CN109081793B - Sulfonamide urease inhibitor and preparation method and application thereof - Google Patents

Sulfonamide urease inhibitor and preparation method and application thereof Download PDF

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CN109081793B
CN109081793B CN201811135753.8A CN201811135753A CN109081793B CN 109081793 B CN109081793 B CN 109081793B CN 201811135753 A CN201811135753 A CN 201811135753A CN 109081793 B CN109081793 B CN 109081793B
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肖竹平
倪伟伟
周天利
符紫娟
易娟
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Jishou University
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    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
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Abstract

A benzene sulfonamide compound has the following structural general formula:

Description

Sulfonamide urease inhibitor and preparation method and application thereof
Technical Field
The invention relates to a preparation method of sulfonamide urease inhibitors and application of the inhibitors in preparing anti-gastritis, anti-gastric ulcer and anti-lithangiuria medicines.
Technical Field
Helicobacter pylori (Helicobacter pylori) causes various diseases such as gastritis, gastric ulcer, duodenal ulcer, gastric atrophy, intestinal metaplasia, gastric cancer, gastric lymphoma and the like. H.pyrori is listed as the first class of carcinogenic factor by the world health organization and the international center for cancer research in 1994. It is statistical that approximately half of the world population is infected with h.pyrori, with infection rates as high as 80-90% in developing countries. The infection rate of China is about 60%. The detection rate of H.pyrori of gastritis patients is 80-90%, and that of peptic ulcer patients is higher, and reaches more than 95%. More than 90% of duodenal ulcers and around 80% of gastric ulcers are caused by h. Eradication of h. pyri is a prerequisite to the treatment of the above-mentioned diseases and to the prevention of relapse. Currently, the most common method for eradicating h.pyri is the triple method: a proton pump inhibitor (omeprazole or lansoprazole) and two antibiotics (amoxicillin, ofloxacin or metronidazole). However, omeprazole has significant side effects: it can cause abdominal pain, emesis, flatulence and other side effects, and can also cause the weight of the liver to increase; it also induces gastric carcinoid and renal failure. Furthermore, H.pyri is susceptible to resistance to the antibiotics used, and therefore, the effectiveness of this approach is decreasing year by year.
It is well known that the stomach is a strongly acidic environment, and the most important reason for the survival of H.pylori in the stomach is its urease activity. The pH value of the ammonia released by the urea hydrolyzed by the urease can be improved, and the latest research shows that urea molecules in the receptor structure are the key factors for sensing the helicobacter pylori and avoiding the gastric acid environment. The action of urease creates a suitable microenvironment for h. Other pathogens, such as Proteus vulgaris (Proteus vulgaris), Proteus mirabilis (Proteus mirabilis), Ureaplasma urealyticum (Ureapalasma urealyticum), etc., when they infect the urinary tract, they cause the pH of urine to rise due to the action of urease, resulting in precipitation of magnesium ammonium phosphate, etc., and then develop into urinary calculi. The pathogenic bacteria with urease activity either hydrolyze urea by urease to generate ammonia to provide nitrogen source for own vital activities or provide a proper microenvironment for the existence of the pathogenic bacteria by using the alkalinity of the ammonia. However, the release of ammonia can cause cytotoxicity, inflammation or ulcer, and also can cause hepatic encephalopathy and the like due to hyperammonemia, and in addition, urease can stimulate the oxidation burst of human neutrophils through immune reaction to generate ammonia chloride, participate in cell damage and induce canceration, so that the urease is an important virulence factor of the pathogenic bacteria. Therefore, the urease activity is blocked, and the germs can be effectively inhibited and even killed, so that the aim of treating the diseases is fulfilled. Meanwhile, virulence factors are not essential for the survival of bacteria like DNA, proteins, etc., so compared to traditional antibiotics, bacteria that inhibit virulence factors are less likely to develop resistance to drugs. These advantages indicate that urease inhibitors would likely be first line agents for the treatment of the above-mentioned diseases.
Urease inhibitors of various structural types have been reported, including phosphodiamides, phenols, quinones, thioureas, hydroxamates, and the like. Phosphoric diamides are reported to have the best activity in urease inhibitors, hydroxamic acids are the only urease inhibitors which have clinical application so far, but phosphoric diamides are unstable in an acid environment, and hydroxamic acids have a teratogenic risk, so that the defects hinder the further development of the phosphoric diamides. Therefore, a novel urease inhibitor needs to be searched urgently, and based on the situation, the invention discovers a novel urease inhibitor of benzene sulfonamides, which has good urease inhibiting activity.
Disclosure of Invention
A novel urease inhibitor with a structure shown as I is designed and synthesized by a computer-aided drug design technology according to the principle of action of a specific drug and a target spot and on the basis of complementarity between a drug molecule and the target spot. Experiments show that all the compounds show excellent inhibitory activity on urease.
Figure GDA0002821883830000021
The invention aims to design and synthesize a series of benzenesulfonamide (I) urease inhibitors, find a novel urease inhibitor with higher activity and lower toxic and side effects, and provide a preparation method of benzenesulfonamide compounds.
The technical scheme of the invention is as follows:
a benzene sulfonamide compound has the following structural general formula:
Figure GDA0002821883830000022
when X ═ CH in formula I, R1、R2、R3、R4And R5Is taken from any one of the following groups:
(1)R1＝R2＝R4＝R5＝H，R3＝F、Cl、Br、H、Me、NO2、NH2CN, OH or OMe;
(2)R2＝R3＝R4＝R5＝H，R1＝OMe、F、Cl、Br、Me、NO2、NH2CN or OH;
(3)R1＝R3＝R4＝R5＝H，R2＝OMe、F、Cl、Me、Br、OH、NH2or NO2；
(4)R1＝R3＝R5＝H，R2＝R4＝Cl、Br、Me、OMe、OH、NO2、NH2Or F;
(5)R3＝R4＝R5＝H，R1＝R2cl, F, Br, Me, OH, OMe or NO2；
(6)R2＝R4＝R5＝H，R1＝R3Cl, Me, OMe, OH, Br or NO2；
(7)R1＝R4＝R5＝H，R2＝R3＝F、Cl、Br、OMe、OH、CN、NO2、NH2Or Me;
(8)R2＝R3＝R5＝H，R1＝R4cl, F, Br, Me, OH, CN or NO2；
(9)R2＝R3＝R4＝H，R1＝R5F, Cl, Br, OH, CN, OMe, or Me;
when X is N, R in formula I1、R2、R3、R4And R5Is taken from any one of the following groups:
(10)R1＝R2＝R4＝R5＝H，R3f, Cl, Br, H, or OMe;
(11)R2＝R3＝R4＝R5＝H，R1＝OMe、F、NO2、NH2CN or Br;
(12)R1＝R3＝R4＝R5＝H，R2＝OMe、Cl、Br、NH2or OH;
(13)R1＝R3＝R5＝H，R2＝R4＝Me、OH、NH2or Cl;
(14)R3＝R4＝R5＝H，R1＝R2＝Cl、F、NO2OMe or OH;
(15)R2＝R4＝R5＝H，R1＝R3＝Cl、NO2or OH;
(16)R1＝R4＝R5＝H，R2＝R3cl, Br, CN, Me or NO2；
(17)R2＝R3＝R5＝H，R1＝R4＝Cl、NO2OH or Me;
(18)R2＝R3＝R4＝H，R1＝R5cl, Br, or CN;
a method for preparing benzene sulfonamide series compounds comprises the following steps:
take 2-R1-3-R2-4-R3-5-R4-6-R5Dissolving substituted benzene sulfonyl chloride (II) into anhydrous methanol, stirring for 20min, adding m-aryl diamine (III) and anhydrous K2CO3The ratio of the amounts of the substances is: 2-R1-3-R2-4-R3-5-R4-6-R5Substituted benzenesulfonyl chlorides (II), meta-aryl diamines (III), anhydrous K2CO3(4-12) reacting at 30-70 ℃ for 4-24 h, cooling, evaporating methanol, adding water, extracting with ethyl acetate for three times, combining organic phases, washing with water, and carrying out anhydrous MgSO4Drying, evaporating the solvent, purifying by silica gel column chromatography, and eluting with the following solvents in volume ratio: AcOEt, petroleum ether is 1: 1.5-1: 9, and white solid N- (3-amino aryl) -2-R is obtained1-3-R2-4-R3-5-R4-6-R5Substituted benzenesulfonamides (I); wherein R is1、R2、R3、R4And R5The definition of (A) is the same as that of the above formula (I).
Figure GDA0002821883830000041
The benzene sulfonamide series compounds have better inhibitory activity on urease, and have better activity than positive control acetohydroxamic acid. Can be used for preparing medicine for resisting gastritis, gastric ulcer or lithangiuria.
Detailed Description
The present invention is further illustrated in detail by the following examples, but it should be noted that the scope of the present invention is not limited by these examples at all.
Example 1: n- (3-aminophenyl) -2, 6-dichlorobenzene sulfonamide (69)
245mg of 2, 6-dichlorobenzenesulfonyl chloride is dissolved in 20mL of anhydrous methanol, stirred for 20min, and 206mg of m-phenylenediamine and anhydrous K are added2CO32.76g, stirring at 70 deg.C for 12h, cooling, evaporating to remove methanol, adding water, extracting with ethyl acetate for three times, combining organic phases, washing with water, anhydrous MgSO4Drying, evaporating the solvent, purifying by silica gel column chromatography, and eluting with the following solvents in volume ratio: AcOEt Petroleum Ether 1:5 gave 310mg of N- (3-aminophenyl) -2, 6-dichlorobenzene sulfonamide as a white solid in 98% yield. Melting point: 157-159 ℃; EIMS m/z: 316[ M ]+]；1H NMR(500MHz，DMSO，δ)：7.54–7.43(m,3H)，6.94(s,1H)，6.84(t,1H)，6.76(dt,1H),6.29(dt,1H),5.86(t,1H),4.12(s,2H)。
Example 2:
according to a method similar to that of example 1, benzenesulfonyl chlorides hydroxamic acid series compounds 1-105 listed in tables 1 and 2 and 3 are synthesized by using benzenesulfonyl chlorides in different substitution forms as raw materials.
Table 1 each R group of benzenesulfonamide series of compounds of general formula I where X ═ CH
Figure GDA0002821883830000042
Figure GDA0002821883830000051
Figure GDA0002821883830000061
Figure GDA0002821883830000071
Table 2 each R group of the benzenesulfonamide series of compounds of general formula I where X ═ N
Figure GDA0002821883830000072
Figure GDA0002821883830000081
Note: the starting materials were all purchased from aldrich
Example 3: enzyme inhibiting activity of compound
A solution of 25. mu.L of Jack bean urease (4U) and 25. mu.L (1mM) of the compound to be detected was added to a 96-well plate, incubated at 37 ℃ for 2 hours, then 55. mu.L of a phosphate buffer containing 100mM urea and 100mM was added, incubated at 30 ℃ for 15 minutes, 45. mu.L of a phenol reagent (a mixed solution of phenol 1% and sodium nitroprusside 0.005%) and 70. mu.L of an alkali reagent (a mixed solution of NaOCl containing NaOH0.5% and active chlorine 0.1%) were added, and after standing at room temperature for 50 minutes, the OD at 630nm was measured with a microplate reader, and the percentage inhibition was calculated by the following formula:
Figure GDA0002821883830000091
all experiments were carried out in a solution of pH 8.2 (0.01M K)2HPO41mM EDTA, 0.01M LiCl), the level of activity and the half-inhibition ratio IC50To represent, IC50The smaller the activity of this compound, the higher the results are shown in Table 3.
The results show that: the partial benzene sulfonamide series compounds have better inhibitory activity on urease, and are higher in activity than positive control acetohydroxamic acid.
TABLE 3 Inhibition of Canavalise (IC) by benzenesulfonamide series of compounds50)
Figure GDA0002821883830000092
Figure GDA0002821883830000101
Figure GDA0002821883830000111
The results show that all the compounds have obvious inhibition effect on the sword bean urease and are 30-2500 times of that of the commercial drug acetohydroxamic acid.
The above embodiments of the invention show: the invention finds a key site of the compound acting with urease, remarkably improves the activity of inhibiting the urease, and acute toxicity experiments on rats show that when the dosage of the compounds 16, 20, 27, 28, 32, 36, 37, 40, 42, 43, 44, 51, 52, 53, 72, 75, 76, 80, 81, 85, 87, 89, 95, 99, 100 and 102 reaches 5g/kg (the dosage is a nontoxic dosage specified by pharmacopoeia), no toxic sign is found in the rats, so that the compounds are safe to be used as medicines under normal dosage.
Melting point, mass spectrum and hydrogen spectrum data of compounds 1-105:
n- (3-aminophenyl) -4-fluorobenzenesulfonamide (1):
Mp 172～174℃；EIMS m/z：266[M+]；1H NMR(400MHz，DMSO，δ)：7.91–7.84(m,2H),7.38–7.30(m,2H),6.87(t,1H),6.76(dt,1H),6.36(dt,2.0Hz,1H),6.03(s,1H),5.86(t,1H),4.11(s,2H)。
n- (3-aminophenyl) -4-chlorobenzenesulfonamide (2):
Mp 179～180℃；EIMS m/z：282[M+]；1H NMR(400MHz，DMSO，δ)：7.72–7.66(m,2H),7.64–7.58(m,2H),6.84–6.73(m,2H),6.36(dt,1H),6.01(s,1H),5.86(t,1H),4.16(s,2H)。
n- (3-aminophenyl) -4-bromobenzenesulfonamide (3):
Mp 182～184℃；EIMS m/z：326[M+]；1H NMR(400MHz，DMSO，δ)：7.81–7.74(m,2H),7.75–7.68(m,2H),6.92(t,1H),6.76(dt,1H),6.36(dt,1H),6.02(s,1H),5.86(t,1H),4.07(s,2H)。
n- (3-aminophenyl) benzenesulfonamide (4):
Mp 199～201℃；EIMS m/z：248[M+]；1H NMR(400MHz，DMSO，δ)：7.71–7.64(m,2H),7.62(ddt,1H),7.55(t,2H),6.83–6.73(m,2H),6.35(dt,1H),6.01(s,1H),5.86(t,1H),4.15(s,2H)。
n- (3-aminophenyl) -4-methylbenzenesulfonamide (5):
Mp 173～175℃；EIMS m/z：262[M+]；1H NMR(400MHz，DMSO，δ)：7.71–7.65(m,2H),7.34(dd,2H),6.83–6.73(m,2H),6.35(dt,1H),6.01(s,1H),5.86(t,1H),4.16(s,2H),2.42(d,3H)。
n- (3-aminophenyl) -4-nitrobenzenesulfonamide (6):
Mp 192～194℃；EIMS m/z：293[M+]；1H NMR(400MHz，DMSO，δ)：8.38–8.32(m,2H),7.95–7.89(m,2H),6.92(t,1H),6.76(dt,1H),6.35(dt,1H),6.04(s,1H),5.86(t,1H),4.06(s,2H)。
n- (3-aminophenyl) -4-methoxybenzenesulfonamide (7):
Mp 208～209℃；EIMS m/z：278[M+]；1H NMR(400MHz，DMSO，δ)：7.58–7.52(m,2H),7.09–7.03(m,2H),6.91(t,1H),6.76(dt,1H),6.36(dt,1H),5.97(s,1H),5.86(t,1H),4.04(s,2H),3.80(s,3H)。
n- (3-aminophenyl) -4-hydroxybenzenesulfonamide (8):
Mp 163～165℃；EIMS m/z：264[M+]；1H NMR(400MHz，DMSO，δ)：7.60–7.53(m,2H),6.95–6.86(m,3H),6.76(dt,1H),6.36(dt,1H),6.00(s,1H),5.86(t,1H),5.08(s,1H),4.06(s,2H)。
n- (3-aminophenyl) -4-cyanobenzenesulfonamide (9):
Mp 145～147℃；EIMS m/z：273[M+]；1H NMR(400MHz，DMSO，δ)：8.09–8.03(m,2H),7.83–7.77(m,2H),6.88(t,1H),6.76(dt,1H),6.36(dt,1H),6.06(s,1H),5.86(t,1H),4.10(s,2H)。
n- (3-aminophenyl) -4-aminobenzenesulfonamide (10):
Mp 172～174℃；EIMS m/z：263[M+]；1H NMR(400MHz，DMSO，δ)：7.45–7.39(m,2H),6.83(t,1H),6.76(dt,1H),6.50–6.44(m,2H),6.37(dt,1H),5.86(t,1H),5.81(s,1H),4.78(s,2H),4.14(s,2H)。
n- (3-aminophenyl) -2-methoxybenzenesulfonamide (11):
Mp 207～209℃；EIMS m/z：278[M+]；1H NMR(400MHz，DMSO，δ)：7.86(dd,1H),7.57(td,1H),7.25–7.17(m,2H),6.82–6.73(m,2H),6.35–6.29(m,1H),6.31(s,1H),5.86(t,1H),4.12(s,2H),3.95(s,3H)。
n- (3-aminophenyl) -2-fluorobenzenesulfonamide (12):
Mp 221～223℃；EIMS m/z：266[M+]；1H NMR(400MHz，DMSO，δ)：7.85(ddd,1H),7.60(tdd,1H),7.27(ddd,1H),7.16(td,1H),6.87(t,1H),6.76(dt,1H),6.36–6.28(m,2H),5.86(t,1H),4.08(s,2H)。
n- (3-aminophenyl) -2-chlorobenzenesulfonamide (13):
Mp 213～214℃；EIMS m/z：282[M+]；1H NMR(400MHz，DMSO，δ)：7.92(dd,1H),7.60(dd,1H),7.49(td,1H),7.28(td,1H),6.81(t,1H),6.76(dt,1H),6.58(s,1H),6.31(dt,1H),5.86(t,1H),4.12(s,2H)。
n- (3-aminophenyl) -2-bromobenzenesulfonamide (14):
Mp 207～209℃；EIMS m/z：326[M+]；1H NMR(400MHz，DMSO，δ)：8.18(dd,1H),7.67(dd,1H),7.50(td,1H),7.42(td,1H),6.87(t,1H),6.79–6.73(m,1H),6.76(s,1H),6.31(dt,1H),5.86(t,1H),4.10(s,2H)。
n- (3-aminophenyl) -2-hydroxybenzenesulfonamide (15):
Mp 198～199℃；EIMS m/z：264[M+]；1H NMR(400MHz，DMSO，δ)：7.83(dd,1H),7.42(td,1H),7.07(td,1H),6.93–6.86(m,2H),6.76(dt,1H),6.34(dt,1H),6.01(s,1H),5.93(s,1H),5.86(t,1H),4.03(s,2H)。
n- (3-aminophenyl) -2-methylbenzenesulfonamide (16):
Mp 163～165℃；EIMS m/z：262[M+]；H NMR(400MHz，DMSO，δ)：7.87(dd,1H),7.54(td,1H),7.41(td,1H),7.34(ddd,1H),6.81(t,1H),6.76(dt,1H),6.34(s,1H),6.36–6.30(m,1H),5.86(t,1H),4.14(s,2H),2.42(d,3H)。
n- (3-aminophenyl) -2-nitrobenzenesulfonamide (17):
Mp 236～239℃；EIMS m/z：293[M+]；1H NMR(400MHz，DMSO，δ)：8.27–8.19(m,1H),8.05–7.98(m,1H),7.88–7.79(m,2H),6.87(t,1H),6.76(dt,1H),6.36(dt,1H),5.95(s,1H),5.86(t,1H),4.09(s,2H)。
n- (3-aminophenyl) -2-aminobenzenesulfonamide (18):
Mp 163～165℃；EIMS m/z：263[M+]；1H NMR(400MHz，DMSO，δ)：1H NMR(500MHz,Chloroform-d)δ7.62(dd,1H),7.27(td,1H),6.85–6.72(m,4H),6.34(ddd,1H),6.13(s,1H),5.86(dd,1H),4.35(s,2H),4.14(s,2H)。
n- (3-aminophenyl) -2-cyanobenzenesulfonamide (19):
Mp 193～195℃；EIMS m/z：273[M+]；1H NMR(400MHz，DMSO，δ)：8.12(dd,1H),7.82(dd,1H),7.72(td,J＝7.5,2.0Hz,1H),7.64(td,1H),6.90–6.83(m,2H),6.76(dt,1H),6.30(dt,1H),5.86(t,1H),4.12(s,2H)。
n- (3-aminophenyl) -3-methoxybenzenesulfonamide (20):
Mp 192～194℃；EIMS m/z：278[M+]；1H NMR(400MHz，DMSO，δ)：7.52(t,1H),7.42–7.32(m,2H),7.17(dt,1H),6.91(t,1H),6.76(dt,1H),6.36(dt,1H),5.98(s,1H),5.86(t,1H),4.05(s,2H),3.81(s,3H)。
n- (3-aminophenyl) -3-hydroxybenzenesulfonamide (21):
Mp 172～174℃；EIMS m/z：264[M+]；1H NMR(400MHz，DMSO，δ)：7.50(dt,1H),7.37(t,1H),7.23–7.16(m,2H),6.92(t,1H),6.76(dt,1H),6.42(s,1H),6.36(dt,1H),5.98(s,1H),5.86(t,1H),4.04(s,2H)。
n- (3-aminophenyl) -3-aminobenzenesulfonamide (22):
Mp 176～178℃；EIMS m/z：263[M+]；1H NMR(400MHz，DMSO，δ)：7.36(dt,1H),7.27(t,1H),7.14(t,1H),6.97(dt,1H),6.85(t,1H),6.76(dt,1H),6.38(dt,1H),5.88–5.81(m,2H),4.13(d,4H)。
n- (3-aminophenyl) -3-fluorobenzenesulfonamide (23):
Mp 152～154℃；EIMS m/z：266[M+]；1H NMR(400MHz，DMSO，δ)：7.64(dt,1H),7.57(dt,1H),7.42(td,J＝7.5,5.6Hz,1H),7.31(ddt,1H),6.87(t,1H),6.76(dt,1H),6.35(dt,1H),6.06(s,1H),5.86(t,1H),4.10(s,2H)。
n- (3-aminophenyl) -3-nitrobenzenesulfonamide (24):
Mp 175～177℃；EIMS m/z：292[M+]；1H NMR(400MHz，DMSO，δ)：8.57–8.49(m,2H),8.26(dt 1H),7.77(t,1H),6.82–6.73(m,2H),6.32(dt,1H),6.14(s,1H),5.86(t,1H),4.16(s,2H)。
n- (3-aminophenyl) -3-methylbenzenesulfonamide (25):
Mp 196～198℃；EIMS m/z：262[M+]；1H NMR(400MHz，DMSO，δ)：7.72(td,1H),7.61(dd,2H),7.40(t,J＝7.5Hz,1H),6.84–6.73(m,2H),6.36(dt,1H),5.99(s,1H),5.86(t,1H),4.15(s,2H),2.42(s,3H)。
n- (3-aminophenyl) -3-chlorobenzenesulfonamide (26):
Mp 204～206℃；EIMS m/z：282[M+]；1H NMR(400MHz，DMSO，δ)：7.83–7.76(m,2H),7.69(dt,1H),7.44(t,1H),6.93(t,1H),6.76(dt,1H),6.36(dt,1H),6.04(s,1H),5.86(t,1H),4.05(s,2H)。
n- (3-aminophenyl) -3-bromobenzenesulfonamide (27):
Mp 235～236℃；EIMS m/z：325[M+]；1H NMR(400MHz，DMSO，δ)：8.18(t,1H),7.77(dt,1H),7.69(dt,1H),7.27(t,1H),6.91(t,1H),6.76(dt,1H),6.34(dt,1H),6.06(s,1H),5.86(t,1H),4.05(s,2H)。
n- (3-aminophenyl) -3, 5-dimethylbenzenesulfonamide (28):
Mp 220～221℃；EIMS m/z：276[M+]；1H NMR(400MHz，DMSO，δ)：7.59(d,2H),7.54–7.49(m,1H),6.89(t,1H),6.76(dt,1H),6.37(dt,1H),5.89–5.84(m,2H),4.14(s,2H),2.34(s,5H)。
n- (3-aminophenyl) -3, 5-difluorobenzenesulfonamide (29):
Mp 207～209℃；EIMS m/z：256[M+]；1H NMR(400MHz，DMSO，δ)：7.44–7.38(m,2H),7.08(tt,1H),6.84–6.73(m,2H),6.35(dt,1H),6.12(s,1H),5.86(t,1H),4.16(s,2H)。
n- (3-aminophenyl) -3, 5-dimethoxybenzenesulfonamide (30):
Mp 192～194℃；EIMS m/z：308[M+]；1H NMR(400MHz，DMSO，δ)：7.14(d,2H),6.83–6.73(m,2H),6.63(t,1H),6.36(dt,1H),6.01(s,1H),5.86(t,1H),4.16(s,2H),3.81(s,6H)。
n- (3-aminophenyl) -3, 5-dichlorobenzene sulfonamide (31):
Mp 172～174℃；EIMS m/z：316[M+]；1H NMR(400MHz，DMSO，δ)：7.80(d,2H),7.58(t,1H),6.84–6.73(m,2H),6.35(dt,J＝7.3,2.1Hz,1H),6.09(s,1H),5.86(t,1H),4.16(s,2H)。
n- (3-aminophenyl) -3, 5-dibromobenzenesulfonamide (32):
Mp 153～154℃；EIMS m/z：404[M+]；1H NMR(400MHz，DMSO，δ)：8.05(d,2H),7.91(t,1H),6.93(t,1H),6.76(dt,1H),6.36(dt,1H),6.05(s,1H),5.86(t,1H),4.06(s,2H)。
n- (3-aminophenyl) -3, 5-dinitrobenzenesulfonamide (33):
Mp 136～138℃；EIMS m/z：338[M+]；1H NMR(400MHz，DMSO，δ)：9.10(t,1H),8.94(d,2H),6.85(t,1H),6.76(dt,1H),6.33(dt,1H),6.24(s,1H),5.86(t,1H),4.12(s,2H)。
n- (3-aminophenyl) -3, 5-diaminobenzenesulfonamide (34):
Mp 179～181℃；EIMS m/z：278[M+]；1H NMR(400MHz，DMSO，δ)：6.84(t,1H),6.76(dt,1H),6.64(d,2H),6.38(dt,1H),6.12(t,1H),5.88–5.81(m,2H),4.14(d,6H)。
n- (3-aminophenyl) -3, 5-dihydroxybenzenesulfonamide (35):
Mp 245～247℃；EIMS m/z：280[M+]；1H NMR(400MHz，DMSO，δ)：6.95(d,2H),6.82–6.73(m,2H),6.55(t,1H),6.49(s,2H),6.35(dt,1H),6.00(s,1H),5.86(t,1H),4.15(s,2H)。
n- (3-aminophenyl) -3, 5-difluorobenzenesulfonamide (36):
Mp 147～149℃；EIMS m/z：284[M+]；1H NMR(400MHz，DMSO，δ)：7.44–7.38(m,2H),7.08(tt,1H),6.84–6.73(m,2H),6.35(dt,1H),6.12(s,1H),5.86(t,1H),4.16(s,2H)。
n- (3-aminophenyl) -2, 3-dichlorobenzene sulfonamide (37):
Mp 182～184℃；EIMS m/z：316[M+]；1H NMR(400MHz，DMSO，δ)：7.91(dd,1H),7.77(dd,1H),7.31(t,1H),6.86(t,1H),6.76(dt,1H),6.66(s,1H),6.33(dt,1H),5.86(t,1H),4.13(s,2H)。
n- (3-aminophenyl) -2, 3-dimethylbenzenesulfonamide (38):
Mp 176～178℃；EIMS m/z：276[M+]；1H NMR(400MHz，DMSO，δ)：7.67(dd,1H),7.33(ddd,1H),7.23(t,1H),6.82–6.73(m,2H),6.33(dt,1H),5.93(s,1H),5.86(t,1H),4.15(s,2H),2.68(s,3H),2.29(d,3H)。
n- (3-aminophenyl) -2, 3-dimethoxybenzenesulfonamide (39):
Mp 162～164℃；EIMS m/z：308[M+]；1H NMR(400MHz，DMSO，δ)：7.83(dd,1H),7.38–7.31(m,2H),6.84–6.73(m,2H),6.36(dt,1H),5.98(s,1H),5.86(t,1H),4.17(s,2H),3.90(s,3H),3.78(s,3H)。
n- (3-aminophenyl) -2, 3-dihydroxybenzenesulfonamide (40):
Mp 208～210℃；EIMS m/z：280[M+]；1H NMR(400MHz，DMSO，δ)：7.40(t,1H),6.99(d,2H),6.88(t,1H),6.76(dt,1H),6.38(dt,1H),6.07(s,1H),5.92(s,1H),5.89–5.84(m,2H),4.12(s,2H)。
n- (3-aminophenyl) -2, 3-dinitrobenzenesulfonamide (41):
Mp 172～174℃；EIMS m/z：338[M+]；1H NMR(400MHz，DMSO，δ)：8.46(dd,1H),8.31(dd,1H),7.89(t,1H),7.33(s,1H),6.85(t,1H),6.76(dt,1H),6.34(dt,1H),5.86(t,1H),4.16(s,2H)。
n- (3-aminophenyl) -2, 3-dibromobenzenesulfonamide (42):
Mp 201～203℃；EIMS m/z：404[M+]；1H NMR(400MHz，DMSO，δ)：8.11(dd,1H),7.83(dd,1H),7.34(t,1H),6.85(t,1H),6.82–6.73(m,2H),6.32(dt,1H),5.86(t,1H),4.13(s,2H)。
n- (3-aminophenyl) -2, 3-difluorobenzenesulfonamide (43):
Mp 143～144℃；EIMS m/z：284[M+]；1H NMR(400MHz，DMSO，δ)：7.74(ddd,1H),7.31–7.20(m,2H),6.87(t,1H),6.76(dt,1H),6.34(dt,1H),6.17(s,1H),5.86(t,1H),4.12(s,2H)。
n- (3-aminophenyl) -2, 4-dichlorobenzene sulfonamide (44):
Mp 172～174℃；EIMS m/z：316[M+]；1H NMR(400MHz，DMSO，δ)：7.87(d,1H),7.76(d,1H),7.44(dd,1H),6.82(t,1H),6.76(dt,1H),6.62(s,1H),6.31(dt,1H),5.86(t,1H),4.13(s,2H)。
n- (3-aminophenyl) -2, 4-dihydroxybenzenesulfonamide (45):
Mp 172～174℃；EIMS m/z：280[M+]；1H NMR(400MHz，DMSO，δ)：8.30(s,1H),7.57(d,1H),6.83–6.73(m,2H),6.54(dd,1H),6.49(d,1H),6.35(dt,1H),6.00(s,1H),5.93(s,1H),5.86(t,1H),4.15(s,2H)。
n- (3-aminophenyl) -2, 4-dinitrobenzenesulfonamide (46):
Mp 212～214℃；EIMS m/z：338[M+]；1H NMR(400MHz，DMSO，δ)：8.74(d,1H),8.57(dd,1H),8.33(d,1H),7.38(s,1H),6.83(t,1H),6.76(dt,1H),6.34(dt,1H),5.86(t,1H),4.16(s,2H)。
n- (3-aminophenyl) -2, 4-dimethylbenzenesulfonamide (47):
Mp 194～195℃；EIMS m/z：276[M+]；1H NMR(400MHz，DMSO，δ)：7.80(d,1H),7.14(q,1H),7.07–7.01(m,1H),6.82–6.73(m,2H),6.34(dt,1H),5.92(s,1H),5.86(t,1H),4.15(s,2H),2.61(d,3H),2.36(d,3H)。
n- (3-aminophenyl) -2, 4-dibromobenzenesulfonamide (48):
Mp 212～214℃；EIMS m/z：404[M+]；1H NMR(400MHz，DMSO，δ)：7.87–7.79(m,2H),7.58(dd,1H),6.82(t,1H),6.79–6.73(m,2H),6.31(dt,1H),5.86(t,1H),4.13(s,2H)。
n- (3-aminophenyl) -2, 4-dimethoxybenzenesulfonamide (49):
Mp 174～176℃；EIMS m/z：308[M+]；1H NMR(400MHz，DMSO，δ)：7.92(d,1H),6.94(dd,1H),6.91–6.84(m,2H),6.76(dt,1H),6.49(s,1H),6.37(dt,1H),5.86(t,1H),4.14(s,2H),3.78(s,3H),3.44(s,3H)。
n- (3-aminophenyl) -3, 4-dichlorobenzene sulfonamide (50):
Mp 187～189℃；EIMS m/z：316[M+]；1H NMR(400MHz，DMSO，δ)：8.08(d,1H),7.65(dd,1H),7.59(d,1H),6.83–6.73(m,2H),6.34(dt,1H),6.11(s,1H),5.86(t,1H),4.16(s,2H)。
n- (3-aminophenyl) -3, 4-dibromobenzenesulfonamide (51):
Mp 182～184℃；EIMS m/z：404[M+]；1H NMR(400MHz，DMSO，δ)：8.14(d,1H),7.68(dd,1H),7.54(d,1H),6.83–6.73(m,2H),6.34(dt,1H),6.06(s,1H),5.86(t,1H),4.15(s,2H)。
n- (3-aminophenyl) -3, 4-dinitrobenzenesulfonamide (52):
Mp 162～163℃；EIMS m/z：338[M+]；1H NMR(400MHz，DMSO，δ)：8.62(d,1H),8.46(dd,1H),8.34(d,1H),6.93(t,1H),6.76(dt,1H),6.43(dt,1H),5.92(s,1H),5.86(t,1H),4.09(s,2H)。
n- (3-aminophenyl) -3, 4-dimethylbenzenesulfonamide (53):
Mp 154～156℃；EIMS m/z：276[M+]；1H NMR(400MHz，DMSO，δ)：7.69(dd,1H),7.52(dd,1H),7.22(dd,1H),6.83(t,1H),6.76(dt,1H),6.36(dt,1H),5.99(s,1H),5.86(t,1H),4.14(s,2H),2.34(d,3H),2.23(d,3H)。
n- (3-aminophenyl) -3, 4-difluorobenzenesulfonamide (54):
Mp 172～174℃；EIMS m/z：284[M+]；1H NMR(400MHz，DMSO，δ)：7.77(ddd,1H),7.61(ddd,1H),7.43(ddd,1H),6.92(t,1H),6.76(dt,1H),6.36(dt,1H),6.08(s,1H),5.86(t,1H),4.06(s,2H)。
n- (3-aminophenyl) -3, 4-dihydroxybenzenesulfonamide (55):
Mp 157～159℃；EIMS m/z：280[M+]；1H NMR(400MHz，DMSO，δ)：7.36(d,1H),7.27(dd,1H),6.96–6.85(m,2H),6.81–6.73(m,2H),6.37(dt,1H),6.01(s,1H),5.86(t,1H),5.25(s,1H),4.12(s,2H)。
n- (3-aminophenyl) -3, 4-dimethoxybenzenesulfonamide (56):
Mp 174～176℃；EIMS m/z：308[M+]；1H NMR(400MHz，DMSO，δ)：7.61–7.52(m,2H),7.15(d,1H),6.90(t,1H),6.76(dt,1H),6.37(dt,1H),5.95(s,1H),5.86(t,1H),4.06(s,2H),3.89(d,6H)。
n- (3-aminophenyl) -3, 4-diaminobenzenesulfonamide (57):
Mp 212～214℃；EIMS m/z：278[M+]；1H NMR(400MHz，DMSO，δ)：6.97–6.87(m,2H),6.84(t,1H),6.76(dt,1H),6.59(d,1H),6.38(dt,1H),5.88–5.81(m,2H),4.35(s,4H),4.13(s,2H)。
n- (3-aminophenyl) -3, 4-dicyanobenzenesulfonamide (58):
Mp 181～182℃；EIMS m/z：298[M+]；1H NMR(400MHz，DMSO，δ)：1H NMR(500MHz,Chloroform-d)δ8.55(d,1H),8.27(dd,1H),7.96(d,1H),6.82(t,1H),6.76(dt,1H),6.37(dt,1H),6.12(s,1H),5.86(t,1H),4.16(s,2H)。
n- (3-aminophenyl) -2, 5-difluorobenzenesulfonamide (59):
Mp 134～136℃；EIMS m/z：284[M+]；1H NMR(400MHz，DMSO，δ)：1H NMR(500MHz,Chloroform-d)δ7.60(ddd,1H),7.33(dddd,1H),7.26(ddd,1H),6.85(t,1H),6.76(dt,1H),6.38–6.29(m,2H),5.86(t,1H),4.10(s,2H)。
n- (3-aminophenyl) -2, 5-dichlorobenzene sulfonamide (60):
Mp 136～137℃；EIMS m/z：316[M+]；1H NMR(400MHz，DMSO，δ)：1H NMR(500MHz,Chloroform-d)δ7.97(d,1H),7.74–7.65(m,2H),6.82(t,1H),6.76(dt,1H),6.59(s,1H),6.31(dt,1H),5.86(t,1H),4.13(s,2H)。
n- (3-aminophenyl) -2, 5-dibromobenzenesulfonamide (61):
Mp 207～208℃；EIMS m/z：404[M+]；1H NMR(400MHz，DMSO，δ)：8.13(d,1H),7.64–7.55(m,2H),6.82(t,1H),6.76(dt,1H),6.73(s,1H),6.32(dt,1H),5.86(t,1H),4.13(s,2H)。
n- (3-aminophenyl) -2, 5-dimethylbenzenesulfonamide (62):
Mp 206～208℃；EIMS m/z：276[M+]；1H NMR(400MHz，DMSO，δ)：7.69–7.65(m,1H),7.37–7.31(m,1H),7.28(dd,1H),6.84–6.73(m,2H),6.34(dt,1H),5.91(s,1H),5.86(t,1H),4.13(s,2H),2.59(d,3H),2.24(d,3H)。
n- (3-aminophenyl) -2, 5-dicyanobenzenesulfonamide (63):
Mp 213～214℃；EIMS m/z：298[M+]；1H NMR(400MHz，DMSO，δ)：8.56(d,1H),8.04–7.94(m,2H),6.98(t,1H),6.76(dt,1H),6.36(dt,1H),6.17(s,1H),5.86(t,1H),4.08(s,2H)。
n- (3-aminophenyl) -2, 5-dinitrobenzenesulfonamide (64):
Mp 217～219℃；EIMS m/z：336[M+]；1H NMR(400MHz，DMSO，δ)：9.16(d,2H),8.60(dd,1H),8.28(d,1H),6.89(t,1H),6.76(dt,1H),6.36(dt,1H),5.86(t,1H),4.14(s,2H)。
n- (3-aminophenyl) -2, 5-dihydroxybenzenesulfonamide (65):
Mp 168～169℃；EIMS m/z：280[M+]；1H NMR(400MHz，DMSO，δ)：7.24(d,1H),7.17(dd,1H),6.88(t,1H),6.86–6.80(m,2H),6.76(dt,1H),6.42–6.34(m,2H),5.93(s,1H),5.86(t,1H),4.13(s,2H)。
n- (3-aminophenyl) -2, 6-difluorobenzenesulfonamide (66):
Mp 201～202℃；EIMS m/z：284[M+]；1H NMR(400MHz，DMSO，δ)：7.61(tt,1H),7.00(td,J＝7.7,1.1Hz,2H),6.87(t,1H),6.76(dt,1H),6.42(s,1H),6.30(dt,1H),5.86(t,1H),4.10(s,2H)。
n- (3-aminophenyl) -2, 6-dinitrobenzenesulfonamide (67):
Mp 217～218℃；EIMS m/z：338[M+]；1H NMR(400MHz，DMSO，δ)：8.39(d,2H),8.26(s,1H),7.90(t,1H),6.89(t,1H),6.76(dt,1H),6.38(dt,1H),5.86(t,1H),4.13(s,2H)。
n- (3-aminophenyl) -2, 6-dibromobenzenesulfonamide (68):
Mp 209～210℃；EIMS m/z：404[M+]；1H NMR(400MHz，DMSO，δ)：7.58(d,2H),7.29(t,1H),6.97–6.87(m,2H),6.76(dt,1H),6.31(dt,1H),5.86(t,1H),4.10(s,2H)。
n- (3-aminophenyl) -2, 6-dichlorobenzene sulfonamide (69):
Mp 217～218℃；EIMS m/z：316[M+]；1H NMR(400MHz，DMSO，δ)：7.50(dd,1H),7.48–7.42(m,2H),6.88(t,1H),6.76(s,1H),6.79–6.73(m,1H),6.30(dt,1H),5.86(t,1H),4.09(s,2H)。
n- (3-aminophenyl) -2, 6-dihydroxybenzenesulfonamide (70):
Mp 214～216℃；EIMS m/z：280[M+]；1H NMR(400MHz，DMSO，δ)：7.31(t,1H),6.81–6.72(m,2H),6.59(d,2H),6.35(ddd,1H),6.00(s,1H),5.93(s,2H),5.86(dd,1H),4.14(s,2H)。
n- (3-aminophenyl) -2, 6-dicyanobenzenesulfonamide (71):
Mp 219～221℃；EIMS m/z：298[M+]；1H NMR(400MHz，DMSO，δ)：8.08(d,2H),7.89(t,1H),7.10(s,1H),6.85(t,1H),6.76(dt,1H),6.30(dt,1H),5.86(t,1H),4.16(s,2H)。
n- (3-aminophenyl) -2, 6-dimethoxybenzenesulfonamide (72):
Mp 223～224℃；EIMS m/z：308[M+]；1H NMR(400MHz，DMSO，δ)：7.59(t,1H),7.01(d,2H),6.85(t,1H),6.76(dt,1H),6.40(s,1H),6.32(dt,1H),5.86(t,1H),4.07(s,2H),3.44(s,6H)。
n- (3-aminophenyl) -2, 6-dimethylbenzenesulfonamide (73):
Mp 216～217℃；EIMS m/z：276[M+]；1H NMR(400MHz，DMSO，δ)：7.48(t,1H),7.26(d,2H),6.82–6.73(m,2H),6.34(dt,1H),5.86(t,1H),5.80(s,1H),4.14(s,2H),2.52(s,6H)。
n- (6-aminopyridin-2-yl) -4-fluorobenzenesulfonamide (74):
Mp 223～224℃；EIMS m/z：267[M+]；1H NMR(400MHz，DMSO，δ)：8.02–7.94(m,2H),7.38–7.30(m,2H),7.12(t,1H),6.73(dd,1H),6.21(dd,1H),5.98(s,1H),3.06(s,2H)。
n- (6-aminopyridin-2-yl) -4-chlorobenzenesulfonamide (75):
Mp 219～221℃；EIMS m/z：283[M+]；1H NMR(400MHz，DMSO，δ)：7.73–7.67(m,2H),7.64–7.58(m,2H),7.11(t,1H),6.73(dd,1H),6.21(dd,1H),5.96(s,1H),3.04(s,2H)。
n- (6-aminopyridin-2-yl) -4-bromobenzenesulfonamide (76):
Mp 203～204℃；EIMS m/z：327[M+]；1H NMR(400MHz，DMSO，δ)：7.79–7.69(m,4H),7.11(t,1H),6.73(dd,1H),6.21(dd,1H),5.97(s,1H),3.06(s,2H)。
n- (6-aminopyridin-2-yl) benzenesulfonamide (77):
Mp 194～196℃；EIMS m/z：249[M+]；1H NMR(400MHz，DMSO，δ)：7.87–7.80(m,2H),7.62(ddt,1H),7.55(t,J＝7.4Hz,2H),7.09(t,1H),6.73(dd,1H),6.25–6.18(m,2H),3.16(s,2H)。
n- (6-aminopyridin-2-yl) -4-methoxybenzenesulfonamide (78):
Mp 215～216℃；EIMS m/z：279[M+]；1H NMR(400MHz，DMSO，δ)：7.65–7.59(m,2H),7.11(t,1H),7.09–7.03(m,2H),6.73(dd,1H),6.21(dd,1H),5.95(s,1H),3.80(s,3H),3.03(s,2H)。
n- (6-aminopyridin-2-yl) -2-methoxybenzenesulfonamide (79):
Mp 223～224℃；EIMS m/z：279[M+]；1H NMR(400MHz，DMSO，δ)：7.81(dd,1H),7.56(td,1H),7.17(qd,2H),7.08(t,1H),6.73(dd,1H),6.38(s,1H),6.21(dd,1H),3.95(s,3H),3.05(s,2H)。
n- (6-aminopyridin-2-yl) -2-fluorobenzenesulfonamide (80):
Mp 179～181℃；EIMS m/z：267[M+]；1H NMR(400MHz，DMSO，δ)：7.80(ddd,1H),7.63(tdd,1H),7.28(ddd,1H),7.17(td,1H),7.08(t,1H),6.73(dd,1H),6.28–6.18(m,2H),3.06(s,2H)。
n- (6-aminopyridin-2-yl) -2-cyanobenzenesulfonamide (81):
Mp 198～199℃；EIMS m/z：274[M+]；1H NMR(400MHz，DMSO，δ)：8.19(dd,1H),7.85(dd,1H),7.75(dtd,2H),7.13(t,1H),6.73(dd,1H),6.21(dd,1H),5.96(s,1H),3.07(s,2H)。
n- (6-aminopyridin-2-yl) -2-bromobenzenesulfonamide (82):
Mp 169～171℃；EIMS m/z：327[M+]；1H NMR(400MHz，DMSO，δ)：8.25(dd,1H),7.67(dd,1H),7.50(td,1H),7.42(td,1H),7.12(t,1H),6.73(dd,1H),6.21(dd,1H),6.06(s,1H),3.08(s,2H)。
n- (6-aminopyridin-2-yl) -3-methoxybenzenesulfonamide (83):
Mp 189～191℃；EIMS m/z：279[M+]；1H NMR(400MHz，DMSO，δ)：7.49(t,1H),7.42–7.32(m,2H),7.17(dt,1H),7.11(t,1H),6.73(dd,1H),6.21(dd,1H),5.96(s,1H),3.81(s,3H),3.04(s,2H)。
n- (6-aminopyridin-2-yl) -3-hydroxybenzenesulfonamide (84):
Mp 192～193℃；EIMS m/z：265[M+]；1H NMR(400MHz，DMSO，δ)：7.47(dt,1H),7.37(t,1H),7.23(t,1H),7.15(ddd,2H),6.73(dd,1H),6.49(s,1H),6.21(dd,1H),5.98(s,1H),2.49(s,2H)。
n- (6-aminopyridin-2-yl) -3-chlorobenzenesulfonamide (85):
Mp 189～190℃；EIMS m/z：283[M+]；1H NMR(400MHz，DMSO，δ)：7.94(t,1H),7.69(dt,1H),7.62(dt,1H),7.34(t,1H),7.10(t,1H),6.73(dd,1H),6.21(dd,1H),6.01(s,1H),3.05(s,2H)。
n- (6-aminopyridin-2-yl) -3-bromobenzenesulfonamide (86):
Mp 203～204℃；EIMS m/z：327[M+]；1H NMR(400MHz，DMSO，δ)：8.13(t,1H),7.77(dt,1H),7.70(dt,1H),7.29(t,1H),7.10(t,1H),6.73(dd,1H),6.21(dd,1H),6.00(s,1H),3.05(s,2H)。
n- (6-aminopyridin-2-yl) -3-aminobenzenesulfonamide (87):
Mp198～200℃；EIMS m/z：264[M+]；1H NMR(400MHz，DMSO，δ)：7.30(dt,1H),7.23(t,1H),7.15(t,1H),6.98(t,1H),6.90(dt,1H),6.73(dd,1H),6.21(dd,1H),5.94(s,1H),4.06(s,2H),2.46(s,2H)。
n- (6-aminopyridin-2-yl) -3, 5-dichloroaminobenzenesulfonamide (88):
Mp178～180℃；EIMS m/z：317[M+]；1H NMR(400MHz，DMSO，δ)：7.75(d,2H),7.59(t,1H),7.12(t,1H),6.73(dd,1H),6.21(dd,1H),5.96(s,1H),3.07(s,2H)。
3, 5-diamino-N- (6-aminopyridin-2-yl) benzenesulfonamide (89):
Mp196～197℃；EIMS m/z：279[M+]；1H NMR(400MHz，DMSO，δ)：7.09(t,1H),6.73(dd,1H),6.67(d,2H),6.21(dd,1H),6.15–6.08(m,2H),4.14(s,4H),3.16(s,2H)。
n- (6-aminopyridin-2-yl) -2, 3-dichloroaminobenzenesulfonamide (90):
Mp193～194℃；EIMS m/z：317[M+]；1H NMR(400MHz，DMSO，δ)：7.89(ddd,2H),7.32(t,1H),7.09(t,1H),6.73(dd,1H),6.21(dd,1H),6.11(s,1H),3.17(s,2H)。
n- (6-aminopyridin-2-yl) -2, 3-difluoroaminobenzenesulfonamide (91):
Mp194～195℃；EIMS m/z：285[M+]；1H NMR(400MHz，DMSO，δ)：7.73(ddd,1H),7.33–7.21(m,2H),7.13(t,1H),6.73(dd,1H),6.21(dd,1H),5.87(s,1H),3.05(s,2H)。
n- (6-Aminopyridin-2-yl) -2, 3-dinitroaminobenzenesulfonamide (92):
Mp222～223℃；EIMS m/z：339[M+]；1H NMR(400MHz，DMSO，δ)：8.72(s,1H),8.57(dd,1H),8.37(dd,1H),7.99(t,1H),7.09(t,1H),6.73(dd1H),6.21(dd,1H),3.19(s,2H)。
n- (6-aminopyridin-2-yl) -2, 3-dimethoxyaminobenzenesulfonamide (93):
Mp235～237℃；EIMS m/z：309[M+]；1H NMR(400MHz，DMSO，δ)：7.70(dd,1H),7.31(t,1H),7.26(dd,1H),7.09(t,1H),6.73(dd,1H),6.21(dd,1H),5.96(s,1H),3.89(d,6H),3.05(s,2H)。
n- (6-aminopyridin-2-yl) -2, 3-dihydroxyaminobenzenesulfonamide (94):
Mp256～257℃；EIMS m/z：281[M+]；1H NMR(400MHz，DMSO，δ)：7.16–7.09(m,2H),6.94(dd,1H),6.86(t,1H),6.73(dd,1H),6.21(dd,1H),6.04(s,1H),5.97(s,1H),5.87(s,1H),3.05(s,2H)。
n- (6-aminopyridin-2-yl) -2, 4-dichloroaminobenzenesulfonamide (95):
Mp232～233℃；EIMS m/z：317[M+]；1H NMR(400MHz，DMSO，δ)：7.92(d,1H),7.81(d,1H),7.52(dd,1H),7.09(t,1H),6.73(dd,1H),6.21(dd,1H),6.10(s,1H),3.17(s,2H)。
n- (6-aminopyridin-2-yl) -3, 4-dichloroaminobenzenesulfonamide (96):
Mp241～242℃；EIMS m/z：317[M+]；1H NMR(400MHz，DMSO，δ)：7.85(d,1H),7.76(dd,1H),7.71(d,1H),7.13(t,1H),6.73(dd,1H),6.21(dd,1H),5.93(s,1H),3.07(s,2H)。
n- (6-aminopyridin-2-yl) -3, 4-dibromoaminobenzenesulfonamide (97):
Mp231～232℃；EIMS m/z：405[M+]；1H NMR(400MHz，DMSO，δ)：7.90(d,1H),7.80(dd,1H),7.66(d,1H),7.14(t,1H),6.73(dd,1H),6.21(dd,1H),5.91(s,1H),3.07(s,2H)。
n- (6-Aminopyridin-2-yl) -3, 4-dinitroaminobenzenesulfonamide (98):
Mp241～243℃；EIMS m/z：339[M+]；1H NMR(400MHz，DMSO，δ)：8.53(d,1H),8.40(dd,1H),8.31(d,1H),7.20(t,1H),6.73(dd,1H),6.21(dd,1H),5.89(s,1H),3.05(s,2H)。
n- (6-Aminopyridin-2-yl) -3, 4-dimethylaminobenzenesulfonamide (99):
Mp197～198℃；EIMS m/z：277[M+]；1H NMR(400MHz，DMSO，δ)：7.74–7.66(m,2H),7.27(dd,1H),7.06(t,1H),6.73(dd,1H),6.45(s,1H),6.21(dd,1H),3.16(s,2H),2.32(dd,6H)。
n- (6-aminopyridin-2-yl) -3, 4-dicyanoanilide (100):
Mp198～199℃；EIMS m/z：299[M+]；1H NMR(400MHz，DMSO，δ)：8.55(d,1H),8.41(dd,1H),8.09(d,1H),7.12(t,1H),6.73(dd,1H),6.21(dd,1H),6.14(s,1H),2.84(s,2H)。
n- (6-aminopyridin-2-yl) -2, 5-dichloroaminobenzenesulfonamide (101):
Mp175～177℃；EIMS m/z：317[M+]；1H NMR(400MHz，DMSO，δ)：8.04(d,1H),7.74–7.65(m,2H),7.09(t,1H),6.73(dd,1H),6.21(dd,1H),6.10(s,1H),3.17(s,2H)。
n- (6-aminopyridin-2-yl) -2, 5-dinitroaminobenzenesulfonamide (102):
Mp163～165℃；EIMS m/z：339[M+]；1H NMR(400MHz，DMSO，δ)：8.96(d,1H),8.52(dd,1H),8.12(d,1H),7.08(t,1H),6.73(dd,1H),6.29(s,1H),6.21(dd,1H),3.24(s,2H)。
n- (6-aminopyridin-2-yl) -2, 6-dichloroaminobenzenesulfonamide (103):
Mp153～155℃；EIMS m/z：317[M+]；1H NMR(400MHz，DMSO，δ)：7.57(dd,1H),7.54–7.49(m,2H),7.08(t,1H),7.01(s,1H),6.73(dd,1H),6.21(dd,1H),3.17(s,2H)。
n- (6-aminopyridin-2-yl) -2, 6-dicyanoanilide (104):
Mp163～165℃；EIMS m/z：299[M+]；1H NMR(400MHz，DMSO，δ)：8.18(d,2H),7.97(t,1H),7.11(t,1H),6.73(dd,1H),6.21(dd,1H),6.19(s,1H),3.00(s,2H)。
n- (6-Aminopyridin-2-yl) -2, 6-dinitroaminobenzenesulfonamide (105):
Mp179～180℃；EIMS m/z：339[M+]；1H NMR(400MHz，DMSO，δ)：8.39(d,2H),7.89(t,1H),7.32(s,1H),7.09(t,1H),6.73(dd,1H),6.21(dd,1H),3.19(s,2H)。

Claims (3)

1. a benzene sulfonamide compound is characterized by having the following structural general formula:
Figure FDA0002876594430000011
when X ═ CH in formula I, R1、R2、R3、R4And R5Is taken from any one of the following groups:
(1)R1＝R2＝R4＝R5＝H，R3＝OH；
(2)R2＝R3＝R4＝R5＝H，R1＝NH2or OH;
(3)R1＝R3＝R4＝R5＝H，R2＝OH；
(4)R1＝R3＝R5＝H，R2＝R4＝Br、OMe、OH、NO2、NH2；
(5)R3＝R4＝R5＝H，R1＝R2f, Br, Me, OH, OMe or NO2；
(6)R2＝R4＝R5＝H，R1＝R3Cl, OH or NO2；
(7)R1＝R4＝R5＝H，R2＝R3＝Br、OH、CN、NO2Or NH2；
(8)R2＝R3＝R5＝H，R1＝R4OH, CN or NO2；
(9)R2＝R3＝R4＝H，R1＝R5Br, OH, CN, OMe, or Me;
when X is N, R in formula I1、R2、R3、R4And R5Is taken from any one of the following groups:
(10)R2＝R3＝R4＝R5＝H，R1＝OMe、F、NO2、NH2CN or Br;
(11)R1＝R3＝R4＝R5＝H，R2＝OMe、Br、NH2or OH;
(12)R1＝R3＝R5＝H，R2＝R4＝Me、OH、NH2or Cl;
(13)R3＝R4＝R5＝H，R1＝R2＝Cl、F、NO2OMe or OH;
(14)R2＝R4＝R5＝H，R1＝R3＝Cl、NO2or OH;
(15)R1＝R4＝R5＝H，R2＝R3cl, Br, CN, Me or NO2；
(16)R2＝R3＝R5＝H，R1＝R4＝Cl、NO2OH or Me;
(17)R2＝R3＝R4＝H，R1＝R5cl, Br, or CN.
2. A process for the preparation of the benzenesulfonamide series of compounds as claimed in claim 1, characterized in that: it comprises the following steps:
Figure FDA0002876594430000012
take 2-R1-3-R2-4-R3-5-R4-6-R5Dissolving substituted benzene sulfonyl chloride (II) into anhydrous methanol, stirring for 20min, adding m-aryl diamine (III) and anhydrous K2CO3The ratio of the amounts of the substances is: 2-R1-3-R2-4-R3-5-R4-6-R5Substituted benzenesulfonyl chlorides (II) meta-aryl diamines (I)II) Anhydrous K2CO3(4-12) reacting at 30-70 ℃ for 4-24 h, cooling, evaporating methanol, adding water, extracting with ethyl acetate for three times, combining organic phases, washing with water, and carrying out anhydrous MgSO4Drying, evaporating the solvent, purifying by silica gel column chromatography, and eluting with the following solvents in volume ratio: AcOEt, petroleum ether is 1: 1.5-1: 9, and white solid N- (3-amino aryl) -2-R is obtained1-3-R2-4-R3-5-R4-6-R5Substituted benzenesulfonamides (I); wherein R is1、R2、R3、R4And R5Is as defined in claim 1 for formula (I).
3. The application of a benzene sulfonamide series compound in preparing a urease inhibitor is disclosed, wherein the benzene sulfonamide compound has the following structural general formula:
Figure FDA0002876594430000021
when X ═ CH in formula I, R1、R2、R3、R4And R5Is taken from any one of the following groups:
(18)R1＝R2＝R4＝R5＝H，R3＝F、Cl、Br、H、Me、NO2、NH2CN, OH or OMe;
(19)R2＝R3＝R4＝R5＝H，R1＝OMe、F、Cl、Br、Me、NO2、NH2CN or OH;
(20)R1＝R3＝R4＝R5＝H，R2＝OMe、F、Cl、Me、Br、OH、NH2or NO2；
(21)R1＝R3＝R5＝H，R2＝R4＝Cl、Br、Me、OMe、OH、NO2、NH2Or F;
(22)R3＝R4＝R5＝H，R1＝R2cl, F, Br, Me, OH, OMe or NO2；
(23)R2＝R4＝R5＝H，R1＝R3Cl, Me, OMe, OH, Br or NO2；
(24)R1＝R4＝R5＝H，R2＝R3＝F、Cl、Br、OMe、OH、CN、NO2、NH2Or Me;
(25)R2＝R3＝R5＝H，R1＝R4cl, F, Br, Me, OH, CN or NO2；
(26)R2＝R3＝R4＝H，R1＝R5F, Cl, Br, OH, CN, OMe, or Me;
when X is N, R in formula I1、R2、R3、R4And R5Is taken from any one of the following groups:
(27)R1＝R2＝R4＝R5＝H，R3f, Cl, Br, H, or OMe;
(28)R2＝R3＝R4＝R5＝H，R1＝OMe、F、NO2、NH2CN or Br;
(29)R1＝R3＝R4＝R5＝H，R2＝OMe、Cl、Br、NH2or OH;
(30)R1＝R3＝R5＝H，R2＝R4＝Me、OH、NH2or Cl;
(31)R3＝R4＝R5＝H，R1＝R2＝Cl、F、NO2OMe or OH;
(32)R2＝R4＝R5＝H，R1＝R3＝Cl、NO2or OH;
(33)R1＝R4＝R5＝H，R2＝R3＝Cl、Br、CN、me or NO2；
(34)R2＝R3＝R5＝H，R1＝R4＝Cl、NO2OH or Me;
(35)R2＝R3＝R4＝H，R1＝R5cl, Br, or CN.
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