ES2273002T7 - Camptotecinas con un anillo lactona modificado. - Google Patents
Camptotecinas con un anillo lactona modificado. Download PDFInfo
- Publication number
- ES2273002T7 ES2273002T7 ES03730480T ES03730480T ES2273002T7 ES 2273002 T7 ES2273002 T7 ES 2273002T7 ES 03730480 T ES03730480 T ES 03730480T ES 03730480 T ES03730480 T ES 03730480T ES 2273002 T7 ES2273002 T7 ES 2273002T7
- Authority
- ES
- Spain
- Prior art keywords
- homocamptothecin
- group
- branched
- linear
- alkyl
- 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.)
- Active
Links
- 150000002596 lactones Chemical class 0.000 title description 18
- -1 2-methylbutoxy Chemical group 0.000 claims description 65
- 150000001875 compounds Chemical class 0.000 claims description 46
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 19
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 229940127093 camptothecin Drugs 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 239000004480 active ingredient Substances 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
- 239000013067 intermediate product Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 102000003915 DNA Topoisomerases Human genes 0.000 claims description 5
- 108090000323 DNA Topoisomerases Proteins 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 230000001093 anti-cancer Effects 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- 238000006680 Reformatsky reaction Methods 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 229940035893 uracil Drugs 0.000 claims description 3
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 230000003071 parasitic effect Effects 0.000 claims description 2
- 125000000468 ketone group Chemical group 0.000 claims 2
- 208000030852 Parasitic disease Diseases 0.000 claims 1
- 208000036142 Viral infection Diseases 0.000 claims 1
- 150000002923 oximes Chemical class 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 230000009385 viral infection Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 41
- 239000000460 chlorine Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 239000003480 eluent Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 238000002483 medication Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 229940041181 antineoplastic drug Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 201000005202 lung cancer Diseases 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 238000009510 drug design Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000007654 immersion Methods 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- RDEIXVOBVLKYNT-VQBXQJRRSA-N (2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(1-aminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol;(2r,3r,4r,5r)-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,6s)-3-amino-6-(aminomethyl)oxan-2-yl]o Chemical compound OS(O)(=O)=O.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@@H](CN)O2)N)[C@@H](N)C[C@H]1N.O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H](CC[C@H](O2)C(C)N)N)[C@@H](N)C[C@H]1N.O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N RDEIXVOBVLKYNT-VQBXQJRRSA-N 0.000 description 1
- 125000006726 (C1-C5) alkenyl group Chemical group 0.000 description 1
- PAEZRCINULFAGO-OAQYLSRUSA-N (R)-homocamptothecin Chemical compound CC[C@@]1(O)CC(=O)OCC(C2=O)=C1C=C1N2CC2=CC3=CC=CC=C3N=C21 PAEZRCINULFAGO-OAQYLSRUSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000006507 2,4-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(F)C(=C1[H])C([H])([H])* 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004924 2-naphthylethyl group Chemical group C1=C(C=CC2=CC=CC=C12)CC* 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
- 125000006189 4-phenyl benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- NPDLYUOYAGBHFB-WDSKDSINSA-N Asn-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NPDLYUOYAGBHFB-WDSKDSINSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 241000759905 Camptotheca acuminata Species 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000872931 Myoporum sandwicense Species 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 241000209018 Nyssaceae Species 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003096 antiparasitic agent Substances 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 group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002983 circular dichroism Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 231100000050 cytotoxic potential Toxicity 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910000358 iron sulfate Inorganic materials 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940046892 lead acetate Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000005249 lung adenocarcinoma Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- OAYUEHJARDXAEF-QZTJIDSGSA-N n-[(1r,2r)-2-[(3,5-dinitrobenzoyl)amino]cyclohexyl]-3,5-dinitrobenzamide Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC(C(=O)N[C@H]2[C@@H](CCCC2)NC(=O)C=2C=C(C=C(C=2)[N+]([O-])=O)[N+]([O-])=O)=C1 OAYUEHJARDXAEF-QZTJIDSGSA-N 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000003303 reheating Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Epoxy Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITRM02A0305 | 2002-05-31 | ||
| IT2002RM000305A ITRM20020305A1 (it) | 2002-05-31 | 2002-05-31 | Camptotecine con anello lattonico modificato. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES2273002T3 ES2273002T3 (es) | 2007-05-01 |
| ES2273002T7 true ES2273002T7 (es) | 2011-08-01 |
Family
ID=11456338
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03730480T Active ES2273002T7 (es) | 2002-05-31 | 2003-05-28 | Camptotecinas con un anillo lactona modificado. |
| ES06116366T Expired - Lifetime ES2312090T3 (es) | 2002-05-31 | 2003-05-28 | Camptotecinas con un anillo de lactona modificado. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06116366T Expired - Lifetime ES2312090T3 (es) | 2002-05-31 | 2003-05-28 | Camptotecinas con un anillo de lactona modificado. |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US7273873B2 (enExample) |
| EP (2) | EP1719775B1 (enExample) |
| JP (1) | JP4693410B2 (enExample) |
| KR (1) | KR101042042B1 (enExample) |
| CN (1) | CN1656100A (enExample) |
| AR (1) | AR040139A1 (enExample) |
| AT (2) | ATE403659T1 (enExample) |
| AU (2) | AU2003241160B2 (enExample) |
| BR (2) | BR0311333A (enExample) |
| CA (2) | CA2485201C (enExample) |
| CY (2) | CY1107311T1 (enExample) |
| DE (2) | DE60322754D1 (enExample) |
| DK (2) | DK1719775T3 (enExample) |
| ES (2) | ES2273002T7 (enExample) |
| IT (1) | ITRM20020305A1 (enExample) |
| MX (1) | MXPA04011682A (enExample) |
| PE (1) | PE20050120A1 (enExample) |
| PL (1) | PL374346A1 (enExample) |
| PT (2) | PT1511752E (enExample) |
| SI (2) | SI1511752T1 (enExample) |
| TW (1) | TWI325866B (enExample) |
| WO (1) | WO2003101995A2 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2852606A1 (fr) * | 2003-03-18 | 2004-09-24 | Inst Nat Sante Rech Med | Moyens pour inhiber simultanement l'expression de plusieurs genes impliques dans une pathologie |
| ITRM20030344A1 (it) * | 2003-07-14 | 2005-01-15 | Ist Naz Stud Cura Dei Tumori | 7-n-poliamminoalchil(ossi)imminometilcamptotecine recanti gruppi protettivi. |
| PL2170900T3 (pl) * | 2007-08-01 | 2013-04-30 | Sigma Tau Ind Farmaceuti | Krystaliczna forma II 7-(dimetoksymetylo)kamptotecyny, jej zastosowanie jako związek pośredni oraz otrzymane z niej produkty |
| CN102746314B (zh) * | 2011-04-18 | 2016-07-06 | 华东师范大学 | 含有稳定7元内酯环的喜树碱类化合物、制备方法和用途 |
| CN104530066A (zh) * | 2015-01-06 | 2015-04-22 | 华东师范大学 | 一类新型高喜树碱衍生物、制备方法和用途 |
| CN112566666A (zh) | 2018-05-14 | 2021-03-26 | 努瓦申生物公司 | 靶向抗癌核激素受体的化合物 |
| AU2020274113A1 (en) | 2019-05-14 | 2021-11-11 | Nuvation Bio Inc. | Anti-cancer nuclear hormone receptor-targeting compounds |
| TW202131930A (zh) | 2019-11-13 | 2021-09-01 | 美商諾維雪碧歐公司 | 抗癌核荷爾蒙受體標靶化合物 |
| IL306010A (en) | 2021-03-23 | 2023-11-01 | Nuvation Bio Inc | Anticancer compounds against the nuclear hormone receptor |
| CA3218577A1 (en) | 2021-05-03 | 2022-11-10 | Nuvation Bio Inc. | Anti-cancer nuclear hormone receptor-targeting compounds |
| WO2024073626A2 (en) * | 2022-09-28 | 2024-04-04 | Nuvation Bio Inc. | Anti-cancer nuclear hormone receptor-targeting compounds |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS57116076A (en) * | 1981-01-09 | 1982-07-19 | Yakult Honsha Co Ltd | Novel camptothecin derivative and its preparation |
| US4399276A (en) * | 1981-01-09 | 1983-08-16 | Kabushiki Kaisha Yakult Honsha | 7-Substituted camptothecin derivatives |
| FR2532591A1 (fr) | 1982-09-02 | 1984-03-09 | Hutchinson | Nouveau dispositif de securite pour pneumatiques de vehicules ou autres engins |
| EP1251125B1 (fr) * | 1995-06-21 | 2005-12-07 | Société de Conseils et de Recherches d'Applications Scientifiques (S.C.R.A.S.) | Nouveaux analogues de la camptoth-cine, des proc-d-s de pr-paration, leur application comme m-dicaments et les compositions pharmaceutiques les contenant |
| DK1044977T3 (da) * | 1999-03-09 | 2002-07-08 | Sigma Tau Ind Farmaceuti | Camptothecinderivater med antitumoraktivitet |
-
2002
- 2002-05-31 IT IT2002RM000305A patent/ITRM20020305A1/it unknown
-
2003
- 2003-05-26 TW TW092114164A patent/TWI325866B/zh not_active IP Right Cessation
- 2003-05-28 PT PT03730480T patent/PT1511752E/pt unknown
- 2003-05-28 DE DE60322754T patent/DE60322754D1/de not_active Expired - Lifetime
- 2003-05-28 AT AT06116366T patent/ATE403659T1/de active
- 2003-05-28 SI SI200330509T patent/SI1511752T1/sl unknown
- 2003-05-28 PL PL03374346A patent/PL374346A1/xx unknown
- 2003-05-28 CA CA2485201A patent/CA2485201C/en not_active Expired - Fee Related
- 2003-05-28 DK DK06116366T patent/DK1719775T3/da active
- 2003-05-28 BR BR0311333-7A patent/BR0311333A/pt not_active IP Right Cessation
- 2003-05-28 BR BR0311329-9A patent/BR0311329A/pt not_active IP Right Cessation
- 2003-05-28 MX MXPA04011682A patent/MXPA04011682A/es active IP Right Grant
- 2003-05-28 ES ES03730480T patent/ES2273002T7/es active Active
- 2003-05-28 KR KR1020047016880A patent/KR101042042B1/ko not_active Expired - Fee Related
- 2003-05-28 AU AU2003241160A patent/AU2003241160B2/en not_active Ceased
- 2003-05-28 CA CA2706635A patent/CA2706635A1/en not_active Abandoned
- 2003-05-28 US US10/511,724 patent/US7273873B2/en not_active Expired - Fee Related
- 2003-05-28 WO PCT/IT2003/000328 patent/WO2003101995A2/en not_active Ceased
- 2003-05-28 DE DE60308368T patent/DE60308368T3/de not_active Expired - Lifetime
- 2003-05-28 CN CNA038125439A patent/CN1656100A/zh active Pending
- 2003-05-28 DK DK03730480.5T patent/DK1511752T5/da active
- 2003-05-28 JP JP2004509686A patent/JP4693410B2/ja not_active Expired - Fee Related
- 2003-05-28 AT AT03730480T patent/ATE339422T1/de active
- 2003-05-28 EP EP06116366A patent/EP1719775B1/en not_active Expired - Lifetime
- 2003-05-28 EP EP03730480A patent/EP1511752B3/en not_active Expired - Lifetime
- 2003-05-28 PT PT06116366T patent/PT1719775E/pt unknown
- 2003-05-28 ES ES06116366T patent/ES2312090T3/es not_active Expired - Lifetime
- 2003-05-28 SI SI200331380T patent/SI1719775T1/sl unknown
- 2003-05-30 AR ARP030101915A patent/AR040139A1/es unknown
- 2003-05-30 PE PE2003000529A patent/PE20050120A1/es not_active Application Discontinuation
-
2006
- 2006-11-14 CY CY20061101648T patent/CY1107311T1/el unknown
-
2008
- 2008-10-31 CY CY20081101240T patent/CY1108793T1/el unknown
-
2009
- 2009-11-12 AU AU2009236044A patent/AU2009236044B8/en not_active Ceased
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2009236044B8 (en) | Camptothecins with a modified lactone ring | |
| KR100191193B1 (ko) | 6환 화합물 | |
| ES2561356T3 (es) | Derivados de camptotecina con actividad antitumoral | |
| ES2331569T3 (es) | Esteres de camptotecinas en la posicion 20. | |
| WO1996041806A1 (en) | Novel water-soluble fluoroethylcamptothecin derivative and process for production thereof | |
| WO2007104214A1 (en) | Camptothecin derivatives and their use | |
| WO2012007619A1 (es) | Proceso de obtención de derivados solubles en agua de 20(s)camptotecina como agentes antitumorales | |
| ES2319293T3 (es) | Derivados 7-imino de campotecina que tienen actividad antitumoral. | |
| WO2011154574A1 (es) | Derivados de camptotecina como agentes antitumorales | |
| ES2395930T3 (es) | Procedimiento estereoselectivo y formas cristalinas de una camptotecina | |
| ES2350711T3 (es) | Derivados de camptotecina con actividad antitumoral. |