IL105329A - Pharmacological preparation for the treatment of malignancies using history (2-lomethylidene and antineoplastic preparation specific for phase S or phase M - Google Patents
Pharmacological preparation for the treatment of malignancies using history (2-lomethylidene and antineoplastic preparation specific for phase S or phase MInfo
- Publication number
- IL105329A IL105329A IL105329A IL10532993A IL105329A IL 105329 A IL105329 A IL 105329A IL 105329 A IL105329 A IL 105329A IL 10532993 A IL10532993 A IL 10532993A IL 105329 A IL105329 A IL 105329A
- Authority
- IL
- Israel
- Prior art keywords
- group
- halogen
- hydrogen
- formula
- phase
- Prior art date
Links
- 230000018199 S phase Effects 0.000 title claims abstract description 36
- 230000027311 M phase Effects 0.000 title claims abstract description 30
- 238000002560 therapeutic procedure Methods 0.000 title claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- 206010028980 Neoplasm Diseases 0.000 title description 16
- 239000002246 antineoplastic agent Substances 0.000 title description 7
- 201000011510 cancer Diseases 0.000 title description 7
- 229940034982 antineoplastic agent Drugs 0.000 title description 6
- 230000000118 anti-neoplastic effect Effects 0.000 claims abstract description 42
- 201000010099 disease Diseases 0.000 claims abstract description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 31
- 230000001613 neoplastic effect Effects 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 42
- 229910052736 halogen Chemical group 0.000 claims description 41
- 150000002367 halogens Chemical group 0.000 claims description 41
- 239000003795 chemical substances by application Substances 0.000 claims description 34
- 238000011282 treatment Methods 0.000 claims description 31
- 239000001257 hydrogen Substances 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 21
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical group O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 14
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical group FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 13
- 229960002949 fluorouracil Drugs 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- -1 oxy, methylene Chemical group 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 150000003254 radicals Chemical group 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 9
- 229960000684 cytarabine Drugs 0.000 claims description 9
- 229960003048 vinblastine Drugs 0.000 claims description 9
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical group C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 9
- 201000009030 Carcinoma Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 229910003204 NH2 Inorganic materials 0.000 claims description 5
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 5
- 208000032839 leukemia Diseases 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims 16
- 229940122803 Vinca alkaloid Drugs 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000002814 antineoplastic antimetabolite Substances 0.000 description 14
- 229960000485 methotrexate Drugs 0.000 description 14
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 13
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 13
- 229960003087 tioguanine Drugs 0.000 description 13
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 8
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 8
- 229960000624 procarbazine Drugs 0.000 description 8
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 7
- 229960004618 prednisone Drugs 0.000 description 7
- 229960004528 vincristine Drugs 0.000 description 7
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 7
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 7
- RGWOFTGZWJGPHG-NKWVEPMBSA-N (2r)-3-hydroxy-2-[(1r)-2-oxo-1-(6-oxo-3h-purin-9-yl)ethoxy]propanal Chemical compound N1C=NC(=O)C2=C1N([C@@H](C=O)O[C@H](CO)C=O)C=N2 RGWOFTGZWJGPHG-NKWVEPMBSA-N 0.000 description 6
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 6
- XPYQFIISZQCINN-QVXDJYSKSA-N 4-amino-1-[(2r,3e,4s,5r)-3-(fluoromethylidene)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one;hydrate Chemical compound O.O=C1N=C(N)C=CN1[C@H]1C(=C/F)/[C@H](O)[C@@H](CO)O1 XPYQFIISZQCINN-QVXDJYSKSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 208000035269 cancer or benign tumor Diseases 0.000 description 6
- GFFXZLZWLOBBLO-ASKVSEFXSA-N tezacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(=C/F)/[C@H](O)[C@@H](CO)O1 GFFXZLZWLOBBLO-ASKVSEFXSA-N 0.000 description 6
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 5
- 208000017604 Hodgkin disease Diseases 0.000 description 5
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- 238000011260 co-administration Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000002195 synergetic effect Effects 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 230000001028 anti-proliverative effect Effects 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000001382 Experimental Melanoma Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 3
- 230000000340 anti-metabolite Effects 0.000 description 3
- 229940100197 antimetabolite Drugs 0.000 description 3
- 239000002256 antimetabolite Substances 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 229940127089 cytotoxic agent Drugs 0.000 description 3
- 239000002254 cytotoxic agent Substances 0.000 description 3
- 231100000599 cytotoxic agent Toxicity 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229960001428 mercaptopurine Drugs 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 2
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- HMYLOZKRIDEWHK-UHFFFAOYSA-N [3,4-diethyl-2-(fluoromethyl)phenyl]sulfonylphosphonic acid Chemical compound CCC1=CC=C(S(=O)(=O)P(O)(O)=O)C(CF)=C1CC HMYLOZKRIDEWHK-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 238000001030 gas--liquid chromatography Methods 0.000 description 2
- 201000003911 head and neck carcinoma Diseases 0.000 description 2
- 229960001330 hydroxycarbamide Drugs 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000000527 lymphocytic effect Effects 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229910000761 Aluminium amalgam Inorganic materials 0.000 description 1
- 201000003076 Angiosarcoma Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 201000000274 Carcinosarcoma Diseases 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 208000006332 Choriocarcinoma Diseases 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000032027 Essential Thrombocythemia Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000001258 Hemangiosarcoma Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229940127395 Ribonucleotide Reductase Inhibitors Drugs 0.000 description 1
- 208000008383 Wilms tumor Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 208000017733 acquired polycythemia vera Diseases 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000008275 breast carcinoma Diseases 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
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- DENHPZASLKBBHA-UHFFFAOYSA-N fluoromethylsulfonylbenzene Chemical compound FCS(=O)(=O)C1=CC=CC=C1 DENHPZASLKBBHA-UHFFFAOYSA-N 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 201000011066 hemangioma Diseases 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 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
- 206010024627 liposarcoma Diseases 0.000 description 1
- 210000003563 lymphoid tissue Anatomy 0.000 description 1
- 230000000684 melanotic effect Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
- 230000001394 metastastic effect Effects 0.000 description 1
- 206010061289 metastatic neoplasm Diseases 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000035773 mitosis phase Effects 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
- 208000037244 polycythemia vera Diseases 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86639992A | 1992-04-10 | 1992-04-10 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL105329A0 IL105329A0 (en) | 1993-08-18 |
| IL105329A true IL105329A (en) | 1998-06-15 |
Family
ID=25347526
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL105329A IL105329A (en) | 1992-04-10 | 1993-04-07 | Pharmacological preparation for the treatment of malignancies using history (2-lomethylidene and antineoplastic preparation specific for phase S or phase M |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US20040102461A1 (fr) |
| EP (1) | EP0664708B1 (fr) |
| JP (1) | JP3713668B2 (fr) |
| KR (1) | KR100258668B1 (fr) |
| AT (1) | ATE170077T1 (fr) |
| AU (1) | AU667527B2 (fr) |
| CA (1) | CA2117891C (fr) |
| DE (1) | DE69320646T2 (fr) |
| DK (1) | DK0664708T3 (fr) |
| ES (1) | ES2123642T3 (fr) |
| HU (1) | HU219476B (fr) |
| IL (1) | IL105329A (fr) |
| MX (1) | MX9302038A (fr) |
| NZ (1) | NZ251211A (fr) |
| TW (1) | TW362971B (fr) |
| WO (1) | WO1993020825A1 (fr) |
| ZA (1) | ZA932455B (fr) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2768295A (en) * | 1994-07-11 | 1996-02-09 | Hoechst Marion Roussel, Inc. | Method of treating a neoplastic disease state by conjunctive therapy with 2'-fluoromethylidene derivatives and radiation or chemotherapy |
| US5811408A (en) * | 1994-07-12 | 1998-09-22 | Yamasa Corporation | 2'-deoxy-2'-(substituted or unsubstituted)methylidene-4'-thionucleosides |
| ATE265213T1 (de) | 1997-09-04 | 2004-05-15 | Novoneuron Inc | Noribogain zur behandlung von schmerzen und drogenabhängigkeit |
| US7220737B1 (en) | 1997-09-04 | 2007-05-22 | Novoneuron, Inc | Noribogaine in the treatment of pain and drug addiction |
| US6544962B1 (en) | 2000-11-02 | 2003-04-08 | Matrix Pharmaceutical, Inc. | Methods for treating cellular proliferative disorders |
| JP2005522443A (ja) * | 2002-02-14 | 2005-07-28 | フアーマセツト・リミテツド | 改変フッ素化ヌクレオシド類似体 |
| AU2003280867A1 (en) * | 2002-11-04 | 2004-06-07 | Charite-Universitatsme Dizin Berlin | Specific haplotypes of the mdr1 gene and their use in diagnosis and therapy |
| US8765737B1 (en) | 2010-05-11 | 2014-07-01 | Demerx, Inc. | Methods and compositions for preparing and purifying noribogaine |
| US8362007B1 (en) | 2010-05-11 | 2013-01-29 | Demerx, Inc. | Substituted noribogaine |
| US9394294B2 (en) | 2010-05-11 | 2016-07-19 | Demerx, Inc. | Methods and compositions for preparing and purifying noribogaine |
| US8741891B1 (en) | 2010-06-22 | 2014-06-03 | Demerx, Inc. | N-substituted noribogaine prodrugs |
| US8637648B1 (en) | 2010-06-22 | 2014-01-28 | Demerx, Inc. | Compositions comprising noribogaine and an excipient to facilitate transport across the blood brain barrier |
| US8802832B2 (en) | 2010-06-22 | 2014-08-12 | Demerx, Inc. | Compositions comprising noribogaine and an excipient to facilitate transport across the blood brain barrier |
| US9586954B2 (en) | 2010-06-22 | 2017-03-07 | Demerx, Inc. | N-substituted noribogaine prodrugs |
| CA2806232A1 (fr) | 2010-07-23 | 2012-01-26 | Demerx, Inc. | Compositions de noribogaine |
| EP2481740B1 (fr) | 2011-01-26 | 2015-11-04 | DemeRx, Inc. | Procédés et compositions pour préparer de la noribogaïne à partir de voacangine |
| US9617274B1 (en) | 2011-08-26 | 2017-04-11 | Demerx, Inc. | Synthetic noribogaine |
| CA2855994A1 (fr) | 2011-12-09 | 2013-06-13 | Demerx, Inc. | Esters phosphoriques de noribogaine |
| SG10201913554YA (en) | 2011-12-22 | 2020-03-30 | Alios Biopharma Inc | Substituted nucleosides, nucleotides and analogs thereof |
| CA2858820C (fr) | 2012-01-25 | 2021-08-17 | Demerx, Inc. | Voacangine synthetique |
| US9150584B2 (en) | 2012-01-25 | 2015-10-06 | Demerx, Inc. | Indole and benzofuran fused isoquinuclidene derivatives and processes for preparing them |
| US9441007B2 (en) | 2012-03-21 | 2016-09-13 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| USRE48171E1 (en) | 2012-03-21 | 2020-08-25 | Janssen Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| CA2896133A1 (fr) | 2012-12-20 | 2014-06-26 | Demerx, Inc. | Noribogaine substituee |
| US9045481B2 (en) | 2012-12-20 | 2015-06-02 | Demerx, Inc. | Substituted noribogaine |
| US8940728B2 (en) | 2012-12-20 | 2015-01-27 | Demerx, Inc. | Substituted noribogaine |
| WO2015195673A2 (fr) | 2014-06-18 | 2015-12-23 | Demerx, Inc. | Dérivés d'indole et de benzofurane halogénés d'isoquinuclidène et procédés pour leur préparation. |
-
1993
- 1993-03-15 HU HU9402914A patent/HU219476B/hu not_active IP Right Cessation
- 1993-03-15 JP JP51832893A patent/JP3713668B2/ja not_active Expired - Fee Related
- 1993-03-15 AU AU38131/93A patent/AU667527B2/en not_active Ceased
- 1993-03-15 KR KR1019940703561A patent/KR100258668B1/ko not_active Expired - Fee Related
- 1993-03-15 DK DK93907581T patent/DK0664708T3/da active
- 1993-03-15 NZ NZ251211A patent/NZ251211A/en not_active IP Right Cessation
- 1993-03-15 AT AT93907581T patent/ATE170077T1/de not_active IP Right Cessation
- 1993-03-15 CA CA002117891A patent/CA2117891C/fr not_active Expired - Fee Related
- 1993-03-15 ES ES93907581T patent/ES2123642T3/es not_active Expired - Lifetime
- 1993-03-15 EP EP93907581A patent/EP0664708B1/fr not_active Expired - Lifetime
- 1993-03-15 DE DE69320646T patent/DE69320646T2/de not_active Expired - Fee Related
- 1993-03-15 WO PCT/US1993/002490 patent/WO1993020825A1/fr not_active Ceased
- 1993-04-05 ZA ZA932455A patent/ZA932455B/xx unknown
- 1993-04-07 MX MX9302038A patent/MX9302038A/es not_active IP Right Cessation
- 1993-04-07 IL IL105329A patent/IL105329A/en not_active IP Right Cessation
- 1993-04-08 TW TW082102613A patent/TW362971B/zh not_active IP Right Cessation
-
1998
- 1998-09-25 US US09/160,977 patent/US20040102461A1/en not_active Abandoned
-
2004
- 2004-09-17 US US10/943,429 patent/US20050032738A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20040102461A1 (en) | 2004-05-27 |
| CA2117891C (fr) | 1998-07-07 |
| DE69320646D1 (de) | 1998-10-01 |
| EP0664708A1 (fr) | 1995-08-02 |
| TW362971B (en) | 1999-07-01 |
| WO1993020825A1 (fr) | 1993-10-28 |
| ATE170077T1 (de) | 1998-09-15 |
| CA2117891A1 (fr) | 1993-10-28 |
| HU9402914D0 (en) | 1995-01-30 |
| HU219476B (hu) | 2001-04-28 |
| EP0664708A4 (fr) | 1995-04-24 |
| MX9302038A (es) | 1993-10-01 |
| JP3713668B2 (ja) | 2005-11-09 |
| HUT71224A (en) | 1995-11-28 |
| KR100258668B1 (ko) | 2000-07-01 |
| DE69320646T2 (de) | 1999-01-14 |
| IL105329A0 (en) | 1993-08-18 |
| ES2123642T3 (es) | 1999-01-16 |
| DK0664708T3 (da) | 1998-11-02 |
| AU3813193A (en) | 1993-11-18 |
| JPH07505653A (ja) | 1995-06-22 |
| US20050032738A1 (en) | 2005-02-10 |
| EP0664708B1 (fr) | 1998-08-26 |
| KR950700749A (ko) | 1995-02-20 |
| ZA932455B (en) | 1993-10-20 |
| AU667527B2 (en) | 1996-03-28 |
| NZ251211A (en) | 1997-05-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0664708B1 (fr) | Procede de traitement du cancer par association therapeutique de derives de 2'-halomethylidene et d'un agent antineoplasique specifique par rapport a la phase s ou m | |
| US5561136A (en) | Method of treating cancer by conjunctive therapy with N,N'-bis[ethylamino)propyl]-1,7-heptanediamine and a cytotoxic agent | |
| EP3171870B1 (fr) | Inhibiteurs de protéine phosphatase 2a pour traiter des syndromes myélodysplasiques | |
| AU2020319058A1 (en) | Macrocyclic compounds as sting agonists and methods and uses thereof | |
| JP5730854B2 (ja) | デシタビンとシチジンデアミナーゼ阻害剤との組合せ、およびがんの治療におけるその使用 | |
| JP2012522842A (ja) | シチジンベースの抗新生物薬とシチジンデアミナーゼ阻害薬との組合せ、および癌の治療におけるその使用 | |
| US20110028421A1 (en) | Use of alkylphosphocholines in combination with antimetabolites for the treatment of benign and malignant oncoses in humans and mammals | |
| EP3068406B1 (fr) | Promédicament réciproque comportant des acides gras à chaîne courte et de la zébularine ou de la 1'-cyano-cytarabine pour un traitement de cancer | |
| JP5687687B2 (ja) | 癌を治療するための(2’−デオキシ−リボフラノシル)−1,3,4,7−テトラヒドロ−(1,3)ジアゼピン−2−オン誘導体 | |
| EP2780011B1 (fr) | Polythérapie utilisée pour le cancer de l'ovaire | |
| EP0490380B1 (fr) | Utilisation de N,N'-bis 3-(ethylamino)propyl-1,7-heptanediamine et un agent cytotoxique | |
| JP5581200B2 (ja) | シチジン誘導体及びカルボプラチンを含有する抗腫瘍剤 | |
| US20060258736A1 (en) | Dosing regimen | |
| HK1060066B (en) | Pharmaceutical combinations based on pyridoindolone derivatives and anticancer agents | |
| HK1060066A1 (en) | Pharmaceutical combinations based on pyridoindolone derivatives and anticancer agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |