DE202022106287U1 - A method for the synthesis and biological evaluation of new sulfonamide analogues - Google Patents

Abstract

System (100) for the synthesis of sulfonamides, the system (100) comprising:
a 45-55 ml flask (102) for reacting a defined concentration of 1-2(furoyl)piperazine with a defined concentration of 3-fluorobenzene-suflonyl chloride dissolved in a defined amount of tetrahydrofuran (THF) in the presence of trimethylamine as the base, the reaction being carried out at room temperatures to form a sulfonamide compound;
a plurality of test tubes (104) connected to the flask (102) for mixing 0.5-1.5 ml of the prepared sulfonamide compound varying in concentration from 25-100 µg/ml with 3-5 ml of a 2,2-diphenyl- 1-picrylhydrazyl (DPPH) methanol solution;
a thin layer chromatography (TLC) (106) connected to the plurality of test tubes (104) for monitoring the progress of the reaction to obtain the sulfonamide compound; and
an ultraviolet-visible (UV-V) spectrometer (108) connected to the plurality of test tubes (104) to measure the absorbance level of the sulfonamide compound formed.

Description

FIELD OF THE INVENTION

The present invention relates to the field of synthesis and analysis of chemical compounds. In particular, the present invention relates to a system for the synthesis and in vitro biological evaluation of sulfonamides.

BACKGROUND OF THE INVENTION

Sulfonamides are one of the most common functionalities in medicinal chemistry that are incorporated into the structures of therapeutically valuable molecules. Sulfonamides (-SO2-N-) are important synthetic, primarily bacteriostatic agents that are used both in human therapy and in animal husbandry. The antimicrobial sulfonamides are the unchanged parent compounds or an acetylated metabolite that can be reactivated by bacterial cleavage of the acetyl group. The uses of sulfonamides have been proven to extend from their primary function as anti-tumor, anti-thyroid, anti-cancer, hypoglycemic, anti-microbial, anti-COX, anti-carboxylic anhydrase, anti-diuretic and anti-inflammatory, the Enzyme dihydropteroate synthetase (DHPS) - the key enzyme in folate synthesis -, anti-impotents and also as azo dyes to improve light stability, water solubility and fixation to fibers.

US7842718B2 discloses heterocyclic sulfonamide inhibitors of beta-amyloid production, wherein R1, R2, R3, R4, R5, R6, T, W, X, Y and Z are as defined herein, together with pharmaceutically acceptable salts, hydrates and/or prodrugs be provided by it.

CA2846574C discloses quinoxaline benzenesulfonamide derivatives which are kinase inhibitors, pharmaceutical compositions thereof and their use in the treatment of cancer.

EP2448582B1 discloses a compound of formula, or a pharmaceutically acceptable salt thereof, wherein: W, X, Y and Z are each independently selected from CH or N; D and D1 are independently selected from a bond or NRb; L a bond, -C(O)-, -(CRcRc)m-, -OC(O)-, -(CRcRc)m-OC(O)-, -(CRcRc)mC(O)-, -NRbC( S)- or -NRbC(O)-; R1 is selected from alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl; each of which is substituted with 0-5 occurrences of Rd; each R3 is independently selected from halo, haloalkyl, alkyl, hydroxyl and -ORa; each Ra is independently selected from alkyl, acyl, hydroxyalkyl and haloalkyl; each Rb is independently selected from hydrogen and alkyl; each Rc is independently selected from hydrogen, halogen, alkyl, alkoxy and haloalkoxy, or two Rc together with the carbon atoms to which they are attached form an optionally substituted cycloalkyl; each Rd is independently selected from halo, haloalkyl, haloalkoxy, alkyl, alkynyl, nitro, cyano, hydroxyl, -C(O)Ra, -OC(O)Ra, -C(O)ORa, -SRa, -NRaRb and - ORa, or two Rd together with the carbon atoms to which they are attached form an optionally substituted heterocycle.

US7199131B2 discloses imidazoquinoline and tetrahydro-imidazoquinoline compounds containing a sulfonamide or sulfonamide functionality at the 1-position that are useful as immune response modifiers. The compounds and compositions of the present invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of diseases including viral diseases and neoplastic diseases.

However, none of the prior art mentioned above discloses the synthesis of the sulfonamide based on a one-step synthesis method.

Therefore, in order to overcome the above limitations, there is a need to develop an apparatus for synthesizing sulfonamides and analyzing their properties.

The technical advance disclosed by the present invention overcomes the limitations and disadvantages of existing and conventional systems and methods.

SUMMARY OF THE INVENTION

The present invention relates generally to a system for synthesizing sulfonamides.

An object of the present invention is to provide a system for synthesizing sulfonamides;

Another object of the present invention is the analysis of the properties of sulfonamides;

Another object of the present invention is to perform in vitro antioxidant studies using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) methods;

Another aim of the present invention is to obtain excellent yields; and

A further aim of the present invention is to provide inexpensive starting substrates and pharmacologically important new antioxidant drug candidates.

• einen 45-55 ml-Kolben zur Umsetzung einer definierten Konzentration von 1-2(Furoyl)piperazin mit einer definierten Konzentration von 3-Fluorbenzol-Suflonylchlorid, gelöst in einer definierten Menge Tetrahydrofuran (THF), in Gegenwart von Trimethylamin als Base, wobei die Reaktion bei Raumtemperatur unter Bildung einer Sulfonamidverbindung durchgeführt wird;
• eine Vielzahl von Reagenzgläsern, die mit dem Kolben verbunden sind, zum Mischen von 0.5-1.5 mL der hergestellten Sulfonamidverbindung in einer variierenden Konzentration von 25-100 µg/mL mit 3-5 mL einer 2,2-Diphenyl-1-picrylhydrazyl (DPPH)-Methanol-Lösung;
• eine Dünnschichtchromatographie (TLC), die mit der Mehrzahl von Reagenzgläsern verbunden ist, um den Reaktionsfortschritt zu überwachen, um die Sulfonamidverbindung zu erhalten; und
• ein ultraviolett-sichtbares (UV-V) Spektrometer, das mit der Vielzahl von Reagenzgläsern verbunden ist, um den Absorptionswert der gebildeten Sulfonamidverbindung zu messen.

In one embodiment, a system for synthesizing sulfonamides, the system comprising:

• a 45-55 ml flask for reacting a defined concentration of 1-2(furoyl)piperazine with a defined concentration of 3-fluorobenzene-sulfonyl chloride dissolved in a defined amount of tetrahydrofuran (THF) in the presence of trimethylamine as a base, the reaction is carried out at room temperature to form a sulfonamide compound;
• a plurality of test tubes attached to the flask to mix 0.5-1.5 mL of the prepared sulfonamide compound at a varying concentration of 25-100 µg/mL with 3-5 mL of a 2,2-diphenyl-1-picrylhydrazyl (DPPH )-methanol solution;
• a thin layer chromatography (TLC) connected to the plurality of test tubes to monitor the progress of the reaction to obtain the sulfonamide compound; and
• an ultraviolet-visible (UV-V) spectrometer connected to the plurality of test tubes to measure the absorbance level of the sulfonamide compound formed.

In one embodiment, the defined concentration of 1-2(furoyl)piperazine is 0.001 mol, the defined amount of THF is 20-30 ml and the defined concentration of 3-fluorobenzene-sulfonyl chloride is 0.001 mol.

In one embodiment, the reaction is carried out for 3-4 hours to obtain the sulfonamide compound.

In one embodiment, the sulfonamide compound is (4-((3-Fluorophenyl)sulfonyl)piperazin-1-yl)furan-2-yl)methanone.

In one embodiment, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay is used to assess the scavenging activity of the synthesized compounds.

In one embodiment, the DPPH radical test is prepared by dissolving 3-5 mg of DPPH in 80-120 mL of methanol to obtain a 0.004% DPPH solution.

In one embodiment, ascorbic acid is used to measure the antioxidant activity of the sulfonamide compound.

In one embodiment, the UV-V spectrometer measures absorbance after incubating the multiple test tubes for 25-35 minutes in the dark with occasional shaking.

In order to further clarify the advantages and features of the present invention, a more detailed description of the invention will be made by reference to specific embodiments thereof illustrated in the attached figure. It is understood that this figure represents only typical embodiments of the invention and therefore should not be considered as limiting its scope. The invention will be described and illustrated with additional specificity and detail with the accompanying figure.

character list

• 1 ein Blockdiagramm eines Systems zur Synthese von Sulfonamiden zeigt.

These and other features, aspects and advantages of the present invention will be better understood when the following detailed description is read with reference to the accompanying figure, in which like characters represent like parts throughout the figures, wherein:

• 1 shows a block diagram of a system for the synthesis of sulfonamides.

Those skilled in the art will understand that the elements in the figure are shown for simplicity and are not necessarily drawn to scale. For example, the flow charts illustrate the method of key steps to enhance understanding of aspects of the present disclosure. Furthermore, one or more components of the device in the figure may be represented by conventional symbols, and the figure only shows the specific details relevant to understanding the embodiments of the present disclosure, not to encircle the figure with details to overload, which are easily recognizable to those skilled in the art familiar with the present description.

DETAILED DESCRIPTION:

For the purposes of promoting an understanding of the invention, reference will now be made to the embodiment illustrated in the Figure and specific language will be used to describe the same. It should be understood, however, that no limitation on the scope of the invention is intended, and such alterations and further modifications to the illustrated system and such further applications of the principles of the invention set forth therein are contemplated as would occur to those skilled in the art invention would normally come to mind.

Those skilled in the art will understand that the foregoing general description and the following detailed description are exemplary and explanatory of the invention and are not intended to be limiting.

When this specification refers to "an aspect," "another aspect," or the like, it means that a particular feature, structure, or characteristic described in connection with the embodiment is present in at least one embodiment of the present invention. Therefore, the phrases "in one embodiment," "in another embodiment," and similar phrases throughout this specification may or may not all refer to the same embodiment.

The terms "comprises," "including," or other variations thereof are intended to cover non-exclusive inclusion, such that a method or method that includes a list of steps includes not only those steps, but may also include other steps that are not expressly stated or pertaining to any such process or method. Likewise, any device or subsystem or element or structure or component preceded by "comprises...a" does not, without further limitation, exclude the existence of other devices or other subsystem or other element or other structure or other component or additional device 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 skilled in the art to which this invention pertains. The system, methods, and examples provided herein are for purposes of illustration only and are not intended to be limiting.

Embodiments of the present invention are described in detail below with reference to the attached figure.

1 Figure 12 shows a block diagram of a system (100) for synthesizing sulfonamides, the system (100) comprising: a 45-55 ml flask (102), a plurality of test tubes (104), a thin layer chromatography (TLC) (106) and a UV-V spectrometer (108).

The 45-55 ml flask (102) for reacting a defined concentration of 1-2(furoyl)piperazine with a defined concentration of 3-fluorobenzene-suflonyl chloride dissolved in a defined amount of Tet rahydrofuran (THF), in the presence of trimethylamine as a base, the reaction being carried out at room temperatures to form a sulfonamide compound. The defined concentration of 1-2(Furoyl)piperazine is 0.001 mol, the defined amount of THF is 20-30 ml and the defined concentration of 3-fluorobenzene-suflonyl chloride is 0.001 mol. The reaction is carried out for 3-4 hours to obtain the sulfonamide compound. The sulfonamide compound is (4-((3-Fluorophenyl)sulfonyl)piperazin-1-yl)furan-2-yl)methanone.

The plurality of test tubes (104) are connected to the flask (102) to add 0.5-1.5 mL of the prepared sulfonamide compound at varying concentrations of 25-100 µg/mL with 3-5 mL of 2.2-diphenyl-1-picrylhydrazyl (DPPH ):methanol solution to mix. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical test is used to examine the radical scavenging activity of the synthesized compounds. For the DPPH radical test, 3-5 mg DPPH is dissolved in 80-120 ml methanol to obtain a DPPH solution with a concentration of 0.004%.

Thin layer chromatography (TLC) (106) is connected to the plurality of test tubes (104) to monitor the progress of the reaction to recover the sulfonamide compound.

The UV-V spectrometer (108) is connected to the plurality of test tubes (104) to measure the absorbance value of the sulfonamide compound formed. The ascorbic acid is used to measure the antioxidant activity of the sulfonamide compound. The UV-V spectrometer (108) measures absorbance after incubating the multiple test tubes (104) for 25-35 minutes in the dark with occasional shaking.

In one embodiment, a 50 mL round bottom flask filled with 1-2(furoyl)piperazine (0.001 mol) is reacted with 3-fluorobenzenesulfonyl chloride (0.001 mol) dissolved in 25 mL tetrahydrofuran (THF) in the presence of trimethylamine as a base . The reaction is carried out at room temperature for 3-4 h to form (4-((3-fluorophenyl)sulfonyl)piperazin-1-yl)furan-2-yl)methanone (3a). The progress of the reaction was monitored by thin layer chromatography (TLC) in good to excellent yields (86-96%).

A simple 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay [1] was used to examine the radical scavenging activity of the synthesized compounds 3(ae). Ascorbic acid was used as a positive control to compare the antioxidant activity of the title compounds. DPPH (4 mg) was dissolved in 100 mL of methanol to obtain a 0.004% DPPH solution. Various concentrations (25, 50, 75 and 100 µg/ml) of the title compounds were prepared by dilution with methanol. 1 mL of these test solutions was added to 4 mL DPPH:methanol solution in a set of test tubes and then incubated for 30 minutes in the dark with occasional shaking. The absorbance of the incubated test samples was measured at 517 nm with a UV-Vis spectrophotometer. The percentage of DPPH scavenger activity was calculated using the following formula. The experiments were evaluated in triplicate and the means were summarized in Table 1. $$\%Hemm\mathrm{and}nGvOnDPPH=\frac{\left(Ab{s}_{KOnt\mathrm{right}Olle}-Ab{s}_{M\mathrm{and}ste\mathrm{right}}\right)}{Ab{s}_{KOnt\mathrm{right}Olle}}\times 100$$

"Abs _control " stands for the absorbance of the DPPH solution and "Abs _sample " for the absorbance of the sample and the DPPH solution. Table 1. DPPH radical scavenging activity of the synthesized compounds 3(ae) links DPPH putrefaction activity 25 µg/mL 50 µg/mL 75 µg/mL 100 µg/mL 3a 55.22 66.64 65.42 66.41 3b 68.11 76.12 79.42 85.21 3e 63.43 70.62 72.38 78.81 3d 69.42 75.18 80.14 83.60 3e 67.80 73.18 77.23 82.56 default 74.65 82.50 90.15 94.50 Empty ---- ---- ---- ----

The hydrogen peroxide scavenging activity of the newly synthesized compounds 3(ae) was determined. A solution of hydrogen peroxide (40 mM) was prepared in phosphate buffer at pH 7.4-7.5 and 100 µg/mL of the test compound was added to the H ₂ O ₂ solution (0.6 mL, 40 mM) in 3.4 mL phosphate buffer. The test tubes were incubated in the dark for 30 minutes with occasional shaking. The absorbance of the test samples and the phosphate buffer without hydrogen peroxide was measured at 230 nm with a UV spectrophotometer. Ascorbic acid was used as a standard. The percent scavenging activity of hydrogen peroxide was calculated using the formula given. The experiments were evaluated in triplicate and the means were summarized in Table 2. $$\%Hemm\mathrm{and}nGvOn{\text{H}}_2{\text{O}}_2=\frac{\left(Ab{s}_{KOnt\mathrm{right}Olle}-Ab{s}_{M\mathrm{and}ste\mathrm{right}}\right)}{Ab{s}_{KOnt\mathrm{right}Olle}}\times 100$$

Here, Abs _control was the absorbance of the H ₂ O ₂ standard and Abs _sample was the absorbance in the presence of the sample and the H ₂ O ₂ standard. Table 2. H ₂ O ₂ scavenging activity of the synthesized compounds 3(ae) links H ₂ O ₂ putrefaction activity 25 µg/mL 50 µg/mL 75 µg/mL 100 µg/mL 3a 56.20 61.62 65. 44 67.41 3b 69.11 76.11 82.41 85.25 3e 64.23 69.61 72.38 79.80 3d 66.52 74.76 81.52 83.61 3e 67.81 78.48 80.21 82.56 default 74.84 81.68 88.14 92.42 Empty - - - -

The figure and the preceding description give examples of embodiments. Those skilled in the art will understand that one or more of the elements described may well be combined into a single functional element. Alternatively, certain elements can be broken down into multiple functional elements. Elements from one embodiment may be added to another embodiment. For example, the order of the processes described herein may be changed and is not limited to the manner described herein. Additionally, the actions of a flowchart need not be performed in the order shown; Also, not all actions have to be carried out. Also, the actions that are not dependent on other actions can be performed in parallel with the other actions. The scope of the embodiments is in no way limited by these specific examples. Numerous variations are possible, regardless of whether they are explicitly mentioned in the description or not, e.g. B. Differences in structure, dimensions and use of materials. The scope of the embodiments is at least as broad as indicated in the following claims.

Advantages, other benefits, and solutions to problems have been described above with respect to particular embodiments. However, the benefits, advantages, problem solutions, and components that can cause an advantage, benefit, or solution to occur or become more pronounced are not to be construed as a critical, required, or essential feature or component of any or all claims.

Reference List

100

A system (100) for the synthesis of sulfonamides.

102

Pistons

104

test tube

106

thin layer chromatography

108

Ultraviolet-Visual (Uv-V) Spectrometer

QUOTES INCLUDED IN DESCRIPTION

This list of the documents cited by the applicant was generated automatically and is included solely for the better information of the reader. The list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions.

Patent Literature Cited

• US7842718B2 [0003]
• EP 2448582 B1 [0005]
• US7199131B2 [0006]

Claims (8)

System (100) for the synthesis of sulfonamides, the system (100) comprising: a 45-55 ml flask (102) for reacting a defined concentration of 1-2(furoyl)piperazine with a defined concentration of 3-fluorobenzene-suflonyl chloride dissolved in a defined amount of tetrahydrofuran (THF) in the presence of trimethylamine as the base, the reaction being carried out at room temperatures to form a sulfonamide compound; a plurality of test tubes (104) connected to the flask (102) for mixing 0.5-1.5 ml of the prepared sulfonamide compound varying in concentration from 25-100 µg/ml with 3-5 ml of a 2,2-diphenyl- 1-picrylhydrazyl (DPPH) methanol solution; a thin layer chromatography (TLC) (106) connected to the plurality of test tubes (104) for monitoring the progress of the reaction to obtain the sulfonamide compound; and an ultraviolet-visible (UV-V) spectrometer (108) connected to the plurality of test tubes (104) to measure the absorbance level of the sulfonamide compound formed. system after claim 1 , where the defined concentration of 1-2(furoyl)piperazine is 0.001 mol, the defined amount of THF is 20-30 ml and the defined concentration of 3-fluorobenzene-suflonyl chloride is 0.001 mol. system after claim 1 , wherein the reaction is carried out for 3-4 hours to obtain the sulfonamide compound. system after claim 1 wherein the sulfonamide compound is (4-((3-Fluorophenyl)sulfonyl)piperazin-1-yl)furan-2-yl)methanone. system after claim 1 , using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay to examine the radical scavenging activity of the synthesized compounds. system after claim 5 , where the DPPH radical test is prepared by dissolving 3-5mg of DPPH in 80-120mL of methanol to obtain 0.004% concentration of DPPH solution. system after claim 1 , where ascorbic acid is used to measure the antioxidant activity of the sulfonamide compound. system after claim 1 , wherein the UV-V spectrometer (108) measures absorbance after the multiple test tubes (104) have been incubated for 25-35 minutes in the dark with occasional shaking.

Images