WO2025174271A1 - Conjugués de flavanones - Google Patents
Conjugués de flavanonesInfo
- Publication number
- WO2025174271A1 WO2025174271A1 PCT/RU2025/000019 RU2025000019W WO2025174271A1 WO 2025174271 A1 WO2025174271 A1 WO 2025174271A1 RU 2025000019 W RU2025000019 W RU 2025000019W WO 2025174271 A1 WO2025174271 A1 WO 2025174271A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- flavanone
- compounds
- aminoguanidine
- flavanones
- general formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/32—2,3-Dihydro derivatives, e.g. flavanones
Definitions
- the claimed invention relates to organic chemistry, namely to flavanone derivatives and, in particular, to flavanone derivatives with increased solubility in water.
- the said compounds can find application in medicine as medicinal preparations.
- Flavanones (2-phenylchroman-4-one derivatives) of the general formula where Ri is H; OH or carbohydrate residue; R 2 is H or OCH 3 are natural polyphenolic compounds that can be obtained from plant materials. Due to their high and versatile activity, combined with low toxicity, flavanones are of great interest in the development of new drugs.
- SUBSTITUTE SHEET (RULE 26) (1) hesperidium, consisting of an aglycone (hesperetin) and a carbohydrate moiety (rutinoside), namely 5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-7-(2R,3S,4R,5R,6R)-3,4,5-TpHTHflpoKCH-6-(2S,3R,4S,5S)-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxymethyl]tetrahydropyran-2-yl]-oxy-chroman-4-one,
- Hesperidium is used as a venoprotective and antioxidant agent. Data have been published on the possibility of using hesperidin in rheumatoid arthritis, its ability to reduce diastolic pressure and suppress the proliferation and growth of cancer cells [Umar S., Kumar A., Sajad M., et al. Rheumatol. Int. 33: 657-663, 2013; Homayouni F., Haidari F., Hedayati M. et al. Phytother. Res., 32: 1073-1079, 2018; Devi K.P., Rajavel T., Nabavi S.F. Ind. Crop. Prod., 76: 582-589, 2015].
- Hesperetin like hesperidium, has antioxidant and anti-inflammatory effects [Parhiz H., Roohbakhsh A., Soltani F., Rezaee R., Iranshahi M. Phytother. Res. 29, 323, 2015]; it induces apoptosis of tumor cells as a result of influencing the formation of reactive oxygen species [Zhang J., Wu D., et.al. Dig. Dis. Sci. 60, 2985, 2015].
- Naringenin has pronounced anti-inflammatory and antioxidant activity in combination with antibacterial
- Dihydroquercetin (taxifolin) is a highly active antioxidant, which also has anti-inflammatory, antimicrobial and antitumor effects.
- taxifolin is a highly active antioxidant, which also has anti-inflammatory, antimicrobial and antitumor effects.
- the possibility of using taxifolin in the treatment of cardiovascular and liver diseases has been shown [Das A., Baidya R., Chakraborty T., et.al. Biomedicine & Pharmacotherapy. 142, 112004, 2021, doi: 10.1016/j .biopha.2021.112004].
- 1 g of hesperidin dissolves in 50 l of water.
- the solubility of hesperetin is approximately 48 mg/l; naringenin - 4.38 mg/l; dihydroquercetin - 700 mg/l, which is completely insufficient to obtain a solution of such a concentration that is acceptable for the manufacture of a drug. Therefore, a number of attempts have been made to increase the solubility of flavanones in aqueous media and, accordingly, their bioavailability.
- SUBSTITUTE SHEET (RULE 26) Another option for increasing the bioavailability and effectiveness of flavanone is the use of micronization (grinding particles to a micron size, for example, using ultrasound) [Hnatek L. Vnitr. Lek. 61(9): 807-814, 2015].
- micronization grinding particles to a micron size, for example, using ultrasound
- the possibilities for practical use of the drugs remain limited, and the cost of the dosage form increases significantly.
- the result that the claimed invention is aimed at achieving is the production of flavanones with increased solubility in water.
- the claimed flavanone derivatives can be obtained by reacting the starting compounds (hesperitin, naringenin and dihydroquercetin) with aminoguanidine hydrochloride in an organic solvent in the presence of hydrochloric acid.
- Aminoguanidine (2-aminoguanidine), which has the structural formula: was investigated as a potential drug that interferes with protein glycosylation, the drug passed two stages of clinical trials, but further testing was interrupted due to potential side effects. Nevertheless, aminoguanidine derivatives are still considered as promising compounds in the screening of new drugs [Aldini G., Vistoli G., Stefek M., et al. Free Radic. Res., 47 (Suppl. 1): 93-137, 2013].
- synthesis of hydrazones of the claimed general formula is carried out in an organic solvent, preferably in methanol or isopropyl alcohol, predominantly in methanol.
- naringenin and 160 mg (1.45 mmol) of aminoguanidine hydrochloride are dissolved in 10 ml of methanol.
- One drop of hydrochloric acid is added to the solution and the mixture is heated at boiling for 5 hours.
- the reaction mixture is cooled and left for 10 hours at +4°C.
- the formed precipitate is filtered off and dried in air. 200 mg (0.62 mmol, 62%) of naringenin hydrazone hydrochloride and aminoguanidine are obtained.
- conjugation with aminoguanidine allows increasing the solubility of the studied compounds in the range from 20 to 900 times.
- the method for obtaining conjugates of flavonones with aminoguanidine is simple and is accompanied by a sufficiently high yield of the target product, which makes it possible to organize industrial production of the claimed products.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
L'invention se rapporte à la chimie organique, notamment à des dérivés de flavanones, en particulier à des dérivés de flavanones modifiés par un groupe guanidine. Les composés précités peuvent être utilisés en médecine en qualité de préparations médicamenteuses. L'invention concerne des composés correspondant à la formule générale dans laquelle R1,R2, R4 représentent Н ou ОН; R3 représente ОН ou ОСН3. Les composés ayant ladite formule générale, c'est à dire des hydrazones de flavanones, possèdent une solubilité accrue dans l'eau et sont ainsi bien plus bio-disponibles que les flavanones de base.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2024103820 | 2024-02-14 | ||
| RU2024103820A RU2845063C1 (ru) | 2024-02-14 | Конъюгаты флаванонов |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2025174271A1 true WO2025174271A1 (fr) | 2025-08-21 |
Family
ID=96773336
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/RU2025/000019 Pending WO2025174271A1 (fr) | 2024-02-14 | 2025-01-30 | Conjugués de flavanones |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2025174271A1 (fr) |
-
2025
- 2025-01-30 WO PCT/RU2025/000019 patent/WO2025174271A1/fr active Pending
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| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
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