Hydrogen sulfide donor in the form of an organic salt and a method for its production

Abstract

Hydrogen sulfide donor in the form of organic salt and its preparation method. The hydrogen sulfide donor is a salt structure formed by an organic compound with alkaline structure and hydrogen sulfide. The structure of the hydrogen sulfide donor is simple, the preparation method is simple and easy to operate, and different forms of hydrogen sulfide donor can be obtained according to the needs of research and development. After entering the organism, the process of dissociation and providing hydrogen sulfide in vivo is simple, fast and effective, without any enzyme or other complex conditions, and has great application prospect and value.

Description

Technical Field

[0001] This invention relates to a novel form of hydrogen sulfide donor that may have research and / or pharmaceutical value. Background Technology

[0002] Hydrogen sulfide (H2S) is widely recognized as having no medicinal use due to its foul odor and high toxicity, and is classified as a poisonous gas. However, in the past decade or so, our understanding of its effects on physiological and pathological processes in biological systems has surprisingly revealed that endogenous H2S has a wide range of biological effects and great medical potential.

[0003] Hydrogen sulfide has a molecular weight of 34, a boiling point of -63.33℃, and is 1.13 times heavier than air. It is a gas at room temperature, and its odor can be detected at concentrations of 0.02~0.13 ppm in the air. At 10℃, 0.5g of hydrogen sulfide dissolves in 100ml of water, while at 20℃, only 0.3g dissolves. The solution has a pH of 4.5, pKa of 17.04, and pH of 211.96. It can form stable salts with alkali metals such as Na, K, and Ca, as well as alkaline earth metals, or with NH3.

[0004] Since the discovery that H2S is an endogenous molecular gas in living organisms, it has attracted widespread attention, just like NO and CO, becoming a hot topic and cutting-edge subject in global scientific research. Research areas mainly include the mechanisms of H2S formation in vivo, molecular biology studies of H2S in vivo, including its molecular regulatory mechanisms on cells, the correlation between H2S and major diseases and its molecular mechanisms, and research on hydrogen sulfide donors to develop its medical value.

[0005] Studies have found that H2S present in the body can be naturally produced in vivo using at least three enzymes—thiosulfate lyase (CSE), cystathionine β-synthase (CBS), and 3-thiopyruvate transferase (3-MST)—using sulfur-containing amino acids such as L-cysteine ​​as substrates. It can also be produced spontaneously by erythrocytes through reactions involving glucose and reduced glutathione (GSH). The metabolic processes of sulfur-containing amino acids in the body are as follows... Figure 1 As shown.

[0006] Current research on the in vivo biological regulation of H2S focuses particularly on its relationship with diseases such as asthma, atherosclerosis, diabetes, and hypertension. Recently, the relationship between H2S and oncology has also attracted considerable attention, with the main targets being the expression of enzymes or genes associated with H2S.

[0007] As reported (Qiangian Sun et al. Hypertension, 2016, 67(3)541-9), excessive salt intake can lead to hypertension. Therefore, the World Health Organization recommends that healthy individuals consume less than 6g of salt per day. Studies have found that introducing H2S donors such as taurine into the body to form exogenous H2S can serve as an endogenous defense system against salt-induced hypertension, as H2S levels are significantly reduced in the plasma of individuals with prehypertension.

[0008] Existing studies have shown that the use of inorganic H2S donors, including Na2S and (NH4)2S, has yielded meaningful results in studies on cerebral ischemia, blood flow, and hemorheology in animals (Yu Zhao et al. Design, Synthesis and Cardioprolective Effect of N-Mercapto-Based Hydrogen Sulfide Donors J. of Med, chem(2015, 58(18):7501-7511)).

[0009] Currently, three classes of H2S donors have been reported: inorganic H2S donors such as Na2S, NaHS, and CaS; organic H2S donors such as sulfur-containing organic compounds; and H2S donors from organic synthesis, such as thiol-containing aspirin and thiol-containing ibuprofen. Molecular biological research, including studies on their chemical structure, pharmacological activities, effects on cellular biological regulation, influence on enzymes, and gene expression, has become increasingly extensive and in-depth (Philip K. Moore, Chemistry Biochemistry and Pharacology of Hydrogen Sulfide, Springer International Publishing, Switzerland 2015). Summary of the Invention

[0010] In view of this, the present invention provides a novel structural form of hydrogen sulfide (H2S) donor that has research and / or drug development value, namely, a hydrogen sulfide donor in the form of an organic salt, and further provides a corresponding preparation method thereof.

[0011] The hydrogen sulfide donor in the form of an organic salt described in this invention is a salt structure formed by an organic compound with a basic structure and hydrogen sulfide (H2S). Since hydrogen sulfide is an acidic component, the organic compound molecule that can form a salt with it must have a corresponding basic structure, and the stronger the basicity, the higher the stability of the formed salt. Generally, the donor in the form of a salt structure formed by the organic compound with a basic structure and a pH value ≥ 9.5 in a 1 mol / L solution usually exhibits sufficient stability.

[0012] As is well known, most organic compounds with basic structures contain nitrogen (N) in their molecular structure or have nitrogen-containing groups, including open-chain, monocyclic or polycyclic aliphatic compounds, and compounds with aromatic rings and / or heterocyclic structures (R or R1-R4 in each structure can be C). 1-3 The alkane or alkene, where X can be a group containing O, S, or N, n = 1 to 2. For example, it may include, but is not limited to, the compounds listed below.

[0013] Since the hydrogen sulfide donor of the present invention is a salt structure formed by an organic compound with a basic structure and hydrogen sulfide, it can, like inorganic hydrogen sulfide donors such as sodium sulfide and sodium hydrosulfide, facilitate the convenient and rapid release of hydrogen sulfide during dissolution in the body fluids of organisms or the human body, without requiring other forms of organic hydrogen sulfide donors that, as previously reported, require complex physiological / biochemical reactions with the participation of different enzymes to release hydrogen sulfide in vivo.

[0014] Among the aforementioned organic compounds with basic structures that can form salts with hydrogen sulfide, their intervention or influence on the physiological processes of organisms (especially the human body) can include compounds that can produce relevant physiological and / or pharmacological activities on organisms, as well as so-called "neutral compounds" that, although they do not have any physiological and / or pharmacological activity on organisms, will not produce adverse consequences and are therefore acceptable to organisms. For the latter type of "neutral compounds," after the donor that forms a salt structure with hydrogen sulfide enters the organism and dissociates, the only active component is hydrogen sulfide. Therefore, while such hydrogen sulfide donors may also be used for drug development, their greater advantage lies in the study of the relevant physiological / pharmacological effects of hydrogen sulfide under conditions where other factors can be excluded. Based on research and understanding of the relevant physiological / pharmacological effects of hydrogen sulfide, selecting hydrogen sulfide donors formed by salting alkaline organic compounds that have corresponding physiological and / or pharmacological activities on organisms, especially the human body, to achieve the goal of synergistic or complementary effects of their beneficial effects and / or mutual restraint or cancellation of their respective adverse effects can not only be used for the study of the effects of hydrogen sulfide, but also directly applied to drug development.

[0015] Specifically, the aforementioned basic organic compounds containing nitrogen or having nitrogen-containing groups may include compounds with one of the following structures: guanidine, amidine, hydrazine, or amine. For example, the basic organic compounds containing nitrogen or having nitrogen-containing groups may include, but are not limited to, basic amino acid compounds such as arginine, methionine, cystine, and cysteine.

[0016] Furthermore, the basic organic compounds containing nitrogen or having nitrogen-containing groups may also include alkaloids that have or do not have physiological / pharmacological activity, as previously reported and / or used.

[0017] Among the various organic base compounds that can be used as hydrogen sulfide donors, the preferred compounds are those that have been shown to be effective in treating existing diseases closely related to hydrogen sulfide, such as metformin or similar excellent drugs for treating diabetes. These compounds can be formulated into hydrogen sulfide salts to become drug-hydrogen sulfide donor compounds, thereby facilitating the formation of dual targets or synergistic effects.

[0018] Since hydrogen sulfide is an acidic gaseous substance with some solubility in water, and the basic organic compounds that can form salts with hydrogen sulfide also generally have some solubility in water, the conventional method for preparing the organic salt form of hydrogen sulfide donor described in this invention involves dissolving the compound in water or another good solvent of the raw material compound, introducing hydrogen sulfide gas to form a salt, and then separating it from the reaction solvent through conventional post-treatment methods such as precipitation, filtration, concentration, or recrystallization to obtain the target compound in solid form. These are all conventional salt-forming reactions and methods and processes for preparing salt compounds well known in the art. For example, hydrogen sulfide salts of commonly used pharmaceutical-type base compounds such as arginine hydrogen sulfide, guanethidine, clonidine, morpholine guanidine, phenformin, and cimetidine can all be prepared using this method. In addition, this method can also be used to prepare hydrogen sulfide salts of alkaloids such as berberine and berberine. For currently available non-pharmaceutical basic compounds such as hydrazine compounds, preparing them as hydrogen sulfide salts can also be used for in-depth exploration, research, and understanding of the properties of hydrogen sulfide salts.

[0019] For certain basic compounds, such as free bases, which are not very stable or are highly unstable, their common or commercially available forms are often stable salts such as hydrochlorides, sulfates, and carbonates. Therefore, another convenient and alternative method for preparing their corresponding hydrogen sulfide salts is to treat them with appropriate basic reagents such as sodium hydroxide, barium hydroxide, or silver ammonia, or under strongly basic conditions such as sodium ethoxide or sodium methoxide, or with strongly or weakly basic ion exchange resins, to obtain the free base. Then, hydrogen sulfide gas is directly introduced, or a solution of hydrogen sulfide in water or ethanol is used to convert it into a hydrogen sulfide salt. The reaction temperature can generally be carried out in the range of -10 to 50°C. After filtration or concentration by low-temperature vacuum drying, the hydrogen sulfide salt product can be obtained.

[0020] The present invention will be further described in detail below with reference to the specific embodiments shown in the accompanying drawings. However, this should not be construed as limiting the scope of the present invention to the following examples. Various substitutions or modifications made based on ordinary technical knowledge and common practice in the art without departing from the above-described technical concept of the present invention should be included within the scope of the present invention. Attached Figure Description

[0021] Figure 1 This is a schematic diagram illustrating the metabolic process of sulfur-containing amino acids in the body as shown by existing research. Detailed Implementation

[0022] Example 1 Preparation of guanidine free base (1) At room temperature, 500 mL of anhydrous ethanol was added to a 1000 mL pear-shaped flask containing anhydrous calcium chloride (or other suitable desiccant) drying tubes. Then, 2.53 g (110 mmol) of pre-cut metallic sodium was added in batches, and after complete dissolution, a sodium ethoxide solution was obtained. 18.10 g (110 mmol) of metformin hydrochloride was added to the sodium ethoxide solution in portions, resulting in a large amount of white solid suspension. After the addition was complete, the mixture was heated to 60 °C and reacted for 1 hour. After cooling to room temperature and filtering, 6.0 g of white solid was obtained. After drying with a phosphorus pentoxide desiccator, 13.88 g of crude white solid was obtained. 5 g of the crude product was desalted by sonication with acetone, and the filtrate was concentrated to dryness to obtain a white solid, free metformin base. Melting point: 108-110 °C. 1 H NMR (400MHz, D2O): δ2.87 (s, 6H); 13 C NMR (100MHz, D2O): δ37.14(2C), 158.44, 161.55. The structure is as follows: .

[0023] Example 2 Preparation of guanidine free base (2) 1.65 g (10 mmol) of metformin hydrochloride was dissolved in 10 mL of water at room temperature. 5 mL of 2 mol / L sodium hydroxide aqueous solution was added, and the mixture was stirred at room temperature for 1 hour. The solution was then concentrated under reduced pressure to remove water, yielding a white solid. This white solid was desalted with acetone to obtain a strongly basic white solid, metformin free base. The crude product has a melting point of 90-100 °C, and the recrystallized product has a melting point of 110-112 °C.

[0024] Example 3 Preparation of guanidine free base (3) Potassium hydroxide (5.88 g, 105 mmol) was added to a suspension of 16.6 g (100 mmol) of metformin hydrochloride in 70 mL of isopropanol under stirring at 50 °C. After reacting at 50 °C for two hours, the mixture was cooled to room temperature and filtered. The filter cake was washed with isopropanol and acetone. The washings and filtrate were combined and concentrated. The resulting solid was desalted with acetone to give a strongly basic white solid, metformin free base. Melting point: 110-112 °C.

[0025] Example 4 Preparation of guanidine free base (4) At room temperature, 460 mg (2 mmol) of silver oxide was suspended in 8 mL of distilled water with vigorous stirring. 9.5 mL of concentrated ammonia solution diluted 10 times was added dropwise. After the reaction solution became clear, the solution was added to the newly prepared silver ammonia solution ([Ag(NH3)2)). + OH -Adding 660 mg (4 mmol) of metformin hydrochloride to the solution immediately produces a large amount of white precipitate. After stirring for 30 minutes at room temperature, the solution is filtered, and the filtrate is concentrated under reduced pressure to obtain the product.

[0026] Example 5 Preparation of guanidine free base (5) Dissolve 1.21 g (10 mmol) of guanidine sulfate in 10 mL of distilled water at room temperature, add 5 mL (2 mol / L) of freshly prepared barium hydroxide aqueous solution, stir at room temperature for 30 minutes, and then evaporate the water under reduced pressure to obtain a light yellow oily substance. After standing at room temperature overnight, the substance solidifies to obtain the target compound.

[0027] 13 C NMR (100MHz, DO): δ160.98, 162.45.

[0028] Example 6 1,1-Dimethylbiguanidine hydrogen sulfide (C4H 11 N5.H2S, MW:163.24) Take 26g (0.2mol) of 1,1,-dimethylbiguanide from one of Examples 1 to 4 and mix it with 100mL of water. Add 100mL of an aqueous solution containing 6.8g of hydrogen sulfide while maintaining 2℃, mix well, and freeze-dry the mixture for 24h to obtain 32g of white solid. Collect the solid to obtain the target compound.

[0029] 1 H NMR (400MHz, D2O): δ3.01 (s, 6H); 13 C NMR (100MHz, D2O): δ37.45(2C), 158.39, 160.15.

[0030] Elemental analysis results: for C4H 15 N5OS; Cacld (calculated value): C 29.43%, H 8.03%, N 42.90%, S 19.64%; Found (measured values): C 28.16%, H 8.36%, N 41.39%, S 17.46%.

[0031] The sample moisture content was 11.58%. The content of reducing substances determined by iodometric titration was 88.2%. The structure is: .

[0032] Example 7 L-arginine hydrogen sulfide (C6H) 14 N4O2.H2S, MW:208.28 Take 38.4 g (0.2 mol) of L-arginine monohydrate, mix it with 100 mL of water, keep it at 25 °C and pass hydrogen sulfide gas through it for 0.5 h, then freeze-dry the mixture for 24 h to obtain 44 g of white solid, which is collected as the product.

[0033] 1 H NMR (400MHz, D2O): δ1.54-1.74 (m, 4H), 3.17(t, J =6.7Hz, 2H), 3.43(t, J =6.0Hz, 1H); 13 C NMR (100MHz, D2O): δ24.44, 31.58, 40.73, 54.94, 156.70, 179.27.

[0034] The sample had a moisture content of 12.9%.

[0035] The content of reducing substances determined by iodometric titration was 69.2%. The structure is: .

[0036] Example 8 Morpholine biguanide hydrogen sulfide (C6H) 13 N5O.H2S, MW:205.28) Take 34.2 g (0.2 mol) of morpholine biguanide, mix it with 100 mL of water, maintain the temperature at 25 °C and pass hydrogen sulfide gas through it for 0.5 h, then remove the water by rotary evaporation at 50 °C to obtain 46 g of white solid, which is then collected to obtain the target compound.

[0037] 1 H NMR (400MHz, D2O): δ3.35(t, J =4.0Hz, 1H), 3.46 (t, J =4.0Hz, 2H), 3.67(t, J =4.0Hz, 1H), 3.71(t, J =4.0Hz, 2H); 13 C NMR (100MHz, D2O): δ45.08, 65.99, 158.86, 160.33; Elemental analysis results: for C6H 15 N5OS, Cacld: C 35.11%, H 7.37%, N 34.12%, S15.62%; Found: C 29.31%, H 8.36%, N 27.29%, S 12.46%.

[0038] The sample had a moisture content of 16.26%.

[0039] The content of reducing substances determined by iodometric titration was 76.3%. The structure is: .

[0040] Example 9: p-Guidinobenzoic acid hydrogen sulfide (C8H9N3O2.H2S, MW: 213.26) Take 35.8 g (0.2 mol) of p-guanidinobenzoic acid, mix it with 100 mL of anhydrous ethanol, keep it at 10 °C and pass hydrogen sulfide gas through it for 1 h, then remove the solvent by rotary evaporation at 45 °C to obtain 41 g of white solid, which is then collected to obtain the target compound.

[0041] Elemental analysis results: for C8H 11 N3O2S, Cacld: C 45.06%, H 5.20%, N 19.70%, S15.04%; Found: C 38.99%, H 5.56%, N 17.29%, S 13.03%.

[0042] The sample had a moisture content of 3.72%.

[0043] The content of reducing substances determined by iodometric titration was 85.5%. The structure is: .

[0044] Example 10: Cyanoguanidine hydrogen sulfide (C2H4N4.H2S, MW: 118.16) Take 16.8 g (0.2 mol) of cyanoguanidine and mix it with 100 mL of anhydrous ethanol. Keep the temperature at 2 °C and add 100 mL of ethanol solution containing 6.8 g of hydrogen sulfide. Then, remove the solvent by rotary evaporation at 45 °C to obtain 23 g of white solid. Collect the solid to obtain the target compound.

[0045] Elemental analysis results: for C2H6N4S, Cacld: C 20.33%, H 5.12%, N 47.42%, S 27.14%; Found: C 16.59%, H 5.59%, N 38.68%, S 22.14%.

[0046] The sample had a moisture content of 5.36%.

[0047] The content of reducing substances determined by iodometric titration was 86.2%. The structure is: .

[0048] Example 11 Guanidine acetate hydrogen sulfide (C3H7N3O2.H2S, MW:151.19) Take 23.4 g (0.2 mol) of guanidine acetate and mix it with 100 mL of dichloromethane. Add the mixture dropwise into a three-necked flask filled with hydrogen sulfide gas at room temperature and stir for 3 h at room temperature. A white solid precipitates out. Filter the mixture and dry it under vacuum to obtain 26 g of white solid, which is the target compound.

[0049] Elemental analysis results: for C3H9N3O2S, Cacld: C 23.83%, H 6.00%, N 27.79%, S 21.21%; Found: C 20.68%, H 6.43%, N 24.26%, S 18.41%.

[0050] The sample moisture content was 3.58%; The content of reducing substances determined by iodometric titration was 90.2%. The structure is: .

[0051] Example 12 Famotidine hydrogen sulfide (C8H) 15 N7O2S3.H2S, MW: 371.53 Take 6.74 g (0.02 mol) of famotidine and mix it with 100 mL of tetrahydrofuran. After passing hydrogen sulfide gas through the mixture at 30 °C for 2 h, remove the solvent by rotary evaporation at 40 °C to obtain 7.3 g of white solid. Collect the solid to obtain the target compound.

[0052] Elemental analysis results: for C8H 17 N7O2S4, Cacld: C 25.86%, H 4.61%, N 26.39%, S34.52%; Found: C 23.18%, H 5.03%, N 23.58%, S 30.85%.

[0053] The sample had a moisture content of 4.62%.

[0054] The content of reducing substances determined by iodometric titration was 93.7%. The structure is: .

[0055] Example 13 Guanethidine hydrogen sulfide (C9H) 21 N5.H2S, MW:233.38) Take 4.00 g (0.02 mol) of guanethidine and mix it with 100 mL of tetrahydrofuran. Add the mixture dropwise to a reaction flask filled with hydrogen sulfide gas at room temperature. After reacting at room temperature for 12 h, freeze the mixture at 0-5 °C to precipitate a solid. Filter the mixture to obtain 3.6 g of white solid, which is then collected to obtain the target compound.

[0056] Elemental analysis results: for C9H 23 N5S, Cacld: C 46.32%, H 9.93%, N 30.01%, S 13.74%; Found: C 41.31%, H 10.93%, N 26.69%, S 12.22%.

[0057] The sample had a moisture content of 3.93%.

[0058] The content of reducing substances determined by iodometric titration was 92.6%. The structure is: .

[0059] Example 14 Clonidine hydrogen sulfide (C9H9Cl2N3.H2S, MW:264.17) Take 4.58 g (0.02 mol) of clonidine and mix it with 50 mL of dichloromethane. Add 50 mL of ethanol solution containing 3.9 g of hydrogen sulfide at 0 °C. After reacting at 0 °C for 2 h, freeze at 0-5 °C to precipitate solid. Filter to obtain 3.6 g of white solid. Collect the solid to obtain the target compound.

[0060] Elemental analysis results: for C9H 11 Cl2N3S, Cacld: C 40.92%, H 4.20%, Cl 26.84%, N15.91%, S 12.14%; Found: C 37.16%, H 4.33%, Cl 24.34%, N 14.65%, S 11.02%.

[0061] The sample had a moisture content of 2.72%.

[0062] The content of reducing substances determined by iodometric titration was 93.3%. The structure is: .

[0063] Example 15 Cimetidine Hydrosulfide (C 10 H 16 N6S.H2S, MW:286.42) Mix 5.04 g (0.02 mol) of cimetidine with 50 mL of ethyl acetate. Add 50 mL of ethyl acetate solution containing 3.9 g of hydrogen sulfide at 0 °C. After reacting at 0 °C for 3 h, refrigerate at 0-5 °C to precipitate solid. Filter to obtain 2.9 g of white solid, which is then collected to obtain the target compound.

[0064] Elemental analysis results: for C 10 H 18 N6S2, Cacld: C 41.93%, H 6.33%, N 29.34%, S22.39%; Found: C 36.11%, H 6.76%, N 25.51%, S 19.26%.

[0065] The sample had a moisture content of 6.52%.

[0066] The content of reducing substances determined by iodometric titration was 91.9%. The structure is: .

[0067] Example 16 Guanidinol chlorophenol hydrogen sulfide (C9H) 12 Cl2N4O.H2S, MW:297.20) Take 5.25 g (0.02 mol) of guanidinol and mix it with 100 mL of dichloromethane. After maintaining the temperature at 0 °C and passing dry hydrogen sulfide gas through it for 5 h, place it in a refrigerator at 0-5 °C. The solid precipitates out, and after filtration, 2.6 g of white solid is obtained. Collect the solid to obtain the target compound.

[0068] Elemental analysis results: for C9H 14 Cl2N4OS, Cacld: C 36.37%, H 4.75%, Cl 23.86%, N18.85%, S 10.79%; Found: C 33.36%, H 5.07%, Cl 21.93%, N 17.29%, S 9.92%.

[0069] The sample had a moisture content of 3.37%.

[0070] The content of reducing substances determined by iodometric titration was 95.2%. The structure is: .

[0071] Example 17 1,8-Dazabicycloundec-7-ene (DBU) hydrogen sulfide (C9H 16 N2.H2S, MW:186.32) Take 0.4 g (0.2 mol) of DBU and mix it with 100 mL of water. Keep the temperature at 25 °C and add 100 mL of aqueous solution containing 6.8 g of hydrogen sulfide. Mix the solution and then rotary evaporate the mixture at 50 °C to obtain 39 g of solid. Collect the solid to obtain the target compound.

[0072] Elemental analysis results: for C9H 18 N2S, Cacld: C 58.02%, H 9.74%, N 15.04%, S 17.21%; Found: C 29.11%, H 11.67%, N 7.51%, S 8.56%.

[0073] The sample had a moisture content of 18.33%.

[0074] The content of reducing substances determined by iodometric titration was 62.6%. The structure is: .

[0075] Example 18 4-Dimethylaminopyridine (DMAP) hydrogen sulfide salt (C7H 10 N2.H2S, MW: 156.25 Dissolve 24.4 g (0.2 mol) of DMAP in 100 ml of dichloromethane. Add hydrogen sulfide gas dropwise to a three-necked flask at -5°C and react for 1.5 h. The color of the reaction solution gradually darkens. After standing overnight, a pale yellow solid precipitates. Filter and collect to obtain 8.6 g of the target compound.

[0076] Elemental analysis results: for C7H 12 N2S, Cacld: C 53.81%, H 7.74%, N 17.93%, S 20.52%; Found: C 43.82%, H 8.68%, N 14.61%, S 16.72%.

[0077] The sample had a moisture content of 5.62%.

[0078] The content of reducing substances determined by iodometric titration was 85.9%. The structure is: .

[0079] Example 19 Piperazine hydrogen sulfide (C4H) 10 N2.H2S, MW: 120.22) Dissolve 17.2 g (0.2 mol) of piperazine in 100 ml of anhydrous ethanol. Pass dry hydrogen sulfide gas through the solution at room temperature. Immediately, a white needle-like solid precipitates out. Stir for 5 min, filter, and collect 2.9 g of the target compound.

[0080] Elemental analysis results: for C4H 12 N2S, Cacld: C 39.96%, H 10.06%, N 23.30%, S26.67%; Found: C 36.02%, H 8.68%, N 20.91%, S 23.92%.

[0081] The sample had a moisture content of 2.98%.

[0082] The content of reducing substances determined by iodometric titration was 92.9%. The structure is: .

[0083] Example 20 Tryptamine hydrogen sulfide (C 10 H 12 N2.H2S, MW:194.30) Dissolve 3.2 g (0.02 mol) of tryptamine in 30 ml of anhydrous ethanol, pass dry hydrogen sulfide gas through it, and a white solid immediately precipitates out. Stir for 30 min, filter, and collect to obtain 0.8 g of the target compound.

[0084] 1 H NMR (400MHz, D2O): δ2.96 (t, J =9.0Hz, 2H), 3.11 (t, J =8.8Hz, 2H), 7.03(t, J =4.0Hz, 1H), 7.08-7.13(m, 2H), 7.34(d, J =4.0Hz, 1H), 7.49(d, J =4.0Hz, 1H); 13 C NMR (100MHz, D2O): δ22.93, 40.10, 109.39, 112.35, 118.58, 119.71,122.48, 124.53, 126.75, 136.71; Elemental analysis results: for C 10 H 14 N2S, Cacld: C 61.82%, H 7.26%, N 14.42%, S 16.50%; Found: C 55.82%, H 8.12%, N 13.02%, S 15.02%.

[0085] The sample had a moisture content of 3.65%.

[0086] The content of reducing substances determined by iodometric titration was 93.7%. The structure is: .

Claims

1. A hydrogen sulfide donor in the form of organic salts for use in organisms, characterized by: A substance consisting of a basic organic compound with a guanidine structure that has physiological and / or pharmacological activity, and a salt structure formed by hydrogen sulfide.

2. The hydrogen sulfide donor as described in claim 1, characterized in that... The organic compound with a basic structure is arginine.

3. The hydrogen sulfide donor as described in claim 1, characterized in that... The organic compounds with a basic structure are pharmaceutical compounds.

4. A method for preparing the hydrogen sulfide donor according to any one of claims 1-3, characterized in that: The organic compound with a basic structure is dissolved in a solvent, and hydrogen sulfide gas is introduced to form a salt. The salt is then separated from the reaction solvent to obtain the target product.

5. The preparation method according to claim 4, characterized in that: The organic compound with a basic structure is a non-hydrogen sulfide salt or other salt compound. After converting the salt compound into a free basic form under alkaline conditions, hydrogen sulfide gas is introduced or a solution of hydrogen sulfide in water or alcohol is added to form the target product of hydrogen sulfide, which is then separated.

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