CN102603585A - N-phenyl-2-mercaptobenzamide derivatives, preparation method and application thereof - Google Patents

N-phenyl-2-mercaptobenzamide derivatives, preparation method and application thereof Download PDF

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CN102603585A
CN102603585A CN2011100227596A CN201110022759A CN102603585A CN 102603585 A CN102603585 A CN 102603585A CN 2011100227596 A CN2011100227596 A CN 2011100227596A CN 201110022759 A CN201110022759 A CN 201110022759A CN 102603585 A CN102603585 A CN 102603585A
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李锐
魏于全
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Sichuan University
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Abstract

Belonging to the technical field of chemical medicines, the invention specifically relates to N-phenyl-2-mercaptobenzamide derivatives, a preparation method and application thereof. Technically, the invention aims to provide a category of new compounds, N-phenyl-2-mercaptobenzamide derivatives, the structural of which is shown as formula I. The N-phenyl-2-mercaptobenzamide derivatives shown in formula I of the invention take the accessory protein Vif (virus infection factor) as a target, and protects the natural antiviral ability of APOBEC3G (apolipoprote in B mRNA-editing enzyme catalytic polypeptidelike3G) through inhibiting the functions of the Vif, thus providing a new choice for treatment of HIV-1.

Description

N-phenyl-2-sulfydryl benzamide derivatives
Technical field
The invention belongs to chemical medical technical field, particularly N-phenyl-2-sulfydryl benzamide derivatives.
Background technology
AIDS, promptly (acquired immunodeficiency syndrome is that what to be caused by the HIV virus infection is master's syndromes with T cellular immune function defective ADIS) to acquired immunity authority syndromes.AIDS originates from Africa, and the back is brought the U.S. into by the immigrant, and since confirming AIDS first in June, 1981, AIDS is rapid spread in the world, the existing 5,300 ten thousand people's infected by HIV that surpass in the whole world, and existing more than 2,000 ten thousand people death so far.High infection rate and sickness rate descend sufferer's life-span, bring great disaster for society and economy.
HIV is a kind of RNA viruses, belongs to retrovirus, and radius is about the sphere of 120 nanometers.HIV is divided into two kinds of hypotypes, and HIV-1 and HIV-2, most of in the world AIDS patient are infected by HIV-1, and its genome is made up of about 9200bp.Gene mainly encode 3 structural protein Gag, Pol and Env; Regulate albumen Tat and Rev for two kinds, and 4 kinds of accessory protein Vif (virion infectivity factor), Nef (negative regulator factor), Vpr (viral protein R) and Vpu (viralprotein U).
The current anti-hiv inhibitor that has gone on the market can be divided into 6 types: nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitor, proteinase inhibitor, accessory receptor suppressor factor, fusion inhibitor and integrase inhibitor, but do not find a kind of specifics of treating AIDS so far as yet.Scientist Chinese descendant in America proposed in 1996 to unite to make through the antiviral more than three kinds or three kinds to be used for treating AIDS, i.e. therapeuticcocktail of anti-retrovirals.This method is mixed use with proteinase inhibitor with multiple antiviral, reduces the chemical sproof possibility of generation of single drug, thereby delays the course of disease, prolongs patient's life, improves the quality of living.Yet HIV self variability is strong, is very easy to variation and generation resistance strain, and therefore exploitation is extremely urgent based on the inverase of novel targets.Accessory protein is in the existence of HIV and duplicate and also play an important role, and up to the present, and still none is to be target spot to the HIV accessory protein in the medicine that has gone on the market.Vif albumen is to find the earliest and the viral relevant accessory protein of infection ability.APOBEC3G (apolipoprote in B mRNA-editing enzyme catalytic polypeptidelike3G; Apolipoprotein B mRNA editing enzymes catalytic polypeptide appearance albumen 3G) be a member of Isocytosine deaminase extended familys; Has natural HIV-resistant activity; Discover that it can make the cytosine(Cyt) deamination of (-) cDNA of HIV-1 rt formation is uridylic; Cause the sudden change of virus transcription product, thereby reach the effect that suppresses virus replication.But should activity by the VIF antagonism.If develop the inverase that can suppress VIF, make APOBEC3G can exercise normal function, so new selection will be provided for the treatment of anti-HIV-1.
Summary of the invention
Technical problem to be solved by this invention provides one type of new compound N-phenyl-2-sulfydryl benzamide derivatives, and structure is suc as formula shown in the I:
R 1For having 1～6 substituent phenyl, substituting group independently is H, nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group;
R 2～R 6Independently be H, F, Cl, Br, OH, NO 2, NH 2Or C 1～C 8Alkoxyl group;
R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H;
n＝0～2。
Preferably, N-phenyl-2-sulfydryl benzamide derivatives structure is suc as formula shown in the I, R 1For having 1～6 substituent phenyl, substituting group independently is nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group;
R 2～R 6Independently be H, F, Cl, Br, OH, NO 2, NH 2Or C 1～C 8Alkoxyl group;
R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H;
n＝0～2。
Preferably, N-phenyl-2-sulfydryl benzamide derivatives structure is suc as formula shown in the I, R 1For having 1～6 substituent phenyl, substituting group independently is nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group;
R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H;
R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H;
n＝0～2。
Preferably, N-phenyl-2-sulfydryl benzamide derivatives structure is suc as formula shown in the I, R 1For having 1～6 substituent phenyl, substituting group independently is nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group;
R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H;
R 7～R 10Independently be H, F, Cl or Br; And R 7～R 10In have a substituting group at least for H;
n＝0～2。
Preferably, N-phenyl-2-sulfydryl benzamide derivatives structure is suc as formula shown in the I, R 1For having 1～6 substituent phenyl, substituting group is a nitro;
R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 4Alkoxyl group, and R 2～R 6In have a substituting group at least for H;
R 7～R 10Independently be H, F, Cl or Br, and R 7～R 10In have a substituting group at least for H;
n＝0～2。
Preferably, N-phenyl-2-sulfydryl benzamide derivatives structure is suc as formula shown in the I, R 1Be p-nitrophenyl;
R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 4Alkoxyl group, and R 2～R 6In have a substituting group at least for H;
R 7～R 10Independently be H, F or Cl, and R 7～R 10In have a substituting group at least for H;
n＝0～2。
Preferably, N-phenyl-2-sulfydryl benzamide derivatives structure is suc as formula shown in the I, R 1Be p-nitrophenyl;
R 2～R 6Independently be H or C 1～C 4Alkoxyl group, and R 2～R 6In have a substituting group at least for H;
R 7～R 10Independently be H, F or Cl, and R 7～R 10In have a substituting group at least for H;
n＝0～2。
Optimum, N-phenyl-2-sulfydryl benzamide derivatives structure is suc as formula shown in the I, R 1Be p-nitrophenyl;
R 2～R 6Independently be H or C 1～C 4Alkoxyl group, and R 2～R 6In have a substituting group at least for H;
R 8Be F or Cl, R 7, R 9And R 10Be H;
n＝0～2。
Further, the structure of N-phenyl-2-sulfydryl benzamide derivatives is suc as formula shown in the II:
Figure BDA0000044600200000041
R wherein 2～R 6Independently be H, F, Cl, Br, OH, NO 2, NH 2Or C 1～C 8Alkoxyl group;
R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H;
R 11～R 15Independently be H, nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group.
Preferably, the structure of N-phenyl-2-sulfydryl benzamide derivatives is suc as formula shown in the II, R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H; R 11～R 15Independently be H, nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group.
Preferably, the structure of N-phenyl-2-sulfydryl benzamide derivatives is suc as formula shown in the II, R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl, Br, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H; R 11～R 15Independently be H, nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group.
Further preferred, the structure of N-phenyl-2-sulfydryl benzamide derivatives is suc as formula shown in the II, R 2～R 6Independently be H or C 1～C 8Alkoxyl group; And R 2～R 6In have a substituting group at least for H;
R 7～R 10Independently be H, F, Cl or Br, and R 7～R 10In have a substituting group at least for H;
R 11～R 15Independently be H or nitro, and R 11～R 15In have a substituting group at least for H.
Optimum, the structure of N-phenyl-2-sulfydryl benzamide derivatives is suc as formula shown in the II, R 2～R 6Independently be H or methoxyl group, and R 2～R 6In 1 or 2 substituting group is arranged is methoxyl group;
R 8Be F or Cl, R 7, R 9And R 10Be H;
R 11～R 15Independently be H or nitro, and R 11～R 15In have a substituting group at least for H.
Further, the structure of N-phenyl-2-sulfydryl benzamide derivatives is shown in formula III:
Figure BDA0000044600200000051
R wherein 2～R 6Independently be H, F, Cl, Br, OH, NO 2, NH 2Or C 1～C 8Alkoxyl group;
R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H.
Preferably, the structure of N-phenyl-2-sulfydryl benzamide derivatives shown in formula III, R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H;
R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H.
Preferably, the structure of N-phenyl-2-sulfydryl benzamide derivatives shown in formula III, R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H;
R 7～R 10Independently be H, F, Cl, Br, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H.
Further preferred, the structure of N-phenyl-2-sulfydryl benzamide derivatives shown in formula III, R 2～R 6Independently be H or C 1～C 8Alkoxyl group; And R 2～R 6In have a substituting group at least for H;
R 7～R 10Independently be H, F, Cl or Br, and R 7～R 10In have a substituting group at least for H.
Further preferred, the structure of N-phenyl-2-sulfydryl benzamide derivatives shown in formula III, R 2～R 6Independently be H or C 1～C 4Alkoxyl group, and R 2～R 6In have a substituting group at least for H;
R 7～R 10Independently be H, F, Cl or Br, and R 7～R 10In have a substituting group at least for H.
Optimum, the structure of N-phenyl-2-sulfydryl benzamide derivatives shown in formula III, R 2～R 6Independently be H or methoxyl group, and R 2～R 6In 1 or 2 substituting group is arranged is methoxyl group;
R 8Be F or Cl, R 7, R 9And R 10Be H.
Second technical problem to be solved by this invention provides the preparation method of the phenyl of N-shown in the formula I-2-sulfydryl benzamide derivatives,
Figure BDA0000044600200000061
R 1For having 1～6 substituent phenyl, substituting group independently is H, nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group;
R 2～R 6Independently be H, F, Cl, Br, OH, NO 2, NH 2Or C 1～C 8Alkoxyl group;
R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H;
When Y was Br, Z was SH; When Y was SH, Z was Br; N=0～2.
1) compd A and compd B are dissolved in DMF, with anhydrous K 2CO 3With copper powder be catalyzer, in 50～60 ℃ of reactions, use the ethyl acetate extraction reaction solution, the organic layer of extraction concentrate bullion, the bullion separation and purification promptly gets Compound C;
2) Compound C is dissolved in SOCl 2, among the DMF, back flow reaction adds anhydrous THF and stirs after the solvent evaporated, add the reaction of Compound D and diisopropylethylamine again, use ethyl acetate extraction after the solvent evaporated, the organic layer of extraction concentrated bullion, the bullion separation and purification promptly gets product.
Step 1), 2) said separation purification method is column chromatography chromatogram.
The step 1) reaction times is 6～10 hours.Before concentrating, the organic layer of extraction uses the water washing after drying.
Step 2) reflux time is 1～5 hour.The organic layer of extraction concentrates preceding with saturated common salt water washing after drying.
The preparation method of the phenyl of N-shown in the formula II-2-sulfydryl benzamide derivatives is identical with the preparation method of the phenyl of N-shown in the above-mentioned formula I-2-sulfydryl benzamide derivatives, just the structure of compd B be
Figure BDA0000044600200000062
Compound C structure is
Figure BDA0000044600200000071
The preparation method of the phenyl of N-shown in the formula III-2-sulfydryl benzamide derivatives is identical with the preparation method of the phenyl of N-shown in the above-mentioned formula I-2-sulfydryl benzamide derivatives, just the structure of compd B be
Figure BDA0000044600200000072
Compound C structure is
Figure BDA0000044600200000073
The 3rd technical problem to be solved by this invention provides the purposes of the phenyl of N-shown in formula I, formula II or the formula III-2-sulfydryl benzamide derivatives; N-phenyl-2-sulfydryl benzamide derivatives has stronger anti-HIV effect shown in the external HIV virus strain test-results proof formula I; And toxicity is low; Its TI (therapeutic index, therapeutic index) is greater than 200.
Pharmaceutical composition, it is to be activeconstituents with the phenyl of N-shown in formula I, formula II or the formula III-2-sulfydryl benzamide derivatives, adds conventional auxiliary material and forms.
The 4th technical problem to be solved by this invention provides the used midbody of the phenyl of N-shown in formula I, formula II or the formula III-when 2-sulfydryl benzamide derivatives prepares, and structure is suc as formula shown in the IV:
Figure BDA0000044600200000081
K is F or Cl.
The phenyl of N-shown in the formula I of the present invention-2-sulfydryl benzamide derivatives is to be target spot with accessory protein Vif (the virus infection factor), protects the natural anti-virus ability of APOBEC3G through the function that suppresses Vif, for the treatment of anti-HIV-1 provides new selection.
Embodiment
The preparation of embodiment 1N-(2-p-methoxy-phenyl)-2-(4-nitrophenylsulfenyl) benzamide derivatives
Figure BDA0000044600200000082
With compound I a:5-chloro-N-(2-p-methoxy-phenyl)-2-(4-nitrophenylsulfenyl) BM is example, and synthetic route is as follows:
Figure BDA0000044600200000083
1, the benzoic preparation of 5-chloro-2-(4-nitrophenylsulfenyl):
(0.235g, 1mmol) (0.202g 1mmol) after the mixing, joins among the 10ml DMF, adds anhydrous K again with the p-nitrophenyl thiophenol with 5-chloro-2-bromo-benzoic acid 2CO 3(0.069g, 0.5mmol) and copper powder (0.032g, 0.5mmol), reacting by heating liquid to 55 ℃ stirred 8 hours, was cooled to room temperature.With ethyl acetate extraction 3 times, organic layer is with washing 7 times, anhydrous MgSO 4Drying concentrates, and bullion uses column chromatography purifying and promptly gets product (0.177g), productive rate 57%.
1H?NMR(400MHz，DMSO-d 6)：7.052(d，J＝8.4，1H)，7.351(m，1H)，7.576(d，J＝8.8，2H)，7.671(s，1H)，7.968(d，J＝2.4，1H)，8.208(d，J＝8.4，1H)，13.104(br，1H)。
2, the preparation of 5-chloro-N-(2-p-methoxy-phenyl)-2-(4-nitrophenylsulfenyl) BM:
(0.54g 1.8mmol) is dissolved in 10ml 8OCl with 5-chloro-2-(4-nitrophenylsulfenyl) phenylformic acid 2In, be heated to 77 ℃ and refluxed 3 hours, be cooled to room temperature, revolve and do 8OCl 2, add the anhydrous THF stirring at room of 15ml, add again ORTHO ANISIDINE (0.123g, 1mmol) and diisopropylethylamine (0.903g, 7mmol), reaction 3 was as a child revolved and was done THF, with ethyl acetate extraction 3 times, organic layer is washed 1 time with saturated aqueous common salt, anhydrous MgSO 4Drying concentrates, and bullion uses column chromatography purifying and promptly gets product (0.298g), productive rate 72%.
1H?NMR(400MHz，CDCl 3)：3.799(S，3H)，6.870(d，J＝8，1H)，6.669(m，1H)，7.084(m，1H)，7.278(m，2H)，7.492(m，2H)，7.772(s，1H)，8.073(d，J＝8.8，2H)，8.360(s，1H)，8.376(s，1H)。ESI-MS：[M+H] +?m/z?415.
The compound method of Ib is with reference to the synthetic route of Ia.The 5-fluoro-2-(4-nitrophenylsulfenyl) that makes is benzoic 1HNMR (400MHz, DMSO-d 6): 7.372 (m, 1H), 7.433 (m, 1H), 7.494 (d, J=8.8,1H), 7.718 (m, 1H), 7.821 (d, J=4.4,1H), 8.196 (d, J=8.8,1H), 8.248 (d, J=8.8,1H), 13.664 (br, 1H)
The 5-fluoro-N-(2-p-methoxy-phenyl) that makes-2-(4-nitrophenylsulfenyl) BM 1H NMR (400MHz, CDCl 3): 3.771 (S, 3H), 6.859 (d, J=8,1H), 6.965 (m, 1H), 7.078 (m, 1H), 7.246 (m, 3H), 7.552 (m, 1H), 7.618 (m, 1H), 8.061 (d, J=8.8,2H), 8.369 (d, J=7.2,1H), 8.451 (S, 1H).ESI-MS：[M+H] +?m/z?399.
Activity experiment:
Adopt international experimental technique that the anti-HIV-1 activity of medicine is detected according to SFDA " the non-Study on clinical pharmacodynamics technical director's principle of inverase (2006) ".Active result is as shown in table 1, and wherein CC50 and EC50 have done mensuration respectively twice.
Table 1
Figure BDA0000044600200000091
Figure BDA0000044600200000101
Can find out from table 1; Compound I a, Ib have the active ability of vitro inhibition HIV-1; Particularly the active ability of compound I a vitro inhibition HIV-1 is stronger; Its toxicity is low simultaneously, has high therapeutic index, thereby can be used in the new anti HIV-1 virus micromolecular inhibitor that acts on HIV-1 accessory protein VIF of preparation.

Claims (10)

1.N-phenyl-2-sulfydryl benzamide derivatives, structure is suc as formula shown in the I:
Figure FDA0000044600190000011
R 1For having 1～6 substituent phenyl, substituting group independently is H, nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group;
R 2～R 6Independently be H, F, Cl, Br, OH, NO 2, NH 2Or C 1～C 8Alkoxyl group;
R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H;
n＝0～2。
2. N-phenyl according to claim 1-2-sulfydryl benzamide derivatives is characterized in that: R 1For having 1～6 substituent phenyl, substituting group independently is nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group;
Preferably: R 1For having 1～6 substituent phenyl, substituting group independently is nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H;
Further preferably: R 1For having 1～6 substituent phenyl, substituting group independently is nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl or Br; And R 7～R 10In have a substituting group at least for H;
Further preferred, R 1For having 1～6 substituent phenyl, substituting group is a nitro; R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 4Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl or Br, and R 7～R 10In have a substituting group at least for H;
Further preferred, R 1Be p-nitrophenyl; R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 4Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F or Cl, and R 7～R 10In have a substituting group at least for H;
Further preferred, R 1Be p-nitrophenyl; R 2～R 6Independently be H or C 1～C 4Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F or Cl, and R 7～R 10In have a substituting group at least for H;
Optimum, R 1Be p-nitrophenyl; R 2～R 6Independently be H or C 1～C 4Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 8Be F or Cl, R 7, R 9And R 10Be H.
3. N-phenyl according to claim 1-2-sulfydryl benzamide derivatives is characterized in that: n=0, and structure is suc as formula shown in the II:
R 11～R 15Independently be H, nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group.
4. N-phenyl according to claim 3-2-sulfydryl benzamide derivatives is characterized in that:
R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H;
Preferably, R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl, Br, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H; R 11～R 15Independently be H, nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group;
Further preferred, R 2～R 6Independently be H or C 1～C 8Alkoxyl group; And R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl or Br, and R 7～R 10In have a substituting group at least for H; R 11～R 15Independently be H or nitro, and R 11～R 15In have a substituting group at least for H;
Optimum, R 2～R 6Independently be H or methoxyl group, and R 2～R 6In 1 or 2 substituting group is arranged is methoxyl group; R 8Be F or Cl, R 7, R 9And R 10Be H; R 11～R 15Independently be H or nitro, and R 11～R 15In have a substituting group at least for H.
5. N-phenyl according to claim 3-2-sulfydryl benzamide derivatives is characterized in that: R 13Be nitro, R 11, R 12, R 14And R 15Be H, structure is shown in formula III:
Figure FDA0000044600190000031
6. N-phenyl according to claim 5-2-sulfydryl benzamide derivatives is characterized in that:
R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H;
Preferably, R 2～R 6Independently be H, F, Cl, Br, NO 2Or C 1～C 8Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl, Br, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H;
Further preferred, R 2～R 6Independently be H or C 1～C 8Alkoxyl group; And R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl or Br, and R 7～R 10In have a substituting group at least for H;
Further preferred, R 2～R 6Independently be H or C 1～C 4Alkoxyl group, and R 2～R 6In have a substituting group at least for H; R 7～R 10Independently be H, F, Cl or Br, and R 7～R 10In have a substituting group at least for H;
Optimum, R 2～R 6Independently be H or methoxyl group, and R 2～R 6In 1 or 2 substituting group is arranged is methoxyl group; R 8Be F or Cl, R 7, R 9And R 10Be H.
7. the preparation method of the phenyl of N-shown in the claim 1 or 2-2-sulfydryl benzamide derivatives,
Figure FDA0000044600190000041
R 1For having 1～6 substituent phenyl, substituting group independently is H, nitro, C 1～C 8Alkyl or C 1～C 8Alkoxyl group;
R 2～R 6Independently be H, F, Cl, Br, OH, NO 2, NH 2Or C 1～C 8Alkoxyl group;
R 7～R 10Independently be H, F, Cl, Br, OH, NH 2, CF 3, C 1～C 8Alkyl or C 1～C 8Alkoxyl group; And R 7～R 10In have a substituting group at least for H;
When Y was Br, Z was SH; When Y was SH, Z was Br; N=0～2;
1) compd A and compd B are dissolved in DMF, with anhydrous K 2CO 3With copper powder be catalyzer, in 50～60 ℃ of reactions, use the ethyl acetate extraction reaction solution, the organic layer of extraction concentrate bullion, the bullion separation and purification promptly gets Compound C;
2) Compound C is dissolved in SOCl 2, among the DMF, back flow reaction adds anhydrous THF and stirs after the solvent evaporated, add the reaction of Compound D and diisopropylethylamine again, use ethyl acetate extraction after the solvent evaporated, the organic layer of extraction concentrated bullion, the bullion separation and purification promptly gets product.
8. the purposes of claim 1～6 N-phenyl-2-sulfydryl benzamide derivatives shown in each in the preparation anti-AIDS drug.
9. pharmaceutical composition, it is to be activeconstituents with claim 1～6 N-phenyl-2-sulfydryl benzamide derivatives shown in each, adds conventional auxiliary material and forms.
10. used midbody during preparation claim 1～6 N-phenyl shown in each-2-sulfydryl benzamide derivatives, structure is suc as formula shown in the IV:
Figure FDA0000044600190000051
K is F or Cl.
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