System for the synthesis of N-(3-(Methylthio)propyl)-thiosemicarbazide-derived imine derivatives for the treatment of diabetics

Abstract

A system for the synthesis of N-(3-(Methylthio)propyl) thiosemicarbazide-derived imine derivatives, comprising: a first reaction vessel configured to combine hydrazine monohydrate and ethanol; a second reaction vessel configured to prepare a solution of 3-(methylthio)propylisothiocyanate in an ethanol-water mixture; a backflow device configured to: combine thiosemicarbazide with substituted aldehydes or ketones in methanol; maintain a reaction temperature of 75°C; and to maintain the reaction for a specified period of time; a temperature control unit configured to maintain the temperature range during synthesis; a filter unit configured to filter the mixture to obtain derivatives; and a synthesis control module configured to monitor and control reaction conditions.

Description

FIELD OF THE INVENTIONThe present disclosure relates to a system for the synthesis of N-(3-(methylthio)propyl) thiosemicarbazide-derived imine derivatives. More particularly, the present invention relates to a system comprising one or more reaction vessels and a reflux apparatus for synthesizing imine derivatives of N-(3-(methylthio)propyl) thiosemicarbazide 5(ay).BACKGROUND OF THE INVENTIONDiabetes mellitus, particularly type 2 diabetes (T2D), affects over 536.6 million people worldwide and is expected to grow to 783.2 million people up to 2045. The treatment of diabetes often focuses on the control of post-eating blood glucose levels, which is mainly regulated by two enzymes: α-amylase and α-glucosidase. While current treatments target both enzymes, inhibition of the α-amylase can lead to undesirable gastrointestinal effects. Therefore, selective inhibition of α-glucosidase is a more favorable therapeutic approach.Existing α-glucosidase inhibitors such as voglibose, acarbose and miglitol are carbohydrate-like compounds which do not selectively inhibit both enzymes, leading to undesirable side effects. This limitation emphasizes the need for more selective α-glucosidase inhibitors.Heterocyclic compounds, particularly those containing nitrogen, have been found promising in drug development, with about 90% of the active drugs containing heterocyclic skeletons. Among them, thiosemicarbazones have proven to be particularly promising due to their structural versatility, strong donor capabilities, and diverse pharmacological profiles. The thiourea-based functional core of thiosemicarbazone (C=S and NH) has shown potential in various therapeutic applications including diabetes treatment.This invention addresses the need for selective α-glucosidase inhibitors by developing a system configured for the synthesis of novel imine derivatives derived from N-(3-(methylthio)propyl) thiosemicarbazide, which synthesized derivatives possess the therapeutic potential of heterocyclic compounds with the known advantages of thiosemicarbazone structures.SUMMARY OF THE INVENTIONThe present disclosure relates to a system for the synthesis of N-(3-(methylthio)propyl) thiosemicarbazide-derived imine derivatives. The present invention relates to an integrated system for the synthesis of N-(3-(methylthio)propyl) thiosemicarbazide-derived imine derivatives. The system comprises a plurality of components matched to one another, including reaction vessels, reflux apparatus, temperature control units, filter systems and a synthesis control module. These components cooperate to allow precise and controlled synthesis of compounds that target α-glucosidase inhibition for the treatment of diabetes.The present disclosure is intended to provide a system for the synthesis of N-(3-(methylthio)propyl) thiosemicarbazide-derived imine derivatives. The system comprises: a first reaction vessel configured to combine hydrazine monohydrate and ethanol; a second reaction vessel configured to produce a solution of 3-(methylthio)propyl isothiocyanate in an ethanol-water mixture; a reflux apparatus configured to combine thiosemicarbazide with substituted aldehydes or ketones in methanol, maintain a reaction temperature of 75°C, and maintain the reaction for a predetermined period of time; a temperature control unit configured to maintain the temperature range during the synthesis; a filtration unit configured to filter the mixture to obtain derivatives; and a synthesis control module configured to monitor and control the reaction conditions.An object of the present disclosure is to provide a system for synthesizing N-(3-(methylthio)propyl) thiosemicarbazide-derived imine derivatives.Another object of the present disclosure is to provide an automated, temperature controlled system for synthesizing novel thiosemicarbazide-derived imine derivatives having potential antidiabetic properties.Another object of the present disclosure is to enable efficient production and isolation of target compounds by coordinated filtration and collection systems.In order to further clarify the advantages and features of the present disclosure, a more detailed description of the invention will be given with reference to specific embodiments thereof illustrated in the accompanying drawings. It should be noted that these drawings illustrate only typical embodiments of the invention and are therefore not to be considered as limiting the scope thereof. The invention will be described and explained with additional details and details with reference to the accompanying drawings.BRIEF DESCRIPTION OF THE FIGURESThese and other features, aspects, and advantages of the present disclosure will become more fully understood when the following detailed description is read with reference to the accompanying drawings, in which like characters represent like parts throughout. The following applies here: FIG. 1 is a block diagram of a system for synthesizing N-(3-(methylthio)propyl) thiosemicarbazide-derived imine derivatives according to an embodiment of the present disclosure; and FIG. 2 is a diagram showing the scheme for synthesizing the above imine derivatives according to an embodiment of the present disclosure.Moreover, those skilled in the art will appreciate that elements are shown in the drawings for simplicity and need not necessarily be drawn to scale. For example, the flowcharts illustrate the method using the major steps to improve understanding of aspects of the present disclosure. Moreover, with respect to the construction of the apparatus, one or more components of the apparatus may have been represented in the drawings by conventional symbols, and the drawings may only show the specific details relevant to understanding the embodiments of the present disclosure so as not to obscure the drawings with details readily apparent to those skilled in the art having the benefit of the description herein.DETAILED DESCRIPTION:In order to aid in the understanding of the principles of the invention, reference will now be made to the embodiment illustrated in the drawings and described in specific language. It is to be understood, however, that no limitation of the scope of the invention is intended, since such changes and further modifications to the illustrated system and such further applications of the principles of the invention as illustrated therein are contemplated, as would normally occur to one skilled in the art to which the invention pertains.It will be understood by those skilled in the art that the foregoing general description and the following detailed description are exemplary and explanatory of the invention and are not intended to be limiting thereof.References throughout this specification to "one aspect," "another aspect," or similar language mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure. Thus, the appearances of the phrase "in one embodiment," "in another embodiment," and similar language in this specification may or may not all refer to the same embodiment.The terms "comprises," "comprising," or other variations thereof are intended to cover a non-exclusive inclusion, such that a process or method comprising a list of steps not only comprises those steps, but may also comprise other steps not expressly listed or inherent in such a process or method. Likewise, one or more devices or subsystems or elements or structures or components preceded by "comprises...a" do not exclude, without further limitations, the existence of other devices or other subsystems or other elements or other structures or other components or additional devices or additional subsystems or additional elements or additional structures or additional components.Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The system, methods, and examples provided herein are illustrative only and are not to be considered limiting.Embodiments of the present disclosure will be described in detail below with reference to the accompanying drawings.FIG. 1 illustrates a block diagram of a system ( 100) for synthesizing N-(3-(methylthio)propyl) thiosemicarbazide-derived imine derivatives 5(ay) according to an embodiment of the present disclosure;Referring to FIG. 1, the system (100) comprises: a first reaction vessel (102) configured to combine hydrazine monohydrate and ethanol; a second reaction vessel (104) configured to prepare a solution of 3-(methylthio)propyl isothiocyanate in an ethanol-water mixture; a reflux apparatus (106) configured to combine thiosemicarbazide with substituted aldehydes or ketones in methanol and acetic acid, to maintain a reaction temperature of 75° C. and to maintain the reaction for a predetermined period of time; a temperature control unit (108) configured to maintain the temperature range during the synthesis; a filtration unit (110) configured to filter the mixture to obtain derivatives; and a synthesis control module (112) configured to monitor and control reaction conditions.In one embodiment, the first reaction vessel (102) is further equipped with a dropwise addition mechanism (102a) for receiving the solution from the second reaction vessel (104); and the first reaction vessel (102) is connected to an ice bath system (102b) configured to maintain the reaction temperature at 0-5°C.In one embodiment, the first reaction vessel (102) comprises: a temperature sensor; a stirring mechanism; and a controlled addition port configured to regulate the dropwise addition rate of the 3-(methylthio)propyl. Isothiocyanate solution.In one embodiment, the reflux apparatus (106) comprises: a heating jacket, a condenser unit, a temperature monitoring system, a catalyst addition port configured to introduce acetic acid as catalyst, and a reaction time control mechanism configured to maintain the reflux conditions for 4-6 hours, monitor the reaction history by automatically sampling, and adjust the reaction parameters based on the monitored history.In one embodiment, the filtration unit (110) comprises: a primary filtration system for collecting the N-(3-(methylthio)propyl) thiosemicarbazide intermediate; a washing mechanism configured to wash the collected product with ethanol; and a secondary filtration system for collecting the final imine derivatives.In one embodiment, the synthesis control module (112) includes: a reaction progress monitoring unit, a thin layer chromatography analysis system, and a reaction completion detection mechanism.In one embodiment, the temperature controller (108) includes: an ice bath temperature controller, a reflux temperature controller, and a plurality of temperature sensors positioned at different reaction points.In one embodiment, the system (100) further comprises: a product collection system (114) configured to isolate precipitated products, perform washes with methanol, and dry the collected products under controlled conditions.In one embodiment, the system (100) further comprises a characterization unit (116) configured to evaluate the properties of the imine derivatives produced.The invention provides an integrated system for the synthesis of N-(3-(methylthio)propyl)-thiosemicarbazide-derived imine derivatives for the treatment of diabetes. The system employs a series of controlled reaction vessels, the first vessel combining hydrazine monohydrate with ethanol while the second produces a 3-(methylthio)propyl. Isothiocyanate solution. A special dropwise addition mechanism facilitates controlled mixing while maintaining the optimum temperature through an ice bath system. The reflux apparatus then combines the intermediates with aldehydes or ketones under precise temperature control at 75°C. The system has comprehensive monitoring functions, including temperature sensors, reaction trace and product inspection analysis tools. Advanced filtration and collection systems assure proper isolation and purification of the final products. The entire process is controlled by a synthesis control module which maintains optimum reaction conditions throughout the synthesis.FIG. 2 is a diagram showing the scheme for synthesizing the above imine derivatives according to an embodiment of the present disclosure.A system for synthesizing N-(3-(methylthio)propyl) thiosemicarbazide and its imine derivatives comprises a first reaction vessel configured to combine an excess of hydrazine monohydrate with ethanol and a second reaction vessel configured to prepare a solution of 3-(methylthio)propyl isothiocyanate in an ethanol-water mixture. The solution from the second vessel is added dropwise to the first vessel while the reaction is maintained in an ice bath for 30 minutes. A filtration unit is used to separate the resulting product, which is then washed with ethanol and dried. The system further comprises a reflux apparatus configured to combine the isolated thiosemicarbazide with substituted aldehydes or ketones in methanol in the presence of acetic acid as catalyst and to maintain the reaction at 75 °C for a predetermined period of 4 to 6 hours, wherein the course of the reaction is monitored by thin layer chromatography. A temperature control unit is configured to maintain the required reaction temperature and a synthesis control module is configured to monitor and control the overall reaction conditions. Finally, a filtration unit is configured to separate the imine derivatives formed during the reflux phase, which are then washed with methanol.Figure 2 illustrates the synthesis of N-(3-(methylthio)propyl) thiosemicarbazide. (3) was carried out by dissolving an excess of hydrazine monohydrate (1) in ethanol. Separately, a solution of 3-(methylthio)propyl isothiocyanate (2) in 5 ml of a mixture of ethanol and water was prepared. This solution was then added dropwise to the hydrazine monohydrate solution while the reaction was kept in an ice bath for 30 minutes. After completion of the reaction, the resulting product was isolated by filtration, washed thoroughly with ethanol, and then dried. The synthesis of imine derivatives 5(ay) was accomplished by the reaction of N-(3-(methylthio)propyl) thiosemicarbazide (3) (0.5 mmol) with the corresponding substituted aldehydes or ketones (0.5 mmol) in the presence of methanol as reaction medium. A few drops of acetic acid were added as catalyst. The reaction mixture was refluxed at 75°C for 4 to 6 hours and the course of the reaction monitored by thin layer chromatography (TLC). During the reaction, the formation of precipitates was observed, which were then collected by filtration, washed with methanol and dried to obtain the final imine derivatives.The compounds synthesized with the proposed system are listed below. The properties of each compound will be explained below.(E)-N -(3-(methylthio)propyl)-2-(4-(pyrrolidin-1-yl)benzylidene)hydrazine-1-carbotioamide (5a)Cream-colored solid: m.p.: 202-204° C.: Percent yield: 72: δ H(600 MHz, DMSO-d 6) 11.15 (1 H, s), 8.34 (1 H, t, J 6.0), 7.92 (1 H, s), 7.63-7.52 (2 H, m), 6.58-6.50 (2 H, m), 3.62 (2 H, q, J 6.8), 3.30-3.25 (4 H, m), 2.50 (10 H, p, J 1.9), 2.07 (3 H, s), 1.99-1.93 (4 H, m), 1.86 (2 H, dq, J 8.3, 7.1)._ner3-C-NMR (151 MHz, DMSO) δ 176.74, 149.24, 143.72, 129.21, 121.25, 111.90, 47.72, 43.06, 31.25, 28.92, 25.42, 15.12.(E)-N -(3-(methylthio)propyl)-2-(4-thiomorpholinobenzylidene)hydrazine-1-carbothioamide (5b)Yellowish solid: mp 183-18 5° C.: Percent yield: 80: δ H(600 MHz, DMSO-d 6) 11.24 (1 H, s), 8.42 (1 H, t, J 6.0), 7.94 (1 H, s), 7.64-7.57 (2 H, m), 6.97-6.89 (2 H, m), 3.69-3.64 (4 H, m), 3.62 (2 H, q, J 6.7), 2.68-2.61 (4 H, m), 2.50 (12 H, p, J 1.9), 2.07 (3 H, s), 1.86 (2 H, dq, J 8.2, 7.1)._ner6_C-NMR (151 MHz, DMSO) δ 177.00, 151.40, 142.93, 129.17, 124.13, 115.38, 50.59, 43.11, 31.25, 28.86, 25.52, 15.12.(E)-N -(3-(methylthio)propyl)-2-(4-morpholinobenzylidene)hydrazine-1-carbothioamide (5c)Cream-colored solid: m.p.: 178-180° C.: percent yield: 77: δ H(600 MHz, DMSO-d 6) 11.27 (1 H, s), 8.45 (1 H, t, J 6.0), 7.96 (1 H, s), 7.70-7.59 (2 H, m), 7.01-6.92 (2 H, m), 3.78-3.70 (4 H, m), 3.63 (2 H, q, J 6.7), 3.20 (4 H, dd, J 6.0, 3.8), 2.52-2.50 (2 H, m), 2.07 (3 H, s), 1.87 (2 H, p, J 7.2) 13 C-NMR (151 MHz, DMSO) δ 177.03, 152.53, 142.89, 128.91, 124.92, 114.73, 66.43, 47.99, 43.12, 31.25, 28.86, 15.12.(E)-2-((1-Benzyl-1H-indol-3-yl)methylene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5d)White solid: m.p.: 1.53-15.5°C: Yield in percent: 78: δ H(600 MHz, DMSO-d 6) 11.22 (1 H, s), 8.33 (1 H, s), 8.26 (1 H, d, J 7.8), 8.01 (2 H, d, J 11.8), 7.52 (1 H, d, J 8.2), 7.32 (2 H, t, J 7.6), 7.29-7.13 (5 H, m), 5.45 (2 H, s), 3.71 (2 H, q, J 6.8), 2.55 (2 H, t, J 7.2), 2.08 (3 H, s), 1.91 (2 H, t, J 7.2) 13 C-NMR (151 MHz, DMSO) δ 176.53, 140.49, 137.92, 137.37, 134.38, 129.11, 128.06, 127.65, 125.11, 123.37, 122.76, 121.43, 111.30, 111.14, 49.85, 43.15, 31.32, 28.86, 15.19.(E)-2-((1H -Indol-4-yl)methylene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5e)Brown crystals: mp: 123-125 °C: Yield in percent: 85: δ H(600 MHz, DMSO-d 6) 11.40 (1 H, s), 11.37 (1 H, s), 8.46 (1 H, s), 8.23 (1 H, d, J 6.2), 7.49 (2 H, d, J 5.1), 7.42 (1 H, d, J 7.3), 7.16 (1 H, t, J 7.7), 6.91 (1 H, s), 3.70 (2 H, q, J 6.8), 2.54 (2 H, t, J 7.3), 2.08 (3 H, d, J 2.4), 1.91 (2 H, t, J 7.3). 13 C-NMR (151 MHz, DMSO) δ 177.23, 144.30, 136.81, 127.29, 125.57, 125.31, 121.31, 120.65, 113.98, 101.44, 43.24, 31.26, 28.76, 15.15.(E)-2-((1H -Indol-3-yl)methylene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5f)White solid: m.p.: 1.43-1.45° C.: Yield in percent: 88: δ H(600 MHz, DMSO-d 6) 11.61 (1 H, s), 11.19 (1 H, s), 8.31 (1 H, s), 8.22 (1 H, d, J 7.8), 7.99 (1 H, t, J 6.0), 7.82 (1 H, d, J 2.8), 7.44 (1 H, d, J 8.0), 7.21 (1 H, t, J 7.5), 7.15 (1 H, t, J 7.4), 3.71 (2 H, q, J 6.7), 2.55 n (H, s), 1.91 (2 H, q, J 7.2) 13 C-NMR (151 MHz, DMSO) δ 176.48, 141.04, 137.53, 131.37, 124.43, 123.11, 122.41, 121.02, 112.29, 111.60, 43.11, 31.31, 28.87, 15.17.(E)-2-(5-Fluoro-2-oxoindolin-3-ylidene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5g)Brown solid: mp: 178-180° C., percent yield: 84: δ H(600 MHz, DMSO-d 6) 12.47 (1 H, s), 11.20 (1 H, s), 9.36 (1 H, t, J 5.9), 7.49 (1 H, dd, J 8.0, 2.7), 7.18 (1 H, td, J 9.1, 2.7), 6.92 (1 H, dd, J 8.6, 4.1), 3.70 (2 H, q, J 6.8), 2.53 (2 H, t, J 7.2), 2.08 (3 H, s), 1.91 (2 H, p, J 7.2), 13 C-NMR (151 MHz, DMSO) δ 177.57, 163.17, 159.48, 157.91, 138.96, 131.59, 131.57, 121.90, 121.83, 117.91, 117.75, 112.62, 112.56, 108.32, 108.15, 43.81, 31.10, 28.24, 15.11.(E)-N-(3-(methylthio)propyl)-2-(4-nitrobenzylidene)hydrazine-1-carbothioamide (5h)Yellow solid: mp 195-197° C.: percent yield: 7.5: δ H(600 MHz, DMSO-d 6) 11.76 (1 H, s), 8.82 (1 H, t, J 6.0), 8.29-8.21 (2 H, m), 8.13 (1 H, s), 8.11-8.05 (2 H, m), 3.70-3.61 (2 H, m), 2.51 (2 H, d, J 7.1), 2.07 (3 H, s), 1.94-1.85 (2 H, m). 13 C-NMR (151 MHz, DMSO) δ 177.80, 148.01, 141.22, 139.73, 128.54, 124.27, 43.31, 31.21, 28.67, 15.14.(E)-2-(2-Hydroxy-5-methylbenzylidene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5i)White solid: m.p.: 123-125 °C: Percent yield: 72: δ H(600 MHz, DMSO-d 6) 11.37 (1 H, s), 9.66 (1 H, s), 8.47 (1 H, t, J 6.0), 8.35 (1 H, s), 7.72-7.67 (1 H, m), 7.03 (1 H, dd, J 8.3, 2.3), 6.77 (1 H, d, J 8.3), 3.64 (2 H, q, J 6.7), 2.53-2.49 (3 H, m), 2.23 (3 H, s), 2.07 (3 H, s), 1.88 (2 H, p, J 7.2) 13 C-NMR (151 MHz, DMSO) δ 177.26, 154.77, 140.07, 132.24, 128.26, 126.98, 120.42, 116.43, 43.22, 31.27, 28.80, 20.61, 15.13.(E)-2-(5-Bromo-2-hydroxybenzylidene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5j)Cream-colored solid: m.p.: 13.1-133° C.: percent yield: 69: δ H(600 MHz, DMSO-d 6) 11.46 (1 H, s), 10.26 (1 H, s), 8.66 (1 H, t, J 6.0), 8.31 (1 H, s), 8.15 (1 H, d, J 2.6), 7.35 (1 H, dd, J 8.7, 2.6), 6.83 (1 H, d, J 8.7), 3.64 (2 H, q, J 6.7), 2.53-2.49 (3 H, m), 2.08 (3 H, s), 1.88 (2 H, p, J 7.2) 13 C-NMR (151 MHz, DMSO) δ 177.40, 156.04, 137.60, 133.68, 128.52, 123.37, 118.67, 111.50, 43.23, 31.26, 28.78, 15.16.(E)-N -(3-(methylthio)propyl)-2-((1-tosyl-1H-indol-3-yl)methylene)hydrazine-1-carbthioamide (5k)Brown solid: mp: 178-180° C.: Yield in percent: 7 1: δ H(600 MHz, DMSO-d 6) 11.51 (1 H, s), 8.31 (2 H, d, J 17.2), 8.26 (1 H, d, J 7.9), 8.17 (1 H, d, J 6.4), 7.96 (1 H, d, J 8.3), 7.92 (2 H, d, J 8.0), 7.39 (4 H, ddd, J 25.6, 18.9, 7.8), 3.69 (2 H, q, J 6.9), 2.56-2.48 (3 H, m), 2.31 (3 H, s), 2.06 (3 H, s), 1.90 (2 H, t, J 7.3). 13 C-NMR (151 MHz, DMSO) δ 177.26, 146.36, 137.96, 135.17, 134.18, 130.84, 130.28, 127.37, 127.16, 126.24, 124.73, 123.50, 118.12, 113.54, 43.30, 31.25, 28.69, 21.51, 15.16.(E)-2-(1-Benzyl-2-oxoindolin-3-ylidene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (51)Yellow solid: m.p.: 13 0-132° C.: Percent yield: 72: δ H(600 MHz, DMSO-d 6) 12.53 (1 H, s), 9.40 (1 H, t, J 6.0), 7.73 (1 H, d, J7.5), 7.36 (5 H, dt, J20.0, 7.7), 7.28 (1 H, t, J7.3), 7.16 (1 H, t, J7.6), 7.04 (1 H, d, J 8.0), 4.99 (2 H, s), 3.72 (2 H, q, J 6.8), 2.54 (2 H, t, J 7.3), 2.08 (3 H, s), 1.93 (2 H, p, J 7.4). 13 C-NMR (151 MHz, DMSO) δ 177.58, 161.28, 142.93, 136.21, 131.45, 131.15, 129.18, 128.09, 127.91, 123.44, 121.18, 119.96, 110.83, 43.90, 43.01, 31.13, 28.25, 15.11.(E)-2-(5-Chloro-2-oxoindolin-3-ylidene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5m)Yellow solid: m.p.: 180-182°C: Percent yield: 79:δH(600 MHz, DMSO d6) 12.41 (1 H, s), 11.29 (1H, s), 9.41 (1H, t, J 5.9), 7.73 (1H, d, J 2.3), 7.38 (1H, dd, J 8.3, 2.3), 6.94 (1H, d, J 8.3), 3.70 (2H, q, J 6.7), 2.53 (2H, t, J 7.3), 2.08 (3H, s), 1.91 (2H, p, J 7.2), 13 C-NMR (151 MHz, DMSO) δ 177.56, 162.86, 141.38, 130.98, 130.83, 126.95, 122.37, 120.89, 113.02, 43.80, 31.10, 28.26, 15.12.(E)-2-((6-Methoxynaphthalen-2-yl)methylene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5n)White solid: mp 189-191° C.: Yield in percent: 7 3: δ H(600 MHz, DMSO-d 6) 11.50 (1 H, s), 8.63 (1 H, t, J 6.0), 8.19 (1 H, s), 8.16 (1 H, dd, J 8.7, 1.7), 8.01 (1 H, s), 7.88 (1 H, d, J8.9), 7.84 (1 H, d, J 8.6), 7.37 (1 H, d, J2.5), 7.20 (1 H, dd, J 9.0, 2.5), 3.90 (3 H, s), 3.67 (2 H, q, J 6.7), 2.53 (2 H, t, J 7.3), 2.09 (3 h, d, J 1.4), 1.90 (2 h, p, J7.2) 13 C-NMR (151 MHz, DMSO) δ 177.38, 158.64, 142.78, 135.65, 130.27, 130.25, 129.24, 128.64, 127.62, 123.98, 119.50, 106.86, 55.77, 43.22, 31.25, 28.84, 15.14.(E)-2-(2-Hydroxy-5-nitrobenzylidene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5o)Yellow solid: mp 203-205° C.: Percent yield: 77:δH(600 MHz, DMSO-d6) 11.57 (2H, d, J7.1), 8.80 (1H, d, J 2.9), 8.77 (1H, t, J 6.0), 8.39 (1H, s), 8.12 (1H, dd, J 9.1, 2.9), 7.06 (1H, d, J 9.1), 3.66 (2H, q, J 6.8), 2.54-2.51 (3H, m), 2.08 (3H, s), 1.93-1.85 (2H, m). 13 C-NMR (151 MHz, DMSO) δ 177.53, 162.38, 140.73, 137.08, 126.79, 122.47, 121.90, 116.97, 43.31, 31.27, 28.71, 15.15.(E)-N -(3-(methylthio)propyl)-2-(4-(piperidin-1-yl)benzylidene)hydrazine-1-carbothioamide (5p)Violet solid: mp 163-165° C.: percent yield: 82: δ H(600 MHz, DMSO-d 6) 11.23 (1 H, s), 8.41 (1 H, t, J 6.0), 7.94 (1 H, s), 7.64-7.56 (2 H, m), 6.97-6.90 (2 H, m), 3.63 (2 H, q, J 6.7), 3.25 (4 H, t, J 5.2), 2.50 (3 H, t, J 7.2), 2.07 (3 H, s), 1.87 (2 H, p, J 7.2), 1.59 (6 H, p, J 6.7, 5.8)._ner44_C-NMR (151 MHz, DMSO) δ 176.94, 152.77, 143.08, 128.98, 123.79, 115.02, 48.96, 43.10, 31.25, 28.88, 25.47, 24.39, 15.12.(E)-2-(4-(diethylamino)-2-hydroxybenzylidene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5q)Light brown solid: m.p.: 118-120° C.: Yield in percent: 88: δ H(600 MHz, DMSO-d 6) 11.09 (1 H, s), 9.51 (1 H, s), 8.27 (1 H, t, J 5.9), 8.20 (1 H, s), 7.55 (1 H, d, J 8.8), 6.22 (1 H, dd, J 8.9, 2.4), 6.10 (1 H, d, J 2.5), 3.61 (2 H, q, J 6.7), 3.36-3.32 (5 H, m), 2.55-2.47 (3 H, m), 2.07 (3 H, s), 1.85 7.9, 6.4), 1.10 (6 H, t, J 7.0). 13 C-NMR (151 MHz, DMSO) δ 176.39, 158.53, 150.51, 142.30, 129.32, 107.99, 104.38, 97.75, 44.30, 43.09, 31.24, 28.91, 15.12, 13.03, 13.01.(E)-2-(2-Hydroxy-3-methoxybenzylidene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5r)White solid: melting point: 2.04-2.06 °C: percent yield: 89: δ H(600 MHz, DMSO-d 6) 11.42 (1 H, s), 9.19 (1 H, s), 8.50 (1 H, t, J 6.0), 8.40 (1 H, s), 7.55 (1 H, d, J 8.0), 6.97 (1 H, d, J 7.9), 6.80 (1 H, t, J 7.9), 3.82 (3 H, s), 3.63 (2 H, q, J 6.7), 2.51 (6 H, dd, J 4.3, 2.3), 2.07 (3 H, s), 187 (2 H, p, J 72) 13 C-NMR (151 MHz, DMSO) δ 17732, 14840, 146.40, 139.51, 121.33, 119.38, 118.57, 113.23, 56.36, 43.18, 31.23, 28.78, 15.11.(E)-2-(1-(8-Methoxy-2-oxo-2 H -chromen-3-yl)ethylidene)-N -(3-(methylthio)propyl)hydrazine-1-carbothioamide (5s)Yellow solid: mp 132-135° C.: percent yield: 85: δ H(600 MHz, DMSO-d 6) 10.44 (1 H, s), 8.58 (1 H, t, J 6.0), 8.31 (1 H, s), 7.33 (3 H, s), 3.93 (3 H, s), 3.65 (2 H, q, J 6.7), 2.54-2.48 (3 H, m), 2.26 (3 H, s), 2.06 (3 H, s), 1.87 (2 H, p, J 7.2), 13 C-NMR (151 MHz, DMSO) δ 178.67, 159.26, 146.76, 146.25, 143.12, 142.47, 126.68, 125.18, 120.66, 119.87, 115.03, 56.60, 43.30, 31.18, 28.55, 16.48, 15.10.(E)-2-((7-Fluoro-4-oxo-4H-chromen-3-yl)methylene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5t)Cream-colored solid: m.p.: 21.6-21.8° C.: Yield in percent: 85: δ H(500 MHz, DMSO-d 6) 11.64 - 11.47 (1 H, m), 9.11 (1 H, s), 8.59 (1 H, t, J 5.9), 8.18-8.12 (2 H, m), 7.68 (1 H, dd, J 9.5, 2.4), 7.40 (1 H, td, J 8.7, 2.5), 3.62 (2 H, dt, J 8.1, 6.1), 2.53-2.48 (4 H, m), 2.06 (3 H, s), 1.86 6.6). 13 C-NMR (126 MHz, DMSO) δ 177.30, 174.16, 166.21, 164.20, 157.00, 156.89, 155.27, 133.50, 128.27, 128.18, 120.69, 120.67, 118.68, 114.86, 114.67, 105.83, 105.62, 42.78, 30.86, 28.49, 14.82.(E)-2-((7-Bromo-4-oxo-4 H -chromen-3-yl)methylene)-N -(3-(methylthio)propyl)hydrazine-1-carbothioamide (5u)Cream-colored solid: m.p.: 221-223° C.: Yield in percent: 83:δH(500 MHz, DMSO d6) 11.57 (1 H, s), 9.11 (1H, s), 8.59 (1H, t, J 5.9), 8.14 (1H, s), 8.07 (1H, d, J 1.8), 8.00 (1H, d, J 8.5), 7.70 (1H, dd, J 8.5, 1.8), 3.66-3.58 (2H, m), 2.53-2.49 (3H, m), 2.06 (3H, s), 1.90-1.80 (2H, m). 13 C-NMR (126 MHz, DMSO) δ 177.30, 174.41, 156.06, 155.17, 133.41, 129.41, 127.66, 127.18, 122.66, 121.79, 118.88, 42.77, 30.85, 28.48, 14.82.(E)-2-((6-Hydroxy-4-oxo-4H-chromen-3-yl)methylene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5v)Cream-colored solid: m.p.: 228-230° C.: Yield in percent: 79:δH(600 MHz, DMSO-d6) 11.54 (1H, s), 10.10 (1H, s), 9.06 (1H, s), 8.57 (1H, t, J 5.9), 8.17 (1H, s), 7.57 (1H, d, J 9.0), 7.36 (1H, d, J 3.0), 7.24 (1H, dd, J 9.1, 3.0), 3.61 (2H, dt, J 7.8, 6.0), 2.52-2.46 (5H, m), 2.06 (3H, s), 1.85 J 8.4, 6.6). 13 C-NMR (151 MHz, DMSO) δ 177.24, 177.17, 174.75, 155.44, 154.89, 149.66, 134.37, 134.34, 124.45, 123.50, 120.26, 117.40, 107.86, 42.78, 42.65, 30.87, 28.52, 14.83.(E)-2-((6-Methoxy-4-oxo-4H-chromen-3-yl)methylene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5w)Cream-colored solid: m.p.: 21.0-21.2° C.: percent yield: 82: δ H(600 MHz, DMSO-d 6) 11.54 (1 H, s), 9.10 (1 H, s), 8.59 (1 H, t, J 5.9), 8.19 (1 H, s), 7.67 (1 H, d, J 9.1), 7.48-7.38 (2 H, m), 3.86 (3 H, s), 3.66-3.58 (2 H, m), 2.52-2.47 (5 H, m), 2.06 (3 H, s), 1.86 (2 H, p, J 7.2), 13 C-NMR (151 MHz, DMSO) δ 177.27, 177.20, 177.15, 174.64, 157.10, 154.96, 150.67, 134.12, 124.27, 123.66, 120.52, 117.72, 105.15, 55.97, 42.78, 42.66, 30.87, 28.51, 14.83.(E)-2-((6-Methoxy-8-nitro-4-oxo-4H-chromen-3-yl)methylene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5x)Cream-colored solid: m.p.: 23.8-2.40° C.: percent yield: 78: δ H(500 MHz, DMSO-d 6) 11.59 (1 H, s), 9.25 (1 H, s), 8.60 (1 H, t, J 5.9), 8.11 (2 H, d, J3.4), 7.77 (1 H, d, J 3.2), 3.94 (3 H, s), 3.61 (2 H, q, J 6.7), 2.53-2.46 (4 H, m), 2.06 (3 H, s), 1.85 (2 H, t, J 7.2), 13 C-NMR (126 MHz, DMSO) δ 177.33, 173.12, 155.57, 154.78, 142.41, 139.54, 132.57, 125.95, 118.50, 112.15, 56.78, 42.77, 30.85, 28.48, 14.83.(E)-2-(4-(4-Methylpiperazin-1-yl)benzylidene)-N-(3-(methylthio)propyl)hydrazine-1-carbothioamide (5y)Cream-colored solid: m.p.: 203-205° C.: Percent yield: 72: δ H(500 MHz, DMSO-d6) 11.21 (1 H, s), 8.40 (1 H, t, J 5.9), 7.94 (1 H, s), 7.63-7.56 (2 H, m), 6.98-6.89 (2 H, m), 3.62 (2 H, q, J 6.7), 3.24-3.18 (4 H, m), 2.53-2.45 (4 H, m), 2.42 (4 H, t, J 5.0), 2.21 (3 H, s), 2.05 (3 H, s), 1.85 (2 H, p, J 7.2) 13 C-NMR (126 MHz, DMSO) δ 176.71, 152.09, 142.65, 128.57, 124.10, 114.55, 54.57, 47.31, 45.88, 42.78, 30.93, 28.54, 14.79.In one embodiment, the proposed system includes a computing module having a processor configured to perform molecular docking studies, in silico pharmacokinetics and ADME studies, a 2D MLR-based QSAR study, and molecular dynamic studies based on input data relating to derivatives produced.Molecular docking studies were performed with AutoOckTool 1.5.6.1 to ensure accurate protein and ligand preparation, lattice generation and docking analysis. Ligand stability was optimized by minimizing the energy at the MM2 level with Chem3D Pro. The protein structures used in the study were obtained from the protein database, in particular using the PDB IDs 3A4A and 3TOP as mentioned in previous studies. Ligand-receptor interactions were extensively analyzed in 2D and 3D using the BIOVIA Discovery Studio Visualizer software.The pharmacokinetic and ADME profiles (absorption, distribution, metabolism and excretion) of all synthesized compounds were evaluated using the SwissADME Web tool. This evaluation provided insight into the pharmaceutical similarity, bioavailability and metabolic properties of the compounds.A 2D MLR-based QSAR study was performed with QSARINS-2.2.4 for GA MLR (Genetic Algorithm-Multiple Linear Regression) analyses. Chemical structures in the SMILES format were converted to 3D representations with OpenAbel 3.1, followed by descriptor calculations with PyDe. Strongly correlated descriptors were systematically removed, resulting in a refined dataset with over 600 descriptors for further QSAR models. The study followed established protocols referred to in the prior literature.Using the Desmond module, molecular dynamics simulations were performed on the complex "3TOP_5x". The system was set up with an explicit solvent model using TIP3P water in a periodic box of 10 Å×10 Å×10 Å. The force field OPLS-2005 was applied and Na+ions as well as NaCl were incorporated to maintain charge balance and physiological conditions. The system was subjected to a 100 ns simulation, while maintaining the parameters and conditions specified in the previous literature.Diabetes mellitus is a chronic and severe disease requiring effective therapeutic measures. In response to this need, the synthesis and biological evaluation of N-(3-(methylthio)propyl) thiosemicarbazide-derived imine derivatives as promising α-glucosidase inhibitors were studied. A series of 25 compounds, designated 5(ay), were synthesized using the proposed system consisting of reaction vessels and reflux apparatus, as well as other units for performing the operations, which system performs the synthesis by facilitating the reaction of N-(3-(methylthio)propyl) thiosemicarbazide with various heterocyclic compounds. Structural confirmation of these derivatives has been achieved using several spectroscopic techniques. In vitro evaluation of these compounds showed their significant ability to inhibit α-glucosidase, with several derivatives showing remarkable activity. The IC50values of these inhibitors were between 11.28±0.24 μM and 89.36±1.37 μM and thus clearly exceeded the reference drug acarbose, which had an IC50value of 871.40±1.24 μM. Among the synthesized compounds, 5x having an IC50 value of 11.28 ± 0.24 μM showed the highest inhibitory activity.In addition to the experimental results, insilico studies including molecular docking and simulations provided important findings on the binding interactions between the imine derivatives and the active site of the enzyme α-glucosidase. Computer-assisted analysis reinforced the experimental results by illustrating the molecular interactions responsible for enzyme inhibition. Moreover, quantitative structure-activity relationship analysis (QSAR) was performed to establish a correlation between the chemical structures of the synthesized derivatives and their α-glucosidase inhibitory activity. The QSAR model identified important molecular descriptors affecting inhibitory power and provided valuable evidence for rational development and optimization of more effective inhibitors. The overall results suggest that imine derivatives based on N-(3-(methylthio)propyl) thiosemicarbazide have a considerable potential as α-glucosidase inhibitors, which justifies further studies for their development as therapeutics for the treatment of diabetes.Design and synthesis of these imine derivatives have demonstrated their great potential in glucose regulation by effective inhibition of α-glucosidase. The in vitro tests confirmed the ability of several compounds to regulate the postprandial glucose level, thus underlined their potential therapeutic area of application. The findings obtained from the insilico studies further reinforced the experimental results by clarifying the binding interactions and molecular mechanisms underlying inhibitory activity. These results emphasize the therapeutic relevance of imine derivatives based on N-(3-(methylthio)propyl) thiosemicarbazide and form a solid basis for future research to optimize their structures and increase their biological activity. Further research in this area could lead to the development of novel and effective treatment methods for diabetes and thus would meet an urgent need for the treatment of metabolic disorders.The drawings and the foregoing description provide examples of embodiments. Those skilled in the art will appreciate that one or more of the described elements may well be combined into a single functional element. Alternatively, certain elements may be divided into multiple functional elements. Elements from one embodiment may be added to another embodiment. For example, orders of the processes described herein may be changed and are not limited to the manner described herein. Moreover, the actions of any flow chart need not be implemented in the order shown; nor do all actions necessarily need to be performed. Also, those actions that are not dependent on other actions may be performed in parallel with the other actions. The scope of the embodiments is in no way limited by these specific examples. Numerous variations, whether or not explicitly stated in the specification, such as differences in structure, dimension, and material usage, are possible. The scope of the embodiments is at least as broad as recited in the following claims.Advantages, other advantages, and solutions to problems have been described above with respect to certain embodiments. However, the advantages, benefits, solutions to problems, and any components that may result in an advantage, solution occurring or becoming clearer are not to be construed as a critical, required, or essential feature or component of any or all claims.REFERENCES100 Block diagram of a system for synthesizing N-(3-(methylthio)propyl)-thiosemicarbazide-derived imine derivatives. 102 First reaction vessel 102 a Mechanism 102 b Eisbad bath system 104 Second reaction vessel 106 Reflux apparatus 108 Temperature controller 110 Filter system 112 Synthesis control module 114 Product collection system 116 Characterization unit

Claims

A system for synthesizing N-(3-(methylthio)propyl)thiosemicarbazide-derived imine derivatives, comprising: a first reaction vessel configured to combine hydrazine monohydrate and ethanol; a second reaction vessel configured to prepare a solution of 3-(methylthio)propyl isothiocyanate in an ethanol-water mixture; a reflux apparatus configured to: combine thiosemicarbazide with substituted aldehydes or ketones in methanol; maintain a reaction temperature of 75 °C; and maintain the reaction for a predetermined period of time; a temperature control unit configured to maintain the temperature range during the synthesis; a filter unit configured to filter the mixture to obtain derivatives; and a synthesis control module configured to monitor and control reaction conditions.The system of claim 1, wherein the first reaction vessel is further equipped with a dropwise addition mechanism for receiving the solution from the second reaction vessel; and the first reaction vessel is coupled to an ice bath system equipped to maintain the reaction temperature at 0-5°C;The system of claim 1, wherein the first reaction vessel comprises: a temperature sensor; a stirring mechanism; and a controlled addition port configured to regulate the dropwise addition rate of the 3-(methylthio)propyl. Isothiocyanate solution.The system of claim 1, wherein the reflux apparatus comprises: a heating jacket; a condenser unit; a temperature monitoring system; a catalyst addition port configured to introduce acetic acid as catalyst; and a reaction time control mechanism configured to maintain the reflux conditions for 4-6 hours, monitor the reaction history by automatic sampling, and adjust the reaction parameters based on the monitored history.The system of claim 1, wherein the filtration unit comprises: a primary filtration system for collecting the N-(3-(methylthio)propyl) thiosemicarbazide intermediate; a washing mechanism configured to wash the collected product with ethanol; and a secondary filtration system for collecting the final imine derivatives.The system of claim 1, wherein the synthesis control module comprises: a reaction history monitoring unit, a thin layer chromatography analysis system, and a reaction completion detection mechanism.The system of claim 1, wherein the temperature control unit comprises: an ice bath temperature controller, a reflux temperature controller, and a plurality of temperature sensors positioned at different reaction points.The system of claim 1, further comprising: a product collection system configured to isolate precipitated products, perform washes with methanol, and dry the collected products under controlled conditions.The system of claim 1, further comprising a characterization unit configured to evaluate the properties of the imine derivatives produced.

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