[go: up one dir, main page]

WO2017178992A1 - Complexes d'imidazo[1,2-a]pyridine ayant une activité anticancéreuse - Google Patents

Complexes d'imidazo[1,2-a]pyridine ayant une activité anticancéreuse Download PDF

Info

Publication number
WO2017178992A1
WO2017178992A1 PCT/IB2017/052122 IB2017052122W WO2017178992A1 WO 2017178992 A1 WO2017178992 A1 WO 2017178992A1 IB 2017052122 W IB2017052122 W IB 2017052122W WO 2017178992 A1 WO2017178992 A1 WO 2017178992A1
Authority
WO
WIPO (PCT)
Prior art keywords
copper
imidazo
pyridin
formula
complex
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.)
Ceased
Application number
PCT/IB2017/052122
Other languages
English (en)
Inventor
Charles Bernard De Koning
Leonie HARMSE
Jean DAM
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of the Witwatersrand, Johannesburg
Original Assignee
University of the Witwatersrand, Johannesburg
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.)
Filing date
Publication date
Application filed by University of the Witwatersrand, Johannesburg filed Critical University of the Witwatersrand, Johannesburg
Publication of WO2017178992A1 publication Critical patent/WO2017178992A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F1/00—Compounds containing elements of Groups 1 or 11 of the Periodic Table
    • C07F1/08—Copper compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • This invention relates to novel metal complexes of imidazo[l,2-a]pyridine derivatives and/or analogues thereof, and extends to their manufacture. This invention further extends to copper complexes of imidazo[l,2-a]pyridine derivatives and/or analogues thereof for use in the treatment of cancer, particularly breast cancer, colorectal cancer, and leukemia.
  • Cancer is considered as a leading cause of death in developed countries and consequently new and innovative anti-cancer pharmaceuticals are required to be developed.
  • Many standard therapies are toxic to healthy non-cancerous cells resulting in unwanted side effects and/or serious life threatening adverse effects. Further, cancer often becomes resistant to known therapies resulting in its further spread and/or a need for increased and more toxic dosage regimes being administered to the cancer sufferer.
  • One such standard therapy includes the administration of cisplatin, a very toxic and expensive chemotherapeutic.
  • Imidazo[l,2-a]pyridines are a class of chemical compounds known to display a wide range of biological activities.
  • imidazo[l,2-a]pyridines are known to treat insomnia and anxiety and have been investigated in the treatment of HIV, possibly impacting several independent biochemical pathways.
  • the Applicant has previously shown that certain derivatives and/or analogues of imidazo[l,2-a]pyridines show biological activity against colon cancer (see PCT/IB2010/051427).
  • a metal complex of an imidazo[l,2- a]pyridine ligand and/or a metal complex of an imidazo[l,2-a]pyridine ligand derivative and/or an analogue thereof is provided.
  • the metal complex may further include at least one second ligand interacting with the metal.
  • the interaction between the imidazo[l,2-a]pyridine ligand and the metal, and the interaction between the second ligand and the metal may each be a molecular interaction, and may be at least one of the following group of molecular interactions: ionic, covalent, dative, coordinative, and van der Waals.
  • the at least one second ligand may be an oxygen containing ligand and/or a halogen interacting with the metal.
  • the at least one second ligand is an oxygen containing ligand.
  • the oxygen containing second ligand may include at least one of the following groups: nitrates, acetates, sulphates and phosphates. Typically, the oxygen containing second ligand is nitrate and/or acetate.
  • the metal may be a metal ion.
  • the metal ion may be copper.
  • the copper may be Cu 1+ and/or Cu 2+ .
  • the metal is Cu 2+ .
  • the metal complex may be a copper (II) complex of an imidazo[l,2-a]pyridine ligand derivative and/or analogue.
  • Said copper (II) complex may provide a distorted square planar geometry.
  • the copper (II) complex of an imidazo[l,2-a]pyridine ligand derivative and/or analogue to provide a distorted square planar geometry, wherein the oxygen containing second ligand provides at least one oxygen atom being in a position out of plane relative to the remainder of the complex.
  • the copper (II) complex of an imidazo[l,2-a]pyridine ligand derivative and/or analogue may form dimers.
  • the imidazo[l,2-a] pyridine ligand derivative and/or analogue may be a compound of Formula A:
  • Ri, R 2 and R 3 may each be a hydrogen or a halogen
  • R may be any one of the following group: benzyl and cyclohexyl.
  • R R 2 and R 3 may each be any one of the following group: hydrogen, bromine and chlorine.
  • R3 may vary around an aromatic ring structure, and this is indicated by a line representing a bond projecting into said ring structure.
  • the copper (II) complex of an imidazo[l,2-a]pyridine ligand derivative and/or analogue thereof may include at least one of the following group: copper N-benzyl-6-bromo-2-(pyridin-2-yl)imidazo[ 1 ,2-a]pyridin-3 -amine acetate
  • the cancer may include at least one of the following group: breast cancer, colorectal cancer, colon cancer, and leukemia.
  • the metal complex may further include at least one second ligand interacting with the metal.
  • the interaction between the imidazo[l,2-a]pyridine ligand and the metal, and the interaction between the second ligand and the metal may each be a molecular interaction, and may be at least one of the following group of molecular interactions: ionic, covalent, dative, coordinative, and van der Waals.
  • the at least one second ligand may be an oxygen containing ligand and/or a halogen interacting with the metal.
  • the at least one second ligand is an oxygen containing ligand.
  • the oxygen containing second ligand may include at least one of the following groups: nitrates, acetates, sulphates and phosphates.
  • the oxygen containing ligand is nitrate and/or acetate.
  • R ls R 2 and R 3 may each be any one of the following group: hydrogen, bromine and chlorine.
  • R 3 may vary around an aromatic ring structure, and this is indicated by a line representing a bond projecting into said ring structure.
  • Formula (A2.1) copper 6-bromo-N-cyclohexyl-2-(pyridin-2-yl)imidazo[l,2-a]pyridin-3 -amine acetate
  • Formula (A2.2) copper 6-bromo-N-cyclohexyl-2-(pyridin-2-yl)imidazo[l,2-a]pyridin-3-amine nitrate
  • cancer may include at least one of the following group: breast cancer, colorectal cancer, colon cancer, and leukemia.
  • oxygen containing second ligand may include at least one of the following groups: nitrates, acetates, sulphates and phosphates.
  • oxygen containing ligand is nitrate and/or acetate.
  • FIGURE 1 shows crystallographic data of a compound of Formula (Al);
  • FIGURE 2 shows crystallographic data of a compound of Formula (A2.1);
  • FIGURE 3 shows crystallographic data of a compound of Formula (A2.2);
  • FIGURE 4 shows crystallographic data of a compound of Formula (A3);
  • FIGURE 5 shows crystallographic data of a compound of Formula (A4);
  • FIGURE 6 shows crystallographic data of a compound of Formula (A5);
  • FIGURE 7 shows crystallographic data of a compound of Formula (A6);
  • FIGURE 9 shows the effect of Formula (A2.1) on cell and nuclear morphology on MCF-7 and HL-60 cells after a 48 h exposure period indicates apoptotic and necrotic cell death.
  • MCF-7 and HL-60 cells were treated with Formula (A2.1) at a concentration of 1.5 ⁇ and 2.0 ⁇ , respectively. Images were captured at a 400 ⁇ magnification and scalebars represent 20 micron.
  • N normal nucleus
  • NN necrotic nucleus
  • AN apoptotic nucleus
  • LAN late apoptotic nucleus
  • MCF-7 cells shows the formation of cytoplasmic vacuoles, acidic granules, deformed- and apoptotic nuclei.
  • Cells were treated with 10 ⁇ of the test compounds for 24 h. Images were captured at a 400 ⁇ ⁇ magnification and scalebars represent 20 micrometers.
  • N nucleus
  • CN contracted nucleus
  • AN apoptotic nucleus
  • DN deformed nucleus
  • AG acidic granules
  • F filopodia
  • V vacuoles;
  • FIGURE 11 shows the formation of cytoplasmic vacuoles do not co-localize with the acidic granules.
  • metal complexes preferably copper complexes, of imidazo[l,2-a]pyridine derivatives and/or analogues, and their use in the treatment of cancer, preferably breast cancer, colon cancer, colorectal cancer and/or leukemia.
  • Cisplatin is a known anti-cancer agent that has a square planar geometry.
  • the square planar geometry of cisplatin is enabled by the electron configuration of platinum and its ions.
  • Cisplatin and its derivatives are expensive to manufacture, have low solubility and are toxic to healthy cells with long term neurotoxic effects on surviving patients.
  • Imidazo[l,2-a]pyridines may have a plethora of different functional groups which may readily impact of their physico-chemical properties. Based on the sheer number of possibilities and lack of guiding selection principles it is difficult to predict which imidazo[l,2-a]pyridine derivative and/or analogue would, when complexed with copper, provide for an anti-cancer agent, preferably an anti-breast cancer, anti-colon cancer and/or anti-leukemia agent. Similarly, the sheer number of known uses for imidazo[l,2-a]pyridines in biological applications suggests several independent and unpredictable mechanisms of action.
  • the metal complex typically further includes at least one oxygen containing second ligand interacting with the metal.
  • the interaction between the imidazo[l,2-a]pyridine ligand and the metal, and the interaction between the second ligand and the metal may each be a molecular interaction, and may be at least one of the following group of molecular interactions: ionic, covalent, dative, coordinative, and van der Waals.
  • the metal complex typically includes at least one oxygen containing second ligand interacting with the metal.
  • the oxygen containing second ligand may include at least one of the following groups: nitrates, acetates, sulphates and phosphates.
  • the oxygen containing second ligand is nitrate and/or acetate.
  • the metal is typically a metal ion.
  • the metal ion is typically copper.
  • the copper may be Cu 1+ and/or Cu 2+ .
  • the metal is Cu 2+ .
  • the metal complex may be a copper (II) complex of an imidazo[l,2- a]pyridine ligand derivative and/or analogue.
  • Said copper (II) complex may provide a distorted square planar geometry.
  • the copper (II) complex of an imidazo[l,2-a]pyridine ligand derivative and/or analogue which provides a distorted square planar geometry, wherein the oxygen containing ligand provides at least one oxygen atom being in a position out of plane relative to the square planar arrangement.
  • the copper (II) complex of an imidazo[l,2-a]pyridine ligand derivative and/or analogue may form dimers.
  • the complex of Formula (A6) shows two distorted square planar copper (II) complexes forming a dimer. This is also seen in the accompanying crystallographic data herein below.
  • the imidazo[l,2-a]pyridine derivative ligand and/or analogue may be a compound of Formula A:
  • Ri, R.2 and R 3 may each be a hydrogen or a halogen
  • R4 may be any one of the following group: benzyl and cyclohexyl.
  • R l5 R 2 and R 3 may each be any one of the following group: hydrogen, bromine and chlorine.
  • R 3 may vary around an aromatic ring structure, and this is indicated by a line representing a bond projecting into said ring structure.
  • the copper (II) complex of an imidazo[l,2-a]pyridine ligand derivative and/or analogue may include at least one of the following group:
  • Formula (A2.1) copper 6-bromo-N-cyclohexyl-2-(pyridin-2-yl)imidazo[l,2-a]pyridin-3 -amine acetate
  • Formula (A2.2) copper 6-bromo-N-cyclohexyl-2-(pyridin-2-yl)imidazo[l,2-a]pyridin-3-amine nitrate
  • a metal complex of an imidazo[l,2- a]pyridine ligand and/or a metal complex of an imidazo[l,2-a]pyridine ligand derivative and/or an analogue thereof for use in treating cancer, as described in the Summary above.
  • the cancer may include at least one of the following group: breast cancer, colorectal cancer, colon cancer, and leukemia.
  • the metal complexes according to this disclosure have been found to be active against several different cancer cell lines.
  • imidazo[l,2-a]pyridines are synthesized according to the Groebke-Blackburn-Bienayme multicomponent reaction, wherein functionalized imidazo[l,2-a]pyridines are synthesized in a single step from substituted 2-aminopyridines, isocyanides and aldehydes in the presence of an acid catalyst such as zinc(II)chloride or scandium triflate. All the reagents and chemicals were purchased from Sigma-Aldrich, Merck or ACE Chemicals and used without further purification unless otherwise noted.
  • the relevant imidazo[l,2-a]pyridine was added to diethylether to form a solution.
  • Equimolar amounts of an appropriate metal salt for example copper(II)chloride (CuCl 2 ), copper(II)acetate (Cu(Ac) 2 ) and copper(II)nitrate (Cu(N0 3 ) 2 ) were added to the solution and stirred for over 18 hours at room temperature. During this time a powder formed in the solution and this was collected by filtration and washed with diethylether to remove any unreacted imidazo[l,2-a]pyridine. The copper complexes were then dissolved in acetone, filtered and concentrated in vacuo to remove any unreacted copper salts. The powder was then crystallized slowly from suitable solvents to afford x-ray quality crystals. Infra-red (IR) studies were also conducted.
  • CuCl 2 copper(II)chloride
  • Cu(Ac) 2 ) copper(II)nitrate
  • N-benzyl-6-bromo-2-(pyridin-2-yl)imidazo[l,2-a]pyridin-3 -amine (Ligand Al) was synthesized as follows. Combining 5-bromo-2-aminopyridine (2.304 g, 13.317 mmol), benzyl isocyanide (1.56 g, 13.317 mmol, 1 eq) and pyridinecarbaldehyde (1.27 ml, 13.317 mmol, 1 eq)) with Montmorrillionite K-10 Clay (2.30 g) and following the general procedure with EtOH as the solvent resulted in 13 (2.037g, 40 %), which was collected as a yellow powder after recrystallization from ether.
  • N-benzyl-6-bromo-2-(pyridin-2-yl)imidazo[l,2-a]pyridin-3 -amine (Ligand Al) (0.200 g, 0.527 mmol) and copper(II) acetate monohydrate (0.116 g, 0.570 mmol, 1.1 eq) were used as described above.
  • the product Formula (Al) (0.320 g, 99 %) was recrystallized by vapour diffusion from MeOD and ether. The structure of the complex was confirmed by single crystal X-ray crystallography.
  • IR (v ⁇ crn 1 ) 3428, 3246, 3084, 3029, 2999, 2925, 1577, 1564, 1526, 1498, 1482, 1391, 1330, 1244, 1204, 1166, 1124, 1096, 1045, 1018, 975, 930, 842, 813, 785, 750, 704, 675, 647, 617.
  • 6-bromo-N-cyclohexyl-2-(pyridine-2-yl)imidazo[l,2-a]pyridine-3-amine (0.200 g,0.539 mmol) (Ligand A2) was synthesized as follows: 2-Amino-5-bromopyridine (2.00 g, 11.56 mmol), 2- pyridinecarboxaldehyde (1.24 g, 11.56 mmol, 1 eq), cyclohexyl isocyanide (1.26 g, 11.56 mmol, 1 eq) and Montmorrillionite K-10 Clay (2.00 g) were combined and the general procedure followed.
  • Ligand A2 was not active against any cancer cell lines, however, copper (II) complex compound of Formula (A2.1) was active against all tested cancer cell lines (see Table 1). The Applicant did not expect that the complex of Formula (A2.1) would be active against all the tested cancer cell lines.
  • IR (v m .cm _1 ) 3327, 3094, 2924, 2854, 1610, 1568, 1479, 1452, 1410, 1302, 1275, 1246, 1161, 1113, 1097, 1069, 1009, 970, 893, 872, 808, 783, 750, 708, 675, 652.
  • Ligand A2 was not active against any cancer cell lines, however, copper (II) complex compound of Formula (A2.2) was active against all tested cancer cell lines (see Table 1). The Applicant did not expect that the complex of Formula (A2.2) would be active against all the tested cell lines.
  • N-cyclohexyl-2-(pyridin-2-yl)imidazo[l,2-a]pyridin-3-amine (Ligand A3) was synthesized as follows: 2- Aminopyridine (1.00 g, 10.626 mmol), 2-pyridinecarboxaldehyde (1.14 g, 10.626 mmol, 1 eq), cyclohexyl isocyanide (1.16 g, 10.626 mmol, 1 eq) and Montmorrillionite K-10 Clay (1.2 g) were combined and the general procedure followed. The resulting mixture was purified by recrystallization from an ether/DCM mixture to afford Ligand A3 as yellow crystals (2.31 g, 74 %).
  • 6-chloro-N-cyclohexyl-2-(pyridin-2-yl)imidazo[l,2-a]pyridin-3 -amine (Ligand A4) was synthesized as follows. 2-amino-5-chloropyridine (1.00 g, 7.78 mmol), 2-pyridinecarboxaldehyde (0.833 g, 7.78 mmol, 1 eq), cyclohexyl isocyanide (0.857 g, 7.78 mmol, 1 eq) and Montmorrillionite K-10 Clay (1.0 g) were combined in ethanol.
  • JR (v ⁇ c f 1 ) 3379, 3282, 3282, 3067, 2930, 2858, 1610, 1568, 1528, 1502, 1477, 1400, 1331 , 1292, 1242, 1 151, 1 128, 1097, 1078, 1047, 1022, 877, 822, 787, 756, 725, 679, 621.
  • Ligand A4 was not active against any cancer cell lines, however, copper (II) complex compound of Formula A4 was active against all tested cancer cell lines (see Table 1). This was unexpected.
  • Ligand A5 was not active against any cancer cell lines, however, copper (II) complex compound of Formula (A5) was active against all tested cancer cell lines (see Table 1). The Applicant did not expect that the complex of Formula (A5) would be active against all the tested cancer cell lines.
  • Ligand A6 was not active against any cancer cell lines, however, copper (II) complex compound of Formula (A6) was active against all tested cancer cell lines (see Table 1). The Applicant did not expect that the complex of Formula (A6) would be active against all the tested cancer cell lines.
  • Suitable ligand crystals for single crystal X-ray diffraction were grown from deuterated methanol unless otherwise stated. However, complex of Formula (A2.2) was crystallized from deuterated chloroform. Following mounting of the crystals on a glass fibre, the intensity data for the crystals were collected on a Bruker APEX II CCD area detector diffractometer with graphite monochromated Mo-K a radiation (50 kV, 30 mA) at 173K. The collection method involved ⁇ -scans having a width of 0.5°. Data reduction was carried out using SAINT+ version 6.02.6 software and SADABS was used to make empirical absorption corrections. The crystal structures were solved through direct methods using SHELXS-97.
  • Whole blood was collected from human volunteers in heparin containing blood collection tubes.
  • White blood cells (leucocytes) were isolated under sterile conditions from whole blood by differential centrifugation by using the Histopaque -1077 solution (Sigma-Aldrich). Briefly, a volume of blood was carefully layered (without mixing the two phases) over an equal volume of Histopaque -1077 solution in a 50 mL centrifuge tube and centrifuged for 30 mins at 250 x g at room temperature. The leucocytes collect at the plasma/ Histopaque-1077 interphase and erythrocytes and granulocytes sediment to the bottom of the tube. Following centrifugation the upper phase containing plasma and platelets were aspirated and discarded.
  • Initial testing involved exposing the relevant cancer cells to the imidazo[l,2-a]pyridine ligands, copper salts, zinc complexes thereof, as well as the copper complexes thereof, at a final concentration of 100 ⁇ at 37 °C for 48 hours.
  • Cell viability was measured with tetrazolium based MTT assay.
  • Compounds were considered to be active when the viability of the cells had decreased by 80% when compared to the negative control.
  • These compounds were further tested to determine the 50% inhibitory concentration IC 50 values (see Table 1 below) which is an indication of the relative potency of a compound.
  • IC 50 values below about 20 ⁇ were considered active against cancer cells.
  • IC 50 values greater than about 20 ⁇ were considered inactive against cancer cells.
  • the copper complexes for Formulas Al to A6 showed significant anti-cancer activity (with all IC 50 values well below 20 ⁇ and frequently below 15 ⁇ and below 10 ⁇ ) across a range of cancer cell lines.
  • Ligand (A4) NA 23 ⁇ 3 NA 29.2 ⁇ 0.7
  • MCF-7 cells treated with a lower concentration of Formula (A5) appears to favour fragmentation off the nucleus indicating that 29 at a lower concentrations cause apoptosis ( Figure 12).
  • the lower concentration also caused the formation of acidic granules in a high percentage of cells which were not evident when the cells were treated with 10 ⁇ ( Figures 10 and 12).
  • Cells treated with Formula (A3) also showed the presence of apoptotic nuclei ( Figure 10, panel h and p).
  • the complex of Formula (A2.2) showed the presence of contracted nuclei (CN) and a loss of the normal round or oval shaped nuclei (block arrow) in Figure 10, panel 1, which is indicative of pre-apoptotic changes.
  • the Applicant has surprisingly shown that the metal complexes according to the first aspect of this invention described above are active against cancer.
  • the Applicant has found that by providing cancer cells (known to harbor excessive amounts of copper) with more copper complexes is lethal to cancer cells. Further, the ligands and metal salts used to manufacture the copper complexes of the invention individually showed no anti-cancer activity. The results are surprising and unexpected.

Landscapes

  • 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)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

Cette invention concerne un complexe métallique à base d'un ligand d'imidazo[1,2-a] pyridine et/ou un complexe métallique à base d'un dérivé et/ou d'un analogue du ligand d'imidazo[1,2-a]pyridine, lesdits complexes métalliques étant destinés à être utilisés dans le traitement du cancer. Généralement, le cancer est le cancer du sein, le cancer colorectal, le cancer du côlon et/ou la leucémie.
PCT/IB2017/052122 2016-04-12 2017-04-12 Complexes d'imidazo[1,2-a]pyridine ayant une activité anticancéreuse Ceased WO2017178992A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ZA2016/02478 2016-04-12
ZA201602478 2016-04-12

Publications (1)

Publication Number Publication Date
WO2017178992A1 true WO2017178992A1 (fr) 2017-10-19

Family

ID=58739301

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2017/052122 Ceased WO2017178992A1 (fr) 2016-04-12 2017-04-12 Complexes d'imidazo[1,2-a]pyridine ayant une activité anticancéreuse

Country Status (1)

Country Link
WO (1) WO2017178992A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3615532A4 (fr) * 2017-04-28 2020-11-18 Dana Farber Cancer Institute, Inc. Inhibiteurs de trim33 et méthodes d'utilisation
US11297399B1 (en) 2017-03-27 2022-04-05 Snap Inc. Generating a stitched data stream

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010116302A1 (fr) * 2009-04-07 2010-10-14 University Of The Witwatersrand, Johannesburg Dérivés d'imidazo[1,2-a] pyridine-6-carboxamides, leur utilisation pour le traitement du cancer du côlon et leur procédé de fabrication

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010116302A1 (fr) * 2009-04-07 2010-10-14 University Of The Witwatersrand, Johannesburg Dérivés d'imidazo[1,2-a] pyridine-6-carboxamides, leur utilisation pour le traitement du cancer du côlon et leur procédé de fabrication

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
BALL, P., NATURE, vol. 381, 1996, pages 648 - 650
D. MONTAGNER ET AL: ") complex targeting the translocator protein: in vitro and in vivo antitumor potential and mechanistic insights", CHEMICAL COMMUNICATIONS - CHEMCOM., vol. 53, no. 1, 1 January 2017 (2017-01-01), pages 134 - 137, XP055380770, ISSN: 1359-7345, DOI: 10.1039/C6CC08100B *
DAM JEAN ET AL: "Synthesis of copper and zinc 2-(pyridin-2-yl)imidazo[1,2-a]pyridine complexes and their potential anticancer activity", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, EDITIONS SCIENTIFIQUE ELSEVIER, PARIS, FR, vol. 126, 11 November 2016 (2016-11-11), pages 353 - 368, XP029885675, ISSN: 0223-5234, DOI: 10.1016/J.EJMECH.2016.10.041 *
JOLANTA SAWICKA ET AL: "Synthesis and coordination ability of substituted imidazo-pyridines, structural analogues of oxine. Influence of copper(II) and nickel(II) ions on toxicity of the organic ligand", JOURNAL OF INORGANIC BIOCHEMISTRY, vol. 44, no. 2, 1 November 1991 (1991-11-01), US, pages 117 - 125, XP055380776, ISSN: 0162-0134, DOI: 10.1016/0162-0134(91)84024-4 *
MADDOX, J., NATURE, vol. 335, 1988, pages 201
NICOLA MARGIOTTA ET AL: ") with a ligand targeting the translocator protein (TSPO)", DALTON TRANSACTIONS: THE INTERNATIONAL JOURNAL FOR INORGANIC, ORGANOMETALLIC AND BIOINORGANIC CHEMISTRY, vol. 43, no. 43, 1 January 2014 (2014-01-01), GB, pages 16252 - 16264, XP055380771, ISSN: 1477-9226, DOI: 10.1039/C4DT01540A *
NICOLA MARGIOTTA ET AL: "Platinum(II) Complexes with Bioactive Carrier Ligands Having High Affinity for the Translocator Protein", JOURNAL OF MEDICINAL CHEMISTRY, vol. 53, no. 14, 22 July 2010 (2010-07-22), pages 5144 - 5154, XP055380773, ISSN: 0022-2623, DOI: 10.1021/jm100429r *
TAURAI FLLOYD KUREBWA: "The Effect of imidazo[1 ,2-a]pyridine amines on MCF-7 and MDA-MB-231 Breast Cancer Cells", A DISSERTATION SUBMITTED TO THE FACULTY OF HEALTH SCIENCES, UNIVERSITY OF THE WITWATERSRAND, JOHANNESBURG, IN FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTERS OF SCIENCE IN MEDICINE (PHARMACOLOGY), 1 January 2015 (2015-01-01), pages 1 - 142, XP055381320, Retrieved from the Internet <URL:http://mobile.wiredspace.wits.ac.za/bitstream/handle/10539/21597/kurebwa Flloyd Taurai, 2015.pdf?sequence=1&isAllowed=y> [retrieved on 20170614] *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11297399B1 (en) 2017-03-27 2022-04-05 Snap Inc. Generating a stitched data stream
EP3615532A4 (fr) * 2017-04-28 2020-11-18 Dana Farber Cancer Institute, Inc. Inhibiteurs de trim33 et méthodes d'utilisation
AU2018258588A8 (en) * 2017-04-28 2022-03-03 Dana-Farber Cancer Institute, Inc. Inhibitors of TRIM33 and methods of use
AU2018258588B2 (en) * 2017-04-28 2022-06-02 Dana-Farber Cancer Institute, Inc. Inhibitors of TRIM33 and methods of use
US11731967B2 (en) 2017-04-28 2023-08-22 Dana-Farber Cancer Institute, Inc. Inhibitors of TRIM33 and methods of use

Similar Documents

Publication Publication Date Title
Dam et al. Synthesis of copper and zinc 2-(pyridin-2-yl) imidazo [1, 2-a] pyridine complexes and their potential anticancer activity
Alkış et al. Cobalt and ruthenium complexes with pyrimidine based schiff base: Synthesis, characterization, anticancer activities and electrochemotherapy efficiency
Arafath et al. Synthesis, characterization and anticancer studies of Ni (II), Pd (II) and Pt (II) complexes with Schiff base derived from N-methylhydrazinecarbothioamide and 2-hydroxy-5-methoxy-3-nitrobenzaldehyde
Qin et al. Synthesis of two platinum (II) complexes with 2-methyl-8-quinolinol derivatives as ligands and study of their antitumor activities
Visbal et al. Cytotoxicity and biodistribution studies of luminescent Au (I) and Ag (I) N-heterocyclic carbenes. Searching for new biological targets
Yang et al. Organotin (IV) complexes derived from Schiff base N’-[(1E)-(2-hydroxy-3-methoxyphenyl) methylidene] pyridine-3-carbohydrazone: Synthesis, in vitro cytotoxicities and DNA/BSA interaction
Lopes et al. New copper (I) and heteronuclear copper (I)–ruthenium (II) complexes: synthesis, structural characterization and cytotoxicity
Choroba et al. In vitro antiproliferative effect of vanadium complexes bearing 8-hydroxyquinoline-based ligands–the substituent effect
Eremina et al. Cu (II), Co (II), Mn (II) complexes with 5-phenyltetrazole and polypyridyl ligands: Synthesis, characterization and evaluation of the cytotoxicity and antimicrobial activity
CN106939025B (zh) 一类诱导细胞胀亡的铱配合物及其制备方法和抗肿瘤应用
Ayyannan et al. Design, synthesis, structure and biological evaluation of new palladium (II) hydrazone complexes
Antonenko et al. Cytotoxic activity of organotin carboxylates based on synthetic phenolic antioxidants and polycyclic bile acids
Raja et al. Biological activities of pyrenyl-derived thiosemicarbazone half-sandwich complexes
Samanta et al. Silver (I), Gold (I) and Gold (III)-N-Heterocyclic carbene complexes of naphthyl substituted annelated ligand: Synthesis, structure and cytotoxicity
Du et al. Organotin (IV) complexes derived from 1, 4-naphthalenedicarboxylic acid: synthesis, structure, in vitro cytostatic activity
CN111548360B (zh) 一种二硫代氨基碳酸混价铜配合物及其制备和应用
CN115624544B (zh) 查耳酮类似物作为活性物质在制备抗肿瘤药物中的应用
Pantelić et al. Synthesis, characterization and in vitro biological evaluation of novel organotin (IV) compounds with derivatives of 2-(5-arylidene-2, 4-dioxothiazolidin-3-yl) propanoic acid
CN116143842A (zh) 氧化异阿朴菲生物碱与n-杂环卡宾的环金属铱配合物及其合成方法和应用
Rechitskaya et al. Tuning of cytotoxic activity by bio-mimetic ligands in ruthenium nitrosyl complexes
CN104230998B (zh) 一种线粒体靶向的铱-n-杂环卡宾配合物及其制备方法和应用
Wu et al. Rigid dinuclear ruthenium-arene complexes showing strong DNA interactions
Jiang et al. Systematic evaluation of the antitumor activity of three ruthenium polypyridyl complexes
Kasalović et al. Novel triphenyltin (iv) compounds with carboxylato N-functionalized 2-quinolones as promising potential anticancer drug candidates: In vitro and in vivo evaluation
Peega et al. Synthesis and evaluation of the anticancer activity of [Pt (diimine)(N, N-dibutyl-N′-acylthiourea)]+ complexes

Legal Events

Date Code Title Description
NENP Non-entry into the national phase

Ref country code: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 17724633

Country of ref document: EP

Kind code of ref document: A1

122 Ep: pct application non-entry in european phase

Ref document number: 17724633

Country of ref document: EP

Kind code of ref document: A1