CN1168707C - 4-guanidinobenzamide antifertility compounds - Google Patents

Abstract

The invention relates to the technical field of medicine, and relates to a class of 4-guanidinobenzamide antifertility compounds capable of inhibiting the activity of human sperm acrosome. The general structural formula of this type of compound is the right formula: wherein the R group represents -CH ₂ CH ₂ CH ₃ -(CH ₂ ) ₇ CH ₃ -C(CH ₃ ) ₃ -COCH=CH ₂ , and the compound of the present invention is chemically stable , which can significantly inhibit the activity of human sperm acrosome, is a class of high-efficiency, low-toxic anti-fertility compounds, and can be used to prepare anti-fertility drugs.

Description

4-guanidinobenzamide antifertility compound

Technical field: the present invention relates to the technical field of medicine, and is a class of 4-guanidinobenzamide antifertility compounds capable of inhibiting the activity of human sperm acrosome.

Background technique:

Implementing family planning and controlling population growth is a global task and a basic national policy of our country. At present, the commonly used contraceptive methods in clinical practice mainly include: surgical operation, permanent or reversible blocking of fallopian tubes or vas deferens, this method is very worrying for a couple who only have one child, and it is difficult for the public to accept; contraceptive tools, such as condoms, cervical Caps, contraceptive rings, etc. prevent sperm movement, and these methods also have many problems, such as foreign body sensation and irritation of condoms, problems such as detachment of IUDs, pregnancy with rings, and bleeding; contraceptive drugs have been used the most over the years. It is a hormonal contraceptive, which interferes with the physiological functions of normal people, has large side effects, and is limited in application. In addition, external contraceptives are also used clinically, but due to the unsatisfactory contraceptive effect of these drugs and other side effects, they have not been widely used clinically. Today, searching for male contraceptives with high efficiency, low toxicity, and especially a unique contraceptive mechanism has become a new hot spot for researchers from all over the world.

Numerous studies have shown that the acrosome of the human sperm acrosome is an essential proteolytic enzyme for the combination of sperm and eggs during fertilization, and inhibiting acrosome can prevent fertilization and achieve the purpose of contraception. Researchers from various countries have successively carried out the work of searching for human sperm acrosinase inhibitors. The main research in this area includes: searching for protease inhibitors from natural animals, plants and microorganisms. Schill et al. used gelatin thin-layer technology to study the penetration of protease inhibitors on sperm acrosomal membranes. The results showed that the above two types of protease inhibitors had poor inhibitory effects and could not be further developed as contraceptives. Joyce C et al. found that p-toluenesulfonyllysyl chloromethyl ketone (TLCK) has a good inhibitory effect on acrosinase, but unfortunately TLCK is extremely carcinogenic. Kaminsk et al. have synthesized a series of aromatic 4-guanidino benzoate salts by substituting p-nitrophenol with phenol, and the anti-fertility tests in vitro and in animals have shown that they have low toxicity and high anti-fertility effects (J.Med.Chem. 1986, 29:514～519), but because of the phenolic ester structure of this kind of compound, its chemical property is not stable. But studies have shown that 4-guanidinobenzoic acid is an essential structure for acrosome inhibitors.

Summary of the invention: As we all know, the ester bond and the amide bond are isosteres, and the amide bond is more stable than the ester bond. Therefore, the present invention prepares 4-guanidinobenzoic acid into 4-guanidinobenzoic acid amide compounds. The compounds are stable in chemical properties, have remarkable activity of inhibiting human sperm acrosome enzyme, and are novel anti-fertility compounds with high efficiency and low toxicity.

The structural formula general formula of compound of the present invention is:

Wherein the R group represents -CH ₂ CH ₂ CH ₃ -(CH ₂ ) ₇ CH ₃ -C(CH ₃ ) ₃ -COCH=CH ₂

The synthetic route of compound of the present invention is described in two steps:

One, the synthetic route of key intermediate 4-guanidinobenzoyl chloride hydrochloride is as follows:

The specific operation process is:

1. Take p-aminobenzoic acid in an aqueous solution, and react with ammonium thiocyanate in the presence of hydrochloric acid to generate isothioureidobenzoic acid hydrochloride;

2. Isothioureidobenzoic acid hydrochloride reacts with iodomethane in ethanol solution to generate 4-{[(amino-methylthio)methyl]amino}benzoic acid hydroiodide;

3. 4-{[(amino-methylthio)methyl]amino}benzoic acid hydroiodide reacts with excess ammonia water to generate 4-guanidinobenzoic acid;

4. 4-guanidinobenzoic acid reacts with excess thionyl chloride to generate 4-guanidinobenzoyl chloride hydrochloride.

Two, the synthesis of target compound, synthetic route is as follows:

The operation process is:

The amine compound is dissolved in tetrahydrofuran, and reacted with freshly prepared 4-guanidinobenzoyl chloride hydrochloride under the action of triethylamine to obtain 4-guanidinobenzamide compound.

Detailed ways:

Reagents and materials:

Reagents and materials and names Specifications Buying company

p-Aminobenzoic acid CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

Hydrochloric acid CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

Ammonium Thiocyanate CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

Absolute Ethanol CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

Iodomethane CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

Ammonia Water CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

Propylamine CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

Tert-butylamine CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

4-Fluoroaniline CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

2,4-Dichloroaniline CP  China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

4-Nitroaniline CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

4-Methylaniline CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

2-Aminopyridine CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

Triethylamine CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

Tetrahydrofuran CP CP China National Pharmaceutical (Group) Shanghai Chemical Reagent Company

1. Preparation of intermediates

Embodiment 1: the preparation of intermediate 4-guanidinobenzoyl chloride hydrochloride

(1) Synthesis of isothioureidobenzoic acid hydrochloride

0.5mole of p-aminobenzoic acid, 1500ml of water, 0.5mole of concentrated hydrochloric acid, 0.55mole of ammonium thiocyanate, in a water bath at 60-70°C, stirring and reacting to obtain a white solid crude product of isothioureidobenzoic acid hydrochloride, and then The solid was poured into 400ml of 10% NaOH solution, decolorized with activated carbon, and the filtrate was neutralized to pH 2-3 with 20% hydrochloric acid to obtain 101 g of isothioureidobenzoic acid hydrochloride as a white solid, with a yield of 86.8%.

(2) Synthesis of 4-{[(amino-methylthio)methyl]amino}benzoic acid hydroiodide

Isothioureidobenzoic acid hydrochloride 0.5 mole, absolute ethanol 650ml, iodomethane 1 mole, in a water bath at 90°C, stirred and refluxed for 2 hours to obtain 4-{[(amino-methylthio)methyl]amino}benzene Formic acid hydroiodide solid 141g, yield 83.1%.

(3) Synthesis of 4-guanidinobenzoic acid

4-{[(amino-methylthio)methyl]amino}benzoic acid hydroiodide 0.5 mole, ammonia water 2.5 mole, stirred at 40-50°C for 2 hours to obtain a white solid, filtered, washed with water, and recrystallized with ethanol Obtain 78g of 4-guanidinobenzoic acid, productive rate 87.7% (element analysis: real value C 53.61%; H 5.07%; N 23.42%).

(4) Synthesis of 4-p-guanidinobenzoyl chloride hydrochloride

0.1 mole of 4-guanidinobenzoic acid and 1 mole of thionyl chloride were stirred and refluxed for 1 hour, allowed to cool, the solid was filtered, and the solid was washed with petroleum ether to obtain 19 g of 4-guanidinobenzoyl chloride hydrochloride with a yield of 81.2%.

Two, preparation has the 4-guanidinobenzamide compound of different R group

Example 2

Preparation of N-propyl-4-guanidinobenzamide: (R group is CH ₂ CH ₂ CH ₃ )

Take 0.02 mole of propylamine, 30 ml of tetrahydrofuran, and 3 ml of triethylamine, stir, add 0.04 mole of 4-guanidinobenzoyl chloride hydrochloride (freshly prepared), and stir at room temperature for 2 hours to obtain N-propyl-4-guanidinobenzene The crude formamide was purified by column chromatography to obtain 3.5 g of N-propyl-4-guanidinobenzamide as a white solid.

Example 3: Preparation of N-(4-fluoro-phenyl)-4-guanidinobenzamide (R group is 4-fluorophenyl)

Take 0.01 mole of 4-fluoroaniline, 15 ml of tetrahydrofuran, and 3 ml of triethylamine, add 0.015 mole of 4-guanidinobenzoyl chloride hydrochloride under stirring, react at 0°C for 1.5 hours, and react at room temperature for 6 hours to obtain N- The crude (4-fluoro-phenyl)-4-guanidinobenzamide was purified by column chromatography to obtain 3.1 g of refined N-(4-fluoro-phenyl)-4-guanidinobenzamide.

Embodiment 4: Preparation of N-(4-aminosulfonylphenyl)-4-guanidinobenzamide (R group is 4-aminosulfonylphenyl)

0.01 mole of 4-aminobenzenesulfonamide, 15 ml of tetrahydrofuran, 3 ml of triethylamine, 5 ml of nitrogen-nitrogen dimethylformamide (DMF), stirred and dissolved, at 15°C, 0.01 mole of 4-guanidinobenzoyl chloride hydrochloride was added, After the addition, react at 65°C for 12 hours to obtain crude N-(4-aminosulfonylphenyl)-4-guanidinobenzamide, which is purified by column chromatography to obtain N-(4-aminosulfonylphenyl) - 2.8g of 4-guanidinobenzamide refined product.

Embodiment 5: Preparation of N-(4-ethoxyformylphenyl)-4-guanidinobenzamide (R group is 4-ethoxyformylphenyl)

0.01 mole of ethyl p-aminobenzoate, 15 ml of tetrahydrofuran, 2.5 ml of triethylamine, stir to dissolve, add 0.01 mole of p-guanidinobenzoyl chloride hydrochloride under ice cooling, stir for 3 hours, a yellow precipitate is formed, filter to obtain N- The crude product of (4-ethoxyformylphenyl)-4-guanidinobenzamide was purified with methanol to obtain 2.9 g of N-(4-ethoxyformylphenyl)-4-guanidinobenzamide.

Embodiment 6: the preparation of N-(2-pyridyl)-4-guanidinobenzamide

Take 0.01 mole of 2-aminopyridine, 20 ml of tetrahydrofuran, and 3 ml of triethylamine, add 0.02 mole of p-guanidinobenzoyl chloride hydrochloride at room temperature, stir and react at 55°C for 6 hours to obtain N-(2-pyridyl)-4 -Guanidinobenzamide crude product, the crude product was purified by column chromatography to obtain 1.9 g of pure N-(2-pyridyl)-4-guanidinobenzamide.

For the 4-guanidinobenzamide compounds whose R groups are -(CH ₂ ) ₇ CH ₃ -C(CH ₃ ) ₃ -COCH=CH ₂ , the preparation method is the same as in Example 2.

The R bases are

的4-胍基苯甲酰胺类化合物，制备方法同实施例3。

The 4-guanidine benzamide compound, preparation method is the same as embodiment 3.

的4-胍基苯甲酰胺类化合物，制备方法同实施例4。The R bases are

The 4-guanidine benzamide compound, preparation method is the same as embodiment 4.

The base R is N-(4-methoxyformylphenyl)-4-guanidinobenzamide, the preparation method is with embodiment 5.

All 4-guanidine benzamide compounds can be made into hydrochloride, sulfate, methanesulfonate.

The synthesized compounds are shown in Table 1, and the H NMR spectra of some 4-guanidinobenzamide compounds are shown in Table 2.

Table 1 Structure and molecular formula of 4-guanidinobenzamides

General structural formula:

Compound No. R Group Molecular Formula

1 -CH ₂ CH ₂ CH ₃ C ₁₁ H ₁₇ ClN ₄ O

2 -(CH ₂ ) ₇ CH ₃ C ₁₆ H ₂₇ ClN ₄ O

3 -C(CH ₃ ) ₃ C ₁₂ H ₁₉ ClN ₄ O

4 C ₁₁ H ₁₃ ClN ₄ O ₂

5 C ₁₄ H ₁₅ ClN ₄ O

6 C ₁₄ H ₁₄ ClN ₄ F

             C₁₄H₁₄ClN₄I7

C ₁₄ H ₁₄ ClN ₄ I

            C₁₄H₁₃Cl₃ON₄ 8

C ₁₄ H ₁₃ Cl ₃ ON ₄

9 C ₁₄ H ₁₄ ClO ₃ N ₅

10 C ₁₄ H ₁₃ ClO ₅ N ₆

      C₁₄H₁₈ClO₃N₅S11

C ₁₄ H ₁₈ ClO ₃ N ₅ S

12 C ₁₅ H ₁₄ ClON ₄ F ₃

          C₁₅H₁₇ClON₄ 13

C ₁₅ H ₁₇ ClON ₄

          C₁₆H₁₉ClON₄ 14

C ₁₆ H ₁₉ ClON ₄

                C₁₆H₁₉ClON₄ 15

C ₁₆ H ₁₉ ClON ₄

Compound No. R Group Molecular Formula

                C₆H₁₇ClO₃N₄ 16

C ₆ H ₁₇ ClO ₃ N ₄

            C₁₇H₁₉ClN₄O₃ 17

C ₁₇ H ₁₉ ClN ₄ O ₃

18 C ₁₃ H ₁₄ ClN ₅ O

19 C ₁₁ H ₁₂ N ₆ ClO

                          C₁₃H₁₄N₅ClO20

C ₁₃ H ₁₄ N ₅ ClO

                              C₁₁H₁₂N₅ClO₂ twenty one

C ₁₁ H ₁₂ N ₅ ClO ₂

Table 2 NMR spectrum of some 4-guanidinobenzamide compounds

General structural formula:

                                          

Compound No. R group HNMR DMSO-D61 -CH ₂ CH ₂ CH ₃ 0.85(t, 3H) 1.4～1.6(m, 2H) 3.1～3.3(m, 2H) 7.25(d, J=8.50Hz, 2H) 7.737 (s, 3H)

7.95(d, J=8.50Hz, 2H) 8.5～8.6(m, 1H) 10.40(s, 1H) 2 -(CH ₂ ) ₇ CH ₃ 0.85(m, 5H) 1.1～1.6(m, 10H) 3.1～ 3.3(m, 2H) 7.25(d, J=8.50Hz, 2H) 7.74(s, 3H)

                      7.90 (d, J = 8.5 Hz, 2H) 8.04 (s, 1H) 8.55 (t, 1H) 10.41 (s, 1H)

7.15(d，J＝8.6Hz，2H)7.35(d，J＝8.4Hz，2H)7.65(d，J＝8.4Hz，2H)8.05(d，J＝8.6Hz，2H)10.44(s，1H)7.08(m，1H)10.45(s，1H)

7.15(d, J=8.6Hz, 2H) 7.35(d, J=8.4Hz, 2H) 7.65(d, J=8.4Hz, 2H) 8.05(d, J=8.6Hz, 2H) 10.44(s, 1H) 7.08(m, 1H)10.45(s, 1H)

6.95(d, J=8.5Hz, 2H) 7.8(s, 3H) 7.35(d, J=8.6Hz, 2H) 7.95(d, J=8.5Hz, 2H) 8.05(d, J=8.6Hz, 2H) 10.44(s, 1H) 10.48(s, 1H)

7.35(d, J=8.6Hz, 2H) 7.8～7.9(m, 4H) 7.35(d, J=8.5Hz, 2H) 7.77(s, 3H) 10.42(s, 1H)

2.16(s，3H)2.27(s，3H)6.9～7.2(m，3H)7.35(d，J＝8.5Hz，2H)7.77(s，3H)8.05(d，J＝8.5Hz，2H)9.90(s，1H)10.44(s，1H)

( s, 1H) 10.44 (s, 1H)

2.15(s, 3H) 2.27(s, 3H) 6.95(m, 3H) 7.15(d, J=8.50Hz, 2H) 7.35(d, J=8.40Hz, 2H) 7.72(s, 3H) 8.05(d, J=8.5Hz, 2H) 9.89(s, 1H) 10.34(s, 1H)

pharmacological test

Sperm acrosin is a tryptase with gelatin-dissolving properties. Sperm incubated on an ultra-thin gelatin film, the acrosome ruptures and depolymerizes first, leading to the release of acrosome enzyme, and then dissolves on the gelatin matrix to form a visible halo around the sperm head, and the positive reaction of the sperm halo can be observed through a microscope Halo rate and halo diameter, the former reflects the percentage of sperm with fertilization ability, and the latter reflects the acrosome activity of a single sperm. In this experiment, the gelatin substrate membrane method was used to observe the inhibition of 19 compounds on human sperm acrosome enzyme activity, and the positive rate and average halo diameter of human sperm acrosome enzyme reaction to gelatin were measured. The results are shown in Table 3, Table 4 and Table 5.

The detection method is as follows:

1. Preparation of gelatin film

Soak 408mg of dry gelatin in 12ml of distilled water for 15 minutes, and dissolve it in a water bath at 40°C. Then heat the gelatin solution to 50°C, then accurately measure 0.1ml of the gelatin solution, drop it on a clean glass slide, and make a 45×20mm2 film. Then put it in a refrigerator at 4°C for 3-5 minutes, and dry it at room temperature for 18 hours. The dried gelatin film was fixed with 0.05% glutaraldehyde, then the pH of the film was adjusted to 7.0±0.05 with barbiturate buffer solution, and titrated with 0.5% trypan blue.

2. Processing of sperm

Wash the sperm twice with 0.1mol/L pH7.4 phosphate buffer, adjust the sperm concentration to 50×106/ml, add 0.2ml of Sperm suspension, incubate at room temperature for 5 minutes Take a drop (about 50 μl) of the above sperm mixture and drop it on the gelatin film, spread the sperm suspension evenly on another clean glass slide, and then place it in a 37°C incubator and incubate for 3 hours. Take it out, air dry, and seal with neutral resin.

3. Determination

Observed by light microscope, any white bright area around the sperm head is a positive reaction. Mean halo positive rate (mean halorate mHR) (%): Count 100 sperm in each field of view, and count the number of positive sperm among them.

Mean halo diameter (mean halo diameter, mHD) (microns), the halo diameter is measured with a microscope micrometer. When the halo is not circular but half-moon, take half of the sum of its length as the diameter of the halo. Measure the diameter of 50 sperm halos and take the average value.

4. Results

The experiment was divided into experimental group, blank control group and positive control group (TLCK group). The results showed that all the compounds in the experimental group had the effect of inhibiting sperm acrosin to varying degrees. Wherein the No. 17 compound in Table 4 has the strongest inhibitory activity of acrosome enzyme.

Table 3 The detection results of fatty amine compounds on the inhibition of human sperm acrosome enzyme activity

Compound No. Tube No. R Group Positive Rate Reaction Halo Diameter X±SD Drug Concentration (mg/ml)

1′ 0% 0 1×10 ^-3

2′ 45% 22.91±0.46 1×10 ^-5

1-CH ₂ CH ₂ CH ₃

3′ 48% 22.94±0.48 1×10 ^-7

4′ 56% 23.27±0.49 1×10 ^-9

1′ 0% 0 1×10 ^-3

2′ 38% 12.30±0.33 1×10 ^-5

2 -(CH ₂ ) ₇ CH ₃

3′ 43% 19.93±0.50 1×10 ^-7

4′ 56% 21.95±0.30 1×10 ^-9

1′ 10% 5.87±0.73 1×10 ^-3

2′ 38% 8.64±0.85 1×10 ^-5

3 -C(CH ₃ ) ₃

3′ 51% 19.93±0.38 1×10 ^-7

4′ 68% 25.97±4.26 1×10 ^-9

1′ 0% 0 1×10 ^-3

2′ 15% 8.98±0.25 1×10 ^-5

                 

4 3' 31％ 10.97±0.37 1×10 ^-7

4′ 52% 23.27±0.26 1×10 ^-9

Control 68% 26.27±0.47 8% DMSO

Table 4 Detection results of the inhibition of human sperm acrosome activity by substituted aniline compounds

Compound No. Tube No. R Group Positive Rate Reaction Halo Diameter Drug Concentration

X±SD (mg/ml)

1′ 12% 6.60±0.19 1×10 ^-3

2′ 40% 14.25±0.39 1×10 ^-5

5

3′ 45% 17.29±0.48 1×10 ^-7

4′ 61% 26.93±0.51 1×10 ^-9

1′ 21% 14.96±0.35 1×10 ^-3

2′ 38% 21.61±0.52 1×10 ^-5

6

3′ 40% 25.27±0.20 1×10 ^-7

4′ 45% 25.93±0.27 1×10 ^-9

1′ 0% 0 1×10 ^-3

2′ 40% 15.44±0.47 1×10 ^-5

7

3′ 58% 21.66±1.16 1×10 ^-7

4′ 66% 22.86±0.77 1×10 ^-9

1′ 0% 0 1×10 ^-3

2′ 10% 19.28±0.47 1×10 ^-5

8

3′ 21% 22.61±0.48 1×10 ^-7

4′ 60% 25.92±0.35 1×10 ^-9

1′ 0% 0 1×10 ^-3

2′ 10% 14.63±0.48 1×10 ^-5

9

3′ 21% 20.58±0.55 1×10 ^-7

4′ 43% 26.60±0.47 1×10 ^-9

1′ 0% 0 1×10 ^-3

2'

10

3′ 21% 18.14±0.66 1×10 ^-7

4′ 43% 19.89±0.33 1×10 ^-9

1′ 0% 0 1×10 ^-3

2′ 6% 5.72±0.56 1×10 ^-5

11

3′ 20% 15.37±0.47 1×10 ^-7

4′ 33% 16.01±0.57 1×10 ^-9

Compound No. Tube No. R Group Positive Rate Reaction Halo Diameter Drug Concentration

X±SD (mg/ml)

1′ 0% 0 1×10 ^-3

2′ 10% 8.55±0.45 1×10 ^-5

12

3′ 38% 19.66±0.44 1×10 ^-7

4′ 44% 21.11±0.67 1×10 ^-9

1′ 0% 0 1×10 ^-3

2′ 30% 9.64±0.28 1×10 ^-5

13

3′ 45% 17.30±0.31 1×10 ^-7

4′ 54% 20.89±0.43 1×10 ^-9

1′ 4% 5.38±0.41 1×10 ^-3

2′ 38% 14.29±0.39 1×10 ^-5

14

3′ 58% 25.60±0.36 1×10 ^-7

4′ 66% 25.97±0.30 1×10 ^-9

1′ 13% 7.21±0.28 1×10 ^-3

2′ 40% 17.34±0.84 1×10 ^-5

15

3′ 48% 21.61±0.38 1×10 ^-7

4′ 61% 27.90±0.40 1×10 ^-9

1′ 0% 0 1×10 ^-3

2′ 30% 11.84±0.41 1×10 ^-5

16

3′ 58% 18.32±0.40 1×10 ^-7

4′ 66% 19.99±0.71 1×10 ^-9

1′ 0% 0 1×10 ^-3

2′ 3% 4.25±0.29 1×10 ^-5

17

3′ 16% 9.32±0.45 1×10 ^-7

4′ 25% 14.18±0.36 1×10 ^-9

Control 70% 22.86±0.75 8% DMSO

Table 5 Heterocyclic arylamine compounds and TLCK inhibit human sperm acrosome activity detection results

Compound No. Tube No. R Group Positive Rate Reaction Halo Diameter Drug Concentration

X±SD (mg/ml)

1′ 0% 0 1×10 ^-3

2′ 18% 9.64±0.47 1×10 ^-5

18 3' 33% 11.32±0.37 1×10 ^-7

4′ 50% 22.61±1.16 1×10 ^-9

Control 80% 29.59±0.37 8% DMSO

0% 0 5.0

12.8 % 6.59 ± 1.58 4.0

28.9% 8.95±1.68 3.0

Positive 36.0% 10.57±1.46 2.5

sex

                                                                                            

right

58.6% 12.75±2.00 1.0

According to

63.50% 15.82±2.16 0.5

Group

70.70% 19.49±1.82 0.25

77.10 % 21.51 ± 3.41 0.125

Claims (2)

1.4-the guanidinobenzamides compound, its general structure is

Wherein the R group is represented-CH ₂CH ₂CH ₃-(CH ₂) ₇CH ₃-C (CH ₃) ₃-COCH=CH ₂

2. the described 4-guanidinobenzamides of claim 1 compound is used to prepare the purposes of antifertility drug.