CN115141128B - 3-Aryl-3- (sulfanilamide) acrylic acid derivative and preparation method and application thereof - Google Patents

Abstract

The present invention belongs to the field of medical technology, specifically 3-aryl-3-(sulfonylbenzamide)propionic (ene) acid derivatives and preparation methods and applications thereof. A novel 3-substituted aryl-3-(4-sulfonylbenzamide)propionic (ene) acid derivative having a structure shown in the general formula (1). This class of compounds achieves the catalytic activity of inhibiting enzymes and has potential applications as anti-glaucoma drugs. The definition of R in the general formula (1) of the present invention is shown in the specification.

Description

3-Aryl-3-(sulfonylbenzamide)propionic (enoic) acid derivatives and their preparation methods and applications

Technical Field

The invention belongs to the field of medical technology and relates to 3-substituted aryl-3-(4-sulfonamidobenzamido) acrylic (enoic) acid derivatives and a preparation method and medical use thereof.

Background Art

Carbonic anhydrase (CA, EC 4.2.1.1) is a zinc-containing metalloproteinase that has catalytic activity in the reversible hydration reaction of CO ₂ and is ubiquitous in eukaryotes and prokaryotes. The relationship between CAII and glaucoma was reported as early as 1949 to 1955. The main component of aqueous humor is bicarbonate in the form of sodium salt. The water required for aqueous humor is obtained through the passive osmotic process of the ciliary tissue in the eye. CA in the non-pigmented epithelial cells of the ciliary body catalyzes the hydration reaction of CO ₂ to produce HCO ₃ ^- , which is then secreted into the aqueous humor with the help of ion channels or transporters. CA II inhibitors can inhibit the activity of CA, reduce the production of HCO ₃ ^- , thereby inhibiting the passive transport process of water into the aqueous humor, and thus inhibiting the production of aqueous humor. Glaucoma patients have increased intraocular pressure due to poor aqueous humor outflow. CA II inhibitors reduce the production of aqueous humor and play a role in lowering intraocular pressure. They are clinically used to treat glaucoma.

CA II contains a distinct active cavity, which is nearly conical, and the active site contains a zinc ion bound to a hydroxide ion. The active site also contains a hydrophobic region composed of hydrophobic amino acids, and the opposite side is a hydrophilic region composed of hydrophilic amino acids. The direction of the development of CA II inhibitors will be to block and occupy the zinc ion, hydrophilic region and hydrophobic region. There are few reports of CA II inhibitors that can bind to three active sites. Therefore, it is of great significance to obtain a CA II inhibitor that can bind to zinc ions, hydrophobic regions and hydrophilic regions at the same time.

Summary of the invention

The invention aims to design and synthesize 3-substituted aryl-3-(4-sulfonamidobenzamido) acrylic (enoic) acid derivatives and their preparation method and medical use.

To achieve the above purpose, the technical solution adopted by the present invention is:

A 3-aryl-3-(sulfonylbenzamide)propionic (enoic) acid derivative, characterized in that: the compound is as shown in the general formula (1)

In the general formula:

It is a single bond or a double bond, and the double bond includes cis and trans structures;

_R1 is selected from H, hydroxyl, C1-6 alkyl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, which are unsubstituted or substituted with at least one of the following groups, wherein the following groups are selected from one or more of halogen, hydroxyl, cyano, nitro and amino; amino which is unsubstituted or substituted with the following groups, such as the following groups are selected from C1-6 alkyl, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C2-6 alkenylcarbonyl or C2-6 alkynylcarbonyl; sulfamide or amide which are unsubstituted or substituted with the following groups, wherein the following groups replacing the amino group in the sulfamide or amide are selected from C C1-6 alkyl, C1-6 aminoalkyl, C1-6 hydroxyalkyl, C1-6 alkoxyalkyl, C1-6 cyanoalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C2-6 alkenylcarbonyl or C2-6 alkynylcarbonyl; phenyl, biphenyl, naphthyl, benzyl, pyridine ring, pyrazole ring, pyrrole ring, pyrimidine ring, quinoline ring, imidazole ring, morpholine ring, piperazine ring, pyridazine ring, pyrazine ring, piperidine ring, thiophene ring, pyran ring, indole ring, furan ring, the following groups are selected from hydroxyl, hydroxymethyl, mercapto, amino, sulfamide, carboxyl, ester, cyano, nitro, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-7 cycloalkyl, benzyloxycarbonyl, C1-6 haloalkyl;

_R2 is selected from H, potassium ion, sodium ion, lithium ion or ammonium ion; C1-6 alkyl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy which is unsubstituted or substituted with at least one of the following groups, wherein the following groups are selected from one or more of halogen, hydroxyl, cyano, nitro and amino;

Or, optical isomers and diastereomers of the compound represented by general formula (1).

Preferably, in the general formula:

It is a single bond or a double bond, and the double bond includes cis and trans structures;

R ₁ is selected from H, hydroxyl, C1-6 alkyl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, amino, sulfamide, amide, phenyl which is unsubstituted or substituted by at least one of the following groups, biphenyl, naphthyl, benzyl, pyridine ring, pyrazole ring, pyrrole ring, pyrimidine ring, quinoline ring, imidazole ring, morpholine ring, piperazine ring, pyridazine ring, pyrazine ring, piperidine ring, thiophene ring, pyran ring, indole ring, furan ring, and the following groups are selected from hydroxyl, hydroxymethyl, thiol, amino, sulfamide, carboxyl, ester, cyano, nitro, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-7 cycloalkyl, benzyloxycarbonyl, C1-6 haloalkyl;

R2 is selected from H, potassium ion, sodium ion, lithium ion or ammonium ion; C1-6 alkyl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy which is unsubstituted or substituted with at least one of the following groups, wherein the following groups are selected from one or more of halogen, hydroxyl, cyano, nitro and amino;

Or, optical isomers and diastereomers of the compound represented by general formula (1).

Further preferably, in the general formula:

It is a single bond or a double bond, and the double bond includes cis and trans structures;

R ₁ is selected from H, hydroxyl, C1-6 alkyl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, phenyl, biphenyl, naphthyl, benzyl, pyridine ring, pyrazole ring, pyrrole ring, pyrimidine ring, quinoline ring, imidazole ring, morpholine ring, piperazine ring, pyridazine ring, pyrazine ring, piperidine ring, thiophene ring, pyran ring, indole ring, furan ring, the following groups are selected from hydroxyl, hydroxymethyl, thiol, amino, sulfamide, carboxyl, ester, cyano, nitro, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-7 cycloalkyl, benzyloxycarbonyl, C1-6 haloalkyl;

_R2 is selected from H, potassium ion, sodium ion, lithium ion or ammonium ion; C1-6 alkyl, C3-8 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy which is unsubstituted or substituted with at least one of the following groups, wherein the following groups are selected from one or more of halogen, hydroxyl, cyano, nitro and amino;

Or, optical isomers and diastereomers of the compound represented by general formula (1).

In further preferred embodiment, in the general formula:

It is a single bond or a double bond, and the double bond includes cis and trans structures;

R ₁ is selected from H, hydroxyl, phenyl, biphenyl, naphthyl, furan ring, thiophene ring, pyridine ring which are unsubstituted or substituted by at least one of the following groups, the following groups are selected from halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-7 cycloalkyl, benzyloxycarbonyl, C1-6 haloalkyl;

_R2 is selected from H, potassium ion, sodium ion, lithium ion or ammonium ion; C1-3 alkyl which is unsubstituted or substituted by at least one of the following groups, the following groups are selected from one or more of halogen, hydroxyl, cyano, nitro and amino;

Or, optical isomers and diastereomers of the compound represented by general formula (1).

Still more preferably, in the general formula:

It is a single bond or a double bond, and the double bond includes cis and trans structures;

_R1 is selected from phenyl, biphenyl, naphthyl, furan ring, thiophene ring, pyridine ring, which are unsubstituted or substituted with at least one of the following groups, the following groups are selected from halogen, C1-6 alkyl, benzyloxycarbonyl, C1-6 haloalkyl;

_R2 is selected from H, potassium ion or sodium ion; C1-3 alkyl which is unsubstituted or substituted by at least one of the following groups, wherein the following groups are selected from one or more of halogen, hydroxyl, cyano, nitro and amino;

Or, optical isomers and diastereomers of the compound represented by general formula (1).

More preferably, the compound represented by the general formula (1) is the following S1-S20, D1-D21 compounds and their optical isomers and diastereomers;

A method for preparing the compound, the reaction formula is as follows: first, an aryl ethyl ketone reacts with a carbonate to obtain an intermediate 1, which is then treated with ammonium formate to obtain an intermediate 2, and the intermediate 2 is acylated with p-sulfonylaminobenzoyl chloride to obtain a compound of the general formula (1), or is further hydrolyzed to obtain a compound of the general formula (1);

Alternatively, the substituted aromatic aldehyde, malonic acid and ammonium formate are first reacted to obtain intermediate 3, which is then esterified with concentrated sulfuric acid to obtain intermediate 4, and intermediate 4 is reacted with p-sulfonylaminobenzoic acid under EDCI catalysis to obtain the compound of general formula (1), or is hydrolyzed to obtain the compound of general formula (1), or is further salified to obtain the compound of general formula (1).

A pharmaceutical composition comprises the compound and its optically active form, diastereoisomer and a pharmaceutically acceptable carrier.

The invention discloses an application of a compound and a composition, and an application of the compound and its optically active form, diastereoisomer or the composition in preparing a drug for inhibiting carbonic anhydrase.

Application of the compound and its optically active form, diastereoisomer or the composition in preparing anti-glaucoma drugs.

The advantages of the present invention are:

The compounds of the present invention are obtained according to the three regions of the active center, hydrophobic region and hydrophilic region of the enzyme. The compounds of the general formula (1) are obtained. The compounds have three active fragments of sulfonamide, substituted aromatic or heteroaromatic group and free carboxyl group in structure. They can form coordination bonds, van der Waals forces and hydrogen bonds with Zn2 ⁺ and the hydrophobic region and hydrophilic region in carbonic anhydrase II, thereby inhibiting the catalytic activity of the enzyme. The compounds have potential application as anti-glaucoma drugs.

DETAILED DESCRIPTION

The following examples will provide a better understanding of the compounds of the present invention and their preparation. These examples are intended to illustrate but not to limit the scope of the present invention.

Example 1: Sodium (Z)-3-phenyl-3-(4-sulfonamidobenzamido)acrylate (S1)

Acetophenone (3.00 g, 25.00 mmol) and dimethyl carbonate (6.75 g, 75.00 mmol, 3 eq) were added to a 100 mL eggplant-shaped bottle. Sodium hydrogen (2.00 g, 50.00 mmol, 2 eq, mass fraction 60%) was added in batches under ice bath and stirring, and stirring was continued for 30 min, and then stirred and refluxed for 1.5 h. Under stirring, the reaction solution was poured into 100 mL ice water, 3 M hydrochloric acid was used to adjust pH = 3, and ethyl acetate was extracted (3 x 15 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Rapid silica gel column chromatography (petroleum ether (PE) : ethyl acetate (EA) = 5: 1) was used to separate the yellow oil, with a yield of 3.41 g and a yield of 76.63%. HRMS(ESI): Calcd.for C ₁₀ H ₁₀ O ₃ [M+Na] ⁺ :201.0522, Found 201.0516[M+Na] ⁺ .

The yellow oil obtained in the previous step (3.41 g, 19.16 mmol), ammonium formate (6.04 g, 95.80 mmol, 5 eq), and 30 mL of methanol were added to a 100 mL eggplant-shaped flask. The mixture was stirred and refluxed for 8 h. The solvent was evaporated under reduced pressure, 30 mL of water was added, and the mixture was extracted with ethyl acetate (3 x 15 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain 2a as a yellow oil with a yield of 2.14 g and a yield of 63.11%. No further purification was required.

Add the yellow oil obtained in the previous step (2.14 g, 12.09 mmol) and 15 mL of acetonitrile to a 100 mL eggplant-shaped bottle. Add 1.58 g of acetonitrile solution (15 mL) of p-sulfabenzoyl chloride (1.58 g, 7.25 mmol) slowly in an ice bath and under stirring. Continue stirring for 30 min, then stir at room temperature overnight. Add 20 mL of saturated sodium bicarbonate solution to the reaction solution, extract with ethyl acetate (3 x 15 mL), combine the organic phases, dry over anhydrous sodium sulfate, remove the solvent under reduced pressure, and separate by rapid silica gel column chromatography (petroleum ether (PE) : ethyl acetate (EA) = 5: 1) to obtain a yellow solid, with a yield of 0.33 g and a yield of 12.64%. HRMS (ESI): Calcd. for C ₁₇ H ₁₆ N ₂ O ₅ S [M+Na] ⁺ : 383.0672, Found 383.0663 [M+Na] ⁺ .

The yellow solid (0.33 g, 0.92 mmol) obtained in the previous step and 10 mL of tetrahydrofuran were added to a 100 mL eggplant-shaped flask. 3.68 mL (3.68 mmol, 4 eq) of 1 M sodium hydroxide solution was added dropwise under ice bath and stirring, and then the mixture was stirred at room temperature for 4 h. Part of the solvent was evaporated under reduced pressure, carbon dioxide was introduced until the pH of the reaction solution was 7, the solvent was evaporated under reduced pressure, 5 mL of tetrahydrofuran/5 mL of ethanol were added, and the mixture was stirred for 1 h, filtered with suction, filtered with diatomaceous earth, and the filtrate was taken. After the solvent was evaporated under reduced pressure, S1 was separated by reverse phase column chromatography (methanol: water = 1: 4) as a white solid, with an amount of 0.10 g and a yield of 29.64%. Mp 161.6-162.8℃； ¹ H NMR(600MHz，DMSO-d ₆ )δ14.44(s，1H)，8.08(d，J＝8.4Hz，2H)，7.97(d，J＝8.5Hz，2H)，7.60(s，2H)，7.39-7.27(m，5H)，5.29(s，1H). ¹³ C NMR(151MHz，DMSO)δ171.98，162.97，146.79，146.13，137.75，137.32，128.17，127.89，127.72，126.64，126.11，113.93.HRMS(ESI)：Calcd.for C ₁₆ H ₁₃ N ₂ O ₅ SNa[M-Na] ^- : 345.0551, Found 345.0496[M-Na] ^- .

Example 2: Sodium (Z)-3-(2-naphthyl)-3-(4-sulfonamidobenzamido)acrylate (S2)

The preparation method of the compound of Example 2 is the same as that of Example 1, with 2-naphthyl acetonide (3.00 g, 17.65 mmol) as the raw material, referring to the synthesis method of S1, S2 is obtained as a white solid, the yield is 0.16 g, and the yield is 37.37%. Mp 172.8-173.9℃; ¹ H NMR (600MHz, DMSO-d ₆ )δ14.76(s, 1H), 8.09(d, J＝8.2Hz, 2H), 7.97(d, J＝8.2Hz, 2H), 7.95-7.88(m, 3H), 7.87-7.81(m, 1H), 7.54-7.44(m, 3H), 5.40(s, 1H). ¹³ C NMR (151MHz, DMSO) δ171.83, 163.01, 146.91, 145.98, 137.66, 135.24, 132.71, 128.16, 127.43, 126.72, 126.14, 126.07, 125.46, 124.89, 114.40. HRMS (ESI ): Calcd.for C ₂₀ H ₁₅ N ₂ O ₅ SNa[M-Na] ^- : 395.0707, Found 395.0637[M-Na] ^- .

Example 3: Sodium (Z)-3-(1-naphthyl)-3-(4-sulfonamidobenzamido)acrylate (S3)

The preparation method of the compound of Example 3 is the same as that of Example 1, with 1-naphthone (3.00 g, 17.65 mmol) as the raw material, referring to the synthesis method of S1, S3 is obtained as a white solid, the amount is 0.34 g, and the yield is 58.51%. Mp 172.2-173.6℃; ¹ H NMR (600 MHz, DMSO-d ₆ )δ15.48(s, 1H), 8.01(d, J＝8.4 Hz, 2H), 7.96(d, J＝8.3 Hz, 1H), 7.96-7.90(m, 3H), 7.88(d, J＝8.3 Hz, 1H), 7.61-7.36(m, 6H), 5.09(s, 1H). ¹³ C NMR (151MHz, DMSO) δ171.83, 161.29, 146.75, 145.05, 137.50, 136.25, 132.63, 131.18, 128.08, 127.91, 127.66, 126.07, 125.98, 125.60, 125.27, 125.0 9, 124.81, 113.90.HRMS(ESI): Calcd.forC ₂₀ H ₁₅ N ₂ O ₅ SNa[M-Na] ^- : 395.0707, Found 395.0741[M-Na] ^- .

Example 4: Sodium (Z)-3-(2-pyridyl)-3-(4-sulfonamidobenzamido)acrylate (S4)

The preparation method of the compound of Example 4 is the same as that of Example 1, with 2-acetylpyridine (3.00 g, 24.79 mmol) as the raw material, referring to the synthesis method of S1, S4 is obtained as a white solid, the amount is 0.057 g, and the yield is 18.59%. Mp 163.5-165.7℃; ¹ HNMR (600MHz, DMSO-d ₆ )δ14.33(s, 1H), 8.56-8.46(m, 1H), 8.05(d, J＝8.4Hz, 2H), 7.96(d, J＝8.4Hz, 2H), 7.79-7.71(m, 1H), 7.38(d, J＝7.9Hz, 1H), 7.33-7.27(m, 1H), 5.54(s, 1H). ¹³ CNMR (151MHz, DMSO) δ171.55, 162.93, 155.11, 148.39, 147.09, 144.95, 137.30, 135.92, 128.06, 126.03, 122.67, 121.98, 115.51.HRMS (ESI): Calcd.for C ₁₅ H _{1 2} N ₃ O ₅ SNa[M-Na] ^- : 346.0503, Found 346.0525[M-Na] ^- .

Example 5: (Z)-3-(3-pyridyl)-3-(4-sulfonamidobenzamido)acrylate sodium (S5)

The preparation method of the compound of Example 5 is the same as that of Example 1, with 3-acetylpyridine (3.00 g, 24.79 mmol) as the raw material, referring to the synthesis method of S1, S5 is obtained as a white solid, the amount is 0.11 g, and the yield is 51.25%. Mp 163.1-165.3℃; ¹ H NMR (600MHz, DMSO-d ₆ )δ14.92(s, 1H), 8.64-8.42(m, 2H), 8.06(d, J＝7.9Hz, 2H), 7.95(d, J＝7.8Hz, 2H), 7.73(d, J＝7.4Hz, 1H), 7.48(s, 2H), 7.40-7.30(m, 1H), 5.29(s, 1H). ¹³ C NMR (151MHz, DMSO) δ171.03, 162.91, 148.52, 147.20, 147.06, 143.06, 137.39, 134.11, 133.05, 128.04, 125.97, 122.71, 115.17.HRMS (ESI): Calcd.for C ₁₅ H ₁₂ N ₃ O ₅ SNa[M-Na] ^- : 346.0503, Found 346.0519[M-Na] ^- .

Example 6: Sodium (Z)-3-(4-pyridyl)-3-(4-sulfonamidobenzamido)acrylate (S6)

The preparation method of the compound of Example 6 is the same as that of Example 1, using 4-acetylpyridine (3.00 g, 24.79 mmol) as the raw material and referring to the synthesis method of S1, S6 is obtained as a white solid with an amount of 0.041 g and a yield of 30.85%. Mp 163.8-165.3℃； ¹ HNMR(600MHz，DMSO-d ₆ )δ14.57(s，1H)，8.51(d，J＝5.1Hz，2H)，8.06(d，J＝8.1Hz，2H)，7.97(d，J＝8.1Hz，2H)，7.58(s，2H)，7.33(d，J＝5.1Hz，2H)，5.42(s，1H). ¹³ C NMR(151MHz，DMSO)δ171.02，163.07，149.06，147.01，144.92，143.67，137.20，128.13，126.07，121.32，115.99.HRMS(ESI)：Calcd.for C ₁₅ H ₁₂ N ₃ O ₅ SNa[M-Na] ^- : 346.0503, Found 346.0532[M-Na] ^- .

Example 7: Sodium (Z)-3-(4-methoxyphenyl)-3-(4-sulfonamidobenzamido)acrylate (S7)

The preparation method of the compound of Example 7 is the same as that of Example 1, with 4-methoxyacetophenone (3.00 g, 20.00 mmol) as the raw material, referring to the synthesis method of S1, S7 is obtained as a white solid, the yield is 0.13 g, and the yield is 50.95%. Mp 165.3-167.4℃; ¹ H NMR (600MHz, DMSO-d ₆ )δ14.50(s, 1H), 8.07(d, J＝8.3Hz, 2H), 8.00-7.90(m, 2H), 7.56(s, 2H), 7.33-7.22(m, 2H), 6.88(d, J＝8.7Hz, 2H), 5.40-5.00(m, 1H), 3.77(s, 3H). ¹³ C NMR (151MHz, DMSO) δ172.07, 162.94, 159.10, 146.73, 145.72, 137.90, 129.51, 128.07, 127.88, 125.97, 113.04, 112.74, 55.12.HRMS (ESI): Calcd.for C ₁₇ H ₁₅ N ₂ O ₆ SNa[M-Na] ^- : 375.0656, Found 375.0622[M-Na] ^- .

Example 8: Sodium (Z)-3-(3-methoxyphenyl)-3-(4-sulfonamidobenzamido)acrylate (S8)

The preparation method of the compound of Example 8 is the same as that of Example 1, with 3-methoxyacetophenone (3.00 g, 20.00 mmol) as the raw material, referring to the synthesis method of S1, S8 is obtained as a white solid, the yield is 0.11 g, and the yield is 35.93%. Mp 166.5-168.2℃; ¹ H NMR (600 MHz, DMSO-d ₆ )δ14.42(s, 1H), 8.07(d, J＝6.8Hz, 2H), 7.96(s, 2H), 7.60(s, 2H), 7.24(s, 1H), 6.90(m, 3H), 5.40-5.21(m, 1H), 3.75(s, 3H). ¹³ C NMR (151MHz, DMSO) δ171.79, 162.90, 158.71, 146.75, 145.82, 138.83, 137.76, 128.71, 128.10, 126.02, 119.07, 114.08, 113.27, 112.17, 55.05.HRMS (ESI) ：Calcd.for C ₁₇ H ₁₅ N ₂ O ₆ SNa[M-Na] ^- ：375.0656，Found375.0624[M-Na] ^- .

Example 9: Sodium (Z)-3-(4-fluorophenyl)-3-(4-sulfonamidobenzamido)acrylate (S9)

The preparation method of the compound of Example 9 is the same as that of Example 1, using 4-fluoroacetophenone (3.00 g, 21.74 mmol) as raw material and referring to the synthesis method of S1, S9 is obtained as a white solid with an amount of 0.11 g and a yield of 51.30%. Mp 162.2-163.7℃； ¹ H NMR(600MHz，DMSO-d ₆ )δ14.67(s，1H)，8.06(d，J＝8.4Hz，2H)，7.95(d，J＝8.3Hz，2H)，7.44-7.34(m，2H)，7.20-7.10(m，2H)，5.24(s，1H). ¹³ C NMR(151MHz，DMSO)δ169.87，161.22，160.93，159.31，145.30，143.25，135.85，131.95，126.86，126.32，124.25，112.79.HRMS(ESI)：Calcd.for C ₁₆ H ₁₂ N ₂ O ₅ SNaF[M-Na] ^- : 363.0456, Found 363.0415[M-Na] ^- .

Example 10: Sodium (Z)-3-(3-fluorophenyl)-3-(4-sulfonamidobenzamido)acrylate (S10)

The preparation method of the compound of Example 10 is the same as that of Example 1, with 3-fluoroacetophenone (3.00 g, 21.74 mmol) as the raw material, referring to the synthesis method of S1, S10 is obtained as a white solid, the amount is 0.16 g, and the yield is 46.08%. Mp 161.9-163.0℃; ¹ HNMR (600MHz, DMSO-d ₆ )δ14.48(s, 1H), 8.06(d, J＝8.3Hz, 2H), 7.96(d, J＝8.3Hz, 2H), 7.52(s, 2H), 7.36(q, J＝8.3Hz, 1H), 7.20(d, J＝7.7Hz, 1H), 7.17-7.10(m, 2H), 5.33(s, 1H). ¹³ CNMR (151MHz, DMSO) δ171.48, 163.04, 162.54, 160.94, 146.98, 144.69, 139.93, 137.51, 129.64, 128.15, 126.04, 122.71, 114.60, 113.52.HRMS (ESI): Calcd.for C ₁₆ H ₁₂ N ₂ O ₅ SNaF[M-Na] ^- : 363.0456, Found 363.0375[M-Na] ^- .

Example 11: Sodium (Z)-3-(4-methylphenyl)-3-(4-sulfonamidobenzamido)acrylate (S11)

The preparation method of the compound of Example 11 is the same as that of Example 1, with 4-methylacetophenone (3.00 g, 22.39 mmol) as the raw material, referring to the synthesis method of S1, S11 is obtained as a white solid, the yield is 0.15 g, and the yield is 44.50%. Mp 163.7-165.6℃; ¹ HNMR (600MHz, DMSO-d ₆ )δ14.50(s, 1H), 8.06(d, J＝8.0Hz, 2H), 7.95(d, J＝8.0Hz, 2H), 7.23(d, J＝7.7Hz, 2H), 7.12(d, J＝7.6Hz, 2H), 5.25(s, 1H), 2.31(s, 3H). ¹³ C NMR (151MHz, DMSO) δ172.00, 162.92, 146.87, 146.04, 137.78, 137.12, 134.42, 128.24, 128.07, 126.51, 126.01, 113.36, 20.86.HRMS (ESI): Calcd.for C ₁₇ H ₁₅ N ₂ O ₅ SNa[M-Na] ^- : 359.0707, Found359.0726[M-Na] ^- .

Example 12: (Z)-3-(3-methylphenyl)-3-(4-sulfonamidobenzamido)acrylate sodium (S12)

The preparation method of the compound of Example 12 is the same as that of Example 1, with 3-methylacetophenone (3.00 g, 22.39 mmol) as the raw material, referring to the synthesis method of S1, S12 is obtained as a white solid, the amount is 0.09 g, and the yield is 20.49%. Mp 162.7-163.8℃; ¹ HNMR (600MHz, DMSO-d ₆ )δ14.56(s, 1H), 8.09-8.03(m, 2H), 7.95(d, J＝8.4Hz, 2H), 7.25-7.18(m, 1H), 7.17-7.10(m, 3H), 5.25(s, 1H), 2.31(s, 3H). ¹³ C NMR (151MHz, DMSO) δ171.81, 162.86, 146.93, 146.08, 137.70, 137.34, 136.61, 128.43, 128.07, 127.51, 127.03, 125.98, 123.80, 113.88, 21.05.HRMS (ESI) ：Calcd.for C ₁₇ H ₁₅ N ₂ O ₅ SNa[M-Na] ^- ：359.0707，Found359.0728[M-Na] ^- .

Example 13: Sodium (Z)-3-(4-chlorophenyl)-3-(4-sulfonamidobenzamido)acrylate (S13)

The preparation method of the compound of Example 13 is the same as that of Example 1, using 4-chloroacetophenone (3.00 g, 19.48 mmol) as raw material and referring to the synthesis method of S1, S13 is obtained as a white solid with an amount of 0.18 g and a yield of 44.10%. Mp 174.1-175.7℃； ¹ HNMR(600MHz，DMSO-d ₆ )δ14.34(s，1H)，8.51-7.82(m，4H)，7.38(s，6H)，5.33(s，1H). ¹³ C NMR(151MHz，DMSO)δ172.04，163.11，147.14，145.05，137.40，136.18，132.49，128.48，128.15，127.74，126.12，114.09.HRMS(ESI)：Calcd.for C ₁₆ H ₁₂ N ₂ O ₅ SNaCl[M-Na] ^- ：379.0161，Found379.0191[M-Na] ^- .

Example 14: Sodium (Z)-3-(3-chlorophenyl)-3-(4-sulfonamidobenzamido)acrylate (S14)

The preparation method of the compound of Example 14 is the same as that of Example 1, with 3-chloroacetophenone (3.00 g, 19.48 mmol) as the raw material, referring to the synthesis method of S1, S14 is obtained as a white solid, with an amount of 0.13 g and a yield of 32.67%. Mp 174.5-176.1°C; ¹ HNMR (600 MHz, DMSO-d ₆ ) δ14.64 (s, 1H), 8.06 (d, J=8.4 Hz, 2H), 7.95 (d, J=8.4 Hz, 2H), 7.39-7.34 (m, 3H), 7.33-7.30 (m, 1H), 5.29 (s, 1H). ¹³ C NMR (151MHz, DMSO) δ171.29, 162.99, 147.02, 144.48, 139.60, 137.43, 132.37, 129.54, 128.11, 127.58, 126.30, 126.00, 125.29, 114.86.HRMS (ESI): Calcd.for C ₁₆ H ₁₂ N ₂ O ₅ SNaCl[M-Na] ^- : 379.0161, Found 379.0185[M-Na] ^- .

Example 15: Sodium (Z)-3-(3,4-dichlorophenyl)-3-(4-sulfonamidobenzamido)acrylate (S15)

The preparation method of the compound of Example 15 is the same as that of Example 1, with 3,4-dichloroacetophenone (3.00 g, 16.04 mmol) as the raw material, referring to the synthesis method of S1, S15 is obtained as a white solid, the yield is 0.25 g, and the yield is 66.32%. Mp 180.3-181.5℃; ¹ H NMR (600MHz, DMSO-d ₆ )δ14.75(s, 1H), 8.06(d, J＝8.2Hz, 2H), 7.95(d, J＝8.5Hz, 2H), 7.64-7.54(m, 2H), 7.41-7.29(m, 1H), 5.32(s, 1H). ¹³ C NMR (151MHz, DMSO) δ171.03, 163.06, 147.12, 143.51, 138.18, 137.29, 130.39, 130.13, 129.81, 128.40, 128.10, 126.94, 125.99, 115.19.HRMS (ESI): Calcd.for C ₁₆ H ₁₁ N ₂ O ₅ SNaCl ₂ [M-Na] ^- : 412.9771, Found 412.9809[M-Na] ^- .

Example 16: Sodium (Z)-3-(3,4-difluorophenyl)-3-(4-sulfonamidobenzamido)acrylate (S16)

The preparation method of the compound of Example 16 is the same as that of Example 1, with 3,4-difluoroacetophenone (3.00 g, 19.23 mmol) as the raw material, referring to the synthesis method of S1, S16 is obtained as a white solid, the yield is 0.24 g, and the yield is 63.58%. Mp 165.1-166.9℃; ¹ H NMR (600MHz, DMSO-d ₆ )δ14.69(s, 1H), 8.06(d, J＝8.3Hz, 2H), 7.96(d, J＝8.2Hz, 2H), 7.45-7.33(m, 2H), 7.26-7.18(m, 1H), 5.30(s, 1H). ¹³ C NMR (151MHz, DMSO) δ171.23, 163.03, 149.72, 148.30, 146.96, 143.86, 137.49, 135.00, 128.11, 125.98, 123.45, 116.61, 115.77, 114.74.HRMS (ESI): Calcd.for C ₁₆ H ₁₁ N ₂ O ₅ SNaF ₂ [M-Na] ^- : 381.0362, Found 381.0390 [M-Na] ^- .

Example 17: (Z)-3-(3,4-dimethylphenyl)-3-(4-sulfonamidobenzamido)acrylate sodium (S17)

The preparation method of the compound of Example 17 is the same as that of Example 1, with 3,4-dimethylacetophenone (3.00 g, 20.27 mmol) as the raw material, referring to the synthesis method of S1, S17 is obtained as a white solid, the yield is 0.11 g, and the yield is 25.06%. Mp 175.3-176.8°C; ¹ H NMR (600 MHz, DMSO-d ₆ ) δ14.57 (s, 1H), 8.06 (d, J=8.4 Hz, 2H), 7.95 (d, J=8.4 Hz, 2H), 7.56 (s, 2H), 7.12 (s, 1H), 7.09-7.02 (m, 2H), 5.22 (s, 1H). 2.28-2.17 (m, 6H). ¹³ C NMR (151MHz, DMSO) δ171.89, 162.83, 146.71, 146.06, 137.87, 135.81, 135.18, 134.86, 128.73, 128.07, 127.56, 125.97, 124. 06, 113.36, 19.45, 19.18.HRMS(ESI): Calcd.forC ₁₈ H ₁₇ N ₂ O ₅ SNa[M-Na] ^- : 373.0864, Found 373.0886[M-Na] ^- .

Example 18: Sodium (Z)-3-(2-thienyl)-3-(4-sulfonamidobenzamido)acrylate (S18)

The preparation method of the compound of Example 18 is the same as that of Example 1, with 2-acetylthiophene (3.00 g, 23.81 mmol) as the raw material, referring to the synthesis method of S1, S18 is obtained as a white solid, with an amount of 0.042 g, and a yield of 16.44%. Mp 152.7-153.9°C; ¹ H NMR (600 MHz, DMSO-d ₆ ) δ14.55 (s, 1H), 8.08 (d, J=8.3 Hz, 2H), 7.96 (d, J=8.3 Hz, 2H), 7.65-7.44 (m, 3H), 7.15 (d, J=2.8 Hz, 1H), 7.05-6.99 (m, 1H), 5.43 (s, 1H). ¹³ C NMR (151MHz, DMSO) δ171.19, 163.48, 146.80, 139.65, 139.36, 137.71, 128.13, 126.88, 126.00, 125.94, 125.63, 113.75. HRMS (ESI): Calcd. for C ₁₄ H ₁₁ N ₂ O ₅ S ₂ Na[M-Na] ^- : 351.0115, Found 351.0142[M-Na] ^- .

Example 19: Sodium (Z)-3-(2-furyl)-3-(4-sulfonamidobenzamido)acrylate (S19)

The preparation method of the compound of Example 19 is the same as that of Example 1, with 2-acetylfuran (3.00 g, 27.27 mmol) as the raw material, referring to the synthesis method of S1, S19 is obtained as a white solid, with an amount of 0.071 g, and a yield of 36.53%. Mp 150.3-151.8°C; ¹ H NMR (600 MHz, DMSO-d ₆ ) δ14.44 (s, 1H), 8.07 (d, J=8.4 Hz, 2H), 7.95 (d, J=8.4 Hz, 2H), 7.65 (s, 1H), 7.47 (s, 2H), 6.59 (d, J=3.2 Hz, 1H), 6.53-6.48 (m, 1H), 5.52 (s, 1H). ¹³ C NMR (151MHz, DMSO) δ171.43, 163.17, 149.71, 146.98, 142.76, 137.53, 135.81, 128.10, 125.99, 111.80, 111.24, 109.45. HRMS (ESI): Calcd. for C ₁₄ H ₁₁ N ₂ O ₆ S Na[M-Na] ^- :335.0343, Found335.0375[M-Na] ^- .

Example 20: (Z)-3-(4-fluorophenyl)-3-(4-sulfonamidobenzamido)acrylate (S20)

4-Fluoroacetophenone (3.00 g, 21.74 mmol) and dimethyl carbonate (5.87 g, 65.22 mmol, 3 eq) were added to a 100 mL eggplant-shaped bottle. Sodium hydrogen (1.74 g, 43.48 mmol, 2 eq, mass fraction 60%) was added in batches under ice bath and stirring, and stirring was continued for 30 min, and then stirred and refluxed for 1.5 h. Under stirring, the reaction solution was poured into 100 mL ice water, 3 M hydrochloric acid was used to adjust pH = 3, and ethyl acetate was extracted (3 x 15 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. After separation by rapid silica gel column chromatography (petroleum ether (PE): ethyl acetate (EA) = 5:1), a yellow oil was obtained, with a yield of 3.24 g and a yield of 76.04%. HRMS(ESI): Calcd.for C ₁₀ H ₉ O ₃ F[M+Na] ⁺ :219.0428, Found 219.0419[M+Na] ⁺ .

The yellow oil obtained in the previous step (3.24 g, 16.53 mmol), ammonium formate (5.21 g, 82.65 mmol, 5 eq), and 30 mL of methanol were added to a 100 mL eggplant-shaped bottle. The mixture was stirred and refluxed for 8 h. The solvent was evaporated under reduced pressure, 30 mL of water was added, and the mixture was extracted with ethyl acetate (3 x 15 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a yellow oil with a yield of 1.95 g and a yield of 60.49%. No further purification was required.

Add the yellow oil (1.95 g, 10.00 mmol) obtained in the previous step and 15 mL of acetonitrile to a 100 mL eggplant-shaped bottle. Add 1.31 g of acetonitrile solution (15 mL) of p-sulfabenzoyl chloride (1.31 g, 6.00 mmol) slowly in an ice bath and under stirring. Continue stirring for 30 min, then stir at room temperature overnight. Add 20 mL of saturated sodium bicarbonate solution to the reaction solution, extract with ethyl acetate (3 x 15 mL), combine the organic phases, dry over anhydrous sodium sulfate, evaporate the solvent under reduced pressure, and separate by rapid silica gel column chromatography (petroleum ether (PE): ethyl acetate (EA) = 5: 1) to obtain S20 as a yellow solid, with an amount of 0.21 g and a yield of 9.26%. HRMS (ESI): Calcd. for C ₁₇ H ₁₅ N ₂ O ₅ SF [M+Na] ⁺ : 401.0578, Found 401.0565 [M + Na] ⁺ . ¹ H NMR (400MHz, DMSO-d ₆ ) δ 10.94 (s, 1H), 8.12 (d, J=7.4Hz, 2H), 7.99 (d, J=6 .9Hz, 2H), 7.61 (dd, J=8.8, 5.4Hz, 2H), 7.55 (s, 3H), 7.25 (t, J=8.8Hz, 2H), 5.81 (s, 1H), 3.69 (s, 3H).

Example 21: Sodium 3-phenyl-3-(4-sulfonamidobenzamido)propionate (D1)

Add benzaldehyde (3.00 g, 28.30 mmol), malonic acid (2.94 g, 28.30 mmol, 1 eq), ammonium formate (3.57 g, 56.60 mmol, 2 eq), and 40 mL of ethanol into a 100 mL eggplant-shaped bottle. Stir and reflux for 8 h. Filter, wash with ethanol, wash with n-hexane, and dry to obtain a white solid with a yield of 1.85 g and a yield of 55.36%. HRMS (ESI): Calcd. for C ₉ H ₁₁ NO ₂ [MH] ^- : 164.0717, Found 164.0715 [MH] ^- .

A 100 mL eggplant-shaped bottle was added with the white solid (1.85 g, 11.21 mmol) obtained in the previous step and 40 mL of methanol. 1.12 mL of concentrated sulfuric acid was added dropwise at -10°C with stirring. The mixture was then stirred at room temperature for 24 h. After the solvent was evaporated under reduced pressure, the pH was adjusted to 12 with 2M sodium hydroxide solution, and the mixture was extracted with dichloromethane (3 x 15 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a colorless oil with a yield of 1.75 g and a yield of 87.20%.

A 100 mL eggplant-shaped bottle was added with the colorless oil obtained in the previous step (1.75 g, 9.78 mmol), p-sulfonamidobenzoic acid (2.96 g, 14.67 mmol, 1.5 eq), EDCI (2.80 g, 14.67 mmol, 1.5 eq), DMAP (1.19 g, 9.78 mmol, 1.0 eq), and 40 mL of acetonitrile. The mixture was stirred at room temperature for 4 h. The mixture was filtered and the filtrate was taken. 60 mL of water was added and the mixture was extracted with dichloromethane (3 x 20 mL). The organic phases were combined and washed with 1 M hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and water (20 mL) in sequence. The mixture was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to obtain a white solid with a yield of 2.74 g and a yield of 77.42%. HRMS (ESI): Calcd. for C ₁₇ H ₁₈ N ₂ O ₅ S[M+Na] ⁺ : 385.0829, Found 385.0855[M+Na] ⁺ .

The white solid (2.74 g, 7.57 mmol) obtained in the previous step and 10 mL of tetrahydrofuran were added to a 100 mL eggplant-shaped bottle. Under stirring at room temperature, 18.93 mL of 1 M sodium hydroxide solution (18.93 mmol, 2.5 eq) was added dropwise and stirring was continued for 4 h. Part of the solvent was evaporated under reduced pressure, and pH was adjusted to 3 with 1 M hydrochloric acid to produce a white precipitate, which was filtered, washed with water, and dried to obtain 7a as a white solid, with an amount of 2.52 g and a yield of 95.67%. HRMS (ESI): Calcd. for C ₁₆ H ₁₅ N ₂ O ₅ SNa[M-Na] ^- : 347.0707, Found 347.0699[M-Na] ^- .

The white solid (0.20 g, 0.57 mmol) obtained in the previous step and 10 mL of ethanol were added to a 25 mL eggplant-shaped bottle. Under stirring at room temperature, 0.31 mL (0.63 mmol, 1.1 eq) of 2M sodium hydroxide solution was added dropwise, and stirring was continued for 1 h to produce a white precipitate, which was filtered, washed with ethanol, and dried to obtain D1 as a white solid, with a yield of 0.11 g and a yield of 51.73%. Mp 320.9-322.1℃; ¹ H NMR (600MHz, DMSO-d ₆ ) δ10.42 (d, J=7.1Hz, 1H), 7.92 (d, J=8.2Hz, 2H), 7.88-7.83 (m, 2H), 7.37 (d, J=7.5Hz, 2H), 7.30-7.22 (m, 2H) , 7.20-7.14(m, 1H), 5.22(q, J=5.7Hz, 1H), 2.50-2.43(m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.85, 164.03, 148.98, 144.57, 136.66, 127.96, 127.26, 126.45, 126.23, 125.52, 51.06, 43.47. HRMS (ESI): Calcd. for C ₁₆ H ₁₅ N ₂ O ₅ SNa [ M-Na] ^- : 347.0707, Found 347.0674 [M-Na] ^- .

Example 22: Sodium 3-(2-naphthyl)-3-(4-sulfonamidobenzamido)propionate (D2)

The preparation method of the compound of Example 22 is the same as that of Example 21, with 2-naphthaldehyde (3.00 g, 19.23 mmol) as the raw material, referring to the synthesis method of D1, D2 is obtained as a white solid, the amount is 0.12 g, and the yield is 56.86%. Mp 344.6-345.7℃; ¹ H NMR (600MHz, DMSO-d ₆ )δ10.54(d, J＝7.1Hz, 1H), 7.96(d, J＝8.3Hz, 2H), 7.88(d, J＝8.3Hz, 2H), 7.86-7.80(m, 4H), 7.59(d, J＝8.5Hz, 1H), 7.50-7.40(m, 2H), 5.39(q, J＝5.8Hz, 1H), 2.70-2.54(m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.80, 164.17, 149.41, 142.12, 136.48, 132.84, 131.98, 127.65, 127.50, 127.38, 127.25, 125.88, 125.53, 125.50, 125.36, 124.4 0, 51.27, 43.41.HRMS(ESI): Calcd.for C ₂₀ H ₁₇ N ₂ O ₅ SNa[M-Na] ^- : 397.0864, Found 397.0921[M-Na] ^- .

Example 23: Sodium 3-(1-naphthyl)-3-(4-sulfonamidobenzamido)propionate (D3)

The preparation method of the compound of Example 23 is the same as that of Example 21, using 1-naphthaldehyde (3.00 g, 19.23 mmol) as raw material and referring to the synthesis method of D1, D3 is obtained as a white solid with an amount of 0.15 g and a yield of 71.07%. Mp 345.5-346.8℃; ¹ H NMR (600MHz, DMSO-d ₆ ) δ 10.53 (s, 1H), 8.26 (d, J = 8.5Hz, 1H), 7.97 (d, J = 8.4Hz, 2H), 7.93 (d, J = 7.9Hz, 1H), 7.87 (d, J = 8.4Hz, 2H), ^{7. 13} C NMR (151MHz, DMSO) δ174.73, 164.11, 149.47, 140.20, 136.43, 133.40, 130.37, 128.64, 127.31, 126.72, 125.95, 125.47, 125.43, 125.41, 123.30, 122.6 6, 47.74, 42.92.HRMS(ESI): Calcd.for C ₂₀ H ₁₇ N ₂ O ₅ SNa[M-Na] ^- : 397.0864, Found 397.0855[M-Na] ^- .

Example 24: Sodium 3-(2-pyridyl)-3-(4-sulfonamidobenzamido)propionate (D4)

The preparation method of the compound of Example 24 is the same as that of Example 21, using pyridine-2-carboxaldehyde (3.00 g, 28.04 mmol) as raw material and referring to the synthesis method of D1, D4 is obtained as a white solid with an amount of 0.12 g and a yield of 56.44%. Mp 327.4-328.7℃; ¹ HNMR (600MHz, DMSO-d ₆ ) δ 10.37 (s, 1H), 8.48 (d, J = 3.8Hz, 1H), 7.96 (d, J = 8.0Hz, 2H), 7.88 (d, J = 8.0Hz, 2H), 7.71-7.63 (m, 1H), 7.35 (d, J=7.7Hz, 1H), 7.23-7.15 (m, 1H), 5.22 (s, 1H), 2.65-2.52 (m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.82, 164.30, 162.73, 148.56, 136.67, 136.61, 136.19, 127.36, 125.60, 121.61, 120.29, 52.95, 41.82. HRMS (ESI): Calcd.forC ₁₅ H ₁₄ N ₃ O ₅ SNa[M-Na] ^- : 348.0660, Found 348.0661[M-Na] ^- .

Example 25: Sodium 3-(3-pyridyl)-3-(4-sulfonamidobenzamido)propionate (D5)

The preparation method of the compound of Example 25 is the same as that of Example 21, using pyridine-3-carboxaldehyde (3.00 g, 28.04 mmol) as raw material and referring to the synthesis method of D1, D5 is obtained as a white solid with an amount of 0.081 g and a yield of 38.10%. Mp 328.1-329.0℃; ¹ HNMR (600MHz, DMSO-d ₆ ) δ10.19 (d, J=7.2Hz, 1H), 8.59 (s, 1H), 8.38 (d, J=5.7Hz, 1H), 7.86 (d, J=8.3Hz, 2H), 7.81 (d, J=8.3Hz, 2H), 7. 77(d, J=7.9Hz, 1H), 7.34-7.24(m, 1H), 5.27(s, 1H), 2.61-2.52(m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.55, 164.46, 151.60, 148.31, 147.55, 139.76, 135.28, 134.10, 126.99, 125.30, 123.23, 49.19, 43.21. HRMS (ESI): Calcd. for C ₁₅ H ₁₄ N ₃ O ₅ SNa[M-Na] ^- : 348.0660, Found 348.0661[M-Na] ^- .

Example 26: Sodium 3-(4-pyridyl)-3-(4-sulfonamidobenzamido)propionate (D6)

The preparation method of the compound of Example 26 is the same as that of Example 21, with pyridine-4-carboxaldehyde (3.00 g, 28.04 mmol) as the raw material, referring to the synthesis method of D1, D6 is obtained as a white solid, the yield is 0.19 g, and the yield is 89.37%. Mp 325.3-326.8℃; ¹ HNMR (600MHz, DMSO-d ₆ )δ10.33(s, 1H), 8.44(d, J＝5.5Hz, 2H), 7.88(d, J＝8.0Hz, 2H), 7.83(d, J＝8.1Hz, 2H), 7.35(d, J＝4.9Hz, 2H), 5.19(s, 1H), 2.51-2.40(m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.65, 164.99, 153.63, 151.77, 149.73, 135.81, 127.48, 125.81, 122.24, 50.77, 43.18.HRMS (ESI): Calcd.for C ₁₅ H ₁₄ N ₃ O ₅ SNa [M-Na] ^- : 348.0660, Found 348.0674[M-Na] ^- .

Example 27: Sodium 3-(4-methoxyphenyl)-3-(4-sulfonamidobenzamido)propionate (D7)

The preparation method of the compound of Example 27 is the same as that of Example 21, with 4-methoxybenzaldehyde (3.00 g, 22.06 mmol) as the raw material, referring to the synthesis method of D1, D7 is obtained as a white solid, the amount is 0.12 g, and the yield is 56.70%. Mp 330.3-331.3℃; ¹ H NMR (600 MHz, DMSO-d ₆ )δ10.34 (d, J＝7.3 Hz, 1H), 7.87 (d, J＝8.3 Hz, 2H), 7.82 (d, J＝8.3 Hz, 2H), 7.29 (d, J＝8.6 Hz, 2H), 6.81 (d, J＝8.7 Hz, 2H), 5.17 (q, J＝5.7 Hz, 1H), 3.70 (s, 3H), 2.49-2.39 (m, 2H). ¹³ C NMR (151MHz, DMSO) δ175.09, 164.03, 157.77, 150.49, 136.63, 136.08, 127.55, 127.00, 125.35, 113.33, 55.02, 50.35, 43.50. HRMS (ESI): Calcd.forC ₁₇ H ₁₇ N ₂ O ₆ SNa[M-Na] ^- : 377.0813, Found 377.0813[M-Na] ^- .

Example 28: Sodium 3-(3-methoxyphenyl)-3-(4-sulfonamidobenzamido)propionate (D8)

The preparation method of the compound of Example 28 is the same as that of Example 21, with 3-methoxybenzaldehyde (3.00 g, 22.06 mmol) as the raw material, referring to the synthesis method of D1, D8 is obtained as a white solid, the yield is 0.052 g, and the yield is 24.57%. Mp 330.5-332.0℃; ¹ H NMR (600MHz, DMSO-d ₆ )δ10.49(s, 1H), 8.25-7.58(m, 4H), 7.33-6.65(m, 4H), 5.94(s, 2H), 5.15(s, 1H), 3.71(s, 3H), 2.54-2.22(m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.72, 164.06, 159.04, 150.20, 146.31, 136.16, 128.93, 127.02, 125.39, 118.75, 112.41, 111.31, 54.88, 50.96, 43.34.HRMS (ESI): Cal cd.for C ₁₇ H ₁₇ N ₂ O ₆ SNa[M-Na] ^- : 377.0813, Found 377.0843[M-Na] ^- .

Example 29: Sodium 3-(4-fluorophenyl)-3-(4-sulfonamidobenzamido)propionate (D9)

The preparation method of the compound of Example 29 is the same as that of Example 21, using 4-fluorobenzaldehyde (3.00 g, 24.19 mmol) as raw material and referring to the synthesis method of D1, D9 is obtained as a white solid with an amount of 0.066 g and a yield of 31.13%. Mp 324.3-325.8℃; ¹ HNMR (600MHz, DMSO-d ₆ ) δ 10.53 (s, 1H), 8.06-7.80 (m, 4H), 7.40 (s, 2H), 7.07 (s, 2H), 5.20 (s, 1H), 2.49-2.40 (m, 2H). ¹³ C NMR (151MHz , DMSO) δ174.40, 163.76, 161.68, 160.08, 140.66, 137.71, 128.36, 127.61, 125.79, 114.66, 50.54, 43.44.HRMS (ESI): Calcd.forC ₁₆ H ₁₄ N ₂ O ₅ SNaF [M-Na] ^- :365.0613, Found 365.0574[M-Na] ^- .

Example 30: Sodium 3-(3-fluorophenyl)-3-(4-sulfonamidobenzamido)propionate (D10)

The preparation method of the compound of Example 30 is the same as that of Example 21, with 3-fluorobenzaldehyde (3.00 g, 24.19 mmol) as the raw material, referring to the synthesis method of D1, D10 is obtained as a white solid, the yield is 0.10 g, and the yield is 47.16%. Mp 324.6-325.9℃; ¹ HNMR (400MHz, DMSO-d ₆ )δ10.70-10.18 (m, 1H), 8.03-7.76 (m, 4H), 7.42-7.12 (m, 3H), 7.08-6.88 (m, 1H), 5.23 (s, 1H), 2.50-2.31 (m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.89, 164.56, 163.36, 161.76, 149.09, 148.08, 137.08, 130.26, 127.79, 126.03, 123.07, 113.53, 51.23, 43.72.HRMS (ESI): Calcd.for C _{1 6} H ₁₄ N ₂ O ₅ SNaF[M-Na] ^- : 365.06133, Found 365.0561[M-Na] ^- .

Example 31: Sodium 3-(4-methylphenyl)-3-(4-sulfonamidobenzamido)propionate (D11)

The preparation method of the compound of Example 31 is the same as that of Example 21, with 4-methylbenzaldehyde (3.00 g, 25.00 mmol) as the raw material, and referring to the synthesis method of D1, D11 is obtained as a white solid, with an amount of 0.10 g and a yield of 47.14%. Mp 328.4-329.7°C; ¹ H NMR (600 MHz, DMSO-d ₆ ) δ10.56 (d, J=7.1 Hz, 1H), 7.95 (d, J=8.2 Hz, 2H), 7.89 (d, J=8.2 Hz, 2H), 7.24 (d, J=7.8 Hz, 2H), 7.05 (d, J=7.8 Hz, 2H), 5.15 (q, J=5.6 Hz, 1H), 2.49-2.37 (m, 2H), 2.24 (s, 3H). ¹³ C NMR (151MHz, DMSO) δ175.17, 164.17, 147.71, 142.00, 137.90, 135.59, 128.94, 127.87, 126.81, 126.12, 51.24, 43.87, 21.09.HRMS (ESI): Calcd.forC ₁₇ H ₁₇ N ₂ O ₅ SNa[M-Na] ^- : 361.0864, Found 361.0870[M-Na] ^-

Example 32: Sodium 3-(3-methylphenyl)-3-(4-sulfonamidobenzamido)propionate (D12)

The preparation method of the compound of Example 32 is the same as that of Example 21, using 3-methylbenzaldehyde (3.00 g, 25.00 mmol) as raw material and referring to the synthesis method of D1, D12 is obtained as a white solid with an amount of 0.14 g and a yield of 65.99%. Mp 328.8-330.2℃; ¹ H NMR (600MHz, DMSO-d ₆ ) δ10.58 (d, J=7.1Hz, 1H), 7.99 (d, J=8.3Hz, 2H), 7.92 (d, J=8.3Hz, 2H), 7.55 (s, 2H), 7.22-7.09 (m, 3H), 6.98 (d, J=6.9Hz, 1H), 5.17 (q, J=5.8Hz, 1H), 2.49-2.41 (m, 2H), 2.26 (s, 3H). ¹³ C NMR (151MHz, DMSO) δ175.11, 164.11, 146.70, 144.92, 138.29, 137.30, 128.34, 128.04, 127.53, 127.36, 126.23, 123.99, 51.54, 43.87, 21.64.HRMS (ESI): Cal cd.for C ₁₇ H ₁₇ N ₂ O ₅ SNa[M-Na] ^- : 361.0864, Found 361.0874[M-Na] ^-

Example 33: Sodium 3-(4-chlorophenyl)-3-(4-sulfonamidobenzamido)propionate (D13)

The preparation method of the compound of Example 33 is the same as that of Example 21, with 4-chlorobenzaldehyde (3.00 g, 21.43 mmol) as the raw material, referring to the synthesis method of D1, D13 is obtained as a white solid, the yield is 0.17 g, and the yield is 80.37%. Mp 350.2-351.6℃; ¹ HNMR (600MHz, DMSO-d ₆ )δ10.59(s, 1H), 7.98(d, J＝8.2Hz, 2H), 7.92(d, J＝8.2Hz, 2H), 7.54(s, 2H), 7.39(d, J＝8.3Hz, 2H), 7.31(d, J＝8.3Hz, 2H), 5.19(d, J＝5.8Hz, 1H), 2.49-2.36(m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.18, 163.79, 146.30, 143.50, 137.62, 130.80, 128.38, 127.88, 127.61, 125.78, 50.65, 43.25.HRMS (ESI): Calcd. for C ₁₆ H ₁₄ N ₂ O ₅ SNaCl [M-Na] ^- : 381.0317, Found 381.0324 [M-Na] ^-

Example 34: Sodium 3-(3-chlorophenyl)-3-(4-sulfonamidobenzamido)propionate (D14)

The preparation method of the compound of Example 34 is the same as that of Example 21, using 3-chlorobenzaldehyde (3.00 g, 21.43 mmol) as raw material and referring to the synthesis method of D1, D14 is obtained as a white solid with an amount of 0.16 g and a yield of 75.64%. Mp 350.5-351.8℃; ¹ HNMR (600MHz, DMSO-d ₆ ) δ 10.63 (s, 1H), 8.04 (d, J = 8.3Hz, 2H), 7.97 (d, J = 8.3Hz, 2H), 7.60 (s, 2H), 7.45 (s, 1H), 7.39 (d, J = 7.7Hz, 1H) ), 7.37-7.32 (m, 1H), 7.29 (d, J=7.8Hz, 1H), 5.26 (s, 1H), 2.58-2.52 (m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.14, 163.84, 147.11, 146.37, 137.52, 132.68, 129.89, 127.62, 126.32, 126.29, 125.81, 125.33, 50.85, 43.20. HRMS (ESI): Calcd.for[M -Na] ^- C ₁₆ H ₁₄ N ₂ O ₅ SNaCl: 381.0317, Found 381.0331[M-Na] ^-

Example 35: Sodium 3-(3,4-dichlorophenyl)-3-(4-sulfonamidobenzamido)propionate (D15)

The preparation method of the compound of Example 35 is the same as that of Example 21, using 3,4-dichlorobenzaldehyde (3.00 g, 17.24 mmol) as raw material and referring to the synthesis method of D1, D15 is obtained as a white solid with an amount of 0.19 g and a yield of 90.23%. Mp 361.3-363.4℃; ¹ H NMR (600MHz, DMSO-d ₆ ) δ10.51 (d, J=6.5Hz, 1H), 7.99 (d, J=8.3Hz, 2H), 7.92 (d, J=8.3Hz, 2H), 7.60 (s, 1H), 7.52 (d, J=8.3Hz, 1H), 7. 48 (s, 2H), 7.37 (d, J=8.4Hz, 1H), 5.20 (q, J=6.2Hz, 1H), 2.52-2.34 (m, 2H). ¹³ C NMR (151MHz, DMSO) δ173.90, 163.97, 146.66, 145.76, 137.28, 130.54, 130.17, 128.82, 128.55, 127.62, 127.06, 125.79, 50.48, 43.15.HRMS (ESI): Calcd.for C _{1 6} H ₁₃ N ₂ O ₅ SNaCl ₂ [M-Na] ^- : 414.9928, Found 414.9946 [M-Na] ^- .

Example 36: Sodium 3-(3,4-difluorophenyl)-3-(4-sulfonamidobenzamido)propionate (D16)

The preparation method of the compound of Example 36 is the same as that of Example 21, using 3,4-difluorobenzaldehyde (3.00 g, 21.13 mmol) as raw material and referring to the synthesis method of D1, D16 is obtained as a white solid with an amount of 0.19 g and a yield of 89.85%. Mp 370.0-371.6℃; ¹ H NMR (600MHz, DMSO-d ₆ ) δ10.54 (d, J=7.0Hz, 1H), 7.99 (d, J=8.2Hz, 2H), 7.92 (d, J=8.2Hz, 2H), 7.55 (s, 2H), 7.45-7.36 (m, 1H), 7.31 (q, J=8.6Hz, 1H), 7.22 (s, 1H), 5.20 (q, J=5.9Hz, 1H), 2.50-2.34 (m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.51, 164.35, 149.80, 148.21, 146.83, 142.82, 137.97, 128.10, 126.25, 123.67, 117.35, 115.92, 50.89, 43.74.HRMS (ESI): Calcd.for C _{1 6} H ₁₃ N ₂ O ₅ SNaF ₂ [M-Na] ^- : 383.0519, Found 383.0540 [M-Na] ^-

Example 37: Sodium 3-(3,4-dimethylphenyl)-3-(4-sulfonamidobenzamido)propionate (D17)

The preparation method of the compound of Example 37 is the same as that of Example 21, using 3,4-dimethylbenzaldehyde (3.00 g, 22.39 mmol) as raw material and referring to the synthesis method of D1, D17 is obtained as a white solid with an amount of 0.17 g and a yield of 80.30%. Mp351.6-352.7℃; ¹ H NMR (600MHz, DMSO-d ₆ ) δ10.55 (d, J=7.2Hz, 1H), 7.97 (d, J=8.3Hz, 2H), 7.91 (d, J=8.3Hz, 2H), 7.48 (s, 2H), 7.11 (s, 1H), 7.07 (d, J= ^{7 13} C NMR (151MHz, DMSO) δ174.77, 163.59, 146.41, 141.89, 137.82, 135.35, 133.86, 129.03, 127.66, 127.52, 125.74, 123.78, 50.82, 43.47, 19.57, 18.97.HRMS (ESI): Calcd.for[M-Na] ^- C ₁₈ H ₁₉ N ₂ O ₅ SNa: 375.1020, Found 375.1040[M-Na] ^- .

Example 38: Sodium 3-(3,4-dimethoxyphenyl)-3-(4-sulfonamidobenzamido)propionate (D18)

The preparation method of the compound of Example 38 is the same as that of Example 21, using 3,4-dimethoxybenzaldehyde (3.00 g, 18.07 mmol) as raw material and referring to the synthesis method of D1, D18 is obtained as a white solid with an amount of 0.16 g and a yield of 75.91%. Mp356.4-358.8℃; ¹ H NMR (600MHz, DMSO-d ₆ ) δ10.47 (d, J=7.2Hz, 1H), 7.98 (d, J=8.3Hz, 2H), 7.91 (d, J=8.3Hz, 2H), 7.54 (s, 2H), 7.01 (s, 1H), 6.88 (d, J=7 .2Hz, 1H), 6.82 (d, J=8.3Hz, 1H), 5.16 (q, J=5.8Hz, 1H), 3.70 (d, J=7.3Hz, 6H), 2.49-2.38 (m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.83, 163.70, 148.39, 147.37, 146.25, 137.94, 137.20, 127.58, 125.76, 118.35, 111.58, 110.74, 55.59, 55.44, 50.85, 43.66.HRMS (ESI): Calcd.for C ₁₈ H ₁₉ N ₂ O ₇ SNa[M-Na] ^- : 407.0918, Found 407.0949[M-Na] ^- .

Example 39: Sodium 3-(4-phenylphenyl)-3-(4-sulfonamidobenzamido)propionate (D19)

The preparation method of the compound of Example 39 is the same as that of Example 21, using 4-phenylbenzaldehyde (3.00 g, 16.48 mmol) as raw material and referring to the synthesis method of D1, D19 is obtained as a white solid with an amount of 0.17 g and a yield of 80.81%. Mp 371.4-372.6℃; ¹ H NMR (600MHz, DMSO-d ₆ ) δ 10.53 (s, 1H), 7.96-7.89 (m, 2H), 7.85 (d, J = 7.6Hz, 2H), 7.62 (d, J = 7.0Hz 2H), 7.55 (d, J = 7.0Hz, 2H), 7.49-7 .42(m, 4H), 7.37-7.29(m, 1H), 5.25(s, 1H), 2.62-2.51(m, 2H). ¹³ C NMR (151MHz, DMSO) δ174.94, 164.21, 151.14, 143.86, 140.25, 138.26, 135.66, 128.90, 127.17, 127.09, 126.99, 126.58, 126.35, 125.34, 50.71, 43.39. HRMS(ESI): Calcd.for C ₂₂ H ₁₉ N ₂ O ₅ SNa[M-Na] ^- : 423.1020, Found 423.1050[M-Na] ^- .

Example 20: Methyl 3-(4-methoxyphenyl)-3-(4-sulfonamidobenzamido)propionate (D20)

4-Methoxybenzaldehyde (3.00 g, 22.06 mmol), malonic acid (2.35 g, 22.06 mmol, 1 eq), ammonium formate (2.81 g, 44.12 mmol, 2 eq), and ethanol 40 mL were added to a 100 mL eggplant-shaped bottle. The mixture was stirred and refluxed for 8 h. The mixture was filtered, washed with ethanol and n-hexane, and dried to obtain a white solid with a yield of 1.86 g and a yield of 43.24%. HRMS (ESI): Calcd. for _{C 10} H ₁₃ NO ₃ [MH] ^- : 194.0823, Found 194.0839 [MH] ^- .

A 100 mL eggplant-shaped bottle was added with the white solid (1.86 g, 9.54 mmol) obtained in the previous step and 40 mL of methanol. 0.95 mL of concentrated sulfuric acid was added dropwise at -10°C with stirring. The mixture was then stirred at room temperature for 24 h. After the solvent was evaporated under reduced pressure, the pH was adjusted to 12 with 2M sodium hydroxide solution, and the mixture was extracted with dichloromethane (3 x 15 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a colorless oil with a yield of 1.61 g and a yield of 80.76%.

A 100 mL eggplant-shaped flask was added with the colorless oil obtained in the previous step (1.61 g, 7.70 mmol), p-sulfonamidobenzoic acid (2.33 g, 11.55 mmol, 1.5 eq), EDCI (2.20 g, 11.55 mmol, 1.5 eq), DMAP (0.94 g, 7.70 mmol, 1.0 eq), and 40 mL of acetonitrile. The mixture was stirred at room temperature for 4 h. The mixture was filtered, the filtrate was taken, 60 mL of water was added, and the mixture was extracted with dichloromethane (3 x 20 mL). The organic phases were combined and washed with 1 M hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and water (20 mL) in sequence, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain D20 as a white solid with an amount of 2.10 g and a yield of 69.54%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ9.01 (dd, J=8.4, 2.1Hz, 1H), 8.03-7.95 (m, 2H), 7.94-7.88 (m, 2H), 7.47 (s, 1H), 7.37-7.29 (m, 2H), 7.04-6.75 (m, 2H), 5.42 ( td, J=8.6, 6.2Hz, 1H), 3.73 (s, 3H), 3.56 (s, 3H), 3.09-2.76 (m, 2H). HRMS (ESI): Calcd. for C ₁₇ H ₁₈ N ₂ O ₅ S[M+Na] ⁺ : 385.0829, Found 385.0855 [M+Na] ⁺ .

Example 20: 3-(4-chlorophenyl)-3-(4-sulfonamidobenzamido)propanoic acid (D21)

4-Chlorobenzaldehyde (3.00 g, 21.43 mmol), malonic acid (2.23 g, 21.43 mmol, 1 eq), ammonium formate (2.70 g, 42.86 mmol, 2 eq), and 40 mL of ethanol were added to a 100 mL eggplant-shaped bottle. The mixture was stirred and refluxed for 8 h. The mixture was filtered, washed with ethanol and n-hexane, and dried to obtain a white solid with a yield of 2.77 g and a yield of 64.96%. HRMS (ESI): Calcd. for _{C 9} H ₁₀ NO ₂ Cl [MH] ^- : 198.0327, Found 198.0327 [MH] ^- .

A 100 mL eggplant-shaped bottle was added with the white solid (2.77 g, 13.92 mmol) obtained in the previous step and 40 mL of methanol. 1.39 mL of concentrated sulfuric acid was added dropwise at -10°C with stirring. The mixture was then stirred at room temperature for 24 h. After the solvent was evaporated under reduced pressure, the pH was adjusted to 12 with 2M sodium hydroxide solution, and the mixture was extracted with dichloromethane (3 x 15 mL). The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a colorless oil with a yield of 2.54 g and a yield of 85.67%.

A 100 mL eggplant-shaped flask was added with the colorless oil obtained in the previous step (2.54 g, 11.92 mmol), p-sulfonamidobenzoic acid (3.61 g, 17.88 mmol, 1.5 eq), EDCI (3.41 g, 17.88 mmol, 1.5 eq), DMAP (1.45 g, 11.92 mmol, 1.0 eq), and 40 mL of acetonitrile. The mixture was stirred at room temperature for 4 h. The mixture was filtered and the filtrate was taken. 60 mL of water was added and the mixture was extracted with dichloromethane (3 x 20 mL). The organic phases were combined and washed with 1 M hydrochloric acid (20 mL), saturated sodium bicarbonate (20 mL), and water (20 mL) in sequence. The mixture was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to obtain a white solid with a yield of 3.15 g and a yield of 66.71%. HRMS (ESI): Calcd. for C ₁₇ H ₁₇ N ₂ O ₅ SCl[M+Na] ⁺ : 419.0439, Found 419.0489 [M+Na] ⁺ .

The white solid (3.15 g, 7.95 mmol) obtained in the previous step and 10 mL of tetrahydrofuran were added to a 100 mL eggplant-shaped bottle. Under stirring at room temperature, 19.88 mL (19.88 mmol, 2.5 eq) of 1 M sodium hydroxide solution was added dropwise, and stirring was continued for 4 h. Part of the solvent was evaporated under reduced pressure, and pH was adjusted to 3 with 1 M hydrochloric acid to produce a white precipitate, which was filtered, washed with water, and dried to obtain D21 as a white solid, with an amount of 2.50 g and a yield of 82.27%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 12.35 (s, 1H), 9.14 (s, 1H), 8.14-7.97 (m, 2H), 7.92 (d, J = 8.2Hz, 2H), 7.49 (s, 1H), 7.45 (d, J = 8.8Hz, 2H), 7.42-7.37 (m, 2H), 5.41 (s, 1H), 3.09-2.67 (m, 2H). HRMS (ESI): Calcd. for C ₁₆ H ₁₄ N ₂ O ₅ SNaCl [MH] ^- : 381.0317, Found 381.0317 [MH] ^- .

Pharmacological studies of the present invention

The inhibitory effects of compounds S1-S20 and D1-D21 on carbonic anhydrase II were determined by enzymatic hydrolysis.

The substrate (4-nitrophenyl acetate) was diluted to 2mM with Tris assay buffer, the enzyme was diluted to 20ng/uL with assay buffer, 50uL of 20ng/uL enzyme was added to a 96-well plate, compounds S1-S20, D1-D21 prepared in the above examples of inhibitors were added, incubated at room temperature for 15min, 25uL of 2mM substrate was added to initiate the reaction, and the absorbance at 348nm was read by a microplate reader after 10min. The inhibition rate of 6 different concentrations (2.00μM, 400.00nM, 80.00nM, 16.00nM, 3.20nM, 0.64nM) was tested to obtain the IC ₅₀ value, and the inhibition rate calculation formula is as follows:

% inhibition rate = (1-enzyme activity of sample well/enzyme activity of blank well) * 100

^a Human recombinant enzyme, assayed by the esterase method (4-nitrophenylacetate as substrate).

p-Sulfamoylbenzoic acid

From the above, it can be seen that the inhibitory activities of S1-S20 and D1-D21 of the present invention are better than those of the positive control drug p-sulfonylaminobenzoic acid. The 3-substituted aryl-3-(4-sulfonylaminobenzamide)propionic (enoic) acid derivatives designed and synthesized by the present invention simultaneously bind to the zinc ion, hydrophobic region and hydrophilic region of the CA II inhibitor, thereby significantly improving its inhibitory effect.

Claims (4)

1. A 3-aryl-3- (sulfanilide) acrylic (olefine) acid compound characterized in that: the compound is

。

2. A pharmaceutical composition characterized by: a composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

3. Use of a compound according to claim 1 or a pharmaceutical composition according to claim 2 for the manufacture of a medicament for inhibiting carbonic anhydrase.

4. Use according to claim 3, characterized in that: use of a compound according to claim 1 or a pharmaceutical composition according to claim 2 for the preparation of an anti-glaucoma drug.