclobutyl, cyclopenta；Can be with the oxacycloalkyl of 3-8 yuan of rings and the azacycloalkyl of 3-8 yuan of rings Containing 1 hetero atom, multiple hetero atoms can also be contained simultaneously；

(3) substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be monosubstituted or polysubstituted in phenyl ring, nitrogenous hexa-atomic heteroaromatic and five yuan of heteroaromatics；It is hexa-atomic Heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five yuan of heteroaromatics can also may be used containing a hetero atom So that containing multiple hetero atoms, hetero atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br；

(4) condensed ring or condensed hetero ring of substituted or non-substituted armaticity, substituted or non-substituted nonaromatic condensed ring or Condensed hetero ring, including substituted or non-substituted naphthalene nucleus, substituted or non-substituted benzo hexa-member heterocycle, substituted or non-substituted benzo five Circle heterocycles, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be on wherein described naphthalene nucleus, benzo hexa-member heterocycle or benzo five-membered heterocycle it is monosubstituted or It is polysubstituted；Benzo hexa-member heterocycle or benzo five-membered heterocycle can also contain multiple hetero atoms, miscellaneous original containing a hetero atom Son is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br.

According to formula I of the present invention, currently preferred compound and with physiologically acceptable salt, including but not limited to lead to Compound shown in formula (IA)：

In Formulas I A,

B is selected from CR₃, N, wherein R₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, acetenyl, third Alkynyl, cyclopropyl, the methylene of ring third, F, Cl, Br, substitution C1-3 straight or branched alkyls, wherein substituent be selected from F, Cl, Br、CN、ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, methyl, ethyl；R₄And R₇ It is asynchronously hydrogen；

(3) substituted or non-substituted C3-7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, substitution or The azacycloalkyl of non-substituted 3-8 yuan of rings, wherein described substituent be selected from C1-5 straight or branched alkyls, F, Cl, Br, CN、ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkane Base, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；It can contain 1 in the oxacycloalkyl or azacycloalkyl of 3-8 yuan of rings Individual hetero atom, multiple hetero atoms can also be contained simultaneously；

Described Re₁、Re₂、Rf₁、Re₃、Re₄、Rf₂、Re₅、Rf₃、Re₆、Rf₄Also can be independently selected from substituted or non-substituted C3-7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, the azacyclo- of substituted or non-substituted 3-8 yuan of rings Alkyl, wherein described substituent is selected from C1-5 straight or branched alkyls, F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、 COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、 Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, Cyclobutyl, cyclopenta；Can also simultaneously it contain containing 1 hetero atom in the oxacycloalkyl or azacycloalkyl of 3-8 yuan of rings There are multiple hetero atoms；

(2) substituted or non-substituted C1-4 straight or branched alkyls, substituted or non-substituted C2-4 straight or brancheds alkenyl, Substituted or non-substituted C2-4 straight or branched alkynyls, wherein substituent are selected from F, Cl, Br, CN, NO₂、CONRh₁Ri₁、 COORh₂、SO₂Rh₃、SO₂NRh₄Ri₂, wherein described Rh₁、Ri₁、Rh₂、Rh₃、Rh₄、Ri₂Independently selected from H, methyl, ethyl, Propyl group, isopropyl, cyclopropyl, the methylene of ring third, cyclobutyl；

(3) substituted or non-substituted C3-6 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-6 yuan of rings, substitution or The azacycloalkyl of non-substituted 3-6 yuan of rings, wherein substituent are selected from methyl, ethyl, propyl group, isopropyl, CF₃、CH₂CF₃、 CHF₂、F、Cl、Br、CN、CONRh₁Ri₁、COORh₂、SO₂Rh₃、SO₂NRh₄Ri₂、ORh₅、SRh₆、NRh₇Ri₃、NRh₈CORi₄、 NRh₉COORi₅, wherein described Rh₁、Ri₁、Rh₂、Rh₃、Rh₄、Ri₂、Rh₅、Rh₆、Rh₇、Ri₃、Rh₈、Ri₄、Rh₉、Ri₅

Independently selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third, cyclobutyl；3-6 yuan of rings It can also can simultaneously contain multiple hetero atoms containing 1 hetero atom in oxacycloalkyl or the azacycloalkyl of 3-6 yuan of rings；

(4)ORj₁、NRj₂Rk₁、SRj₃、NRj₄CORk₂、NRj₅COORk₃、NRj₆SO₂Rk₄, wherein described Rj₁、Rj₂、 Rk₁、Rj₃、Rj₄、Rk₂、Rj₅、Rk₃、Rj₆、Rk₄Independently selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third Base, cyclobutyl, CF₃, CH₂CF₃, CHF₂；R is selected from following group or structure fragment：

(2) substituted or non-substituted C3-7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, substitution or The azacycloalkyl of non-substituted 3-8 yuan of rings, wherein described substituent be selected from C1-5 straight or branched alkyls, F, Cl, Br, CN、ORx₁、SRx₂、NRx₃Ry₁、NRx₄CORy₂、COORx₅、CONRx₆Ry₃、NRx₇COORy₄、SO₂NRx₈Ry₅, described Rx₁、 Rx₂、Rx₃、Ry₁、Rx₄、Ry₂、Rx₅、Rx₆、Ry₃、Rx₇、Ry₄、Rx₈、Ry₅Independently selected from H, C1-4 straight or branched alkyl, ring Propyl group, the methylene of ring third, cyclobutyl, cyclopenta；Can be with the oxacycloalkyl of 3-8 yuan of rings or the azacycloalkyl of 3-8 yuan of rings Containing 1 hetero atom, multiple hetero atoms can also be contained simultaneously；

(3) substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be monosubstituted or polysubstituted in phenyl ring, nitrogenous hexa-atomic heteroaromatic or five yuan of heteroaromatics；It is hexa-atomic Heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five yuan of heteroaromatics can also may be used containing a hetero atom So that containing multiple hetero atoms, hetero atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br；

According to formula IA of the present invention, currently preferred compound and physiologically acceptable salt including but not limited to lead to Compound shown in formula (IAa)：

In Formulas I Aa,

A and substituent R, R₄, R₅, R₆, R₇Define same formula (IA) definition；R₄And R₇It is asynchronously hydrogen；R₃Selected from hydrogen, first Base, ethyl, propyl group, isopropyl, vinyl, acrylic, acetenyl, propinyl, cyclopropyl, the methylene of ring third, F, Cl, Br, take The C1-3 straight or branched alkyls in generation, wherein substituent are selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、 CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、 Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, methyl, ethyl.

According to formula IAa of the present invention, currently preferred compound and physiologically acceptable salt including but not limited to lead to Compound shown in formula (IAa-1)：

In Formulas I Aa-1,

R₁Selected from hydrogen, substituted or non-substituted C1-6 straight or branched alkyls, substituted or non-substituted C2-6 straight chains or branch Alkenyl or alkynyl, wherein substituent are selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、 NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, cyclopropyl, the methylene of ring third, cyclobutyl, oxetanylmethoxy, cyclopenta, wherein Described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight chain or branch Alkyl group, cyclopropyl, the methylene of ring third, cyclobutyl；

R₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, acetenyl, propinyl, cyclopropyl, ring Third methylene, F, Cl, Br, the C1-3 straight or branched alkyls of substitution, wherein substituent are selected from F, Cl, Br, CN, ORa₁、SRa₂、 NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、 Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, methyl, ethyl；

Substituent R, R₄, R₅, R₆, R₇Define same formula (IAa) definition；R₄And R₇It is asynchronously hydrogen.

According to formula IAa-1 of the present invention, currently preferred compound and physiologically acceptable salt include but is not limited to Compound shown in formula (IAa-1a)：

In Formulas I Aa-1a,

Substituent R, R₅, R₆, R₇Define the definition with formula IAa-1；

Y is selected from O, S, NRp₁、CH₂、CO、NRp₂CO、OCH₂、NHCH₂、SCH₂、CH₂CH₂；Wherein described Rp₁、Rp₂It is selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；

Ar₁Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic is substituted or non-substituted Five yuan of heteroaromatics, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、 SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、 Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 Straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, five yuan Can be monosubstituted or polysubstituted in heteroaromatic；Hexa-atomic heteroaromatic be able to can also contain multiple containing 1 N atom Nitrogen-atoms；Five yuan of heteroaromatics can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected From 1,2,3；Wherein described halogen includes F, Cl, Br.

According to formula IAa-1a of the present invention, currently preferred compound and physiologically acceptable salt, including but do not limit In the compound shown in formula (IAa-1a-1)：

In Formulas I Aa-1a-1,

R'₁Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, CHF₂、CF₃、CH₂CF₃, cyclopropyl, the methylene of ring third, oxa- Cyclobutyl；

Y is selected from O, S, NH, CH₂、CO、NHCO、OCH₂、NHCH₂、SCH₂、CH₂CH₂；

Ar₁Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic is substituted or non-substituted Five yuan of heteroaromatics, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、 SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、 Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 Straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, five yuan Can be monosubstituted or polysubstituted in heteroaromatic；Hexa-atomic heteroaromatic be able to can also contain multiple containing 1 N atom Nitrogen-atoms；Five yuan of heteroaromatics can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected From 1,2,3；Wherein described halogen includes F, Cl, Br；

R'₇Selected from following atom or group or structure fragment, including

H、F、Cl、Br、CN、NO₂、CONH₂、CONHCH₃、CON(CH₃)₂、SO₂CH₃、SO₂NH₂、SO₂NHCH₃, methyl, second Base, CF₃、CHF₂、CH₂CF₃, cyclopropyl, OCH₃、OCF₃、OCF₂CH₃、OCH₂CF₃、NH₂、NHCH₃、N(CH₃)₂、NHCOCH₃、 NHCOOCH₃；

R'₅And R'₆Following atom or group or structure fragment are independently selected from, including

H、F、Cl、Br、CN、NO₂、CONH₂、CONHCH₃、CON(CH₃)₂、SO₂CH₃、SO₂NH₂、SO₂NHCH₃, methyl, second Base, acetenyl, vinyl, propinyl, acrylic, CF₃、CHF₂、CH₂CF₃, cyclopropyl, methylene cyclopropyl, OCH₃、 OCH₂CH₃、OCF₃、OCF₂CH₃、OCH₂CF₃、NH₂、NHCH₃、N(CH₃)₂、NHCOCH₃、NHCOOCH₃；

Ar' is selected from following group or structure fragment：

(1) substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be monosubstituted or polysubstituted in phenyl ring, nitrogenous hexa-atomic heteroaromatic and five yuan of heteroaromatics；It is hexa-atomic Heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five yuan of heteroaromatics can also may be used containing a hetero atom So that containing multiple hetero atoms, hetero atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br；

(2) condensed ring or condensed hetero ring of substituted or non-substituted armaticity, substituted or non-substituted nonaromatic condensed ring or Condensed hetero ring, including substituted or non-substituted naphthalene nucleus, substituted or non-substituted benzo hexa-member heterocycle, substituted or non-substituted benzo five Circle heterocycles, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be on wherein described naphthalene nucleus, benzo hexa-member heterocycle or benzo five-membered heterocycle it is monosubstituted or It is polysubstituted；Benzo hexa-member heterocycle or benzo five-membered heterocycle can also contain multiple hetero atoms, miscellaneous original containing a hetero atom Son is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br.

According to formula IAa-1a-1 of the present invention, currently preferred compound and physiologically acceptable salt, including but not It is limited to the compound shown in formula (IAa-1a-1a)：

In Formulas I Aa-1a-1a,

Ar' is selected from following group or structure fragment：

According to formula IAa-1a-1 of the present invention, currently preferred compound and its physiologically acceptable salt, including but It is not limited to the compound shown in formula (IAa-1a-1b)：

In Formulas I Aa-1a-1b,

Ar' is selected from following group or structure fragment：

According to formula IAa-1 of the present invention, currently preferred compound and its physiologically acceptable salt, including but do not limit In the compound shown in formula (IAa-1b)：

In Formulas I Aa-1b,

Substituent R, R₅, R₆, R₇Define the definition with formula IAa-1；

Ar₂Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic is substituted or non-substituted Five yuan of heteroaromatics, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、 SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、 Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 Straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, five yuan Can be monosubstituted or polysubstituted in heteroaromatic；Hexa-atomic heteroaromatic be able to can also contain multiple containing 1 N atom Nitrogen-atoms；Five yuan of heteroaromatics can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected From 1,2,3；Wherein described halogen includes F, Cl, Br.

According to formula IAa of the present invention, currently preferred compound and its physiologically acceptable salt include but is not limited to Compound shown in formula (IAa-2)：

In Formulas I Aa-2,

X is selected from O, S, Se, C=O；

Substituent R, R₄, R₅, R₆, R₇Define the definition with formula IAa；R₄And R₇It is asynchronously hydrogen.

According to formula IAa-2 of the present invention, currently preferred compound and its physiologically acceptable salt, including but do not limit In the compound shown in formula (IAa-2a)：

In Formulas I Aa-2a,

X is selected from O, S, Se, C=O；

Ar₃Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic is substituted or non-substituted Five yuan of heteroaromatics, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、 SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、 Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 Straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, five yuan Can be monosubstituted or polysubstituted in heteroaromatic；Hexa-atomic heteroaromatic be able to can also contain multiple containing 1 N atom Nitrogen-atoms；Five yuan of heteroaromatics can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected From 1,2,3；Wherein described halogen includes F, Cl, Br；

Substituent R, R₄, R₅, R₆Define the definition with formula IAa-2.

According to formula IAa-2a of the present invention, currently preferred compound and its physiologically acceptable salt, including but not It is limited to the compound shown in formula (IAa-2a-1)：

In Formulas I Aa-2a-1,

X is selected from O, S, Se, C=O；

R'₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, CHF₂、CF₃、CH₂CF₃, cyclopropyl, the methylene of ring third, oxa- Cyclobutyl；

R'₄Selected from following atom or group or structure fragment, including

Ar' is selected from following group or structure fragment：

According to formula IAa-2a-1 of the present invention, currently preferred compound and its physiologically acceptable salt, including but It is not limited to the compound shown in formula (IAa-2a-1a)：

In Formulas I Aa-2a-1a,

X is selected from O, S, Se, C=O；

Ar' is selected from following group or structure fragment：

According to formula IA of the present invention, currently preferred compound and its physiologically acceptable salt include but is not limited to Compound shown in formula (IAb)：

In Formulas I Ab,

A and substituent R, R₄, R₅, R₆, R₇Define the definition with formula IA.

According to formula IAb of the present invention, currently preferred compound and its physiologically acceptable salt include but is not limited to Compound shown in formula (IAb-1)：

In Formulas I Ab-1,

Substituent R, R₄, R₅, R₆, R₇Define the definition with formula IAb；R₄And R₇It is asynchronously hydrogen.

According to formula IAb-1 of the present invention, currently preferred compound and its physiologically acceptable salt, including but do not limit In the compound shown in formula (IAb-1a)：

In Formulas I Ab-1a,

Substituent R, R₅, R₆, R₇Define the definition with formula IAb-1；

Ar₄Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic is substituted or non-substituted Five yuan of heteroaromatics, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、 SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、 Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 Straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, five yuan Can be monosubstituted or polysubstituted in heteroaromatic；Hexa-atomic heteroaromatic be able to can also contain multiple containing 1 N atom Nitrogen-atoms；Five yuan of heteroaromatics can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected From 1,2,3；Wherein described halogen includes F, Cl, Br.

According to formula IAb-1a of the present invention, currently preferred compound and its physiologically acceptable salt, including but not It is limited to the compound shown in formula (IAb-1a-1)：

In Formulas I Ab-1a-1,

Ar₄Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic is substituted or non-substituted Five yuan of heteroaromatics, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl、Br、NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、 SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、 Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 Straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, five yuan Can be monosubstituted or polysubstituted in heteroaromatic；Hexa-atomic heteroaromatic be able to can also contain multiple containing 1 N atom Nitrogen-atoms；Five yuan of heteroaromatics can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected From 1,2,3；Wherein described halogen includes F, Cl, Br；

R'₇Selected from following atom or group or structure fragment, including

Ar' is selected from following group or structure fragment：

According to formula IAb-1a-1 of the present invention, currently preferred compound and its physiologically acceptable salt, including but It is not limited to the compound shown in formula (IAb-1a-1a)：

In Formulas I Ab-1a-1a,

Ar' is selected from following group or structure fragment：

According to formula IAb of the present invention, currently preferred compound and its physiologically acceptable salt include but is not limited to Compound shown in formula (IAb-2)：

In Formulas I Ab-2,

X is selected from O, S, Se, C=O；

Substituent R, R₄, R₅, R₆, R₇Define the definition with formula IAb.

According to formula I of the present invention, currently preferred compound and its physiologically acceptable salt including but not limited to lead to Compound shown in formula (IB)：

In Formulas I B,

R₄Selected from following atom or group or structure fragment, including

(3) substituted or non-substituted C3-6 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-6 yuan of rings, substitution or The azacycloalkyl of non-substituted 3-6 yuan of rings, wherein substituent are selected from methyl, ethyl, propyl group, isopropyl, CF₃、CH₂CF₃、 CHF₂、F、Cl、Br、CN、CONRh₁Ri₁、COORh₂、SO₂Rh₃、SO₂NRh₄Ri₂、ORh₅、SRh₆、NRh₇Ri₃、NRh₈CORi₄、 NRh₉COORi₅, wherein described Rh₁、Ri₁、Rh₂、Rh₃、Rh₄、Ri₂、Rh₅、Rh₆、Rh₇、Ri₃、Rh₈、Ri₄、Rh₉、Ri₅Independently Selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third, cyclobutyl；The oxacycloalkyl and 3-6 of 3-6 yuan of rings It can also can simultaneously contain multiple hetero atoms containing 1 hetero atom in the azacycloalkyl of yuan of rings；

R is selected from following group or structure fragment：

Currently preferred compound and its physiologically acceptable salt, including but not limited to, described R₁Selected from H, Methyl, ethyl, n-propyl, isopropyl, vinyl, acetenyl.

Currently preferred compound and its physiologically acceptable salt, including but not limited to, described R'₁Selected from H, Methyl, ethyl, n-propyl, isopropyl, vinyl, acetenyl.

Currently preferred compound and its physiologically acceptable salt, including but not limited to, described R₃Selected from H, Methyl, ethyl, vinyl, acetenyl.

Currently preferred compound and its physiologically acceptable salt, including but not limited to, described R'₃Selected from H, Methyl, ethyl, vinyl, acetenyl.

To complete the purpose of the present invention, compound preferably includes but is not limited to：

The second aspect of technical solution of the present invention there is provided the preparation method of compound described in first aspect, the skill of use Art scheme comprises the following steps：

(1) compound A obtains compound B through the hydrolysis under alkalescence condition；

(2) with corresponding sulfamide compound condensation reaction occurs for compound B, obtains the change described in first aspect present invention Compound；

The wherein definition of A, B, D, E, F, G, R with first aspect present invention to compound.

In addition, the initiation material and intermediate in above-mentioned reaction are readily obtained, each step reaction can be according to the document reported Or synthesis can be easy to the conventional method in organic synthesis to those skilled in the art.Chemical combination described in formula I Thing can exist in the form of solvate or non-solvent compound, and carrying out crystallization using different solvents is likely to be obtained different solvents Compound.Pharmaceutically acceptable salt described in formula I includes the salt of different sour salt, such as following inorganic acid or organic acid：Hydrochloric acid, hydrogen Bromic acid, phosphoric acid, sulfuric acid, methanesulfonic acid, p-methyl benzenesulfonic acid, trifluoroacetic acid, matrimony vine acid, maleic acid, tartaric acid, fumaric acid, citric acid, Lactic acid.Pharmaceutically acceptable salt described in formula I also includes different alkali metal salts (lithium, sodium, sylvite), alkali salt (calcium, magnesium Salt) and ammonium salt, and the salt of the organic base of physiologically acceptable cation can be provided, and such as methylamine, dimethylamine, trimethylamine, piperidines, The salt of morpholine and three (2- ethoxys) amine.All these salt within the scope of the present invention can all be prepared using conventional method.

The third aspect of technical solution of the present invention there is provided a kind of pharmaceutical composition, and described pharmaceutical composition includes conduct Compound or pharmaceutically acceptable salt thereof described in technical solution of the present invention first aspect and common carrier pharmaceutically.

Present invention also offers the pharmaceutical composition using the compounds of this invention as active ingredient, said composition includes this hair At least one of bright compound and pharmaceutically acceptable carrier.Described pharmaceutical composition be selected from tablet, capsule, pill, Injection, sustained release preparation, controlled release preparation or various particulate delivery systems.The pharmaceutical composition can be according to method well known in the art Prepare.Can be by by the compounds of this invention and one or more pharmaceutically acceptable solids or liquid excipient and/or assistant agent With reference to any formulation used suitable for human or animal is made.Content of the compounds of this invention in its pharmaceutical composition be usually 0.1-95 weight %.

The compounds of this invention or pharmaceutical composition containing it can be administered in a unit, and method of administration can be enteron aisle Or non-bowel, such as oral, intravenous injection, intramuscular injection, hypodermic injection, nasal cavity, oral mucosa, eye, lung and respiratory tract, skin, Vagina, rectum etc..

Form of administration can be liquid dosage form, solid dosage forms or semisolid dosage form.Liquid dosage form can be solution (including True solution and colloidal solution), emulsion (including o/w types, w/o types and emulsion), supensoid agent, injection (including liquid drugs injection, powder-injection And transfusion), eye drops, nasal drop, lotion and liniment etc.；Solid dosage forms can be tablet (including ordinary tablet, enteric coatel tablets, lozenge, Dispersible tablet, chewable tablets, effervescent tablet, oral disnitegration tablet), capsule (including hard shell capsules, soft capsule, capsulae enterosolubilis), granule, dissipate Agent, micropill, dripping pill, suppository, film, paster, the agent of gas (powder) mist, spray etc.；Semisolid dosage form can be ointment, gel Agent, paste etc..

The compounds of this invention can be made ordinary preparation, may be made as sustained release preparation, controlled release preparation, targeting preparation and various Particulate delivery system.

These preparations are prepared according to method well known to the skilled artisan in the art.For manufacture tablet, capsule, bag Auxiliary material used in clothing agent is conventional auxiliary agent, such as starch, gelatin, Arabic gum, silica, polyethylene glycol, liquid dosage form institute Solvent for example has water, ethanol, propane diols, plant oil such as corn oil, peanut oil, olive oil etc..Contain chemical combination of the present invention Can also there are other auxiliary agents, such as surfactant, lubricant, disintegrant, preservative, flavouring, pigment etc. in the preparation of thing.

In order to which the compounds of this invention is made into tablet, various excipient well known in the art can be widely used, including it is dilute Release agent, binder, wetting agent, disintegrant, lubricant, glidant.Diluent can be starch, dextrin, sucrose, glucose, breast Sugar, mannitol, sorbierite, xylitol, microcrystalline cellulose, calcium sulfate, calcium monohydrogen phosphate, calcium carbonate etc.；Wetting agent can be water, second Alcohol, isopropanol etc.；Adhesive can be starch slurry, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, Arabic gum Slurry, gelatine size, sodium carboxymethylcellulose, methylcellulose, hydroxypropyl methyl cellulose, ethyl cellulose, acrylic resin, card Ripple nurse, polyvinylpyrrolidone, polyethylene glycol etc.；Disintegrant can be dried starch, microcrystalline cellulose, low substituted hydroxy-propyl fiber Element, PVPP, Ac-Di-Sol, sodium carboxymethyl starch, sodium acid carbonate and citric acid, polyoxy second Alkene sorbitan fatty acid ester, dodecyl sodium sulfate etc.；Lubricant and glidant can be talcum powder, silica, tristearin Hydrochlorate, tartaric acid, atoleine, polyethylene glycol etc..

Tablet can also be further made to coating tablet, such as sugar coated tablet, thin membrane coated tablet, enteric coated tablets, or double Synusia and multilayer tablet.

In order to which administration unit is made into capsule, active ingredient the compounds of this invention can be mixed with diluent, glidant Close, mixture is placed directly within hard shell capsules or soft capsule.Also can active ingredient the compounds of this invention is first and diluent, bonding Particle or micropill is made in agent, disintegrant, then is placed in hard shell capsules or soft capsule.For preparing each dilute of the compounds of this invention tablet Release the capsule that agent, binder, wetting agent, disintegrant, glidant kind can also be used for preparing the compounds of this invention.

For the compounds of this invention is made into injection, water, ethanol, isopropanol, propane diols or their mixture can be used Make solvent and add appropriate solubilizer commonly used in the art, cosolvent, pH adjustments agent, osmotic pressure regulator.Solubilizer or hydrotropy Agent can be poloxamer, lecithin, hydroxypropyl-β-cyclodextrin etc.；PH adjustment agent can be phosphate, acetate, hydrochloric acid, hydrogen Sodium oxide molybdena etc.；Osmotic pressure regulator can be sodium chloride, mannitol, glucose, phosphate, acetate etc..Such as prepare freeze-dried powder Injection, can also add mannitol, glucose etc. as proppant.

In addition, if desired, colouring agent, preservative, spices, flavouring or other additions can also be added into pharmaceutical preparation Agent.

To reach medication purpose, strengthen therapeutic effect, medicine of the invention or pharmaceutical composition known can be given with any Prescription method is administered.

The dosage of the compounds of this invention pharmaceutical composition is according to the property and serious journey to be prevented or treated disease The individual instances of degree, patient or animal, method of administration and formulation etc. can have large-scale change.In general, the present inventionization The daily Suitable dosage ranges of compound are 0.01-500mg/Kg body weight, preferably 0.1-300mg/Kg body weight.Above-mentioned dosage can With a dosage unit or it is divided into several dosage unit administrations, this depends on the clinical experience of doctor and including being controlled with other The dosage regimen for the treatment of means.

The compound or composition of the present invention can individually be taken, or merge with other treatment medicine or symptomatic drugs and use. When the compound of the present invention exists with other medicines to act synergistically, its dosage should be adjusted according to actual conditions.

The fourth aspect of technical solution of the present invention there is provided the compound and its pharmaceutical salts described in first aspect present invention Prepare FBPase inhibitor and prepare prevention and or the treatment disease and disorder agent relevant with FBPase in answer With.Described application, it is characterised in that the disease relevant with FBPase and illness be selected from diabetes, diabetes it is chronic concurrent Disease and obesity.Described diabetes are selected from type i diabetes and type ii diabetes；The chronic complicating diseases of the diabetes are selected from and regarded Nethike embrane, kidney, nervous system lesion and vascular complication, ischemic heart disease or atherosclerosis.

Embodiment

Invention is described further below with reference to embodiment, but not limit the scope of the invention.

The structure of compound is determined by nuclear magnetic resonance (NMR) or high resolution mass spectrum (HRMS).NMR measure is With Varian mercury 300 or Varian mercury 400, measure solvent is CDCl₃、DMSO-d₆、acetone-d₆、 CD₃OD, is inside designated as TMS, and chemical shift is provided using ppm as unit.Ms measure Thermo Exactive Plus types Mass spectrograph.M.p. it is with DEG C fusing point provided, the non-correction up of temperature.Silica gel column chromatography is load typically using 200~300 mesh silica gel Body.

Test agents useful for same pure for chemical pure or analysis.Solvent for use is that analysis is pure, and anhydrous solvent used is by the U.S. INNOVATIVE TECHNOLOGY production solvent purification system and obtain, other solvents are unspecified then unprocessed.

Abbreviated list：

TLC：Thin-layer chromatography PPA：Polyphosphoric acids

DMSO：Dimethyl sulfoxide (DMSO) DMAP：DMAP

CDCl₃：Deuterochloroform DMSO-d₆：Deuterated dimethyl sulfoxide

acetone-d₆：Deuterated acetone CD₃OD：Deuterated methanol

HOBt：1- hydroxy benzo triazoles Pd (OAc)₂：Palladium

DCM：Dichloromethane NBS：N- bromo-succinimides

NCS：N- chlorosuccinimides TFA：Trifluoroacetic acid

DMF：N,N-dimethylformamide THF：Tetrahydrofuran

DMAP：DMAP Et₃N：Triethylamine

TBAB：TBAB TBAF：Tetrabutyl ammonium fluoride

EA：Ethyl acetate

EDCI：1- ethyls-(3- dimethylaminopropyls) phosphinylidyne diimmonium salt hydrochlorate

HATU：2- (7- azos BTA)-N, N, N', N'- tetramethylurea hexafluorophosphoric acid ester

XantPhos：Double diphenylphosphine -9,9- dimethyl the xanthenes of 4,5-

DavePhos：2- dicyclohexylphosphinos -2'- (N, TMSDMA N dimethylamine)-biphenyl

PdCl₂(dppf)：[double (diphenylphosphino) ferrocene of 1,1'-] palladium chloride

Pd₃(dba)₂：Three (dibenzalacetone) two palladium

(tBu)₃P·HBF₄：Tri-butyl phosphine tetrafluoroborate

TBDMSCl：Tert-butyl chloro-silicane

min：Minute；h：Hour

P/E：Petrol ether/ethyl acetate；D/M：Methylene chloride/methanol

Josiphos：(R) -1- [(SP) -2- (diphenylphosphine) ferrocene] ethyl dicyclohexylphosphontetrafluoroborate

The preparation 1 of intermediate：

The chloro- 1H- indole -2-ethyl formates of 7- nitros -4-

A) 2- nitros -5- chlorophenylhydxazine hydrochlorides

2- nitro -5- chloroanilines (5g, 29.0mmol) are dissolved in concentrated hydrochloric acid (57.2g, 580mmol), 40 DEG C of reaction 2h. - 10 DEG C are subsequently cooled to, natrium nitrosum (2.1g, 30.45mmol) aqueous solution (20mL) is instilled, 2h is reacted.- 30 DEG C are cooled to, Drop to the pre- SnCl for being cooled to -30 DEG C₂In concentrated hydrochloric acid (30mL) solution of (19.6g, 87mmol), -20 DEG C of reaction 1h rise to room Temperature, is filtered, and is dried, is obtained faint yellow solid 7.0g, yield is 100%, mp:178-180℃.

¹H NMR(DMSO-d₆)δ(ppm):9.39 (brs, 1H), 8.15 (d, J=8.8Hz, 1H), 7.45 (s, 1H), 7.06 (d, J=8.4Hz, 1H), 3.83 (brs, 3H)；HRMS(ESI):m/z,calcd for C₆H₇ClN₃O₂[M+H⁺]:188.0221, found 188.0220.

B) 2- (2- (2- nitro -5- chlorphenyls) hydrazono-) ethyl propionate

2- nitro -5- chlorophenylhydxazine hydrochlorides (1g, 4.46mmol) are dissolved in methanol (20mL), ethyl pyruvate is instilled (544mg, 4.69mmol), is stirred at room temperature 5min, separates out faint yellow solid, filters to obtain faint yellow solid 469mg, yield is 36.8%, mp:107-109℃.

¹H NMR(acetone-d₆)δ(ppm):10.82 (br, 1H), 8.24 (d, J=8.8Hz, 1H), 7.95 (s, 1H), 7.10(dd,J₁=9.2Hz, J₂=1.6Hz, 1H), 4.32 (q, J=7.2Hz, 2H), 2.26 (s, 3H), 1.35 (t, J= 7.2Hz,3H)；HRMS(ESI):m/z,calcd for C₁₁H₁₃ClN₃O₄[M+H⁺]:286.0589,found 286.0582.

C) the chloro- 1H- indole -2-ethyl formates of 7- nitros -4-

2- (2- (2- nitro -5- chlorphenyls) hydrazono-) ethyl propionate (2.84g, 9.94mmol) is added to PPA (57g) In, 80 DEG C of reaction 12h, raw material disappears.It is cooled under room temperature, ice-water bath, adds 50mL frozen water, stirs, EA extractions (30mL × 3), column chromatography (P/E=50:1) faint yellow solid 810mg is obtained, yield is 30%, mp:170-171℃.

¹H NMR(acetone-d₆)δ(ppm):11.01 (brs, 1H), 8.31 (d, J=8.7Hz, 1H), 7.45 (d, J= 8.4Hz, 1H), 7.40 (s, 1H), 4.45 (q, J=7.2Hz, 2H), 1.42 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z, calcd for C₁₁H₁₀ClN₂O₄[M+H⁺]:269.0324,found 269.0318.

Embodiment 1：7- nitros -4- chloro- N- (phenyl sulfonyl) -1H- indole 2-carboxamides

A) the chloro- 1H- indole-2-carboxylic acids of 7- nitros -4-

The chloro- 1H- indole -2-ethyl formates (350mg, 1.3mmol) of 7- nitros -4- are dissolved in THF (8mL) and EtOH In (4mL), NaOH solution (260mg, 6.5mmol, 4mL H is added₂O), react at room temperature, overnight.Solvent is evaporated off, 20mL is added Water, EA is washed (20mL × 2), aqueous phase 1M salt acid for adjusting pH about 2-3, separates out solid, is filtered, and is dried, and is obtained off-white powder shape and is consolidated Body 310mg, yield is 99%, mp:220-222℃.

¹H NMR(DMSO-d₆)δ(ppm):13.74 (brs, 1H), 11.57 (s, 1H), 8.26 (d, J=8.8Hz, 1H), 7.46 (d, J=8.4Hz, 1H), 7.32 (s, 1H)

B) the chloro- N- of 7- nitros -4- (phenyl sulfonyl) -1H- indole 2-carboxamides

The chloro- 1H- indole-2-carboxylic acids (80mg, 0.33mmol) of 7- nitros -4- are dissolved in DCM (10mL), sequentially added EDCI (82mg, 0.43mmol), DMAP (21mg, 0.17mmol) and Et₃N (67mg, 0.66mmol), after stirring, is added Benzsulfamide (78mg, 0.50mmol), is stirred at room temperature 3d, and raw material disappears.Solvent is evaporated off, EA (30mL) dissolution residual substance, 1M is dilute Salt pickling (20mL × 3), is washed (20mL × 2), column chromatography (D/M=10:1) pale yellow powder shape solid 80mg, is obtained, EA is tied again Brilliant to obtain 58mg, yield is 46%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.97 (brs, 1H), 8.28 (d, J=8.8Hz, 1H), 8.05 (d, J= 7.2Hz, 2H), 7.75 (t, J=7.2Hz, 1H), 7.67 (t, J=7.2Hz, 2H), 7.61 (s, 1H), 7.46 (d, J=8.4Hz, 1H).

Embodiment 2：7- nitros -4- chloro- N- (mesyl) -1H- indole 2-carboxamides

The chloro- 1H- indole-2-carboxylic acids (80mg, 0.33mmol) of 7- nitros -4- are dissolved in DCM (10mL), sequentially added HATU (188mg, 0.50mmol), DMAP (20mg, 0.17mmol) and Et₃N (67mg, 0.66mmol), after stirring, is added Methanesulfomide (63mg, 0.66mmol), is stirred at room temperature, overnight, and raw material disappears.Solvent, EA (30mL) dissolution residual substance, 1M is evaporated off Watery hydrochloric acid is washed (20mL × 3), is washed (20mL × 2), EA recrystallizations, obtains off-white powder shape solid 72mg, yield is 69%, mp:>250℃。

¹H NMR(DMSO-d₆)δ(ppm):12.08 (s, 1H), 8.31 (d, J=8.4Hz, 1H), 7.67 (s, 1H), 7.49 (d, J=8.8Hz, 1H), 3.44 (s, 3H)

Embodiment 3：4- ((3- methoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

The chloro- 1H- indole -2-ethyl formates (220mg, 0.82mmol) of 7- nitros -4- are dissolved in toluene (12mL), Sequentially add Pd₂(dba)₃(75mg, 0.082mmol), XantPhos (95mg, 0.16mmol) and Na₂CO₃(261mg, 2.46mmol,2mL H₂O), after stirring, 3- aminoanisoles (302mg, 2.46mmol) are added, under argon gas protection, backflow 5h is reacted, raw material disappears.Room temperature is cooled to, solvent is evaporated off, EA (30mL) dissolution residual substance, saturated common salt washes (20mL × 3), Wash (20mL × 2), column chromatography (P/E=20:1) pale yellow powder shape solid 285mg, is obtained, yield is 98%, mp:188-190 ℃。

¹H NMR(DMSO-d₆)δ(ppm):10.94 (s, 1H), 9.64 (s, 1H), 8.13 (d, J=9.3Hz, 1H), 7.84 (s, 1H), 7.35 (t, J=7.8Hz, 1H), 6.96 (d, J=7.8Hz, 1H), 6.92-6.93 (m, 1H), 6.77-6.82 (m, 2H), 4.37 (q, J=7.5Hz, 2H), 3.78 (s, 3H), 1.36 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₈H₁₈N₃O₅[M+H⁺]:356.1241,found 356.1231.

B) 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates (250mg, 0.70mmol) is molten In being dissolved in THF (6mL) and EtOH (3mL), NaOH solution (140mg, 3.5mmol, 3mL H is added₂O), react at room temperature, mistake Night.Solvent is evaporated off, 15mL water is added, EA is washed (10mL × 2), aqueous phase 1M salt acid for adjusting pH about 2-3, solid is separated out, filters, does It is dry, Red-brown powder shape solid 227mg is obtained, yield is 99%.mp:217-219℃.

¹H NMR(DMSO-d₆)δ(ppm):10.73 (s, 1H), 9.62 (s, 1H), 8.12 (d, J=9.2Hz, 1H), 7.75 (s, 1H), 7.35 (t, J=8.0Hz, 1H), 6.96 (d, J=8.0Hz, 1H), 6.92 (s, 1H), 6.77-6.80 (m, 2H), 3.77(s,3H)；HRMS(ESI):m/z,calcd for C₁₆H₁₄N₃O₅[M+H⁺]:328.0928,found 328.0921.

C) 4- ((3- methoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids (80mg, 0.244mmol) are dissolved in DCM In (10mL), HATU (139mg, 0.366mmol), DMAP (15mg, 0.122mmol) and Et are sequentially added₃N (49mg, 0.482mmol), after stirring, benzsulfamide (58mg, 0.366mmol) is added, is stirred at room temperature, overnight, raw material disappears. Solvent is evaporated off, EA (30mL) dissolution residual substance, 2M watery hydrochloric acid is washed (20mL × 3), washes (20mL × 2), EA recrystallizations obtain yellow Pulverulent solids 90mg, yield is 79%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.10(brs,1H),11.90(brs,1H),9.65(s,1H),8.15(d,J =8.8Hz, 1H), 8.05 (d, J=7.6Hz, 2H), 7.86 (s, 1H), 7.75 (t, J=7.2Hz, 1H), 7.67 (t, J= 7.6Hz, 2H), 7.35 (t, J=8.4Hz, 1H), 6.95 (d, J=8.0Hz, 1H), 6.91 (s, 1H), 6.78 (d, J=9.6Hz, 2H),3.78(s,3H).

Embodiment 4：4- ((3- methoxyphenyls) amino) -7- amino-N- (benzenesulfonyl) -1H- indole 2-carboxamides

By 4- ((3- methoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides (80mg, 0.17mmol) it is dissolved in water (2mL), adds Fe powder (35mg, 0.62mmol) and ammonium chloride (10mg, 0.17mmol), microwave is anti- Answer (100w, 100 DEG C, 40min, 150psi).Reaction solution is dissolved in DCM and methanol, filtered, filtrate concentration obtains off-white color and consolidated Body.EA (20mL) is added, is washed (10mL × 2), concentration, solid sequentially adds a small amount of EA and DCM stirrings, filtering obtains celadon Solid 13mg, yield is 18%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.38(brs,1H),6.35-7.98(m,16H),3.63(s,3H).

Embodiment 5：4- ((3- methoxyphenyls) amino) -7- nitros-N- (mesyl) -1H- indole 2-carboxamides

4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids (80mg, 0.244mmol) are dissolved in DCM In (10mL), HATU (139mg, 0.366mmol), DMAP (15mg, 0.122mmol) and Et are sequentially added₃N (49mg, 0.482mmol), after stirring, Methanesulfomide (35mg, 0.366mmol) is added, is stirred at room temperature, overnight, raw material disappears. Solvent is evaporated off, EA (30mL) dissolution residual substance, 2M watery hydrochloric acid is washed (20mL × 3), washes (20mL × 2), EA recrystallizations obtain yellow Pulverulent solids 74mg, yield is 75%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):12.67 (brs, 1H), 11.99 (s, 1H), 9.69 (s, 1H), 8.17 (d, J= 9.3Hz, 1H), 7.98 (s, 1H), 7.36 (t, J=8.1Hz, 1H), 6.98 (d, J=8.1Hz, 1H), 6.93 (s, 1H), 6.81 (d, J=9.0Hz, 2H), 3.79 (s, 3H), 3.43 (s, 3H)

Embodiment 6：4- ((3- methoxyphenyls) amino) -7- nitros-N- (Cyclopropylsulfonyl) -1H- indoles -2- formyls Amine

It is former using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and cyclopropylsulfonamide as starting Material, c) methods described in preparation process be the same as Example 3, obtains yellow solid 44mg, yield is 83%, mp:270-272℃.

¹H NMR(DMSO-d₆)δ(ppm):12.63 (brs, 1H), 11.95 (s, 1H), 9.69 (s, 1H), 8.17 (d, J= 9.2Hz, 1H), 7.98 (s, 1H), 7.36 (t, J=8.0Hz, 1H), 6.98 (d, J=8.0Hz, 1H), 6.94 (s, 1H), 6.81 (d, J=8.8Hz, 2H), 3.79 (s, 3H), 3.18 (m, 1H), 1.16-1.19 (m, 4H)

Embodiment 7：4- (phenyl amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides 1928

A) 4- (phenyl amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and aniline as initiation material, in preparation process be the same as Example 3 A) methods described, obtains yellow solid 70mg, and yield is 76%, mp:237-240℃.

¹H NMR(DMSO-d₆)δ(ppm):13.37 (brs, 1H), 10.72 (s, 1H), 9.65 (s, 1H), 8.11 (d, J= 9.2Hz, 1H), 7.74 (s, 1H), 7.46 (t, J=7.6Hz, 2H), 7.38 (d, J=7.6Hz, 1H), 7.22 (t, J=6.8Hz, 1H), 6.71 (q, J=9.2Hz, 1H)；HRMS(ESI):m/z,calcd for C₁₅H₁₂N₃O₄[M+H⁺]:298.0822,found 298.0811.

B) 4- (phenyl amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- (phenyl amino) -7- nitro -1H- indole -2-ethyl formates as initiation material, preparation process be the same as Example 3 Middle b) methods described, obtains yellow solid 70mg, and yield is 76%, mp:237-240℃.

C) 4- (phenyl amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- (phenyl amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, preparation process is with real C) methods described is applied in example 3, yellow solid 122mg is obtained, yield is 76%, mp:272-273℃.

¹H NMR(DMSO-d₆)δ(ppm):13.10 (brs, 1H), 11.89 (s, 1H), 9.70 (s, 1H), 8.14 (d, J= 9.2Hz, 1H), 8.05 (d, J=7.6Hz, 2H), 7.85 (s, 1H), 7.75 (t, J=7.2Hz, 1H), 7.67 (t, J=7.6Hz, 2H), 7.45 (t, J=7.6Hz, 2H), 7.37 (d, J=8.0Hz, 1H), 7.23 (t, J=7.6Hz, 1H), 6.70 (d, J= 9.2Hz,1H).

Embodiment 8：4- ((2- methoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) 4- ((2- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 2- aminoanisoles as initiation material, preparation process is with real A) methods described is applied in example 3, yellow solid 270mg is obtained, yield is 82%, mp:137-139℃.

¹H NMR(CDCl₃)δ(ppm):10.46 (brs, 1H), 8.20 (d, J=9.2Hz, 1H), 7.51 (d, J=8.0Hz, 1H), 7.39 (d, J=1.2Hz, 1H), 7.16 (t, J=8.0Hz, 2H), 7.00-7.04 (m, 3H), 6.92 (d, J=8.8Hz, 1H), 4.46 (q, J=7.2Hz, 2H), 3.92 (s, 3H), 1.45 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₈H₁₈N₃O₅[M+H⁺]:356.1241,found 356.1231.

B) 4- ((2- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- ((2- methoxyphenyls) amino), -7- nitro -1H- indole -2-ethyl formates is initiation materials, preparation process B) methods described in be the same as Example 3, obtains yellow solid 130mg, yield is 78%, mp:245-246℃.

¹H NMR(DMSO-d₆)δ(ppm):10.65 (s, 1H), 9.38 (s, 1H), 8.05 (d, J=9.2Hz, 1H), 7.70 (s, 1H), 7.33-7.37 (m, 2H), 7.21 (d, J=8.0Hz, 1H), 7.06 (t, J=7.6Hz, 1H), 6.14 (d, J= 9.2Hz,1H),3.78(s,3H)；HRMS(ESI):m/z,calcd for C₁₆H₁₄N₃O₅[M+H⁺]:328.0928,found 328.0923.

C) 4- ((2- methoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- ((2- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, system C) methods described in standby process be the same as Example 3, obtains orange powder shape solid 80mg, yield is 92%, mp:245-246℃.

¹H NMR(DMSO-d₆)δ(ppm):13.10(brs,1H),11.83(brs,1H),9.38(s,1H),8.07(d,J =9.6Hz, 1H), 8.04 (d, J=8.0Hz, 2H), 7.79 (s, 1H), 7.74 (t, J=7.2Hz, 1H), 7.66 (t, J= 7.2Hz, 2H), 7.36-7.30 (m, 2H), 7.19 (d, J=8.4Hz, 1H), 7.04 (t, J=7.6Hz, 1H), 6.12 (d, J= 9.2Hz,1H),3.76(s,3H).

Embodiment 9：4- ((4- methoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) 4- ((4- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- aminoanisoles as initiation material, preparation process is with real A) methods described is applied in example 3, yellow solid 389mg is obtained, yield is 84%, mp:209-211℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.14 (d, J=9.3Hz, 1H), 7.33 (d, J=2.4Hz, 1H), 7.25 (d, J=8.7Hz, 2H), 6.98 (d, J=9.0Hz, 1H), 6.72 (brs, 1H), 6.50 (d, J=9.0Hz, 1H), 4.43 (q, J=7.2Hz, 2H), 3.86 (s, 1H), 1.43 (t, J=7.5Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₈H₁₈N₃O₅[M+H⁺]:356.1231,found 356.1241.

B) 4- ((4- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((4- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is same B) methods described in embodiment 3, obtains yellow solid 300mg, yield is 99%, mp:254-255℃.

¹H NMR(DMSO-d₆)δ(ppm):10.59 (s, 1H), 9.55 (s, 1H), 8.05 (d, J=9.3Hz, 1H), 7.61 (s, 1H), 7.31 (d, J=8.4Hz, 2H), 7.04 (d, J=8.4Hz, 2H), 6.48 (d, J=9.3Hz, 1H), 3.80 (s, 3H)；HRMS(ESI):m/z,calcd for C₁₆H₁₄N₃O₅[M+H⁺]:328.0928,found 328.0921.

C) 4- ((4- methoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- ((4- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, system C) method in standby process be the same as Example 3, obtains red-brown powder shape solid 65mg, yield is 45%, mp:258-260℃.

¹H NMR(DMSO-d₆)δ(ppm):13.10(brs,1H),11.86(brs,1H),9.61(s,1H),8.10(d,J =9.0Hz, 1H), 8.04 (d, J=7.5Hz, 2H), 7.80 (s, 1H), 7.75 (t, J=7.2Hz, 1H), 7.67 (t, J= 7.5Hz, 2H), 7.28 (d, J=9.0Hz, 2H), 7.03 (d, J=9.0Hz, 2H), 6.46 (d, J=9.0Hz, 1H), 3.79 (s, 3H).

Embodiment 10：4- ((3,4- Dimethoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indoles -2- first Acid amides

A) 4- ((3,4- Dimethoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

With the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3,4- dimethoxyaniline for initiation material, preparation process A) methods described in be the same as Example 3, obtains Orange red solid 420mg, yield is 98%, mp:205-206℃.

¹H NMR(CDCl₃)δ(ppm):10.46 (brs, 1H), 8.15 (d, J=9.0Hz, 1H), 7.35 (d, J=1.8Hz, 1H), 6.78-6.95 (m, 4H), 6.55 (d, J=8.7Hz, 1H), 4.43 (q, J=7.2Hz, 2H), 3.93 (s, 1H), 3.88 (s, 3H), 1.42 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₉H₂₀N₃O₆[M+H⁺]:386.1347, found 386.1333.

B) 4- ((3,4- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3,4- Dimethoxyphenyl) amino) -7- nitro -1H- indole -2-ethyl formates for initiation material, prepare B) methods described in process be the same as Example 3, obtains yellow solid 291mg, yield is 98%, mp:267-269℃.

¹H NMR(DMSO-d₆)δ(ppm):13.34 (brs, 1H), 10.69 (s, 1H), 9.61 (s, 1H), 8.09 (d, J= 9.3Hz, 1H), 7.72 (d, J=2.1Hz, 1H), 7.04 (d, J=8.7Hz, 1H), 6.91-6.97 (m, 2H), 6.58 (d, J= 9.3Hz,1H),3.79(s,3H),3.77(s,3H)；HRMS(ESI):m/z,calcd for C₁₇H₁₆N₃O₆[M+H⁺]: 358.1034,found 358.1029.

C) 4- ((3,4- Dimethoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

It is former using 4- ((3,4- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as starting Material, c) methods described in preparation process be the same as Example 3, obtains red-brown powder shape solid 116mg, yield is 83%, mp:198- 199℃。

¹H NMR(DMSO-d₆)δ(ppm):13.10(brs,1H),11.60(brs,1H),9.59(s,1H),8.09(d,J =9.3Hz, 1H), 8.02 (d, J=7.5Hz, 2H), 7.73-7.62 (m, 4H), 7.03 (d, J=8.4Hz, 1H), 6.95-6.88 (m, 2H), 6.56 (d, J=9.3Hz, 1H), 3.79 (s, 3H), 3.76 (s, 3H)

Embodiment 11：4- ((3,5- Dimethoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indoles -2- first Acid amides

A) 4- ((3,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

With the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3,5- dimethoxyaniline for initiation material, preparation process A) methods described in be the same as Example 3, obtains Orange red solid 324mg, yield is 99%, mp:171-172℃.

¹H NMR(DMSO-d₆)δ(ppm):10.95 (s, 1H), 9.60 (s, 1H), 8.15 (d, J=9.0Hz, 1H), 7.84 (s, 1H), 6.88 (d, J=9.3Hz, 1H), 6.54 (d, J=1.8Hz, 2H), 6.37 (t, J=2.1Hz, 1H), 4.38 (q, J= 7.5Hz, 2H), 3.77 (s, 6H), 1.37 (t, J=7.5Hz, 3H)

B) 4- ((3,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3,5- Dimethoxyphenyl) amino) -7- nitro -1H- indole -2-ethyl formates for initiation material, prepare B) methods described in process be the same as Example 3, obtains red brown solid 186mg, yield is 91%, mp:242-243℃.

¹H NMR(DMSO-d₆)δ(ppm):10.76 (s, 1H), 9.66 (s, 1H), 8.14 (d, J=9.0Hz, 1H), 7.78 (d, J=1.8Hz, 1H), 6.86 (d, J=9.6Hz, 1H), 6.55 (d, J=1.5Hz, 2H), 6.37 (s, 1H), 3.77 (s, 6H).

C) 4- ((3,5- Dimethoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

It is former using 4- ((3,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as starting Material, c) methods described in preparation process be the same as Example 3, obtains orange red pulverulent solids 95mg, yield is 98%, mp:171-172 ℃。

¹H NMR(DMSO-d₆)δ(ppm):13.08(brs,1H),11.87(brs,1H),9.60(s,1H),8.16(d,J =9.2Hz, 1H), 8.05 (d, J=8.0Hz, 2H), 7.85 (s, 1H), 7.74 (t, J=7.6Hz, 1H), 7.67 (d, J= 7.6Hz, 2H), 6.83 (d, J=9.2Hz, 1H), 6.51 (s, 2H), 6.36 (s, 1H), 3.75 (s, 6H)；¹³C NMR(125MHz, DMSO-d₆):δ161.05,146.89,140.94,129.20,127.70,124.17,102.67,100.83,96.79, 55.30.HRMS(ESI):m/z,calcd.for C₂₃H₂₁N₄O₇S[M+H]⁺:497.1126,found 497.1115.

Embodiment 12：4- ((3,4,5- trimethoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indoles -2- Formamide

A) 4- ((3,4,5- trimethoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

With the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3,4,5- trimethoxy-anilines are initiation material, are prepared A) methods described in journey be the same as Example 3, obtains Orange red solid 292mg, yield is 94%, mp:179-181℃.

¹H NMR(CDCl₃)δ(ppm):10.46 (brs, 1H), 8.18 (d, J=9.2Hz, 1H), 7.35 (d, J=1.2Hz, 1H), 6.75 (brs, 1H), 6.70 (d, J=9.2Hz, 1H), 6.56 (s, 2H), 4.44 (q, J=7.2Hz, 2H), 3.89 (s, 1H), 3.86 (s, 6H), 1.43 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₂₀H₂₂N₃O₇[M+H⁺]: 416.1452,found 416.1439.

B) 4- ((3,4,5- trimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3,4,5- trimethoxyphenyl) amino) -7- nitro -1H- indole -2-ethyl formates for initiation material, system B) methods described in standby process be the same as Example 3, obtains yellow solid 145mg, yield is 82%, mp:278-280℃.

¹H NMR(DMSO-d₆)δ(ppm):10.73 (brs, 1H), 9.66 (s, 1H), 8.12 (d, J=9.0Hz, 1H), 7.76 (d, J=2.1Hz, 1H), 6.78 (d, J=9.3Hz, 1H), 6.70 (s, 2H), 3.80 (s, 6H), 3.69 (s, 3H)；HRMS (ESI):m/z,calcd for C₁₈H₁₈N₃O₇[M+H⁺]:388.1139,found 388.1133.

C) 4- ((3,4,5- trimethoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- ((3,4,5- trimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as starting C) methods described in raw material, preparation process be the same as Example 3, obtains red-brown powder shape solid 40mg, yield is 35%, mp:212- 214℃。

¹H NMR(DMSO-d₆)δ(ppm):9.51 (brs, 1H), 8.06 (d, J=8.8Hz, 1H), 7.94 (brs, 2H), 7.53 (brs, 4H), 6.76 (d, J=9.2Hz, 1H), 6.67 (s, 2H), 3.78 (s, 6H), 3.68 (s, 3H)；HRMS(ESI): m/z,calcd.for C₂₄H₂₃N₄O₈S[M+H]⁺:527.1231,found 527.1224.

Embodiment 13：4- ((3- aminomethyl phenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) 4- ((3- aminomethyl phenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- methylanilines as initiation material, preparation process is with implementation A) methods described in example 3, obtains yellow solid 260mg, yield is 93%, mp:190-191℃.

¹H NMR(DMSO-d₆)δ(ppm):10.89 (s, 1H), 9.62 (s, 1H), 8.13 (d, J=9.2Hz, 1H), 7.83 (s, 1H), 7.33 (t, J=8.0Hz, 1H), 7.16-7.19 (m, 2H), 7.04 (d, J=7.6Hz, 1H), 6.72 (d, J= 9.2Hz, 1H), 4.37 (q, J=7.2Hz, 2H), 2.34 (s, 3H), 1.36 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z, calcd for C₁₈H₁₈N₃O₄[M+H⁺]:340.1292,found 340.1289.

B) 4- ((3- aminomethyl phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- ((3- aminomethyl phenyls) amino), -7- nitro -1H- indole -2-ethyl formates is initiation materials, and preparation process is same B) methods described in embodiment 3, obtains yellow solid 90mg, yield is 80%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):10.43 (s, 1H), 9.49 (s, 1H), 8.03 (d, J=8.8Hz, 1H), 7.47 (s, 1H), 7.31 (t, J=8.0Hz, 1H), 7.16-7.19 (m, 2H), 7.01 (d, J=7.6Hz, 1H), 6.69 (d, J= 9.2Hz,1H),2.33(s,3H)；HRMS(ESI):m/z,calcd for C₁₆H₁₄N₃O₄[M+H+]:312.0979,found 312.0976.

C) 4- ((3- aminomethyl phenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- ((3- aminomethyl phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, prepare C) methods described in process be the same as Example 3, obtains red-brown powder shape solid 20mg, yield is 23%, mp:216-218℃.

¹H NMR(DMSO-d₆)δ(ppm):9.52 (s, 1H), 8.07 (d, J=8.8Hz, 1H), 7.95 (m, 2H), 7.55 (brs, 4H), 7.32 (t, J=7.6Hz, 1H), 7.18-7.15 (m, 2H), 7.03 (d, J=7.6Hz, 1H), 6.69 (d, J= 9.2Hz,1H),2.34(s,3H).

Embodiment 14：4- ((4- aminomethyl phenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) 4- ((4- aminomethyl phenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 4- methylanilines as initiation material, preparation process is with implementation A) methods described in example 3, obtains yellow solid 256mg, yield is 81%, mp:232-234℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.16 (d, J=9.2Hz, 1H), 7.33 (s, 1H), 7.25 (d, J=7.2Hz, 2H), 7.21 (d, J=8.0Hz, 2H), 6.71 (brs, 1H), 6.65 (d, J=8.8Hz, 2H), 4.44 (q, J =7.2Hz, 2H), 2.40 (s, 3H), 1.43 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₈H₁₈N₃O₄[M +H⁺]:340.1292,found 340.1281.

B) 4- ((4- aminomethyl phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- ((4- aminomethyl phenyls) amino), -7- nitro -1H- indole -2-ethyl formates is initiation materials, and preparation process is same B) methods described in embodiment 3, obtains yellow solid 160mg, yield is 97%, mp:257-259℃.

¹H NMR(DMSO-d₆)δ(ppm):10.70 (s, 1H), 9.61 (s, 1H), 8.09 (d, J=9.2Hz, 1H), 7.74 (s, 1H), 7.27 (s, 4H), 6.62 (d, J=9.2Hz, 1H), 2.34 (s, 3H)；HRMS(ESI):m/z,calcd for C₁₆H₁₄N₃O₄[M+H⁺]:312.0979,found 312.0973.

C) 4- ((4- aminomethyl phenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- ((4- aminomethyl phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, prepare C) methods described in process be the same as Example 3, obtains red-brown powder shape solid 102mg, yield is 92%, mp:237-239℃.

¹H NMR(DMSO-d₆)δ(ppm):13.10(brs,1H),11.87(brs,1H),9.64(s,1H),8.12(d,J =9.2Hz, 1H), 8.04 (d, J=7.6Hz, 2H), 7.83 (s, 1H), 7.74 (t, J=7.2Hz, 1H), 7.67 (t, J= 7.6Hz, 2H), 7.28-7.23 (m, 4H), 6.60 (d, J=9.2Hz, 1H), 2.33 (s, 3H)

Embodiment 15：4- ((3- cyano-phenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) 4- ((3- cyano-phenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- cyano-anilines as initiation material, preparation process is with implementation A) methods described in example 3, obtains yellow solid 259mg, yield is 90%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):10.97 (s, 1H), 9.71 (s, 1H), 8.13 (d, J=9.2Hz, 1H), 7.70- (t, J=7.2Hz, the 3H) of 7.60 (m, 5H), 6.86 (d, J=9.2Hz, 1H), 4.36 (q, J=7.2Hz, 2H), 1.36

B) 4- ((3- cyano-phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- ((3- cyano-phenyls) amino), -7- nitro -1H- indole -2-ethyl formates is initiation materials, and preparation process is same B) methods described in embodiment 3, obtains yellow solid 117mg, yield is 99%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.83 (s, 1H), 9.71 (s, 1H), 8.14 (d, J= 8.8Hz, 1H), 7.79 (s, 1H), 7.71-7.61 (m, 4H), 6.87 (d, J=9.2Hz, 1H)

C) 4- ((3- cyano-phenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- ((3- cyano-phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, prepare C) methods described in process be the same as Example 3, obtains red-brown powder shape solid 58mg, yield is 81%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.10(brs,1H),11.92(brs,1H),9.76(brs,1H),8.18(d, J=8.8Hz, 1H), 8.05 (d, J=8.0Hz, 2H), 7.82-7.62 (m, 8H), 6.85 (d, J=9.2Hz, 1H)

Embodiment 16：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (3- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 3- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains yellow powdery solid 40mg, yield is 88%, mp:153- 154℃。

¹H NMR(DMSO-d₆)δ(ppm):11.84 (brs, 2H), 9.63 (s, 1H), 8.14 (d, J=9.2Hz, 1H), 7.84 (s, 1H), 7.61-7.55 (m, 2H), 7.51 (s, 1H), 7.36-7.29 (m, 2H), 6.94 (d, J=8.0Hz, 1H), 6.90 (s, 1H), 6.78 (t, J=9.2Hz, 2H), 3.84 (s, 3H), 3.76 (s, 3H)；HRMS(ESI):m/z,calcd.for C₂₃H₂₁N₄O₇S[M+H]⁺:497.1131,found 497.1117.

Embodiment 17：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains yellow powdery solid 50mg, yield is 55%, mp:>250 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.85(brs,1H),9.62(brs,1H),8.13(d, J=9.2Hz, 1H), 7.96 (d, J=8.4Hz, 2H), 7.82 (s, 1H), 7.33 (t, J=8.0Hz, 1H), 7.15 (d, J= 8.4Hz, 2H), 6.94 (d, J=8.0Hz, 2H), 6.89 (s, 1H), 6.77 (t, J=9.6Hz, 2H), 3.85 (s, 3H), 3.76 (s,3H)；¹³C NMR(100MHz,DMSO-d₆):δ163.22,160.10,157.24,147.05,140.34,131.96, 130.68,130.25,130.17,128.61,127.17,124.10,116.71,114.98,114.29,110.48,110.39, 108.47,102.26,55.78,55.16.HRMS(ESI):m/z,calcd.for C₂₃H₂₁N₄O₇S[M+H]⁺:497.1126, found 497.1117.

Embodiment 18：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (2- fluorophenylsulphonyls) -1H- indole 2-carboxamides

It is former using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 2- fluorobenzenesulfonamides as starting Material, c) methods described in preparation process be the same as Example 11, obtains yellow powdery solid 70mg, yield is 79%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.93 (brs, 1H), 9.65 (s, 1H), 8.16 (d, J=9.3Hz, 1H), 8.04 (t, J=6.9Hz, 1H), 7.85-7.79 (m, 2H), 7.48 (t, J=7.8Hz, 2H), 7.34 (t, J=8.1Hz, 1H), (s, the 3H) of 6.94 (d, J=8.4Hz, 1H), 6.90 (s, 1H), 6.78 (t, J=6.3Hz, 2H), 3.77

Embodiment 19：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (3- fluorophenylsulphonyls) -1H- indole 2-carboxamides

It is former using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 3- fluorobenzenesulfonamides as starting Material, c) methods described in preparation process be the same as Example 3, obtains yellow powdery solid 48mg, yield is 54%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.84 (brs, 1H), 9.66 (s, 1H), 8.15 (d, J=9.2Hz, 1H), 7.91-7.83(m,3H),7.74(dd,J₁=13.6Hz, J₂=8.0Hz, 1H), 7.63 (t, J=8.0Hz, 1H), 7.35 (t, J =8.0Hz, 1H), 6.95 (d, J=8.0Hz, 1H), 6.91 (s, 1H), 6.79 (t, J=9.2Hz, 2H), 3.78 (s, 3H)； HRMS(ESI):m/z,calcd.for C₂₂H₁₈N₄O₆FS[M+H]⁺:485.0931,found 485.0918.

Embodiment 20：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- fluorophenylsulphonyls) -1H- indole 2-carboxamides

It is former using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- fluorobenzenesulfonamides as starting Material, c) methods described in preparation process be the same as Example 3, obtains yellow powdery solid 66mg, yield is 74%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.88(brs,1H),9.66(s,1H),8.16-8.11(m,3H),7.86(s, 1H), 7.51 (t, J=8.8Hz, 2H), 7.35 (t, J=8.0Hz, 1H), 6.95 (d, J=8.0Hz, 1H), 6.91 (s, 1H), 6.79 (t, J=9.6Hz, 2H), 3.78 (s, 3H)；HRMS(ESI):m/z,calcd.for C₂₂H₁₈N₄O₆FS[M+H]⁺: 485.0931,found 485.0919.

Embodiment 21：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- Methyl benzenesulfonyls base) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methyl benzenesulfonamides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains orange-yellow pulverulent solids 77mg, yield is 75%, mp:240- 242℃。

¹H NMR(DMSO-d₆)δ(ppm):12.98(brs,1H),11.89(brs,1H),9.67(s,1H),8.15(d,J =9.2Hz, 1H), 7.93 (d, J=8.4Hz, 2H), 7.85 (s, 1H), 7.46 (d, J=8.4Hz, 1H), 7.35 (t, J= 8.4Hz, 1H), 6.95 (d, J=8.4Hz, 1H), 6.91 (s, 1H), 6.81-6.76 (m, 2H), 3.77 (s, 3H), 2.41 (s, 3H)；¹³C NMR(125MHz,DMSO-d₆):δ160.12,157.31,147.11,144.48,140.35,136.40,132.02, 130.31,129.65,128.54,127.83,127.30,124.10,167.73,115.02,110.53,108.49,102.28, 55.19,21.13.HRMS(ESI):m/z,calcd.forC₂₃H₂₁N₄O₆S[M+H]⁺:481.1176,found 481.1167.

Embodiment 22：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- tnBuoromethyl-benzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- trifluoromethyl benzene sulfonamides as C) methods described in initiation material, preparation process be the same as Example 3, obtains orange powder shape solid 68mg, yield is 69%, mp: 259-260℃。

¹H NMR(DMSO-d₆)δ(ppm):11.74 (brs, 1H), 9.64 (s, 1H), 8.24 (d, J=8.4Hz, 2H), 8.15 (d, J=9.2Hz, 1H), 8.04 (d, J=8.0Hz, 2H), 7.82 (s, 1H), 7.35 (d, J=8.0Hz, 1H), 6.95 (d, J=8.0Hz, 1H), 6.90 (s, 1H), 6.79 (d, J=8.8Hz, 1H), 6.77 (d, J=9.2Hz, 1H), 3.77 (s, 3H).

Embodiment 23：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (3- nitrobenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 3- nitrobenzene sulfonamides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains orange powder shape solid 74mg, yield is 79%, mp:255-256 ℃。

¹H NMR(DMSO-d₆)δ(ppm):11.74 (brs, 1H), 9.64 (s, 1H), 8.75 (s, 1H), 8.56 (d, J= 8.4Hz, 1H), 8.46 (d, J=8.0Hz, 1H), 8.15 (d, J=9.2Hz, 1H), 7.97 (t, J=8.0Hz, 1H), 7.85 (s, 1H), 7.35 (t, J=8.4Hz, 1H), 6.50 (d, J=8.0Hz, 1H), 6.91 (s, 1H), 6.79 (d, J=8.4Hz, 1H), 6.77 (d, J=9.2Hz, 1H), 3.78 (s, 3H)

Embodiment 24：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- nitrobenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- nitrobenzene sulfonamides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains orange powder shape solid 70mg, yield is 86%, mp:259-261 ℃。

¹H NMR(DMSO-d₆)δ(ppm):11.73 (brs, 1H), 9.67 (s, 1H), 8.45 (d, J=8.8Hz, 2H), 8.29 (d, J=8.8Hz, 2H), 8.15 (d, J=9.2Hz, 1H), 7.84 (s, 1H), 7.35 (t, J=8.0Hz, 1H), 6.95 (d, J=8.4Hz, 1H), 6.91 (s, 1H), 6.78 (t, J=9.2Hz, 2H), 3.78 (s, 3H)

Embodiment 25：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- difluoro-methoxies benzenesulfonyl) -1H- indoles -2- formyls Amine

With 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- difluoro-methoxy benzsulfamides For initiation material, c) methods described in preparation process be the same as Example 3 obtains orange powder shape solid 68mg, yield is 70%, mp: 260-262℃。

¹H NMR(DMSO-d₆)δ(ppm):13.10(brs,1H),11.87(brs,1H),9.66(s,1H),8.15(d,J =9.2Hz, 1H), 8.11 (d, J=8.4Hz, 2H), 7.85 (s, 1H), 7.43 (t, J=73.6Hz, 1H), 7.43 (d, J= 8.4Hz, 2H), 7.35 (t, J=8.0Hz, 1H), 6.95 (d, J=8.0Hz, 1H), 6.91 (s, 1H), 6.78 (t, J=9.2Hz, 2H),3.79(s,3H).

Embodiment 26：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- trifluoromethoxies benzenesulfonyl) -1H- indoles -2- formyls Amine

With 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- trifluoro-metoxybenzene sulfamides For initiation material, c) methods described in preparation process be the same as Example 3 obtains orange powder shape solid 75mg, yield is 74%, mp: 263-265℃。

¹H NMR(DMSO-d₆)δ(ppm):11.80(brs,1H),9.66(s,1H),8.19-8.14(m,3H),7.85(s, 1H), 7.65 (d, J=8.4Hz, 2H), 7.35 (d, J=8.0Hz, 1H), 6.95 (d, J=8.0Hz, 1H), 6.91 (s, 1H), 6.79 (t, J=9.2Hz, 2H), 3.78 (s, 3H)

Embodiment 27：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- cyanophenylsulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- cvanobenzenesulfonamides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains orange powder shape solid 70mg, yield is 78%, mp:239-240 ℃。

¹H NMR(DMSO-d₆)δ(ppm):11.84 (brs, 1H), 9.64 (s, 1H), 8.18 (d, J=8.4Hz, 2H), 8.14 (d, J=8.8Hz, 1H), 8.12 (d, J=8.4Hz, 2H), 7.80 (s, 1H), 7.35 (d, J=8.4Hz, 1H), 6.95 (d, J=8.0Hz, 2H), 6.91 (s, 1H), 6.80 (d, J=8.4Hz, 1H), 6.77 (d, J=9.2Hz, 1H), 3.78 (s, 3H).

Embodiment 28：

4- ((3- methoxyphenyls) amino) -7- nitros-N- ((4,5- dichloro-thiophene -2- bases) sulfonyl) -1H- indoles - 2- formamides

With 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4,5- dichloro-thiophene -2- sulfonyls Sulfonamide is c) methods described in initiation material, preparation process be the same as Example 3, obtains orange powder shape solid 80mg, yield is 80%, mp:246-248℃.

¹H NMR(DMSO-d₆)δ(ppm):10.28 (brs, 1H), 9.50 (s, 1H), 8.05 (d, J=9.3Hz, 1H), 7.50-7.48 (m, 2H), 7.34 (t, J=8.1Hz, 1H), 8.47 (d, J=7.5Hz, 1H), 6.93 (s, 1H), 6.80-6.76 (m,2H),3.78(s,3H)；HRMS(ESI):m/z,calcd.for C₂₀H₁₅N₄O₆Cl₂S₂[M+H]⁺:540.9810,found 540.9798.

Embodiment 29：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (thiophene -2- bases sulfonyl) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and thiophene -2- sulfonylsulfonamides as C) methods described in initiation material, preparation process be the same as Example 3, obtains orange powder shape solid 70mg, yield is 81%, mp: 249-251℃。

¹H NMR(DMSO-d₆)δ(ppm):11.84 (brs, 1H), 9.67 (s, 1H), 8.15 (d, J=9.2Hz, 1H), 8.08 (d, J=4.8Hz, 1H), 7.91 (d, J=4.8Hz, 2H), 7.35 (t, J=8.4Hz, 1H), 7.24 (t, J=4.4Hz, 1H), 6.96 (d, J=8.0Hz, 1H), 6.92 (s, 1H), 6.80 (d, J=8.0Hz, 1H), 6.78 (d, J=9.2Hz, 1H), 3.78(s,3H).

Embodiment 30：

4- ((3- methoxyphenyls) amino) -7- nitros-N- (naphthalene -2- bases sulfonyl) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and naphthalene -2- sulfonylsulfonamides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains orange red pulverulent solids 80mg, yield is 84%, mp: 254-255℃。

¹H NMR(DMSO-d₆)δ(ppm):13.16(brs,1H),11.88(brs,1H),9.63(s,1H),8.73(s, 1H), 8.27 (d, J=8.0Hz, 1H), 8.18 (d, J=8.8Hz, 1H), 8.15 (d, J=9.2Hz, 1H), 8.08 (d, J= 8.0Hz, 1H), 8.01 (d, J=8.8Hz, 1H), 7.82 (s, 1H), 7.78-7.69 (m, 2H), 7.34 (t, J=8.0Hz, 1H), 6.93 (d, J=8.0Hz, 1H), 6.89 (s, 1H), 6.77 (t, J=9.2Hz, 2H), 3.76 (s, 3H)；HRMS(ESI):m/z, calcd.for C₂₆H₂₁N₄O₆S[M+H]⁺:517.1182,found 517.1193.

Embodiment 31：

4- ((3- aminomethyl phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- aminomethyl phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 11, obtains orange red pulverulent solids 53mg, yield is 88%, mp:265- 267℃。

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.88(brs,1H),9.63(s,1H),8.13(d,J =8.8Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.84 (s, 1H), 7.33 (t, J=8.0Hz, 1H), 7.18-7.15 (m, 4H), (s, the 3H) of 7.05 (d, J=7.2Hz, 1H), 6.69 (d, J=9.2Hz, 1H), 3.86 (s, 3H), 2.34¹³C NMR (125MHz,DMSO-d₆):δ147.42,139.01,138.96,132.01,130.21,129.36,127.32,125.76, 123.88,123.71,120.29,116.52,114.33,101.96,55.82,21.01.HRMS(ESI):m/z,calcd.for C₂₃H₂₁N₄O₆S[M+H]⁺:481.1182,found481.1171.

Embodiment 32：4- ((3- Trifluoromethoxyphen-ls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) 4- ((3- Trifluoromethoxyphen-ls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- trifluoro-methoxyanilines as initiation material, preparation process A) methods described in be the same as Example 3, obtains Orange red solid 300mg, yield is 89%, mp:220-221℃.

¹H NMR(CDCl₃)δ(ppm):10.48 (brs, 1H), 8.22 (d, J=8.8Hz, 1H), 7.45 (t, J=8.0Hz, 1H), 7.34 (s, 1H), 7.26 (m, 1H), 7.18 (s, 1H), 7.08 (d, J=8.0Hz, 1H), 6.84 (d, J=9.2Hz, 1H), (t, J=7.2Hz, the 3H) of 6.72 (s, 1H), 4.45 (q, J=7.2Hz, 2H), 1.44

B) 4- ((3- Trifluoromethoxyphen-ls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- ((3- Trifluoromethoxyphen-ls) amino) -7- nitro -1H- indole -2-ethyl formates as initiation material, prepare B) methods described in process be the same as Example 3, obtains yellow-brown solid 200mg, yield is 98%, mp:280-282℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.82 (s, 1H), 9.81 (s, 1H), 8.16 (d, J= 9.0Hz, 1H), 7.76 (d, J=2.4Hz, 1H), 7.56 (t, J=8.12Hz, 1H), 7.45 (d, J=7.8Hz, 1H), 7.35 (s, 1H), 7.16 (d, J=8.4Hz, 1H), 6.87 (d, J=9.0Hz, 1H)

C) 4- ((3- Trifluoromethoxyphen-ls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

With 4- ((3- Trifluoromethoxyphen-ls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains orange red pulverulent solids 68mg, yield is 52%, mp:234-235℃。

¹H NMR(DMSO-d₆)δ(ppm):12.93(brs,1H),11.91(brs,1H),9.74(s,1H),8.18(d,J =8.8Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.81 (s, 1H), 7.55 (t, J=8.4Hz, 1H), 7.43 (d, J= 8.4Hz, 1H), 7.31 (s, 1H), 7.20-7.16 (m, 3H), 6.85 (d, J=8.8Hz, 1H), 3.86 (s, 3H)

Embodiment 33：

4- ((3,4,5- trimethoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

With 4- ((3,4,5- trimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains red-brown powder shape solid 33mg, yield is 42%, mp:268-270℃。

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.88(brs,1H),9.62(s,1H),8.13(d,J =9.2Hz, 1H), 7.98 (d, J=8.4Hz, 2H), 7.83 (s, 1H), 7.17 (d, J=8.4Hz, 1H), 6.75 (d, J= 9.2Hz,1H),6.66(s,2H),3.86(s,3H),3.78(s,6H),3.68(s,3H)；¹³CNMR(125MHz,DMSO-d₆):δ 163.26,157.26,153.35,147.60,134.83,134.80,132.03,130.24,127.45,123.75,116.36, 114.34,110.45,102.24,101.12,60.16,55.93,55.82.HRMS(ESI):m/z,calcd.for C₂₅H₂₅N₄O₉S[M+H]⁺:557.1325,found557.1337.

Embodiment 34：4- ((3- ethoxyl phenenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) 4- ((3- ethoxyl phenenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- phenetidines as initiation material, preparation process is with real A) methods described is applied in example 3, Orange red solid 258mg is obtained, yield is 94%, mp:193-195℃.

¹HNMR(DMSO-d₆)δ(ppm):10.92 (s, 1H), 9.63 (s, 1H), 8.14 (d, J=9.2Hz, 1H), 7.84 (s, 1H), 7.34 (t, J=8.0Hz, 1H), 6.96 (d, J=8.0Hz, 1H), 6.91 (s, 1H), 6.80 (d, J=8.8Hz, 1H), 6.78 (d, J=6.4Hz, 1H), 4.38 (q, J=7.2Hz, 2H), 4.05 (q, J=7.2Hz, 2H), 1.39-1.33 (m, 6H).

B) 4- ((3- ethoxyl phenenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- ((3- ethoxyl phenenyls) amino), -7- nitro -1H- indole -2-ethyl formates is initiation materials, preparation process B) methods described in be the same as Example 3, obtains yellow-brown solid 156mg, yield is 98%, mp:231-233℃.

¹H NMR(DMSO-d₆)δ(ppm):10.73 (s, 1H), 9.61 (s, 1H), 8.13 (d, J=9.2Hz, 1H), 7.74 (s, 1H), 7.35 (t, J=8.0Hz, 1H), 6.96 (d J=8.0Hz, 1H), 6.91 (s, 1H), 6.79 (d, J=9.2Hz, 2H), 4.05 (q, J=7.2Hz, 1H), 1.34 (t, J=7.2Hz, 1H)

C) 4- ((3- ethoxyl phenenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- ethoxyl phenenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains yellow powdery solid 60mg, yield is 57%, mp:225- 227℃。

¹H NMR(DMSO-d₆)δ(ppm):12.98(brs,1H),11.88(brs,1H),9.65(s,1H),8.15(d,J =9.2Hz, 1H), 7.98 (d, J=8.8Hz, 1H), 7.84 (s, 1H), 7.33 (t, J=8.0Hz, 1H), 7.17 (d, J= 8.8Hz, 1H), 6.93 (d, J=8.0Hz, 1H), 6.89 (s, 1H), 6.78 (d, J=6.4Hz, 1H), 6.76 (d, J=8.8Hz, 1H), 4.04 (q, J=6.8Hz, 2H), 3.86 (s, 3H), 1.33 (t, J=6.8Hz, 3H)；HRMS(ESI):m/z, calcd.for C₂₄H₂₃N₄O₇S[M+H]⁺:511.1287,found511.1277.

Embodiment 35：

4- ((3,5- Dimethoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

With 4- ((3,4- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains orange red pulverulent solids 70mg, yield is 80%, mp:180-182℃。

¹H NMR(DMSO-d₆)δ(ppm):12.90(brs,1H),11.89(brs,1H),9.60(s,1H),8.16(d,J =8.8Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.85 (s, 1H), 7.17 (d, J=8.8Hz, 2H), 6.83 (d, J= 9.2Hz, 1H), 6.52 (d, J=1.6Hz, 2H), 6.36 (s, 1H), 3.86 (s, 3H), 3.76 (s, 6H)

Embodiment 36：4- ((3,4- methylenedioxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) 4- ((3,4- methylenedioxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

With the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and the sub- dimethoxyaniline of 3,4- for initiation material, prepared A) methods described in journey be the same as Example 3, obtains red brown solid 316mg, yield is 92%, mp:169-170℃.

¹H NMR(DMSO-d₆)δ(ppm):10.88 (s, 1H), 9.57 (s, 1H), 8.10 (d, J=9.2Hz, 1H), 7.80 (s, 1H), 7.00 (d, J=8.4Hz, 1H), 6.98 (s, 1H), 6.84 (d, J=8.4Hz, 1H), 6.55 (d, J=8.8Hz, 1H), (t, J=7.2Hz, the 3H) of 6.09 (s, 2H), 4.37 (q, J=7.2Hz, 2H), 1.36

B) 4- ((3,4- methylenedioxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3,4- sub- Dimethoxyphenyl) amino), -7- nitro -1H- indole -2-ethyl formates is initiation materials, system B) methods described in standby process be the same as Example 3, obtains red brown solid 216mg, yield is 100%, mp:240-242℃.

¹H NMR(DMSO-d₆)δ(ppm):13.40 (brs, 1H), 10.70 (s, 1H), 9.59 (s, 1H), 8.09 (d, J= 8.8Hz, 1H), 7.72 (s, 1H), 7.01 (d, J=8.0Hz, 1H), 6.98 (s, 1H), 6.84 (d, J=8.4Hz, 1H), 6.54 (d, J=9.2Hz, 1H), 6.09 (s, 2H)

C) 4- ((3,4- methylenedioxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((3,4- methylenedioxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains red-brown powder shape solid 75mg, yield is 70%, mp:250-252℃。

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.87(brs,1H),9.57(s,1H),8.11(d,J =9.2Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.78 (s, 1H), 7.17 (d, J=8.8Hz, 2H), 6.99 (d, J= 8.0Hz, 1H), 6.95 (s, 1H), 6.81 (d, J=9.2Hz, 1H), 6.51 (d, J=9.2Hz, 1H), 6.08 (s, 2H), 3.86 (s,3H).

Embodiment 37：C) 4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) 4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- methoxyl group -4- chloroanilines as initiation material, prepared A) methods described in journey be the same as Example 3, obtains red brown solid 296mg, yield is 81%, mp:242-244℃.

¹H NMR(DMSO-d₆)δ(ppm):10.98 (s, 1H), 9.69 (s, 1H), 8.14 (d, J=9.2Hz, 1H), 7.83 (s, 1H), 7.47 (d, J=8.4Hz, 1H), 7.13 (s, 1H), 6.99 (d, J=8.4Hz, 1H), 6.87 (d, J=9.2Hz, 1H), (t, J=7.2Hz, the 3H) of 4.38 (q, J=7.2Hz, 2H), 3.88 (s, 3H), 1.37

B) 4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates as initiation material, system B) methods described in standby process be the same as Example 3, obtains orange solids 185mg, yield is 100%, mp:255-258℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.79 (s, 1H), 9.69 (s, 1H), 8.14 (d, J= 9.2Hz, 1H), 7.75 (s, 1H), 7.47 (d, J=8.8Hz, 1H), 7.14 (s, 1H), 6.99 (d, J=8.4Hz, 1H), 6.85 (d, J=9.2Hz, 1H), 3.88 (s, 3H)

C) 4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains orange powder shape solid 94mg, yield is 91%, mp: 275-277℃。

¹H NMR(DMSO-d₆)δ(ppm):12.92(brs,1H),11.90(brs,1H),9.70(s,1H),8.15(d,J =9.2Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.83 (s, 1H), 7.46 (d, J=8.4Hz, 1H), 7.17 (d, J= 8.4Hz, 2H), 7.11 (s, 1H), 6.96 (d, J=8.4Hz, 1H), 6.82 (d, J=9.2Hz, 1H), 3.86 (s, 6H)；¹³C NMR(125MHz,DMSO-d₆):δ163.26,155.05,146.65,139.47,131.92,130.31,130.23,127.12, 124.43,118.99,116.97,116.47,115.27,114.34,107.42,102.52,56.11,55.82.HRMS (ESI):m/z,calcd.for C₂₃H₂₀N₄O₇ClS[M+H]⁺:531.0741,found 531.0732.

Embodiment 38：

4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

It is former using 4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as starting Material, c) methods described in preparation process be the same as Example 3, obtains yellow powdery solid 47mg, yield is 85%, mp:>280℃

¹H NMR(DMSO-d₆)δ(ppm):13.05(brs,1H),11.88(brs,1H),9.70(s,1H),8.15(d,J =9.2Hz, 1H), 8.05 (d, J=7.6Hz, 2H), 7.83 (s, 1H), 7.74 (t, J=7.2Hz, 1H), 7.67 (t, J= 7.6Hz, 2H), 7.46 (d, J=8.8Hz, 1H), 7.11 (s, 1H), 6.96 (d, J=8.4Hz, 1H), 6.82 (d, J=9.2Hz, 1H),3.86(s,3H).

Embodiment 39：4- ((3- methoxyl group -4- fluorophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) 4- ((3- methoxyl group -4- fluorophenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- methoxyl group -4- fluoroanilines as initiation material, prepared A) methods described in journey be the same as Example 3, obtains yellow solid 120mg, yield is 58%, mp:224-225℃.

¹H NMR(CDCl₃)δ(ppm):10.48 (brs, 1H), 8.18 (d, J=9.6Hz, 1H), 7.32 (d, J=2.1Hz, 1H), 7.15 (d, J=9.0Hz, 1H), 6.92 (d, J=7.2Hz, 1H), 6.86 (d, J=8.4Hz, 1H), 6.63 (d, J= 8.7Hz, 2H), 4.45 (q, J=7.2Hz, 2H), 3.90 (s, 3H), 1.44 (t, J=7.2Hz, 3H)

B) 4- ((3- methoxyl group -4- fluorophenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- ((3- methoxyl group -4- fluorophenyls) amino) -7- nitro -1H- indole -2-ethyl formates as initiation material, system B) methods described in standby process be the same as Example 3, obtains brick-red solid 90mg, yield is 88%, mp:268-270℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.74 (s, 1H), 9.64 (s, 1H), 8.11 (d, J= 8.8Hz,1H),7.73(s,1H),7.30(dd,J₁=9.2Hz, J₂=10.8Hz, 1H), 7.16 (d, J=7.6Hz, 1H), 6.95 (d, J=8.4Hz, 1H), 6.70 (d, J=9.2Hz, 1H), 3.86 (s, 3H)

C) 4- ((3- methoxyl group -4- fluorophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((3- methoxyl group -4- fluorophenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains yellow powdery solid 24mg, yield is 65%, mp:> 290℃。

¹H NMR(DMSO-d₆)δ(ppm):12.92 (brs, 1H), 11.89 (s, 1H), 9.65 (s, 1H), 8.13 (d, J= 9.2Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.81 (s, 1H), 7.28 (dd, J₁=11.2Hz, J₁=8.8Hz, 1H), 7.17 (d, J=8.8Hz, 2H), 7.13 (d, J=7.6Hz, 1H), 6.93-6.91 (m, 1H), 6.67 (d, J=9.2Hz, 1H), 3.86 (s,3H),3.84(s,3H)；HRMS(ESI):m/z,calcd.for C₂₃H₂₀N₄O₇FS[M+H]⁺:515.1037,found 515.1025.

Embodiment 40：4- ((3- methoxyl group -5- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) 4- ((3- methoxyl group -5- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- methoxyl group -5- chloroanilines as initiation material, prepared A) methods described in journey be the same as Example 3, obtains orange solids 285mg, yield is 98%, mp:225-227℃.

¹H NMR(DMSO-d₆)δ(ppm):11.02 (s, 1H), 9.63 (s, 1H), 8.18 (d, J=8.8Hz, 1H), 7.81 (s, 1H), 7.01 (s, 1H), 6.91 (s, 2H), 6.85 (s, 1H), 4.38 (q, J=7.2Hz, 2H), 3.81 (s, 3H), 1.37 (t, J=7.2Hz, 3H)

B) 4- ((3- methoxyl group -5- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- ((3- methoxyl group -5- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates as initiation material, system B) methods described in standby process be the same as Example 3, obtains Orange red solid 183mg, yield is 96%, mp:269-272℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.81 (s, 1H), 9.62 (s, 1H), 8.17 (d, J= 9.2Hz, 1H), 7.72 (s, 1H), 7.01 (s, 1H), 6.90 (s, 1H), 6.89 (d, J=9.6Hz, 1H), 6.85 (s, 1H), 3.80(s,3H).

C) 4- ((3- methoxyl group -5- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((3- methoxyl group -5- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains yellow powdery solid 91mg, yield is 80%, mp: 278-280℃。

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.90(brs,1H),9.64(s,1H),8.19(d,J =9.2Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.82 (s, 1H), 7.17 (d, J=8.8Hz, 2H), 6.99 (s, 1H), 6.88 (s, 1H), 6.87 (d, J=9.6Hz, 1H), 6.84 (s, 1H), 3.86 (s, 3H), 3.79 (s, 3H)；HRMS(ESI):m/ z,calcd.for C₂₃H₂₀N₄O₇ClS[M+H]⁺:531.0741,found531.0732.

The 4- of embodiment 41. ((3- methoxyl group -5- chlorphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- indoles -2- Formamide

It is former using 4- ((3- methoxyl group -5- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as starting Material, c) methods described in preparation process be the same as Example 3, obtains yellow powdery solid 44mg, yield is 80%, mp:269-271 ℃。

¹H NMR(DMSO-d₆)δ(ppm):13.05(brs,1H),11.88(brs,1H),9.64(s,1H),8.19(d,J =9.2Hz, 1H), 8.04 (d, J=7.6Hz, 2H), 7.81 (s, 1H), 7.74 (t, J=7.2Hz, 1H), 7.66 (t, J= 7.6Hz, 2H), 6.99 (s, 1H), 6.88 (s, 1H), 6.87 (d, J=9.2Hz, 1H), 6.84 (s, 1H), 3.79 (s, 3H)

Embodiment 42:4- ((5- methoxyl group -2- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) 4- ((5- methoxyl group -2- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 5- methoxyl group -2- chloroanilines as initiation material, prepared A) methods described in journey be the same as Example 3, obtains yellow solid 180mg, yield is 83%, mp:175-177℃.

¹H NMR(CDCl₃)δ(ppm):10.48 (brs, 1H), 8.23 (d, J=8.8Hz, 1H), 7.39 (d, J= 10.0Hz, 2H), 7.10 (d, J=2.4Hz, 1H), 6.91 (d, J=9.2Hz, 1H), 6.85 (s, 1H), 6.69 (dd, J₁= 2.1Hz,J₂=9.2Hz, 1H), 4.46 (q, J=7.2Hz, 2H), 3.81 (s, 3H), 1.45 (t, J=7.2Hz, 3H)

B) 4- ((5- methoxyl group -2- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 4- ((5- methoxyl group -2- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates as initiation material, system B) methods described in standby process be the same as Example 3, obtains Orange red solid 110mg, yield is 97%, mp:220-222℃.

¹H NMR(DMSO-d₆)δ(ppm):10.71 (s, 1H), 9.63 (s, 1H), 8.07 (d, J=8.8Hz, 1H), 7.68 (s, 1H), 7.53 (d, J=8.8Hz, 1H), 7.07 (d, J=2.4Hz, 1H), 7.16 (d, J₁=2.1Hz, J₂=8.8Hz, 1H), 6.14 (d, J=9.2Hz, 1H), 3.76 (s, 3H)

C) 4- ((5- methoxyl group -2- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((5- methoxyl group -2- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and to methoxybenzenesulphoismide For initiation material, c) methods described in preparation process be the same as Example 3 obtains yellow powdery solid 55mg, yield is 63%, mp:> 290℃。

¹H NMR(DMSO-d₆)δ(ppm):12.92(brs,1H),11.85(brs,1H),9.58(s,1H),8.11(d,J =9.2Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.75 (d, J=8.4Hz, 1H), 7.54 (d, J=8.8Hz, 1H), 7.16 (d, J=8.4Hz, 2H), 7.07 (d, J=2.1Hz, 1H), 6.99 (dd, J₁=2.1Hz, J₂=8.8Hz, 1H), 6.15 (d, J= 8.8Hz,1H),3.86(s,3H),3.78(s,3H).

Embodiment 43:4- ((5- methoxyl groups -2,4 dichloro benzene base) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) 4- ((5- methoxyl groups -2,4 dichloro benzene base) amino) -7- nitro -1H- indole -2-ethyl formates

With the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 5- methoxyl groups -2,4- dichloroaniline for initiation material, system A) methods described in standby process be the same as Example 3, obtains orange/yellow solid 206mg, yield is 81%, mp:215-217℃.

¹H NMR(CDCl₃)δ(ppm):10.48 (s, 1H), 8.23 (d, J=8.8Hz, 1H), 7.51 (s, 1H), 7.36 (s, 1H), 7.10 (s, 1H), 6.82 (d, J=8.8Hz, 1H), 6.76 (s, 1H), 4.47 (q, J=7.2Hz, 2H), 3.87 (s, 3H), 1.45 (t, J=7.2Hz, 3H)

B) 4- ((5- methoxyl groups -2,4 dichloro benzene base) amino) -7- nitro -1H- indole-2-carboxylic acids

It is former by starting of 4- ((5- methoxyl groups -2,4 dichloro benzene base) amino) -7- nitro -1H- indole -2-ethyl formates Material, b) methods described in preparation process be the same as Example 3, obtains Orange red solid 86mg, yield is 77%, mp:264-266℃.

¹H NMR(DMSO-d₆)δ(ppm):10.77 (s, 1H), 9.64 (s, 1H), 8.09 (d, J=8.8Hz, 1H), 7.80 (s, 1H), 7.72 (s, 1H), 7.32 (s, 1H), 6.23 (d, J=8.8Hz, 1H), 3.87 (s, 3H)

C) 4- ((5- methoxyl groups -2,4 dichloro benzene base) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

With 4- ((5- methoxyl groups -2,4 dichloro benzene base) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphurs Acid amides is c) methods described in initiation material, preparation process be the same as Example 3, obtains Red-brown powder shape solid 44mg, yield is 78%, mp:289-291℃.

¹H NMR(DMSO-d₆)δ(ppm):12.92(brs,1H),11.88(brs,1H),9.63(s,1H),8.11(d,J =8.8Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.79 (s, 1H), 7.77 (s, 1H), 7.29 (s, 1H), 7.17 (d, J= 8.8Hz, 1H), 6.21 (d, J=9.2Hz, 1H), 3.86 (s, 3H), 3.85 (s, 3H)

The 4- of embodiment 44 ((3- fluorophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

A) 4- ((3- fluorophenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- fluoroanilines as initiation material, preparation process be the same as Example A) methods described in 3, obtains yellow solid 242mg, yield is 95%, mp:215-216℃.

¹H NMR(acetone-d₆)δ(ppm):10.59 (brs, 1H), 8.87 (s, 1H), 8.20 (d, J=9.2Hz, 1H), 7.66 (s, 1H), 7.51-7.45 (m, 1H), 7.30 (d, J=8.0Hz, 1H), 7.22 (d, J=10.4Hz, 1H), 7.01-6.95 (m, 2H), 4.41 (q, J=7.2Hz, 2H), 1.40 (t, J=7.2Hz, 3H)

B) 4- ((3- fluorophenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- fluorophenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with implementation B) methods described in example 3, obtains yellow solid 60mg, yield is 48%, mp:>250℃.

¹HNMR(DMSO-d₆)δ(ppm):13.32 (brs, 1H), 10.77 (s, 1H), 9.66 (s, 1H), 8.13 (d, J= 9.2Hz, 1H), 7.73 (s, 1H), 7.49-7.43 (m, 1H), 7.23-7.19 (m, 2H), 7.00 (t, J=8.0Hz, 1H), 6.85 (d, J=9.2Hz, 1H)

C) 4- ((3- fluorophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

It is former using 4- ((3- fluorophenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting Material, c) methods described in preparation process be the same as Example 3, obtains pale yellow powder shape solid 29mg, yield is 59%, mp:>290℃.

¹H NMR(DMSO-d₆)δ(ppm):12.87 (brs, 1H), 11.92 (s, 1H), 9.70 (s, 1H), 8.18 (d, J= 9.0Hz, 1H), 7.98 (d, J=9.0Hz, 2H), 7.83 (d, J=2.1Hz, 1H), 7.48-7.43 (m, 1H), 7.23-7.20 (m, 2H), 7.17 (d, J=8.7Hz, 2H), 7.02 (t, J=9.0Hz, 2H), 6.84 (d, J=9.0Hz, 1H), 3.86 (s, 3H).

The 4- of embodiment 45. ((4- fluorophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

A) 4- ((4- fluorophenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 4- fluoroanilines as initiation material, preparation process be the same as Example A) methods described in 3, obtains yellow solid 250mg, yield is 98%, mp:205-207℃.

¹H NMR(acetone-d₆)δ(ppm):10.59 (brs, 1H), 8.82 (s, 1H), 8.16 (d, J=9.2Hz, 1H), 7.67 (s, 1H), 7.51-7.48 (m, 2H), 7.25 (t, J=8.8Hz, 1H), 6.74 (dd, J₁=4.0Hz, J₂=8.8Hz, 1H), 4.41 (q, J=7.2Hz, 2H), 1.40 (t, J=7.2Hz, 3H)

B) 4- ((4- fluorophenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((4- fluorophenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with implementation B) methods described in example 3, obtains yellow solid 113mg, yield is 81%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):10.72 (s, 1H), 9.61 (s, 1H), 8.09 (d, J=9.2Hz, 1H), 7.70 (s, 1H), 7.42-7.39 (m, 2H), 7.29 (t, J=8.8Hz, 2H), 6.59 (d, J=9.2Hz, 1H)

C) 4- ((4- fluorophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

It is former using 4- ((4- fluorophenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting Material, c) methods described in preparation process be the same as Example 3, obtains Red-brown powder shape solid 56mg, yield is 73%, mp:>290℃.

¹H NMR(DMSO-d₆)δ(ppm):12.93(brs,1H),11.90(brs,1H),9.66(s,1H),8.13(d,J =9.3Hz, 1H), 7.98 (d, J=8.7Hz, 2H), 7.81 (d, J=2.1Hz, 1H), 7.42-7.38 (m, 2H), 7.30 (t, J =8.4Hz, 2H), 7.18 (d, J=8.7Hz, 2H), 6.58 (d, J=9.0Hz, 1H), 3.86 (s, 3H)

The 4- of embodiment 46. ((2- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

A) 4- ((2- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 2- chloroanilines as initiation material, preparation process be the same as Example A) methods described in 3, obtains Orange red solid 130mg, yield is 65%, mp:136-137℃.

¹H NMR(CDCl₃)δ(ppm):10.48 (brs, 1H), 8.21 (d, J=8.8Hz, 1H), 7.57 (d, J=8.0Hz, 1H), 7.52 (d, J=8.0Hz, 1H), 7.37 (s, 1H), 7.34 (t, J=8.0Hz, 1H), 7.15 (t, J=8.0Hz, 1H), 6.87 (s, 1H), 6.83 (d, J=9.2Hz, 1H), 4.46 (q, J=7.2Hz, 2H), 3.86 (s, 3H), 1.45 (t, J= 7.2Hz,3H).

B) 4- ((2- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((2- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with implementation B) methods described in example 3, obtains yellow solid 118mg, yield is 98%, mp:265-267℃.

¹H NMR(DMSO-d₆)δ(ppm):10.72 (s, 1H), 9.62 (s, 1H), 8.09 (d, J=8.8Hz, 1H), 7.68 (d, J=8.0Hz, 1H), 7.65 (s, 1H), 7.54 (d, J=7.6Hz, 1H), 7.49 (t, J=7.2Hz, 1H), 7.42 (t, J= 7.2Hz, 1H), 6.12 (t, J=9.2Hz, 1H)

C) 4- ((2- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

It is former using 4- ((2- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting Material, c) methods described in preparation process be the same as Example 3, obtains yellow powdery solid 42mg, yield is 70%, mp:285-287 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.92(brs,1H),11.88(brs,1H),9.60(s,1H),8.11(d,J =9.2Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.72 (s, 1H), 7.66 (d, J=8.0Hz, 1H), 7.52-7.45 (m, 2H), (s, the 3H) of 7.41 (t, J=6.8Hz, 2H), 7.17 (d, J=8.8Hz, 2H), 6.10 (d, J=8.8Hz, 1H), 3.86

The 4- of embodiment 47. ((3- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

It is former using 4- ((3- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting Material, c) methods described in preparation process be the same as Example 3, obtains orange red pulverulent solids 54mg, yield is 72%, mp:275-277 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.93(brs,1H),11.90(brs,1H),9.68(s,1H),8.18(d,J =9.2Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.81 (s, 1H), 7.46 (t, J=8.4Hz, 1H), 7.41 (s, 1H), 7.35 (d, J=8.0Hz, 1H), 7.24 (d, J=7.6Hz, 1H), 7.17 (d, J=8.8Hz, 2H), 6.81 (d, J=8.8Hz, 1H),3.86(s,3H).

The 4- of embodiment 48. ((4- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

A) .4- ((4- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 4- chloroanilines as initiation material, preparation process be the same as Example A) methods described in 3, obtains yellow solid 265mg, yield is 99%, mp:244-245℃.

¹H NMR(acetone-d₆)δ(ppm):10.63 (brs, 1H), 8.87 (s, 1H), 8.19 (d, J=9.2Hz, 1H), 7.69 (s, 1H), 7.48 (m, 4H), 6.89-6.91 (m, 1H), 4.41 (q, J=7.2Hz, 2H), 1.40 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₇H₁₅ClN₃O₄[M+H⁺]:360.0746,found360.0736.

B) .4- ((4- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((4- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with implementation B) methods described in example 3, obtains yellow solid 145mg, yield is 82%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.78 (s, 1H), 10.77 (s, 1H), 9.65 (s, 1H), 8.12 (d, J= 9.2Hz, 1H), 7.72 (s, 1H), 7.49 (d, J=8.8Hz, 2H), 7.40 (d, J=8.4Hz, 2H), 6.74 (d, J=9.2Hz, 1H)；HRMS(ESI):m/z,calcd for C₁₅H₁₁ClN₃O₄[M+H⁺]:332.0432,found 332.0430.

C) .4- ((4- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

It is former using 4- ((4- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting Material, c) methods described in preparation process be the same as Example 3, obtains orange powder shape solid 44mg, yield is 73%, mp:>290℃.

¹H NMR(DMSO-d₆)δ(ppm):12.93(brs,1H),11.89(brs,1H),9.68(s,1H),8.15(d,J =9.0Hz, 1H), 7.98 (d, J=8.7Hz, 2H), 7.81 (d, J=1.5Hz, 1H), 7.49 (d, J=8.7Hz, 2H), 7.38 (d, J=8.7Hz, 2H), 7.17 (d, J=9.0Hz, 2H), 6.73 (d, J=9.3Hz, 1H), 3.86 (s, 3H)；¹³C NMR (125MHz,DMSO-d₆):δ163.24,157.29,146.66,138.28,131.89,130.73,130.22,129.44, 128.84,128.39,127.06,124.45,124.39,116.94,114.32,110.30,102.12,55.81.HRMS (ESI):m/z,calcd.for C₂₂H₁₈N₄O₆ClS[M+H]⁺:501.0636,found 501.0619.

Embodiment 49：4- ((3,4- dichlorophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((3,4- dichlorophenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3,4-DCA as initiation material, preparation process is with real A) methods described is applied in example 3, yellow solid 152mg is obtained, yield is 69%, mp:227-229℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.21 (d, J=8.8Hz, 1H), 7.49 (d, J=8.8Hz, 1H), 7.43 (d, J=1.5Hz, 1H), 7.34 (d, J=1.2Hz, 1H), 7.17 (d, J₁=1.2Hz, J₂=8.8Hz, 1H), (t, J=7.2Hz, the 3H) of 6.78 (d, J=8.8Hz, 1H), 6.66 (s, 1H), 4.45 (q, J=7.2Hz, 2H), 1.44

B) .4- ((3,4- dichlorophenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3,4- dichlorophenyl) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is same B) methods described in embodiment 3, obtains yellow solid 78mg, yield is 76%, mp:280-282℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.84 (s, 1H), 9.69 (s, 1H), 8.16 (d, J= 8.8Hz, 1H), 7.72 (d, J=1.2Hz, 1H), 7.67 (d, J=8.8Hz, 1H), 7.62 (d, J=1.5Hz, 1H), 7.16 (d, J₁=1.5Hz, J₂=8.8Hz, 1H), 6.87 (d, J=8.8Hz, 1H)

C) .4- ((3,4- dichlorophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 4- ((3,4- dichlorophenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains yellow powdery solid 43mg, yield is 74%, mp:>290 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.93(brs,1H),11.92(brs,1H),9.71(s,1H),8.18(d,J =9.2Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.80 (s, 1H), 7.66 (d, J=8.8Hz, 1H), 7.60 (s, 1H), (s, the 3H) of 7.37 (d, J=8.8Hz, 1H), 7.17 (d, J=8.4Hz, 2H), 6.84 (d, J=8.8Hz, 1H), 3.86

Embodiment 50：4- ((3,4- difluorophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((3,4- difluorophenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 2- chloroanilines as initiation material, preparation process be the same as Example A) methods described in 3, obtains Orange red solid 160mg, yield is 79%, mp:240-242℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (s, 1H), 8.20 (d, J=8.8Hz, 1H), 7.32 (s, 1H), 7.26- 7.16 (m, 3H), 7.05 (d, J=8.4Hz, 1H), 6.68 (d, J=8.8Hz, 1H), 6.61 (s, 1H), 4.45 (q, J= 7.2Hz, 2H), 1.44 (t, J=7.2Hz, 3H)

B) .4- ((3,4- difluorophenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3,4- difluorophenyl) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is same B) methods described in embodiment 3, obtains red brown solid 100mg, yield is 90%, mp:269-272℃.

¹H NMR(DMSO-d₆)δ(ppm):13.40 (brs, 1H), 10.80 (s, 1H), 9.66 (s, 1H), 8.14 (d, J= 9.2Hz, 1H), 7.72 (s, 1H), 7.55-7.45 (m, 2H), 7.23 (d, J=8.8Hz, 1H), 7.75 (d, J=9.2Hz, 1H)

C) .4- ((3,4- difluorophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 4- ((3,4- difluorophenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains yellow powdery solid 51mg, yield is 85%, mp:>280 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.92(brs,1H),11.91(brs,1H),9.66(s,1H),8.15(d,J =9.2Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.79 (s, 1H), 7.54-7.43 (m, 2H), 7.21-7.16 (m, 3H), 6.73 (d, J=9.2Hz, 1H), 3.86 (s, 3H)

Embodiment 51：4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and the fluoro- 3- chloroanilines of 4- as initiation material, preparation process is same A) methods described in embodiment 3, obtains orange solids 140mg, yield is 67%, mp:230-232℃.

¹H NMR(acetone-d₆)δ(ppm):10.61 (brs, 1H), 8.82 (brs, 1H), 8.19 (d, J=9.0Hz, 1H), 7.66 (d, J=1.8Hz, 1H), 7.60 (dd, J₁=2.7Hz, J₂=6.3Hz, 1H), 7.51-7.44 (m, 1H), 7.41 (t, J=8.7Hz, 1H), 6.86 (d, J=8.7Hz, 1H), 4.41 (q, J=7.2Hz, 2H), 1.40 (t, J=7.2Hz, 3H)

B) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process B) methods described in be the same as Example 3, obtains red brown solid 90mg, yield is 97%, mp:242-244℃.

¹H NMR(DMSO-d₆)δ(ppm):10.80 (s, 1H), 9.71 (s, 1H), 8.14 (d, J=9.2Hz, 1H), 7.74 (s,1H),7.60(dd,J₁=1.8Hz, J₂=6.4Hz, 1H), 7.50 (t, J=8.8Hz, 1H), 7.43-7.40 (m, 1H), 6.72 (d, J=9.2Hz, 1H)

C) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains yellow powdery solid 57mg, yield is 78%, mp:>280 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.91(brs,1H),9.69(s,1H),8.16(d,J =8.8Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.80 (s, 1H), 7.57 (d, J₁=1.5Hz, J₂=6.4Hz, 1H), 7.49 (t, J=9.6Hz, 1H), 7.39-7.37 (m, 1H), 7.17 (d, J=8.8Hz, 2H), 6.69 (d, J=9.2Hz, 1H), 3.86 (s,3H).¹³C NMR(125MHz,DMSO-d₆):δ163.28,156.24(J_CF=244.5Hz), 153.32,146.73, 136.59(J_CF=3.0Hz), 131.85,130.62,130.25,128.85,127.12,124.86,124.58,123.65 (J_CF =7.1Hz), 120.07 (J_CF=18.6Hz), 117.67 (J_CF=21.9Hz), 116.86,114.35,110.19,101.97, 55.82.HRMS(ESI):m/z,calcd.for C₂₂H₁₇N₄O₆FClS[M+H]⁺:519.0536,found 519.0532.

Embodiment 52：4- ((the fluoro- 4- chlorphenyls of 3-) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((the fluoro- 4- chlorphenyls of 3-) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and the fluoro- 4- chloroanilines of 3- as initiation material, preparation process is same A) methods described in embodiment 3, obtains orange solids 155mg, yield is 74%, mp:230-232℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.21 (d, J=9.2Hz, 1H), 7.44 (t, J=8.4Hz, 1H), 7.34 (s, 1H), 7.14 (d, J=10.0Hz, 1H), 7.05 (d, J=8.4Hz, 1H), 6.82 (d, J=9.2Hz, 1H), (t, J=7.2Hz, the 3H) of 6.68 (s, 1H), 4.45 (q, J=7.2Hz, 2H), 1.44

B) .4- ((the fluoro- 4- chlorphenyls of 3-) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((the fluoro- 4- chlorphenyls of 3-) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process B) methods described in be the same as Example 3, obtains yellow solid 115mg, yield is 96%, mp:255-258℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.84 (s, 1H), 9.71 (s, 1H), 8.16 (d, J= 8.8Hz, 1H), 7.73 (s, 1H), 7.62 (t, J=8.8Hz, 1H), 7.43 (d, J=10.8Hz, 1H), 7.26 (d, J= 8.4Hz, 1H), 6.90 (d, J=9.2Hz, 1H)

C) .4- ((the fluoro- 4- chlorphenyls of 3-) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 4- ((the fluoro- 4- chlorphenyls of 3-) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains yellow powdery solid 62mg, yield is 84%, mp:>280 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.95(brs,1H),11.90(brs,1H),9.73(s,1H),8.17(d,J =8.8Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.80 (s, 1H), 7.61 (t, J=8.8Hz, 1H), 7.41 (d, J= 11.2Hz, 1H), 7.23 (d, J=8.8Hz, 1H), 7.17 (d, J=8.8Hz, 2H), 6.88 (d, J=8.8Hz, 1H), 3.86 (s,3H).

Embodiment 53：4- ((the fluoro- 5- chlorphenyls of 2-) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((the fluoro- 5- chlorphenyls of 2-) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and the fluoro- 5- chloroanilines of 2- as initiation material, preparation process is same A) methods described in embodiment 3, obtains yellow solid 166mg, yield is 79%, mp:199-200℃.

¹H NMR(CDCl₃)δ(ppm):10.48 (brs, 1H), 8.25 (d, J=9.2Hz, 1H), 7.52-7.51 (m, 1H), 7.37 (d, J=1.6Hz, 1H), 7.19-7.11 (m, 2H), 6.85 (d, J=8.8Hz, 1H), 6.61 (s, 1H), 4.46 (q, J= 7.2Hz, 2H), 1.44 (t, J=7.2Hz, 3H)

B) .4- ((the fluoro- 5- chlorphenyls of 2-) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((the fluoro- 5- chlorphenyls of 2-) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process B) methods described in be the same as Example 3, obtains yellow solid 76mg, yield is 72%, mp:234-236℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.82 (s, 1H), 9.58 (s, 1H), 8.14 (d, J= 9.2Hz,1H),7.71(s,1H),7.60-7.58(m,1H),7.50-7.41(m,2H),6.36(d,J₁=1.5Hz, J₂= 8.8Hz,1H).

C) .4- ((the fluoro- 5- chlorphenyls of 2-) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 4- ((the fluoro- 5- chlorphenyls of 2-) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains yellow powdery solid 43mg, yield is 73%, mp:>280 ℃。

¹HNMR(DMSO-d₆)δ(ppm):12.94 (brs, 1H), 11.90 (brs, 1H), 9.58 (s, 1H), 8.16 (d, J= 9.2Hz, 1H), 7.97 (d, J=8.4Hz, 2H), 7.77 (s, 1H), 7.56 (d, J=6.8Hz, 1H), 7.49-7.42 (m, 2H), (s, the 3H) of 7.17 (d, J=8.4Hz, 2H), 6.35 (d, J=8.8Hz, 1H), 3.86

Embodiment 54：4- ((3- trifluoromethyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .4- ((3- trifluoromethyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- 5-trifluoromethylanilines as initiation material, preparation process is same A) methods described in embodiment 3, obtains yellow solid 360mg, yield is 98%, mp:>250℃.

¹H NMR(acetone-d₆)δ(ppm):10.62 (s, 1H), 8.96 (s, 1H), 8.21 (d, J=9.2Hz, 1H), 7.67-7.80 (m, 4H), 7.52 (d, J=7.6Hz, 1H), 6.99-7.01 (m, 1H), 4.41 (q, J=7.2Hz, 2H), 1.40 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₈H₁₅F₃N₃O₄[M+H⁺]:394.1009,found 394.0997.

B) .4- ((3- trifluoromethyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- trifluoromethyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process B) methods described in be the same as Example 3, obtains yellow solid 42mg, yield is 37%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):10.81 (s, 1H), 9.75 (s, 1H), 8.16 (d, J=9.2Hz, 1H), 7.64- 7.71 (m, 4H), 7.51 (d, J=7.2Hz, 1H), 6.85 (d, J=9.2Hz, 1H)；HRMS(ESI):m/z,calcd for C₁₆H₁₁F₃N₃O₄[M+H⁺]:366.0696,found 366.0694.

C) .4- ((3- trifluoromethyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

Using 4- ((3- trifluoromethyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as C) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 34mg, yield is 67%, mp:> 280℃。

¹H NMR(DMSO-d₆)δ(ppm):12.93(brs,1H),11.92(brs,1H),9.78(s,1H),8.19(d,J =9.2Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.82 (s, 1H), 7.72-7.65 (m, 3H), 7.52 (d, J=7.6Hz, 1H), (s, the 3H) of 7.17 (d, J=8.4Hz, 2H), 6.84 (d, J=8.8Hz, 1H), 3.86

Embodiment 55：4- ((4- trifluoromethyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .4- ((4- trifluoromethyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 4- 5-trifluoromethylanilines as initiation material, preparation process is same A) methods described in embodiment 3, obtains yellow solid 250mg, yield is 86%, mp:239-241℃.

¹H NMR(acetone-d₆)δ(ppm):10.67 (brs, 1H), 9.05 (s, 1H), 8.23 (d, J=8.8Hz, 1H), 7.77 (d, J=8.4Hz, 2H), 7.69 (s, 1H), 7.66 (d, J=8.4Hz, 2H), 7.12-7.15 (m, 1H), 4.41 (q, J= 7.2Hz, 2H), 1.39 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd forC₁₈H₁₅F₃N₃O₄[M+H⁺]: 394.1009,found 394.0997.

B) .4- ((4- trifluoromethyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((4- trifluoromethyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process B) methods described in be the same as Example 3, obtains yellow solid 90mg, yield is 69%, mp:244-246℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.84 (s, 1H), 9.79 (s, 1H), 8.15 (d, J= 8.8Hz, 1H), 7.74-7.76 (m, 3H), 7.55 (d, J=8.0Hz, 2H), 6.98 (d, J=8.8Hz, 1H)；HRMS(ESI): m/z,calcd for C₁₆H₁₁F₃N₃O₄[M+H⁺]:366.0696,found 366.0694.

C) .4- ((4- trifluoromethyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

Using 4- ((4- trifluoromethyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as C) methods described in initiation material, preparation process be the same as Example 3, obtains orange red pulverulent solids 45mg, yield is 76%, mp: 278-280℃。

¹H NMR(DMSO-d₆)δ(ppm):12.88(brs,1H),11.92(brs,1H),9.83(s,1H),8.19(d,J =8.8Hz, 1H), 7.98 (d, J=8.4Hz, 2H), 7.84 (s, 1H), 7.76 (d, J=8.0Hz, 2H), 7.55 (d, J= 8.0Hz, 2H), 7.17 (d, J=8.4Hz, 2H), 6.97 (d, J=8.8Hz, 1H), 3.86 (s, 3H)

Embodiment 56：4- ((4- cyano-phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

A) .4- ((4- cyano-phenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 4- cyano-anilines as initiation material, preparation process is with implementation A) methods described in example 3, obtains yellow solid 242mg, yield is 84%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.08 (s, 1H), 9.83 (s, 1H), 8.17 (d, J=8.8Hz, 1H), 7.82 (d, J=8.4Hz, 2H), 7.78 (s, 1H), 7.50 (d, J=8.8Hz, 2H), 7.04 (d, J=9.2Hz, 1H), 4.37 (q, J= 7.2Hz, 2H), 1.36 (t, J=7.2Hz, 3H)

B) .4- ((4- cyano-phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((4- cyano-phenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with real B) methods described is applied in example 3, yellow solid 107mg is obtained, yield is 97%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.44 (brs, 1H), 10.90 (s, 1H), 9.83 (s, 1H), 8.17 (d, J= 8.8Hz, 1H), 7.82 (d, J=8.4Hz, 2H), 7.77 (s, 1H), 7.50 (d, J=8.4Hz, 2H), 7.04 (d, J=8.8Hz, 1H).

C) .4- ((4- cyano-phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((4- cyano-phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and -4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains orange powder shape solid 45mg, yield is 74%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):12.98(brs,1H),11.93(brs,1H),9.89(s,1H),8.22(d,J =9.3Hz, 1H), 7.98 (d, J=9.0Hz, 2H), 7.83 (d, J=8.1Hz, 3H), 7.49 (d, J=8.7Hz, 2H), 7.17 (d, J=8.7Hz, 2H), 7.03 (t, J=9.3Hz, 1H), 3.86 (s, 3H)

Embodiment 57：4- ((3- nitrobenzophenones) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

A) .4- ((3- nitrobenzophenones) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- nitroanilines as initiation material, preparation process is with implementation A) methods described in example 3, obtains yellow solid 265mg, yield is 87%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.05 (s, 1H), 9.84 (s, 1H), 8.17 (d, J=9.2Hz, 1H), 8.14 (s, 1H), 7.96 (d, J=8.0Hz, 1H), 7.84 (d, J=8.0Hz, 1H), 7.79 (s, 1H), 7.69 (t, J=8.0Hz, 1H), 6.96 (d, J=8.8Hz, 1H), 4.37 (q, J=7.2Hz, 2H), 1.36 (t, J=7.2Hz, 3H)；HRMS(ESI):m/ z,calcd for C₁₇H₁₅N₄O₆[M+H⁺]:371.0986,found371.0981.

B) .4- ((3- nitrobenzophenones) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- nitrobenzophenones) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with real B) methods described is applied in example 3, yellow solid 105mg is obtained, yield is 93%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.42(brs,1H),10.86(s,1H),9.84(s,1H),8.15-8.17 (m, 2H), 7.96 (d, J=8.0Hz, 1H), 7.84 (d, J=8.0Hz, 1H), 7.72 (s, 1H), 7.69 (t, J=8.0Hz, 1H), 6.95 (d, J=9.2Hz, 1H)；HRMS(ESI):m/z,calcd forC₁₅H₁₀N₄O₆[M+H⁺]:343.0673,found 343.0665.

C) .4- ((3- nitrobenzophenones) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- nitrobenzophenones) amino) -7- nitro -1H- indole-2-carboxylic acids and -4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains orange powder shape solid 50mg, yield is 83%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):12.94 (brs, 1H), 11.93 (s, 1H), 9.89 (s, 1H), 8.20 (d, J= 9.0Hz, 1H), 8.15 (t, J=2.1Hz, 1H), 7.98 (d, J=8.7Hz, 3H), 7.84-7.82 (m, 2H), 7.70 (t, J= 7.8Hz, 1H), 6.17 (d, J=9.0Hz, 2H), 6.95 (d, J=9.3Hz, 1H), 3.86 (s, 3H)

Embodiment 58：4- ((4- nitrobenzophenones) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

A) .4- ((4- nitrobenzophenones) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 4- nitroanilines as initiation material, preparation process is with implementation A) methods described in example 3, obtains yellow solid 259mg, yield is 90%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.16 (s, 1H), 10.00 (s, 1H), 8.24 (d, J=8.8Hz, 2H), 8.21 (d, J=9.2Hz, 1H), 7.78 (s, 1H), 7.53 (d, J=9.2Hz, 2H), 7.15 (d, J=8.8Hz, 1H), 4.37 (q, J= 7.2Hz, 2H), 1.36 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcdfor C₁₇H₁₄N₄O₆[M+H⁺]:371.0986, found 371.0973.

B) .4- ((4- nitrobenzophenones) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((4- nitrobenzophenones) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with real B) methods described is applied in example 3, yellow solid 113mg is obtained, yield is 88%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):10.97 (s, 1H), 10.03 (s, 1H), 8.25 (d, J=8.8Hz, 2H), 8.21 (d, J=8.8Hz, 1H), 7.12 (s, 1H), 7.53 (d, J=8.8Hz, 2H), 7.15 (d, J=9.2Hz, 1H)；HRMS(ESI): m/z,calcd for C₁₅H₁₁N₄O₆[M+H⁺]:343.0673,found343.0672.

C) .4- ((4- nitrobenzophenones) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((4- nitrobenzophenones) amino) -7- nitro -1H- indole-2-carboxylic acids and -4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains orange powder shape solid 50mg, yield is 83%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):12.95(brs,1H),11.94(brs,1H),10.09(s,1H),8.25(d,J =9.0Hz, 3H), 7.98 (d, J=9.0Hz, 2H), 7.82 (d, J=1.8Hz, 1H), 7.52 (d, J=9.0Hz, 2H), 7.16 (t, J=8.7Hz, 3H), 3.86 (s, 3H)

Embodiment 59：4- ((2,4- Dimethoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .4- ((2,4- Dimethoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

With the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 2,4- dimethoxyaniline for initiation material, preparation process A) methods described in be the same as Example 3, obtains yellow solid 156mg, yield is 73%, mp:219-220℃.

¹H NMR(CDCl₃)δ(ppm):10.45 (brs, 1H), 8.15 (d, J=9.0Hz, 1H), 7.36-7.34 (m, 2H), 6.73 (s, 1H), 6.61 (d, J=9.6Hz, 1H), 6.59-6.53 (m, 2H), 4.44 (q, J=7.2Hz, 2H), 3.86 (s, 3H), 3.85 (s, 3H), 1.44 (t, J=7.2Hz, 3H)

B) .4- ((2,4- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((2,4- Dimethoxyphenyl) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, prepared B) methods described in journey be the same as Example 3, obtains yellow solid 87mg, yield is 90%, mp:220-222℃.

¹H NMR(DMSO-d₆)δ(ppm):13.28 (brs, 1H), 10.62 (s, 1H), 9.31 (s, 1H), 8.02 (d, J= 9.0Hz, 1H), 7.67 (d, J=2.1Hz, 1H), 7.23 (d, J=8.4Hz, 1H), 6.76 (d, J=2.1Hz, 1H), 7.16 (d, J₁=2.4Hz, J₂=8.4Hz, 1H), 6.04 (d, J=9.0Hz, 1H), 3.83 (s, 3H), 3.76 (s, 3H)

C) .4- ((2,4- Dimethoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((2,4- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains Red-brown powder shape solid 55mg, yield is 89%, mp:254-255℃。

¹H NMR(DMSO-d₆)δ(ppm):12.89(brs,1H),11.82(brs,1H),9.30(s,1H),8.04(d,J =9.2Hz, 1H), 7.97 (d, J=8.0Hz, 2H), 7.75 (s, 1H), 7.22-7.16 (m, 3H), 6.74 (s, 1H), 6.61 (d, J=8.4Hz, 1H), 6.02 (d, J=9.2Hz, 1H), 3.86 (s, 3H), 3.82 (s, 3H), 3.73 (s, 3H)

Embodiment 60：4- ((2,3- Dimethoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .4- ((2,3- Dimethoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

With the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 2,3- dimethoxyaniline for initiation material, preparation process A) methods described in be the same as Example 3, obtains yellow solid 176mg, yield is 82%, mp:160-161℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.22 (d, J=9.3Hz, 1H), 7.39 (d, J=2.1Hz, 1H), 7.15-7.07 (m, 3H), 6.97 (d, J=9.0Hz, 1H), 6.75 (dd, J₁=1.8Hz, J₂=7.5Hz, 1H), 4.46 (q, J=7.2Hz, 2H), 3.93 (s, 3H), 3.87 (s, 3H), 1.45 (t, J=7.2Hz, 3H)

B) .4- ((2,3- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((2,3- Dimethoxyphenyl) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, prepared B) methods described in journey be the same as Example 3, obtains yellow solid 95mg, yield is 90%, mp:244-247℃.

¹H NMR(DMSO-d₆)δ(ppm):13.32 (brs, 1H), 10.68 (s, 1H), 9.40 (s, 1H), 8.07 (d, J= 9.2Hz, 1H), 7.74 (s, 1H), 7.16 (t, J=8.4Hz, 1H), 7.06 (d, J=8.4Hz, 1H), 6.95 (d, J=8.0Hz, 1H), (s, the 3H) of 6.23 (d, J=8.8Hz, 1H), 3.87 (s, 3H), 3.64

C) .4- ((2,3- Dimethoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((2,3- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains Red-brown powder shape solid 60mg, yield is 95%, mp:220-222℃。

¹H NMR(DMSO-d₆)δ(ppm):12.90 (brs, 1H), 11.85 (s, 1H), 9.40 (s, 1H), 8.09 (d, J= 9.6Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.81 (s, 1H), 7.17 (d, J=8.8Hz, 2H), 7.15 (t, J=8.0Hz, 1H), 7.04 (d, J=8.4Hz, 1H), 6.92 (d, J=8.0Hz, 1H), 6.21 (d, J=9.2Hz, 1H), 3.86 (s, 3H), 3.85(s,3H),3.60(s,3H).

Embodiment 61:4- ((2,5- Dimethoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .4- ((2,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

With the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 2,5- dimethoxyaniline for initiation material, preparation process A) methods described in be the same as Example 3, obtains orange/yellow solid 185mg, yield is 86%, mp:167-169℃.

¹H NMR(CDCl₃)δ(ppm):10.46 (brs, 1H), 8.21 (d, J=8.8Hz, 1H), 7.39 (d, J=1.6Hz, 1H), 7.11 (d, J=2.8Hz, 1H), 7.06 (s, 1H), 7.00 (d, J=9.2Hz, 1H), 6.91 (d, J=9.2Hz, 1H), 6.65(dd,J₁=2.4Hz, J₂=8.8Hz, 1H), 4.46 (q, J=7.2Hz, 2H), 3.88 (s, 3H), 3.80 (s, 3H), 1.45 (t, J=7.2Hz, 3H)

B) .4- ((2,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((2,5- Dimethoxyphenyl) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, prepared B) methods described in journey be the same as Example 3, obtains orange red pulverulent solids 94mg, yield is 92%, mp:255-258℃.

¹H NMR(DMSO-d₆)δ(ppm):13.31 (brs, 1H), 10.66 (s, 1H), 9.38 (s, 1H), 8.06 (d, J= 9.2Hz, 1H), 7.71 (s, 1H), 7.13 (d, J=8.8Hz, 1H), 6.93-6.90 (m, 2H), 6.20 (d, J=9.2Hz, 1H), 3.74(s,3H),3.72(s,3H).

C) .4- ((2,5- Dimethoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((2,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains Red-brown powder shape solid 55mg, yield is 83%, mp:274-276℃。

¹H NMR(DMSO-d₆)δ(ppm):12.90 (brs, 1H), 11.83 (s, 1H), 9.36 (s, 1H), 8.08 (d, J= 9.2Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.80 (s, 1H), 7.17 (d, J=8.8Hz, 2H), 7.12-7.10 (m, 1H), (s, the 3H) of 6.90 (s, 2H), 6.18 (d, J=8.8Hz, 1H), 3.86 (s, 3H), 3.72 (s, 3H), 3.69

Embodiment 62:4- ((4- methyl -3- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) .4- ((4- methyl -3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 4- methyl -3- aminoanisoles as initiation material, prepare A) methods described in process be the same as Example 3, obtains yellow solid 160mg, yield is 78%, mp:186-188℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.16 (d, J=9.0Hz, 1H), 7.35 (d, J=2.1Hz, 1H), 7.18 (d, J=8.1Hz, 1H), 6.83 (dd, J₁=2.1Hz, J₂=8.1Hz, 1H), 6.78 (d, J=1.8Hz, 1H), 6.69 (d, J=9.3Hz, 1H), 4.44 (q, J=7.2Hz, 2H), 3.83 (s, 3H), 2.24 (s, 3H), 1.43 (t, J= 7.5Hz,3H).

B) .4- ((4- methyl -3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((4- methyl -3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, system B) methods described in standby process be the same as Example 3, obtains orange red pulverulent solids 101mg, yield is 99%, mp:265-267℃.

¹H NMR(DMSO-d₆)δ(ppm):13.34 (brs, 1H), 10.71 (s, 1H), 9.65 (s, 1H), 8.10 (d, J= 9.0Hz, 1H), 7.75 (d, J=1.8Hz, 1H), 7.21 (d, J=8.1Hz, 1H), 6.93 (s, 1H), 6.89 (d, J=7.8Hz, 1H), (s, the 3H) of 6.72 (d, J=9.0Hz, 1H), 3.80 (s, 3H), 2.17

C) .4- ((4- methyl -3- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

With 4- ((4- methyl -3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains Red-brown powder shape solid 57mg, yield is 89%, mp:268-270℃。

¹H NMR(DMSO-d₆)δ(ppm):12.91 (brs, 1H), 11.88 (s, 1H), 9.66 (s, 1H), 8.12 (d, J= 9.2Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.84 (s, 1H), 7.18 (t, J=7.6Hz, 3H), 6.91 (s, 1H), 6.86 (d, J=8.0Hz, 1H), 6.69 (d, J=9.2Hz, 1H), 3.86 (s, 3H), 3.79 (s, 3H), 2.16 (s, 3H)

Embodiment 63:4- ((2- methyl -5- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) .4- ((2- methyl -5- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 2- methyl -5- aminoanisoles as initiation material, prepare A) methods described in process be the same as Example 3, obtains yellow solid 190mg, yield is 92%, mp:185-187℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.15 (d, J=9.2Hz, 1H), 7.35 (d, J=1.6Hz, 1H), 7.24 (d, J=8.4Hz, 1H), 6.90 (d, J=2.0Hz, 1H), 6.81 (dd, J₁=2.4Hz, J₂=8.4Hz, 1H), 6.57 (s, 1H), 6.37 (d, J=7.2Hz, 1H), 4.44 (q, J=7.2Hz, 2H), 3.80 (s, 3H), 2.20 (s, 3H), 1.43 (t, J=7.2Hz, 3H)

B) .4- ((2- methyl -5- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((2- methyl -5- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, system B) methods described in standby process be the same as Example 3, obtains brown powder solid 89mg, yield is 80%, mp:250-252℃.

¹H NMR(DMSO-d₆)δ(ppm):13.32 (brs, 1H), 10.69 (s, 1H), 9.45 (s, 1H), 8.07 (d, J= 9.2Hz, 1H), 7.67 (s, 1H), 7.31 (d, J=8.0Hz, 1H), 6.89 (d, J=7.6Hz, 2H), 6.10 (d, J=8.8Hz, 1H),3.75(s,3H),2.11(s,3H).

C) .4- ((2- methyl -5- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

With 4- ((2- methyl -5- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 30mg, yield is 45%, mp:245-246℃。

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.87(brs,1H),9.46(s,1H),8.09(d,J =9.2Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.75 (s, 1H), 7.29 (d, J=8.4Hz, 1H), 6.88 (d, J= 8.8Hz, 1H), 6.85 (s, 1H), 6.07 (d, J=9.2Hz, 1H), 3.86 (s, 3H), 3.74 (s, 3H), 2.07 (s, 3H)

Embodiment 64:4- ((3- methoxyl group -5- trifluoromethyls) amino) -7- nitros-N- (4- methoxybenzene sulphonyl Base) -1H- indole 2-carboxamides

A) .4- ((3- methoxyl group -5- trifluoromethyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- methoxyl group -5- 5-trifluoromethylanilines as initiation material, A) methods described in preparation process be the same as Example 3, obtains Orange red solid 190mg, yield is 81%, mp:214-216℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.22 (d, J=8.8Hz, 1H), 7.38 (d, J=1.2Hz, 1H), 7.15 (s, 1H), 7.03 (s, 1H), 6.97 (s, 1H), 6.85 (d, J=8.8Hz, 1H), 6.80 (s, 1H), 4.45 (q, J =7.2Hz, 2H), 3.88 (s, 3H), 1.43 (t, J=7.2Hz, 3H)

B) .4- ((3- methoxyl group -5- trifluoromethyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Originated with 4- ((3- methoxyl group -5- trifluoromethyls) amino) -7- nitro -1H- indole -2-ethyl formates former Material, b) methods described in preparation process be the same as Example 3, obtains orange powder shape solid 117mg, yield is 95%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.85 (s, 1H), 9.76 (s, 1H), 8.19 (d, J= 8.8Hz, 1H), 7.74 (s, 1H), 7.25 (s, 1H), 7.24 (s, 1H), 7.04 (s, 1H), 6.93 (d, J=8.8Hz, 1H), 3.87(s,3H).

C) .4- ((3- methoxyl group -5- trifluoromethyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

With 4- ((3- methoxyl group -5- trifluoromethyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenes Sulfonamide is c) methods described in initiation material, preparation process be the same as Example 3, obtains orange powder shape solid 68mg, yield is 96%, mp:275-277℃.

¹H NMR(DMSO-d₆)δ(ppm):12.92 (brs, 1H), 11.93 (s, 1H), 9.75 (s, 1H), 8.20 (d, J= 8.8Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.83 (s, 1H), 7.22 (s, 1H), 7.21 (s, 1H), 7.17 (d, J= 8.8Hz, 2H), 7.03 (s, 1H), 6.90 (d, J=8.8Hz, 1H), 3.86 (s, 3H), 3.85 (s, 3H)

Embodiment 65:4- ((the fluoro- 4- methoxyphenyls of 3-) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) .4- ((the fluoro- 4- methoxyphenyls of 3-) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and the fluoro- 4- aminoanisoles of 3- as initiation material, prepared A) methods described in journey be the same as Example 3, obtains orange red powder solid 170mg, yield is 82%, mp:210-212℃.

¹H NMR(acetone-d₆)δ(ppm):10.59 (brs, 1H), 8.77 (s, 1H), 8.16 (d, J=9.2Hz, 1H), (7.66 s, 1H), 7.28-7.23 (m, 3H), 6.76-6.73 (m, 1H), 4.41 (q, J=7.2Hz, 2H), 3.94 (s, 3H), 1.40 (t, J=7.2Hz, 3H)

B) .4- ((the fluoro- 4- methoxyphenyls of 3-) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((the fluoro- 4- methoxyphenyls of 3-) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, prepare B) methods described in process be the same as Example 3, obtains yellow powdery solid 100mg, yield is 103%, mp:258-260℃.

¹HNMR(DMSO-d₆)δ(ppm):10.73 (s, 1H), 9.62 (s, 1H), 8.11 (d, J=9.2Hz, 1H), 7.72 (s, 1H), 7.30-7.24 (m, 2H), 7.19-7.17 (m, 1H), 6.60 (d, J=8.8Hz, 1H), 3.88 (s, 3H)

C) .4- ((the fluoro- 4- methoxyphenyls of 3-) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((the fluoro- 4- methoxyphenyls of 3-) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains orange powder shape solid 42mg, yield is 56%, mp:> 280℃。

¹H NMR(DMSO-d₆)δ(ppm):12.90 (brs, 1H), 11.87 (s, 1H), 9.59 (s, 1H), 8.11 (d, J= 9.2Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.78 (s, 1H), 7.26-7.21 (m, 2H), 7.17-7.13 (m, 3H), 6.56 (d, J=9.2Hz, 1H), 3.85 (s, 6H)；HRMS(ESI):m/z,calcd.forC₂₃H₂₀N₄O₇FS[M+H]⁺:515.7037, found 515.1025.

Embodiment 66:4- ((3,5- dimethyl -4- methoxyphenyls) amino) -7- nitros-N- (4- methoxybenzene sulphonyl Base) -1H- indole 2-carboxamides

A) .4- ((3,5- dimethyl -4- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

With the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3,5- dimethyl -4- aminoanisoles for initiation material, A) methods described in preparation process be the same as Example 3, obtains yellow powder solid 160mg, yield is 75%, mp:188-189℃.

¹H NMR(CDCl₃)δ(ppm):10.46 (brs, 1H), 8.16 (d, J=9.2Hz, 1H), 7.33 (d, J=1.6Hz, 1H), 6.98 (s, 2H), 6.68 (brs, 1H), 6.63 (d, J=9.2Hz, 1H), 4.43 (q, J=7.2Hz, 2H), 3.77 (s, 3H), 2.32 (s, 3H), 1.43 (t, J=7.2Hz, 3H)

B) .4- ((3,5- dimethyl -4- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Originated with 4- ((3,5- dimethyl -4- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates former Material, b) methods described in preparation process be the same as Example 3, obtains brick-red pulverulent solids 136mg, yield is 98%, mp:235- 237℃。

¹H NMR(DMSO-d₆)δ(ppm):13.31 (brs, 1H), 10.69 (s, 1H), 9.52 (s, 1H), 8.10 (d, J= 8.8Hz, 1H), 7.74 (s, 1H), 7.05 (s, 2H), 6.61 (d, J=8.8Hz, 1H), 3.69 (s, 3H), 2.26 (s, 6H)

C) .4- ((3,5- dimethyl -4- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

With 4- ((3,5- dimethyl -4- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenes Sulfonamide is c) methods described in initiation material, preparation process be the same as Example 3, obtains orange red pulverulent solids 63mg, yield is 86%, mp:260-263℃.

¹H NMR(DMSO-d₆)δ(ppm):12.91 (brs, 1H), 11.87 (s, 1H), 9.54 (s, 1H), 8.12 (d, J= 9.2Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.83 (s, 1H), 7.17 (d, J=8.8Hz, 2H), 7.03 (s, 2H), 6.58 (d, J=9.2Hz, 1H), 3.86 (s, 3H), 3.68 (s, 3H), 2.25 (s, 6H)

Embodiment 67:4- ((4- trifluoromethoxy -3- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) .4- ((4- trifluoromethoxy -3- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 4- trifluoromethoxy -3- chloroanilines as initiation material, system A) methods described in standby process be the same as Example 3, obtains yellow powder solid 175mg, yield is 71%, mp:260-263℃.

¹H NMR(CDCl₃)δ(ppm):10.46 (brs, 1H), 8.22 (d, J=8.8Hz, 1H), 7.45 (d, J=2.0Hz, 1H), 7.38 (d, J=7.6Hz, 2H), 7.23-7.24 (m, 1H), 6.81 (d, J=8.8Hz, 1H), 6.78 (s, 1H), 4.44 (q, J=7.2Hz, 2H), 1.43 (t, J=7.2Hz, 3H)

B) .4- ((4- trifluoromethoxy -3- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((4- trifluoromethoxy -3- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, B) methods described in preparation process be the same as Example 3, obtains orange red pulverulent solids 110mg, yield is 98%, mp:255-258 ℃。

¹H NMR(DMSO-d₆)δ(ppm):13.43 (brs, 1H), 10.87 (s, 1H), 9.72 (s, 1H), 8.18 (d, J= 9.2Hz, 1H), 7.21 (d, J=0.8Hz, 1H), 7.65 (d, J=2.0Hz, 1H), 7.62 (d, J=8.8Hz, 1H), 7.16 (dd,J₁=2.4Hz, J₂=9.2Hz, 1H), 6.92 (d, J=8.8Hz, 1H)

C) .4- ((4- trifluoromethoxy -3- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

With 4- ((4- trifluoromethoxy -3- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphurs Acid amides is c) methods described in initiation material, preparation process be the same as Example 3, obtains orange red pulverulent solids 69mg, yield is 99%, mp:274-277℃.

¹H NMR(DMSO-d₆)δ(ppm):12.94(brs,1H),11.93(brs,1H),9.73(s,1H),8.19(d,J =8.8Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.81 (s, 1H), 7.63-7.60 (m, 2H), 7.45 (dd, J₁=2.0Hz, J₂=8.8Hz, 1H), 7.17 (d, J=8.8Hz, 2H), 6.89 (d, J=8.8Hz, 1H), 3.86 (s, 3H)

Embodiment 68:4- ((3- difluoro-methoxies phenyl) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .4- ((3- difluoro-methoxies phenyl) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- difluoro-methoxy-anilines as initiation material, preparation process A) methods described in be the same as Example 3, obtains orange red powder solid 180mg, yield is 83%, mp:226-228℃.

¹H NMR(CDCl₃)δ(ppm):10.48 (brs, 1H), 8.21 (d, J=8.7Hz, 1H), 7.42 (t, J=8.1Hz, 1H), 7.34 (d, J=2.4Hz, 1H), 7.17 (d, J=7.8Hz, 1H), 7.10 (s, 1H), 6.99 (d, J=8.7Hz, 1H), 6.84 (d, J=8.7Hz, 1H), 6.71 (s, 1H), 6.56 (d, J=73.2Hz, 1H), 4.45 (q, J=7.2Hz, 2H), 1.44 (t, J=7.2Hz, 3H)

B) .4- ((3- difluoro-methoxies phenyl) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- difluoro-methoxies phenyl) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, prepared B) methods described in journey be the same as Example 3, obtains orange powder shape solid 109mg, yield is 95%, mp:243-245℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41 (brs, 1H), 10.81 (s, 1H), 9.71 (s, 1H), 8.15 (d, J= 8.8Hz, 1H), 7.76 (d, J=2.0Hz, 1H), 7.49 (t, J=8.4Hz, 1H), 7.30 (s, 1H), 7.28 (t, J= 81.2Hz, 1H), 7.18 (s, 1H), 7.00 (d, J=6.8Hz, 1H), 6.86 (d, J=9.2Hz, 1H)

C) .4- ((3- difluoro-methoxies phenyl) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((3- difluoro-methoxies phenyl) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains orange powder shape solid 49mg, yield is 80%, mp: 259-261℃。

¹H NMR(DMSO-d₆)δ(ppm):12.93 (brs, 1H), 11.91 (s, 1H), 9.71 (s, 1H), 8.17 (d, J= 9.2Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.83 (s, 1H), 7.48 (t, J=8.0Hz, 1H), 7.28 (t, J= 74.0Hz, 1H), 7.17 (d, J=8.8Hz, 2H), 7.15 (s, 1H), 7.00 (d, J=8.4Hz, 1H), 6.83 (d, J= 9.2Hz,1H),3.86(s,3H),.

Embodiment 69:4- ((3- acetylamino phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .4- ((3- acetylamino phenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- acetylaminoanilines as initiation material, preparation process is same A) methods described in embodiment 3, obtains brick-red solid 170mg, yield is 54%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):10.91 (s, 1H), 10.05 (s, 1H), 9.69 (s, 1H), 8.12 (d, J= 9.3Hz, 1H), 7.85-7.86 (m, 1H), 7.79 (s, 1H), 7.29-7.35 (m, 2H), 7.04 (d, J=6.9Hz, 1H), 6.77 (d, J=9.3Hz, 1H), 4.37 (q, J=7.2Hz, 2H), 2.05 (s, 3H), 1.35 (t, J=7.2Hz, 3H)；HRMS(ESI): m/z,calcd for C₁₉H₁₉N₄O₅[M+H⁺]:383.1350,found383.1336.

B) .4- ((3- acetylamino phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- acetylamino phenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process B) methods described in be the same as Example 3, obtains red brown solid 100mg, yield is 98%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):10.72 (s, 1H), 10.08 (s, 1H), 9.69 (s, 1H), 8.11 (d, J= 9.2Hz, 1H), 7.78 (m, 2H), 7.33-7.36 (m, 2H), 7.04 (d, J=5.6Hz, 1H), 6.75 (d, J=8.8Hz, 1H), 2.05(s,3H)；HRMS(ESI):m/z,calcd for C₁₇H₁₅N₄O₅[M+H⁺]:355.1037,found 355.1033.

C) .4- ((3- acetylamino phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

Using 4- ((3- acetylamino phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as C) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 15mg, yield is 42%, mp: 235-237℃。

¹HNMR(DMSO-d₆)δ(ppm):12.92(brs,1H),10.04(s,1H),9.64(s,1H),8.09(s,1H), 7.93 (s, 2H), 7.75 (s, 2H), 7.33 (d, 2H), 7.11 (s, 2H), 7.03 (s, 1H), 6.73 (d, J=8.8Hz, 1H), 3.84(s,3H),2.05(s,3H).

Embodiment 70:4- ((3- Carbamoylphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .4- ((3- Carbamoylphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- carbamyls aniline as initiation material, preparation process is same A) methods described in embodiment 3, obtains yellow solid 265mg, yield is 77%, mp:232-234℃.

¹H NMR(DMSO-d₆)δ(ppm):11.24 (brs, 1H), 10.60 (brs, 1H), 8.32 (d, J=8.8Hz, 1H), 8.02 (d, J=8.8Hz, 1H), 7.94 (s, 1H), 7.19 (t, J=7.6Hz, 1H), 7.13-7.10 (m, 2H), 6.80 (t, J= 8.0Hz, 1H), 5.38 (s, 2H), 4.38 (q, J=6.8Hz, 2H), 1.35 (t, J=6.8Hz, 3H)

B) .4- ((3- Carbamoylphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- Carbamoylphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process B) methods described in be the same as Example 3, obtains yellow solid 33mg, yield is 71%, mp:218-220℃.

¹H NMR(DMSO-d₆)δ(ppm):11.08 (brs, 1H), 10.72 (brs, 1H), 8.33 (d, J=9.2Hz, 1H), 8.03 (d, J=8.8Hz, 1H), 7.86 (s, 1H), 7.56 (d, J=6.8Hz, 1H), 7.50 (s, 1H), 7.42 (t, J= 7.6Hz, 1H), 7.17 (d, J=6.8Hz, 1H)

C) .4- ((3- Carbamoylphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

Using 4- ((3- Carbamoylphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as C) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 10mg, yield is 16%, mp: 270-272℃。

¹H NMR(DMSO-d₆)δ(ppm):9.59(brs,1H),8.13-8.01(m,2H),7.86(m,3H),7.67(m, 2H),7.51-7.41(m,4H),6.98(m,2H),6.78-6.72(m,2H),3.80(s,3H).

Embodiment 71:4- ((3- ethylphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

A) .4- ((3- ethylphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- MEAs initiation material, preparation process is with implementation A) methods described in example 3, obtains orange red powder solid 116mg, yield is 59%, mp:156-157℃.

¹H NMR(DMSO-d₆)δ(ppm):10.46 (s, 1H), 8.17 (d, J=8.8Hz, 1H), 7.35 (t, J=7.6Hz, 2H), 7.15 (s, 2H), 7.10 (d, J=7.6Hz, 1H), 6.81 (s, 1H), 4.44 (q, J=7.2Hz, 2H), 2.69 (q, J= 7.6Hz, 2H), 1.43 (t, J=7.2Hz, 3H), 1.44 (t, J=7.2Hz, 3H)

B) .4- ((3- ethylphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- ethylphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with real B) methods described is applied in example 3, yellow powdery solid 80mg is obtained, yield is 96%, mp:258-260℃.

¹HNMR(DMSO-d₆)δ(ppm):10.28 (s, 1H), 9.47 (s, 1H), 8.01 (d, J=9.2Hz, 1H), 7.34 (t, J=7.6Hz, 2H), 7.21 (d, J=10.4Hz, 2H), 7.04 (d, J=7.2Hz, 1H), 6.70 (d, J=8.8Hz, 1H), 2.64 (q, J=7.2Hz, 2H), 1.21 (t, J=7.2Hz, 3H)

C) .4- ((3- ethylphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- ethylphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains yellow powdery solid 33mg, yield is 54%, mp:231-233 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.88(brs,1H),9.65(s,1H),8.14(d,J =9.2Hz, 1H), 7.98 (d, J=8.4Hz, 2H), 7.83 (s, 1H), 7.36 (t, J=7.6Hz, 1H), 7.22-7.13 (m, 4H), 7.08 (d, J=7.6Hz, 1H), 6.69 (d, J=8.8Hz, 1H), 3.86 (s, 3H), 2.63 (q, J=7.2Hz, 2H), 1.20 (t, J=7.2Hz, 3H)

Embodiment 72:4- ((3- (methoxy) phenyl) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) .4- ((3- (methoxy) phenyl) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- (methoxy) aniline as initiation material, prepared A) methods described in journey be the same as Example 3, obtains yellow powder solid 159mg, yield is 77%, mp:171-173℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.18 (d, J=9.3Hz, 1H), 7.42 (t, J=7.8Hz, 1H), 7.35 (d, J=1.8Hz, 1H), 7.32 (s, 1H), 7.19-7.24 (m, 2H), 6.82 (s, 1H), 6.76 (d, J= 9.0Hz, 1H), 4.49 (s, 2H), 4.44 (q, J=7.2Hz, 2H), 3.44 (s, 3H), 1.43 (t, J=6.9Hz, 3H)

B) .4- ((3- (methoxy) phenyl) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- (methoxy) phenyl) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, prepare B) methods described in process be the same as Example 3, obtains brown yellow powder solid 97mg, yield is 87%, mp:248-250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.33 (brs, 1H), 10.75 (s, 1H), 9.67 (s, 1H), 8.13 (d, J= 9.2Hz, 1H), 7.76 (d, J=1.2Hz, 1H), 7.44 (t, J=7.6Hz, 1H), 7.32 (d, J=7.6Hz, 2H), 7.17 (d, J=7.6Hz, 1H), 6.74 (d, J=9.2Hz, 1H), 4.46 (s, 2H), 3.32 (s, 3H)

C) .4- ((3- (methoxy) phenyl) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

With 4- ((3- (methoxy) phenyl) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 42mg, yield is 64%, mp:230-232℃。

¹H NMR(DMSO-d₆)δ(ppm):12.92 (brs, 1H), 11.90 (s, 1H), 9.69 (s, 1H), 8.15 (d, J= 8.8Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.84 (s, 1H), 7.42 (t, J=7.6Hz, 1H), 7.30 (d, J=7.2Hz, 2H), (s, the 3H) of 7.18-7.11 (m, 3H), 6.71 (d, J=9.2Hz, 1H), 4.45 (s, 2H), 3.86 (s, 3H), 3.31

Embodiment 73:4- ((morpholinyl phenyl) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((morpholinyl phenyl) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and morpholinyl aniline as initiation material, preparation process is with real A) methods described is applied in example 3, yellow powder solid 182mg is obtained, yield is 79%, mp:186-188℃.

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.18 (d, J=9.0Hz, 1H), 7.35-7.31 (m, 2H), 6.83-6.76 (m, 5H), 4.45 (q, J=7.2Hz, 2H), 3.88 (t, J=4.2Hz, 4H), 3.20 (t, J=4.2Hz, 4H), 1.44 (t, J=6.9Hz, 3H)

B) .4- ((morpholinyl phenyl) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((morpholinyl phenyl) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is same B) methods described in embodiment 3, obtains yellow powdery solid 110mg, yield is 103%, mp:188-190℃.

¹H NMR(DMSO-d₆)δ(ppm):10.73 (s, 1H), 9.72 (s, 1H), 8.12 (d, J=9.0Hz, 1H), 7.78 (d, J=2.1Hz, 1H), 7.36 (t, J=8.1Hz, 1H), 7.10 (s, 1H), 6.97 (m, 2H), 6.77 (d, J=9.6Hz, 1H),3.81(m,4H),3.23(m,4H).

C) .4- ((morpholinyl phenyl) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 4- ((morpholinyl phenyl) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains orange powder shape solid 70mg, yield is 97%, mp:188- 189℃。

¹H NMR(DMSO-d₆)δ(ppm):12.91 (brs, 1H), 11.90 (s, 1H), 9.64 (s, 1H), 8.14 (d, J= 9.3Hz, 1H), 7.98 (d, J=8.4Hz, 2H), 7.84 (s, 1H), 7.31 (t, J=7.8Hz, 1H), 7.18 (d, J=8.7Hz, 2H), 6.92 (s, 1H), 6.85 (t, J=7.8Hz, 2H), 6.72 (d, J=9.0Hz, 1H), 3.86 (s, 3H), 3.75 (m, 4H), 3.15(m,4H)；HRMS(ESI):m/z,calcd.forC₂₆H₂₆N₅O₇S[M+H]⁺:552.1553,found 552.1538.

Embodiment 74:4- ((4- morpholino phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((4- morpholino phenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 4- morpholinyl phenylamines as initiation material, preparation process is with real A) methods described is applied in example 3, yellow powder solid 197mg is obtained, yield is 86%, mp:262-265℃.

¹H NMR(acetone-d₆)δ(ppm):10.58 (brs, 1H), 8.76 (brs, 1H), 8.14 (d, J=9.0Hz, 1H), 7.68 (d, J=2.4Hz, 1H), 7.33 (d, J=8.7Hz, 2H), 7.09 (d, J=8.7Hz, 2H), 6.65 (dd, J₁= 2.7Hz,J₂=9.3Hz, 1H), 4.41 (q, J=7.2Hz, 2H), 3.81 (t, J=4.8Hz, 4H), 3.20 (q, J=4.8Hz, 4H), 1.40 (t, J=6.9Hz, 3H)

B) .4- ((4- morpholino phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((4- morpholino phenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is same B) methods described in embodiment 3, obtains yellow powdery solid 106mg, yield is 99%, mp:196-198℃.

¹H NMR(DMSO-d₆)δ(ppm):10.70 (brs, 1H), 9.67 (s, 1H), 8.09 (d, J=9.2Hz, 1H), 7.75 (s, 1H), 7.32 (d, J=8.4Hz, 2H), 7.26 (m, 2H), 6.58 (d, J=8.8Hz, 1H), 3.85 (s, 4H), 3.26 (s,4H).

C) .4- ((4- morpholino phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 4- ((4- morpholino phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains orange powder shape solid 56mg, yield is 78%, mp:180- 182℃。

¹H NMR(DMSO-d₆)δ(ppm):12.92 (brs, 1H), 11.89 (s, 1H), 9.67 (s, 1H), 8.11 (d, J= 9.0Hz, 1H), 7.98 (d, J=9.0Hz, 2H), 7.83 (d, J=1.8Hz, 1H), 7.28 (d, J=9.0Hz, 2H), 7.18 (d, J=8.7Hz, 4H), 6.54 (d, J=9.0Hz, 1H), 3.86 (s, 3H), 3.82 (s, 4H), 3.22 (s, 4H)

Embodiment 75:4- ((3- ((tertbutyloxycarbonyl) amino) phenyl) amino) -7- nitros-N- (4- methoxybenzene sulphonyl Base) -1H- indole 2-carboxamides

A) .4- ((3- ((tertbutyloxycarbonyl) amino) phenyl) amino) -7- nitro -1H- indole -2-ethyl formates

The chloro- 7- nitros -1H- indole -2-ethyl formates (200mg, 0.744mmol) of 4- are dissolved in toluene (12mL), Sequentially add Pd₂(dba)₃(34mg, 0.037mmol), Davephos (29mg, 0.074mmol) and K₃PO₄(474mg, 2.23mmol, 2.5mL H₂O), after stirring, N-Boc- m-phenylene diamine (MPD)s (310mg, 1.49mmol) are added, under argon gas protection, Back flow reaction 1h, raw material disappears.Room temperature is cooled to, is concentrated, EA (30mL) dissolution residual substance, saturated common salt washing (20mL is added × 3), wash (20mL × 2), column chromatography (P/E=10:1-D), yellow powdery solid, P/E=10 are obtained:1 mixed solution is washed (2mL), is filtered, and is dried, is obtained yellow powdery solid 266mg, yield is 81%；mp:205-207℃.

¹H NMR(CDCl₃)δ(ppm):10.46 (brs, 1H), 8.18 (d, J=8.8Hz, 1H), 7.61 (s, 1H), 7.34- 7.30 (m, 2H), 6.70 (d, J=8.0Hz, 2H), 6.82 (d, J=8.8Hz, 1H), 6.78 (s, 1H), 6.56 (s, 1H), 4.45 (q, J=7.2Hz, 2H), 1.52 (s, 9H), 1.44 (t, J=7.2Hz, 3H)

B) .4- ((3- ((tertbutyloxycarbonyl) amino) phenyl) amino) -7- nitro -1H- indole-2-carboxylic acids

Originated with 4- ((3- ((tertbutyloxycarbonyl) amino) phenyl) amino) -7- nitro -1H- indole -2-ethyl formates former Material, b) methods described in preparation process be the same as Example 3, obtains yellow powdery solid 65mg, yield is 98%, mp:210-212 ℃。

¹H NMR(DMSO-d₆)δ(ppm):13.38(s,1H),10.71(s,1H),9.64(s,1H),9.49(s,1H), 8.11 (d, J=5.2Hz, 1H), 7.74 (s, 1H), 7.61 (s, 1H), 7.31 (t, J=8.0Hz, 1H), 7.26 (d, J= 8.0Hz, 1H), 6.74 (d, J=9.2Hz, 1H), 1.48 (s, 9H)

C) .4- ((3- ((tertbutyloxycarbonyl) amino) phenyl) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

With 4- ((3- ((tertbutyloxycarbonyl) amino) phenyl) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxyl groups Benzsulfamide is c) methods described in initiation material, preparation process be the same as Example 3, obtains orange powder shape solid 67mg, yield is 73%, mp:213-215℃.

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.87(brs,1H),9.67(s,1H),9.48(s, 1H), 8.13 (d, J=9.2Hz, 1H), 7.98 (d, J=8.4Hz, 2H), 7.85 (s, 1H), 7.58 (s, 1H), 7.30 (t, J= 8.0Hz, 1H), 7.25 (d, J=7.6Hz, 1H), 7.17 (d, J=8.4Hz, 2H), 6.96 (d, J=7.2Hz, 1H), 6.71 (d, J=9.2Hz, 1H), 3.86 (s, 3H), 1.47 (s, 9H)

Embodiment 76:4- ((3- aminophenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

By 4- ((3- ((tertbutyloxycarbonyl) amino) phenyl) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides (23mg, 0.040mmol) are dissolved in DCM (2mL), add TFA (1mL) room temperature reactions 2h.It is evaporated off molten Agent, adds 3mL ether, and ultrasound filters, dries, obtain orange red pulverulent solids 18mg, yield is 95%, mp:235-237℃.

¹H NMR(DMSO-d₆)δ(ppm):11.90 (s, 1H), 9.61 (s, 1H), 8.14 (d, J=8.8Hz, 1H), 7.98 (d, J=8.8Hz, 2H), 7.84 (s, 1H), 7.23-7.16 (m, 3H), 6.82 (m, 2H), 6.73 (d, J=9.2Hz, 1H), 6.68 (d, J=6.8Hz, 1H), 3.86 (s, 3H)

Embodiment 77:The chloro- N- of 7- nitros -4- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using the chloro- 1H- indole-2-carboxylic acids of 7- nitros -4- and 4- methoxybenzenesulphoismides as initiation material, preparation process is with real C) methods described is applied in example 3, yellow powdery solid 300mg is obtained, yield is 98%, mp:246-248℃.

¹H NMR(DMSO-d₆)δ(ppm):11.94 (s, 1H), 8.26 (d, J=8.4Hz, 1H), 7.96 (d, J=8.4Hz, 2H), (s, the 3H) of 7.58 (s, 1H), 7.44 (d, J=8.4Hz, 1H), 7.15 (d, J=8.8Hz, 2H), 3.84

Embodiment 78:4- ((3- hydroxy phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

Using the chloro- N- of 7- nitros -4- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides and 3- acetoxyl groups aniline as A) methods described in initiation material, preparation process be the same as Example 3, obtains orange-yellow powder solid 90mg, yield is 85%, mp: 185-187℃。

¹H NMR(DMSO-d₆)δ(ppm):12.90(s,1H),11.84(s,1H),9.62(s,1H),9.55(s,1H), 8.12 (d, J=9.2Hz, 1H), 7.95 (d, J=8.0Hz, 2H), 7.78 (brs, 1H), 7.22 (t, J=8.0Hz, 1H), 7.14 (d, J=6.8Hz, 2H), 6.79 (d, J=8.0Hz, 1H), 6.75 (s, 1H), 6.73 (d, J=9.2Hz, 1H), 6.62 (d, J= 8.0Hz,1H),3.85(s,3H)；¹³C NMR(125MHz,DMSO-d₆):δ158.31,147.23,140.19,130.22, 130.04,123.90,116.71,114.11,113.57,112.08,109.81,102.26,55.74.HRMS(ESI):m/z, calcd for C₂₂H₁₉N₄O₇S[M+H⁺]:483.0974,found 483.0959.

Embodiment 79:4- (pyridin-3-yl amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

A) .4- (pyridin-3-yl amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- aminopyridines as initiation material, preparation process is with implementation A) methods described in example 3, obtains yellow solid 221mg, yield is 73%, mp:201-203℃.

¹H NMR(DMSO-d₆)δ(ppm):10.98 (s, 1H), 9.67 (s, 1H), 8.63 (s, 1H), 8.40 (d, J= 4.4Hz, 1H), 8.13 (d, J=9.2Hz, 1H), 7.82 (d, J=9.2Hz, 1H), 7.81 (s, 1H), 7.47 (dd, J₁= 4.8Hz,J₂=8.0Hz, 1H), 6.75 (d, J=9.2Hz, 1H), 4.37 (q, J=6.8Hz, 2H), 1.36 (t, J=7.2Hz, 3H).

B) .4- (pyridin-3-yl amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- (pyridin-3-yl amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with implementation B) methods described in example 3, obtains yellow solid 115mg, yield is 100%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):10.96(brs,1H),10.52(brs,1H),8.90(s,1H),8.54(d,J =5.2Hz, 1H), 8.47 (d, J=8.4Hz, 1H), 8.18 (d, J=8.8Hz, 1H), 7.94 (dd, J₁=5.8Hz, J₂= 8.0Hz, 1H), 7.83 (s, 1H), 7.08 (t, J=8.8Hz, 1H)

C) .4- (pyridin-3-yl amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

It is former using 4- (pyridin-3-yl amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting Material, c) methods described in preparation process be the same as Example 3, obtains orange powder shape solid 51mg, yield is 81%, mp:257-260 ℃。

¹H NMR(DMSO-d₆)δ(ppm):11.88(s,1H),9.96(s,1H),8.67(s,1H),8.43(s,1H), 8.16 (d, J=8.8Hz, 1H), 7.98 (d, J=8.4Hz, 2H), 7.88 (s, 2H), 7.52 (s, 1H), 7.17 (d, J= 8.0Hz, 2H), 6.76 (d, J=8.8Hz, 1H), 3.86 (s, 3H)

Embodiment 80:4- (pyridin-4-yl amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

A) .4- (pyridin-4-yl amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 4-aminopyridine as initiation material, preparation process is with implementation A) methods described in example 3, obtains yellow solid 258mg, yield is 85%, mp:227-229℃.

¹H NMR(DMSO-d₆)δ(ppm):11.16 (s, 1H), 9.78 (s, 1H), 8.46 (m, 2H), 8.21 (d, J= 8.8Hz, 1H), 7.80 (s, 1H), 7.33 (d, J=5.2Hz, 2H), 7.17 (d, J=8.8Hz, 1H), 4.37 (q, J=6.8Hz, 2H), 1.36 (t, J=7.2Hz, 3H)

B) .4- (pyridin-4-yl amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- (pyridin-4-yl amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with implementation B) methods described in example 3, obtains yellow solid 115mg, yield is 97%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.35 (s, 1H), 11.19 (s, 1H), 8.47 (d, J=6.8Hz, 2H), 8.33 (d, J=8.8Hz, 1H), 7.56 (s, 1H), 7.52 (d, J=6.4Hz, 2H), 7.39 (d, J=8.8Hz, 1H)

C) .4- (pyridin-4-yl amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

It is former using 4- (pyridin-4-yl amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting Material, c) methods described in preparation process be the same as Example 3, obtains orange powder shape solid 35mg, yield is 56%, mp:255-258 ℃。

¹H NMR(DMSO-d₆)δ(ppm):10.23 (s, 1H), 9.64 (s, 1H), 8.42 (d, J=6.0Hz, 2H), 8.10 (d, J=8.7Hz, 2H), 7.80 (d, J=9.0Hz, 2H), 7.35 (s, 1H), 7.30 (d, J=5.7Hz, 2H), 7.11 (d, J= 9.3Hz, 1H), 6.93 (d, J=8.7Hz, 2H), 3.78 (s, 3H)

Embodiment 81:4- (3- methoxyphenoxies) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

A) .4- (3- methoxyphenoxies) -7- nitro -1H- indole -2-ethyl formates

The chloro- 7- nitros -1H- indole -2-ethyl formates (150mg, 0.56mmol) of 4- are dissolved in DME (2mL), added successively Enter potassium carbonate (139mg, 1.12mmol) and 3- metoxyphenols (139mg, 1.12mmol), microwave reaction (60w, 130 DEG C, 45min, 150psi).Water (30mL), EA (20mL × 2) extractions, saturated common salt washing (20mL × 3), water are added into reaction solution Wash (20mL × 3), column chromatography (P/E=20:1) yellow powdery solid 144mg, is obtained, yield is 73%, mp:73-75℃.

¹H NMR(CDCl₃)δ(ppm):10.39 (brs, 1H), 8.20 (d, J=9.2Hz, 1H), 7.46 (s, 1H), 7.35 (t, J=8.0Hz, 1H), 6.84 (d, J=8.0Hz, 1H), 7.74 (d, J=8.4Hz, 1H), 6.72 (s, 1H), 6.52 (d, J= 8.8Hz, 1H), 4.46 (q, J=7.2Hz, 2H), 3.82 (s, 3H), 1.44 (t, J=7.2Hz, 3H)

B) .4- (3- methoxyphenoxies) -7- nitro -1H- indole-2-carboxylic acids

With 4- (3- methoxyphenoxies) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with implementation B) methods described in example 3, obtains yellow powdery solid 171mg, yield is 71%, mp:203-205℃.

¹H NMR(DMSO-d₆)δ(ppm):13.57 (brs, 1H), 11.22 (s, 1H), 8.26 (d, J=9.2Hz, 1H), 7.42 (t, J=8.4Hz, 1H), 7.25 (s, 1H), 6.92 (d, J=8.0Hz, 1H), 6.88 (s, 1H), 6.82 (d, J= 8.0Hz, 1H), 6.58 (d, J=9.2Hz, 1H), 3.78 (s, 3H)

C) .4- (3- methoxyphenoxies) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

It is former using 4- (3- methoxyphenoxies) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting Material, c) methods described in preparation process be the same as Example 3, obtains pale yellow powder shape solid 78mg, yield is 86%, mp:242-244 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.90 (brs, 1H), 11.79 (s, 1H), 8.27 (d, J=9.2Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.52 (s, 1H), 7.41 (d, J=8.4Hz, 1H), 7.17 (d, J=8.8Hz, 2H), 6.92 (d, J=8.4Hz, 1H), 6.85 (s, 1H), 6.79 (d, J=8.0Hz, 1H), 6.56 (d, J=8.8Hz, 1H), 3.86 (s, 3H),3.77(s,3H)；HRMS(ESI):m/z,calcd.for C₂₃H₂₀N₃O₈S[M+H]⁺:498.0971,found 498.0957.

Embodiment 82:4- benzoyl -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) .4- benzyls -7- nitros -1H- indole -2-ethyl formates

By the chloro- 7- nitros -1H- indole -2-ethyl formates (100mg, 0.37mmol) of 4-, Pd (dppf) Cl₂(27mg, 0.037)、K₃PO₄(237mg, 1.12mmol), CsF (57mg, 0.37mmol) and benzyl boric acid pinacol ester (243mg, 1.12mmol) it is dissolved in Isosorbide-5-Nitrae-dioxane (2mL) and water (0.5mL), argon gas protection, microwave reaction (60w, 100 DEG C, 120min, 150psi).Concentration, adds EA (30mL) dissolution residual substance, and saturated common salt washes (20mL × 3), washing (20mL × 2), column chromatography (P/E=200:1-100:1) off-white powder 88mg, is obtained, yield is 58%, mp:126-128℃.

¹H NMR(acetone-d₆)δ(ppm):10.74 (brs, 1H), 8.27 (d, J=8.4Hz, 1H), 7.55 (s, 1H), 7.36-7.29 (m, 4H), 7.24-7.22 (m, 2H), 4.47 (s, 2H), 4.43 (q, J=7.2Hz, 2H), 1.40 (t, J= 7.2Hz,3H).

B) .4- benzoyls -7- nitros -1H- indole-2-carboxylic acids

It is b) described in preparation process be the same as Example 3 with 4- benzyl -7- nitro -1H- indole -2-ethyl formate initiation materials Method, obtains brown powder solid 40mg, and yield is 60%, mp:179-182℃.

¹H NMR(DMSO-d₆)δ(ppm):11.51 (s, 1H), 8.36 (d, J=8.0Hz, 1H), 7.80 (d, J=7.6Hz, 2H), 7.74 (t, J=7.6Hz, 1H), 7.59 (t, J=7.2Hz, 2H), 7.55 (d, J=8.0Hz, 1H), 7.21 (s, 1H)； HRMS(ESI):m/z,calcd for C₁₆H₁₁N₂O₅[M+H⁺]:311.0668,found311.0653.

C) .4- benzoyls -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- benzoyl -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as initiation material, prepared C) methods described in journey be the same as Example 3, obtains yellow powdery solid 15mg, yield is 38%, mp:235-237℃.

¹H NMR(DMSO-d₆)δ(ppm):12.98 (brs, 1H), 11.94 (s, 1H), 8.39 (d, J=8.4Hz, 1H), 7.96 (d, J=8.8Hz, 2H), 7.79-7.73 (m, 3H), 7.59 (t, J=7.6Hz, 2H), 7.55 (t, J=8.0Hz, 2H), 7.16 (d, J=8.8Hz, 2H), 3.85 (s, 3H)；HRMS(ESI):m/z,calcd forC₂₃H₂₇N₃O₇S[M+H⁺]: 480.0865,found 480.0844.

Embodiment 83:4- ((3- methoxybenzenes) sulfenyl) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

A) .4- ((3- methoxybenzenes) sulfenyl) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- methoxybenzenethiols as initiation material, preparation process is same A) methods described in embodiment 81, obtains yellow powder solid 188mg, yield is 56%, mp:119-120℃.

¹H NMR(acetone-d₆)δ(ppm):10.48 (brs, 1H), 8.18 (d, J=8.4Hz, 1H), 7.47 (t, J= 8.0Hz, 1H), 7.38 (s, 1H), 7.20 (d, J=7.2Hz, 2H), 7.11 (d, J=9.2Hz, 1H), 6.85 (d, J=8.4Hz, 1H), (t, J=7.2Hz, the 3H) of 4.44 (q, J=7.2Hz, 2H), 3.85 (s, 3H), 1.42

B) .4- ((3- methoxybenzenes) sulfenyl) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- methoxybenzenes) sulfenyl) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with real B) methods described is applied in example 3, pale yellow powder shape solid 110mg is obtained, yield is 99%, mp:188-190℃.

¹H NMR(DMSO-d₆)δ(ppm):11.19 (s, 1H), 8.16 (d, J=8.4Hz, 1H), 7.45 (t, J=8.1Hz, 1H), (s, the 3H) of 7.22 (s, 1H), 7.17-7.09 (m, 3H), 6.78 (d, J=8.4Hz, 1H), 3.78

C) .4- ((3- methoxybenzenes) sulfenyl) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxybenzenes) sulfenyl) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 50mg, yield is 73%, mp:200- 202℃。

¹H NMR(DMSO-d₆)δ(ppm):12.88 (brs, 1H), 11.81 (s, 1H), 8.48 (d, J=9.0Hz, 1H), 7.98 (d, J=9.0Hz, 2H), 7.59 (s, 1H), 7.45 (t, J=7.2Hz, 1H), 7.19-7.10 (m, 5H), 6.75 (d, J= 8.4Hz,1H),3.86(s,1H),3.78(s,3H).

Embodiment 84:4- ((3- Trifluoromethoxyphen-ls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .4- ((3- methoxyphenyls) (methyl) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- methoxy-. N-methyls aniline as initiation material, prepare A) methods described in process be the same as Example 75, obtains orange/yellow solid 124mg, yield is 53%, mp:101-103℃.

¹H NMR(CDCl₃)δ(ppm):10.44 (brs, 1H), 8.22 (d, J=9.6Hz, 1H), 7.36 (t, J=8.4Hz, 1H),6.90(dd,J₁=2.1Hz, J₂=8.7Hz, 1H), 6.83 (dd, J₁=1.2Hz, J₂=8.1Hz, 1H), 6.77 (t, J= 2.1Hz, 1H), 6.50 (d, J=9.0Hz, 1H), 6.26 (d, J=2.7Hz, 1H), 4.34 (q, J=7.2Hz, 2H), 3.81 (s, 3H), 3.60 (s, 3H), 1.35 (t, J=7.5Hz, 3H)

B) .4- ((3- methoxyphenyls) (methyl) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- methoxyphenyls) (methyl) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, prepare B) methods described in process be the same as Example 3, obtains yellow solid 90mg, yield is 98%, mp:213-215℃.

¹H NMR(DMSO-d₆)δ(ppm):10.61 (s, 1H), 8.19 (d, J=9.0Hz, 1H), 7.40 (t, J=8.1Hz, 1H), 6.99 (d, J=8.4Hz, 1H), 6.94 (s, 1H), 6.88 (d, J=6.9Hz, 1H), 6.69 (d, J=9.3Hz, 1H), 5.92(s,1H),3.76(s,3H),3.55(s,3H).

C) .4- ((3- Trifluoromethoxyphen-ls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((3- methoxyphenyls) (methyl) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains orange powder shape solid 73mg, yield is 90%, mp:245-247℃。

¹H NMR(DMSO-d₆)δ(ppm):12.82 (brs, 1H), 11.66 (s, 1H), 8.19 (d, J=9.2Hz, 1H), 7.90 (d, J=8.8Hz, 2H), 7.37 (t, J=8.0Hz, 1H), 7.14 (d, J=8.4Hz, 2H), 6.96 (d, J=8.4Hz, 1H), 6.90 (s, 1H), 6.82 (d, J=7.6Hz, 1H), 6.61 (d, J=9.2Hz, 1H), 6.37 (s, 1H), 3.85 (s, 3H), 3.75(s,3H),3.55(s,3H)；¹³C NMR(125MHz,DMSO-d₆):δ163.21,160.54,150.49,148.33, 132.52,130.86,130.21,126.41,124.04,118.24,116.51,114.31,112.78,111.76,105.90, 55.79,55.39,42.93.HRMS(ESI):m/z,calcd.for C₂₄H₂₃N₄O₇S[M+H]⁺:511.1287,found 511.1277.

Embodiment 85:4- ((3- methoxy-benzyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((3- methoxy-benzyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3- methoxybenzylamines as initiation material, preparation process is with real A) methods described is applied in example 81, yellow powder solid 270mg is obtained, yield is 98%, mp:162-163℃.

¹H NMR(CDCl₃)δ(ppm):10.44 (brs, 1H), 8.19 (d, J=8.7Hz, 1H), 7.31 (t, J=8.1Hz, 1H), 7.28 (d, J=7.8Hz, 1H), 6.96 (d, J=7.5Hz, 1H), 6.91-6.87 (m, 2H), 6.29 (d, J=9.0Hz, 1H), 5.46 (brs, 1H), 4.59 (s, 2H), 4.42 (q, J=7.2Hz, 2H), 3.81 (s, 3H), 1.42 (t, J=6.9Hz, 3H).

B) .4- ((3- methoxy-benzyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- methoxy-benzyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is same B) methods described in embodiment 3, obtains pale yellow powder shape solid 140mg, yield is 98%, mp:235-237℃.

¹H NMR(DMSO-d₆)δ(ppm):13.26 (brs, 1H), 10.60 (s, 1H), 8.60 (t, J=6.0Hz, 1H), 8.05 (d, J=8.8Hz, 1H), 7.73 (s, 1H), 7.26 (d, J=8.0Hz, 1H), 6.94 (d, J=7.2Hz, 1H), 6.83 (d, J=8.0Hz, 1H), 6.33 (d, J=9.2Hz, 1H), 4.60 (d, J=6.0Hz, 2H), 3.73 (s, 3H)

C) .4- ((3- methoxy-benzyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 4- ((3- methoxy-benzyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 55mg, yield is 92%, mp: 233-234℃。

¹H NMR(DMSO-d₆)δ(ppm):12.86 (brs, 1H), 11.78 (brs, 1H), 8.62 (t, J=5.6Hz, 1H), 8.06 (d, J=9.2Hz, 1H), 7.96 (d, J=8.8Hz, 2H), 7.81 (brs, 1H), 7.24 (t, J=8.0Hz, 1H), 7.16 (d, J=8.4Hz, 2H), 6.91 (d, J=7.2Hz, 2H), 6.82 (d, J=7.6Hz, 1H), 6.30 (d, J=9.2Hz, 1H), (s, the 3H) of 4.58 (d, J=6.0Hz, 2H), 3.86 (s, 3H), 3.71

Embodiment 86:4- benzamido -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) .4- benzamidos -7- nitros -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and benzamide as initiation material, preparation process be the same as Example A) methods described in 75, obtains yellow powder solid 235mg, yield is 89%, mp:220-222℃.

¹H NMR(CDCl₃)δ(ppm):10.48 (s, 1H), 8.39-8.31 (m, 3H), 7.97 (d, J=7.6Hz, 2H), 7.66 (t, J=7.2Hz, 1H), 7.58 (t, J=7.2Hz, 2H), 7.38 (s, 1H), 4.48 (q, J=7.2Hz, 2H), 1.46 (t, J=7.2Hz, 3H)

B) .4- benzamidos -7- nitros -1H- indole-2-carboxylic acids

With 4- benzamido -7- nitro -1H- indole -2-ethyl formate initiation materials, in preparation process be the same as Example 3 B) methods described, obtains yellow powdery solid 72mg, and yield is 65%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):11.03 (s, 1H), 10.72 (s, 1H), 8.33 (d, J=8.8Hz, 1H), (t, J=7.6Hz, the 2H) of 8.05-8.01 (m, 3H), 7.86 (s, 1H), 7.66 (t, J=7.2Hz, 1H), 7.58

C) .4- benzamidos -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- benzamido -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as initiation material, prepare C) methods described in process be the same as Example 3, obtains orange powder shape solid 46mg, yield is 75%, mp:253-255℃.

¹H NMR(DMSO-d₆)δ(ppm):12.94 (brs, 1H), 11.84 (s, 1H), 10.75 (s, 1H), 8.36 (d, J= 8.8Hz, 1H), 8.02-7.94 (m, 6H), 7.66 (t, J=7.2Hz, 1H), 7.58 (t, J=7.2Hz, 2H), 7.16 (d, J= 8.8Hz,2H),3.85(s,3H).

Embodiment 87:4- isobutyl group -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) .4- isobutyl groups -7- nitros -1H- indole -2-ethyl formates

The chloro- 7- nitros -1H- indole -2-ethyl formates (250mg, 0.93mmol) of 4- are dissolved in toluene (12mL), Sequentially add Pd (OAc)₂(21mg, 0.093mmol), (tBu)₃P·HBF₄(54mg, 0.19mmol) and K₃PO₄(987mg, 4.65mmol,1mL H₂O), after stirring, isobutaneboronic acid (284mg, 2.79mmol) is added, under argon gas protection, 90 DEG C anti- 2h is answered, raw material disappears.Room temperature is cooled to, is concentrated, EA (40mL) dissolution residual substance, saturated common salt washing (20mL × 3), water is added Wash (20mL × 2), column chromatography (P/E=100:1) off-white powder 216mg, is obtained, yield is 80%, mp:108-109℃.

¹H NMR(CDCl₃)δ(ppm):10.36 (s, 1H), 8.23 (d, J=8.0Hz, 1H), 7.38 (s, 1H), 7.05 (d, J=8.0Hz, 1H), 4.47 (q, J=7.2Hz, 2H), 2.86 (d, J=7.2Hz, 2H), 2.04-2.15 (m, 1H), 1.46 (t, J =7.2Hz, 2H), 0.97 (d, J=7.2Hz, 6H)；HRMS(ESI):m/z,calcdfor C₁₅H₁₉N₂O₄[M+H⁺]: 291.1339,found 291.1331.

B) .4- isobutyl groups -7- nitros -1H- indole-2-carboxylic acids

With 4- isobutyl group -7- nitro -1H- indole -2-ethyl formate initiation materials, b) institute in preparation process be the same as Example 3 Method is stated, off-white powder 116mg is obtained, yield is 82%, mp:195-197℃.

¹H NMR(DMSO-d₆)δ(ppm):13.53 (s, 1H), 11.02 (s, 1H), 8.21 (d, J=8.4Hz, 1H), 7.49 (s, 1H), 7.15 (d, J=8.0Hz, 1H), 2.88 (d, J=7.2Hz, 2H), 1.96-2.06 (m, 1H), 0.91 (d, J= 6.4Hz,6H)；HRMS(ESI):m/z,calcd for C₁₃H₁₅N₂O₄[M+H⁺]:263.1026,found 263.1024.

C) .4- isobutyl groups -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- isobutyl group -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, preparation process be the same as Example C) methods described in 3, obtains pale yellow powder shape solid 60mg, yield is 78%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.10 (brs, 1H), 11.64 (brs, 1H), 8.23 (d, J=8.1Hz, 1H), 8.07 (d, J=7.2Hz, 2H), 7.76-7.68 (m, 4H), 7.14 (d, J=7.8Hz, 1H), 2.84 (d, J=6.6Hz, 2H), 2.04-2.00 (m, 1H), 0.90 (d, J=6.0Hz, 6H)

Embodiment 88:4- (propylcarbamic) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) .4- (propylcarbamic) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and n-propylamine as initiation material, preparation process be the same as Example 81 Middle a) methods described, obtains yellow powder solid 193mg, and yield is 71%, mp:155-157℃.

¹H NMR(CDCl₃)δ(ppm):10.43 (brs, 1H), 8.21 (d, J=8.8Hz, 1H), 6.26 (d, J=8.8Hz, 1H), 5.15 (s, 1H), 4.43 (q, J=7.2Hz, 2H), 3.39 (t, J=7.2Hz, 2H), 1.78 (sext, J=7.2Hz, 2H), 1.43 (t, J=7.2Hz, 3H), 1.07 (t, J=7.2Hz, 3H)

B) .4- (propylcarbamic) -7- nitro -1H- indole-2-carboxylic acids

With 4- (propylcarbamic) -7- nitro -1H- indole -2-ethyl formate initiation materials, in preparation process be the same as Example 3 B) methods described, obtains yellow powdery solid 86mg, and yield is 96%, mp:234-236℃.

¹H NMR(DMSO-d₆)δ(ppm):13.23 (brs, 1H), 10.56 (s, 1H), 8.09 (d, J=9.2Hz, 1H), 8.02 (t, J=5.2Hz, 1H), 7.71 (s, 1H), 6.38 (d, J=7.2Hz, 1H), 3.34 (q, J=6.4Hz, 2H), 1.67 (sext, J=7.2Hz, 2H), 0.97 (t, J=7.2Hz, 3H)

C) .4- (propylcarbamic) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- (propylcarbamic) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as initiation material, prepare C) methods described in process be the same as Example 3, obtains pale yellow powder shape solid 50mg, yield is 81%, mp:284-286℃.

¹H NMR(DMSO-d₆)δ(ppm):12.85 (brs, 1H), 11.75 (s, 1H), 8.10 (d, J=8.8Hz, 2H), 7.97 (d, J=8.8Hz, 2H), 7.81 (s, 1H), 7.16 (d, J=8.8Hz, 2H), 6.36 (d, J=9.2Hz, 1H), 3.86 (s, 3H), 3.32 (q, J=6.0Hz, 2H), 1.65 (sext, 2H), 0.94 (t, J=7.2Hz, 1H)

Embodiment 89:4- ((2- methoxy ethyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((2- methoxy ethyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 2- methoxies ethamine as initiation material, preparation process is with implementation A) methods described in example 81, obtains yellow powder solid 178mg, yield is 78%, mp:155-156℃.

¹H NMR(CDCl₃)δ(ppm):10.44 (brs, 1H), 8.22 (d, J=9.0Hz, 1H), 7.28 (d, J=2.1Hz, 1H), 6.27 (d, J=9.0Hz, 1H), 5.45 (s, 1H), 4.43 (q, J=7.2Hz, 2H), 3.71 (t, J=5.1Hz, 2H), (t, J=7.2Hz, the 3H) of 3.58 (t, J=5.1Hz, 2H), 3.45 (s, 3H), 1.43

B) .4- ((2- methoxy ethyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((2- methoxy ethyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is same B) methods described in embodiment 3, obtains yellow powdery solid 98mg, yield is 92%, mp:226-228℃.

¹H NMR(DMSO-d₆)δ(ppm):13.24 (brs, 1H), 10.57 (s, 1H), 8.09 (d, J=8.8Hz, 2H), (s, the 3H) of 7.72 (s, 1H), 6.43 (d, J=9.2Hz, 1H), 3.58 (s, 4H), 3.29

C) .4- ((2- methoxy ethyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 4- ((2- methoxy ethyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 40mg, yield is 58%, mp: 208-210℃。

¹H NMR(DMSO-d₆)δ(ppm):12.83 (brs, 1H), 11.74 (s, 1H), 8.10 (d, J=9.2Hz, 1H), 8.05 (s, 1H), 7.95 (d, J=8.4Hz, 2H), 7.77 (s, 1H), 7.15 (d, J=7.6Hz, 2H), 6.40 (d, J= 9.2Hz,1H),3.85(s,3H),3.56(s,4H),3.27(s,3H)；¹³C NMR(125MHz,DMSO-d₆):δ163.11, 150.65,131.76,130.07,127.81,122.08,114.85,114.20,70.05,58.14,55.75,42.46.HRMS (ESI):m/z,calcd.for C₁₉H₂₁N₄O₇S[M+H]⁺:449.1131,found 449.1115.

Embodiment 90:4- ((3- methoxy-propyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((3- methoxy-propyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and 3 methoxypropyl amine as initiation material, preparation process is with real A) methods described is applied in example 81, yellow powder solid 135mg is obtained, yield is 56%, mp:125-127℃.

¹H NMR(CDCl₃)δ(ppm):10.43 (brs, 1H), 8.21 (d, J=9.0Hz, 1H), 7.20 (d, J=2.1Hz, 1H), 6.24 (d, J=9.0Hz, 1H), 6.01 (brs, 1H), 4.43 (q, J=7.2Hz, 2H), 3.62 (t, J=5.1Hz, 2H), (t, J=7.2Hz, the 3H) of 3.54 (t, J=6.0Hz, 2H), 3.44 (s, 3H), 2.05-2.01 (m, 2H), 1.43

B) .4- ((3- methoxy-propyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 4- ((3- methoxy-propyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is same B) methods described in embodiment 3, obtains yellow powdery solid 49mg, yield is 76%, mp:216-218℃.

¹H NMR(DMSO-d₆)δ(ppm):10.55 (s, 1H), 8.08 (d, J=9.3Hz, 1H), 7.99 (brs, 1H), 7.67 (d, J=2.1Hz, 1H), 6.36 (d, J=9.3Hz, 1H), 3.43-3.39 (m, 4H), 3.24 (s, 3H), 3.83 (s, 3H),1.88-1.84(m,2H).

C) .4- ((3- methoxy-propyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 4- ((3- methoxy-propyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 38mg, yield is 69%, mp: 249-250℃。

¹H NMR(DMSO-d₆)δ(ppm):12.86 (brs, 1H), 11.77 (s, 1H), 8.12 (d, J=9.2Hz, 1H), 8.01 (brs, 1H), 7.97 (d, J=8.4Hz, 2H), 7.77 (s, 1H), 7.16 (d, J=8.8Hz, 2H), 6.35 (d, J= 9.2Hz, 1H), 3.86 (s, 3H), 3.41 (t, J=5.6Hz, 4H), 3.24 (s, 3H), 1.89-1.83 (m, 2H)

Embodiment 91:4- morpholinyl -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) .4- morpholinyls -7- nitros -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and morpholine as initiation material, in preparation process be the same as Example 3 A) methods described, obtains yellow solid 147mg, and yield is 50%, mp:167-168℃.

¹H NMR(CDCl₃)δ(ppm):10.51 (s, 1H), 8.22 (d, J=9.2Hz, 1H), 7.32 (d, J=1.6Hz, 1H), 6.53 (d, J=8.8Hz, 1H), 4.46 (q, J=7.2Hz, 2H), 3.95 (t, J=4.4Hz, 4H), 3.60 (t, J= 4.4Hz, 4H), 1.45 (t, J=7.2Hz, 3H)

B) .4- morpholinyls -7- nitros -1H- indole-2-carboxylic acids

With 4- morpholinyl -7- nitro -1H- indole -2-ethyl formate initiation materials, b) institute in preparation process be the same as Example 3 Method is stated, yellow solid 115mg is obtained, yield is 99%, mp:247-248℃.

¹H NMR(DMSO-d₆)δ(ppm):13.44 (brs, 1H), 10.81 (s, 1H), 8.14 (d, J=9.0Hz, 1H), 7.46 (d, J=1.8Hz, 1H), 6.70 (d, J=9.6Hz, 1H), 3.81 (t, J=4.5Hz, 4H), 3.64 (t, J=4.2Hz, 4H).

C) .4- morpholinyls -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- morpholinyl -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, preparation process be the same as Example C) methods described in 3, obtains pale yellow powder shape solid 62mg, yield is 67%, mp:258-259℃.

¹H NMR(DMSO-d₆)δ(ppm):10.99 (brs, 1H), 8.11 (d, J=8.8Hz, 1H), 7.98 (d, J= 7.2Hz, 2H), 7.64-7.56 (m, 3H), 7.50 (brs, 1H), 6.65 (d, J=9.2Hz, 1H), 3.81 (t, J=4.0Hz, 4H), 3.61 (t, J=4.0Hz, 4H)

Embodiment 92:4- (N-Boc- piperazine -1- bases) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) .4- (N-Boc- piperazine -1- bases) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and N-Boc- piperazines as initiation material, preparation process is with implementation A) methods described in example 3, obtains yellow solid 140mg, yield is 30%, mp:143-144℃.

¹H NMR(CDCl₃)δ(ppm):10.51 (s, 1H), 8.21 (d, J=8.8Hz, 1H), 7.33 (s, 1H), 6.49 (d, J=8.8Hz, 1H), 4.45 (q, J=7.2Hz, 2H), 3.710-3.70 (m, 4H), 3.62 (t, J=4.0Hz, 4H), 1.51 (s, 9H), 1.44 (t, J=7.2Hz, 3H)

B) .4- (N-Boc- piperazine -1- bases) -7- nitro -1H- indole-2-carboxylic acids

With 4- (N-Boc- piperazine -1- bases) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process is with real B) methods described is applied in example 3, yellow solid 100mg is obtained, yield is 98%, mp:208-210℃.

¹H NMR(DMSO-d₆)δ(ppm):13.50 (brs, 1H), 10.79 (s, 1H), 8.13 (d, J=8.8Hz, 1H), (7.45 s, 1H), 6.63 (d, J=9.2Hz, 1H), 3.72 (s, 4H), 3.59 (s, 4H), 1.44 (s, 9H)

C) .4- (N-Boc- piperazine -1- bases) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- (N-Boc- piperazine -1- bases) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, prepare C) methods described in process be the same as Example 3, obtains orange powder shape solid 80mg, yield is 67%, mp:240-241℃.

¹H NMR(DMSO-d₆)δ(ppm):12.90 (brs, 1H), 11.33 (s, 1H), 8.13 (d, J=9.2Hz, 1H), 8.04 (d, J=7.6Hz, 2H), 7.77-7.73 (m, 2H), 7.66 (t, J=7.6Hz, 2H), 6.60 (d, J=9.2Hz, 1H), 3.71(s,4H),3.59(s,4H),1.44(s,9H).

Embodiment 93:4- (piperazine -1- bases) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

By 4- (N-Boc- piperazine -1- bases) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides (23mg, 0.043mmol) it is dissolved in MeOH (1mL), adds 2.77M HCl Isosorbide-5-Nitrae-dioxane (2mL), reacts at room temperature 30min, raw material Disappear, solid is separated out in whipping process.Filtering, dries, obtains pale yellow powder shape solid 19mg, yield is 95%, mp:239- 241℃。

¹HNMR(DMSO-d₆)δ(ppm):13.00 (brs, 1H), 11.50 (s, 1H), 9.27 (s, 1H), 8.19 (d, J= 8.8Hz, 1H), 8.04 (d, J=7.6Hz, 2H), 7.76-7.73 (m, 2H), 7.66 (t, J=7.6Hz, 2H), 6.74 (d, J= 9.2Hz,1H),3.79(s,4H),3.33(s,4H).

Embodiment 94:4- (Cyclohexylamino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) .4- (Cyclohexylamino) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and cyclohexylamine as initiation material, preparation process be the same as Example 3 Middle a) methods described, obtains yellow solid 130mg, and yield is 53%, mp:175-178℃.

¹H NMR(CDCl₃)δ(ppm):10.44 (s, 1H), 8.20 (d, J=8.8Hz, 1H), 7.24 (s, 1H), 6.28 (d, J=9.2Hz, 1H), 5.01 (d, J=7.2Hz, 1H), 4.43 (d, J=7.2Hz, 1H), 3.62-3.60 (m, 1H), 2.14 (d, J =11.6Hz, 2H), 1.84 (d, J=13.2Hz, 2H), 1.72 (d, J=15.5Hz, 2H), 1.51-1.28 (m, 8H)

B) .4- (Cyclohexylamino) -7- nitro -1H- indole-2-carboxylic acids

With 4- (Cyclohexylamino) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process be the same as Example 3 Middle b) methods described, obtains yellow solid 70mg, and yield is 73%, mp:205-208℃.

¹H NMR(DMSO-d₆)δ(ppm):13.21(s,1H),10.54(s,1H),8.06(m,1H),7.79(s,1H), 7.72(m,1H),6.42(m,1H),3.62(m 1H),3.34(m,2H),1.97(m,2H),1.77(m,2H),1.66(m,1H), 1.38(m,3H),1.23(m,2H).

C) .4- (Cyclohexylamino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- (Cyclohexylamino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as initiation material, system C) methods described in standby process be the same as Example 3, obtains orange powder shape solid 45mg, yield is 73%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):12.81 (s, 1H), 11.74 (s, 1H), 8.09 (d, J=8.8Hz, 1H), 7.96 (d, J=8.0Hz, 2H), 7.87 (s, 1H), 7.73 (d, J=6.8Hz, 1H), 7.16 (d, J=8.4Hz, 2H), 6.40 (d, J= 9.2Hz, 1H), 3.85 (s, 3H), 3.60 (s, 1H), 1.99-1.95 (m, 2H), 1.75 (m, 2H), 1.64 (d, J=11.2Hz, 1H),1.37-1.35(m,4H),1.18(m,1H).

The preparation 2 of intermediate：

The chloro- 1H- indole -2-ethyl formates of 5- methyl -7- nitros -4-

A) .4- methyl -2- nitros -5- chlorophenylhydxazine hydrochlorides

Using 4- methyl -2- nitro -5- chlorobenzenes amine hydrochlorates as initiation material, preparation process with the preparation 1 of intermediate a) Described method, obtains faint yellow solid 6.24g, and yield is 98%.

¹H NMR(DMSO-d₆)δ(ppm):9.19(s,1H),8.15(s,1H),7.51(s,1H),2.31(s,3H).

B) .2- (2- (4- methyl -2- nitro -5- chlorphenyls) hydrazono-) ethyl propionate

Using 4- methyl -2- nitro -5- chlorophenylhydxazine hydrochlorides and ethyl pyruvate as initiation material, the same intermediate of preparation process Preparation 1 in b) described in method, obtain faint yellow solid 6.73g, yield is 84%.

¹H NMR(CDCl₃)δ(ppm):10.82 (s, 1H), 8.08 (s, 1H), 8.03 (s, 1H), 4.37 (q, J=6.8Hz, 2H), (t, J=6.8Hz, the 3H) of 2.37-2.36 (m, 3H), 2.26-2.23 (m, 3H), 1.41

C) the chloro- 1H- indole -2-ethyl formates of .5- methyl -7- nitros -4-

Using 2- (2- (4- methyl -2- nitro -5- chlorphenyls) hydrazono-) ethyl propionate as initiation material, preparation process is with In the preparation 1 of mesosome c) described in method, obtain faint yellow solid 846mg, yield is 13%, mp:179-180℃.

¹H NMR(CDCl₃)δ(ppm):10.28 (brs, 1H), 8.18 (s, 1H), 7.40 (s, 1H), 4.47 (q, J= 7.2Hz, 2H), 2.55 (s, 3H), 1.45 (t, J=7.2Hz, 3H)

Embodiment 95:5- methyl -4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) .5- methyl -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the 5- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 3- aminoanisoles as initiation material, prepare A) methods described in process be the same as Example 75, obtains yellow powder solid 220mg, yield is 84%, mp:190-192℃.

¹H NMR(CDCl₃)δ(ppm):10.32 (brs, 1H), 8.18 (s, 1H), 7.27 (t, J=8.0Hz, 1H), 6.77 (d, J=8.4Hz, 1H), 6.72 (d, J=8.0Hz, 1H), 6.66 (d, J=6.0Hz, 2H), 6.29 (brs, 1H), 4.36 (q, J =7.2Hz, 2H), 3.79 (s, 3H), 2.38 (s, 3H), 1.36 (t, J=7.2Hz, 3H)

B) .5- methyl -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 5- methyl -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, system B) methods described in standby process be the same as Example 3, obtains yellow powdery solid 80mg, yield is 64%, mp:250-253℃.

¹H NMR(DMSO-d₆)δ(ppm):13.29(brs,1H),10.64(s,1H),8.80(s,1H),8.13(s,1H), 7.27 (t, J=8.4Hz, 1H), 6.76 (d, J=8.4Hz, 1H), 6.68-6.70 (m, 2H), 6.53 (s, 1H), 3.73 (s, 3H),2.31(s,3H).

C) .5- methyl -4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

With 5- methyl -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 60mg, yield is 91%, mp:215-217℃。

¹H NMR(DMSO-d₆)δ(ppm):12.83(brs,1H),11.64(brs,1H),8.76(s,1H),8.15(s, 1H), 7.90 (d, J=8.4Hz, 2H), 7.24 (t, J=8.0Hz, 1H), 7.13 (d, J=8.4Hz, 2H), 6.75-6.72 (m, 2H), (s, the 3H) of 6.65 (s, 1H), 6.62 (d, J=8.0Hz, 1H), 3.84 (s, 3H), 3.71 (s, 3H), 2.30

The preparation 3 of intermediate：The chloro- 1H- indole -2-ethyl formates of 7- nitros -4,5- two

A) .2- nitros -4,5- dichloride phenyl hydrazine hydrochloric acid salts

With 2- nitros -4,5- chlorophenylhydxazine hydrochloride be initiation material, preparation process with the preparation 1 of intermediate a) described in Method, obtains faint yellow solid 2.8g, and yield is 45%.

¹H-NMR(DMSO-d₆)δ(ppm):9.36(s,1H),8.29(s,1H),7.72(s,1H).

B) .2- (2- (2- nitro -4,5- dichlorophenyls) hydrazono-) ethyl propionate

With 2- nitros -4,5- dichloride phenyl hydrazine hydrochloric acid salt and ethyl pyruvate for initiation material, preparation process is with intermediate Prepare 1 in b) described in method, obtain faint yellow solid 2.0g, yield is 58%.

¹H NMR(CDCl₃)δ(ppm):10.82 (s, 1H), 8.32 (s, 1H), 8.15 (s, 1H), 4.37 (q, J=7.2Hz, 2H), 2.25 (s, 3H), 1.41 (t, J=6.8Hz, 3H)

C) the chloro- 1H- indole -2-ethyl formates of .7- nitros -4,5- two

With 2- (2- (2- nitros -4,5- dichlorophenyl) hydrazono-) ethyl propionate for initiation material, preparation process is with middle In the preparation 1 of body c) described in method, obtain faint yellow solid 710mg, yield is 38%, mp:168-169℃.

¹H NMR(CDCl₃)δ(ppm):10.37 (brs, 1H), 8.37 (s, 1H), 7.42 (s, 1H), 4.48 (q, J= 7.2Hz, 2H), 1.46 (t, J=7.2Hz, 3H)

Embodiment 96:4- ((3- methoxyphenyls) amino) the chloro- N- of -7- nitros -5- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) .4- ((3- methoxyphenyls) amino) the chloro- 1H- indole -2-ethyl formates of -7- nitros -5-

With the chloro- 1H- indole -2-ethyl formates of 7- nitros -4,5- bis- and 3- aminoanisoles for initiation material, preparation process A) methods described in be the same as Example 75, obtains yellow powder solid 177mg, yield is 63%, mp:179-180℃.

¹H NMR(CDCl₃)δ(ppm):10.39 (brs, 1H), 8.38 (s, 1H), 7.34 (t, J=8.0Hz, 1H), 7.09 (s, 1H), 6.89 (d, J=8.4Hz, 1H), 6.84 (d, J=8.0Hz, 1H), 6.79 (s, 1H), 6.48 (s, 1H), 4.35 (q, J =7.2Hz, 2H), 3.81 (s, 3H), 1.35 (t, J=7.2Hz, 3H)

B) .4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- nitros -5-

With 4- ((3- methoxyphenyls) amino) the chloro- 1H- indole -2-ethyl formates initiation materials of -7- nitros -5-, prepare B) methods described in process be the same as Example 3, obtains yellow powdery solid 112mg, yield is 99%, mp:249-250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.41(s,1H),10.90(s,1H),9.19(s,1H),8.28(s,1H), 7.32 (t, J=8.0Hz, 1H), 6.86 (d, J=8.4Hz, 1H), 6.82 (s, 1H), 6.79 (d, J=8.0Hz, 1H), 6.35 (s,1H),3.74(s,3H).

C) .4- ((3- methoxyphenyls) amino) the chloro- N- of -7- nitros -5- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- nitros -5- and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains yellow powdery solid 71mg, yield is 93%, mp: 216-218℃。

¹H NMR(DMSO-d₆)δ(ppm):12.90(brs,1H),11.82(brs,1H),9.15(s,1H),8.29(s, 1H), 7.89 (d, J=8.4Hz, 2H), 7.28 (t, J=8.0Hz, 1H), 7.12 (d, J=8.4Hz, 2H), 6.83 (d, J= 8.0Hz, 1H), 6.78 (s, 1H), 6.73 (d, J=8.0Hz, 1H), 6.56 (brs, 1H), 3.84 (s, 3H), 3.72 (s, 3H)；¹³C NMR(125MHz,DMSO-d₆):δ163.25,159.90,143.29,141.51,131.19,130.24,129.91, 125.46,124.40,117.21,115.86,114.31,111.01,110.88,109.39,55.80,55.21.HRMS (ESI):m/z,calcd.for C₂₃H₂₀N₄O₇ClS[M+H]⁺:531.0741,found 531.0729.

The preparation 4 of intermediate：The chloro- 1H- indole -2-ethyl formates of the fluoro- 4- of 7- nitros -5-

A) the fluoro- 5- chlorophenylhydxazine hydrochlorides BJB-3048 of .2- nitros -4- and b) 2- (2- (the fluoro- 5- chlorphenyls of 2- nitros -4-) Hydrazono-) ethyl propionate

Using the fluoro- 5- chlorobenzenes amine hydrochlorates of 2- nitros -4- as initiation material, preparation process is with a) institute in the preparation 1 of intermediate The method stated, obtains faint yellow solid 6.24g, and yield is 98%.

Using the fluoro- 5- chlorophenylhydxazine hydrochlorides of 2- nitros -4- and ethyl pyruvate as initiation material, preparation process is with intermediate Prepare 1 in b) described in method, obtain faint yellow solid 6.30g, yield is 79%.

¹H NMR(CDCl₃) δ (ppm) 10.81 (s, 1H), 8.12 (d, J=6.8Hz, 1H), 8.01 (d, J=8.8Hz, 1H), (t, J=6.8Hz, the 3H) of 4.37 (q, J=7.2Hz, 2H), 2.24 (s, 3H), 1.41

C) the chloro- 1H- indole -2-ethyl formates of the fluoro- 4- of .7- nitros -5-

Using 2- (2- (the fluoro- 5- chlorphenyls of 2- nitros -4-) hydrazono-) ethyl propionate as initiation material, preparation process is with middle In the preparation 1 of body c) described in method, obtain faint yellow solid 681mg, yield is 14%, mp:166-168℃.

¹H NMR(CDCl₃)δ(ppm):10.35 (brs, 1H), 8.14 (d, J=9.2Hz, 1H), 7.45 (s, 1H), 4.48 (q, J=7.2Hz, 2H), 1.46 (t, J=7.2Hz, 3H)

Embodiment 97:4- ((3- methoxyphenyls) amino) the fluoro- N- of -7- nitros -5- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) .4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole -2-ethyl formates of -7- nitros -5-

Using the chloro- 1H- indole -2-ethyl formates of the fluoro- 4- of 7- nitros -5- and 3- aminoanisoles as initiation material, prepared A) methods described in journey be the same as Example 75, obtains yellow powder solid 271mg, yield is 83%, mp:165-167℃.

¹H NMR(CDCl₃)δ(ppm):10.39 (brs, 1H), 8.14 (d, J=12.0Hz, 1H), 7.32 (t, J= 8.0Hz, 1H), 6.84 (t, J=8.0Hz, 2H), 6.77 (s, 1H), 6.73 (brs, 1H), 6.68 (s, 1H), 4.37 (q, J= 7.2Hz, 2H), 3.81 (s, 3H), 1.36 (t, J=7.2Hz, 3H)

B) .4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole-2-carboxylic acids of -7- nitros -5-

With 4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole -2-ethyl formates initiation materials of -7- nitros -5-, prepare B) methods described in process be the same as Example 3, obtains yellow powdery solid 120mg, yield is 96%, mp:245-248℃.

¹H NMR(DMSO-d₆)δ(ppm):13.45 (s, 1H), 10.87 (s, 1H), 9.50 (s, 1H), 8.16 (d, J= 12.4Hz, 1H), 7.29 (t, J=8.0Hz, 1H), 6.95 (s, 1H), 6.78-6.76 (m, 3H), 3.74 (s, 3H)

C) .4- ((3- methoxyphenyls) amino) the fluoro- N- of -7- nitros -5- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole-2-carboxylic acids of -7- nitros -5- and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains orange red pulverulent solids 74mg, yield is 82%, mp:128-130℃。

¹H NMR(DMSO-d₆)δ(ppm):12.92(brs,1H),11.80(brs,1H),9.49(s,1H),8.17(d,J =12.8Hz, 1H), 7.93 (d, J=8.8Hz, 1H), 7.27 (t, J=8.0Hz, 1H), 7.14 (d, J=8.8Hz, 2H), 7.10 (s, 1H), 6.77 (d, J=8.4Hz, 1H), 6.72 (s, 2H), 3.84 (s, 3H), 3.73 (s, 3H)

The preparation 5 of intermediate：The chloro- 1H- indole -2-ethyl formates of 1- methyl -7- nitros -4-

The chloro- 7- nitros -1H- indole -2-ethyl formates (200mg, 0.74mmol) of 4- are dissolved in DMF (6mL), added successively Enter cesium carbonate (723mg, 2.23mmol) and iodomethane (211mg, 1.49mmol), room temperature 3h, raw material disappears.Reaction solution is poured into In water (20mL), EA (20mL × 2) extractions, saturated common salt washing (20mL × 3) is washed (20mL × 3), concentration, EA recrystallizations, Pale yellow powder shape solid 200mg is obtained, yield is 95%, mp:118-120℃.

¹H NMR(CDCl₃)δ(ppm):7.81 (d, J=8.4Hz, 1H), 7.52 (s, 1H), 7.20 (d, J=8.4Hz, 1H), (t, J=7.2Hz, the 3H) of 4.42 (q, J=7.2Hz, 2H), 4.01 (s, 3H), 1.44

Embodiment 98:1- methyl -4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) .1- methyl -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 3- aminoanisoles as initiation material, prepare A) methods described in process be the same as Example 3, obtains yellow solid 197mg, yield is 84%, mp:202-204℃.

¹H NMR(CDCl₃)δ(ppm):7.98 (d, J=8.8Hz, 1H), 7.43 (s, 1H), 7.31 (t, J=8.0Hz, 1H), 6.87 (d, J=8.4Hz, 1H), 6.83 (s, 1H), 6.82 (d, J=8.8Hz, 1H), 6.74 (d, J=8.0Hz, 1H), (t, J=7.2Hz, the 3H) of 6.56 (s, 1H), 4.40 (q, J=7.2Hz, 2H), 4.01 (s, 3H), 3.83 (s, 3H), 1.42

B) .1- methyl -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 1- methyl -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, system B) methods described in standby process be the same as Example 3, obtains yellow powdery solid 157mg, yield is 98%, mp:236-238℃.

¹H NMR(DMSO-d₆)δ(ppm):13.16 (brs, 1H), 9.32 (s, 1H), 7.99 (d, J=8.8Hz, 1H), 7.90 (s, 1H), 7.33 (t, J=8.0Hz, 1H), 6.95 (d, J=8.0Hz, 1H), 6.90 (s, 1H), 6.80 (d, J= 8.8Hz, 1H), 6.74 (d, J=8.0Hz, 1H), 3.86 (s, 3H), 3.78 (s, 3H)

C) .1- methyl -4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

With 1- methyl -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 39mg, yield is 50%, mp:252-254℃。

¹H NMR(DMSO-d₆)δ(ppm):12.65 (brs, 1H), 9.39 (s, 1H), 7.99 (d, J=10.0Hz, 1H), 7.96 (d, J=9.2Hz, 2H), 7.89 (s, 1H), 7.33 (t, J=8.4Hz, 1H), 7.18 (d, J=8.8Hz, 2H), 6.94 (d, J=8.0Hz, 1H), 6.89 (s, 1H), 6.82 (d, J=8.8Hz, 1H), 6.75 (t, J=8.0Hz, 1H), 3.87 (s, 3H),3.78(s,3H),3.62(s,3H)；¹³C NMR(125MHz,DMSO-d₆):δ163.19,160.14,159.20, 145.52,141.06,133.82,130.93,130.31,130.05,128.43,127.63,117.27,114.34,113.87, 110.42,109.55,107.37,101.87,55.81,55.13,36.56.HRMS(ESI):m/z,calcd.for C₂₄H₂₃N₄O₇S[M+H]⁺:511.1282,found 511.1274.

Embodiment 99:1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) .1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and the fluoro- 3- chloroanilines of 4- as initiation material, prepare A) methods described in process be the same as Example 3, obtains yellow solid 152mg, yield is 73%, mp:223-224℃.

¹H NMR(acetone-d₆)δ(ppm):8.58 (s, 1H), 8.00 (d, J=8.8Hz, 1H), 7.77 (s, 1H), 7.56 (d, J=6.4Hz, 1H), 7.43 (m, 1H), 7.38 (t, J=8.8Hz, 1H), 6.84 (d, J=8.8Hz, 1H), 4.39 (q, J=7.2Hz, 2H), 3.98 (s, 3H), 1.39 (t, J=7.2Hz, 3H)

B) .1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitro -1H- indole-2-carboxylic acids

With 1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, system B) methods described in standby process be the same as Example 3, obtains orange powder shape solid 100mg, yield is 98%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):9.28 (s, 1H), 7.90 (d, J=8.8Hz, 1H), 7.62 (s, 1H), 7.52 (d, J=9.2Hz, 1H), 7.44 (t, J=8.8Hz, 1H), 7.37-7.35 (m, 1H), 6.71 (d, J=9.2Hz, 1H), 3.89 (s,3H).

C) .1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

With 1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphurs Acid amides is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 46mg, yield is 63%, mp:275-277℃。

¹H NMR(DMSO-d₆)δ(ppm):12.65 (brs, 1H), 9.42 (s, 1H), 7.98 (d, J=8.8Hz, 1H), 7.95 (d, J=8.8Hz, 1H), 7.82 (s, 1H), 7.51 (d, J=6.8Hz, 1H), 7.47 (d, J=9.2Hz, 1H), 7.36- (s, the 3H) of 7.33 (m, 1H), 7.17 (d, J=8.8Hz, 2H), 6.74 (d, J=8.8Hz, 1H), 3.86 (s, 3H), 3.64

Embodiment 100:1- methyl -4- ((3,5- Dimethoxyphenyls) amino) -7- nitros-N- (4- methoxybenzene sulphonyl Base) -1H- indole 2-carboxamides

A) .1- methyl -4- ((3,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

With the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 3,5- dimethoxyaniline for initiation material, A) methods described in preparation process be the same as Example 3, obtains yellow solid 264mg, yield is 92%, mp:190-191℃.

¹H NMR(CDCl₃)δ(ppm):7.99 (d, J=8.8Hz, 1H), 7.43 (s, 1H), 6.86 (d, J=8.8Hz, 1H), 7.43 (s, 1H), 6.44 (s, 2H), 6.30 (s, 1H), 4.40 (q, J=7.2Hz, 2H), 4.01 (s, 3H), 3.80 (s, 6H), 1.42 (t, J=7.2Hz, 3H)

B) .1- methyl -4- ((3,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Originated with 1- methyl -4- ((3,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates former Material, b) methods described in preparation process be the same as Example 3, obtains orange powder shape solid 138mg, yield is 75%, mp:243-244 ℃。

¹H NMR(DMSO-d₆)δ(ppm):13.17 (brs, 1H), 9.27 (s, 1H), 7.90 (d, J=8.0Hz, 1H), (s, the 6H) of 7.88 (s, 1H), 6.86 (d, J=8.8Hz, 1H), 6.52 (s, 2H), 6.31 (s, 1H), 3.86 (s, 3H), 3.76

C) .1- methyl -4- ((3,5- Dimethoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

With 1- methyl -4- ((3,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenes Sulfonamide is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 59mg, yield is 91%, mp:255-257℃.

¹H NMR(DMSO-d₆)δ(ppm):12.63 (brs, 1H), 9.34 (s, 1H), 7.99 (d, J=8.8Hz, 1H), 7.95 (d, J=8.8Hz, 2H), 7.88 (s, 1H), 7.18 (d, J=8.8Hz, 2H), 6.87 (d, J=8.8Hz, 1H), 6.50 (s,2H),6.31(s,1H),3.86(s,3H),3.76(s,6H),3.62(s,3H)；¹³C NMR(125MHz,DMSO-d₆):δ 163.15,161.08,159.27,145.24,141.67,133.75,131.03,130.03,128.32,127.75,177.44, 114.32,110.33,102.37,99.64,95,84,55.80,55.24,36.54.HRMS(ESI):m/z,calcd.for C₂₅H₂₅N₄O₈S[M+H]⁺:541.1393,found541.1379.

Embodiment 101:1- methyl -4- ((3,5- Dimethoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- Yin Diindyl -2- formamides

Using 1- methyl -4- ((3,5- Dimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as C) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 58mg, yield is 95%, mp: 253-255℃。

¹H NMR(DMSO-d₆)δ(ppm):12.80 (brs, 1H), 9.35 (s, 1H), 8.03 (d, J=7.6Hz, 2H), 8.00 (d, J=9.2Hz, 1H), 7.92 (s, 1H), 7.74 (t, J=7.2Hz, 1H), 7.67 (t, J=7.6Hz, 2H), 6.88 (d, J=8.8Hz, 1H), 6.50 (s, 2H), 6.32 (s, 1H), 3.76 (s, 6H), 3.62 (s, 3H)；HRMS(ESI):m/z, calcd.for C₂₄H₂₃N₄O₇S[M+H]⁺:511.1287,found 511.1274.

Embodiment 102:1- methyl -4- ((3,4,5- trimethoxyphenyls) amino) -7- nitros-N- (4- methoxybenzene sulphurs Acyl group) -1H- indole 2-carboxamides

A) .1- methyl -4- ((3,4,5- trimethoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

It is former using the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 3,4,5- dimethoxyanilines as starting Material, a) methods described in preparation process be the same as Example 3, obtains orange solids 290mg, yield is 95%, mp:203-204℃.

¹H NMR(CDCl₃)δ(ppm):7.99 (d, J=8.8Hz, 1H), 7.42 (s, 1H), 6.70 (d, J=8.8Hz, 1H), 6.52 (s, 2H), 6.43 (brs, 1H), 4.40 (q, J=7.2Hz, 2H), 4.02 (s, 3H), 3.88 (s, 3H), 3.85 (s, 6H), 1.42 (t, J=7.2Hz, 3H)

B) .1- methyl -4- ((3,4,5- trimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Originated with 1- methyl -4- ((3,4,5- trimethoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates former Material, b) methods described in preparation process be the same as Example 3, obtains orange powder shape solid 154mg, yield is 82%, mp:257-259 ℃。

¹H NMR(DMSO-d₆)δ(ppm):13.13 (brs, 1H), 9.29 (s, 1H), 7.98 (d, J=9.2Hz, 1H), (s, the 3H) of 7.89 (s, 1H), 6.78 (d, J=9.2Hz, 1H), 6.66 (s, 2H), 3.86 (s, 3H), 3.78 (s, 6H), 3.68

C) .1- methyl -4- ((3,4,5- trimethoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

With 1- methyl -4- ((3,4,5- trimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxyl groups Benzsulfamide is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 57mg, yield is 73%, mp:268-272℃.

¹H NMR(DMSO-d₆)δ(ppm):12.64(brs,1H),9.36(s,1H),7.99-7.96(m,3H),7.88(s, 1H), 7.19 (d, J=8.8Hz, 2H), 7.80 (d, J=8.8Hz, 1H), 6.63 (s, 2H), 3.87 (s, 3H), 3.78 (s, 6H), 3.68(s,3H),3.62(s,3H).

Embodiment 103:1- methyl -4- ((3,4,5- trimethoxyphenyls) amino) -7- nitros-N- (benzenesulfonyl) -1H- Indole 2-carboxamides

With 1- methyl -4- ((3,4,5- trimethoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide For initiation material, c) methods described in preparation process be the same as Example 3 obtains yellow powdery solid 60mg, yield is 89%, mp: 258-259℃。

¹H NMR(DMSO-d₆)δ(ppm):12.80 (brs, 1H), 9.36 (s, 1H), 8.03 (d, J=7.6Hz, 2H), 7.98 (d, J=8.8Hz, 1H), 7.90 (s, 1H), 7.75 (d, J=7.2Hz, 1H), 7.68 (t, J=7.6Hz, 2H), 6.80 (d, J=8.8Hz, 1H), 6.64 (s, 2H), 3.78 (s, 6H), 3.68 (s, 3H), 3.62 (s, 3H)

Embodiment 104:1- methyl -4- ((3- aminomethyl phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) .1- methyl -4- ((3- aminomethyl phenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 3- methylanilines as initiation material, prepared A) methods described in journey be the same as Example 3, obtains orange solids 150mg, yield is 80%, mp:185-187℃.

¹H NMR(CDCl₃)δ(ppm):7.99 (d, J=8.8Hz, 2H), 7.43 (s, 1H), 7.30 (t, J=8.4Hz, 1H), 7.09 (d, J=7.2Hz, 2H), 7.02 (d, J=7.6Hz, 1H), 6.74 (d, J=8.8Hz, 1H), 6.52 (s, 1H), (t, J=7.2Hz, the 3H) of 4.40 (q, J=7.2Hz, 2H), 4.02 (s, 3H), 2.38 (s, 3H), 1.42

B) .1- methyl -4- ((3- aminomethyl phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 1- methyl -4- ((3- aminomethyl phenyls) amino) -7- nitro -1H- indole -2-ethyl formates as initiation material, system B) methods described in standby process be the same as Example 3, obtains orange powder shape solid 100mg, yield is 99%, mp:245-247℃.

¹H NMR(DMSO-d₆)δ(ppm):13.14 (s, 1H), 9.30 (s, 1H), 7.98 (d, J=8.8Hz, 1H), 7.90 (s, 1H), 7.31 (t, J=7.6Hz, 1H), 7.17-7.15 (m, 2H), 7.00 (d, J=7.6Hz, 1H), 6.71 (d, J= 8.8Hz,1H),3.86(s,3H),2.33(s,3H).

C) .1- methyl -4- ((3- aminomethyl phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 1- methyl -4- ((3- aminomethyl phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For c) methods described in initiation material preparation process be the same as Example 3, yellow powdery solid 69mg is obtained, yield is 91%, mp: 255-257℃。

¹H NMR(DMSO-d₆)δ(ppm):12.63(brs,1H),9.37(s,1H),7.99-7.95(m,3H),7.89(s, 1H), 7.32 (t, J=7.6Hz, 1H), 7.19-7.13 (m, 4H), 7.00 (d, J=7.6Hz, 1H), 6.73 (d, J=8.8Hz, 1H),3.87(s,3H),3.68(s,3H),2.34(s,3H)；HRMS(ESI):m/z,calcd.for C₂₄H₂₃N₄O₆S[M+H]⁺: 495.1338,found 495.1323.

Embodiment 105:1- methyl -4- ((3- acetylamino phenyls) amino) -7- nitros-N- (4- methoxybenzene sulphonyl Base) -1H- indole 2-carboxamides

A) .1- methyl -4- ((3- acetylamino phenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 3- acetylaminoanilines as initiation material, system A) methods described in standby process be the same as Example 3, obtains Orange red solid 155mg, yield is 74%, mp:257-260℃.

¹H NMR(DMSO-d₆)δ(ppm):10.02(s,1H),9.43(s,1H),8.01-7.98(m,1H),7.78(s, 1H), 7.35-7.26 (m, 2H), 7.02 (d, J=7.2Hz, 1H), 6.76 (d, J=8.8Hz, 1H), 4.36 (q, J=6.8Hz, 2H), (t, J=6.8Hz, the 3H) of 3.85 (s, 3H), 2.06 (s, 3H), 1.36

B) .1- methyl -4- ((3- acetylamino phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

It is former by starting of 1- methyl -4- ((3- acetylamino phenyls) amino) -7- nitro -1H- indole -2-ethyl formates Material, b) methods described in preparation process be the same as Example 3, obtains orange powder shape solid 100mg, yield is 100%, mp:210-212 ℃。

¹H NMR(DMSO-d₆)δ(ppm):10.05 (s, 1H), 9.37 (s, 1H), 7.96 (d, J=9.2Hz, 1H), 7.91 (s, 1H), 7.76 (s, 1H), 7.31-7.27 (m, 2H), 7.01 (d, J=7.2Hz, 1H), 6.74 (d, J=8.8Hz, 1H), 3.84(s,3H),2.04(s,3H).

C) .1- methyl -4- ((3- acetylamino phenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

With 1- methyl -4- ((3- acetylamino phenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphurs Acid amides is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 60mg, yield is 82%, mp:>260℃。

¹H NMR(DMSO-d₆)δ(ppm):12.62 (brs, 1H), 10.02 (s, 1H), 9.44 (s, 1H), 7.98 (d, J= 8.4Hz, 1H), 7.96 (d, J=8.0Hz, 2H), 7.91 (s, 1H), 7.78 (s, 1H), 7.33 (t, J=8.0Hz, 1H), 7.26 (d, J=8.0Hz, 1H), 7.19 (d, J=8.4Hz, 2H), 7.01 (d, J=7.6Hz, 1H), 6.77 (d, J=8.8Hz, 1H), 3.87(s,3H),3.62(s,3H),2.05(s,3H)；HRMS(ESI):m/z,calcd.for C₂₅H₂₄N₅O₇S[M+H]⁺: 538.1396,found 538.1384.

Embodiment 106:1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitros-N- (4- methoxybenzene sulphonyl Base) -1H- indole 2-carboxamides

A) .1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the N- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 3- methoxyl group -4- chloroanilines as initiation material, A) methods described in preparation process be the same as Example 3, obtains Orange red solid 173mg, yield is 81%, mp:232-234℃.

¹H NMR(CDCl₃)δ(ppm):7.98 (d, J=8.8Hz, 1H), 7.42 (s, 1H), 7.37 (d, J=8.0Hz, 1H), 6.85-6.82 (m, 2H), 6.75 (d, J=8.8Hz, 1H), 6.48 (s, 1H), 4.41 (q, J=7.2Hz, 2H), 4.02 (s, 3H), 3.90 (s, 3H), 1.42 (t, J=7.2Hz, 3H)

B) .1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

Using 1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates as starting B) methods described in raw material, preparation process be the same as Example 3, obtains orange red pulverulent solids 103mg, yield is 96%, mp:258- 260℃。

¹H NMR(DMSO-d₆)δ(ppm):9.42 (s, 1H), 7.99 (d, J=8.8Hz, 1H), 7.89 (s, 1H), 7.43 (d, J=8.4Hz, 1H), 7.11 (s, 1H), 6.96 (d, J=8.4Hz, 1H), 6.85 (d, J=8.8Hz, 1H), 3.86 (s, 6H).

C) .1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

With 1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxyl groups Benzsulfamide is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 56mg, yield is 70%, mp:248-250℃.

¹H NMR(DMSO-d₆)δ(ppm):12.66(brs,1H),9.45(s,1H),8.00-7.95(m,3H),7.87(s, 1H), 7.44 (d, J=8.4Hz, 1H), 7.18 (d, J=8.8Hz, 2H), 7.08 (s, 1H), 6.94 (d, J=8.4Hz, 1H), 6.88 (d, J=8.8Hz, 1H), 3.86 (s, 6H), 3.63 (s, 3H)；HRMS(ESI):m/z,calcd.for C₂₄H₂₂N₄O₇ClS [M+H]⁺:545.0898,found 545.0884.

Embodiment 107:1- methyl -4- ((3- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .1- methyl -4- ((3- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 3- chloroanilines as initiation material, preparation process A) methods described in be the same as Example 3, obtains Orange red solid 162mg, yield is 82%, mp:204-206℃.

¹H NMR(CDCl₃)δ(ppm):7.99 (t, J=8.8Hz, 1H), 7.42 (s, 1H), 7.33 (t, J=8.0Hz, 1H), 7.28 (s, 1H), 7.17-7.14 (m, 2H), 6.80 (d, J=8.8Hz, 1H), 6.49 (s, 1H), 4.41 (q, J= 7.2Hz, 2H), 4.02 (s, 3H), 1.42 (t, J=7.2Hz, 3H)

B) .1- methyl -4- ((3- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 1- methyl -4- ((3- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, prepared B) methods described in journey be the same as Example 3, obtains orange red pulverulent solids 101mg, yield is 99%, mp:237-239℃.

¹H NMR(DMSO-d₆)δ(ppm):13.21 (s, 1H), 9.42 (s, 1H), 8.00 (d, J=8.8Hz, 1H), 7.87 (s, 1H), 7.43 (t, J=8.0Hz, 1H), 7.39 (s, 1H), 7.34 (d, J=8.4Hz, 1H), 7.18 (d, J=8.0Hz, 1H), 6.84 (d, J=8.8Hz, 1H), 3.87 (s, 3H)

C) .1- methyl -4- ((3- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

Using 1- methyl -4- ((3- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as C) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 55mg, yield is 75%, mp: 270-272℃。

¹H NMR(DMSO-d₆)δ(ppm):9.46 (brs, 1H), 8.01 (d, J=8.8Hz, 1H), 7.96 (d, J= 8.8Hz, 2H), 7.86 (s, 1H), 7.44 (t, J=8.0Hz, 1H), 7.37 (s, 1H), 7.32 (d, J=8.4Hz, 2H), 7.18 (d, J=8.4Hz, 3H), 6.86 (d, J=8.8Hz, 1H), 3.87 (s, 3H), 3.77 (s, 3H)

Embodiment 108:1- methyl -4- ((4- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .1- methyl -4- ((4- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 4- chloroanilines as initiation material, preparation process A) methods described in be the same as Example 3, obtains yellow solid 170mg, yield is 86%, mp:246-247℃.

¹H NMR(CDCl₃)δ(ppm):7.97 (d, J=8.8Hz, 1H), 7.42 (s, 1H), 7.38 (d, J=8.4Hz, 2H), 7.22 (d, J=8.4Hz, 2H), 6.70 (d, J=8.8Hz, 1H), 6.46 (s, 1H), 4.40 (q, J=7.2Hz, 2H), 4.02 (s, 3H), 1.42 (t, J=7.2Hz, 3H)

B) .1- methyl -4- ((4- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 1- methyl -4- ((4- chlorphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, prepared B) methods described in journey be the same as Example 3, obtains orange red pulverulent solids 100mg, yield is 98%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):9.25 (s, 1H), 7.88 (d, J=8.8Hz, 1H), 7.59 (s, 1H), 7.43 (d, J=8.4Hz, 2H), 7.36 (d, J=8.8Hz, 2H), 6.74 (d, J=8.8Hz, 1H), 3.89 (s, 3H)

C) .1- methyl -4- ((4- chlorphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

Using 1- methyl -4- ((4- chlorphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as C) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 55mg, yield is 71%, mp:> 280℃。

¹H NMR(DMSO-d₆)δ(ppm):12.65(brs,1H),9.44(s,1H),7.99-7.95(m,3H),7.86(s, 1H), 7.47 (d, J=8.4Hz, 2H), 7.36 (d, J=8.4Hz, 2H), 7.18 (d, J=8.4Hz, 2H), 6.77 (d, J= 8.8Hz,1H),3.87(s,3H),3.63(s,3H).

Embodiment 109:1- methyl -4- ((3- ethoxyl phenenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) .1- methyl -4- ((3- ethoxyl phenenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 3- phenetidines as initiation material, prepare A) methods described in process be the same as Example 3, obtains yellow solid 177mg, yield is 87%, mp:178-180℃.

¹H NMR(CDCl₃)δ(ppm):7.99 (d, J=8.8Hz, 1H), 7.43 (s, 1H), 7.30 (t, J=8.4Hz, 1H), 6.84 (d, J=10.0Hz, 1H), 6.83 (s, 1H), 6.80 (d, J=8.8Hz, 1H), 6.73 (d, J=8.4Hz, 1H), 6.51 (s, 1H), 4.40 (q, J=7.2Hz, 2H), 4.04 (q, J=8.0Hz, 2H), 4.02 (s, 3H), 1.45-1.41 (m, 6H).

B) .1- methyl -4- ((3- ethoxyl phenenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 1- methyl -4- ((3- ethoxyl phenenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, system B) methods described in standby process be the same as Example 3, obtains orange red pulverulent solids 110mg, yield is 99%, mp:238-241℃.

¹H NMR(DMSO-d₆)δ(ppm):13.16 (s, 1H), 9.29 (s, 1H), 7.99 (d, J=8.8Hz, 1H), 7.89 (s, 1H), 7.31 (t, J=8.0Hz, 1H), 6.93 (d, J=8.0Hz, 1H), 6.88 (s, 1H), 6.78 (d, J=8.8Hz, 1H), (t, J=6.8Hz, the 3H) of 6.73 (d, J=7.6Hz, 1H), 4.04 (q, J=6.8Hz, 2H), 3.86 (s, 3H), 1.34

C) .1- methyl -4- ((3- ethoxyl phenenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

With 1- methyl -4- ((3- ethoxyl phenenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 67mg, yield is 85%, mp:243-245℃。

¹H NMR(DMSO-d₆)δ(ppm):12.63 (brs, 1H), 9.37 (s, 1H), 7.99 (d, J=8.8Hz, 1H), 7.96 (d, J=8.8Hz, 2H), 7.88 (s, 1H), 7.32 (t, J=8.0Hz, 1H), 7.18 (d, J=8.8Hz, 2H), 6.91 (d, J=7.6Hz, 1H), 6.86 (s, 1H), 6.80 (d, J=8.8Hz, 1H), 6.73 (d, J=8.4Hz, 1H), 4.04 (q, J= 7.2Hz, 1H), 3.87 (s, 3H), 3.62 (s, 3H), 1.34 (t, J=7.2Hz, 3H)

The preparation 6 of intermediate：The chloro- 1H- indole -2-ethyl formates of 1- ethyl -7- nitros -4-

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and bromoethane as initiation material, preparation process is with intermediate 5 are prepared, faint yellow solid 140mg is obtained, yield is 99%, mp:108-109℃.

¹H NMR(CDCl₃)δ(ppm):7.74 (d, J=8.0Hz, 1H), 7.55 (s, 1H), 7.20 (d, J=8.0Hz, 1H), 4.67 (q, J=7.2Hz, 2H), 4.42 (q, J=7.2Hz, 2H), 1.44 (t, J=7.2Hz, 3H), 1.30 (t, J= 7.2Hz,3H).

Embodiment 110:1- ethyls -4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) .1- ethyls -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of ethyl -7- nitros -4- and 3- aminoanisoles as initiation material, prepare A) methods described in process be the same as Example 3, obtains yellow solid 171mg, yield is 78%, mp:165-167℃.

¹H NMR(CDCl₃)δ(ppm):7.96 (d, J=8.8Hz, 1H), 7.48 (s, 1H), 7.31 (t, J=8.0Hz, 1H), 6.87 (d, J=8.0Hz, 1H), 6.83 (s, 1H), 6.81 (d, J=9.2Hz, 1H), 6.74 (d, J=8.4Hz, 1H), 6.50 (s, 1H), 4.79 (q, J=7.2Hz, 2H), 4.40 (q, J=7.2Hz, 2H), 3.83 (s, 3H), 1.43 (t, J= 7.2Hz, 3H), 1.27 (t, J=7.2Hz, 3H)

B) .1- ethyls -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 1- ethyls -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, system B) methods described in standby process be the same as Example 3, obtains yellow powdery solid 105mg, yield is 98%, mp:221-224℃.

¹H NMR(DMSO-d₆)δ(ppm):13.07 (brs, 1H), 9.32 (s, 1H), 7.98 (d, J=6.8Hz, 2H), 7.33 (t, J=8.0Hz, 1H), 6.95 (d, J=8.0Hz, 1H), 6.91 (s, 1H), 6.80 (d, J=8.8Hz, 1H), 6.74 (d, J=8.0Hz, 1H), 4.69 (q, J=6.8Hz, 1H), 3.77 (s, 3H), 1.10 (d, J=6.8Hz, 3H)

C) .1- ethyls -4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

With 1- ethyls -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 45mg, yield is 51%, mp:241-242℃。

¹H NMR(DMSO-d₆)δ(ppm):12.70(brs,1H),9.40(s,1H),8.00-7.94(m,4H),7.34(t, J=8.0Hz, 1H), 7.19 (d, J=8.4Hz, 2H), 6.95 (d, J=8.0Hz, 1H), 6.90 (s, 1H), 6.82 (d, J= 8.8Hz, 1H), 6.76 (d, J=8.0Hz, 1H), 4.39-4.38 (m, 2H), 3.87 (s, 3H), 3.78 (s, 3H), 0.91 (t, J =6.8Hz, 3H)

The preparation 7 of intermediate：The chloro- 1H- indole -2-ethyl formates of 1- isobutyl group -7- nitros -4-

Using the chloro- 7- nitros -1H- indole -2-ethyl formates of 4- and isobutane bromide as initiation material, preparation process is with middle The preparation 5 of body, obtains faint yellow solid 206mg, and yield is 85%, mp:80-81℃.

¹H NMR(CDCl₃)δ(ppm):7.78 (d, J=8.4Hz, 1H), 7.55 (s, 1H), 7.21 (d, J=8.0Hz, 1H), 4.60 (s, 2H), 4.41 (q, J=7.2Hz, 2H), 1.69-1.62 (m, 1H), 1.44 (t, J=7.2Hz, 3H), 0.66 (d, J=6.4Hz, 6H)

Embodiment 111:1- isobutyl groups -4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- methoxybenzene sulphonyl Base) -1H- indole 2-carboxamides

A) .1- isobutyl groups -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of isobutyl group -7- nitros -4- and 3- aminoanisoles as initiation material, system A) methods described in standby process be the same as Example 3, obtains orange/yellow solid 207mg, yield is 76%, mp:155-156℃.

¹H NMR(CDCl₃)δ(ppm):7.95 (t, J=8.8Hz, 1H), 7.47 (s, 1H), 7.31 (d, J=8.4Hz, 1H), 6.88 (d, J=8.0Hz, 1H), 6.84 (s, 1H), 6.82 (d, J=9.2Hz, 1H), 6.74 (d, J=8.4Hz, 1H), 6.52 (brs, 1H), 4.71 (s, 2H), 4.40 (q, J=7.2Hz, 2H), 3.83 (s, 3H), 1.70-1.62 (m, 1H), 1.42 (t, J=7.2Hz, 3H), 0.64 (d, J=6.4Hz, 6H)

B) .1- isobutyl groups -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids

With 1- isobutyl groups -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole -2-ethyl formate initiation materials, B) methods described in preparation process be the same as Example 3, obtains yellow powdery solid 115mg, yield is 98%, mp:219-222℃.

¹H NMR(DMSO-d₆)δ(ppm):13.19 (s, 1H), 9.35 (s, 1H), 7.97 (d, J=6.4Hz, 2H), 7.33 (t, J=8.0Hz, 1H), 6.97 (d, J=8.0Hz, 1H), 6.93 (s, 1H), 6.81 (d, J=9.2Hz, 1H), 6.75 (d, J= 8.0Hz, 1H), 4.61 (s, 2H), 3.78 (s, 3H), 1.55-1.49 (m, 1H), 0.55 (d, J=6.4Hz, 6H)

C) .1- isobutyl groups -4- ((3- methoxyphenyls) amino) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

With 1- isobutyl groups -4- ((3- methoxyphenyls) amino) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzene sulphurs Acid amides is c) methods described in initiation material, preparation process be the same as Example 3, obtains yellow powdery solid 14mg, yield is 16%, mp:195-196℃。

¹H NMR(DMSO-d₆)δ(ppm):12.68(brs,1H),9.38(s,1H),7.98-7.93(m,3H),7.88(s, 1H), 7.34 (t, J=8.0Hz, 1H), 7.18 (t, J=8.8Hz, 2H), 6.95 (d, J=8.0Hz, 1H), 6.90 (s, 1H), 6.82 (d, J=8.8Hz, 1H), 6.76 (d, J=8.4Hz, 1H), 4.20 (d, J=6.4Hz, 2H), 3.86 (s, 3H), 3.78 (s, 3H), 1.24-1.29 (m, 1H), 0.36 (d, J=6.4Hz, 6H)

Embodiment 112:4- ((3- ethoxyl phenenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

A) .4- ((3- methoxyphenyls) amino) -1H- indole -2-ethyl formates

Using the bromo- 1H- indole -2-ethyl formates of 4- and 3- aminoanisoles as initiation material, preparation process be the same as Example 75 Middle a) methods described, obtains white solid 120mg, and yield is 86%, mp:130-131℃.

¹H NMR(CDCl₃)δ(ppm):8.88 (brs, 1H), 7.25-7.17 (m, 3H), 7.03 (d, J=8.7Hz, 1H), 7.00 (d, J=8.1Hz, 1H), 6.75-6.73 (m, 2H), 6.55-6.52 (m, 1H), 4.40 (q, J=7.2Hz, 2H), 3.79 (s, 3H), 1.41 (t, J=7.5Hz, 3H)

B) .4- ((3- methoxyphenyls) amino) -1H- indole-2-carboxylic acids

With 4- ((3- methoxyphenyls) amino) -1H- indole -2-ethyl formate initiation materials, preparation process be the same as Example 3 Middle b) methods described, obtains verdigris color pulverulent solids 90mg, and yield is 90%, mp:169-170℃.

¹H NMR(acetone-d₆)δ(ppm):11.10(brs,1H),10.79(s,1H),7.57(s,1H),7.39(s, 1H), 7.20-7.15 (m, 2H), 7.09 (d, J=8.4Hz, 1H), 6.98 (d, J=7.6Hz, 1H), 6.84 (d, J=7.6Hz, 2H), 6.48 (d, J=8.8Hz, 1H), 3.76 (s, 3H)

C) .4- ((3- ethoxyl phenenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as initiation material, C) methods described in preparation process be the same as Example 3, obtains brown powder solid 36mg, yield is 56%, mp:159-160℃.

¹H NMR(DMSO-d₆)δ(ppm):12.35 (brs, 1H), 11.64 (s, 1H), 8.22 (s, 1H), 7.94 (d, J= 8.8Hz, 2H), 7.54 (s, 1H), 7.15 (d, J=8.4Hz, 2H), 7.13-7.10 (m, 2H), 6.95 (d, J=8.4Hz, 1H), 6.83 (d, J=7.6Hz, 1H), 6.69 (d, J=8.4Hz, 1H), 6.65 (s, 1H), 6.41 (d, J=8.0Hz, 1H), 3.85 (s,3H),3.70(s,3H)；¹³C NMR(125MHz,DMSO-d₆):δ163.10,160.10,159.23,145.19,138.93, 137.21,131.12,130.06,129.75,126.79,126.09,119.87,114.21,109.42,106.79,106.64, 105.20,105.04,102.49,55.79,54.79.HRMS(ESI):m/z,calcd.for C₂₃H₂₂N₃O₅S[M+H]⁺: 452.1280,found 452.1264.

Embodiment 113:4- ((the fluoro- 3- chlorphenyls of 4-) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

A) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole -2-ethyl formates

Using the bromo- 1H- indole -2-ethyl formates of 4- and the fluoro- 3- chloroanilines of 4- as initiation material, preparation process be the same as Example 75 Middle a) methods described, obtains white solid 155mg, and yield is 73%, mp:168-170℃.

¹H NMR(acetone-d₆)δ(ppm):10.93(brs,1H),7.68(s,1H),7.32-7.29(m,2H), (s, the 3H) of 7.23-7.19 (m, 3H), 7.15 (d, J=8.4Hz, 1H), 6.92 (d, J=7.6Hz, 1H), 3.87

B) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole-2-carboxylic acids

With 4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole -2-ethyl formate initiation materials, preparation process be the same as Example B) methods described in 3, obtains verdigris color pulverulent solids 90mg, yield is 94%, mp:182-183℃.

¹H NMR(acetone-d₆)δ(ppm):10.87 (brs, 1H), 7.34 (s, 1H), 7.31 (d, J=5.6Hz, 1H), 7.24-7.14 (m, 4H), 6.92 (d, J=7.2Hz, 1H)

C) .4- ((the fluoro- 3- chlorphenyls of 4-) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as initiation material, C) methods described in preparation process be the same as Example 3, obtains brown powder solid 44mg, yield is 63%, mp:245-247℃.

¹H NMR(DMSO-d₆)δ(ppm):12.35 (brs, 1H), 11.71 (d, J=0.6Hz, 1H), 8.38 (s, 1H), 7.94 (d, J=8.7Hz, 1H), 7.47 (s, 1H), 7.27 (t, J=9.0Hz, 1H), 7.20-7.12 (m, 4H), 7.00 (d, J= 8.4Hz, 2H), 6.79 (d, J=7.5Hz, 1H), 3.84 (s, 3H)

Embodiment 114:4- ((3,4,5- trimethoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((3,4,5- trimethoxyphenyls) amino) -1H- indole -2-ethyl formates

With the bromo- 1H- indole -2-ethyl formates of 4- and 3,4,5- trimethoxy-anilines are initiation material, and preparation process is with real A) methods described is applied in example 75, white solid 210mg is obtained, yield is 83%, mp:219-220℃.

¹H NMR(acetone-d₆)δ(ppm):10.85 (brs, 1H), 7.42 (s, 1H), 7.17 (t, J=8.0Hz, 1H), 7.04 (d, J=8.0Hz, 1H), 6.85 (d, J=7.6Hz, 1H), 6.69 (s, 1H), 6.60 (s, 2H), 3.87 (s, 3H), 3.78 (s,6H),3.70(s,3H).

B) .4- ((3,4,5- trimethoxyphenyls) amino) -1H- indole-2-carboxylic acids

With 4- ((3,4,5- trimethoxyphenyl) amino) -1H- indole -2-ethyl formates for initiation material, preparation process B) methods described in be the same as Example 3, obtains verdigris color pulverulent solids 93mg, yield is 81%, mp:223-225℃.

¹H NMR(acetone-d₆)δ(ppm):10.98(brs,1H),10.77(s,1H),7.46(s,1H),7.42(s, 1H), 7.16 (t, J=8.0Hz, 1H), 7.05 (d, J=8.4Hz, 1H), 6.95 (d, J=7.6Hz, 1H), 6.59 (s, 2H), 3.78(s,6H),3.70(s,3H).

C) .4- ((3,4,5- trimethoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3,4,5- trimethoxyphenyls) amino) -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains brown powder solid 56mg, yield is 84%, mp:129-130 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.36 (brs, 1H), 11.61 (s, 1H), 8.12 (s, 1H), 7.94 (d, J= 8.7Hz, 2H), 7.56 (s, 1H), 7.15 (d, J=9.0Hz, 2H), 7.10 (t, J=7.8Hz, 1H), 6.90 (d, J=8.4Hz, 1H), (s, the 3H) of 6.81 (d, J=7.2Hz, 1H), 6.43 (s, 2H), 3.85 (s, 3H), 3.70 (s, 6H), 3.62

The preparation 8 of intermediate：The bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 6-

A) .2- azidos -3- (the chloro- 2- bromophenyls of 4-) ethyl acrylate

Caustic alcohol (272mg, 4.00mmol) is dissolved in absolute ethyl alcohol (2mL), -5 DEG C are cooled to.By the chloro- 2- bromobenzenes of 4- Formaldehyde (220mg, 0.56mmol) and ethyl azidoacetate (527mg, 4.00mmol) are dissolved in absolute ethyl alcohol (4mL), are added dropwise Enter into above solution, 0 DEG C of reaction 12h, raw material disappears.Reaction solution is poured into NH₄In the Cl aqueous solution (20mL), separate out solid Body, is filtered, and is dried, is obtained white fluffy solid 50mg, yield is 27%.

¹H NMR(CDCl₃)δ(ppm):8.10 (d, J=8.4Hz, 1H), 7.62 (s, 1H), 7.32 (d, J=8.0Hz, 1H), (t, J=7.2Hz, the 3H) of 7.18 (s, 1H), 4.40 (q, J=7.2Hz, 2H), 1.41

B) the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of .6-

2- azidos -3- (the chloro- 2- bromophenyls of 4-) ethyl acrylate (100mg, 0.30mmol) is dissolved in Xylene (6mL) In, flow back 6h, and raw material is remaining on a small quantity.Column chromatography (P/E=20:1) white solid 75mg, is obtained, yield is 82%, mp:190-192 ℃。

¹H NMR(CDCl₃)δ(ppm):8.98(brs,1H),7.38(s,1H),7.35(s,1H),7.23(s,1H),4.43 (q, J=7.2Hz, 2H), 1.43 (t, J=7.2Hz, 3H)

Embodiment 115:4- ((3- methoxyphenyls) amino) the chloro- N- of -6- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

A) .4- ((3- methoxyphenyls) amino) the chloro- 1H- indole -2-ethyl formates of -6-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 6- and 3- aminoanisoles as initiation material, preparation process is with implementation A) methods described in example 75, obtains white solid 190mg, yield is 67%, mp:120-121℃.

¹H NMR(acetone-d₆)δ(ppm):10.97(brs,1H),7.80(s,1H),7.41(s,1H),7.25(t,J =8.0Hz, 1H), 7.05 (s, 1H), 6.92-6.87 (m, 3H), 6.60 (d, J=8.4Hz, 1H), 4.35 (q, J=7.2Hz, 2H), 3.79 (s, 3H), 1.35 (t, J=7.2Hz, 3H)

B) .4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -6-

With 4- ((3- methoxyphenyls) amino) the chloro- 1H- indole -2-ethyl formates initiation materials of -6-, preparation process is with real B) methods described is applied in example 3, white powdery solids 144mg is obtained, yield is 98%, mp:179-180℃.

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.78(s,1H),8.45(s,1H),7.37(s,1H), 7.22 (d, J=8.0Hz, 1H), 6.89 (s, 1H), 6.83 (d, J=8.0Hz, 1H), 6.77 (s, 1H), 6.72 (s, 1H), 6.55 (d, J=8.0Hz, 1H), 3.74 (s, 3H)

C) .4- ((3- methoxyphenyls) amino) the chloro- N- of -6- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -6- and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains brown powder solid 48mg, yield is 56%, mp:253-255 ℃。

¹H NMR(acetone-d₆)δ(ppm):10.94 (brs, 1H), 10.88 (s, 1H), 8.03 (d, J=9.0Hz, 2H), 7.70 (s, 1H), 7.49 (s, 1H), 7.22 (t, J=7.8Hz, 1H), 7.12 (d, J=9.0Hz, 2H), 7.06 (s, 1H), 6.86(s,1H),6.80-6.76(m,2H),6.58(s,J₁=1.8Hz, J₂=8.4Hz, 1H), 3.91 (s, 3H), 3.77 (s, 3H)；¹³C NMR(125MHz,DMSO-d₆):δ163.12,160.12,159.06,143.75,138.98,138.72,131.06, 130.53,130.07,130.00,127.43,117.62,114.22,110.89,106.84,106.55,105.05,104.25, 103.70,55.80,54.91.HRMS(ESI):m/z,calcd.for C₂₃H₂₁N₃O₅ClS[M+H]⁺:486.0890,found 486.0877.

Embodiment 116:4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- N- of -6- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole -2-ethyl formates of -6-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 6- and the fluoro- 3- chloroanilines of 4- as initiation material, preparation process is with real A) methods described is applied in example 75, white solid 294mg is obtained, yield is 81%, mp:212-213℃.

¹H NMR(CDCl₃)δ(ppm):8.87 (brs, 1H), 7.21 (d, J=5.2Hz, 1H), 7.13-7.09 (m, 2H), 7.05-7.01 (m, 2H), 6.75 (s, 1H), 5.89 (s, 1H), 4.41 (q, J=7.2Hz, 2H), 1.41 (t, J=7.2Hz, 3H).

B) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole-2-carboxylic acids of -6-

Using 4- ((the fluoro- 3- chlorphenyls of 4-) amino), the chloro- 1H- indole -2-ethyl formates of -6- is initiation materials, preparation process B) methods described in be the same as Example 3, obtains white powdery solids 130mg, yield is 94%, mp:205-207℃.

¹H NMR(DMSO-d₆)δ(ppm):11.85(s,1H),8.60(brs,1H),7.41-7.32(m,4H),7.24- 7.21(m,1H),6.94(s,1H),6.65(s,1H).

C) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- N- of -6- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole-2-carboxylic acids of -6- and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains ginger-colored pulverulent solids 32mg, yield is 38%, mp:276- 278℃。

¹H NMR(acetone-d₆)δ(ppm):10.99 (s, 1H), 10.85 (brs, 1H), 8.02 (d, J=8.8Hz, 2H),7.83(s,1H),7.43(s,1H),7.28-7.23(m,2H),7.17-7.11(m,4H),6.79(s,1H),3.91(s, 3H).

Embodiment 117:4- ((3,4,5- trimethoxyphenyls) amino) the chloro- N- of -6- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) .4- ((3,4,5- trimethoxyphenyls) amino) the chloro- 1H- indole -2-ethyl formates of -6-

With the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 6- and 3,4,5- trimethoxy-anilines are initiation material, preparation process A) methods described in be the same as Example 75, obtains white solid 247mg, yield is 81%, mp:206-207℃.

¹H NMR(CDCl₃)δ(ppm):8.90(brs,1H),7.18(s,1H),6.96(s,1H),6.82(s,1H),6.45 (s, 2H), 5.90 (brs, 1H), 4.41 (q, J=7.2Hz, 2H), 3.86 (s, 3H), 3.83 (s, 6H), 1.41 (t, J= 7.2Hz,3H).

B) .4- ((3,4,5- trimethoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -6-

With 4- ((3,4,5- trimethoxyphenyl) amino) chloro- 1H- indole -2-ethyl formates of -6- for initiation material, prepare B) methods described in process be the same as Example 3, obtains white powdery solids 110mg, yield is 94%, mp:145-147℃.

¹H NMR(DMSO-d₆)δ(ppm):12.91(brs,1H),11.76(s,1H),8.37(s,1H),7.38(s,1H), 6.85(s,1H),6.68(s,1H),6.55(s,2H),3.75(s,6H),3.64(s,3H).

C) .4- ((3,4,5- trimethoxyphenyls) amino) the chloro- N- of -6- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 4- ((3,4,5- trimethoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -6- and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains ginger-colored pulverulent solids 35mg, yield is 44%, mp:155-157℃。

¹H NMR(acetone-d₆)δ(ppm):10.89 (brs, 1H), 8.02 (d, J=8.8Hz, 2H), 7.60 (s, 1H), 7.49 (s, 1H), 7.11 (d, J=8.0Hz, 1H), 7.02 (s, 1H), 6.79 (s, 1H), 6.51 (s, 2H), 3.90 (s, 3H), 3.77(s,6H),3.71(s,3H).

The preparation 9 of intermediate:The bromo- 1H- indole -2-ethyl formates of the fluoro- 4- of 6-

A) .2- azidos -3- (the fluoro- 2- bromophenyls of 4-) ethyl acrylate

Using the fluoro- 2- bromobenzaldehydes of 4- as initiation material, preparation process obtains white solid with a) described in the preparation 8 of intermediate Body 743mg, yield is 16%.

¹H NMR(CDCl₃)δ(ppm):8.17(dd,J₁=8.8Hz, J₂=6.4Hz, 1H), 8.17 (dd, J₁=8.4Hz, J₂=2.4Hz, 1H), 7.20 (s, 1H), 7.07 (dt, J₁=8.8Hz, J₂=2.0Hz, 1H), 4.40 (q, J=7.2Hz, 2H), 1.41 (t, J=7.2Hz, 3H)

B) the bromo- 1H- indole -2-ethyl formates of the fluoro- 4- of .6-

Using 2- azidos -3- (the fluoro- 2- bromophenyls of 4-), ethyl acrylate is initiation material, system of the preparation process with intermediate It is b) described in standby 8, white solid 636mg is obtained, yield is 79%, mp:172-173℃.

¹H NMR(CDCl₃)δ(ppm):9.23 (s, 1H), 7.24 (s, 1H), 7.16 (d, J=8.8Hz, 1H), 7.07 (d, J =8.8Hz, 1H), 4.43 (q, J=7.2Hz, 2H), 1.43 (t, J=7.2Hz, 3H)

Embodiment 118:4- ((3- methoxyphenyls) amino) the fluoro- N- of -6- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

A) .4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole -2-ethyl formates of -6-

Using the bromo- 1H- indole -2-ethyl formates of the fluoro- 4- of 6- and 3- aminoanisoles as initiation material, preparation process is with implementation A) methods described in example 75, obtains white solid 228mg, yield is 79%, mp:121-122℃.

¹H NMR(CDCl₃)δ(ppm):8.93(brs,1H),7.24-7.21(m,2H),6.80-6.72(m,3H),6.64 (d, J=9.2Hz, 1H), 6.61 (d, J=8.8Hz, 1H), 6.10 (brs, 1H), 4.40 (q, J=7.2Hz, 2H), 3.81 (s, 3H), 1.41 (t, J=7.2Hz, 3H)

B) .4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole-2-carboxylic acids of -6-

With 4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole -2-ethyl formates initiation materials of -6-, preparation process is with real B) methods described is applied in example 3, white powdery solids 146mg is obtained, yield is 99%, mp:228-230℃.

¹H NMR(DMSO-d₆)δ(ppm):12.79(brs,1H),11.72(s,1H),8.47(s,1H),7.40(s,1H), 7.22 (t, J=8.0Hz, 1H), 6.86 (d, J=8.0Hz, 1H), 6.79 (s, 1H), 6.59 (s, 1H), 6.56-6.53 (m, 2H),3.74(s,3H).

C) .4- ((3- methoxyphenyls) amino) the fluoro- N- of -6- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole-2-carboxylic acids of -6- and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains brown powder solid 44mg, yield is 47%, mp:235-237 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.35 (s, 1H), 11.70 (s, 1H), 8.49 (s, 1H), 7.94 (d, J= 8.4Hz, 2H), 7.57 (s, 1H), 7.20 (t, J=8.0Hz, 1H), 7.15 (d, J=8.4Hz, 2H), 6.79 (d, J=8.0Hz, 1H), 6.74 (s, 1H), 6.60 (s, 1H), 6.57 (d, J=4.4Hz, 1H), 6.53 (d, J=8.0Hz, 1H), 3.85 (s, 3H), 3.73(s,3H)；¹³C NMR(125MHz,DMSO-d₆):δ163.08,161.84(J_CF=235.6Hz), 160.13,158.99, 143.69,139.17(J_CF=13.6Hz), 138.38 (J_CF=15.8Hz), 131.17,130.04,129.98,127.14, 115.59,114.20,110.87,107.07,106.61,104.21,93.73(J_CF=29.1Hz), 89.54 (J_CF= 26.3Hz),55.79,54.92.HRMS(ESI):m/z,calcd.for C₂₃H₂₁N₃O₅FS[M+H]⁺:470.1186,found 470.1170.

Embodiment 119:4- ((the fluoro- 3- chlorphenyls of 4-) amino) the fluoro- N- of -6- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the fluoro- 1H- indole -2-ethyl formates of -6-

Using the bromo- 1H- indole -2-ethyl formates of the fluoro- 4- of 6- and 3- aminoanisoles as initiation material, preparation process is with implementation A) methods described in example 75, obtains white solid 250mg, yield is 82%, mp:183-185℃.

¹H NMR(CDCl₃)δ(ppm):8.94 (s, 1H), 7.24 (s, 1H), 7.17 (s, 1H), 7.12 (t, J=8.8Hz, 1H), 7.06-7.04 (m, 1H), 6.67 (d, J=9.2Hz, 1H), 6.53 (d, J=11.6Hz, 1H), 5.94 (brs, 1H), 4.40 (q, J=7.2Hz, 2H), 1.41 (t, J=7.2Hz, 3H)

B) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the fluoro- 1H- indole-2-carboxylic acids of -6-

Using 4- ((the fluoro- 3- chlorphenyls of 4-) amino), the fluoro- 1H- indole -2-ethyl formates of -6- is initiation materials, preparation process B) methods described in be the same as Example 3, obtains white powdery solids 146mg, yield is 93%, mp:226-229℃.

¹H NMR(DMSO-d₆)δ(ppm):12.83(s,1H),11.78(s,1H),8.59(s,1H),7.37-7.33(m, 3H), 7.25-7.23 (m, 1H), 6.63 (d, J=9.2Hz, 1H), 6.53 (d, J=12.4Hz, 1H)

C) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the fluoro- N- of -6- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((the fluoro- 3- chlorphenyls of 4-) amino) the fluoro- 1H- indole-2-carboxylic acids of -6- and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains brown powder solid 42mg, yield is 46%, mp:256-258 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.35 (s, 1H), 11.76 (s, 1H), 8.62 (s, 1H), 7.94 (d, J= 8.4Hz, 2H), 7.50 (s, 1H), 7.34 (t, J=8.8Hz, 1H), 7.27 (dd, J₁=6.0Hz, J₂=1.6Hz, 1H), 7.15 (d, J=8.8Hz, 3H), 6.64 (d, J=9.2Hz, 1H), 6.54 (d, J=8.0Hz, 1H), 3.85 (s, 1H)

The preparation 10 of intermediate：The chloro- 1H- indole -2-ethyl formates of 4- trifluoromethyls -6-

A) .2- azidos -3- (2- trifluoromethyl-4-chlorophenyls) ethyl acrylate

Using 2- trifluoromethyl -4- chlorobenzaldehydes as initiation material, preparation process is obtained with a) described in the preparation 8 of intermediate White solid 912mg, yield is 30%.

¹H NMR(CDCl₃)δ(ppm):8.10 (d, J=8.4Hz, 1H), 7.67 (s, 1H), 7.54 (d, J=8.4Hz, 1H), (t, J=7.2Hz, the 3H) of 7.14 (s, 1H), 4.39 (q, J=7.2Hz, 2H), 1.40

B) the chloro- 1H- indole -2-ethyl formates of .4- trifluoromethyls -6-

Using 2- azidos -3- (2- trifluoromethyl-4-chlorophenyls) ethyl acrylate as initiation material, preparation process is with middle It is b) described in the preparation 8 of body, white solid 147mg is obtained, yield is 43%, mp:190-191℃.

¹H NMR(CDCl₃)δ(ppm):9.27(brs,1H),7.61(s,1H),7.46(s,1H),7.35(s,1H),4.45 (q, J=7.2Hz, 2H), 1.45 (t, J=7.2Hz, 3H)

Embodiment 120:The chloro- N- of 4- trifluoromethyls -6- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) the chloro- 1H- indole-2-carboxylic acids of .4- trifluoromethyls -6-

Using the chloro- 1H- indole -2-ethyl formates of 4- trifluoromethyls -6- as initiation material, in preparation process be the same as Example 3 b) Methods described, obtains white powdery solids 103mg, and yield is 103%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):12.19(s,1H),7.71(s,1H),7.43(s,1H),6.93(s,1H).

B) the chloro- N- of .4- trifluoromethyls -6- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using the chloro- 1H- indole-2-carboxylic acids of 4- trifluoromethyls -6- and 4- methoxybenzenesulphoismides as initiation material, preparation process C) methods described in be the same as Example 3, obtains white powdery solids 42mg, yield is 51%, mp:235-237℃.

¹H NMR(DMSO-d₆)δ(ppm):12.59 (brs, 1H), 12.43 (s, 1H), 7.96 (d, J=8.8Hz, 2H), (s, the 3H) of 7.76-7.72 (m, 1H), 7.70 (s, 1H), 7.52 (s, 1H), 7.08 (d, J=8.4Hz, 2H), 3.85

The preparation 11 of intermediate：4,6- bis- (trifluoromethyl) -1H- indole -2-ethyl formates

A) .2- azidos -3- (2,4- bis- (trifluoromethyl) phenyl) ethyl acrylate

With 2,4- difluoromethyls benzaldehyde for initiation material, preparation process obtains white with a) described in the preparation 8 of intermediate Solid 268mg, yield is 18%.

¹H NMR(CDCl₃)δ(ppm):8.24 (d, J=8.4Hz, 1H), 7.93 (s, 1H), 7.82 (d, J=8.4Hz, 1H), (t, J=7.2Hz, the 3H) of 7.17 (s, 1H), 4.41 (q, J=7.2Hz, 2H), 1.42

B) .4,6- bis- (trifluoromethyl) -1H- indole -2-ethyl formates

With 2- azidos -3- (2,4- bis- (trifluoromethyl) phenyl) ethyl acrylate for initiation material, preparation process is with It is b) described in the preparation 8 of mesosome, white solid 144mg is obtained, yield is 42%, mp:190-191℃.

¹H NMR(CDCl₃)δ(ppm):9.48(brs,1H),7.93(s,1H),7.70(s,1H),7.43(s,1H),4.48 (q, J=7.2Hz, 2H), 1.46 (t, J=7.2Hz, 3H)

Embodiment 121:4,6- bis- (trifluoromethyl)-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) .4,6- bis- (trifluoromethyl) -1H- indole-2-carboxylic acids

With 4,6- bis- (trifluoromethyl) -1H- indole -2-ethyl formate initiation materials, b) institute in preparation process be the same as Example 3 Method is stated, white powdery solids 89mg is obtained, yield is 89%, mp:214-216℃.

¹H NMR(DMSO-d₆)δ(ppm):13.75(brs,1H),12.88(s,1H),8.05(s,1H),7.73(s,1H), 7.19(s,1H).

B) .4,6- bis- (trifluoromethyl)-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

With (the trifluoromethyl) -1H- indole-2-carboxylic acids of 4,6- bis- and 4- methoxybenzenesulphoismides for initiation material, prepared C) methods described in journey be the same as Example 3, obtains white powdery solids 39mg, yield is 42%, mp:262-264℃.

¹H NMR(DMSO-d₆)δ(ppm):12.78 (s, 1H), 8.01 (s, 1H), 7.98 (d, J=8.8Hz, 2H), 7.81 (brs, 1H), 7.72 (s, 1H), 7.16 (d, J=8.8Hz, 2H), 3.85 (s, 3H)

The preparation 12 of intermediate:The bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 7-

A) .2- azidos -3- (the chloro- 2- bromophenyls of 5-) ethyl acrylate

Using the chloro- 2- bromobenzaldehydes of 5- as initiation material, preparation process obtains white solid with a) described in the preparation 8 of intermediate Body 1.06g, yield is 23%.

¹H NMR(CDCl₃)δ(ppm):8.13 (s, 1H), 7.53 (d, J=8.4Hz, 1H), 7.15 (s, 2H), 4.40 (q, J =7.2Hz, 2H), 1.42 (t, J=7.2Hz, 3H)

B) the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of .7-

Using 2- azidos -3- (the chloro- 2- bromophenyls of 5-) ethyl acrylate as initiation material, preparation process is with intermediate It is b) described in preparing 8, white solid 500mg is obtained, yield is 44%, mp:154-155℃.

¹H NMR(CDCl₃)δ(ppm):9.11 (brs, 1H), 7.27 (d, J=8.4Hz, 2H), 7.18 (d, J=8.0Hz, 1H), 4.44 (q, J=7.2Hz, 2H), 1.44 (t, J=7.2Hz, 3H)

Embodiment 122:The bromo- N- of the chloro- 2- of 7- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) the bromo- 1H- indole-2-carboxylic acids of the chloro- 4- of .7-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 7- as initiation material, the b) side in preparation process be the same as Example 3 Method, obtains white powdery solids 110mg, and yield is 93%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.38 (s, 1H), 12.48 (s, 1H), 7.33 (d, J=8.0Hz, 1H), 7.29 (d, J=8.0Hz, 1H), 7.07 (d, J=2.0Hz, 1H)

B) the bromo- N- of the chloro- 2- of .7- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using the bromo- 1H- indole-2-carboxylic acids of the chloro- 4- of 7- and 4- methoxybenzenesulphoismides as initiation material, preparation process is with implementation C) methods described in example 3, obtains off-white powder shape solid 30mg, yield is 31%, mp:123-125℃.

¹H NMR(DMSO-d₆)δ(ppm):12.25 (brs, 1H), 7.97 (d, J=8.8Hz, 2H), 7.55 (brs, 1H), (s, the 3H) of 7.32-7.33 (m, 2H), 7.16 (d, J=8.8Hz, 2H), 3.85 (s, 3H), 3.75

Embodiment 123:4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

A) .4- ((3- methoxyphenyls) amino) the chloro- 1H- indole -2-ethyl formates of -7-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 7- and 3- aminoanisoles as initiation material, preparation process is with implementation A) methods described in example 75, obtains white solid 160mg, yield is 66%, mp:112-113℃.

¹H NMR(CDCl₃)δ(ppm):8.98 (brs, 1H), 7.23 (s, 1H), 7.19 (d, J=10.4Hz, 2H), 6.91 (d, J=8.0Hz, 1H), 6.70 (d, J=10.4Hz, 2H), 6.54 (d, J=8.0Hz, 1H), 5.96 (brs, 1H), 4.42 (q, J=7.2Hz, 2H), 3.78 (s, 3H), 1.41 (t, J=7.2Hz, 3H) .HRMS (ESI):m/z,calcd for C₁₈H₁₈N₂O₃Cl[M+H]⁺:345.1006,found 345.0994.

B) .4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7-

Using 4- ((3- methoxyphenyls) amino), the chloro- 1H- indole -2-ethyl formates of -7- is initiation materials, and preparation process is same B) methods described in embodiment 3, obtains white powdery solids 105mg, yield is 100%, mp:145-146℃.

¹H NMR(DMSO-d₆)δ(ppm):12.96(s,1H),11.78(s,1H),8.31(s,1H),7.46(s,1H), 7.19-7.14 (m, 2H), 6.84 (d, J=8.0Hz, 1H), 6.79 (d, J=8.0Hz, 1H), 6.74 (s, 1H), 6.47 (d, J= 8.0Hz,1H),3.72(s,1H).

C) .4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 21mg, yield is 27%, mp:124- 125℃。

¹H NMR(DMSO-d₆)δ(ppm):12.34 (brs, 1H), 11.68 (s, 1H), 8.35 (s, 1H), 7.96 (d, J= 8.8Hz, 2H), 7.59 (s, 1H), 7.20-7.15 (m, 4H), 6.83 (d, J=8.4Hz, 1H), 6.73 (d, J=8.0Hz, 2H), 6.69 (s, 1H), 6.47 (d, J=8.0Hz, 1H), 3.85 (s, 3H), 3.71 (s, 3H)；¹³C NMR(125MHz,DMSO-d₆):δ 163.21,160.10,158.21,144.23,136.67,135.39,130.82,130.19,129.88,128.04,125.51, 120.38,114.28,110.27,108.82,107.19,106.00,105.97,103.51,55.82,54.86.HRMS (ESI):m/z,calcd.for C₂₃H₂₁N₃O₅ClS[M+H]⁺:486.0890,found 486.0877.

Embodiment 124:4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole -2-ethyl formates of -7-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 7- and the fluoro- 3- chloroanilines of 4- as initiation material, preparation process is with real A) methods described is applied in example 75, white solid 210mg is obtained, yield is 75%, mp:159-160℃.

¹H NMR(CDCl₃)δ(ppm):9.01 (s, 1H), 7.19 (d, J=8.4Hz, 1H), 7.17 (d, J=1.6Hz, 1H),7.15(dd,J₁=6.4Hz, J₂=2.4Hz, 1H), 7.07 (t, J=8.4Hz, 1H), 6.94 (dt, J₁=8.8Hz, J₂= 3.2Hz, 1H), 6.77 (d, J=8.4Hz, 1H), 5.82 (brs, 1H), 4.42 (q, J=7.2Hz, 2H), 1.42 (t, J= 7.2Hz,3H).

B) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole-2-carboxylic acids of -7-

With 4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole -2-ethyl formates initiation materials of -7-, preparation process is same B) methods described in embodiment 3, obtains brown powder solid 122mg, yield is 98%, mp:237-239℃.

¹H NMR(DMSO-d₆)δ(ppm):13.02(brs,1H),11.87(s,1H),8.45(s,1H),7.41(s,1H), (d, J=8.4Hz, the 1H) of 7.33-7.27 (m, 2H), 7.18-7.14 (m, 2H), 6.79

C) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 40mg, yield is 44%, mp:210- 212℃。

¹H NMR(DMSO-d₆)δ(ppm):12.35 (s, 1H), 11.77 (s, 1H), 8.48 (s, 1H), 7.96 (d, J= 8.8Hz, 2H), 7.53 (s, 1H), 7.30 (t, J=8.8Hz, 1H), 7.22 (d, J=8.0Hz, 2H), 7.16 (d, J=8.4Hz, 2H), 7.09-7.07 (m, 1H), 6.78 (d, J=8.0Hz, 1H), 3.85 (s, 3H)；¹³C NMR(100MHz,DMSO-d₆):δ 163.22,158.09,151.50(J_CF=238.0Hz), 140.61,136.16,135.39,130.75,130.17,128.27, 125.48,120.45,119.56(J_CF=18.2Hz), 118.74,117.71 (J_CF=6.1Hz), 117.20 (J_CF= 21.4Hz),114.26,108.46,108.09,106.40,55.78.HRMS(ESI):m/z,calcd.for C₂₂H₁₇N₃O₄Cl₂FS[M+H]⁺:508.0301,found508.0289.

The preparation 13 of intermediate：The bromo- 1H- indole -2-ethyl formates of the fluoro- 4- of 7-

A) .2- azidos -3- (the fluoro- 2- bromophenyls of 5-) ethyl acrylate

Using the fluoro- 2- bromobenzaldehydes of 5- as initiation material, preparation process obtains white solid with a) described in the preparation 8 of intermediate Body 250mg, yield is 23%.

¹H NMR(CDCl₃)δ(ppm):7.94(dd,J₁=10.0Hz, J₂=2.8Hz, 1H), 7.56 (dd, J₁=8.8Hz, J₂=5.6Hz, 1H), 7.19 (s, 1H), 6.92 (dt, J₁=8.0Hz, J₂=2.8Hz, 1H), 4.40 (q, J=7.2Hz, 2H), 1.42 (t, J=7.2Hz, 3H)

B) the bromo- 1H- indole -2-ethyl formates of the fluoro- 4- of .7-

Using 2- azidos -3- (the fluoro- 2- bromophenyls of 5-), ethyl acrylate is initiation material, system of the preparation process with intermediate It is b) described in standby 8, white solid 354mg is obtained, yield is 32%, mp:184-186℃.

¹H NMR(CDCl₃)δ(ppm):9.16(s,1H),7.23(dd,J₁=8.0Hz, J₂=4.0Hz, 1H), 6.92 (t, J=9.2Hz, 1H), 4.44 (q, J=7.2Hz, 2H), 1.44 (t, J=7.2Hz, 3H)

Embodiment 125:4- ((3- methoxyphenyls) amino) the fluoro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

A) .4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole -2-ethyl formates of -7-

Using the bromo- 1H- indole -2-ethyl formates of the fluoro- 4- of 7- and 3- aminoanisoles as initiation material, preparation process is with implementation A) methods described in example 75, obtains white solid 130mg, yield is 51%, mp:150-151℃.

¹H NMR(CDCl₃)δ(ppm):9.08 (s, 1H), 7.20-7.15 (m, 2H), 6.94 (t, J=8.4Hz, 1H), 6.87-6.85 (m, 1H), 6.61 (d, J=8.4Hz, 1H), 6.59 (s, 1H), 6.48 (d, J=8.0Hz, 1H), 4.41 (q, J= 7.2Hz, 2H), 3.77 (s, 1H), 1.41 (t, J=7.2Hz, 3H)

B) .4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole-2-carboxylic acids of -7-

Using 4- ((3- methoxyphenyls) amino), the fluoro- 1H- indole -2-ethyl formates of -7- is initiation materials, and preparation process is same B) methods described in embodiment 3, obtains white powdery solids 100mg, yield is 72%, mp:163-165℃.

¹H NMR(DMSO-d₆)δ(ppm):12.92(brs,1H),12.16(s,1H),8.12(s,1H),7.33(s,1H), 7.12 (t, J=8.0Hz, 1H), 6.94 (t, J=10.4Hz, 1H), 6.75 (dd, J₁=8.8Hz, J₂=3.2Hz, 1H), 6.69 (d, J=8.4Hz, 1H), 6.65 (s, 1H), 6.40 (d, J=8.0Hz, 1H), 3.70 (s, 3H)

C) .4- ((3- methoxyphenyls) amino) the fluoro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) the fluoro- 1H- indole-2-carboxylic acids of -7- and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 25mg, yield is 27%, mp:151- 152℃。

¹H NMR(DMSO-d₆)δ(ppm):12.39 (s, 1H), 12.09 (s, 1H), 8.14 (s, 1H), 7.94 (d, J= 8.4Hz, 2H), 7.55 (s, 1H), 7.16 (d, J=8.8Hz, 2H), 7.10 (t, J=8.0Hz, 1H), 6.98 (t, J=8.8Hz, 1H),6.75(dd,J₁=8.0Hz, J₂=2.8Hz, 1H), 6.60 (d, J=8.0Hz, 1H), 6.56 (s, 1H), 6.38 (d, J= 8.4Hz,1H),3.85(s,3H),3.69(s,3H)；¹³C NMR(125MHz,DMSO-d₆):δ163.17,160.15,158.74, 145.75,144.40(J_CF=238.4Hz), 133.16,130.94,130.13,129.79,128.42,126.28 (J_CF= 15.1Hz),123.37(J_CF=4.9Hz), 114.26,110.01 (J_CF=16.4Hz), 108.72,107.76,107.41 (J_CF =5.0Hz), 104.69,101.81,55.81,54.78.HRMS (ESI):m/z,calcd.for C₂₃H₂₁N₃O₅FS[M+H]⁺: 470.1186,found470.1175.

Embodiment 126:4- ((the fluoro- 3- chlorphenyls of 4-) amino) the fluoro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the fluoro- 1H- indole -2-ethyl formates of -7-

Using the bromo- 1H- indole -2-ethyl formates of the fluoro- 4- of 7- and the fluoro- 3- chloroanilines of 4- as initiation material, preparation process is with real A) methods described is applied in example 75, white solid 200mg is obtained, yield is 65%, mp:182-183℃.

¹H NMR(CDCl₃)δ(ppm):9.02 (s, 1H), 7.13 (t, J=1.5Hz, 1H), 7.05-7.01 (m, 2H), 6.95 (t, J=8.8Hz, 1H), 6.85-6.81 (m, 1H), 6.75 (dd, J₁=8.0Hz, J₂=3.2Hz, 1H), 5.65 (brs, 1H), 4.41 (q, J=7.2Hz, 2H), 1.41 (t, J=7.2Hz, 3H)

B) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the fluoro- 1H- indole-2-carboxylic acids of -7-

Using 4- ((the fluoro- 3- chlorphenyls of 4-) amino), the fluoro- 1H- indole -2-ethyl formates of -7- is initiation materials, preparation process B) methods described in be the same as Example 3, obtains white powdery solids 120mg, yield is 100%, mp:135-137℃.

¹H NMR(DMSO-d₆)δ(ppm):13.02(brs,1H),12.24(s,1H),8.27(s,1H),7.27-7.24 (m, 2H), 7.17-7.15 (m, 1H), 7.05-7.03 (m, 1H), 6.97 (t, J=8.8Hz, 1H), 6.73 (dd, J₁=8.0Hz, J₂=2.8Hz, 1H)

C) .4- ((the fluoro- 3- chlorphenyls of 4-) amino) the fluoro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- ((the fluoro- 3- chlorphenyls of 4-) amino) the fluoro- 1H- indole-2-carboxylic acids of -7- and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 40mg, yield is 44%, mp:259- 261℃。

¹H NMR(DMSO-d₆)δ(ppm):12.39 (s, 1H), 12.16 (s, 1H), 8.29 (s, 1H), 7.94 (d, J= 8.4Hz, 2H), 7.47 (s, 1H), 7.24 (t, J=9.2Hz, 1H), 7.15 (d, J=8.4Hz, 2H), 7.04 (d, J=5.6Hz, 1H), (s, the 3H) of 7.00 (t, J=9.6Hz, 1H), 6.92-6.90 (m, 1H), 6.73 (d, J=5.6Hz, 1H), 3.85

The preparation 14 of intermediate：The bromo- 1H- indole -2-ethyl formates of 4,7- bis-

A) .2- azidos -3- (2,5- dibromo phenyls) ethyl acrylate

With 2,5- dibromo benzaldehydes for initiation material, preparation process obtains white solid with a) described in the preparation 8 of intermediate 1.6g, yield is 23%.

¹H NMR(CDCl₃)δ(ppm):8.27 (d, J=2.0Hz, 1H), 7.46 (d, J=8.4Hz, 1H), 7.29 (dd, J₁ =1.6Hz, J₂=8.4Hz, 1H), 7.13 (s, 1H), 4.40 (q, J=7.2Hz, 2H), 1.41 (t, J=7.2Hz, 3H)

B) the bromo- 1H- indole -2-ethyl formates of .4,7- bis-

With 2- azidos -3- (2,5- dibromo phenyl) ethyl acrylate for initiation material, o-dichlorohenzene is solvent, is prepared Journey obtains white solid 880mg, yield is 59%, mp with b) described in the preparation 8 of intermediate:129-130℃.

¹H NMR(CDCl₃)δ(ppm):9.06 (brs, 1H), 7.33 (d, J=8.4Hz, 2H), 7.22 (d, J=8.0Hz, 1H), 4.45 (q, J=7.2Hz, 2H), 1.44 (t, J=7.2Hz, 3H)

Embodiment 127:4,7- bis- bromo- N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) the bromo- 1H- indole-2-carboxylic acids of .4,7- bis-

With the bromo- 1H- indole -2-ethyl formates initiation materials of 4,7- bis-, b) methods described in preparation process be the same as Example 3, White powdery solids 130mg is obtained, yield is 95%, mp:180-182℃.

¹H NMR(DMSO-d₆)δ(ppm):13.27 (brs, 1H), 12.20 (brs, 1H), 7.41 (d, J=8.0Hz, 1H), 7.25 (d, J=8.0Hz, 1H), 7.07 (s, 1H)

B) the bromo- N- of .4,7- bis- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

With the bromo- 1H- indole-2-carboxylic acids of 4,7- bis- and 4- methoxybenzenesulphoismides for initiation material, preparation process is with implementation C) methods described in example 3, obtains off-white powder shape solid 50mg, yield is 51%, mp:214-215℃.

¹H NMR(DMSO-d₆)δ(ppm):12.52 (brs, 1H), 12.11 (brs, 1H), 7.99 (d, J=8.8Hz, 2H), 7.54 (s, 1H), 7.46 (d, J=8.0Hz, 1H), 7.30 (d, J=8.0Hz, 1H), 7.19 (d, J=8.8Hz, 2H), 3.87 (s,3H).

The preparation 15 of intermediate：The bromo- 1H- indole -2-ethyl formates of 6- methyl -4-

A) .2- azidos -3- (4- methyl -2- bromophenyls) ethyl acrylate

Using 4- methyl -2- bromobenzaldehydes as initiation material, preparation process obtains white with a) described in the preparation 8 of intermediate Solid 2.13g, yield is 27%.

¹H-NMR(400MHz,CDCl₃)δ(ppm):8.03 (d, J=8.4Hz, 1H), 7.44 (s, 1H), 7.25 (s, 1H), (t, J=7.2Hz, the 3H) of 7.15 (d, J=8.4Hz, 1H), 4.39 (q, J=7.2Hz, 2H), 2.34 (s, 3H), 1.41

B) the bromo- 1H- indole -2-ethyl formates of .6- methyl -4-

Using 2- azidos -3- (4- methyl -2- bromophenyls), ethyl acrylate is initiation material, and preparation process is with intermediate It is b) described in preparing 8, white solid 1.70g is obtained, yield is 93%, mp:152-153℃.

¹H NMR(CDCl₃)δ(ppm):8.93(brs,1H),7.21-7.20(m,2H),7.19(s,1H),7.14(s, 1H), (t, J=7.2Hz, the 3H) of 4.41 (q, J=7.2Hz, 2H), 2.44 (s, 3H), 1.42

Embodiment 128:The bromo- N- of 6- methyl -4- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) the bromo- 1H- indole-2-carboxylic acids of .6- methyl -4-

With the bromo- 1H- indole -2-ethyl formates initiation materials of 6- methyl -4-, the b) side in preparation process be the same as Example 3 Method, obtains white powdery solids 134mg, and yield is 100%, mp:241-243℃.

¹H NMR(DMSO-d₆)δ(ppm):13.09(s,1H),12.01(s,1H),7.22(s,1H),7.17(s,1H), 6.92(s,1H),2.40(s,3H).

B) the bromo- N- of .6- methyl -4- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using the bromo- 1H- indole-2-carboxylic acids of 6- methyl -4- and 4- methoxybenzenesulphoismides as initiation material, preparation process is with real C) methods described is applied in example 3, pale yellow powder shape solid 44mg is obtained, yield is 44%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):12.49 (brs, 1H), 11.96 (s, 1H), 7.96 (d, J=9.0Hz, 2H), 7.50(s,1H),7.14-7.10(m,4H),3.85(s,3H),2.37(s,3H).

Embodiment 129:6- methyl -4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .6- methyl -4- ((3- methoxyphenyls) amino) -1H- indole -2-ethyl formates

Using the bromo- 1H- indole -2-ethyl formates of 6- methyl -4- and 3- aminoanisoles as initiation material, preparation process is with real A) methods described is applied in example 75, white solid 236mg is obtained, yield is 82%, mp:132-133℃.

¹H NMR(CDCl₃)δ(ppm):8.72 (s, 1H), 7.20 (t, J=8.4Hz, 1H), 7.16 (s, 1H), 6.83 (s, 2H), 6.73 (d, J=9.2Hz, 2H), 6.53 (d, J=8.4Hz, 1H), 4.38 (q, J=7.2Hz, 2H), 3.79 (s, 3H), 2.40 (s, 3H), 1.40 (t, J=7.2Hz, 3H)

B) .6- methyl -4- ((3- methoxyphenyls) amino) -1H- indole-2-carboxylic acids

Using 6- methyl -4- ((3- methoxyphenyls) amino), -1H- indole -2-ethyl formates is initiation materials, preparation process B) methods described in be the same as Example 3, obtains white powdery solids 120mg, yield is 97%, mp:91-93℃.

¹H NMR(DMSO-d₆)δ(ppm):12.65(brs,1H),11.49(s,1H),8.14(s,1H),7.25(s,1H), 7.15 (t, J=7.2Hz, 1H), 6.77 (d, J=11.2Hz, 1H), 6.74 (s, 2H), 6.69 (s, 1H), 6.43 (dd, J₁= 6.8Hz,J₂=2.4Hz, 1H), 3.71 (s, 3H), 2.31 (s, 3H)

C) .6- methyl -4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 6- methyl -4- ((3- methoxyphenyls) amino) -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 36mg, yield is 33%, mp: 223-225℃。

¹H NMR(DMSO-d₆)δ(ppm):12.27 (s, 1H), 11.48 (s, 1H), 8.16 (s, 1H), 7.93 (d, J= 8.8Hz, 2H), 7.47 (s, 1H), 7.13 (t, J=9.2Hz, 3H), 6.74 (s, 1H), 6.67 (d, J=8.0Hz, 3H), 6.41 (d, J=8.0Hz, 1H), 3.84 (s, 3H), 3.70 (s, 3H), 2.31 (s, 3H)；HRMS(ESI):m/z,calcd.for C₂₄H₂₄N₃O₅S[M+H]⁺:466.1437,found 466.1425.

Embodiment 130:6- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino)-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .6- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole -2-ethyl formates

Using the bromo- 1H- indole -2-ethyl formates of 6- methyl -4- and the fluoro- 3- chloroanilines of 4- as initiation material, preparation process is same A) methods described in embodiment 75, obtains white solid 245mg, yield is 80%, mp:166-167℃.

¹H NMR(CDCl₃)δ(ppm):8.73(s,1H),7.15(dd,J₁=6.0Hz, J₂=2.0Hz, 1H), 7.09 (s, 1H), 7.05 (t, J=8.8Hz, 1H), 6.98-6.95 (m, 1H), 6.85 (s, 1H), 6.67 (s, 1H), 5.75 (brs, 1H), (t, J=7.2Hz, the 3H) of 4.39 (q, J=7.2Hz, 2H), 2.41 (s, 3H), 1.40

B) .6- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole-2-carboxylic acids

, as initiation material, prepared using 6- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole -2-ethyl formates B) methods described in journey be the same as Example 3, obtains brown powder solid 120mg, yield is 94%, mp:155-157℃.

¹H NMR(DMSO-d₆)δ(ppm):11.57 (s, 1H), 8.28 (brs, 1H), 7.29 (t, J=12Hz, 1H), 7.23 (dd,J₁=8.8Hz, J₂=2.8Hz, 1H), 7.19 (s, 1H), 7.16-7.12 (m, 1H), 6.79 (s, 1H), 6.63 (s, 1H), 2.33(s,3H).

C) .6- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 6- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 61mg, yield is 57%, mp: 264-266℃。

¹H NMR(DMSO-d₆)δ(ppm):12.27 (s, 1H), 11.55 (s, 1H), 8.31 (s, 1H), 7.93 (d, J= 8.8Hz, 2H), 7.39 (s, 1H), 7.27 (t, J=8.8Hz, 1H), 7.15-7.11 (m, 3H), 7.00-6.98 (m, 1H), 6.80 (s,1H),6.62(s,1H),3.84(s,3H),2.32(s,3H).

The preparation 16 of intermediate：The bromo- 1H- indole -2-ethyl formates of 7- methyl -4-

A) .2- azidos -3- (5- methyl -2- bromophenyls) ethyl acrylate

Using 5- methyl -2- bromobenzaldehydes as initiation material, preparation process obtains white with a) described in the preparation 8 of intermediate Solid 1.0g, yield is 32%.

¹H NMR(CDCl₃)δ(ppm):7.90 (s, 1H), 7.48 (d, J=8.4Hz, 1H), 7.23 (s, 1H), 6.99 (d, J =8.4Hz, 1H), 4.39 (q, J=7.2Hz, 2H), 2.35 (s, 3H), 1.41 (t, J=7.2Hz, 3H)

B) the bromo- 1H- indole -2-ethyl formates of .7- methyl -4-

Using 2- azidos -3- (5- methyl -2- bromophenyls), ethyl acrylate is initiation material, and preparation process is with intermediate It is b) described in preparing 8, white solid 450mg is obtained, yield is 92%, mp:120-122℃.

¹H NMR(CDCl₃)δ(ppm):8.91 (brs, 1H), 7.26 (s, 1H), 7.24 (d, J=8.0Hz, 1H), 6.97 (d, J=7.6Hz, 1H), 4.43 (q, J=7.2Hz, 2H), 2.48 (s, 3H), 1.43 (t, J=7.2Hz, 3H)

Embodiment 131:The bromo- N- of 7- methyl -4- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) the bromo- 1H- indole-2-carboxylic acids of .7- methyl -4-

With the bromo- 1H- indole -2-ethyl formates initiation materials of 7- methyl -4-, the b) side in preparation process be the same as Example 3 Method, obtains white powdery solids 80mg, and yield is 84%, mp:>280℃.

¹H NMR(acetone-d₆)δ(ppm):11.41 (s, 1H), 10.95 (s, 1H), 7.25 (d, J=7.6Hz, 1H), (s, the 3H) of 7.17 (s, 1H), 7.04 (d, J=7.2Hz, 1H), 2.57

B) the bromo- N- of .7- methyl -4- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using the bromo- 1H- indole-2-carboxylic acids of 7- methyl -4- and 4- methoxybenzenesulphoismides as initiation material, preparation process is with real C) methods described is applied in example 3, off-white powder shape solid 52mg is obtained, yield is 63%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):12.52 (brs, 1H), 11.91 (s, 1H), 7.96 (d, J=9.0Hz, 2H), 7.46 (s, 1H), 7.20 (d, J=7.5Hz, 1H), 6.14 (d, J=8.4Hz, 2H), 6.96 (d, J=7.2Hz, 1H), 3.84 (s,3H),2.43(s,3H).

Embodiment 132:7- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino)-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .7- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole -2-ethyl formates

Using the bromo- 1H- indole -2-ethyl formates of 7- methyl -4- and the fluoro- 3- chloroanilines of 4- as initiation material, preparation process is same A) methods described in embodiment 75, obtains white solid 156mg, yield is 58%, mp:173-174℃.

¹H NMR(CDCl₃)δ(ppm):8.80 (s, 1H), 7.15 (s, 1H), 7.09 (d, J=4.0Hz, 1H), 7.05- 7.01 (m, 2H), 6.90 (s, 1H), 6.82 (d, J=6.8Hz, 1H), 4.41 (q, J=7.2Hz, 2H), 2.48 (s, 3H), 1.40 (t, J=7.2Hz, 3H)

B) .7- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole-2-carboxylic acids

, as initiation material, prepared using 7- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole -2-ethyl formates B) methods described in journey be the same as Example 3, obtains white powdery solids 87mg, yield is 95%, mp:224-226℃.

¹H NMR(DMSO-d₆)δ(ppm):12.82 (s, 1H), 11.58 (s, 1H), 8.21 (s, 1H), 7.24 (t, J= 8.8Hz,2H),7.15(dd,J₁=6.0Hz, J₂=1.6Hz, 1H), 7.03-7.01 (m, 1H), 6.92 (d, J=7.2Hz, 1H), 6.75 (d, J=7.6Hz, 1H), 2.44 (s, 3H)

C) .7- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 7- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains micro-yellow powder shape solid 40mg, yield is 52%, mp: 191-193℃。

¹H NMR(DMSO-d₆)δ(ppm):12.30 (s, 1H), 11.50 (s, 1H), 8.24 (s, 1H), 7.95 (d, J= 8.4Hz, 2H), 7.44 (s, 1H), 7.23 (t, J=9.2Hz, 1H), 7.15 (t, J=8.8Hz, 2H), 7.05 (d, J=6.4Hz, 1H), 6.96-6.91 (m, 2H), 6.74 (d, J=7.6Hz, 1H), 3.85 (s, 3H), 2.41 (s, 3H)；HRMS(ESI):m/z, calcd.for C₂₃H₂₀N₃O₄FClS[M+H]⁺:488.0847,found 488.0835.

The preparation 17 of intermediate：The bromo- 1H- indole -2-ethyl formates of 7- methoxyl groups -4-

A) .2- azidos -3- (5- methoxyl group -2- bromophenyls) ethyl acrylate

Using 5- methoxyl group -2- bromobenzaldehydes as initiation material, preparation process obtains white with a) described in the preparation 8 of intermediate Color solid 2.5g, yield is 40%.

¹H NMR(CDCl₃)δ(ppm):7.72 (d, J=3.0Hz, 1H), 7.49 (d, J=8.7Hz, 1H), 7.22 (s, 1H),6.76(dd,J₁=3.0Hz, J₂=8.7Hz, 1H), 4.39 (q, J=7.2Hz, 2H), 3.83 (s, 3H), 1.41 (t, J= 7.2Hz,3H).

B) the bromo- 1H- indole -2-ethyl formates of .7- methoxyl groups -4-

Using 2- azidos -3- (5- methoxyl group -2- bromophenyls), ethyl acrylate is initiation material, the same intermediate of preparation process Preparation 8 in it is b) described, obtain white solid 1.32g, yield is 58%, mp:140-141℃.

¹H NMR(CDCl₃) δ (ppm) 9.14 (s, 1H), 7.20 (d, J=7.6Hz, 2H), 6.59 (d, J=8.0Hz, 1H), (t, J=7.2Hz, the 3H) of 4.42 (q, J=7.2Hz, 2H), 3.96 (s, 3H), 1.42

Embodiment 133:7- methoxyl groups -4- ((the fluoro- 3- chlorphenyls of 4-) amino)-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .7- methoxyl groups -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole -2-ethyl formates

Using the bromo- 1H- indole -2-ethyl formates of 7- methoxyl groups -4- and the fluoro- 3- chloroanilines of 4- as initiation material, preparation process A) methods described in be the same as Example 75, obtains white solid 176mg, yield is 72%, mp:160-162℃.

¹H NMR(CDCl₃)δ(ppm):9.10(s,1H),7.08(s,1H),7.00-6.96(m,2H),6.84-6.78(m, 2H), (t, J=7.2Hz, the 3H) of 6.65 (d, J=8.4Hz, 1H), 4.39 (q, J=7.2Hz, 2H), 3.97 (s, 3H), 1.39

B) .7- methoxyl groups -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole-2-carboxylic acids

Using 7- methoxyl groups -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole -2-ethyl formates as initiation material, prepare B) methods described in process be the same as Example 3, obtains brown-green pulverulent solids 55mg, yield is 100%, mp:193-195℃.

¹H NMR(DMSO-d₆)δ(ppm):12.76 (brs, 1H), 11.70 (s, 1H), 8.04 (s, 1H), 7.19 (t, J= 8.8Hz, 1H), 7.09 (s, 1H), 7.00 (d, J=5.2Hz, 1H), 6.91-6.88 (m, 1H), 6.76 (d, J=8.0Hz, 1H), 6.70 (d, J=8.0Hz, 1H), 3.87 (s, 3H)

C) .7- methoxyl groups -4- ((the fluoro- 3- chlorphenyls of 4-) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

Using 7- methoxyl groups -4- ((the fluoro- 3- chlorphenyls of 4-) amino) -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as C) methods described in initiation material, preparation process be the same as Example 3, obtains micro-yellow powder shape solid 26mg, yield is 43%, mp: 125-126℃。

¹H NMR(DMSO-d₆)δ(ppm):12.19(s,1H),11.68(s,1H),8.06(s,1H),7.20-7.13(m, 3H), 6.92 (d, J=4.8Hz, 1H), 6.81-6.71 (m, 3H), 3.87 (s, 3H), 3.83 (s, 3H)；HRMS(ESI):m/z, calcd.for C₂₃H₂₀N₃O₅FClS[M+H]⁺:504.0796,found504.0782.

The preparation 18 of intermediate：The bromo- 1H- indole -2-ethyl formates of 7- cyano group -4-

A) .3- (two bromomethyls) -4- Brominals

3- methyl -4- Brominals (10g, 51mmol) are dissolved in carbon tetrachloride (100mL), addition NBS (22.6g, 127.5mmol) with benzoyl peroxide (272mg, 2.5mmol), flow back 14h, and raw material disappears substantially.Room temperature is cooled to, is added Water (400mL), EA extractions (200mL × 2), column chromatography (P/E=20:1) white solid 15g, is obtained, yield is 83%.

¹H NMR(CDCl₃)δ(ppm):8.31 (s, 1H), 7.66 (d, J=8.4Hz, 1H), 7.44 (d, J=8.0Hz, 1H),7.00(s,1H).

B) .3- carboxaldehyde radicals -4- Brominals

By sodium acetate (14.96g, 182.3mmol), calcium carbonate (9.34g, 93.28mmol) and TBAB (3.14g, 9.75mmol) be added to the water (700mL), after stirring, addition 3- (two bromomethyls) -4- Brominals (15g, 42.4mmol), flow back 29h, and feedstock portions are remaining.DCM extracts (200mL × 3), column chromatography (P/E=20:1-D), obtain white solid Body 6.17g, yield is 69%.

¹H NMR(CDCl₃)δ(ppm):10.35 (s, 1H), 8.18 (s, 1H), 7.82 (d, J=8.0Hz, 1H), 7.70 (d, J=8.4Hz, 1H), 7.00 (s, 1H)

C) .2- azidos -3- (5- cyano group -2- bromophenyls) ethyl acrylate

Using 3- carboxaldehyde radicals -4- Brominals as initiation material, preparation process obtains white with a) described in the preparation 8 of intermediate Solid 1.12g, yield is 12%.

¹H NMR(CDCl₃)δ(ppm):8.44 (s, 1H), 7.73 (d, J=8.4Hz, 1H), 7.41 (d, J=8.4Hz, 1H), (t, J=7.2Hz, the 3H) of 7.13 (s, 1H), 4.42 (q, J=7.2Hz, 2H), 1.42

D) the bromo- 1H- indole -2-ethyl formates of .7- cyano group -4-

Using 2- azidos -3- (5- cyano group -2- bromophenyls), ethyl acrylate is initiation material, and preparation process is with intermediate It is b) described in preparing 8, white solid 300mg is obtained, yield is 30%, mp:193-194℃.

¹H NMR(CDCl₃) δ (ppm) 9.55 (s, 1H), 7.50 (d, J=7.6Hz, 1H), 7.42 (d, J=8.0Hz, 1H), (t, J=7.2Hz, the 3H) of 7.34 (s, 1H), 4.48 (q, J=7.2Hz, 2H), 1.45

Embodiment 134:7- cyano group -4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

A) .7- cyano group -4- ((3- methoxyphenyls) amino) -1H- indole -2-ethyl formates

Using the bromo- 1H- indole -2-ethyl formates of 7- cyano group -4- and 3- aminoanisoles as initiation material, preparation process is with real A) methods described is applied in example 75, white solid 164mg is obtained, yield is 89%, mp:189-191℃.

¹H NMR(CDCl₃)δ(ppm):9.29 (s, 1H), 7.49 (d, J=8.4Hz, 2H), 7.31-7.27 (m, 2H), 6.89-6.82 (m, 3H), 6.71 (d, J=8.0Hz, 1H), 6.42 (s, 1H), 4.44 (q, J=7.2Hz, 2H), 3.82 (s, 3H), 1.43 (t, J=7.2Hz, 3H)

B) .7- cyano group -4- ((3- methoxyphenyls) amino) -1H- indole-2-carboxylic acids

Using 7- cyano group -4- ((3- methoxyphenyls) amino), -1H- indole -2-ethyl formates is initiation materials, preparation process B) methods described in be the same as Example 3, obtains white powdery solids 120mg, yield is 95%, mp:265-267℃.

¹H NMR(DMSO-d₆)δ(ppm):11.70 (brs, 1H), 8.78 (s, 1H), 7.44 (d, J=8.0Hz, 1H), 7.35 (s, 1H), 7.24 (t, J=8.0Hz, 1H), 6.89 (d, J=8.0Hz, 1H), 6.84 (s, 1H), 6.80 (d, J= 8.4Hz, 1H), 6.61 (d, J=8.4Hz, 1H), 3.74 (s, 3H)

C) .7- cyano group -4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 7- cyano group -4- ((3- methoxyphenyls) amino) -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains micro-yellow powder shape solid 16mg, yield is 34%, mp: 236-238℃。

¹H NMR(DMSO-d₆)δ(ppm):12.28 (brs, 1H), 12.16 (s, 1H), 8.99 (s, 1H), 7.97 (d, J= 8.8Hz, 2H), 7.69 (s, 1H), 7.56 (d, J=8.0Hz, 1H), 7.28 (t, J=8.0Hz, 2H), 7.17 (d, J=8.4Hz, 2H), 6.88 (d, J=8.0Hz, 1H), 6.83 (s, 1H), 6.81 (d, J=8.8Hz, 1H), 6.67 (d, J=8.0Hz, 1H), 3.86(s,3H),3.75(s,3H).

The preparation 19 of intermediate：The bromo- 1H- indole -2-ethyl formates of 7- trifluoromethyls -4-

A) .2- azidos -3- (5- trifluoromethyl -2- bromophenyls) ethyl acrylate

Using 5- trifluoromethyl -2- bromobenzaldehydes as initiation material, preparation process is obtained with a) described in the preparation 8 of intermediate White solid 1.23g, yield is 17%.

¹H NMR(CDCl₃)δ(ppm):8.38 (s, 1H), 7.73 (d, J=8.4Hz, 1H), 7.41 (d, J=8.4Hz, 1H), (t, J=7.2Hz, the 3H) of 7.20 (s, 1H), 4.42 (q, J=7.2Hz, 2H), 1.42

B) the bromo- 1H- indole -2-ethyl formates of .7- trifluoromethyls -4-

Using 2- azidos -3- (5- trifluoromethyl -2- bromophenyls) ethyl acrylate as initiation material, o-dichlorohenzene is molten Agent, preparation process obtains white solid 624mg, yield is 60%, mp with b) described in the preparation 8 of intermediate:123-124℃.

¹H NMR(CDCl₃)δ(ppm):9.21 (brs, 1H), 7.46-7.43 (m, 2H), 7.34 (s, 1H), 4.46 (q, J= 7.2Hz, 2H), 1.45 (t, J=7.2Hz, 3H)

Embodiment 135:7- trifluoromethyls -4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) .7- trifluoromethyls -4- ((3- methoxyphenyls) amino) -1H- indole -2-ethyl formates

Using the bromo- 1H- indole -2-ethyl formates of 7- trifluoromethyls -4- and 3- aminoanisoles as initiation material, preparation process A) methods described in be the same as Example 75, obtains white solid 181mg, yield is 80%, mp:129-130℃.

¹H NMR(CDCl₃)δ(ppm):9.07 (brs, 1H), 7.44 (d, J=8.0Hz, 1H), 7.28-7.25 (m, 2H), 6.94 (d, J=8.0Hz, 1H), 6.83-6.80 (m, 2H), 6.65 (d, J=8.4Hz, 1H), 6.20 (brs, 1H), 4.43 (q, J =7.2Hz, 2H), 3.81 (s, 3H), 1.43 (t, J=7.2Hz, 3H)

B) .7- trifluoromethyls -4- ((3- methoxyphenyls) amino) -1H- indole-2-carboxylic acids

Using 7- trifluoromethyls -4- ((3- methoxyphenyls) amino) -1H- indole -2-ethyl formates as initiation material, prepare B) methods described in process be the same as Example 3, obtains brown powder solid 95mg, yield is 95%, mp:162-164℃.

¹H NMR(DMSO-d₆)δ(ppm):11.51 (s, 1H), 8.69 (s, 1H), 7.64 (s, 1H), 7.42 (m, J= 8.4Hz, 1H), 7.25 (t, J=8.0Hz, 1H), 6.94-6.86 (m, 3H), 6.60 (d, J=8.0Hz, 1H), 3.75 (s, 3H)

C) .7- trifluoromethyls -4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 7- trifluoromethyls -4- ((3- methoxyphenyls) amino) -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains micro-yellow powder shape solid 28mg, yield is 34%, mp:119-120℃。

¹H NMR(DMSO-d₆)δ(ppm):12.46 (brs, 1H), 11.47 (s, 1H), 8.75 (s, 1H), 7.97 (d, J= 8.8Hz, 2H), 7.72 (s, 1H), 7.46 (d, J=8.4Hz, 1H), 7.25 (t, J=8.0Hz, 1H), 7.16 (d, J=8.4Hz, 2H), (s, the 3H) of 6.87 (d, J=8.0Hz, 2H), 6.83 (s, 1H), 6.61 (d, J=8.0Hz, 1H), 3.86 (s, 3H), 3.74

The preparation 20 of intermediate：The bromo- 1H- indole -2-ethyl formates of the chloro- 7- of 4-

A) .2- azidos -3- (the chloro- 5- bromophenyls of 2-) ethyl acrylate

Using the chloro- 5- bromobenzaldehydes of 2- as initiation material, preparation process obtains white solid with a) described in the preparation 8 of intermediate Body 1.49g, yield is 20%.

¹H NMR(CDCl₃)δ(ppm):8.33 (d, J=1.6Hz, 1H), 6.88 (d, J₁=1.6Hz, J₂=8.8Hz, 1H), (t, J=7.2Hz, the 3H) of 7.27 (d, J=8.8Hz, 1H), 7.18 (s, 1H), 4.40 (q, J=7.2Hz, 2H), 1.41

B) the bromo- 1H- indole -2-ethyl formates of the chloro- 7- of .4-

Using 2- azidos -3- (the chloro- 5- bromophenyls of 2-), ethyl acrylate is initiation material, and o-dichlorohenzene is solvent, prepares Process obtains white solid 825mg, yield is 66%, mp with b) described in the preparation 8 of intermediate:130-131℃.

¹HNMR(CDCl₃)δ(ppm):9.03 (brs, 1H), 7.39 (d, J=8.4Hz, 2H), 7.06 (d, J=8.0Hz, 1H), 4.45 (q, J=7.2Hz, 2H), 1.44 (t, J=7.2Hz, 3H)

Embodiment 136:The chloro- 7- of 4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

A) the chloro- 7- of .4- ((3- methoxyphenyls) amino) -1H- indole -2-ethyl formates

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 7- of 4- and 3- aminoanisoles as initiation material, preparation process is with implementation A) methods described in example 75, obtains white solid 42mg, yield is 18%, mp:102-103℃.

¹H NMR(CDCl₃)δ(ppm):8.96(brs,1H),7.32-7.31(m,2H),7.14-7.09(m,3H),6.40- (t, J=7.2Hz, the 3H) of 6.36 (m, 3H), 4.38 (q, J=7.2Hz, 2H), 3.74 (s, 3H), 1.39

B) the chloro- 7- of .4- ((3- methoxyphenyls) amino) -1H- indole-2-carboxylic acids

Using the chloro- 7- of 4- ((3- methoxyphenyls) amino), -1H- indole -2-ethyl formates is initiation materials, and preparation process is same B) methods described in embodiment 3, obtains grey powder solid 32mg, yield is 97%, mp:84-86℃.

¹H NMR(DMSO-d₆)δ(ppm):13.27 (brs, 1H), 11.89 (s, 1H), 8.09 (s, 1H), 7.19 (t, J= 8.0Hz, 2H), 7.08 (d, J=8.4Hz, 1H), 7.03-7.02 (m, 2H), 6.76 (d, J=8.0Hz, 2H), 6.70 (s, 1H), 6.49 (d, J=8.0Hz, 1H), 3.73 (s, 3H)

C) the chloro- 7- of .4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using the chloro- 7- of 4- ((3- methoxyphenyls) amino) -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains micro-yellow powder shape solid 10mg, yield is 10%, mp:169- 170℃。

¹H NMR(acetone-d₆)δ(ppm):11.01 (brs, 1H), 10.89 (brs, 1H), 8.06 (d, J=8.8Hz, 2H), 7.55 (s, 1H), 7.46 (s, 1H), 7.20-7.06 (m, 5H), 6.71-6.68 (m, 2H), 6.49 (d, J=8.4Hz, 1H),3.91(s,3H),3.75(s,3H).

The preparation 21 of intermediate：The bromo- 1H- indole -2-ethyl formates of the chloro- 7- of 1- methyl -4-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 7- of 4- and iodomethane as initiation material, system of the preparation process with intermediate Described in standby 5, white solid 309mg is obtained, yield is 99%, mp:92-93℃.

¹H NMR(CDCl₃)δ(ppm):7.40 (d, J=8.0Hz, 1H), 7.37 (s, 1H), 6.98 (d, J=8.0Hz, 1H), (t, J=7.2Hz, the 3H) of 4.47 (s, 3H), 4.39 (q, J=7.2Hz, 2H), 1.43

Embodiment 137:1- methyl -7- ((3- methoxyphenyls) amino) the chloro- N- of -4- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) .1- methyl -7- ((3- methoxyphenyls) amino) the chloro- 1H- indole -2-ethyl formates of -4-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 7- of 1- methyl -4- and 3- aminoanisoles as initiation material, prepared A) methods described in journey be the same as Example 3, obtains faint yellow solid 80mg, yield is 28%, mp:40-41℃.

¹H NMR(CDCl₃)δ(ppm):7.40 (s, 1H), 7.10-7.08 (m, 2H), 7.01 (d, J=8.0Hz, 1H), 6.39 (d, J=7.2Hz, 1H), 6.23 (d, J=8.0Hz, 1H), 6.15 (s, 1H), 5.40 (brs, 1H), 4.37 (q, J= 7.2Hz, 2H), 4.20 (s, 3H), 3.72 (s, 3H), 1.41 (t, J=7.2Hz, 3H)

B) .1- methyl -7- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -4-

Using 1- methyl -7- ((3- methoxyphenyls) amino) chloro- 1H- indole -2-ethyl formates of -4- as initiation material, system B) methods described in standby process be the same as Example 3, obtains grey powder solid 83mg, yield is 94%, mp:219-221℃.

¹H NMR(DMSO-d₆)δ(ppm):13.17 (brs, 1H), 7.89 (s, 1H), 7.19 (s, 1H), 7.16 (d, J= 8.0Hz,1H),7.07-7.02(m,2H),6.32-6.29(m,1H),6.20-6.18(m,2H),4.09(s,3H),3.65(s, 3H).

C) .1- methyl -7- ((3- methoxyphenyls) amino) the chloro- N- of -4- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 1- methyl -7- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -4- and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains yellow powdery solid 45mg, yield is 60%, mp: 180-182℃。

¹H NMR(DMSO-d₆)δ(ppm):12.50 (brs, 1H), 7.94 (d, J=8.4Hz, 2H), 7.86 (s, 1H), 7.57 (brs, 1H), 7.18-7.14 (m, 3H), 7.05 (d, J=8.4Hz, 1H), 7.00 (d, J=8.4Hz, 1H), 6.30 (m, 1H),6.14(m,2H),3.91(s,3H),3.84(s,3H),3.63(s,3H).

Embodiment 138:4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H-7- azaindoles - 2- formamides

A) .4- ((3- methoxyphenyls) amino) -1H-7- azaindole -2- Ethyl formates

Using the chloro- 1H-7- azaindoles -2- Ethyl formates of 4- and 3- aminoanisoles as initiation material, preparation process is with real A) methods described is applied in example 75, white solid 194mg is obtained, yield is 64%, mp:215-217℃.

¹H NMR(DMSO-d₆)δ(ppm):12.16 (brs, 1H), 8.93 (s, 1H), 8.05 (d, J=5.6Hz, 1H), 7.50 (s, 1H), 7.28 (t, J=8.4Hz, 1H), 6.93 (d, J=8.0Hz, 1H), 6.87 (s, 1H), 6.76 (d, J= 5.6Hz, 1H), 6.66 (d, J=8.4Hz, 1H), 4.32 (q, J=7.2Hz, 2H), 3.77 (s, 3H), 1.34 (t, J=7.2Hz, 3H).

B) .4- ((3- methoxyphenyls) amino) -1H-7- azaindole -2- formic acid

Using 4- ((3- methoxyphenyls) amino), -1H-7- azaindole -2- Ethyl formates is initiation materials, preparation process B) methods described in be the same as Example 3, obtains grey powder solid 103mg, yield is 100%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):13.20(brs,1H),12.68(brs,1H),9.80(s,1H),8.02(d,J =6.4Hz, 1H), 7.49 (s, 1H), 7.35 (t, J=8.0Hz, 1H), 6.95 (d, J=8.0Hz, 1H), 6.92 (s, 1H), (s, the 3H) of 6.80 (d, J=8.0Hz, 1H), 6.73 (d, J=6.4Hz, 1H), 3.77

C) .4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -1H-7- azaindole 2-carboxamides

Using 4- ((3- methoxyphenyls) amino) -1H-7- azaindole -2- formic acid and 4- methoxybenzenesulphoismides as starting C) methods described in raw material, preparation process be the same as Example 3, obtains micro-yellow powder shape solid 30mg, yield is 19%, mp:>280 ℃。

¹H NMR(DMSO-d₆)δ(ppm):9.32(brs,1H),7.97-7.87(m,2H),7.33(m,2H),7.04- 6.73(m,7H),3.81(s,3H),3.77(s,3H).

The preparation 22 of intermediate:The bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 1- methyl -7-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 7- and iodomethane as initiation material, system of the preparation process with intermediate Standby 5, white solid 436mg is obtained, yield is 93%, mp:75-76℃.

¹H NMR(CDCl₃)δ(ppm):7.32 (s, 1H), 7.19 (d, J=8.0Hz, 1H), 7.13 (d, J=8.0Hz, 1H), (t, J=7.2Hz, the 3H) of 4.46 (s, 3H), 4.39 (q, J=7.2Hz, 2H), 1.43

Embodiment 139:1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) .1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole -2-ethyl formates of -7-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 1- methyl -7- and 3- aminoanisoles as initiation material, prepared A) methods described in journey be the same as Example 75, obtains white solid 146mg, yield is 86%, mp:119-120℃.

¹H NMR(CDCl₃)δ(ppm):7.30 (s, 1H), 7.20 (t, J=8.4Hz, 1H), 7.15 (d, J=8.4Hz, 1H), 6.88 (d, J=7.2Hz, 1H), 6.69 (m, 2H), 6.53 (d, J=6.8Hz, 1H), 4.47 (s, 3H), 4.37 (q, J= 7.2Hz, 2H), 3.79 (s, 3H), 1.40 (t, J=7.2Hz, 3H)

B) .1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7-

Using 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole -2-ethyl formates of -7- as initiation material, system B) methods described in standby process be the same as Example 3, obtains off-white powder shape solid 90mg, yield is 98%, mp:184-185℃.

¹H NMR(DMSO-d₆)δ(ppm):13.00 (s, 1H), 8.34 (s, 1H), 7.61 (s, 1H), 7.17 (t, J= 8.0Hz, 2H), 6.84 (d, J=8.4Hz, 1H), 6.79 (d, J=8.0Hz, 1H), 6.75 (s, 1H), 6.49 (d, J=8.0Hz, 1H),4.35(s,3H),3.72(s,3H).

C) .1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains pale yellow powder shape solid 40mg, yield is 53%, mp:182-183℃。

¹H NMR(DMSO-d₆)δ(ppm):12.48 (brs, 1H), 8.35 (s, 1H), 7.94 (d, J=8.4Hz, 2H), 7.66 (s, 1H), 7.19-7.15 (m, 4H), 6.84 (d, J=8.4Hz, 1H), 6.75 (d, J=8.0Hz, 1H), 6.71 (s, 1H), 6.48 (d, J=8.4Hz, 1H), 4.11 (s, 3H), 3.85 (s, 3H), 3.71 (s, 3H)；¹³C NMR(100MHz,DMSO- d₆):δ163.09,160.09,159.63,144.06,136.99,135.29,131.01,130.00,129.88,128.79, 127.87,120.31,116.27,114.25,110.23,109.41,106.70,106.06,103.54,55.75,54.85, 33.89.HRMS(ESI):m/z,calcd.for C₂₄H₂₃N₃O₅ClS[M+H]⁺:500.1047,found 500.1036.

Embodiment 140:1- methyl -4- ((3- methoxyphenyls) amino) -7- chloro- N- (benzenesulfonyl) -1H- indoles -2- Formamide

It is former using 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and benzsulfamide as starting Material, c) methods described in preparation process be the same as Example 3, obtains pale yellow powder shape solid 89mg, yield is 89%, mp:172-173 ℃。

¹H NMR(DMSO-d₆)δ(ppm):12.66 (brs, 1H), 8.38 (s, 4H), 8.02 (d, J=7.4Hz, 1H), (7.76-7.720 m, 2H), 7.67 (t, J=7.6Hz, 1H), 7.20-7.16 (m, 2H), 6.86 (d, J=8.0Hz, 1H), 6.76 (d, J=8.0Hz, 1H), 6.73 (s, 1H), 6.50 (d, J=8.0Hz, 1H), 4.11 (s, 3H), 3.73 (s, 3H)

Embodiment 141:1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

With 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 3- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains pale yellow powder shape solid 75mg, yield is 71%, mp:145-146℃。

¹H NMR(acetone-d₆)δ(ppm):7.68 (d, J=8.0Hz, 1H), 7.64 (s, 1H), 7.59 (s, 1H), 7.56 (d, J=8.0Hz, 1H), 7.30 (d, J=8.4Hz, 1H), 7.21 (d, J=8.4Hz, 1H), 7.19 (t, J=8.4Hz, 1H), 6.93 (d, J=8.0Hz, 1H), 6.78-6.75 (m, 2H), 6.53 (d, J=8.4Hz, 1H), 4.25 (s, 3H), 3.91 (s,3H),3.76(s,3H)；¹³C NMR(100MHz,DMSO-d₆):δ160.09,159.67,159.14,144.02,140.87, 137.03,135.37,130.43,129.88,128.66,127.99,120.27,119.45,119.23,112.63,110.28, 109.66,106.67,106.11,105.87,103.58,55.65,54.85,33.91.

Embodiment 142:1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- hydroxyls benzenesulfonyl) -1H- Yin Diindyl -2- formamides

A) .4- ((t-Butyldimethylsilyl) epoxide) benzsulfamide

4- hydroxy benzene sulfonamides (200mg, 1.15mmol) are dissolved in DMF (5mL), addition TBDMSCl (260mg, 1.73mmol) with imidazole (118mg, 1.73mmol), react at room temperature, overnight, raw material disappears.Reaction solution is poured into frozen water In, white solid is separated out, is filtered, dries, obtains white crystal 260mg, yield is 79%, mp:114-115℃.

¹H NMR(CDCl₃)δ(ppm):7.81 (d, J=8.4Hz, 2H), 6.92 (d, J=8.4Hz, 2H), 4.74 (s, 2H),0.99(s,9H),0.24(s,6H).

B) .1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- ((4-TBDMSO) benzenesulfonyl) -1H- indoles - 2- formamides

With 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- ((fert-butyidimethylsilyls Silicon substrate) epoxide) benzsulfamide is initiation material, c) methods described in preparation process be the same as Example 3, obtains pale yellow powder shape solid 90mg, yield is 55%, mp:204-206℃.

¹H NMR(DMSO-d₆)δ(ppm):12.51 (s, 1H), 8.37 (s, 1H), 7.92 (d, J=8.8Hz, 2H), 7.68 (s, 1H), 7.20-7.16 (m, 2H), 7.10 (d, J=8.4Hz, 2H), 6.86 (d, J=8.4Hz, 1H), 6.76 (d, J= 8.0Hz, 1H), 6.72 (s, 1H), 6.49 (d, J=8.4Hz, 1H), 4.12 (s, 3H), 3.72 (s, 3H), 0.96 (s, 9H), 0.25(s,6H).

C) .1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- hydroxyls benzenesulfonyl) -1H- indoles -2- first Acid amides

By 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- ((4-TBDMSO) benzenesulfonyl) -1H- indoles - 2- formamides (60mg, 0.10mmol) are dissolved in anhydrous THF (2mL), add TBAF (48mg, 0.15mmol) THF solution (2mL), reacts at room temperature 30min, and raw material disappears.Solvent is evaporated off, EA (20mL) is added, watery hydrochloric acid is washed, column chromatography (D/M=40: 1) greenish yellow solid 35mg, is obtained, yield is 73%, mp:135-137℃.

¹H NMR(DMSO-d₆)δ(ppm):12.40 (s, 1H), 10.62 (s, 1H), 8.36 (s, 1H), 7.84 (d, J= 8.4Hz, 2H), 7.66 (s, 1H), 7.20-7.16 (m, 2H), 6.96 (d, J=8.8Hz, 2H), 6.85 (d, J=8.0Hz, 1H), (s, the 3H) of 6.76 (d, J=8.0Hz, 1H), 6.72 (s, 1H), 6.49 (d, J=8.0Hz, 1H), 4.12 (s, 3H), 3.72

Embodiment 143:1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- (2- methoxyethoxies) benzene sulphurs Acyl group) -1H- indole 2-carboxamides

A) .4- (2- methoxyethoxies) benzsulfamide

4- hydroxy benzene sulfonamides (100mg, 0.58mmol) are dissolved in DMF (6mL), 2- bromo-ethyl-methyl ethers are added (88mg, 0.64mmol) and C_S2CO₃(373mg, 1.15mmol), 50 DEG C of reaction 6h, raw material disappears.Reaction solution is poured into water In (20mL), EA extractions (20mL × 3), column chromatography (D/M=50:1) white crystal 140mg, is obtained, yield is 52%, mp:155- 157℃。

¹H NMR(DMSO-d₆)δ(ppm):7.73 (d, J=8.8Hz, 2H), 7.20 (s, 2H), 7.09 (d, J=8.8Hz, 2H), (s, the 3H) of 4.17 (t, J=4.4Hz, 2H), 3.67 (t, J=4.4Hz, 2H), 3.31

B) .1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- (2- methoxyethoxies) benzenesulfonyl) - 1H- indole 2-carboxamides

With 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- (2- methoxyethoxies) Benzsulfamide is c) methods described in initiation material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 58mg, yield For 51%, mp:179-180℃.

¹H NMR(DMSO-d₆)δ(ppm):12.49 (s, 1H), 8.35 (s, 1H), 7.92 (d, J=8.8Hz, 1H), 7.67 (s, 1H), 7.18-7.15 (m, 4H), 6.84 (d, J=8.4Hz, 1H), 6.75 (d, J=8.0Hz, 1H), 6.71 (s, 1H), 6.48 (d, J=8.4Hz, 1H), 4.20 (t, J=4.0Hz, 2H), 4.11 (s, 3H), 3.71 (s, 3H), 3.67 (t, J= 4.0Hz,2H),3.30(s,3H).

Embodiment 144:1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- (2- hydroxyl-oxethyls) benzene sulphurs Acyl group) -1H- indole 2-carboxamides

A) .4- (2- (TBDMSO) ethyoxyl) benzsulfamide

Using 4- hydroxy benzene sulfonamides and 2- (TBDMSO) bromoethanes as initiation material, in preparation process be the same as Example 143 a) Methods described, obtains white crystal 134mg, and yield is 35%, mp:103-105℃.

¹H NMR(DMSO-d₆)δ(ppm):7.73 (d, J=8.4Hz, 2H), 7.19 (s, 2H), 7.07 (d, J=8.4Hz, 2H), (s, the 6H) of 4.10 (t, J=4.4Hz, 2H), 3.93 (t, J=4.4Hz, 1H), 0.87 (s, 9H), 0.07

B) .1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- (2- (TBDMSO) ethyoxyl) benzene sulfonyls Base) -1H- indole 2-carboxamides and 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- (2- hydroxyl-oxethyls) Benzenesulfonyl) -1H- indole 2-carboxamides

With 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- (2- (TBDMSO) second Epoxide) benzsulfamide is initiation material, c) methods described, column chromatography (D/M=500 in preparation process be the same as Example 3:1) 1-, is obtained Methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- (2- (TBDMSO) ethyoxyl) benzenesulfonyl) -1H- indoles -2- Formamide：Faint yellow solid 4mg, mp:166-168℃；¹H NMR(acetone-d₆)δ(ppm):8.05 (d, J=8.8Hz, 2H), 7.56 (s, 1H), 7.21-7.16 (m, 3H), 6.93 (d, J=8.0Hz, 1H), 6.78-6.75 (m, 2H), 6.52 (d, J= 8.8Hz, 1H), 4.25 (s, 3H), 4.23 (t, J=4.4Hz, 1H), 4.04 (t, J=4.4Hz, 1H), 3.76 (m, 3H), 0.89 (s,9H),0.10(s,6H).

Column chromatography (D/M=20:1) 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- (2- hydroxyl second, is obtained Epoxide) benzenesulfonyl) -1H- indole 2-carboxamides, slightly yellow solid 78mg, mp:177-179℃；

¹H NMR(acetone-d₆)δ(ppm):8.05 (d, J=8.8Hz, 2H), 7.56 (s, 1H), 7.21-7.15 (m, 4H), 6.93 (d, J=8.4Hz, 1H), 6.78-6.75 (m, 2H), 6.53 (d, J=8.0Hz, 1H), 4.25 (s, 3H), 4.21 (t, J=4.4Hz, 2H), 3.90 (t, J=4.8Hz, 2H), 3.76 (s, 3H)

Embodiment 145:1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- (3- methoxy propoxies) benzene Sulfonyl) -1H- indole 2-carboxamides

A) .4- (3- methoxy propoxies) benzsulfamide

Using 4- hydroxy benzene sulfonamides and the bromo- 3- methoxy propanes of 1- as initiation material, in preparation process be the same as Example 143 a) Methods described, obtains white crystal 120mg, and yield is 47%, mp:94-96℃.

¹H NMR(CDCl₃)δ(ppm):7.85 (d, J=8.4Hz, 2H), 6.98 (d, J=8.8Hz, 2H), 4.74 (s, 2H), (t, J=6.0Hz, the 2H) of 4.12 (t, J=6.0Hz, 2H), 3.55 (t, J=6.4Hz, 2H), 3.56 (s, 3H), 2.07

B) .1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- (3- methoxy propoxies) benzenesulfonyl) - 1H- indole 2-carboxamides

With 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- (3- methoxy propyl oxygen Base) benzsulfamide is initiation material, c) methods described in preparation process be the same as Example 3, pale yellow powder shape solid 82mg is obtained, is produced Rate is 69%, mp:189-190℃.

¹H NMR(DMSO-d₆)δ(ppm):8.36 (s, 1H), 7.93 (d, J=8.8Hz, 2H), 7.68 (s, 1H), 7.20- (7.16 m, 4H), 6.86 (d, J=8.0Hz, 1H), 6.76 (d, J=8.0Hz, 1H), 6.72 (s, 1H), 6.49 (d, J= 8.4Hz, 1H), 4.14-4.12 (m, 5H), 3.72 (s, 3H), 3.47 (t, J=6.0Hz, 2H), 3.25 (s, 3H), 1.97 (quint, J=6.4Hz, 2H)

Embodiment 146:1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- (3- hydroxy propyloxy groups) benzene sulphurs Acyl group) -1H- indole 2-carboxamides

A) .4- (3- (TBDMSO) propoxyl group) benzsulfamide

Using 4- hydroxy benzene sulfonamides and 3- (TBDMSO) N-Propyl Bromides as initiation material, in preparation process be the same as Example 143 a) Methods described, obtains white crystal 447mg, and yield is 56%, mp:91-92℃.

¹H NMR(CDCl₃)δ(ppm):7.85 (d, J=8.4Hz, 2H), 6.98 (d, J=8.8Hz, 21H), 4.66 (s, 2H), 4.13 (t, J=6.4Hz, 2H), 3.80 (t, J=5.6Hz, 2H), 2.00 (t, J=6.0Hz, 2H), 0.88 (s, 9H), 0.04(s,6H).

B) .1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- (3- (TBDMSO) propoxyl group) benzene sulfonyls Base) -1H- indole 2-carboxamides

With 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- (3- (TBDMSO) third Epoxide) benzsulfamide is initiation material, c) methods described in preparation process be the same as Example 3, obtains slightly yellow solid 100mg, yield For 68%, mp:209-210℃.

¹H NMR(DMSO-d₆)δ(ppm):12.47 (s, 1H), 8.35 (s, 1H), 7.92 (d, J=8.8Hz, 2H), 7.67 (s, 1H), 7.16-7.14 (m, 4H), 6.84 (d, J=8.4Hz, 1H), 6.75 (d, J=7.6Hz, 1H), 6.71 (s, 1H), 6.48 (d, J=7.6Hz, 1H), 4.15-4.10 (m, 5H), 3.75-3.71 (m, 5H), 1.91 (quint, J=6.0Hz, 2H), 0.82(s,9H),0.00(s,6H).

C) .1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- (3- hydroxy propyloxy groups) benzenesulfonyl) - 1H- indole 2-carboxamides

With 1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- (3- (TBDMSO) propoxyl group) benzene sulfonyls Base) -1H- indole 2-carboxamides are initiation material, c) described in preparation process be the same as Example 142, yellow solid 41mg is obtained, is produced Rate is 82%, mp:170-172℃.

¹H NMR(DMSO-d₆)δ(ppm):12.47 (s, 1H), 8.36 (s, 1H), 7.92 (d, J=8.8Hz, 1H), 7.67 (s, 1H), 7.19-7.15 (m, 4H), 6.85 (d, J=8.4Hz, 1H), 6.75 (d, J=7.6Hz, 1H), 6.72 (m, 1H), 6.48 (d, J=8.0Hz, 1H), 4.14 (t, J=6.4Hz, 2H), 4.11 (s, 3H), 3.72 (s, 3H), 3.55 (t, J= 6.4Hz, 2H), 1.88 (quint, J=6.4Hz, 2H)；HRMS(ESI):m/z,calcd.for C₂₆H₂₇N₃O₆ClS[M+H]⁺: 544.1309,found 544.1298.

Embodiment 147:1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- isobutyl-benzenes sulfonyl) -1H- Indole 2-carboxamides and embodiment 148：1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (3- bromobenzenesulfonyls) - 1H- indole 2-carboxamides

A) .3- isobutyl-benzenes sulfonamide

3- bromophenylsulfonyls amine (500mg, 2.12mmol) is dissolved in toluene (30mL), Pd (dppf) Cl is sequentially added₂ (78mg, 0.11mmol) and Cs₂CO₃(2.06g, 6.36mmol, 6mL H₂O), after stirring, isobutaneboronic acid is added (648mg, 6.36mmol), under argon gas protection, back flow reaction 4h.Room temperature is cooled to, is concentrated, EA (30mL) dissolving residuals are added Thing, saturated common salt washing (20mL × 3) is washed (20mL × 2), column chromatography (D/M=100:1) white powdery solids, are obtained 400mg (impure), takes 60mg to prepare TLC separation, obtains white powdery solids 20mg, be target product, mp:95-97℃.

¹H NMR(CDCl₃)δ(ppm):7.75 (d, J=7.6Hz, 1H), 7.72 (s, 1H), 7.43 (t, J=7.6Hz, 1H), 7.36 (d, J=7.6Hz, 1H), 4.72 (s, 2H), 2.55 (d, J=7.2Hz, 2H), 1.90 (quint, J=6.8Hz, 1H), 0.92 (d, J=6.8Hz, 6H)

B) 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- isobutyl-benzenes sulfonyl) -1H- indoles -2- Formamide BJB-3418-1 and 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- bromobenzenesulfonyls) -1H- Yin Diindyl -2- formamides

With 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 3- isobutyl-benzene sulfonamide Mixture with 3- bromophenylsulfonyl amine is c) methods described, preparation TLC separation in initiation material, preparation process be the same as Example 3, is obtained 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- isobutyl-benzenes sulfonyl) -1H- indole 2-carboxamides: 55mg, mp:178-179℃；

¹H NMR(acetone-d₆)δ(ppm):7.94-7.93(m,2H),7.57-7.56(m,3H),7.21-7.16(m, 2H), 6.93 (d, J=8.0Hz, 1H), 6.78-6.76 (m, 2H), 6.53 (d, J=8.0Hz, 1H), 4.23 (s, 3H), 3.76 (s, 3H), 2.63 (d, J=7.2Hz, 2H), 1.98-1.89 (m, 1H), 0.92 (d, J=6.4Hz, 6H)；HRMS(ESI):m/z, calcd for C₂₇H₂₉N₃O₄ClS[M+H⁺]:526.1567,found526.1553.

Obtain 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- bromobenzenesulfonyls) -1H- indoles -2- formyls Amine:45mg, mp:230-233℃.

¹H NMR(acetone-d₆)δ(ppm):8.13 (s, 1H), 7.96 (d, J=7.6Hz, 1H), 7.60 (t, J= 8.0Hz, 1H), 7.38 (t, J=8.0Hz, 1H), 7.31 (s, 1H), 7.14 (t, J=8.4Hz, 1H), 7.03 (d, J=8.4Hz, 1H), 6.89-6.84 (m, 3H), 6.46 (d, J=8.0Hz, 1H), 4.37 (s, 3H), 3.75 (s, 3H)；HRMS(ESI):m/z, calcd for C₂₃H₂₀N₃O₄BrClS[M+H⁺]:550.0026,found 550.0004.

Embodiment 149：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- ((1-Boc- piperidin-4-yls) Epoxide) benzenesulfonyl) -1H- indole 2-carboxamides

A) .4- ((1-Boc- piperidin-4-yls) epoxide) benzsulfamide

4- hydroxy benzene sulfonamides (100mg, 0.58mmol) are dissolved in acetone (2mL), N-Boc-4- bromine piperidines is added (304mg, 1.15mmol) and K₂CO₃(160mg, 1.15mmol), microwave reaction (100w, 120 DEG C, 12h, 150psi), raw material portion Divide residue.Reaction solution is poured into water (20mL), EA extractions (20mL × 3), column chromatography (D/M=50:1) colorless oil, is obtained, Ether solidifies, filtering, obtains white crystal 60mg, yield is 24%, mp:185-186℃.

¹H NMR(CDCl₃)δ(ppm):7.86 (d, J=8.8Hz, 2H), 6.98 (d, J=8.8Hz, 2H), 4.72 (s, 2H),4.57(m,1H),3.71-3.67(m,2H),3.40-3.34(m,2H),1.94(m,2H),1.78(m,2H),1.47(s, 9H).

B) .1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- ((1-Boc- piperidin-4-yls) epoxide) benzene Sulfonyl) -1H- indole 2-carboxamides

With 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- ((1-Boc- piperidines - 4- yls) epoxide) benzsulfamide is initiation material, c) methods described in preparation process be the same as Example 3, obtains pale yellow powder shape solid 61mg, yield is 60%, mp:143-144℃.

¹H NMR(DMSO-d₆)δ(ppm):12.49 (s, 2H), 8.37 (s, 1H), 7.93 (d, J=8.8Hz, 2H), 7.68 (s, 1H), 7.22-7.16 (m, 4H), 6.86 (d, J=8.0Hz, 1H), 6.76 (d, J=8.4Hz, 1H), 6.72 (s, 1H), 6.49 (d, J=8.4Hz, 1H), 4.72 (s, 1H), 4.13 (s, 3H), 3.72 (s, 3H), 3.69-3.62 (m, 2H), 3.19- 3.13 (m, 2H), 1.95-1.93 (d, J=11.2Hz, 2H), 1.56-1.51 (m, 2H), 1.40 (s, 9H)；HRMS(ESI):m/ z,calcd for C₃₃H₃₈N₄O₇ClS[M+H⁺]:669.2150,found 669.2065.

Embodiment 150：1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- ((piperidin-4-yl) epoxide) benzene Sulfonyl) -1H- indole 2-carboxamides

By 1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- ((1-Boc- piperidin-4-yls) epoxide) benzene sulphurs Acyl group) -1H- indole 2-carboxamides (33mg, 0.049mmol) are dissolved in 4N HCl Isosorbide-5-Nitraes-dioxane (2mL), react at room temperature 2h, Raw material disappears.Concentration, adds ethanol (1mL), and filtering obtains faint yellow solid 30mg, yield is 100%, mp:230-233℃.

¹H NMR(DMSO-d₆)δ(ppm):12.52 (brs, 1H), 8.71 (s, 2H), 8.37 (s, 1H), 7.95 (d, J= 8.4Hz, 2H), 7.69 (s, 1H), 7.23 (d, J=8.8Hz, 2H), 7.20-7.15 (m, 2H), 6.86 (d, J=8.8Hz, 1H), 6.76 (d, J=8.4Hz, 1H), 6.72 (s, 1H), 6.49 (d, J=8.0Hz, 1H), 4.81 (s, 1H), 4.13 (s, 3H), 3.72 (s,3H),3.24(brs,2H),3.09(brs,2H),2.13(m,2H),1.85-1.83(m,2H).

Embodiment 151：1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- (2- morpholines ethyoxyl) benzene sulphurs Acyl group) -1H- indole 2-carboxamides

A) .4- (2- morpholines ethyoxyl) benzsulfamide

Using 4- hydroxy benzene sulfonamides and 4- (2- bromoethyls) morpholine as initiation material, in preparation process be the same as Example 143 a) Methods described, obtains white crystal 244mg, and yield is 74%, mp:168-169℃.

¹H NMR(CDCl₃)δ(ppm):7.86 (d, J=8.8Hz, 2H), 6.99 (d, J=8.4Hz, 2H), 4.74 (s, 2H),4.20(s,2H),3.76(s,4H),2.86(s,2H),2.61(s,4H).

B) .1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- (2- morpholines ethyoxyl) benzenesulfonyl) - 1H- indole 2-carboxamides

With 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- (2- morpholines ethyoxyl) Benzsulfamide is c) methods described in initiation material, preparation process be the same as Example 3, obtains slightly yellow solid 87mg, yield is 69%, mp:137-139℃。

¹H NMR(acetone-d₆)δ(ppm):8.03 (d, J=7.6Hz, 2H), 7.55 (s, 1H), 7.18-7.11 (m, 4H), 6.93 (d, J=7.6Hz, 1H), 6.80-6.77 (m, 2H), 6.52 (d, J=6.8Hz, 1H), 4.29-4.25 (m, 5H), 3.76(s,3H),3.66(m,4H),2.91(s,2H),2.67(s,4H)；HRMS(ESI):m/z,calcd for C₂₉H₃₂N₄O₆ClS[M+H⁺]:599.1731,found 599.1700.

The preparation 23 of intermediate：The bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 1- ethyls -7-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 7- and bromoethane as initiation material, system of the preparation process with intermediate Standby 5, white solid 207mg is obtained, yield is 95%, mp:93-95℃.

¹H NMR(CDCl₃)δ(ppm):7.35 (s, 1H), 7.21 (d, J=8.0Hz, 1H), 7.14 (d, J=8.0Hz, 1H), (q, J=7.6Hz, the 1H) of 5.05 (q, J=7.2Hz, 1H), 4.40 (q, J=7.2Hz, 1H), 1.44

Embodiment 152：1- ethyls -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) .1- ethyls -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole -2-ethyl formates of -7-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 1- ethyls -7- and 3- aminoanisoles as initiation material, prepared A) methods described in journey be the same as Example 75, obtains white solid 100mg, yield is 54%, mp:120-122℃.

¹H NMR(CDCl₃)δ(ppm):7.62 (m, 1H), 7.42 (m, 1H), 7.32 (m, 1H), 7.21 (d, J=8.0Hz, 1H), 7.16 (d, J=8.8Hz, 1H), 6.88 (d, J=8.0Hz, 1H), 6.71 (d, J=8.4Hz, 1H), 6.53 (d, J= 8.0Hz, 1H), 5.05 (q, J=6.8Hz, 2H), 4.37 (q, J=6.8Hz, 2H), 3.79 (s, 3H), 1.47 (t, J=7.2Hz, 3H), 1.41 (t, J=7.2Hz, 3H)

B) .1- ethyls -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7-

With 1- ethyls -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole -2-ethyl formates initiation materials of -7-, prepare B) methods described in process be the same as Example 3, obtains off-white powder shape solid 80mg, yield is 96%, mp:189-191℃.

¹H NMR(DMSO-d₆)δ(ppm):13.00(s,1H),8.33(s,1H),7.63(s,1H),7.19-7.16(m, 2H), 6.85 (d, J=8.4Hz, 1H), 6.80 (d, J=8.0Hz, 1H), 7.56 (s, 1H), 6.49 (d, J=8.0Hz, 1H), (t, J=6.8Hz, the 3H) of 4.97 (q, J=6.8Hz, 2H), 3.72 (s, 3H), 1.35

C) .1- ethyls -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

With 1- ethyls -4- ((3- methoxyphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- methoxybenzenesulphoismides For initiation material, c) methods described in preparation process be the same as Example 3 obtains pale yellow powder shape solid 53mg, yield is 60%, mp:197-199℃。

¹H NMR(DMSO-d₆)δ(ppm):12.46(s,1H),8.37(s,1H),7.96(m,2H),7.71(s,1H), 7.18(m,4H),6.87(m,1H),6.74(m,3H),6.50(m,1H),4.69(m,2H),3.86(s,3H),3.73(s,3H), 1.22(m,3H).

Embodiment 153：1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) the chloro- N- of -7- (4- methoxybenzene sulphonyl Base) -1H- indole 2-carboxamides

A) .1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) the chloro- 1H- indole -2-ethyl formates of -7-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 1- methyl -7- and 3- methoxyl group -4- chloroanilines as initiation material, system A) methods described in standby process be the same as Example 75, obtains white solid 130mg, yield is 52%, mp:120-122℃.

¹H NMR(CDCl₃)δ(ppm):7.26-7.16(m,3H),7.16(m,2H),6.83(m,1H),6.70(m,1H), 6.64 (m, 1H), 5.77 (m, 1H), 4.47 (s, 3H), 4.36 (q, J=7.2Hz, 2H), 3.84 (s, 3H), 1.40 (t, J= 7.2Hz,3H).

B) .1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7-

It is former by starting of 1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) the chloro- 1H- indole -2-ethyl formates of -7- Material, b) methods described in preparation process be the same as Example 3, obtains pale yellow powder shape solid 92mg, yield is 99%, mp:230-232 ℃。

¹H NMR(DMSO-d₆)δ(ppm):13.04 (s, 1H), 8.48 (s, 1H), 7.58 (s, 1H), 7.26 (d, J= 8.4Hz, 1H), 7.18 (d, J=8.4Hz, 1H), 6.94 (s, 1H), 6.88 (d, J=8.4Hz, 1H), 6.78 (d, J=8.4Hz, 1H),4.36(s,3H),3.81(s,3H).

C) .1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

With 1- methyl -4- ((3- methoxyl group -4- chlorphenyls) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- methoxybenzenes Sulfonamide is c) methods described in initiation material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 70mg, yield is 97%, mp:188-189℃.

¹H NMR(DMSO-d₆)δ(ppm):8.51 (s, 1H), 7.95 (d, J=8.8Hz, 2H), 7.66 (s, 1H), 7.26 (d, J=8.8Hz, 1H), 7.21-7.16 (m, 3H), 6.91-6.88 (m, 2H), 6.74 (d, J=8.4Hz, 1H), 4.13 (s, 3H),3.86(s,3H),3.80(s,3H).

Embodiment 154：1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) chloro- N- of -7- (4- MethOxybenzenesulfonyls) - 1H- indole 2-carboxamides

A) .1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole -2-ethyl formates of -7-

Using the bromo- 1H- indole -2-ethyl formates of the chloro- 4- of 1- methyl -7- and the fluoro- 3- chloroanilines of 4- as initiation material, prepared A) methods described in journey be the same as Example 75, obtains white solid 160mg, yield is 74%, mp:129-131℃.

¹H NMR(CDCl₃)δ(ppm):7.64-7.62(m,1H),7.43-7.42(m,1H),7.24(s,1H),7.17- 7.04 (m, 2H), 6.94 (m, 1H), 6.73 (m, 1H), 4.47 (s, 3H), 4.37 (q, J=7.2Hz, 2H), 1.40 (t, J= 7.2Hz,3H).

B) .1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole-2-carboxylic acids of -7-

With 1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole -2-ethyl formates initiation materials of -7-, prepare B) methods described in process be the same as Example 3, obtains pale yellow powder shape solid 87mg, yield is 92%, mp:235-236℃.

¹H NMR(DMSO-d₆)δ(ppm):13.05(s,1H),8.46(s,1H),7.55(s,1H),7.34-7.28(m, 2H), (s, the 3H) of 7.20-7.15 (m, 2H), 6.79 (d, J=8.0Hz, 1H), 4.36

C) .1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- indoles - 2- formamides

With 1- methyl -4- ((the fluoro- 3- chlorphenyls of 4-) amino) the chloro- 1H- indole-2-carboxylic acids of -7- and 4- methoxybenzene sulphonyl Amine is c) methods described in initiation material, preparation process be the same as Example 3, obtains pale yellow powder shape solid 46mg, yield is 78%, mp:241-242℃。

¹H NMR(DMSO-d₆)δ(ppm):12.49 (brs, 1H), 8.48 (s, 1H), 7.93 (d, J=8.4Hz, 2H), 7.60 (s, 1H), 7.31 (t, J=9.2Hz, 1H), 7.23 (d, J=6.4Hz, 1H), 7.19 (d, J=8.4Hz, 1H), 7.16 (d, J=8.8Hz, 2H), 7.11-7.09 (m, 1H), 6.79 (d, J=8.4Hz, 1H), 4.12 (s, 3H), 3.85 (s, 3H)； HRMS(ESI):m/z,calcd.for C₂₃H₁₉N₃O₄FClS[M+H]⁺:522.0457,found 522.0448.

Embodiment 155：4,6- bis- chloro- N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) the chloro- 1H- indole-2-carboxylic acids of .4,6- bis-

With the chloro- 1H- indole -2-ethyl formates of 4,6- bis- for initiation material, the b) side in preparation process be the same as Example 3 Method, obtains off-white powder shape solid 160mg, yield is 100%, mp:226-228℃.

¹H NMR(DMSO-d₆)δ(ppm):12.31 (s, 1H), 7.44 (m, 1H), 7.27 (d, J=1.8Hz, 1H), 7.07- (t, J=7.2Hz, the 2H) of 7.06 (m, 1H), 6.86 (t, J=7.6Hz, 1H), 3.24 (t, J=7.6Hz, 2H), 2.56

B) .4,6- bis- chloro- N- (benzenesulfonyl) -1H- indole 2-carboxamides

With the chloro- 1H- indole-2-carboxylic acids of 4,6- bis- and 4- methoxybenzenesulphoismides for initiation material, preparation process is with implementation C) methods described in example 3, obtains white powdery solids 52mg, yield is 36%, mp:294-295℃.

¹H NMR(DMSO-d₆)δ(ppm):12.62 (brs, 1H), 12.25 (s, 1H), 7.96 (d, J=8.8Hz, 2H), (s, the 3H) of 7.63 (s, 1H), 7.39 (s, 1H), 7.28 (s, 1H), 7.16 (d, J=8.4Hz, 1H), 3.85

The preparation 24 of intermediate：4- nitros -1H- benzimidazolyl-2 radicals-formic acid

A) .2- trichloromethyls -4- nitros -1H- benzimidazoles

3- nitro-o-phenylenediamines (500mg, 3.27mmol) are dissolved in ether (12mL) and DCM (8mL), three chloroethenes are added Acid imide methyl esters (720mg, 4.08mmol), after stirring, adds trifluoroacetic acid (1.79g, 15.67mmol), room temperature reaction 1h, raw material disappears substantially.Solvent is evaporated off, EA (20mL) is added, washes (20mL × 2), column chromatography (P/E=20:1), obtain yellowish Color pulverulent solids 834mg, yield is 91%, mp:128-129℃.

¹H NMR(acetone-d₆)δ(ppm):12.97 (brs, 1H), 8.35 (d, J=8.1Hz, 1H), 8.26 (d, J= 7.8Hz, 1H), 7.61 (t, J=8.1Hz, 2H)

B) .4- nitros -1H- benzimidazolyl-2 radicals-formic acid

Under ice-water bath, by 2N NaOH solutions (975mg, 24.4mmol, 12mL H₂O) instill 2- trichloromethyl -4- nitros - In 1H- benzimidazoles (1.37g, 4.87mmol), stirring reacts at room temperature 2h, reactant is in the pasty state.PH is adjusted with 1N watery hydrochloric acid 2-3, off-white color is changed into from yellow, is filtered, and is dried, is obtained off-white powder shape solid 988mg, yield is 98%, mp:227-228 ℃。

¹H NMR(DMSO-d₆)δ(ppm):8.46 (s, 1H), 8.15 (d, J=7.8Hz, 2H), 7.42 (t, J=7.8Hz, 1H).

Embodiment 156：4- nitros-(N- sulfonyls) -1H- benzimidazolyl-2 radicals-formamide

Using 4- nitros -1H- benzimidazolyl-2 radicals-formic acid and benzsulfamide as initiation material, in preparation process be the same as Example 3 c) Methods described, obtains white powdery solids 135mg, and yield is 81%, mp:227-229℃.

¹H NMR(DMSO-d₆)δ(ppm):8.27 (d, J=8.0Hz, 1H), 8.18 (d, J=8.4Hz, 1H), 8.06 (d, J =7.6Hz, 2H), 7.73 (t, J=7.2Hz, 1H), 7.66 (t, J=7.6Hz, 2H), 7.56 (d, J=8.0Hz, 2H)

Embodiment 157：4- amino-(N- sulfonyls) -1H- benzimidazolyl-2 radicals-ammonium formate

4- nitros-(N- sulfonyls) -1H- benzimidazolyl-2 radicals-formamide (190mg, 0.55mmol) is dissolved in ethanol In (25mL), 10%Pd/C (55mg) is added, normal pressure hydrogenation, overnight, raw material disappear.Filtering, concentration, EA recrystallizations obtain brown Pulverulent solids 147mg, yield 85%, mp:235-237℃.

¹H NMR(DMSO-d₆)δ(ppm):7.94 (d, J=7.2Hz, 2H), 7.52-7.47 (m, 3H), 7.20 (t, J= 8.0Hz, 1H), 6.78 (d, J=8.0Hz, 1H), 6.62 (d, J=8.0Hz, 1H)

The preparation 25 of intermediate：The chloro- 1H- benzimidazolyl-2 radicals-Ethyl formates of 1- methyl -4- amino -7-

A) .4- nitros -1H- benzimidazolyl-2 radicals-Ethyl formate

2- trichloromethyl -4- nitro -1H- benzimidazoles (4.0g, 14.26mmol) are dissolved in ethanol (40mL), are added Sodium carbonate (3.02g, 28.5mmol), flow back 48h, and raw material disappears.DCM (50mL) and methanol (10mL) is added, is filtered out not Molten thing.Concentration, EA recrystallizations, obtains brown solid 3.05g, yield is 91%, mp:146-147℃.

¹H NMR(CDCl₃)δ(ppm):11.19 (brs, 1H), 8.35 (d, J=8.4Hz, 1H), 8.29 (d, J=8.1Hz, 1H),7.55-7.49(m,1H),4.63-4.56(m,2H),1.56-1.50(m,3H).

B) .1- methyl -4- nitros -1H- benzimidazolyl-2 radicals-Ethyl formate

4- nitros -1H- benzimidazolyl-2 radicals-Ethyl formate (1.5g, 6.38mmol) is dissolved in DMF (20mL), adds carbonic acid Caesium (4.13g, 12.76mmol) and iodomethane (1.36g, 9.57mmol), react at room temperature 48h, and raw material is remaining on a small quantity.By reaction solution Pour into frozen water, filter, obtain yellow solid, EA recrystallizations obtain slightly yellow solid 1.29g, yield is 81%, mp:125-126 ℃。

¹H NMR(CDCl₃)δ(ppm):8.24 (d, J=8.0Hz, 1H), 7.80 (d, J=8.4Hz, 1H), 7.55 (t, J= 8.0Hz, 1H), 4.56 (q, J=7.2Hz, 2H), 4.25 (s, 3H), 1.51 (t, J=7.2Hz, 3H)

C) .1- methyl -4- amino -1H- benzimidazolyl-2 radicals-Ethyl formate

1- methyl -4- nitros -1H- benzimidazolyl-2 radicals-Ethyl formate (2.60g, 10.43mmol) is dissolved in ethanol In (40mL), 10%Pd/C (260mg) is added, normal pressure hydrogenation, overnight, raw material disappear.Filtering, concentration, column chromatography (P/E=4: 1-D/M=40:1) off-white powder shape solid 2.10g, yield 92%, mp, are obtained:114-116℃.

¹H NMR(CDCl₃)δ(ppm):7.22 (t, J=8.0Hz, 1H), 6.77 (d, J=8.4Hz, 1H), 6.55 (d, J= 7.6Hz, 1H), 4.53 (q, J=7.2Hz, 2H), 4.18 (s, 3H), 1.49 (t, J=7.2Hz, 3H)

D) the chloro- 1H- benzimidazolyl-2 radicals-Ethyl formates of .1- methyl -4- amino -7-

1- methyl -4- amino -1H- benzimidazolyl-2 radicals-Ethyl formate (600mg, 2.74mmol) is dissolved in DMF (20mL), NCS (402mg, 3.01mmol) DMF solution (10mL) is added, 1.5h is reacted at room temperature, raw material disappears.Column chromatography (P/E=2: 1), obtain：Point 1, slightly yellow solid 73mg；Point 2, faint yellow solid 215mg；Point 3, orange solid 353mg, are target product, production Rate is 51%, mp:141-143℃.

¹H NMR(CDCl₃)δ(ppm):7.23 (s, 1H), 4.84 (s, 2H), 4.53 (q, J=7.2Hz, 2H), 4.45 (s, 3H), 1.48 (t, J=7.2Hz, 3H) (point 1)

¹H NMR(CDCl₃)δ(ppm):7.28 (d, J=8.8Hz, 1H), 7.70 (d, J=8.8Hz, 1H), 4.89 (s, 2H), (t, J=7.2Hz, 3H) of 4.54 (q, J=7.2Hz, 2H), 4.09 (s, 3H), 1.49 (point 2)

¹H NMR(CDCl₃)δ(ppm):7.11 (d, J=8.0Hz, 1H), 6.44 (d, J=8.4Hz, 1H), 4.78 (brs, 2H), (t, J=7.2Hz, 3H) of 4.53 (q, J=7.2Hz, 2H), 4.47 (s, 3H), 1.49 (point 3)

Embodiment 158：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- MethOxybenzenesulfonyls) -1H- Indole 2-carboxamides

A) the chloro- 1H- benzimidazolyl-2 radicals-Ethyl formates of .1- methyl -4- ((3- methoxyphenyls) amino) -7-

It is former using the chloro- 1H- benzimidazolyl-2 radicals-Ethyl formates of 1- methyl -4- amino -7- and 3- methoxyl group -1- bromobenzenes as starting Material, a) methods described in preparation process be the same as Example 75, obtains yellow solid 146mg, yield is 46%, mp:89-91℃.

¹H NMR(CDCl₃)δ(ppm):7.26-7.21 (m, 1H), 7.18 (d, J=8.8Hz, 1H), 7.08 (s, 1H), 7.05 (d, J=8.4Hz, 1H), 6.86 (d, J=8.4Hz, 1H), 6.84 (s, 1H), 6.58 (d, J=8.4Hz, 1H), 4.55 (q, J=7.2Hz, 2H), 4.50 (s, 3H), 3.81 (s, 3H), 1.50 (t, J=7.2Hz, 3H)

B) the .1- methyl -4- chloro- 1H- benzimidazolyl-2 radicals-formic acid of ((3- methoxyphenyls) amino) -7- and 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- benzimidazoles mixtures of -7-

With the chloro- 1H- benzimidazolyl-2 radicals-Ethyl formate initiation materials of 1- methyl -4- ((3- methoxyphenyls) amino) -7-, B) methods described in preparation process be the same as Example 3, obtains pale yellow powder shape solid 70mg, yield is 81%, hydrogen spectrum and high-resolution Mass spectrum is shown as mixture, and ratio is about 9:1, mp:125-126℃.

¹H NMR(DMSO-d₆)δ(ppm):8.15 (s, 1H), 7.15 (t, J=8.0Hz, 1H), 7.10 (d, J=8.0Hz, 1H), 7.00 (d, J=8.0Hz, 1H), 6.90-6.84 (m, 2H), 6.46 (d, J=7.2Hz, 1H), 4.07 (s, 3H), 3.71 (s,3H).

With the 1- methyl -4- chloro- 1H- benzimidazolyl-2 radicals-formic acid of ((3- methoxyphenyls) amino) -7- and 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- 1H- benzimidazoles mixtures of -7- and 4- methoxybenzenesulphoismides are initiation material, are prepared C) methods described in process be the same as Example 3, obtains pale yellow powder shape solid 48mg, yield is 64%, mp:206-207℃.

¹H NMR(DMSO-d₆)δ(ppm):8.31 (s, 1H), 7.99 (d, J=7.5Hz, 2H), 7.24 (d, J=8.5Hz, 1H), 7.22 (d, J=7.5Hz, 1H), 7.18 (d, J=7.5Hz, 2H), 7.06 (d, J=7.5Hz, 1H), 6.90 (d, J= 7.5Hz, 1H), 6.87 (s, 1H), 6.56 (d, J=7.0Hz, 1H), 4.24 (s, 3H), 3.86 (s, 3H), 3.75 (s, 3H)； HRMS(ESI):m/z,calcd.for C₂₃H₂₂N₄O₅ClS[M+H]⁺:501.0999,found 501.0985.

Embodiment 159:The chloro- 7- of 4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -3- methyl-benzene And furans -2- formamides

A) 2- (the chloro- phenoxy groups of the bromo- 5- of 2-)-ethyl 3-oxobutanoate

In 2- bromo-5-chlorophenols (1.495g, 7.2mmol) ethanol (13mL) solution, cesium carbonate is slowly added to Half an hour is stirred at room temperature in ethanol (33mL) solution of (2.58g, 7.92mmol), mixture, adds 2- chloroacetyl acetacetic esters (1.4g, 8.43mmol), is stirred at 50 DEG C.Mixture is cooled to room temperature, column chromatography (petrol ether/ethyl acetate=60:1), obtain Colorless oil 1.4g, yield 54%；¹H NMR(CDCl₃)δ(ppm):11.35 (s, 0.45H), 7.51 (d, J=8.0Hz, 0.45H), 7.48 (d, J=8.0Hz, 0.55H), 6.94 (d, J=8.0Hz, 0.45H), 6.89 (d, J=8.0Hz, 0.55H), 6,78 (s, 0.55H), 6,74 (s, 0.45H), 5.02 (s, 0.55H), 4.33 (q, J=7.2Hz, 0.45H), 4.22 (q, J=7.2Hz, 0.55H), 2.05 (s, 0.45H), 1.53 (s, 0.55H), 1.31 (t, J=6.8Hz, 0.45H), 1.19 (t, J=7.2Hz, 0.55H)。

B) the chloro- 3- methyl benzofurans -2- Ethyl formates of the bromo- 4- of 7-

2- (the chloro- phenoxy groups of the bromo- 5- of 2-)-ethyl 3-oxobutanoate (168mg, 0.5mmol) is dissolved in anhydrous methylene chloride (8mL), is down to 0 DEG C, CF is slowly added thereto₃SO₃After H (1.2mL), 0 DEG C of stirring 50min, move to room temperature and continue to react, directly Disappeared to raw material.Reaction solution is down to 0 DEG C again, adds saturated sodium bicarbonate aqueous solution (7mL) and reaction is quenched, separate organic layer, Water layer is extracted three times with dichloromethane, with (petrol ether/ethyl acetate=10：1) after recrystallizing, white solid 135mg is obtained, is received Rate 85%；m.p.68-69℃；¹H NMR(CDCl₃)δ(ppm):7.48 (d, J=8.4Hz, 1H), 7.13 (d, J=8.4Hz, 1H), 4.46 (q, J=7.2Hz, 2H), 2.80 (s, 3H), 1.41 (t, J=8Hz, 3H).

C) the chloro- 7- of 4- (3- methoxybenzenes amino) -3- methyl benzofuran -2- Ethyl formates

The chloro- 3- methyl benzofurans -2- Ethyl formates (25mg, 0.08mmol) of the bromo- 4- of 7- are dissolved in dimethylbenzene (0.6mL) In, sequentially add Pd₂(dba)₃(7mg, 0.008mmol), tri-butyl phosphine tetrafluoroborate (4.6mg, 0.016mmol) and K₃PO₄(51mg, 0.242mmol), after stirring, adds m-anisidine (29mg, 0.24mmol), micro- under argon gas protection 140 DEG C of reaction 45min of ripple, raw material disappears, column chromatography (P/E=20:1) brown solid 30mg, yield 46% are obtained；m.p.98- 100℃；¹H NMR(DMSO-d₆)δ(ppm):8.39 (s, 1H), 7.25 (q, J=8.0Hz, 2H), 7.15 (t, J=8.0Hz, 1H), 6.70~6.67 (m, 2H), 6.46 (d, J=8.0Hz, 1H), 4.37 (q, J=6.8Hz, 2H), 3.70 (s, 3H), 2.77 (s, 3H), 1.34 (t, J=6.8Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₉H₁₈ClNO₄[M+H]⁺:360.0997, found 360.0983。

D) the chloro- 7- of 4- (3- methoxybenzenes amino) -3- methyl benzofuran -2- formic acid

The chloro- 7- of 4- (3- methoxybenzenes amino) -3- methyl benzofuran -2- Ethyl formates (120mg, 0.33mmol) is molten In THF (2.4mL) and the in the mixed solvent of ethanol (4.8mL), NaOH (67mg, 1.67mmol) water (2.4mL) is added dropwise dropwise 5.5h is stirred at room temperature in solution, reactant mixture, and raw material disappears.THF and ethanol is evaporated off, adds 6mL water, is adjusted to 1M watery hydrochloric acid PH is 2, there is yellow solid precipitation, and suction filtration is dried, obtains greenish yellow solid 103mg, yield 93%；m.p.192-193℃；¹H NMR(CDCl₃)δ(ppm):8.39 (s, 1H), 7.25 (m, 2H), 7.15 (t, J=8.0Hz, 1H), 6.70~6.67 (m, 2H), 6.46 (d, J=8.0Hz, 1H), 3.70 (s, 3H), 2.77 (s, 3H)；HRMS(ESI),[M-H]^-:m/z,330.0304。

E) the chloro- 7- of 4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -3- methl-benzofurans -2- Formamide

Under ice bath, by the chloro- 7- of 4- (3- methoxybenzenes amino) -3- methyl benzofuran -2- formic acid (57mg, 0.17mmol) Be dissolved in DCM (10mL), add after triethylamine (34mg, 0.34mmol), stirring 0.5h, add HATU (99mg, 0.26mmol) and DMAP (10mg, 0.085mmol) and to methoxybenzenesulphoismide (48mg, 0.26mmol), stirring to raw material disappears.Column chromatography (DCM/ methanol=40:1) yellow solid 38mg, yield 45% are obtained；m.p.176-178℃；¹H NMR(DMSO-d₆)δ(ppm): 11.96 (s, 1H), 8.11 (s, 1H), 7.97 (d, J=8.0Hz, 2H), 7.24 (m, 2H), 7.18 (d, J=8.0Hz, 3H), 6.85 (d, J=8.0Hz, 1H), 6.80 (s, 1H), 6.60 (d, J=8.0Hz, 1H), 3.86 (s, 3H), 3.76 (s, 3H), 2.64 (s,3H)；HRMS(ESI):m/z,calcd for C₂₄H₂₁ClN₂O₆S[M+H]⁺:501.0882,found 501.0872。

Embodiment 160:The chloro- 7- of 4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -3- methyl-benzene Bithiophene -2- formamides

A) the chloro- 3- methyl benzothiophenes -2- Ethyl formates of 4-

At 0 DEG C, mercapto is added in dry toluene (14.5mL) solution of the fluoro- 6- chloro-acetophenones (2.5g, 14.5mmol) of 2- Ethyl (2mL, 21.8mmol) and DBU (4.35mL, 29mmol), are slowly increased to room temperature, continue to stir 5h, add water (70mL) is quenched reaction, EA extractions (2x 100mL), pickling, washing, is recrystallized to give white solid 4.83g, yield 65%, m.p.96-97℃。¹H NMR(CDCl₃)δ(ppm):7.69 (d, J=8.0Hz, 1H), 7.37 (t, J=8.0Hz, 1H), 7.31 (d, J=8.0Hz, 1H), 4.39 (q, J=7.2Hz, 2H), 3.12 (s, 3H), 1.41 (t, J=7.2Hz, 3H).

B) the chloro- 3- methyl -7- nitros benzothiophene -2- Ethyl formates of 4-

The chloro- 3- methyl benzothiophenes -2- Ethyl formates (893mg, 3.5mmol) of 4- are dissolved in CF₃COOH (13mL), is cooled to -5 DEG C, add NaNO₃(894mg, 10.5mmol), mixture keeps 0 DEG C of reaction 7h, is poured into 34mL water, saturated sodium bicarbonate is adjusted PH to 8, suction filtration, filter cake column chromatography (P/E=10:1) off-white powder 520mg, yield 50% are obtained；m.p.153-154℃.¹H NMR(CDCl₃)δ(ppm):8.38 (d, J=8.0Hz, 1H), 7.55 (d, J=8.0Hz, 1H), 4.44 (q, J=7.2Hz, 2H), 3.14 (s, 3H), 1.47 (t, J=6.8Hz, 3H).

C) the chloro- 3- methyl benzothiophenes -2- Ethyl formates of 7- amino -4-

The chloro- 3- methyl -7- nitros benzothiophene -2- Ethyl formates (100mg, 0.33mmol) of 4- are dissolved in ethyl acetate (10mL), adds 10%Pd/C (30mg), normal temperature and pressure hydrogenation 12h, filters, concentration, column chromatography (petrol ether/ethyl acetate= 8:1) off-white powder 56mg, yield 60%, are obtained.¹H NMR(CDCl₃)δ(ppm):7.20 (d, J=8.0Hz, 1H), 6.65 (d, J=8.0Hz, 1H), 4.39 (q, J=7.2Hz, 2H), 3.85 (brs, 2H), 3.10 (s, 3H), 1.42 (t, J=6.8Hz, 3H)。

D) the chloro- 7- of 4- (3- methoxybenzenes amino) -3- methyl benzothiophene -2- Ethyl formates

The chloro- 3- methyl benzothiophenes -2- Ethyl formates (227mg, 0.84mmol) of 7- amino -4- are dissolved in dimethylbenzene In (9mL), Pd is sequentially added₂(dba)₃(77mg, 0.084mmol), tri-butyl phosphine tetrafluoroborate (49mg, 0.168mmol) And K₃PO₄(535mg, 2.52mmol), after stirring, adds meta-methoxy bromobenzene (472mg, 2.52mmol), argon gas protection Under, 110 DEG C of reaction 12h, raw material disappears, column chromatography (PE/EA=20:1) red solid 39.5mg is obtained, yield 13%, m.p.164-165℃。¹H NMR(CDCl₃)δ(ppm):7.32~7.17 (m, 3H), 6.61 (m, 1H), 6.55 (m, 2H), 4.38 (q, J=7.2Hz, 2H), 3.77 (s, 3H), 3.12 (s, 3H), 1.40 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₉H₁₈ClNO₃S[M+H]⁺:376.0769,found 376.0754。

E) the chloro- 7- of 4- (3- methoxybenzenes amino) -3- methyl benzothiophene -2- formic acid

The chloro- 7- of 4- (3- methoxybenzenes amino) -3- methyl benzothiophene -2- Ethyl formates (60mg, 0.16mmol) is molten In THF (1.2mL) and the in the mixed solvent of ethanol (2.4mL), the water (1.2mL) that NaOH (32mg, 0.8mmol) is added dropwise dropwise is molten 4h is stirred at room temperature in liquid, reactant mixture, and raw material disappears.THF and ethanol is evaporated off, 5mL water is added, being adjusted to pH with 1M watery hydrochloric acid is 2, there is greenish yellow solid precipitation, suction filtration is dried, obtains greenish yellow solid 49mg, yield 88%, m.p.200-202 DEG C.¹H NMR (CDCl₃)δ(ppm):7.35~7.15 (m, 3H), 6.65~6.52 (m, 3H), 4.39 (q, J=7.2Hz, 2H), 3.79 (s, 3H),3.11(s,3H)。HRMS(ESI),[M-H]^-:m/z,346.0056。

F) the chloro- 7- of 4- ((3- methoxyphenyls) amino)-N- (4- MethOxybenzenesulfonyls) -3- methyl-benzothlophenes -2- Formamide

By the chloro- 7- of 4- (3- methoxybenzenes amino) -3- methyl benzothiophene -2- formic acid (50mg, 0.14mmol), HATU (98mg, 0.26mmol), DMAP (9mg, 0.07mmol), triethylamine (73mg, 0.72mmol) is dissolved in DCM (5mL), stirs 2h Afterwards, add to methoxybenzenesulphoismide (48mg, 0.26mmol), room temperature reaction is stayed overnight, column chromatography (EA:Methanol=20:1) obtain grey White powder 30mg, yield 48%, m.p.284-285 DEG C.¹H NMR(CDCl₃)δ(ppm):8.00 (s, 1H), 7.56 (d, J= 8.0Hz, 2H), 7.28 (d, J=8.0Hz, 1H), 7.12 (m, J=8.0Hz, 2H), 6.90 (d, J=8.0Hz, 2H), 6.56 (d, J=8.0Hz, 2H), 6.40 (d, J=8.0Hz, 1H), 3.78 (s, 3H), 3.69 (s, 3H), 2.98 (s, 3H).HRMS(ESI), [M-H]^-:m/z,516.06。

Embodiment 161:The chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- (pyridine -3- sulfonyls) -1H- Yin Diindyl -2- formamides

A) 3- pyridine sulfonamides

Under Ar protections, excessive ammonia (4.5mL, ammonia content are added in 3- pyridine sulfonyl chlorides (1.457g)：25-28%), rise Stop reaction after 40 DEG C of reactions of temperature, 30min, revolving removes unreacted ammoniacal liquor, add 10mL elutriations and go out second after yellow solid, filtering Alcohol hot recrystallization (1.1g, 85%), mp:244-245℃.¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.98(s,1H), 8.79 (d, J=4.7Hz, 1H), 8.19 (d, J=8.0Hz, 1H), 7.67-7.57 (m, 3H)；HRMS(ESI):m/z, 159.1836[M+H]⁺.

B) the chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- (pyridine -3- sulfonyls) -1H- indoles -2- first Acid amides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (65mg, 0.197mmol) be dissolved in dry DCM, sequentially add HATU (113mg, 0.295mmol), DMAP (12mg, 0.10mmol) and TEA (40mg, 0.40mmol), is stirring evenly and then adding into pyridine -3- sulfonamide (47mg, 0.295mmol), and ambient temperature overnight stops anti- Should after solvent is evaporated off, successively with watery hydrochloric acid, washing, merge EA layers, post separation obtains chartreuse solid (50mg, 55%)；mp: 218-220℃。¹H NMR(400MHz,DMSO-d₆)δ(ppm)：8.99 (s, 1H), 8.64 (s, 1H), 8.23 (d, J=17.2Hz, 2H), 7.50 (s, 1H), 7.39 (s, 1H), 7.13 (d, J=7.8Hz, 1H), 7.03 (d, J=7.8Hz, 1H), 6.77 (dd, J= 21.1,8.4Hz, 3H), 6.43 (d, J=8.0Hz, 1H), 4.25 (s, 3H), 3.71 (s, 3H) .HRMS (ESI):m/z, 471.1045[M+H]⁺

Embodiment 162：The chloro- N- of 7- [(5- isobutyl group thiophene -2-)-sulfonyl] -4- [(3- methoxyphenyls)-amino] - 1- Methyl-1H-indole -2- formamides

A) thiophene -2- nezukones

By thiophene (505mg, 6.02mmol), isobutyric acid (441mg, 5.01mmol) is middle to add PPA (3g, excessive), now Reaction solution is light brown viscous thing, is warming up to 80 DEG C of reaction 4h, stops reaction cooling, add water and be sufficiently stirred for, DCM extractions, then according to Secondary use water, salt washing merges organic layer, dry dark brown yellow viscous oil (618mg, 80%).HRMS(ESI):m/z, 155.1610[M+H]⁺

B) 2- isobutyl groups thiophene

By thiophene -2- nezukones (840mg, 5.45mmol), KOH (1.23g, 21.92mmol) and hydrazine hydrate (1.64g, 32.76mmol) it is dissolved in diethylene glycol, is heated to after 210 degree, reaction 3h, is cooled to room temperature, is diluted with water, ether extraction has Machine layer uses water successively again, and salt washing merges organic layer, post separation give light yellow oil (635mg, 83%)；HRMS(ESI): m/z,139.1294[M-H]^-

C) 5- isobutyl groups thiophene -2- sulfonic acid chlorides

Under argon gas protection, add under ice salt bath, in sulfonic acid chloride (780mg, 5.78mmol) after dry DMF (40mL), 10min and add Enter 2- isobutyl groups thiophene (660mg, 4.71mmol), be warming up to 100 DEG C (oil bath temperature) reaction, now reaction system is brown color Stop reaction after solution, 1h, add excessive trash ice stirring, dissolve rear EA Rapid Extractions, EA/PE=1/10 posts get light yellow oil Shape thing (506mg, 45%).¹H NMR(400MHz,CDCl₃)δ(ppm)：7.72 (d, J=3.9Hz, 1H), 6.84 (d, J= 3.9Hz, 1H), 2.76 (d, J=7.1Hz, 2H), 1.95 (m, J=13.6,6.8Hz, 1H), 0.99 (d, J=6.6Hz, 6H)； HRMS(ESI):m/z,239.2363[M+H]⁺。

D) 5- isobutyl groups thiophene -2- sulfonamide

Under Ar protections, excessive ammonia (4.0mL) is added in 5- isobutyl group thiophene -2- sulfonic acid chlorides (238mg, 1.00mmol), Stop reaction after 40 DEG C of reactions of heating, 1h, revolving removes unreacted ammoniacal liquor, add 10mL washings, EA is extracted three times, and post separation is obtained Light yellow viscous grease (165mg, 75%), directly carries out next step.HRMS(ESI):m/z,220.0390[M+H]⁺。

E) the chloro- N- of 7- [(5- isobutyl group thiophene -2-)-sulfonyl] -4- [(3- methoxyphenyls)-amino] -1- methyl - 1H- indole 2-carboxamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (115mg, 0.35mmol) it is dissolved in dry DCM, sequentially adds HATU (190mg, 0.50mmol), DMAP (22mg, 0.175mmol) and TEA (72mg, 0.7mmol), is stirring evenly and then adding into 5- isobutyl group thiophene -2- sulfonamide (110mg, 0.5mmol), and ambient temperature overnight is stopped Solvent is evaporated off after reaction, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains light yellow solid 110mg, yield 58.8%； mp:212-215℃。¹H NMR(400MHz,DMSO-d₆)δ(ppm)：12.76 (s, 1H), 8.35 (s, 1H), 7.67 (d, J= 14.9Hz, 2H), 7.16 (t, J=7.7Hz, 2H), 6.95 (s, 1H), 6.84 (d, J=8.3Hz, 1H), 6.79-6.65 (m, 2H), 6.47 (d, J=8.1Hz, 1H), 4.16 (s, 3H), 3.70 (s, 3H), 2.73 (d, J=6.8Hz, 2H), 1.92-1.78 (m, 1H), 0.89 (d, J=6.5Hz, 6H)；HRMS(ESI):m/z,532.1165[M+H]⁺。

Embodiment 163：The chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- [(1- methyl indol quinolines -5-)-sulphurs Acyl group] -1H- indole 2-carboxamides

A) 1- methyl indols quinoline

Under Ar gas shieldeds, condition of ice bath, NaH (2.46g, 102.5mmol) is added in anhydrous THF, adds indoline (8.21g, 68.9mmol), is slowly added to iodomethane (14.55g, 102.5mmol), and reaction ice bath to ambient temperature overnight reacts.Stop Concentrate, be diluted with water after reaction, DCM extraction dryings, post separation give light yellow oil (4.77g, 52%).¹H NMR (400MHz,CDCl₃)δ(ppm)：7.14-7.06 (m, 2H), 6.69 (t, J=7.3Hz, 1H), 6.51 (d, J=8.1Hz, 1H), 3.30 (t, J=8.1Hz, 2H), 2.96 (t, J=8.1Hz, 2H), 2.77 (s, 3H)；HRMS(ESI):m/z,134.0989[M+ H]⁺。

B) 1- methyl indols quinoline -5- sulfonic acid

Condition of ice bath, 1- methyl indols quinoline (2.66g, 20mmol) is dissolved in absolute ether, be slowly added to sulfuric acid (2.0g, Diethyl ether solution 20.4mmol), rotation removes ether, temperature reaction 4h after stirring.Stop after reaction plus methanol dilution, there is slightly yellow solid Body is separated out, filtering, EA/PE recrystallizations, obtains white solid product (2.1g, 49%).HRMS(ESI):m/z,212.0441[M- H]^-

C) 1- methyl indols quinoline -5- sulfonic acid chlorides

Under argon gas protection, condition of ice bath, 1- methyl indol quinoline -5- sulfonic acid (450mg, 2.12mmol) is dissolved in anhydrous DCM, Be slowly added to the DCM solution of oxalyl chloride (1.35g, 10.60mmol), instill DMF (0.2mL) afterwards ice bath to reacting at room temperature 2.5h. Stop after reaction, washing, rotation removes DCM, EA/PE recrystallizations obtain faint yellow solid product, next step is directly carried out after drying (260mg, 53%)；HRMS(ESI):m/z,232.0196[M-H]^-

D) synthesis of 1- methyl indols quinoline -5- sulfonamide

Excessive methanolic ammonia solution is added under Ar protections, in 1- methyl indol quinoline -5- sulfonic acid chlorides (377mg, 2.12mmol) (5mL, 35mmol), ice bath stops reaction to reacting at room temperature after 1h, rotate solution, adds 10mL frozen water, and DCM extractions are associated with Machine phase, post separation obtains light yellow solid (140mg, 41%)；mp:172-174℃.¹H NMR(400MHz,DMSO-d₆)δ(ppm): 7.47 (d, J=8.2Hz, 1H), 7.41 (s, 1H), 6.92 (s, 2H), 6.50 (d, J=8.3Hz, 1H), 3.40 (t, J= 8.4Hz, 2H), 2.94 (t, J=8.4Hz, 2H), 2.77 (s, 3H)；HRMS(ESI):m/z,213.0703[M+H]⁺。

E) the chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- [(1- methyl indol quinolines -5-)-sulfonyl] - 1H- indole 2-carboxamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (105mg, 0.32mmol) it is dissolved in dry DCM, sequentially adds HATU (182mg, 0.48mmol), DMAP (20mg, 0.16mmol) and TEA (66mg, 0.66mmol), is stirring evenly and then adding into 1- methyl indol quinoline -5- sulfonamide (101mg, 0.48mmol), ambient temperature overnight, Stop after reaction, solvent is evaporated off, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains light yellow solid (60mg, 36%)； mp:210-212℃。¹H NMR(400MHz,DMSO-d₆)δ(ppm):12.22(s,1H),8.34(s,1H),7.71–7.59(m, 2H), 7.52 (s, 1H), 7.17 (t, J=7.9Hz, 2H), 6.85 (d, J=8.3Hz, 1H), 6.78-6.69 (m, 2H), 6.50 (dd, J=23.4,8.3Hz, 2H), 4.14 (s, 3H), 3.72 (s, 3H), 3.48 (t, J=8.2Hz, 2H), 2.99 (t, J= 8.4Hz,2H),2.81(s,3H)；HRMS(ESI):m/z,525.1279[M+H]⁺。

Embodiment 164：The chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- [(1- methyl isophthalic acids, 2,3,4- tetrahydrochysenes Quinoline -6-)-sulfonyl] -1H- indole 2-carboxamides

A) 1- methyl isophthalic acids, 2,3,4- tetrahydroquinolines

Under Ar gas shieldeds, condition of ice bath, NaH (2.4g, 99.1mmol) is added in anhydrous THF, adds 1,2,3,4- tetrahydrochysenes Quinoline (8.8g, 66.1mmol), is slowly added to MeI (16.9g, 66.1mmol), and reaction ice bath to ambient temperature overnight reacts.Stop anti- Should after concentrate, be diluted with water, DCM extractions are dried, post separation obtains light brown grease (5.5g, 56%).¹H NMR(400MHz, CDCl₃)δ(ppm):7.08 (t, J=7.8Hz, 1H), 6.96 (d, J=7.0Hz, 1H), 6.61 (t, J=7.0Hz, 2H), 3.26-3.19 (m, 2H), 2.89 (s, 3H), 2.77 (t, J=6.5Hz, 2H), 2.03-1.94 (m, 2H)；HRMS(ESI):m/z, 148.1177[M+H]⁺。

B) 1- methyl isophthalic acids, 2,3,4- tetrahydroquinoline -6- sulfonic acid

Condition of ice bath, 1- methyl isophthalic acids, 2,3,4- tetrahydroquinolines (2.94g, 20mmol) are dissolved in absolute ether, are slowly added to The diethyl ether solution of sulfuric acid (2.35g, 24mmol), rotation removes ether, temperature reaction 5.5h after stirring.Stop after reaction plus methanol is dilute Release, there is the precipitation of near-white solid, filtering, EA/PE recrystallizations obtain white solid product (1.62g, 36%), are dried in vacuo and argon Gas shielded carries out next step.HRMS(ESI):m/z,228.0700[M+H]⁺。

C) 1- methyl isophthalic acids, the synthesis of 2,3,4- tetrahydroquinoline -6- sulfonic acid chlorides

Under Ar protections, under condition of ice bath, by 1- methyl isophthalic acids, 2,3,4- tetrahydroquinoline -6- sulfonic acid (455mg, 2.0mmol) are molten In anhydrous DCM, be slowly added to the DCM solution of oxalyl chloride (1.27g, 10.0mmol), instill DMF (0.1mL) afterwards ice bath to room Temperature reaction 2.5h.Stop washing after reaction, rotation is removed after DCM, EA/PE recrystallizations obtain faint yellow solid product, after drying directly entered Row next step (152mg, 31%).

D) 1- methyl isophthalic acids, the synthesis of 2,3,4- tetrahydroquinoline -6- sulfonamide

Excessive methanolic ammonia solution is added under Ar protections, in 1- methyl indol quinoline -6- sulfonic acid chlorides (245mg, 1.0mmol) (4mL, 28mmol), ice bath stops reaction to reacting at room temperature after 1h, rotate solution, adds 10mL frozen water, and DCM extractions are associated with Machine phase, post separation obtains light yellow solid (110mg, 45%)；mp:202-204℃.¹H NMR(400MHz,DMSO-d₆)δ(ppm): 7.39 (d, J=7.1Hz, 1H), 7.28 (s, 1H), 6.86 (s, 2H), 6.57 (d, J=8.7Hz, 1H), 3.29-3.22 (m, 2H), 2.88 (s, 3H), 2.69 (t, J=6.2Hz, 2H), 1.92-1.80 (m, 2H)；HRMS(ESI):m/z,227.0872[M+ H]⁺。

E) the chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- [(1- methyl isophthalic acids, 2,3,4- tetrahydroquinolines - 6-)-sulfonyl] -1H- indole 2-carboxamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (85mg, 0.26mmol) it is dissolved in dry DCM, sequentially adds HATU (147mg, 0.39mmol), DMAP (16mg, 0.13mmol) and TEA (52mg, 0.52mmol), is stirring evenly and then adding into 1- methyl isophthalic acids, 2,3,4- tetrahydroquinoline -6- sulfonamide (88mg, 0.39mmol), ambient temperature overnight, solvent is evaporated off after stopping reaction, successively with watery hydrochloric acid, and washing merges EA layers, post separation obtains light yellow Solid (55mg, 40%)；mp:222-224℃.¹H NMR(400MHz,DMSO-d₆)δ(ppm):12.19(s,1H),8.34(s, 1H), 7.62 (s, 2H), 7.44 (s, 1H), 7.16 (d, J=8.0Hz, 2H), 6.85 (d, J=8.5Hz, 1H), 6.79-6.61 (m, 3H), 6.48 (d, J=7.9Hz, 1H), 4.14 (s, 3H), 3.72 (s, 3H), 3.31-3.24 (m, 2H), 2.94 (s, 3H), 2.73(s,2H),1.87(s,2H)；HRMS(ESI):m/z,539.1378[M+H]⁺。

Embodiment 165：The chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- [(1- methyl indol quinolines -6-)-sulphurs Acyl group] -1H- indole 2-carboxamides

(a) synthesis of 1- methyl indols quinoline -6- sulfonic acid chlorides

Under Ar protections, under ice salt bath, 1- methyl indols quinoline (7.7g, 57.8mmol) is dissolved in anhydrous DCM, adds chlorosulfonic acid (45mL), stirring reaction 16h stops being slowly added in 1L frozen water in the backward system of reaction, is stirred vigorously, reacts and quench completely after 4h Go out, DCM extractions, organic phase is dried, and next step is directly carried out after drying.HRMS(ESI):m/z,232.0192[M+H]⁺。

(b) synthesis of 1- methyl indols quinoline -6- sulfonamide

Excessive methanolic ammonia solution is added under Ar protections, in 1- methyl indol quinoline -6- sulfonic acid chlorides (345mg, 1.49mmol) Stop reaction after (3.5mL, 24.5mmol), ice bath to room temperature reaction, 0.5h, rotate solution, add 10mL frozen water, DCM is extracted, Merge organic phase, post separation obtains light yellow solid (92mg, 29%)；mp:116-117℃.¹H NMR(400MHz,DMSO-d₆)δ (ppm):7.14 (d, J=10.0Hz, 3H), 7.04 (d, J=7.5Hz, 1H), 6.84 (s, 1H), 3.35 (d, J=8.4Hz, 2H), 2.92 (t, J=8.2Hz, 2H), 2.74 (s, 3H)；HRMS(ESI):m/z,213.0699[M+H]⁺。

(c) the chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- [(1- methyl indol quinolines -6-)-sulfonyl] - 1H- indole 2-carboxamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (75mg, 0.23mmol) it is dissolved in dry DCM, sequentially adds HATU (130mg, 0.34mmol), DMAP (14mg, 0.12mmol) and TEA (51mg, 0.50mmol), is stirring evenly and then adding into 1- methyl indol quinoline -6- sulfonamide (72mg, 0.34mmol), ambient temperature overnight, Solvent is evaporated off after stopping reaction, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains light yellow solid (40mg, 34%)；mp: 239-241℃。¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.35 (s, 1H), 7.67 (s, 2H), 7.15 (d, J=7.4Hz, 2H), 6.84 (d, J=7.8Hz, 1H), 6.78-6.67 (m, 2H), 6.47 (d, J=7.8Hz, 1H), 4.09 (d, J=18.9Hz, 4H), 3.87 (d, J=19.0Hz, 2H), 3.70 (s, 3H), 2.95 (t, J=8.1Hz, 2H), 2.74 (s, 3H)；HRMS(ESI): m/z,525.1265[M+H]⁺。

Embodiment 166：The chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- [(1- methyl isophthalic acids, 2,3,4- tetrahydrochysenes Quinoline -7-)-sulfonyl] -1H- indole 2-carboxamides

(a) 1- methyl isophthalic acids, the synthesis of 2,3,4- tetrahydroquinoline -7- sulfonic acid chlorides

Under Ar protections, under ice salt bath, 1- methyl tetrahydroquinoline (6.5g, 44.2mmol) is dissolved in anhydrous DCM, adds chlorine sulphur Sour (30mL), stirring reaction 20h stops being slowly added to frozen water in the backward system of reaction, DCM extractions, after organic phase is dried, directly Carry out next step reaction.

(b) 1- methyl isophthalic acids, the synthesis of 2,3,4- tetrahydroquinoline -7- sulfonamide

Under Ar protections, 1- methyl isophthalic acids, 2,3,4- tetrahydroquinoline -7- sulfonic acid chlorides (995mg, 4.1mmol) are middle to add excess ammonia Methanol solution (3.0mL, 21mmol), ice bath stops reaction to reacting at room temperature after 0.5h, rotate solution, adds 10mL frozen water, DCM is extracted, and merges organic phase, and post separation obtains light yellow solid (172mg, 19%)；；mp:136-138℃.¹H NMR (400MHz,CDCl₃)δ(ppm):7.65 (d, J=8.1Hz, 1H), 7.12-6.99 (m, 3H), 5.11 (s, 2H), 3.20-3.11 (m, 2H), 2.91 (s, 3H), 2.86 (t, J=6.6Hz, 2H), 1.92-1.84 (m, 2H)；HRMS(ESI):m/z,227.1000 [M+H]⁺。

(c) the chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- [(1- methyl isophthalic acids, 2,3,4- tetrahydroquinolines - 7-)-sulfonyl] -1H- indole 2-carboxamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (85mg, 0.26mmol) it is dissolved in dry DCM, sequentially adds HATU (147mg, 0.39mmol), DMAP (16mg, 0.13mmol) and TEA (78mg, 0.77mmol), is stirring evenly and then adding into 1- methyl isophthalic acids, 2,3,4- tetrahydroquinoline -7- sulfonamide (88mg, 0.39mmol), ambient temperature overnight, solvent is evaporated off after stopping reaction, successively with watery hydrochloric acid, and washing merges EA layers, post separation obtains light yellow Solid (45mg, 33%)；mp:209-211℃.¹H NMR(400MHz,CDCl₃) δ 9.38 (s, 1H), 7.91 (d, J=8.1Hz, 1H), 7.31 (s, 1H), 7.17 (dt, J=21.0,7.1Hz, 3H), 6.86 (d, J=8.1Hz, 1H), 6.68 (d, J=9.3Hz, 2H), 6.55 (d, J=8.1Hz, 1H), 6.06 (s, 1H), 4.28 (s, 3H), 3.80 (s, 3H), 3.11 (s, 2H), 2.84 (s, 5H),1.85(s,2H)；HRMS(ESI):m/z,537.1207[M-H]^-。

Embodiment 167：The chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- [(3- methyl -2- oxos -2,3- Dihydrobenzo [d] oxazole -6-)-sulfonyl] -1H- indole 2-carboxamides

(a) synthesis of 3- methylbenzoxazoles ketone

Under Ar gas shieldeds, condition of ice bath, NaH (910mg, 47.9mmol) is added in anhydrous THF, adds benzoxazolone (3.6g, 26.6mmol) is dissolved in anhydrous THF, is slowly added to iodomethane (5.7g, 40mmol), and reaction ice bath is anti-to ambient temperature overnight Should.Stop concentrating after reaction, be diluted with water, DCM extractions are dried, post separation obtains pale red brown solid (2.8g, 71%).¹H NMR(400MHz,CDCl₃)δ(ppm):7.19 (t, J=7.2Hz, 2H), 7.12 (t, J=7.7Hz, 1H), 6.96 (d, J= 7.6Hz,1H),3.41(s,3H)；HRMS(ESI):m/z,150.1635[M+H]⁺。

(b) synthesis of 3- methylbenzoxazoles ketone -6- sulfonic acid chlorides

Under Ar protections, under ice salt bath, 3- methylbenzoxazoles ketone (2.2g, 14.8mmol) is dissolved in anhydrous DCM, adds chlorine Sulfonic acid (38mL), stirring reaction 10h stops being slowly added to frozen water in the backward system of reaction, DCM extractions, organic phase dries revolving, Vacuum drying chamber is placed in, next step reaction is directly used in.HRMS(ESI):m/z,248.0232[M+H]⁺。

(c) synthesis of 3- methylbenzoxazoles ketone -6- sulfonamide

Excessive methanolic ammonia solution is added under Ar protections, in 3- methylbenzoxazole ketone -6- sulfonic acid chlorides (915mg, 3.7mmol) (4.0mL, 28mmol), ice bath stops reaction to reacting at room temperature after 1.5h, rotation removes post separation after solvent and obtains yellow-brown solid (140mg, 17%)；mp:179-181℃.¹H NMR(400MHz,CDCl₃)δ(ppm):7.84(s,1H),7.77(s,1H), 7.07 (d, J=8.4Hz, 1H), 4.77 (s, 2H), 3.47 (s, 3H)；HRMS(ESI):m/z,229.0888[M+H]⁺。

(d) the chloro- 4- of 7- [(3- methoxyphenyls)-amino] -1- methyl-N- [(3- methyl -2- oxo -2,3- dihydrobenzos [d] oxazole -6-)-sulfonyl] -1H- indole 2-carboxamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (105mg, 0.32mmol) it is dissolved in dry DCM, sequentially adds HATU (183mg, 0.48mmol), DMAP (20mg, 0.15mmol) and TEA (97mg, 0.96mmol), be stirring evenly and then adding into 1.5mL DMF dissolving sulfonamide (110mg, 0.48mmol), ambient temperature overnight, Solvent is evaporated off after stopping reaction, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains light yellow solid (65mg, 38%)；mp: 229-231℃。¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.31(s,1H),7.92–7.77(m,2H),7.53(s,1H), 7.40 (d, J=8.1Hz, 1H), 7.24-7.06 (m, 2H), 6.89-6.69 (m, 3H), 6.46 (d, J=7.6Hz, 1H), 4.19 (s,3H),3.72(s,3H),2.84(s,3H)；HRMS(ESI):m/z,539.0864[M-H]^-。

Embodiment 168：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- fluorophenylsulphonyls) -1H- Yin Diindyl -2- formamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (100mg, 0.30mmol) it is dissolved in dry DCM, sequentially adds HATU (172mg, 0.45mmol), DMAP (18mg, 0.15mmol) and TEA (92mg, 0.90mmol), is stirring evenly and then adding into 4- fluorobenzenesulfonamides (80mg, 0.45mmol), and ambient temperature overnight stops steaming after reaction Except solvent, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (75mg, 51.4%).mp:115- 117℃；MS (ESI) m/z (%):486.0633[M-H]^-。

¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.20(s,1H),7.86(s,2H),7.35–7.03(m,4H), 6.97 (s, 1H), 6.74 (d, J=16.7Hz, 3H), 6.40 (s, 1H), 4.27 (s, 3H), 3.69 (s, 3H).

Embodiment 169：1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (3- tnBuoromethyl-benzenesulfonyls) - 1H- indole 2-carboxamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 3- trifluoromethyl benzene sulfonamides (82mg, 0.36mmol), and ambient temperature overnight stops Solvent is evaporated off after reaction, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (65mg, 50.4%). mp:69-70℃；MS (ESI) m/z (%):536.0545[M-H]^-。

¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.31 (m, 3H), 8.13 (d, J=6.8Hz, 1H), 7.93 (d, J= 6.7Hz, 1H), 7.72 (s, 1H), 7.16 (s, 2H), 6.84 (d, J=8.0Hz, 1H), 6.79-6.65 (m, 2H), 6.48 (d, J =7.5Hz, 1H), 4.10 (s, 3H), 3.71 (s, 3H).

Embodiment 170：1- methyl -4- ((3- methoxyphenyls) amino) chloro- N- of -7- (4- tnBuoromethyl-benzenesulfonyls) - 1H- indole 2-carboxamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 4- trifluoromethyl benzene sulfonamides (82mg, 0.36mmol), and ambient temperature overnight stops Solvent is evaporated off after reaction, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (70mg, 54.3%).. mp:80-81℃；MS (ESI) m/z (%):536.0569[M-H]^-。

¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.21(s,1H),8.00(m,2H),7.77(m,2H),7.31(s, 1H),7.11(s,1H),6.98(s,1H),6.76(m,3H),6.40(s,1H),4.25(s,3H),3.69(s,3H)。

Embodiment 171：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- fluorophenylsulphonyls) -1H- Yin Diindyl -2- formamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (100mg, 0.30mmol) it is dissolved in dry DCM, sequentially adds HATU (172mg, 0.45mmol), DMAP (18mg, 0.15mmol) and TEA (92mg, 0.90mmol), is stirring evenly and then adding into 3- fluorobenzenesulfonamides (79mg, 0.45mmol), and ambient temperature overnight stops steaming after reaction Except solvent, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (82mg, 56.2%).mp:108- 110℃；MS (ESI) m/z (%):486.0622[M-H]^-。

¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.21 (s, 1H), 7.60 (d, J=18.7Hz, 2H), 7.45 (s, 1H), 7.29 (s, 2H), 7.11 (s, 1H), 6.98 (s, 1H), 6.74 (d, J=17.1Hz, 3H), 6.41 (s, 1H), 4.27 (s, 3H),3.69(s,3H)。

Embodiment 172：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (2- fluorophenylsulphonyls) -1H- Yin Diindyl -2- formamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (100mg, 0.30mmol) it is dissolved in dry DCM, sequentially adds HATU (172mg, 0.45mmol), DMAP (18mg, 0.15mmol) and TEA (92mg, 0.90mmol), is stirring evenly and then adding into 2- fluorobenzenesulfonamides (79mg, 0.45mmol), and ambient temperature overnight stops steaming after reaction Except solvent, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (72mg, 50.0%).mp:105- 107℃；MS (ESI) m/z (%):486.0624[M-H]^-。

¹H NMR(400MHz,DMSO-d₆)δ8.20(s,1H),7.86(s,2H),7.35–7.03(m,4H),6.97(s, 1H), 6.74 (d, J=16.7Hz, 3H), 6.40 (s, 1H), 4.27 (s, 3H), 3.69 (s, 3H).

Embodiment 173：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- cyanophenylsulfonyls) -1H- Yin Diindyl -2- formamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 4- cvanobenzenesulfonamides (66mg, 0.36mmol), and ambient temperature overnight is stopped after reaction Solvent is evaporated off, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (85mg, 71.4%).mp:60- 62℃；MS (ESI) m/z (%):495.6751[M+H]⁺.

¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.33(s,1H),8.08(m,4H),7.62(s,1H),7.13(m, 2H),6.77(m,3H),6.46(s,1H),4.14(s,3H),3.70(s,3H).

Embodiment 174：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (2- trifluoromethoxy benzene sulfonyls Base) -1H- indole 2-carboxamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 2- trifluoro-metoxybenzene sulfamides (87mg, 0.36mmol), and ambient temperature overnight is stopped Solvent is evaporated off after reaction, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (67mg, 50.8%). mp:136-138℃；MS (ESI) m/z (%):552.0520[M-H]^-.

¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.26(s,1H),8.02(s,1H),7.44(m,4H),7.12(s, 1H),7.03(s,1H),6.88–6.67(m,3H),6.42(s,1H),4.21(s,3H),3.69(s,3H).

Embodiment 175：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- chlorobenzenesulfonyls) -1H- Yin Diindyl -2- formamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 3- chlorobenzene sulfonamides (69mg, 0.36mmol), and ambient temperature overnight stops after reaction Solvent is evaporated off, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (55mg, 45.8%).mp:71- 73℃；MS (ESI) m/z (%):502.0302[M-H]^-.

¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.37 (s, 1H), 7.95 (d, J=9.1Hz, 2H), 7.81 (d, J= 7.9Hz, 1H), 7.74-7.64 (m, 2H), 7.22-7.11 (m, 2H), 6.84 (d, J=8.3Hz, 1H), 6.79-6.68 (m, 2H), (s, the 3H) of 6.47 (d, J=8.0Hz, 1H), 4.12 (s, 3H), 3.71

Embodiment 176：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- cyanophenylsulfonyls) -1H- Yin Diindyl -2- formamides

A) synthesis of 3- cvanobenzenesulfonamides

Under Ar protections, the excessive methanolic ammonia solution of the middle addition of 3- cyanobenzenesulfonyl chlorides (400mg, 2.0mmol) (3.5mL, 17.5mmol), ice bath stops reaction to reacting at room temperature after 0.5h, rotates solution, adds 10mL frozen water, and DCM is extracted four times, is closed And organic phase, recrystallize to obtain light yellow solid (206mg, 56.6%).MS (ESI) m/z (%):183.0320[M+H]⁺.

B) 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- cyanophenylsulfonyls) -1H- indoles -2- first Acid amides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 3- cvanobenzenesulfonamides (66mg, 0.36mmol), and ambient temperature overnight stops reaction After solvent is evaporated off, successively with watery hydrochloric acid, washing, merge EA layers, post separation obtains chartreuse solid (65mg, 55.1%).mp: 80-82℃；MS (ESI) m/z (%):493.0905[M-H]^-.

¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.49–8.07(m,4H),7.85(s,1H),7.68(s,1H), 7.15 (d, J=7.7Hz, 2H), 6.79 (dd, J=37.0,13.4Hz, 3H), 6.47 (s, 1H), 4.12 (s, 3H), 3.70 (s, 3H).

Embodiment 177：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- Methyl benzenesulfonyls base) -1H- Yin Diindyl -2- formamides

A) synthesis of 3- methyl benzenesulfonamides

Under Ar protections, the excessive methanolic ammonia solution of the middle addition of 3- toluene sulfonyl chlorides (380mg, 2.0mmol) (3.5mL, 24.5mmol), ice bath stops reaction to reacting at room temperature after 0.5h, rotates solution, adds 10mL frozen water, and DCM is extracted four times, is closed And organic phase, recrystallize to obtain white solid (275mg, 79.0%).MS (ESI) m/z (%):172.2120[M+H]⁺.

B) 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- Methyl benzenesulfonyls base) -1H- indoles -2- first Acid amides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 3- methyl benzenesulfonamides (70mg, 0.41mmol), and ambient temperature overnight stops reaction After solvent is evaporated off, successively with watery hydrochloric acid, washing, merge EA layers, post separation obtains chartreuse solid (70mg, 59.8%).mp: 72-73℃；MS (ESI) m/z (%):483.10[M-H]^-.

¹H NMR(400MHz,DMSO-d₆)δ(ppm):12.58(s,1H),8.36(s,1H),7.79(s,2H),7.68(s, 1H), 7.52 (d, J=5.1Hz, 2H), 7.16 (dt, J₁=8.0Hz, J₂=3.9Hz, 2H), 6.84 (d, J=8.3Hz, 1H), (s, the 3H) of 6.77-6.70 (m, 2H), 6.47 (d, J=8.2Hz, 1H), 4.10 (s, 3H), 3.71 (s, 3H), 2.41

Embodiment 178：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- chlorobenzenesulfonyls) -1H- Yin Diindyl -2- formamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 4- chlorobenzene sulfonamides (70mg, 0.36mmol), and ambient temperature overnight stops after reaction Solvent is evaporated off, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (56mg, 46.3%).mp:59- 61℃；MS (ESI) m/z (%):502.0553[M-H]^-.

¹H NMR(400MHz,DMSO-d₆)δ(ppm):12.71 (s, 1H), 8.36 (s, 1H), 7.99 (d, J=8.3Hz, 2H), 7.79-7.66 (m, 3H), 7.17 (d, J=5.2Hz, 2H), 6.84 (d, J=8.2Hz, 1H), 6.78-6.69 (m, 2H), (s, the 3H) of 6.47 (d, J=8.1Hz, 1H), 4.10 (s, 3H), 3.71

Embodiment 179：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- Methyl benzenesulfonyls base) -1H- Yin Diindyl -2- formamides

A) synthesis of 4- methyl benzenesulfonamides

Under Ar protections, the excessive methanolic ammonia solution of the middle addition of 4- toluene sulfonyl chlorides (380mg, 2.0mmol) (3.5mL, 24.5mmol), ice bath stops reaction to reacting at room temperature after 1.0h, rotates solution, adds 10mL frozen water, and DCM is extracted four times, is closed And organic phase, recrystallize to obtain white solid (238mg, 68.0%).

B) 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- Methyl benzenesulfonyls base) -1H- indoles -2- first Acid amides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into para toluene sulfonamide (70mg, 0.41mmol), and ambient temperature overnight stops after reaction Solvent is evaporated off, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (75mg, 64.1%).mp:75- 76℃；MS (ESI) m/z (%):482.1079[M-H]^-.

¹H NMR(400MHz,DMSO-d₆)δ(ppm):12.50 (s, 1H), 8.34 (s, 1H), 7.86 (d, J=8.1Hz, 2H), 7.64 (s, 1H), 7.42 (d, J=7.9Hz, 2H), 7.16 (t, J=8.4Hz, 2H), 6.83 (d, J=8.3Hz, 1H), (s, the 3H) of 6.79-6.69 (m, 2H), 6.47 (d, J=8.1Hz, 1H), 4.11 (s, 3H), 3.70 (s, 3H), 2.39

Embodiment 180：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- trifluoromethoxy benzene sulfonyls Base) -1H- indole 2-carboxamides

A) synthesis of 4- trifluoro-metoxybenzene sulfamides

Under Ar protections, the excessive methanolic ammonia solution of the middle addition of 4- trifluoromethoxies benzene sulfonyl chloride (520mg, 2.0mmol) (5mL, 35mmol), ice bath stops reaction to reacting at room temperature after 40min, rotates solution, adds 20mL frozen water, and DCM is extracted four times, is merged Organic phase, recrystallizes to obtain white solid (425mg, 88.5%).

B) 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (4- trifluoromethoxies benzenesulfonyl) -1H- Yin Diindyl -2- formamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 2- trifluoro-metoxybenzene sulfamides (88mg, 0.36mmol), and ambient temperature overnight is stopped Solvent is evaporated off after reaction, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (70mg, 52.0%). mp:96-98℃；MS (ESI) m/z (%):552.0772[M-H]^-.

¹H NMR(400MHz,DMSO-d₆)δ(ppm):12.78 (s, 1H), 8.36 (s, 1H), 8.11 (d, J=8.5Hz, 2H), 7.73-7.59 (m, 3H), 7.16 (m, 2H), 6.84 (d, J=8.3Hz, 1H), 6.79-6.69 (m, 2H), 6.47 (d, J= 8.2Hz,1H),4.12(s,3H),3.71(s,3H).

Embodiment 181：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- [(5- picolines -2-) sulphonyl Base] -1H- indole 2-carboxamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 5- picoline -2- sulfonamide (63mg, 0.36mmol), and ambient temperature overnight is stopped Only react after solvent is evaporated off, successively with watery hydrochloric acid, washing, merge EA layers, post separation obtain chartreuse solid (65mg, 55.6%).mp:58-60℃；MS (ESI) m/z (%):483.1021[M-H]^-.

¹H NMR(400MHz,DMSO-d₆)δ(ppm):12.83(s,1H),8.53(s,1H),8.36(s,1H),8.02(d, J=8.0Hz, 1H), 7.93 (s, 1H), 7.68 (s, 1H), 7.16 (t, J=8.1Hz, 2H), 6.84 (d, J=8.2Hz, 1H), (s, the 3H) of 6.79-6.69 (m, 2H), 6.46 (d, J=8.3Hz, 1H), 4.09 (s, 3H), 3.71 (s, 3H), 2.39

Embodiment 182：1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- trifluoromethoxy benzene sulfonyls Base) -1H- indole 2-carboxamides

A) synthesis of 3- trifluoro-metoxybenzene sulfamides

Excessive methanolic ammonia solution is added under Ar protections, in 3- trifluoromethoxies benzene sulfonyl chloride (200mg, 0.77mmol) (4mL, 28mmol), ice bath stops reaction to reacting at room temperature after 40min, rotate solution, adds 20mL frozen water, DCM extractions four It is secondary, merge organic phase, recrystallize to obtain white solid (115mg, 62.2%).

B) 1- methyl -4- ((3- methoxyphenyls) amino) the chloro- N- of -7- (3- trifluoromethoxies benzenesulfonyl) -1H- Yin Diindyl -2- formamides

Ar protection under, by 1- methyl -4- ((3- methoxyphenyls) amino) chloro- 1H- indole-2-carboxylic acids of -7- (80mg, 0.24mmol) it is dissolved in dry DCM, sequentially adds HATU (140mg, 0.36mmol), DMAP (15mg, 0.12mmol) and TEA (73mg, 0.72mmol), is stirring evenly and then adding into 3- trifluoro-metoxybenzene sulfamides (88mg, 0.36mmol), and ambient temperature overnight is stopped Solvent is evaporated off after reaction, successively with watery hydrochloric acid, washing merges EA layers, post separation obtains chartreuse solid (68mg, 50.7%). mp:75-77℃；MS (ESI) m/z (%):552.0750[M-H]^-.

¹H NMR(400MHz,DMSO-d₆)δ(ppm):8.37 (s, 1H), 8.02 (d, J=7.4Hz, 1H), 7.91 (s, 1H), 7.85-7.68 (m, 3H), 7.16 (m, 2H), 6.84 (d, J=8.3Hz, 1H), 6.79-6.69 (m, 2H), 6.48 (d, J= 7.7Hz,1H),4.11(s,3H),3.71(s,3H).

Embodiment 183:4- ((3- acetylamino phenyls) -7- nitros-N- (trifyl) -1H- indoles -2- formyls Amine

A) .4- (3- acetylamino phenyls) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 1H- indole -2-ethyl formates of 7- nitros -4- and 3- acetamidobenzeneboronic acids as initiation material, preparation process A) methods described in be the same as Example 3, obtains faint yellow solid 248mg, yield is 60%, mp:183-184℃；

¹H NMR(CDCl₃)δ(ppm):10.45 (s, 1H), 8.33 (d, J=8.0Hz, 1H), 7.84 (s, 1H), 7.63 (d, J=7.6Hz, 1H), 7.47-7.51 (m, 3H), 7.39 (d, J=7.6Hz, 1H), 7.30 (d, J=8.4Hz, 1H), 4.45 (q, J =7.2Hz, 2H), 2.23 (s, 3H), 1.43 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₉H₁₈N₃O₅[M +H⁺]:368.1241,found 368.1228.

B) .4- (3- acetylamino phenyls) -7- nitro -1H- indole-2-carboxylic acids

Using 4- (3- acetylamino phenyls) -7- nitro -1H- indole -2-ethyl formates as initiation material, preparation process is with real B) methods described is applied in example 3, faint yellow solid 65mg is obtained, yield is 78%, mp>250℃.

¹H NMR(DMSO-d₆)δ(ppm):13.60 (brs, 1H), 11.27 (s, 1H), 10.17 (s, 1H), 8.35 (d, J= 8.4Hz, 1H), 8.02 (s, 1H), 7.70 (d, J=8.1Hz, 1H), 7.50 (t, J=7.8Hz, 1H), 7.36-7.42 (m, 3H), 2.08(s,3H)；HRMS(ESI):m/z,calcd for C₁₇H₁₄N₃O₅[M+H⁺]:340.0928,found 340.0921.

C) .4- ((3- acetylamino phenyls) -7- nitros-N- (trifyl) -1H- indole 2-carboxamides

Using 4- (3- acetylamino phenyls) -7- nitro -1H- indole-2-carboxylic acids and trifluoro Methanesulfomide as initiation material, system C) methods described in standby process be the same as Example 3, obtains yellow powdery solid 60mg, yield is 72%, mp:190-192℃.

¹H NMR(DMSO-d₆)δ(ppm):10.53 (s, 1H), 10.20 (s, 1H), 8.29 (d, J=9.6Hz, 1H), 7.95 (s, 1H), 7.80 (d, J=8.0Hz, 1H), 7.51 (t, J=8.0Hz, 1H), 7.37 (t, J=8.0Hz, 1H), 7.14 (s, 1H),2.08(s,3H).

Embodiment 184:4- ((3- acetylamino phenyls) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- (3- acetylamino phenyls) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, prepared C) methods described in journey be the same as Example 3, obtains yellow powdery solid 45mg, yield is 80%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.75 (brs, 1H), 10.18 (s, 1H), 8.38 (d, J=8.4Hz, 1H), 8.04 (d, J=8.0Hz, 2H), 7.94 (s, 1H), 7.77-7.64 (m, 5H), 7.52 (t, J=8.0Hz, 2H), 7.41-7.36 (m,2H),2.09(s,3H).

Embodiment 185:4- ((3- acetylamino phenyls) -7- amino-N- (benzenesulfonyl) -1H- indole 2-carboxamides

By 4- ((3- acetylamino phenyls) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides (120mg, 0.25mmol) it is dissolved in methanol (10mL), adds Pd/C (20mg), catalytic hydrogenation 5h, raw material disappears.Filtering, filtrate is dense Contracting, EA (20mL) dissolvings, washing, column chromatography (D/M=50:1) off-white powder shape solid 33mg, mp, are obtained:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):10.87(brs,1H),10.22(brs,2H),10.02(s,1H),7.88- 7.86 (m, 2H), 7.70 (s, 1H), 7.59 (d, J=8.4Hz, 1H), 7.40-7.38 (m, 3H), 7.31 (t, J=7.8Hz, 1H), 7.19 (d, J=7.2Hz, 1H), 6.86 (brs, 1H), 6.80 (d, J=7.5Hz, 1H), 6.36 (d, J=7.8Hz, 1H), 5.48(brs,1H),2.06(s,3H).

Embodiment 186:4- ((3- acetylamino phenyls) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- Formamide

It is former using 4- (3- acetylamino phenyls) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as starting Material, c) methods described in preparation process be the same as Example 3, obtains yellow powdery solid 69mg, yield is 92%, mp:>290℃.

¹H NMR(DMSO-d₆)δ(ppm):12.98(brs,1H),11.75(brs,1H),10.18(s,1H),8.38(d,J =8.0Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.95 (s, 1H), 7.76 (d, J=8.0Hz, 1H), 7.70 (s, 1H), 7.52 (t, J=8.0Hz, 1H), 7.41-7.36 (m, 2H), 7.17 (d, J=8.8Hz, 2H), 3.85 (s, 3H), 1.99 (s, 3H)；¹³C NMR(125MHz,DMSO-d₆):δ168.63,163.35,157.66,143.56,139.92,138.13,132.31, 131.87,130.48,130.33,130.01,129.59,127.91,123.41,123.10,119.98,119.47,119.13, 114.36,109.63,55.84,24.10.HRMS(ESI):m/z,calcd.for C₂₄H₂₁N₄O₇S[M+H]⁺:509.1126, found 509.1119.

Embodiment 187:4- ((3- cyano-phenyls) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) .4- (3- cyano-phenyls) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 1H- indole -2-ethyl formates of 7- nitros -4- and 3- cyanophenylboronic acids as initiation material, preparation process is with real A) methods described is applied in example 3, faint yellow solid 178mg is obtained, yield is 57%, mp:195-197℃；

¹H NMR(acetone-d₆)δ(ppm):10.95 (brs, 1H), 8.44 (d, J=8.4Hz, 1H), 8.17 (s, 1H), 8.12 (d, J=8.0Hz, 1H), 7.96 (d, J=7.6Hz, 1H), 7.85 (t, J=8.0Hz, 1H), 7.55 (d, J=8.4Hz, 1H), 7.48 (s, 1H), 4.44 (q, J=7.2Hz, 2H), 1.39 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₈H₁₄N₃O₄[M+H⁺]:336.0979,found 336.0968.

B) .4- (3- cyano-phenyls) -7- nitro -1H- indole-2-carboxylic acids

With 4- (3- cyano-phenyls) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process be the same as Example 3 Middle b) methods described, obtains faint yellow solid 96mg, and yield is 95%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):11.32 (s, 1H), 8.33 (d, J=8.4Hz, 1H), 8.17 (s, 1H), 8.05 (d, J=7.6Hz, 1H), 7.98 (d, J=7.2Hz, 1H), 7.78 (t, J=7.6Hz, 1H), 7.47 (d, J=8.4Hz, 1H), 7.32(s,1H)；HRMS(ESI):m/z,calcd for C₁₆H₁₀N₃O₄[M+H⁺]:308.0666,found 308.0652.

C) .4- ((3- cyano-phenyls) -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- (3- cyano-phenyls) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, preparation process is same C) methods described in embodiment 3, obtains pale yellow powder shape solid 50mg, yield is 86%, mp:>290℃.

¹H NMR(DMSO-d₆)δ(ppm):11.74 (brs, 1H), 8.38 (d, J=8.4Hz, 1H), 8.19 (s, 1H), 8.07-8.01 (m, 4H), 7.81 (t, J=8.0Hz, 1H), 7.74 (t, J=7.2Hz, 1H), 7.68-7.64 (m, 3H), 7.50 (d, J=8.4Hz, 1H)

Embodiment 188:4- ((3- methoxyphenyls) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

A) .4- (3- methoxyphenyls) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 1H- indole -2-ethyl formates of 7- nitros -4- and 3- methoxyphenylboronic acids as initiation material, preparation process is same A) methods described in embodiment 3, obtains faint yellow solid 268mg, yield is 85%, mp:182-183℃；

¹H NMR(CDCl₃)δ(ppm):10.47 (s, 1H), 8.35 (d, J=8.4Hz, 1H), 7.45-7.47 (m, 2H), 7.31 (d, J=8.4Hz, 1H), 7.25 (d, J=9.2Hz, 1H), 7.18 (s, 1H), 7.04 (d, J=8.4Hz, 1H), 4.46 (q, J=7.2Hz, 2H), 3.89 (s, 3H), 1.43 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₈H₁₇N₂O₅[M+H⁺]:341.1132,found 341.1119.

B) .4- (3- methoxyphenyls) -7- nitro -1H- indole-2-carboxylic acids

With 4- (3- methoxyphenyls) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process be the same as Example B) methods described in 3, obtains faint yellow solid 106mg, yield is 91%, mp:248-249℃.

¹H NMR(DMSO-d₆)δ(ppm):13.59 (brs, 1H), 11.27 (s, 1H), 8.33 (d, J=8.4Hz, 1H), 7.51 (t, J=8.0Hz, 1H), 7.44 (d, J=8.4Hz, 1H), 7.31 (s, 1H), 7.30 (d, J=7.6Hz, 1H), 7.22 (s, 1H), 7.11 (d, J=8.4Hz, 1H), 3.80 (s, 3H)；HRMS(ESI):m/z,calcdfor C₁₆H₁₃N₂O₅[M+H⁺]: 313.0819,found 313.0817.

C) .4- ((3- methoxyphenyls) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- (3- methoxyphenyls) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as initiation material, C) methods described in preparation process be the same as Example 3, obtains pale yellow powder shape solid 51mg, yield is 82%, mp:244-246℃.

¹H NMR(DMSO-d₆)δ(ppm):12.98 (brs, 1H), 11.63 (brs, 1H), 8.35 (d, J=8.4Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.72 (s, 1H), 7.52 (t, J=8.0Hz, 1H), 7.44 (d, J=8.0Hz, 1H), 7.28 (d, J=7.6Hz, 1H), 7.23 (s, 1H), 7.17 (d, J=8.8Hz, 2H), 7.13 (d, J=8.8Hz, 4H), 3.86 (s, 3H),3.85(s,3H).

Embodiment 189:4- ((4- methoxyphenyls) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

A) .4- (4- methoxyphenyls) -7- nitro -1H- indole -2-ethyl formates

Using the chloro- 1H- indole -2-ethyl formates of 7- nitros -4- and 4- methoxyphenylboronic acids as initiation material, preparation process is same A) methods described in embodiment 3, obtains faint yellow solid 260mg, yield is 93%, mp:144-145℃；

¹H NMR(CDCl₃)δ(ppm):10.47 (brs, 1H), 8.34 (d, J=8.4Hz, 1H), 7.63 (d, J=8.4Hz, 2H), 7.48 (s, 1H), 7.27 (d, J=10.4Hz, 1H), 7.08 (d, J=8.4Hz, 2H), 4.46 (q, J=7.2Hz, 2H), 3.91 (s, 3H), 1.44 (t, J=7.2Hz, 3H)

B) .4- (4- methoxyphenyls) -7- nitro -1H- indole-2-carboxylic acids

With 4- (4- methoxyphenyls) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process be the same as Example B) methods described in 3, obtains faint yellow solid 152mg, yield is 89%, mp:235-237℃.

¹H NMR(DMSO-d₆)δ(ppm):13.59 (brs, 1H), 11.22 (s, 1H), 8.33 (d, J=8.4Hz, 1H), 7.71 (d, J=8.4Hz, 2H), 7.40 (d, J=8.4Hz, 1H), 7.35 (s, 1H), 7.17 (d, J=8.8Hz, 2H), 3.86 (s,3H).

C) .4- ((4- methoxyphenyls) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using 4- (4- methoxyphenyls) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as initiation material, C) methods described in preparation process be the same as Example 3, obtains pale yellow powder shape solid 85mg, yield is 85%, mp:253-255℃.

¹HNMR(DMSO-d₆)δ(ppm):12.98 (brs, 1H), 11.59 (brs, 1H), 8.33 (d, J=8.4Hz, 1H), 7.97 (d, J=8.8Hz, 2H), 7.69 (d, J=8.4Hz, 3H), 7.38 (d, J=8.4Hz, 1H), 7.16 (d, J=8.4Hz, 4H),3.86(s,3H),3.85(s,3H)；HRMS(ESI):m/z,calcd.forC₂₃H₂₀N₃O₇S[M+H]⁺:482.1022, found 482.1009.

Embodiment 190:1- methyl -4- (4- methoxyphenyls) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- Yin Diindyl -2- formamides

A) .1- methyl -4- (4- methoxyphenyls) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 4- methoxyphenylboronic acids as initiation material, system A) methods described in standby process be the same as Example 3, obtains faint yellow solid 155mg, yield is 82%, mp:156-157℃.

¹H NMR(CDCl₃)δ(ppm):7.96 (d, J=8.4Hz, 1H), 7.57 (d, J=8.4Hz, 2H), 7.50 (s, 1H), 7.18 (d, J=8.0Hz, 1H), 7.07 (d, J=8.4Hz, 2H), 4.39 (q, J=7.2Hz, 2H), 4.01 (s, 3H), 3.90 (s, 3H), 1.40 (t, J=7.2Hz, 3H)

B) .1- methyl -4- (4- methoxyphenyls) -7- nitro -1H- indole-2-carboxylic acids

With 1- methyl -4- (4- methoxyphenyls) -7- nitro -1H- indole -2-ethyl formate initiation materials, preparation process B) methods described in be the same as Example 3, obtains pale yellow powder shape solid 120mg, yield is 93%, mp:257-259℃.

¹H NMR(DMSO-d₆)δ(ppm):8.06 (d, J=8.0Hz, 1H), 7.64 (d, J=8.4Hz, 2H), 7.39 (s, 1H), (s, the 3H) of 7.32 (d, J=8.4Hz, 1H), 7.15 (d, J=8.4Hz, 2H), 3.90 (s, 3H), 3.85

C) .1- methyl -4- (4- methoxyphenyls) -7- nitros-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- formyls Amine

Using 1- methyl -4- (4- methoxyphenyls) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides to rise C) methods described in beginning raw material, preparation process be the same as Example 3, obtains yellow powdery solid 46mg, yield is 75%, mp:145- 247℃。

¹H NMR(DMSO-d₆)δ(ppm):12.62 (brs, 1H), 8.06 (d, J=8.0Hz, 1H), 7.95 (d, J= 8.8Hz, 2H), 7.79 (s, 1H), 7.68 (d, J=8.4Hz, 2H), 7.32 (d, J=8.0Hz, 1H), 7.19-7.15 (m, 4H), 3.87(s,3H),3.85(s,3H),3.69(s,3H)；HRMS(ESI):m/z,calcd.for C₂₄H₂₂N₃O₇S[M+H]⁺: 496.1179,found 496.1166.

Embodiment 191:1- methyl -4- (3- acetylamino phenyls)-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) .1- methyl -4- (3- acetylamino phenyls) -7- nitro -1H- indole -2-ethyl formates

Using the 1- chloro- 1H- indole -2-ethyl formates of methyl -7- nitros -4- and 3- acetamidobenzeneboronic acids as initiation material, A) methods described in preparation process be the same as Example 75, obtains pale yellow powder shape solid 105mg, yield is 79%, mp:165-166 ℃。

¹H NMR(CDCl₃)δ(ppm):7.95 (d, J=8.0Hz, 1H), 7.75 (s, 1H), 7.63 (d, J=8.0Hz, 1H), 7.51 (s, 1H), 7.49 (t, J=8.0Hz, 1H), 7.36 (d, J=7.2Hz, 1H), 7.22 (d, J=8.0Hz, 1H), (t, J=7.2Hz, the 3H) of 4.40 (q, J=7.2Hz, 2H), 4.01 (s, 3H), 2.23 (s, 3H), 1.40

B) .1- methyl -4- (3- acetylamino phenyls) -7- nitro -1H- indole-2-carboxylic acids

With 1- methyl -4- (3- acetylamino phenyls) -7- nitro -1H- indole -2-ethyl formate initiation materials, prepared B) methods described in journey be the same as Example 3, obtains orange powder shape solid 143mg, yield is 99%, mp:199-201℃.

¹H NMR(DMSO-d₆)δ(ppm):13.48 (brs, 1H), 10.17 (s, 1H), 8.08 (d, J=8.0Hz, 1H), 7.97 (s, 1H), 7.70 (d, J=8.0Hz, 1H), 7.50 (t, J=8.0Hz, 1H), 7.44 (s, 1H), 7.35-7.32 (m, 2H),3.91(s,3H),2.08(s,3H).

C) .1- methyl -4- (3- acetylamino phenyls)-N- (benzenesulfonyl) -1H- indole 2-carboxamides

It is former using 1- methyl -4- (3- acetylamino phenyls) -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as starting Material, c) methods described in preparation process be the same as Example 3, obtains brown powder solid 49mg, yield is 78%, mp:>280℃.

¹H NMR(DMSO-d₆)δ(ppm):10.22 (brs, 1H), 8.10 (d, J=8.0Hz, 1H), 8.02 (d, J= 8.0Hz, 2H), 7.89 (s, 1H), 7.81 (s, 1H), 7.78 (d, J=8.4Hz, 1H), 7.74 (t, J=7.6Hz, 1H), 7.66 (t, J=7.6Hz, 2H), 7.55 (t, J=8.0Hz, 1H), 7.38 (d, J=7.6Hz, 1H), 7.33 (d, J=8.0Hz, 1H), 3.68(s,3H),2.10(s,3H).

Embodiment 192:1- methyl -4- (3- acetylamino phenyls)-N- (4- MethOxybenzenesulfonyls) -1H- indoles -2- first Acid amides

Using 1- methyl -4- (3- acetylamino phenyls) -7- nitro -1H- indole-2-carboxylic acids and 4- methoxybenzenesulphoismides as C) methods described in initiation material, preparation process be the same as Example 3, obtains brown powder solid 46mg, yield is 70%, mp: 240-242℃。

¹H NMR(DMSO-d₆)δ(ppm):12.63 (brs, 1H), 10.22 (s, 1H), 8.10 (d, J=8.0Hz, 1H), 7.95 (d, J=8.8Hz, 2H), 7.89 (s, 1H), 7.78 (d, J=8.8Hz, 2H), 7.54 (t, J=8.0Hz, 1H), 7.37 (d, J=7.6Hz, 1H), 7.32 (d, J=8.0Hz, 1H), 7.17 (d, J=8.8Hz, 2H), 3.85 (s, 3H), 3.68 (s, 3H),2.10(s,3H)；HRMS(ESI):m/z,calcd.for C₂₅H₂₃N₄O₇S[M+H]⁺:523.1287,found 523.1276.

Embodiment 193:4- (3- acetylamino phenyls)-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) .4- (3- acetylamino phenyls) -1H- indole -2-ethyl formates

The bromo- 1H- indole -2-ethyl formates (150mg, 0.56mmol) of 4- are dissolved in Isosorbide-5-Nitrae-dioxane (15mL), successively Add Pd₂(dppf)Cl₂(41mg, 0.056mmol) and Na₂CO₃(178mg, 1.68mmol, 2mL H₂O), after stirring, plus Enter 3- acetamidobenzeneboronic acids (300mg, 1.68mmol), under argon gas protection, 100 DEG C of reaction 2h, raw material disappears.It is cooled to room Temperature, is evaporated off solvent, and EA (30mL) dissolution residual substance, saturated common salt washing (20mL × 3) is washed (20mL × 3), column chromatography (P/E =10:1-D/M=200:1) white powdery solids 190mg, is obtained, yield is 88%, mp:229-230℃.

¹H NMR(DMSO-d₆)δ(ppm):12.08 (s, 1H), 10.08 (s, 1H), 7.91 (s, 1H), 7.65 (d, J= 8.4Hz, 1H), 7.49-7.29 (m, 4H), 7.23 (d, J=1.2Hz, 1H), 7.15 (d, J=7.2Hz, 1H), 4.35 (q, J= 6.9Hz, 2H), 2.08 (s, 3H), 1.34 (t, J=7.2Hz, 3H)

B) .4- (3- acetylamino phenyls) -1H- indole-2-carboxylic acids

With 4- (3- acetylamino phenyls) -1H- indole -2-ethyl formate initiation materials, in preparation process be the same as Example 3 b) Methods described, obtains off-white powder shape solid 100mg, yield is 78%, mp:256-257℃.

¹H NMR(DMSO-d₆)δ(ppm):12.99(brs,1H),11.95(s,1H),10.08(s,1H),7.94(s, 1H), 7.63 (d, J=7.6Hz, 1H), 7.47-7.41 (m, 2H), 7.36-7.30 (m, 2H), 7.21 (s, 1H), 7.15 (d, J= 7.2Hz,1H),2.08(s,3H).

C) .4- (3- acetylamino phenyls)-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 4- (3- acetylamino phenyls) -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, preparation process is with real C) methods described is applied in example 3, white powdery solids 71mg is obtained, yield is 96%, mp:255-257℃.

¹H NMR(DMSO-d₆)δ(ppm):12.59 (brs, 1H), 11.90 (s, 1H), 10.09 (s, 1H), 8.01 (d, J= 8.0Hz, 1H), 7.83 (s, 1H), 7.71 (d, J=8.0Hz, 3H), 7.64 (t, J=7.6Hz, 2H), 7.46 (t, J=8.0Hz, 1H), (s, the 3H) of 7.40 (d, J=8.0Hz, 1H), 7.34 (t, J=8.0Hz, 2H), 7.11 (d, J=7.2Hz, 1H), 2.09

The preparation 26 of intermediate：

The bromo- 1H- indole -2-ethyl formates of 7- nitros -3-

A) 2- (2- (2- nitrobenzophenones) hydrazono-) ethyl propionate

Ortho-nitrophenyl hydrazine hydrochloride (5.0g, 26.4mmol) is dissolved in ethanol (30mL), ethyl pyruvate is instilled (3.7g, 32mmol), reacts at room temperature 10min.Reaction solution is poured into frozen water, filters, obtains yellow powdery solid 5.56g, is produced Rate is 82%, mp:106-107℃.

¹H NMR(CDCl₃)δ(ppm):10.96 (brs, 1H), 8.21 (q, J=8.4Hz, 1H), 8.04 (d, J=8.4Hz, 1H), 7.62 (t, J=8.0Hz, 1H), 7.00 (t, J=8.0Hz, 1H), 4.36 (q, J=7.2Hz, 2H), 2.25 (s, 3H), 1.40 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₁H₁₄N₃O₄[M+H⁺]:252.0979,found 252.0986.

B) 7- nitros -1H- indole -2-ethyl formates

2- (2- (2- nitrobenzophenones) hydrazono-) ethyl propionate (5.3g, 21mmol) is added in PPA (26.5g), 90- 100 DEG C of reaction 2h, raw material disappears.It is cooled under room temperature, ice-water bath, adds 30mL frozen water, EA extractions (40mL × 2), concentration, EA is recrystallized, and obtains faint yellow solid 2.02g, yield is 41%, mp:94-95℃.

¹H NMR(CDCl₃)δ(ppm):10.34 (brs, 1H), 8.30 (d, J=8.0Hz, 1H), 8.05 (d, J=7.6Hz, 1H), 7.36 (s, 1H), 7.28 (t, J=7.6Hz, 1H), 4.47 (q, J=7.2Hz, 2H), 1.45 (t, J=7.2Hz, 3H)； HRMS(ESI):m/z,calcd for C₁₁H₁₁N₂O₄[M+H⁺]:235.0713,found235.0722.

C) the bromo- 1H- indole -2-ethyl formates of 7- nitros -3-

7- nitro -1H- indole -2-ethyl formates (100mg, 0.43mmol) are dissolved in DMF (2mL), under ice-water bath, delayed Slow DMF (2mL) solution for instilling NBS (84mg, 0.473mmol), reacts at room temperature 1.5h, and raw material disappears.Reaction solution is poured into ice Solid is separated out in water, is filtered, dries, obtains off-white powder shape solid 115mg, yield is 85%, mp:135-137℃.

¹H NMR(CDCl₃)δ(ppm):10.41 (brs, 1H), 8.37 (d, J=8.1Hz, 1H), 8.07 (d, J=7.8Hz, 1H), 7.37 (t, J=7.8Hz, 1H), 4.52 (q, J=7.2Hz, 2H), 1.49 (t, J=7.2Hz, 3H)；HRMS(ESI):m/ z,calcd for C₁₁H₁₀BrN₂O₄[M+H⁺]:312.9819,found 312.9815.

Embodiment 194：3- ethyl -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) 3- ethyls -7- nitros -1H- indole -2-ethyl formates

The bromo- 1H- indole -2-ethyl formates (200mg, 0.64mmol) of 7- nitros -3- are dissolved in toluene (15mL), Sequentially add Pd (OAc)₂(7mg, 0.032mmol), Josiphos (20mg, 0.032mmol) and K₃PO₄(679mg, 3.2mmol, 1mL H₂O), after stirring, ethyl-boron dihydroxide (142mg, 1.92mmol) is added, under argon gas protection, 80 DEG C of reaction 4h, raw material disappears Lose.Room temperature is cooled to, is concentrated, EA (40mL) dissolution residual substance is added, saturated common salt washes (20mL × 3), washing (20mL × 2), column chromatography (P/E=100:1) off-white powder shape solid 165mg, is obtained, yield is 99%, mp:94-96℃.

¹H NMR(CDCl₃)δ(ppm):10.13 (brs, 1H), 8.29 (d, J=8.0Hz, 1H), 8.05 (d, J=8.0Hz, 1H), 7.25 (t, J=8.0Hz, 1H), 4.47 (q, J=7.2Hz, 2H), 3.16 (q, J=7.2Hz, 2H), 1.46 (t, J= 6.8Hz, 3H), 1.30 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₃H₁₅N₂O₄[M+H⁺]: 263.1026,found 263.1024.

B) 3- ethyls -7- nitros -1H- indole-2-carboxylic acids

It is b) described in preparation process be the same as Example 3 with 3- ethyl -7- nitro -1H- indole -2-ethyl formate initiation materials Method, obtains faint yellow solid 60mg, and yield is 67%, mp:231-233℃.

¹H NMR(DMSO-d₆)δ(ppm):13.58 (brs, 1H), 10.58 (s, 1H), 8.28 (d, J=8.0Hz, 2H), 7.34 (t, J=8.0Hz, 1H), 3.12 (q, J=7.2Hz, 2H), 1.22 (t, J=7.6Hz, 3H)；HRMS(ESI):m/z, calcd for C₁₁H₁₁N₂O₄[M+H⁺]:235.0713,found 235.0710.

C) 3- ethyls -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 3- ethyl -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, preparation process be the same as Example 3 Middle c) methods described, obtains faint yellow solid 38mg, and yield is 80%, mp:228-230℃.

¹H NMR(DMSO-d₆)δ(ppm):11.84 (brs, 1H), 8.32 (d, J=8.0Hz, 1H), 8.25 (d, J= 8.0Hz, 1H), 8.06 (d, J=7.6Hz, 2H), 7.75 (t, J=7.2Hz, 1H), 7.67 (t, J=7.6Hz, 2H), 7.34 (t, J=8.0Hz, 1H), 3.03 (q, J=7.2Hz, 2H), 1.07 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd.for C₁₇H₁₆N₃O₅S[M+H]⁺:374.0811,found 374.0797.

Embodiment 195：3- isobutyl group -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

A) 3- isobutyl groups -7- nitros -1H- indole -2-ethyl formates

Using the bromo- 1H- indole -2-ethyl formates of 7- nitros -3- and isobutaneboronic acid as initiation material, preparation process is with implementation A) methods described in example 194, obtains faint yellow solid 177mg, yield is 85%, mp:95-96℃.

¹H NMR(CDCl₃)δ(ppm):10.19 (brs, 1H), 8.29 (d, J=8.1Hz, 1H), 8.03 (d, J=7.8Hz, 1H), 7.24 (t, J=8.1Hz, 1H), 4.46 (q, J=7.2Hz, 2H), 3.01 (d, J=7.5Hz, 2H), 1.98-2.07 (m, 1H), 1.46 (t, J=7.2Hz, 3H), 0.96 (d, J=6.6Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₅H₁₉N₂O₄ [M+H⁺]:291.1339,found 291.1335.

B) 3- ethyls -7- nitros -1H- indole-2-carboxylic acids

Using 3- isobutyl group -7- nitro -1H- indole -2-ethyl formates as initiation material, in preparation process be the same as Example 3 b) Methods described, obtains faint yellow solid 60mg, and yield is 56%, mp:185-187℃.

¹H NMR(DMSO-d₆)δ(ppm):13.54 (s, 1H), 10.60 (s, 1H), 8.27 (d, J=8.8Hz, 1H), 8.24 (d, J=8.4Hz, 1H), 7.33 (t, J=8.0Hz, 1H), 2.99 (d, J=6.8Hz, 2H), 1.93-1.99 (m, 1H), 0.89 (d, J=6.4Hz, 3H)；HRMS(ESI):m/z,calcd for C₁₃H₁₅N₂O₄[M+H⁺]:263.1026,found 263.1023.

C) 3- isobutyl groups -7- nitros-N- (benzenesulfonyl) -1H- indole 2-carboxamides

Using 3- isobutyl group -7- nitro -1H- indole-2-carboxylic acids and benzsulfamide as initiation material, preparation process be the same as Example C) methods described in 3, obtains faint yellow solid 60mg, yield is 78%, mp:194-196℃.

¹H NMR(CDCl₃)δ(ppm):10.29 (brs, 1H), 8.62 (brs, 1H), 8.29 (d, J=8.0Hz, 1H), 8.19 (d, J=7.6Hz, 2H), 8.00 (d, J=8.0Hz, 1H), 7.70 (t, J=7.6Hz, 1H), 7.60 (t, J=7.6Hz, 2H), 7.27 (t, J=8.4Hz, 1H), 2.94 (d, J=7.2Hz, 2H), 2.00-1.97 (m, 1H), 1.03 (d, J=6.4Hz, 6H).

The preparation 27 of intermediate：

The bromo- 1H- indole -2-ethyl formates of 7- nitros -5-

A) 2- (2- (2- nitro -4- bromophenyls) hydrazono-) ethyl propionate

2- nitro -4- bromanilines (20g, 92mmol) are dissolved in concentrated hydrochloric acid (100mL), 40 DEG C of reaction 2h.Then cool down To -10 DEG C, natrium nitrosum (6.98g, 101.2mmol) aqueous solution (50mL) is instilled, 2h is reacted.- 30 DEG C are cooled to, precooling is dropped to To -30 DEG C of SnCl₂In concentrated hydrochloric acid (30mL) solution of (62g, 276mmol), -20 DEG C of reaction 1h are warmed to room temperature, filtered, do It is dry, faint yellow solid 24g is obtained, yield is 97%.

Above-mentioned gained solid (24g, 89.33mmol) is dissolved in ethanol (100mL), instillation ethyl pyruvate (11.4g, 98.26mmol), 10min is stirred at room temperature, faint yellow solid is separated out, filtering obtains faint yellow solid 27g, yield is 94%, mp: 124-125℃。

¹H NMR(CDCl₃)δ(ppm):13.91 (brs, 1H), 8.34 (s, 1H), 7.92 (d, J=9.2Hz, 1H), 7.62 (d, J=9.2Hz, 1H), 4.39 (q, J=7.2Hz, 2H), 2.25 (s, 3H), 1.40 (t, J=7.2Hz, 3H)；HRMS(ESI): m/z,calcd for C₁₁H₁₃BrN₃O₄[M+H⁺]:330.0084,found 330.0074.

B) the bromo- 1H- indole -2-ethyl formates of 7- nitros -5-

Using 2- (2- (2- nitro -4- bromophenyls) hydrazono-), ethyl propionate is initiation material, and preparation process is with intermediate Prepare 26 in b) described in method, obtain faint yellow solid 11.7g, yield is 44%, mp:135-137℃.

¹H NMR(CDCl₃)δ(ppm):10.31(brs,1H),8.40(s,1H),8.17(s,1H),7.30(s,1H), 4.47 (q, J=7.2Hz, 2H), 1.45 (t, J=7.2Hz, 3H)；HRMS(ESI):m/z,calcd forC₁₁H₁₀BrN₂O₄[M+H⁺]:312.9818,found 312.9807.

Embodiment 196:The bromo- N- of 7- nitros -5- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

A) the bromo- 1H- indole-2-carboxylic acids of 7- nitros -5-

It is b) described in preparation process be the same as Example 3 using the bromo- 1H- indole -2-ethyl formates of 7- nitros -5- as initiation material Method, obtains yellow solid 180mg, and yield is 99%, mp:192-194℃.

¹H NMR(DMSO-d₆)δ(ppm):10.48(brs,1H),8.31(s,1H),8.18(s,1H),6.90(s,1H).

B) the bromo- N- of 7- nitros -5- (4- MethOxybenzenesulfonyls) -1H- indole 2-carboxamides

Using the bromo- 1H- indole-2-carboxylic acids of 7- nitros -5- and to methoxybenzenesulphoismide as initiation material, preparation process is with real C) methods described is applied in example 3, faint yellow solid 68mg is obtained, yield is 55%, mp:262-264℃.

¹H NMR(DMSO-d₆)δ(ppm):11.93 (brs, 2H), 8.47 (s, 1H), 8.34 (s, 1H), 7.98 (d, J= 8.8Hz, 2H), 7.53 (s, 1H), 7.17 (d, J=8.8Hz, 2H), 3.86 (s, 3H)

Embodiment 197：5- isobutyl group -7- nitros-N- (4- fluorophenylsulphonyls) -1H- indole 2-carboxamides

A) 5- isobutyl groups -7- nitros -1H- indole -2-ethyl formates

The bromo- 1H- indole -2-ethyl formates (291mg, 0.93mmol) of 7- nitros -5- are dissolved in toluene (12mL), Sequentially add Pd (OAc)₂(21mg, 0.093mmol), (tBu)₃P·HBF₄(54mg, 0.19mmol) and K₃PO₄(987mg, 4.65mmol,1mL H₂O), after stirring, isobutaneboronic acid (284mg, 2.79mmol) is added, under argon gas protection, 90 DEG C anti- 2h is answered, raw material disappears.Room temperature is cooled to, is concentrated, EA (40mL) dissolution residual substance, saturated common salt washing (20mL × 3), water is added Wash (20mL × 2), column chromatography (P/E=100:1) off-white powder 238mg, is obtained, yield is 88%, mp:99-100℃.

¹H NMR(CDCl₃)δ(ppm):10.23(brs,1H),8.11(s,1H),7.81(s,1H),7.29(s,1H), 4.46 (q, J=7.2Hz, 2H), 2.65 (d, J=7.2Hz, 2H), 1.91-1.98 (m, 1H), 1.44 (t, J=7.2Hz, 3H), 0.94 (d, J=6.8Hz, 6H)；HRMS(ESI):m/z,calcd for C₁₅H₁₉N₂O₄[M+H⁺]:291.1339,found 291.1330.

B) 5- isobutyl groups -7- nitros -1H- indole-2-carboxylic acids

With 5- isobutyl group -7- nitro -1H- indole -2-ethyl formate initiation materials, b) institute in preparation process be the same as Example 3 Method is stated, yellow solid 155mg is obtained, yield is 100%, mp:>300℃.

¹H NMR(DMSO-d₆)δ(ppm):10.25(brs,1H),7.93(s,1H),7.89(s,1H),6.86(s,1H), 2.63 (d, J=7.2Hz, 2H), 1.86-1.94 (m, 1H), 0.89 (d, J=6.9Hz, 6H)；HRMS(ESI):m/z,calcd for C₁₃H₁₅N₂O₄[M+H⁺]:263.1026,found 263.1026.

C) 5- isobutyl groups -7- nitros-N- (4- fluorophenylsulphonyls) -1H- indole 2-carboxamides

Using 5- isobutyl group -7- nitro -1H- indole-2-carboxylic acids and 4- fluorobenzenesulfonamides as initiation material, preparation process is with real C) methods described is applied in example 3, red brown solid 65mg is obtained, yield is 54%, mp:156-158℃.

¹H NMR(CDCl₃)δ(ppm):10.32(brs,1H),9.22(s,1H),8.26-8.22(m,2H),8.12(d,J =1.2Hz, 1H), 7.80 (s, 1H), 7.31-7.21 (m, 3H), 2.63 (d, J=7.5Hz, 2H), 1.95-1.90 (m, 1H), 0.92 (d, J=6.9Hz, 6H)

Embodiment 198：3- ethyls -5- isobutyl group -7- nitros-N- (4- fluorophenylsulphonyls) -1H- indole 2-carboxamides

A) the bromo- 7- nitros -1H- indole -2-ethyl formates of 5- isobutyl groups -3-

5- isobutyl group -7- nitro -1H- indole -2-ethyl formates (250mg, 0.86mmol) are dissolved in DMF (4mL), ice Under water-bath, it is added dropwise under NBS (168mg, 0.95mmol) DMF solution, ice-water bath, reacts 2h, raw material disappears.By reaction solution Pour into frozen water, separate out faint yellow solid, filter, dry, obtain pale yellow powder shape solid 295mg, yield is 93%, mp:84- 86℃。

¹H NMR(CDCl₃)δ(ppm):10.29 (brs, 1H), 8.17 (s, 1H), 7.80 (s, 1H), 4.50 (q, J= 7.2Hz, 2H), 2.69 (d, J=7.2Hz, 2H), 1.96-2.01 (m, 1H), 1.48 (t, J=7.2Hz, 3H), 0.96 (d, J= 6.8Hz,6H)；HRMS(ESI):m/z,calcd for C₁₅H₁₈BrN₂O₄[M+H⁺]:369.0445,found 369.0441.

B) 3- ethyls -5- isobutyl groups -7- nitro -1H- indole -2-ethyl formates

Using the bromo- 7- nitros -1H- indole -2-ethyl formates of 5- isobutyl groups -3- and ethyl-boron dihydroxide as initiation material, prepared A) methods described in journey be the same as Example 194, obtains faint yellow solid 171mg, yield is 80%, mp:72-73℃.

¹H NMR(CDCl₃)δ(ppm):10.03 (brs, 1H), 8.11 (s, 1H), 7.79 (s, 1H), 4.46 (q, J= 7.2Hz, 2H), 3.14 (q, J=7.2Hz, 2H), 2.66 (d, J=7.2Hz, 2H), 1.91-1.98 (m, 1H), 1.45 (t, J= 7.2Hz, 3H), 1.29 (t, J=7.2Hz, 3H), 0.95 (d, J=6.4Hz, 6H)；HRMS(ESI):m/z,calcd for C₁₇H₂₃N₂O₄[M+H⁺]:319.1652,found 319.16510.

C) 3- ethyls -5- isobutyl groups -7- nitro -1H- indole-2-carboxylic acids

Using 3- ethyl -5- isobutyl group -7- nitro -1H- indole -2-ethyl formates as initiation material, preparation process is with implementation B) methods described in example 3, obtains faint yellow solid 97mg, yield is 89%, mp:168-170℃.

¹H NMR(DMSO-d₆)δ(ppm):10.47 (s, 1H), 8.08 (s, 1H), 8.05 (s, 1H), 3.10 (q, J= 6.9Hz, 2H), 2.68 (d, J=6.9Hz, 2H), 1.90-1.94 (m, 1H), 1.21 (t, J=7.2Hz, 3H), 0.90 (d, J= 6.6Hz,6H)；HRMS(ESI):m/z,calcd for C₁₅H₁₉N₂O₄[M+H⁺]:291.1339,found 291.1337.

D) 3- ethyls -5- isobutyl groups -7- nitros-N- (4- fluorophenylsulphonyls) -1H- indole 2-carboxamides

Using 3- ethyl -5- isobutyl group -7- nitro -1H- indole-2-carboxylic acids and 4- fluorobenzenesulfonamides as initiation material, prepare C) methods described in process be the same as Example 3, obtains red brown solid 20mg, yield is 54%, mp:>250℃.

¹H NMR(DMSO-d₆)δ(ppm):10.00 (brs, 1H), 7.95-7.89 (m, 4H), 7.23 (t, J=9.3Hz, 2H), 3.09 (q, J=7.5Hz, 2H), 2.64 (d, J=6.3Hz, 2H), 1.90 (m, 1H), 1.13 (t, J=7.5Hz, 3H), 0.89 (d, J=6.6Hz, 6H)

Pharmacological evaluation：

Experimental example 1：Compound is evaluated FBP enzyme inhibition activities

Experimental method and result：

1. the recombination expression of people's liver FBP enzymes (FBPase)

By people liver FBPase gene plasmids PET α 8a-FBP transformed competence colibacillus bacterium BL21 (DE3) Rosetta built Cells (Novagen, Inc.), takes competence bacterias of the 100ul containing plasmid to be applied to the LB solids training containing kanamycins (30ug/mL) Support on plate, 37 DEG C of culture 12-14h are to growing obvious single bacterium colony in incubator.Picking is single from solid medium Bacterium colony, is seeded in the LB fluid nutrient mediums containing kanamycins (30ug/ml), 37 DEG C, 200rpm expansion cultures 12h.Expand training Bacterium solution after supporting adds IPTG (the final concentration of 0.1mM for making it in bacterium solution), 16 DEG C in shaking table, 200rpm culture 24h, lures Lead protein expression.Then by bacterium solution after 4 DEG C, 5500rpm centrifuge 5min, supernatant is abandoned, precipitation (thalline) adds FBPase Thalline is resuspended in Tris-Buffer.Ultrasonication thalline, then 4 DEG C, 12,000rpm centrifugations 1min.Supernatant is collected, enzyme is determined Activity, packing is saved backup after -80 DEG C.

The measure of 2.FBP enzymatic activitys

FBPase determination of activity principles：Utilize FBPase and glucose phosphate isomerase and glucose-6-phosphate dehydrogenase (G6PD) Coupling reaction, using spectrophotometer, detect the concentration of reaction product to reflect the activity of enzyme.Reaction consumption NADP⁺Generation NADPH, the absorbance change at 340nm directly reflects the activity of enzyme.FBPase Tris- are added first in reacting hole Buffer(100mM Tris、2mM MgCl₂, 0.1mM EDTA, pH7.5), inhibitor (final concentration 0.08uM, 0.4uM, 2uM or 10uM, full response hole is with FBPaseTris-Buffer replacements) and FBPase (final concentration 0.72unit).10min is incubated at 37 DEG C Afterwards, reaction substrate mixture (final concentration 0.2mM NADP are added⁺, 0.01units glucose phosphate isomerases, 0.01units Portugals Glucose-6-phosphate dehydrogenase and 0.2mM FBP), reaction starts.The absorbance of dynamic monitoring reaction product (NADPH).With The absorbance in full response hole calculates the inhibiting rate of inhibitor reacting hole, the i.e. inhibition strength to enzymatic activity as 100%.It is logical Cross the concentration of inhibitor and the activity of enzyme is inhibited curve.

The part of compounds of the present invention of table 1. is to FBP enzyme inhibition activities.

Experimental example 2：Pharmacodynamic experiment in animal body

Experimental method and result：

1. experimental method

Spontaneous diabetes B KKAy mouse models, 12 week old, the female, -42g of body weight 37.It is real by the Chinese Academy of Medical Sciences Institute of Botany offer is provided, raised in standard environment (7:00am-7:00pm day-night cycles, 22 ± 1 DEG C of temperature), feed small with KKAY Mouse special feed, drinking-water of freely ingesting.Experiment before with reference to fasting blood-glucose (＞ 200mg/dL), triglycerides (＞ 200mg/dL), T-CHOL (＞ 150mg/dL) level and body weight (45-55g), and multiple indexs such as insulin tolerance 40min change of blood sugar, KKAy mouse are randomly divided into 2 groups (every group 10), one group of gavage water is used as model control group, one group of gavage COMPOUNDS EXAMPLE 139 (200mg/kg b.w.) suspensions are used as administration group.Daily gavage once, continuous 35 days.Dynamic monitoring mouse during experiment Fasting blood glucose level.Random blood sugar was determined in the 11st day, glycated hemoglobin levels are determined within the 27th day, pyruvic acid is carried out within the 35th day Sodium tolerance test (PTT).

2. experimental result

Compared with model control group, COMPOUNDS EXAMPLE 139 can substantially reduce spontaneous diabetes B KKAy mouse Fasting blood glucose level (table 1), in administration the 5th day, blood glucose reduction amplitude was 29% (P>0.05), blood glucose reduction afterwards is respectively provided with system Meter learns difference (P<0.001)；Also random blood glucose level (the P of KKAy mouse can be significantly reduced<0.001, table 2)；And make KKAy small Mouse blood glycated hemoglobin levels substantially reduce (P<0.001, table 3).After administration 35 days, COMPOUNDS EXAMPLE 139 can substantially change It is kind to give area (AUC) (table 4) under the blood glucose rising level after Sodium Pyruvate load and blood glucose-time graph.

Table 1：Influence of the long term administration of embodiment 139 to spontaneous diabetes B KKAy mouse fasting blood-glucoses

Compared with model group, * * * P ＜ 0.005.

Table 2：Influence (11st day) of the COMPOUNDS EXAMPLE 139 to KKAy mouse random blood sugars

The * * * P ＜ 0.005 compared with model group.

Table 3：The influence (the 27th day) to KKAy mouse glycated hemoglobin levels is administered in COMPOUNDS EXAMPLE 139

The * * * P ＜ 0.005 compared with model group.

Table 4：Influence (35th day) of the COMPOUNDS EXAMPLE 139 to KKAy mouse Sodium Pyruvate tolerances

Compared with model control group, * P ＜ 0.05, * * * P ＜ 0.005.

Claims

1. compound and its pharmaceutical salts as shown in formula I,

In Formulas I,

A is selected from NR₁、O、S、Se、CR₈R₉, C=O, wherein R₁、R₈And R₉Independently selected from hydrogen, substituted or non-substituted C1-6 straight chains Or branched alkyl, substituted or non-substituted C2-6 straight or branched alkenyl or alkynyls, wherein substituent be selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, cyclopropyl, the methylene of ring third Base, cyclobutyl, oxetanylmethoxy, cyclopenta, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、 Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl；

B is selected from CR₃, N, wherein R₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, acetenyl, propinyl, Cyclopropyl, the methylene of ring third, F, Cl, Br, substitution C1-3 straight or branched alkyls, wherein substituent be selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、 Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, methyl, ethyl；

D is selected from CR₄、N；E is selected from CR₅、N；F is selected from CR₆、N；G is selected from CR₇、N；D, E, F, G can be individually for N, two while for N And/or three are simultaneously N；R₄And R₇It is asynchronously hydrogen；

(1)H、F、Cl、Br、CN、NO₂、CONRc₁Rd₁、COORc₂、SO₂Rc₃、SO₂NRc₄Rd₂, wherein described Rc₁、Rd₁、Rc₂、 Rc₃、Rc₄、Rd₂Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；

(2) substituted or non-substituted C1-8 straight or branched alkyls, substituted or non-substituted C2-8 straight or brancheds alkenyl or alkynes Base, wherein described substituent is selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、 COORa₄、CONRa₅Rb₂、 NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、 Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；

(3) substituted or non-substituted C3-7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, substitution or non-take The azacycloalkyl of the 3-8 yuan of rings in generation, wherein described substituent be selected from C1-5 straight or branched alkyls, F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、 Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, ring Propyl group, the methylene of ring third, cyclobutyl, cyclopenta；Can be miscellaneous containing 1 in the oxacycloalkyl and azacycloalkyl of 3-8 yuan of rings Atom, multiple hetero atoms can also be contained simultaneously；

(4) substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, five yuan of substituted or non-substituted virtues are miscellaneous Ring, wherein substituent are selected from C1-4 straight or branched alkyls, F, Cl, Br, NO that C1-4 straight or branched alkyls, halogen replace₂、 CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb ′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、 Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched Alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, can in five yuan of heteroaromatics To be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five First heteroaromatic can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected from 1,2,3；Its Described in halogen include F, Cl, Br；

(5)ORe₁、NRe₂Rf₁、SRe₃、NRe₄CORf₂、NRe₅COORf₃、NRe₆SO₂Rf₄, wherein described Re₁、Re₂、Rf₁、 Re₃、Re₄、Rf₂、Re₅、Rf₃、Re₆、Rf₄Independently selected from H, substituted or non-substituted C1-8 straight or branched alkyls, substitution or Non-substituted C2-8 straight or brancheds alkenyl, substituted or non-substituted C2-8 straight or branched alkynyls, wherein described substituent Selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, Wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight chain Or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；

Described Re₁、Re₂、Rf₁、Re₃、Re₄、Rf₂、Re₅、Rf₃、Re₆、Rf₄Also can be independently selected from substituted or non-substituted C3- 7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, the azacycloalkyl of substituted or non-substituted 3-8 yuan of rings, Wherein described substituent is selected from C1-5 straight or branched alkyls, F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、 CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、 Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, Cyclopenta；Can be containing 1 hetero atom in the oxacycloalkyl and azacycloalkyl of 3-8 yuan of rings, can also be simultaneously containing multiple Hetero atom；

(6)OAr_a1、NRg₁Ar_a2、SAr_a3、CH₂Ar_a4、COAr_a5、NRg₂COAr_a6、NRg₃COOAr_a7、NRg₄SO₂Ar_a8, wherein institute The Rg stated₁、Rg₂、Rg₃、Rg₄Selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Institute The Ar stated_a1、Ar_a2、Ar_a3、Ar_a4、Ar_a5、Ar_a6、Ar_a7、Ar_a8Selected from substituted or non-substituted phenyl, substituted or non-substituted contains The hexa-atomic heteroaromatic of nitrogen, wherein five yuan of substituted or non-substituted heteroaromatics, substituent are selected from C1-4 straight or branched alkyls, halogen and taken The C1-4 straight or branched alkyls in generation, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、 CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, its Described in Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb ′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described Phenyl ring, nitrogenous hexa-atomic heteroaromatic, in five yuan of heteroaromatics can be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can contain There is 1 N atom, multiple nitrogen-atoms can also be contained；Five yuan of heteroaromatics be able to can also contain multiple miscellaneous containing a hetero atom Atom, hetero atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br；

(7)OCH₂Ar_a9、NHCH₂Ar_a10、SCH₂Ar_a11、CH₂CH₂Ar_a12, described Ar_a9、Ar_a10、Ar_a11、Ar_a12Selected from substitution Or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, five yuan of substituted or non-substituted heteroaromatics, wherein replacing Base is selected from C1-4 straight or branched alkyls, F, Cl, Br, NO that C1-4 straight or branched alkyls, halogen replace₂, CN, (methylenedioxy) Base, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb ′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、 Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, ring Third methylene, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, in five yuan of heteroaromatics can be it is monosubstituted, Can be polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five yuan of heteroaromatics can contain There is a hetero atom, multiple hetero atoms can also be contained, hetero atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen bag Include F, Cl, Br；

(1)H、F、Cl、Br、CN、NO₂、CONRh₁Ri₁、COORh₂、SO₂Rh₃、SO₂NRh₄Ri₂, wherein described Rh₁、Ri₁、Rh₂、 Rh₃、Rh₄、Ri₂Independently selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third, cyclobutyl；

(2) substituted or non-substituted C1-4 straight or branched alkyls, substituted or non-substituted C2-4 straight or brancheds alkenyl, substitution Or non-substituted C2-4 alkynyls, wherein substituent is selected from F, Cl, Br, CN, NO₂、CONRh₁Ri₁、COORh₂、SO₂Rh₃、 SO₂NRh₄Ri₂, wherein described Rh₁、Ri₁、Rh₂、Rh₃、Rh₄、Ri₂Independently selected from H, methyl, ethyl, propyl group, isopropyl, ring Propyl group, the methylene of ring third, cyclobutyl；

(3) substituted or non-substituted C3-6 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-6 yuan of rings, substitution or non-take The azacycloalkyl of the 3-6 yuan of rings in generation, wherein substituent are selected from methyl, ethyl, propyl group, isopropyl, CF₃、CH₂CF₃、CHF₂、F、 Cl、Br、CN、CONRh₁Ri₁、COORh₂、SO₂Rh₃、SO₂NRh₄Ri₂、ORh₅、SRh₆、NRh₇Ri₃、NRh₈CORi₄、 NRh₉COORi₅, wherein described Rh₁、Ri₁、Rh₂、Rh₃、Rh₄、Ri₂、Rh₅、Rh₆、Rh₇、Ri₃、Rh₈、Ri₄、Rh₉、Ri₅Independently Selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third, cyclobutyl；The oxacycloalkyl or 3-6 of 3-6 yuan of rings It can also can simultaneously contain multiple hetero atoms containing 1 hetero atom in the azacycloalkyl of yuan of rings；

(4)ORj₁、NRj₂Rk₁、SRj₃、NRj₄CORk₂、NRj₅COORk₃、NRj₆SO₂Rk₄, wherein described Rj₁、Rj₂、Rk₁、 Rj₃、Rj₄、Rk₂、Rj₅、Rk₃、Rj₆、Rk₄Independently selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third, Cyclobutyl, CF₃, CH₂CF₃, CHF₂；

R is selected from following group or structure fragment：

(1) substituted or non-substituted C1-10 straight or branched alkyls, substituted or non-substituted C2-10 straight or brancheds alkenyl, take Generation or non-substituted C2-10 straight or branched alkynyls, wherein described substituent is selected from F, Cl, Br, CN, ORx₁、SRx₂、 NRx₃Ry₁、NRx₄CORy₂、COORx₅、CONRx₆Ry₃、NRx₇COORy₄、 SO₂NRx₈Ry₅, described Rx₁、Rx₂、Rx₃、Ry₁、 Rx₄、Ry₂、Rx₅、Rx₆、Ry₃、Rx₇、Ry₄、Rx₈、Ry₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, ring third is sub- Methyl, cyclobutyl, cyclopenta；

(2) substituted or non-substituted C3-7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, substitution or non-take The azacycloalkyl of the 3-8 yuan of rings in generation, wherein described substituent be selected from C1-5 straight or branched alkyls, F, Cl, Br, CN, ORx₁、SRx₂、NRx₃Ry₁、NRx₄CORy₂、COORx₅、CONRx₆Ry₃、NRx₇COORy₄、SO₂NRx₈Ry₅, described Rx₁、Rx₂、 Rx₃、Ry₁、Rx₄、Ry₂、Rx₅、Rx₆、Ry₃、Rx₇、Ry₄、Rx₈、Ry₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, The methylene of ring third, cyclobutyl, cyclopenta；It can contain 1 in the oxacycloalkyl of 3-8 yuan of rings and the azacycloalkyl of 3-8 yuan of rings Individual hetero atom, multiple hetero atoms can also be contained simultaneously；

(3) substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, five yuan of substituted or non-substituted virtues are miscellaneous Ring, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be monosubstituted or polysubstituted in phenyl ring, nitrogenous hexa-atomic heteroaromatic and five yuan of heteroaromatics；It is hexa-atomic Heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five yuan of heteroaromatics can also may be used containing a hetero atom So that containing multiple hetero atoms, hetero atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br；

(4) condensed ring or condensed hetero ring of substituted or non-substituted armaticity, substituted or non-substituted nonaromatic condensed ring or thick miscellaneous Ring, including it is substituted or non-substituted naphthalene nucleus, substituted or non-substituted benzo hexa-member heterocycle, substituted or non-substituted benzo five-membered miscellaneous Ring, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be on wherein described naphthalene nucleus, benzo hexa-member heterocycle or benzo five-membered heterocycle it is monosubstituted or It is polysubstituted；Benzo hexa-member heterocycle or benzo five-membered heterocycle can also contain multiple hetero atoms containing a hetero atom, miscellaneous Atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br.

2. compound according to claim 1 and its pharmaceutical salts, it is characterised in that described compound is as shown in formula IA

In Formulas I A,

R₄And R₇It is asynchronously hydrogen；

(2) substituted or non-substituted C1-8 straight or branched alkyls, substituted or non-substituted C2-8 straight or brancheds alkenyl or alkynes Base, wherein described substituent is selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、 SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅ Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；

(3) substituted or non-substituted C3-7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, substitution or non-take The azacycloalkyl of the 3-8 yuan of rings in generation, wherein described substituent be selected from C1-5 straight or branched alkyls, F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、 Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, ring Propyl group, the methylene of ring third, cyclobutyl, cyclopenta；Can be miscellaneous containing 1 in the oxacycloalkyl or azacycloalkyl of 3-8 yuan of rings Atom, multiple hetero atoms can also be contained simultaneously；

(5)ORe₁、NRe₂Rf₁、SRe₃、NRe₄CORf₂、NRe₅COORf₃、NRe₆SO₂Rf₄, wherein described Re₁、Re₂、Rf₁、 Re₃、Re₄、Rf₂、Re₅、Rf₃、Re₆、Rf₄Independently selected from H, substituted or non-substituted C1-8 straight or branched alkyls, substitution or Non-substituted C2-8 straight or brancheds alkenyl, substituted or non-substituted C2-8 straight or branched alkynyls, wherein described substituent Selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, Wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、 Rb₅It is straight independently selected from H, C1-4 Chain or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；

Described Re₁、Re₂、Rf₁、Re₃、Re₄、Rf₂、Re₅、Rf₃、Re₆、Rf₄Also can be independently selected from substituted or non-substituted C3-7 Cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, the azacycloalkyl of substituted or non-substituted 3-8 yuan of rings, its Described in substituent be selected from C1-5 straight or branched alkyls, F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、 CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb5, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、 Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, Cyclopenta；Can be containing 1 hetero atom in the oxacycloalkyl or azacycloalkyl of 3-8 yuan of rings, can also be simultaneously containing multiple Hetero atom；

(7)OCH₂Ar_a9、NHCH₂Ar_a10、SCH₂Ar_a11、CH₂CH₂Ar_a12, described Ar_a9、Ar_a10、Ar_a11、Ar_a12Selected from substitution Or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, five yuan of substituted or non-substituted heteroaromatics, wherein replacing Base is selected from C1-4 straight or branched alkyls, F, Cl, Br, NO that C1-4 straight or branched alkyls, halogen replace₂, CN, (methylenedioxy) Base, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb ′₅、 (CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra ′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched alkyl, ring third Base, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, in five yuan of heteroaromatics can singly take Generation or it is polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five yuan of heteroaromatics It can also contain multiple hetero atoms containing a hetero atom, hetero atom is selected from O, N, S；N is selected from 1,2,3；It is wherein described Halogen includes F, Cl, Br；

(2) substituted or non-substituted C1-4 straight or branched alkyls, substituted or non-substituted C2-4 straight or brancheds alkenyl, substitution Or non-substituted C2-4 straight or branched alkynyls, wherein substituent is selected from F, Cl, Br, CN, NO₂、CONRh₁Ri₁、COORh₂、 SO₂Rh₃、SO₂NRh₄Ri₂, wherein described Rh₁、Ri₁、Rh₂、Rh₃、Rh₄、Ri₂Independently selected from H, methyl, ethyl, propyl group, different Propyl group, cyclopropyl, the methylene of ring third, cyclobutyl；

R is selected from following group or structure fragment：

(1) substituted or non-substituted C1-10 straight or branched alkyls, substituted or non-substituted C2-10 straight or brancheds alkenyl, Substituted or non-substituted C2-10 straight or branched alkynyls, wherein described substituent is selected from F, Cl, Br, CN, ORx₁、SRx₂、 NRx₃Ry₁、NRx₄CORy₂、COORx₅、CONRx₆Ry₃、NRx₇COORy₄、SO₂NRx₈Ry₅, described Rx₁、Rx₂、Rx₃、Ry₁、Rx₄、 Ry₂、Rx₅、Rx₆、Ry₃、Rx₇、Ry₄、Rx₈、Ry₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, Cyclobutyl, cyclopenta；

(2) substituted or non-substituted C3-7 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, substitution or non-take The azacycloalkyl of the 3-8 yuan of rings in generation, wherein described substituent be selected from C1-5 straight or branched alkyls, F, Cl, Br, CN, ORx₁、SRx₂、NRx₃Ry₁、NRx₄CORy₂、COORx₅、CONRx₆Ry₃、NRx₇COORy₄、SO₂NRx₈Ry₅, described Rx₁、Rx₂、 Rx₃、Ry₁、Rx₄、Ry₂、Rx₅、Rx₆、Ry₃、Rx₇、Ry₄、Rx₈、Ry₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, The methylene of ring third, cyclobutyl, cyclopenta；It can contain 1 in the oxacycloalkyl of 3-8 yuan of rings or the azacycloalkyl of 3-8 yuan of rings Individual hetero atom, multiple hetero atoms can also be contained simultaneously；

(3) substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, five yuan of substituted or non-substituted virtues are miscellaneous Ring, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be monosubstituted or polysubstituted in phenyl ring, nitrogenous hexa-atomic heteroaromatic or five yuan of heteroaromatics；It is hexa-atomic Heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five yuan of heteroaromatics can also may be used containing a hetero atom So that containing multiple hetero atoms, hetero atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br；

(4) condensed ring or condensed hetero ring of substituted or non-substituted armaticity, substituted or non-substituted nonaromatic condensed ring or thick miscellaneous Ring, including it is substituted or non-substituted naphthalene nucleus, substituted or non-substituted benzo hexa-member heterocycle, substituted or non-substituted benzo five-membered miscellaneous Ring, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be on wherein described naphthalene nucleus, benzo hexa-member heterocycle or benzo five-membered heterocycle it is monosubstituted or It is polysubstituted；Benzo hexa-member heterocycle or benzo five-membered heterocycle can also contain multiple hetero atoms, miscellaneous original containing a hetero atom Son is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br.

3. compound according to claim 2 and its pharmaceutical salts, it is characterised in that described compound is as shown in formula IAa

In Formulas I Aa,

A and substituent R, R₄, R₅, R₆, R₇Definition is with claim 2；R₄And R₇It is asynchronously hydrogen；

R₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, acetenyl, propinyl, cyclopropyl, the methylene of ring third Base, F, Cl, Br, the C1-3 straight or branched alkyls of substitution, wherein substituent are selected from F, Cl, Br, CN, ORa₁、SRa₂、 NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、 Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, methyl, ethyl.

4. compound according to claim 3 and its pharmaceutical salts, it is characterised in that described compound is as shown in formula IAa-1

In Formulas I Aa-1,

R₁Selected from hydrogen, substituted or non-substituted C1-6 straight or branched alkyls, substituted or non-substituted C2-6 straight or branched alkenyls Or alkynyl, wherein substituent is selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、 SO₂NRa₇Rb₄、NRa₈CORb₅, cyclopropyl, the methylene of ring third, cyclobutyl, oxetanylmethoxy, cyclopenta, wherein described Ra₁、 Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, ring Propyl group, the methylene of ring third, cyclobutyl；

R₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, acetenyl, propinyl, cyclopropyl, the methylene of ring third Base, F, Cl, Br, the C1-3 straight or branched alkyls of substitution, wherein substituent are selected from F, Cl, Br, CN, ORa₁、SRa₂、 NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、 Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, methyl, ethyl；

Substituent R, R₄, R₅, R₆, R₇Definition is with claim 3；R₄And R₇It is asynchronously hydrogen.

5. compound according to claim 4 and its pharmaceutical salts, it is characterised in that described compound is as shown in formula IAa-1a

In Formulas I Aa-1a,

Substituent R, R₅, R₆, R₇Definition is with claim 4；

Y is selected from O, S, NRp₁、CH₂、CO、NRp₂CO、OCH₂、NHCH₂、SCH₂、CH₂CH₂；Wherein described Rp₁、Rp₂Selected from H, first Base, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；

Ar₁Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、 Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched Alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, can in five yuan of heteroaromatics To be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five First heteroaromatic can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected from 1,2,3；Its Described in halogen include F, Cl, Br.

6. compound according to claim 5 and its pharmaceutical salts, it is characterised in that described compound such as formula IAa-1a-1 institutes Show

In Formulas I Aa-1a-1,

R'₁Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, CHF₂、CF₃、CH₂CF₃, cyclopropyl, the methylene of ring third, oxa- ring fourth Base；

Ar₁Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、 Ra′₅、Rb′₂、Ra′₆、Rb′₃、 Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight chain or branch Alkyl group, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, in five yuan of heteroaromatics Can be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom； Five yuan of heteroaromatics can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected from 1,2,3； Wherein described halogen includes F, Cl, Br；

R'₇Selected from following atom or group or structure fragment, including

H、F、Cl、Br、CN、NO₂、CONH₂、CONHCH₃、CON(CH₃)₂、SO₂CH₃、SO₂NH₂、SO₂NHCH₃, methyl, ethyl, CF₃、CHF₂、CH₂CF₃, cyclopropyl, OCH₃、OCF₃、OCF₂CH₃、OCH₂CF₃、NH₂、NHCH₃、N(CH₃)₂、NHCOCH₃、 NHCOOCH₃；

R'₅And R'₆It is independently selected from following atom or group or structure fragment, including H, F, Cl, Br, CN, NO₂、CONH₂、 CONHCH₃、CON(CH₃)₂、SO₂CH₃、SO₂NH₂、SO₂NHCH₃, methyl, ethyl, acetenyl, vinyl, propinyl, acrylic, CF₃、CHF₂、CH₂CF₃, cyclopropyl, methylene cyclopropyl, OCH₃、OCH₂CH₃、OCF₃、OCF₂CH₃、OCH₂CF₃、NH₂、NHCH₃、N (CH₃)₂、NHCOCH₃、NHCOOCH₃；

Ar' is selected from following group or structure fragment：

(1) substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, five yuan of substituted or non-substituted virtues are miscellaneous Ring, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be monosubstituted or polysubstituted in phenyl ring, nitrogenous hexa-atomic heteroaromatic and five yuan of heteroaromatics；It is hexa-atomic Heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five yuan of heteroaromatics can also may be used containing a hetero atom So that containing multiple hetero atoms, hetero atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br；

(2) condensed ring or condensed hetero ring of substituted or non-substituted armaticity, substituted or non-substituted nonaromatic condensed ring or thick miscellaneous Ring, including it is substituted or non-substituted naphthalene nucleus, substituted or non-substituted benzo hexa-member heterocycle, substituted or non-substituted benzo five-membered miscellaneous Ring, wherein described substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br、NO₂, CN, methylene-dioxy, ORs₁、SRs₂、NRs₃Rt₁、NRs₄CORt₂、COORs₅、CONRs₆Rt₃、NRs₇COORt₄、 SO₂NRs₈Rt₅、(CH₂)nNRs₉Rt₆、(CH₂)nORs₁₀, wherein described Rs₁、Rs₂、Rs₃、Rt₁、Rs₄、Rt₂、Rs₅、Rs₆、Rt₃、 Rs₇、Rt₄、Rs₈、Rt₅、Rs₉、Rt₆、Rs₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, ring Butyl, cyclopenta；Can be on wherein described naphthalene nucleus, benzo hexa-member heterocycle or benzo five-membered heterocycle it is monosubstituted or It is polysubstituted；Benzo hexa-member heterocycle or benzo five-membered heterocycle can also contain multiple hetero atoms, miscellaneous original containing a hetero atom Son is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br.

7. compound according to claim 6 and its pharmaceutical salts, solvate or prodrug, it is characterised in that described compound As shown in formula IAa-1a-1a

In Formulas I Aa-1a-1a,

Ar₁Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、 Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched Alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, can in five yuan of heteroaromatics To be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five First heteroaromatic can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected from 1,2,3；Its Described in halogen include F, Cl, Br；

H、F、Cl、Br、CN、NO₂、CONH₂、CONHCH₃、CON(CH₃)₂、SO₂CH₃、SO₂NH₂、SO₂NHCH₃, methyl, ethyl, second Alkynyl, vinyl, propinyl, acrylic, CF₃、CHF₂、CH₂CF₃, cyclopropyl, methylene cyclopropyl, OCH₃、OCH₂CH₃、OCF₃、 OCF₂CH₃、OCH₂CF₃、NH₂、NHCH₃、N(CH₃)₂、NHCOCH₃、NHCOOCH₃；

Ar' is selected from following group or structure fragment：

8. compound according to claim 6 and its pharmaceutical salts, it is characterised in that described compound such as formula IAa-1a-1b It is shown

In Formulas I Aa-1a-1b,

Ar' is selected from following group or structure fragment：

9. compound according to claim 4 and its pharmaceutical salts, it is characterised in that described compound is as shown in formula IAa-1b

In Formulas I Aa-1b,

Substituent R, R₅, R₆, R₇Definition is with claim 4；

Ar₂Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、 Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched Alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, can in five yuan of heteroaromatics To be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five First heteroaromatic can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected from 1,2,3；Its Described in halogen include F, Cl, Br.

10. compound according to claim 3 and its pharmaceutical salts, it is characterised in that described compound is as shown in formula IAa-2

In Formulas I Aa-2,

X is selected from O, S, Se, C=O；

R₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, acetenyl, propinyl, cyclopropyl, the methylene of ring third Base, F, Cl, Br, the C1-3 straight or branched alkyls of substitution, wherein substituent are selected from F, Cl, Br, CN, ORa₁、SRa₂、 NRa₃Rb₁、COORa₄、CONRa₅Rb₂、NRa₆COORb₃、 SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、 Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, methyl, ethyl；

11. compound according to claim 10 and its pharmaceutical salts, it is characterised in that described compound such as formula IAa-2a institutes Show

In Formulas I Aa-2a,

X is selected from O, S, Se, C=O；

Ar₃Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、 Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched Alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, can in five yuan of heteroaromatics To be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five First heteroaromatic can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected from 1,2,3；Its Described in halogen include F, Cl, Br；

Substituent R, R₄, R₅, R₆Definition is with claim 10.

12. compound according to claim 11 and its pharmaceutical salts, it is characterised in that described compound such as formula IAa-2a-1 It is shown

In Formulas I Aa-2a-1,

X is selected from O, S, Se, C=O；

R'₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, CHF₂、CF₃、CH₂CF₃, cyclopropyl, the methylene of ring third, oxa- ring fourth Base；Y is selected from O, S, NH, CH₂、CO、NHCO、OCH₂、NHCH₂、SCH₂、CH₂CH₂；

Ar₃Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、 Ra′₅、Rb′₂、Ra′6、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′6、Ra′₁₀Independently selected from H, C1-4 straight chain or branch Alkyl group, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, in five yuan of heteroaromatics Can be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom； Five yuan of heteroaromatics can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected from 1,2,3； Wherein described halogen includes F, Cl, Br；

R'₄Selected from following atom or group or structure fragment, including

H、F、Cl、Br、CN、NO₂、CONH₂、CONHCH₃、CON(CH₃)₂、SO₂CH₃、SO₂NH₂、SO₂NHCH₃, methyl, ethyl, CF₃、CHF₂、CH₂CF₃, cyclopropyl, OCH₃、OCF₃、OCF₂CH₃、 OCH₂CF₃、NH₂、NHCH₃、N(CH₃)₂、NHCOCH₃、 NHCOOCH₃；

Ar' is selected from following group or structure fragment：

13. compound according to claim 12 and its pharmaceutical salts, it is characterised in that described compound such as formula IAa-2a- Shown in 1a

In Formulas I Aa-2a-1a,

X is selected from O, S, Se, C=O；

R'₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, CHF₂、CF₃、CH₂CF₃, cyclopropyl, the methylene of ring third, oxa- ring fourth Base；

Ar' is selected from following group or structure fragment：

14. compound according to claim 2 and its pharmaceutical salts, it is characterised in that described compound is as shown in formula IAb

In Formulas I Ab,

A and substituent R, R₄, R₅, R₆, R₇Definition is with claim 2.

15. compound according to claim 14 and its pharmaceutical salts, it is characterised in that described compound such as formula IAb-1 institutes Show

In Formulas I Ab-1,

Substituent R, R₄, R₅, R₆, R₇Definition is with claim 14；R₄And R₇It is asynchronously hydrogen.

16. compound according to claim 15 and its pharmaceutical salts, it is characterised in that described compound such as formula IAb-1a institutes Show

In Formulas I Ab-1a,

Substituent R, R₅, R₆, R₇Definition is with claim 15；

Ar₄Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、 Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched Alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, can in five yuan of heteroaromatics To be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five First heteroaromatic can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected from 1,2,3；Its Described in halogen include F, Cl, Br.

17. compound according to claim 16 and its pharmaceutical salts, it is characterised in that described compound such as formula IAb-1a-1 It is shown

In Formulas I Ab-1a-1,

Ar₄Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、 CONRa′₅Rb′₂、NRa′₆COORb′₃、 SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、 Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 Straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, five yuan Can be monosubstituted or polysubstituted in heteroaromatic；Hexa-atomic heteroaromatic be able to can also contain multiple containing 1 N atom Nitrogen-atoms；Five yuan of heteroaromatics can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected From 1,2,3；Wherein described halogen includes F, Cl, Br；

R'₇Selected from following atom or group or structure fragment, including

Ar' is selected from following group or structure fragment：

18. compound according to claim 17 and its pharmaceutical salts, it is characterised in that described compound such as formula IAb-1a- Shown in 1a

In Formulas I Ab-1a-1a,

Ar₄Selected from substituted or non-substituted phenyl, substituted or non-substituted nitrogenous hexa-atomic heteroaromatic, substituted or non-substituted five yuan Heteroaromatic, wherein substituent be selected from C1-4 straight or branched alkyls, halogen replace C1-4 straight or branched alkyls, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、CONRa′₅Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, wherein described Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、 Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched Alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described phenyl ring, nitrogenous hexa-atomic heteroaromatic, can in five yuan of heteroaromatics To be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can also contain multiple nitrogen-atoms containing 1 N atom；Five First heteroaromatic can also contain multiple hetero atoms containing a hetero atom, and hetero atom is selected from O, N, S；N is selected from 1,2,3；Its Described in halogen include F, Cl, Br；

Ar' is selected from following group or structure fragment：

19. compound according to claim 14 and its pharmaceutical salts, it is characterised in that described compound such as formula IAb-2 institutes Show

In Formulas I Ab-2,

X is selected from O, S, Se, C=O；

Substituent R, R₄, R₅, R₆, R₇Definition is with claim 14.

20. compound according to claim 1 and its pharmaceutical salts, it is characterised in that described compound is as shown in formula IB

In Formulas I B,

B is selected from CR₃, N, wherein R₃Selected from hydrogen, methyl, ethyl, propyl group, isopropyl, vinyl, acrylic, acetenyl, propinyl, Cyclopropyl, the methylene of ring third, F, Cl, Br, substitution C1-3 straight or branched alkyls, wherein substituent be selected from F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、CONRa₅Rb₂、 NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、 Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, methyl, ethyl；

R₄Selected from following atom or group or structure fragment, including

Described Re₁、Re₂、Rf₁、Re₃、Re₄、Rf₂、Re₅、Rf₃、Re₆、Rf₄Also can be independently selected from substituted or non-substituted C3-7 Cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-8 yuan of rings, the azacycloalkyl of substituted or non-substituted 3-8 yuan of rings, its Described in substituent be selected from C1-5 straight or branched alkyls, F, Cl, Br, CN, ORa₁、SRa₂、NRa₃Rb₁、COORa₄、 CONRa₅Rb₂、NRa₆COORb₃、SO₂NRa₇Rb₄、NRa₈CORb₅, wherein described Ra₁、Ra₂、Ra₃、Rb₁、Ra₄、Ra₅、Rb₂、 Ra₆、Rb₃、Ra₇、Rb₄、Ra₈、Rb₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, Cyclopenta；Can be containing 1 hetero atom in the oxacycloalkyl and azacycloalkyl of 3-8 yuan of rings, can also be simultaneously containing multiple Hetero atom；

(6)OAr_a1、NRg₁Ar_a2、SAr_a3、CH₂Ar_a4、COAr_a5、NRg₂COAr_a6、NRg₃COOAr_a7、NRg₄SO₂Ar_a8, wherein institute The Rg stated₁、Rg₂、Rg₃、Rg₄Selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Institute The Ar stated_a1、Ar_a2、Ar_a3、Ar_a4、Ar_a5、Ar_a6、Ar_a7、Ar_a8Selected from substituted or non-substituted phenyl, substituted or non-substituted contains The hexa-atomic heteroaromatic of nitrogen, wherein five yuan of substituted or non-substituted heteroaromatics, substituent are selected from C1-4 straight or branched alkyls, halogen and taken The C1-4 straight or branched alkyls in generation, F, Cl, Br, NO₂, CN, methylene-dioxy, ORa '₁、SRa′₂、NRa′₃Rb′₁、COORa′₄、 CONRa′5Rb′₂、NRa′₆COORb′₃、SO₂NRa′₇Rb′₄、NRa′₈CORb′₅、(CH₂)nNRa′₉Rb′₆、(CH₂)nORa′₁₀, its Described in Ra '₁、Ra′₂、Ra′₃、Rb′₁、Ra′₄、Ra′₅、Rb′₂、Ra′₆、Rb′₃、Ra′₇、Rb′₄、Ra′₈、Rb′₅、Ra′₉、Rb ′₆、Ra′₁₀Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, cyclobutyl, cyclopenta；Described Phenyl ring, nitrogenous hexa-atomic heteroaromatic, in five yuan of heteroaromatics can be monosubstituted or polysubstituted；Hexa-atomic heteroaromatic can contain There is 1 N atom, multiple nitrogen-atoms can also be contained；Five yuan of heteroaromatics be able to can also contain multiple miscellaneous containing a hetero atom Atom, hetero atom is selected from O, N, S；N is selected from 1,2,3；Wherein described halogen includes F, Cl, Br；

(3) substituted or non-substituted C3-6 cycloalkyl, the oxacycloalkyl of substituted or non-substituted 3-6 yuan of rings, substitution or non-take The azacycloalkyl of the 3-6 yuan of rings in generation, wherein substituent are selected from methyl, ethyl, propyl group, isopropyl, CF₃、CH₂CF₃、CHF₂、F、 Cl、Br、CN、CONRh₁Ri₁、COORh₂、SO₂Rh₃、SO₂NRh₄Ri₂、ORh₅、SRh₆、NRh₇Ri₃、NRh₈CORi₄、 NRh₉COORi₅, wherein described Rh₁、Ri₁、Rh₂、Rh₃、Rh₄、Ri₂、Rh₅、Rh₆、Rh₇、Ri₃、Rh₈、Ri₄、Rh₉、Ri₅Independently Selected from H, methyl, ethyl, propyl group, isopropyl, cyclopropyl, the methylene of ring third, cyclobutyl；The oxacycloalkyl and 3-6 of 3-6 yuan of rings It can also can simultaneously contain multiple hetero atoms containing 1 hetero atom in the azacycloalkyl of yuan of rings；

R is selected from following group or structure fragment：

(1) substituted or non-substituted C1-10 straight or branched alkyls, substituted or non-substituted C2-10 straight or brancheds alkenyl, take Generation or non-substituted C2-10 straight or branched alkynyls, wherein described substituent is selected from F, Cl, Br, CN, ORx₁、SRx₂、 NRx₃Ry₁、NRx₄CORy₂、COORx₅、CONRx₆Ry₃、NRx₇COORy₄、SO₂NRx₈Ry₅, described Rx₁、Rx₂、Rx₃、Ry₁、Rx₄、 Ry₂、Rx₅、Rx₆、Ry₃、Rx₇、Ry₄、Rx₈、Ry₅Independently selected from H, C1-4 straight or branched alkyl, cyclopropyl, the methylene of ring third, Cyclobutyl, cyclopenta；

21. according to the compound and pharmaceutical salts of claim 4,5,9,15, any one of 16, it is characterised in that wherein described R₁ Selected from H, methyl, ethyl, n-propyl, isopropyl, vinyl, acetenyl.

22. according to the compound and pharmaceutical salts of claim 6,7,8,17, any one of 18, it is characterised in that wherein described R’₁Selected from H, methyl, ethyl, n-propyl, isopropyl, vinyl, acetenyl.

23. according to the compound and pharmaceutical salts of claim 3,4,5,9,10, any one of 11, it is characterised in that wherein described R₃Selected from H, methyl, ethyl, vinyl, acetenyl.

24. according to the compound and pharmaceutical salts of claim 12, any one of 13, it is characterised in that wherein described R'₃It is selected from H, methyl, ethyl, vinyl, acetenyl.

25. according to any one of claim 1-20 compound and its pharmaceutical salts, it is characterised in that described compound choosing From：

26. according to any one of claim 1-25 compound, it is characterised in that the pharmaceutical salts of the compound are selected from and nothing Machine acid, Organic Acid and Base metal ion, alkaline-earth metal ions can provide the organic base combination shape of physiologically acceptable cation Into salt and ammonium salt.

27. compound according to claim 26, it is characterised in that described inorganic acid is selected from hydrochloric acid, hydrobromic acid, phosphoric acid or sulphur Acid；Described organic acid is selected from methanesulfonic acid, p-methyl benzenesulfonic acid, trifluoroacetic acid, matrimony vine acid, maleic acid, tartaric acid, fumaric acid, lemon Lemon acid or lactic acid；Described alkali metal ion is selected from lithium ion, sodium ion, potassium ion；Described alkaline-earth metal ions include calcium Ion, magnesium ion；The described organic base that can provide physiologically acceptable cation is selected from methylamine, dimethylamine, trimethylamine, piperazine Pyridine, morpholine or three (2- ethoxys) amine.

28. prepare the method for any one of claim 1-25 compound, it is characterised in that comprise the following steps：

(2) with corresponding sulfamide compound condensation reaction occurs for compound B, obtains chemical combination in claim any one of 1-25 Thing；

Wherein A, B, D, E, F, G, R are as defined in claim any one of 1-25.

29. a kind of pharmaceutical composition, it is characterised in that any one of claim 1-25 including effective dose compound and Acceptable carrier in pharmacodynamics.

30. the application of any one of claim 1-25 compound and its pharmaceutical salts in FBPase inhibitor is prepared.

31. any one of claim 1-25 compound and its pharmaceutical salts prepare prevention and or treatment it is relevant with FBPase Disease medicine in application.

32. according to the application in claim 31, it is characterised in that the disease relevant with FBPase is selected from diabetes, diabetes Complication and obesity.

33. according to the application of claim 32, it is characterised in that described diabetes are selected from type i diabetes and type ii diabetes； The diabetic complication is selected from retina, kidney, nervous system lesion and vascular complication, ischemic heart disease or dynamic Pulse atherosclerosis.