Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D213/81—Amides; Imides
  • C07D213/82—Amides; Imides in position 3

Definitions

• the invention relates to a new derivative of 4,6-dimethyl-2-sulfanylpyridine exhibiting anticancer activity, to a method of its preparation, and to its use in a treatment of cancer, particularly mammary gland adenocarcinoma, drug resistant colon adenocarcinoma, and human melanoma.
• pyridine derivatives are often studied as potentially useful in cancer therapy.
• compounds containing a pyridine residue in their structure inhibit angiogenesis (Lukasik P.M. et al, Eur. J. Med.Chem. 2012, 57, 311-322; Ahn C.M. et al., Bioorg. Med. Chem. Lett. 2004, 15, 3893-3896), or guide cancer cells toward apoptosis (Ari F. et al, Bioorg. Med. Chem. 2013, 21, 6427-6434; Zhang Y.B. et al., Med. Chem.Res. 2013, 22, 3193-3203).
• Publication CN 102807574 discloses a derivative of pyridothiazepine and methods of its preparation, and uses.
• Derivatives of pyridothiazine exhibit a wide range of anticancer activities, particularly, said compounds demonstrate excellent inhibitory activity against various human cancer cell lines, in in vitro cellular assays.
• the said cell lines include human leukemia cell line OP-l, human colon cancer cell line HT29, human lung cancer cell line E1460, paclitaxel resistant human lung cancer cell line H460TaxR, and doxorubicin resistant human breast cancer cell line MCF-7/Adr.
• CA 2999929 discloses pyridine derivatives, especially substituted derivatives of pyrido[3,2- 5]dipyrimidine and l,5-naphthyridine, and their use in the therapy of cancer, viral, inflammatory and autoimmune diseases.
• the compounds are selective inhibitors of 4- phosphatidylinositol kinase (R14K1Pb) activity. They also affect the acceptance of cell and organ transplants.
• EP 1711495 provides quinoline, quinazoline, pyridine and pyrimidine compounds that are effective in the prevention and treatment of such diseases as hepatocyte growth factor dependent diseases (HGF).
• HGF hepatocyte growth factor dependent diseases
• the invention comprises new compounds, analogs, prodrugs, and pharmaceutically acceptable salts thereof, pharmaceutical compositions, and methods of prophylaxis and treatment of diseases or conditions, including, among others, cancer.
• EP 2740733 discloses 3,4-dihydropyrazino[2,3-b]pyrazin-2(lE[)-one compounds that are inhibitors of MTOR kinase and have a use in oncology and in MTOR / P13K / AKT pathway associated diseases.
• the disclosed compounds could be applied to treat or prevent cancer, inflammatory, immunological and neurodegenerative diseases, diabetes, obesity, neurological diseases, cardiovascular conditions and age-related diseases.
• RU 2561130 provides new 1 ,2,3,4-tetrahydropyrimido ⁇ 1 ,2-a ⁇ pyrimidin-6-one derivatives.
• the invention pertains to new compounds or their inorganic and organic acid addition salts, methods of preparation and use therof.
• the compounds can be used to treat primary tumors and metastases, in particular tumors of stomach, liver, kidney, ovaries, colon, prostate, endometrium, lung (NSCLC and SCLC), gliomas, thyroid tumors, bladder, mammary gland tumors, melanoma, cancers of the lymphatic system or myeloid hematopoietic system, sarcomas, tumors of the brain, larynx, lymphatic system, bone and pancreatic cancer, and also in the treatment of malaria.
• primary tumors and metastases in particular tumors of stomach, liver, kidney, ovaries, colon, prostate, endometrium, lung (NSCLC and SCLC), gliomas, thyroid tumors, bladder, mammary gland tumors, melanoma, cancers of the lymphatic system or myeloid hematopoietic system, sarcomas, tumors of the brain, larynx, lymphatic system, bone and pancreatic cancer, and also in the treatment of malaria.
• US 20080167300 provides pyridine compounds useful in the treatment of diseases associated with bone loss such as osteoporosis, Paget's disease, osteolytic bone loss, bone loss associated with breast cancer metastasis.
• Currently used drugs are very often toxic to healthy cells of the body, therefore they cause a number of side effects, often threatening the patient's life.
• the search for new anticancer drugs is currently focused on compounds that destroy cancer cells and at the same time are safe for healthy tissues.
• the objective of the invention is to provide a new compound that is a candidate drug bearing anti-cancer activity, and exhibit selective antiproliferative and cytotoxic activity against cancer cells.
• a substituted pyridine and a hydrazido- hydrazone group in one structure positively affects the pharmacological and toxicological properties.
• the invention relates to 4,6-dimethyl-2-sulfanylpyridine derivative having the chemical name N'-[(anthracen-9-yl)methylene]-2-[4,6-dimethyl-2-sulfanylpyridin-3-yl-carboxamido]acetic acid hydrazide, and represented by formula 1.
• the invention relates also to a method of preparation of N'-[(antbracen-9-yl)methylene]-2-[4,6- dimethyl-2-sulfanylpyridin-3-yl-carboxamido]acetic acid hydrazide represented by the chemical formula 1, the said method comprising steps:
• Another objective of the invention relates to N'-[(anthracen-9-yl)methylene]-2-[4,6-dimethyl- 2-sulfanylpyridin-3-yl-carboxamido]acetic acid hydrazide, represented by the chemical formula 1 , for use as a medicament.
• Another objective of the invention relates to N'-[(anthracen-9-yl)methylene]-2-[4,6-dimethyl- 2-sulfanylpyridin-3-yl-carboxamido]acetic acid hydrazide, represented by the chemical formula 1, for use in a treatment of cancer diseases.
• the cancer disease is mammary gland adenocarcinoma, drug resistant colorectal adenocarcinoma, and human melanoma.
• Fig. 2 Determination of IC50 coefficient for C25H22N4O2S, for the tested cell lines.
• the precipitated solid is filtered and crystallized from methanol, to give pure N'-[(anthracen-9-yl)methylene]-2-[4,6- dimethyl-2-sulfanylpyridin-3-yl-carboxamido]acetic acid hydrazide, with the melting point 553-554 °K, and the yield 84%.
• the anticancer activity was evaluated by MTT assay, using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide.
• the MTT test is a quantitative colorimetric method used to determine the activity of energy transformations in mitochondria.
• the yellow, water-soluble tetrazole salt (Thiazolyl blue formazan - MTT) is reduced by the action of mitochondrial dehydrogenase to purple, water insoluble formazan crystals.
• the amount of generated crystals is proportional to the oxidative activity of mitochondria, and under strictly defined test conditions to the number of live cells showing metabolic activities. Measurement of mitochondrial activity is performed spectroscopically at 570 nm.
• C25H22N4O2S was added in concentrations from 1 to 500 mM, in at least a triplicate. Cells were exposed for 24 hours, and next the MTT test was performed. The test results are shown in Fig. 1. The obtained results provided the basis for determination of the IC50 coefficient for the tested cell lines.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• General Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Pharmacology & Pharmacy (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)
• Pyridine Compounds (AREA)

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Citations (4)

• 2018
  • 2018-09-17 PL PL427105A patent/PL237497B1/pl unknown
• 2019
  • 2019-09-17 WO PCT/PL2019/000081 patent/WO2020060427A1/en active Application Filing

Patent Citations (4)

Non-Patent Citations (2)

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