ZA200609055B - (Poly) aminoacetamide derivatives of epipodophyllotoxin their process of preparation and their applications in therapeutics and anticancer agents - Google Patents
(Poly) aminoacetamide derivatives of epipodophyllotoxin their process of preparation and their applications in therapeutics and anticancer agents Download PDFInfo
- Publication number
- ZA200609055B ZA200609055B ZA200609055A ZA200609055A ZA200609055B ZA 200609055 B ZA200609055 B ZA 200609055B ZA 200609055 A ZA200609055 A ZA 200609055A ZA 200609055 A ZA200609055 A ZA 200609055A ZA 200609055 B ZA200609055 B ZA 200609055B
- Authority
- ZA
- South Africa
- Prior art keywords
- hexahydrofuro
- dioxol
- hydroxy
- naphtho
- dimethoxyphenyl
- Prior art date
Links
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 title claims description 15
- 238000002360 preparation method Methods 0.000 title claims description 15
- 239000003814 drug Substances 0.000 title claims description 12
- 238000000034 method Methods 0.000 title claims description 12
- 230000008569 process Effects 0.000 title claims description 11
- 239000002246 antineoplastic agent Substances 0.000 title claims description 8
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical class NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 title 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 90
- 150000001875 compounds Chemical class 0.000 claims description 75
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 206010028980 Neoplasm Diseases 0.000 claims description 27
- -1 alkyl radical Chemical class 0.000 claims description 23
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 claims description 23
- 125000006309 butyl amino group Chemical group 0.000 claims description 17
- 150000003254 radicals Chemical group 0.000 claims description 17
- 125000006308 propyl amino group Chemical group 0.000 claims description 15
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 claims description 14
- 229960001237 podophyllotoxin Drugs 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 12
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 12
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 11
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 238000010520 demethylation reaction Methods 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 235000005985 organic acids Nutrition 0.000 claims description 5
- 230000017858 demethylation Effects 0.000 claims description 4
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003880 polar aprotic solvent Substances 0.000 claims description 4
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 206010025323 Lymphomas Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 210000000481 breast Anatomy 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 3
- 210000000496 pancreas Anatomy 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 210000002307 prostate Anatomy 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 210000003932 urinary bladder Anatomy 0.000 claims description 3
- 210000004291 uterus Anatomy 0.000 claims description 3
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 239000002879 Lewis base Substances 0.000 claims description 2
- 229940123237 Taxane Drugs 0.000 claims description 2
- 241000863480 Vinca Species 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 238000011394 anticancer treatment Methods 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 238000011443 conventional therapy Methods 0.000 claims description 2
- 150000007527 lewis bases Chemical class 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 150000003057 platinum Chemical class 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 241000907681 Morpho Species 0.000 claims 1
- SBNKFTQSBPKMBZ-UHFFFAOYSA-N ethenzamide Chemical compound CCOC1=CC=CC=C1C(N)=O SBNKFTQSBPKMBZ-UHFFFAOYSA-N 0.000 claims 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
- 239000000047 product Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- FOVRGQUEGRCWPD-UHFFFAOYSA-N (5aR)-9t-beta-D-Glucopyranosyloxy-5t-(4-hydroxy-3,5-dimethoxy-phenyl)-(5ar,8at)-5,8,8a,9-tetrahydro-5aH-furo[3',4';6,7]naphtho[2,3-d][1,3]dioxol-6-on Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(OC3C(C(O)C(O)C(CO)O3)O)C3C2C(OC3)=O)=C1 FOVRGQUEGRCWPD-UHFFFAOYSA-N 0.000 description 5
- YVCVYCSAAZQOJI-JHQYFNNDSA-N 4'-demethylepipodophyllotoxin Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YVCVYCSAAZQOJI-JHQYFNNDSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229960005420 etoposide Drugs 0.000 description 4
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- YJGVMLPVUAXIQN-LGWHJFRWSA-N (5s,5ar,8ar,9r)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical class COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-LGWHJFRWSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000006434 Ritter amidation reaction Methods 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 2
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 229940045696 antineoplastic drug podophyllotoxin derivative Drugs 0.000 description 2
- NJAPCAIWQRPQPY-UHFFFAOYSA-N benzyl hydrogen carbonate Chemical compound OC(=O)OCC1=CC=CC=C1 NJAPCAIWQRPQPY-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 239000003600 podophyllotoxin derivative Substances 0.000 description 2
- 229920000768 polyamine Chemical group 0.000 description 2
- 230000004224 protection Effects 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000008439 repair process Effects 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 2
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 229960001278 teniposide Drugs 0.000 description 2
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
- WZBGSNYTODILNN-UHFFFAOYSA-N 5-hydroxy-9-(3,4,5-trihydroxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical compound C12=CC=3OCOC=3C=C2C(O)C2COC(=O)C2C1C1=CC(O)=C(O)C(O)=C1 WZBGSNYTODILNN-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003236 benzoyl group Chemical class [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- SYHPANJAVIEQQL-UHFFFAOYSA-N dicarboxy carbonate Chemical class OC(=O)OC(=O)OC(O)=O SYHPANJAVIEQQL-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229930013686 lignan Natural products 0.000 description 1
- 235000009408 lignans Nutrition 0.000 description 1
- 150000005692 lignans Chemical class 0.000 description 1
- 235000015250 liver sausages Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229940127084 other anti-cancer agent Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229940063673 spermidine Drugs 0.000 description 1
- 229940063675 spermine Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 150000003558 thiocarbamic acid derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0404053A FR2869035B1 (fr) | 2004-04-16 | 2004-04-16 | Derives (poly)aminoalkylaminoacetamide d'epipodophyllotoxine leur procede de preparation et leurs applications en therapeutique comme agent anticancereux |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200609055B true ZA200609055B (en) | 2008-06-25 |
Family
ID=34944659
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200609055A ZA200609055B (en) | 2004-04-16 | 2006-10-31 | (Poly) aminoacetamide derivatives of epipodophyllotoxin their process of preparation and their applications in therapeutics and anticancer agents |
Country Status (25)
| Country | Link |
|---|---|
| US (3) | US7846926B2 (fr) |
| EP (1) | EP1742952B1 (fr) |
| JP (1) | JP4876070B2 (fr) |
| CN (1) | CN1946727B (fr) |
| AR (1) | AR048607A1 (fr) |
| AT (1) | ATE402938T1 (fr) |
| AU (1) | AU2005233382C1 (fr) |
| BR (1) | BRPI0509912B8 (fr) |
| CA (1) | CA2562617C (fr) |
| CY (1) | CY1108444T1 (fr) |
| DE (1) | DE602005008578D1 (fr) |
| DK (1) | DK1742952T3 (fr) |
| ES (1) | ES2311985T3 (fr) |
| FR (1) | FR2869035B1 (fr) |
| HK (1) | HK1095812A1 (fr) |
| HR (1) | HRP20080542T3 (fr) |
| MX (1) | MXPA06011886A (fr) |
| MY (1) | MY137712A (fr) |
| PL (1) | PL1742952T3 (fr) |
| PT (1) | PT1742952E (fr) |
| RS (1) | RS50628B (fr) |
| SI (1) | SI1742952T1 (fr) |
| TW (1) | TWI350288B (fr) |
| WO (1) | WO2005100363A1 (fr) |
| ZA (1) | ZA200609055B (fr) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2888849B1 (fr) * | 2005-07-19 | 2007-10-05 | Pierre Fabre Medicament Sa | Procede de preparation de la 4b-amino-4'-demethyl-4-desoxypodophyllotoxine |
| FR2919287B1 (fr) * | 2007-07-26 | 2012-10-12 | Pf Medicament | Nouveaux derives fluorescents de polyamines, leur procede de preparation et leurs applications en tant qu'outils de diagnostic dans le traitement des tumeurs cancereuses. |
| FR2921368B1 (fr) * | 2007-09-25 | 2012-10-12 | Pf Medicament | Nouveau procede de synthese de derives anticancereux de (poly) aminoalkylaminoacetamide d'epipodophyllotoxine. |
| FR2921369B1 (fr) * | 2007-09-25 | 2014-07-11 | Pf Medicament | Nouveau procede de preparation de derives (poly) aminoalkylaminoacetamide d'epipodophyllotoxine,utiles pour leurs applications en therapeutique comme agent anticancereux. |
| FR2935143B1 (fr) * | 2008-08-19 | 2010-12-03 | Pf Medicament | Nouveaus derives (poly)aminoalkylaminoalkylamides, alkyl-urees, ou alkyl-sulfonamides d'epipodophyllotoxine, leur procede de preparation et leur application en therapeuthique comme agent cancereux |
| SG172819A1 (en) | 2008-12-31 | 2011-08-29 | Dow Global Technologies Llc | Enhanced procatalyst composition and process |
| BRPI0918698A8 (pt) | 2008-12-31 | 2017-09-19 | Grace W R & Co | Composição de procatalisador e processo para produzir um polímero baseado em olefina |
| MX2012006370A (es) * | 2009-12-02 | 2012-09-07 | Dow Global Technologies Llc | Compuestos de dicarbonato puenteados por dos atomos como donadores internos en catalizadores para la fabricacion de polipropileno. |
| EP2507269B1 (fr) | 2009-12-02 | 2014-10-29 | W.R. Grace & Co.-Conn. | Composés dicarbonates pontés par trois et quatre atomes, comme donneurs internes dans des catalyseurs pour la fabrication de polypropylène |
| CN102234283B (zh) * | 2010-04-23 | 2013-06-12 | 湖北工业大学 | 4′-去甲基表鬼臼毒素衍生物及其合成方法和应用 |
| EP2638047B1 (fr) * | 2010-11-11 | 2014-07-16 | Council of Scientific and Industrial Research | Dérivés de 4-beta-acrylamidopodophyllotoxin substitués en tant qu'antibiotiques antitumoraux et leur procédé de préparation |
| FR2967675B1 (fr) | 2010-11-24 | 2015-02-27 | Pf Medicament | Derives fluorescents de cyanines polyamines en tant que sonde de diagnostic |
| WO2015161745A1 (fr) * | 2014-04-25 | 2015-10-29 | 中国医药工业研究总院 | Dérivé de podophyllotoxine et procédé de préparation, composition pharmaceutique et utilisation correspondants |
| CN104926841A (zh) * | 2015-06-30 | 2015-09-23 | 遵义医学院 | 青蒿琥酯与鬼臼毒素偶联物在抗白血病药物中的应用及制备方法 |
| WO2018234574A1 (fr) | 2017-06-22 | 2018-12-27 | Ygm Consult Sas | Thérapie combinatoire pour le traitement du cancer |
| CN113801129A (zh) * | 2021-09-30 | 2021-12-17 | 大连民族大学 | 一种鬼臼毒素脂质衍生物、纳米载体及其制备方法和在肿瘤治疗中的应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6323884A (ja) * | 1986-07-17 | 1988-02-01 | Nippon Kayaku Co Ltd | 新規ポドフイロトキシン誘導体 |
| US5300500A (en) * | 1989-02-23 | 1994-04-05 | The University Of North Carolina At Chapel Hill | 4 beta-amino podophyllotoxin analog compounds and methods |
| US5332811A (en) * | 1989-09-12 | 1994-07-26 | The University Of North Carolina At Chapel Hill | Etopside analogs |
| CN1068330A (zh) * | 1991-07-03 | 1993-01-27 | 国家医药管理局上海医药工业研究院 | 4-氮取代-4-脱氧-4′-去甲表鬼臼毒素衍生物及其合成方法 |
| FR2725990B1 (fr) * | 1994-10-21 | 1997-01-10 | Pf Medicament | Derives hydrosolubles d'epipodophyllotoxine, leur procede de preparation, leur utilisation a titre de medicament, et leur utilisation destinee aux traitements anticancereux |
| FR2742439B1 (fr) | 1995-12-14 | 1998-03-06 | Pf Medicament | Procede de preparation de la 4'-demethylepipodophyllotoxine a partir de la podophyllotoxine |
| FR2810321B1 (fr) | 2000-06-20 | 2002-07-26 | Adir | Nouveaux derives de podophyllotoxine carbamate et thiocarbamate, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| ES2247315T3 (es) * | 2002-03-28 | 2006-03-01 | Council Of Scientific And Industrial Research | Analogos de 4b-1" - (2" - (benzoilo substituido) anilino) podofilotoxina para utilizacion com agentes de tratamiento contra el cancer. |
| US6566393B1 (en) * | 2002-06-21 | 2003-05-20 | The University Of North Carolina At Chapel Hill | Etoposide analogs and methods of use thereof |
| US7357802B2 (en) | 2003-02-14 | 2008-04-15 | The Board Of Trustees Of The Leland Stanford Junior University | Electrosurgical system with uniformly enhanced electric field and minimal collateral damage |
| US20070066837A1 (en) | 2003-02-18 | 2007-03-22 | Ahmed Kamal | Podophyllotoxin derivatives as antitumor agents |
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