PL445905A1 - Betulin conjugates with α-amino acid esters, how to produce them and use - Google Patents

Betulin conjugates with α-amino acid esters, how to produce them and use

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Publication number
PL445905A1
PL445905A1 PL445905A PL44590523A PL445905A1 PL 445905 A1 PL445905 A1 PL 445905A1 PL 445905 A PL445905 A PL 445905A PL 44590523 A PL44590523 A PL 44590523A PL 445905 A1 PL445905 A1 PL 445905A1
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PL
Poland
Prior art keywords
mmol
amount
betulin
mmol2
conjugates
Prior art date
Application number
PL445905A
Other languages
Polish (pl)
Inventor
Mirosława Grymel
Anna Lalik
Daria Dolniak-Budny
Paweł Naprawca
Original Assignee
Politechnika Śląska
Priority date (The priority date 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 date listed.)
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Publication date
Application filed by Politechnika Śląska filed Critical Politechnika Śląska
Priority to PL445905A priority Critical patent/PL445905A1/en
Publication of PL445905A1 publication Critical patent/PL445905A1/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Przedmiotem zgłoszenia są koniugaty betuliny z estrami α-aminokwasów, o wzorze ogólnym 3, gdzie R1 = H, CH3, CH(CH3)2, CH2CH(CH3)2, CH2OH, CH(OH)CH3, CH2C6H4OH, CH2CH2SCH3. Zgłoszenie obejmuje także sposób wytwarzania koniugatów betuliny z estrami α-aminokwasów o wzorze ogólnym 3, gdzie R1 = H, CH3, CH(CH3)2, CH2CH(CH3)2, CH2OH, CH(OH)CH3, CH2C6H4OH, CH2CH2SCH3, który polega na tym, że 3-O-acetylo-28-O'-(3'-karboksypropanoilo)betulinę o wzorze 2 w ilości 0.10 mmola kontaktuje się w środowisku gazu intertnego z estrem α-aminokwasu o wzorze ogólnym A, gdzie R1 = H, CH3, CH(CH3)2, CH2CH(CH3)2, CH2OH, CH(OH)CH3, CH2C6H4OH, CH2CH2SCH3, w stosunku molowym od 0.12 do 0.20 mmol A/0.10 mmol 2, w obecności N,N'-dicykloheksylokarbodiimidu (DCC) w ilości od 0.13 do 0.25 mmol DCC/0.10 mmol 2 i 1-hydroksybenzotriazolu (HOBt) w ilości od 0.08 do 0.13 mmol HOBt/0.10 mmol 2, w rozpuszczalnikach organicznych, korzystnie w dichlorometanie (DCM) w ilości od 3 do 10 mL DCM/0.10 mmol 2, tak otrzymaną mieszaninę miesza się w temperaturze od 0°C do 5°C przez 30 minut, następnie w temperaturze pokojowej w czasie od 1 do 2 godzin, po czym w temperaturze od 0°C do 5°C wkrapla się trietyloaminę (Et3N) w ilości od 0.13 do 0.3 mmol Et3N/0.1 mmol 2, dodaje się metanol (MeOH) w ilości od 0.3 do 0 5 mL MeOH/0.10 mmol 2, całość miesza się w temperaturze pokojowej w czasie od 2 do 7 dni, następne odparowuje rozpuszczalnik organiczny pod ciśnieniem od 10 mmHg do 20 mmHg, ekstrahuje rozpuszczalnikami organicznymi, korzystnie octanem etylu, ponownie odparowuje rozpuszczalnik organiczny pod obniżonym ciśnieniem od 10 mmHg do 20 mmHg, następnie oczyszcza metodami chromatograficznymi. Przedmiotem zgłoszenia jest również zastosowanie koniugatów betuliny z estrami ww. α-aminokwasów i otrzymanych powyższym sposobem związków regulujących żywotność i/lub metabolizm komórkowy oraz do wytwarzania leków antynowotworowych.The subject of the application are conjugates of betulin with α-amino acid esters, of general formula 3, where R1 = H, CH3, CH(CH3)2, CH2CH(CH3)2, CH2OH, CH(OH)CH3, CH2C6H4OH, CH2CH2SCH3. The application also covers a method for the preparation of betulin conjugates with α-amino acid esters of the general formula 3, where R1 = H, CH3, CH(CH3)2, CH2CH(CH3)2, CH2OH, CH(OH)CH3, CH2C6H4OH, CH2CH2SCH3, which comprises contacting 3-O-acetyl-28-O'-(3'-carboxypropanoyl)betulin of the formula 2 in an amount of 0.10 mmol in an interstitial gas environment with an α-amino acid ester of the general formula A, where R1 = H, CH3, CH(CH3)2, CH2CH(CH3)2, CH2OH, CH(OH)CH3, CH2C6H4OH, CH2CH2SCH3, in a molar ratio of 0.12 to 0.20 mmol A/0.10 mmol 2, in a molar ratio of 0.12 to 0.20 mmol A/0.10 mmol 2, in the presence of N,N'-dicyclohexylcarbodiimide (DCC) in an amount of 0.13 to 0.25 mmol of DCC/0.10 mmol2 and 1-hydroxybenzotriazole (HOBt) in an amount of 0.08 to 0.13 mmol of HOBt/0.10 mmol2, in organic solvents, preferably in dichloromethane (DCM) in an amount of 3 to 10 mL of DCM/0.10 mmol2, the mixture thus obtained is stirred at a temperature of 0°C to 5°C for 30 minutes, then at room temperature for 1 to 2 hours, then at a temperature of 0°C to 5°C triethylamine (Et3N) is added dropwise in an amount of 0.13 to 0.3 mmol of Et3N/0.1 mmol2, methanol (MeOH) is added in an amount of 0.3 to 10 mL of DCM/0.10 mmol2, and the resulting mixture is stirred for 30 minutes at a temperature of 0°C to 5°C. 0 5 mL MeOH/0.10 mmol 2, the whole is stirred at room temperature for 2 to 7 days, then the organic solvent is evaporated under pressure from 10 mmHg to 20 mmHg, extracted with organic solvents, preferably ethyl acetate, the organic solvent is evaporated again under reduced pressure from 10 mmHg to 20 mmHg, then purified by chromatographic methods. The subject of the application is also the use of betulin conjugates with esters of the above-mentioned α-amino acids and compounds obtained by the above method regulating cell viability and/or metabolism and for the production of anticancer drugs.

PL445905A 2023-08-24 2023-08-24 Betulin conjugates with α-amino acid esters, how to produce them and use PL445905A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PL445905A PL445905A1 (en) 2023-08-24 2023-08-24 Betulin conjugates with α-amino acid esters, how to produce them and use

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PL445905A PL445905A1 (en) 2023-08-24 2023-08-24 Betulin conjugates with α-amino acid esters, how to produce them and use

Publications (1)

Publication Number Publication Date
PL445905A1 true PL445905A1 (en) 2025-03-03

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Family Applications (1)

Application Number Title Priority Date Filing Date
PL445905A PL445905A1 (en) 2023-08-24 2023-08-24 Betulin conjugates with α-amino acid esters, how to produce them and use

Country Status (1)

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PL (1) PL445905A1 (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL387138A1 (en) * 2009-01-27 2010-08-02 Politechnika Wrocławska New mono- and diesters of betulin with amino acids, and method of their manufacturing
PL393257A1 (en) * 2010-12-13 2011-05-23 Uniwersytet Przyrodniczy we Wrocławiu New betulin diesters and process for the preparation thereof
PL434161A1 (en) * 2020-06-02 2021-12-06 Uniwersytet Medyczny Im.Piastów Śląskich We Wrocławiu New betulin derivative, method of its production and application

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL387138A1 (en) * 2009-01-27 2010-08-02 Politechnika Wrocławska New mono- and diesters of betulin with amino acids, and method of their manufacturing
PL393257A1 (en) * 2010-12-13 2011-05-23 Uniwersytet Przyrodniczy we Wrocławiu New betulin diesters and process for the preparation thereof
PL434161A1 (en) * 2020-06-02 2021-12-06 Uniwersytet Medyczny Im.Piastów Śląskich We Wrocławiu New betulin derivative, method of its production and application

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