CA2450942A1 - Method of treating hyperproliferative diseases using active vitamin d analogues - Google Patents
Method of treating hyperproliferative diseases using active vitamin d analogues Download PDFInfo
- Publication number
- CA2450942A1 CA2450942A1 CA002450942A CA2450942A CA2450942A1 CA 2450942 A1 CA2450942 A1 CA 2450942A1 CA 002450942 A CA002450942 A CA 002450942A CA 2450942 A CA2450942 A CA 2450942A CA 2450942 A1 CA2450942 A1 CA 2450942A1
- Authority
- CA
- Canada
- Prior art keywords
- hydrogen
- compound
- accordance
- alpha
- alkenyl
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 40
- 229940046008 vitamin d Drugs 0.000 title claims abstract 19
- 201000010099 disease Diseases 0.000 title claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims 2
- 230000003463 hyperproliferative effect Effects 0.000 title claims 2
- 230000001184 hypocalcaemic effect Effects 0.000 claims abstract 19
- 229930003316 Vitamin D Natural products 0.000 claims abstract 18
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims abstract 18
- 235000019166 vitamin D Nutrition 0.000 claims abstract 18
- 239000011710 vitamin D Substances 0.000 claims abstract 18
- 150000003710 vitamin D derivatives Chemical class 0.000 claims abstract 5
- 230000003211 malignant effect Effects 0.000 claims abstract 4
- 210000005170 neoplastic cell Anatomy 0.000 claims abstract 4
- 208000037147 Hypercalcaemia Diseases 0.000 claims abstract 2
- 230000000148 hypercalcaemia Effects 0.000 claims abstract 2
- 208000030915 hypercalcemia disease Diseases 0.000 claims abstract 2
- 125000003342 alkenyl group Chemical group 0.000 claims 30
- 229910052739 hydrogen Inorganic materials 0.000 claims 23
- 239000001257 hydrogen Substances 0.000 claims 23
- 125000000217 alkyl group Chemical group 0.000 claims 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 17
- -1 vitamin D compound Chemical class 0.000 claims 13
- 229940127089 cytotoxic agent Drugs 0.000 claims 11
- 239000002254 cytotoxic agent Substances 0.000 claims 11
- 231100000599 cytotoxic agent Toxicity 0.000 claims 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 11
- 125000002252 acyl group Chemical group 0.000 claims 10
- 150000001875 compounds Chemical class 0.000 claims 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims 10
- 125000004991 fluoroalkenyl group Chemical group 0.000 claims 10
- 125000003709 fluoroalkyl group Chemical group 0.000 claims 10
- 206010028980 Neoplasm Diseases 0.000 claims 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 7
- 210000004027 cell Anatomy 0.000 claims 7
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 5
- 229910052799 carbon Inorganic materials 0.000 claims 5
- 239000011203 carbon fibre reinforced carbon Chemical group 0.000 claims 5
- 239000003795 chemical substances by application Substances 0.000 claims 5
- 150000002431 hydrogen Chemical class 0.000 claims 5
- 230000001028 anti-proliverative effect Effects 0.000 claims 4
- 230000001225 therapeutic effect Effects 0.000 claims 4
- NEETXMRNUNEBRH-GOTXBORWSA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-1-[(2r,5s)-5,6-dimethylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CC[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C NEETXMRNUNEBRH-GOTXBORWSA-N 0.000 claims 3
- ZGLHBRQAEXKACO-XJRQOBMKSA-N 1alpha,25-dihydroxyvitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](\C=C\[C@H](C)C(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C ZGLHBRQAEXKACO-XJRQOBMKSA-N 0.000 claims 3
- 229940045799 anthracyclines and related substance Drugs 0.000 claims 3
- 230000000340 anti-metabolite Effects 0.000 claims 3
- 229940044684 anti-microtubule agent Drugs 0.000 claims 3
- 229940100197 antimetabolite Drugs 0.000 claims 3
- 239000002256 antimetabolite Substances 0.000 claims 3
- 230000003115 biocidal effect Effects 0.000 claims 3
- HKXBNHCUPKIYDM-CGMHZMFXSA-N doxercalciferol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C HKXBNHCUPKIYDM-CGMHZMFXSA-N 0.000 claims 3
- 229910052697 platinum Inorganic materials 0.000 claims 3
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 2
- 206010025323 Lymphomas Diseases 0.000 claims 2
- 208000037196 Medullary thyroid carcinoma Diseases 0.000 claims 2
- 208000034578 Multiple myelomas Diseases 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 201000000582 Retinoblastoma Diseases 0.000 claims 2
- 206010039491 Sarcoma Diseases 0.000 claims 2
- 229940123237 Taxane Drugs 0.000 claims 2
- 239000003242 anti bacterial agent Substances 0.000 claims 2
- 210000000988 bone and bone Anatomy 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- 208000035269 cancer or benign tumor Diseases 0.000 claims 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims 2
- 210000003128 head Anatomy 0.000 claims 2
- 239000003112 inhibitor Substances 0.000 claims 2
- 230000002401 inhibitory effect Effects 0.000 claims 2
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 claims 2
- 201000001441 melanoma Diseases 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 2
- 210000003739 neck Anatomy 0.000 claims 2
- 210000004872 soft tissue Anatomy 0.000 claims 2
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims 2
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 claims 2
- 210000003932 urinary bladder Anatomy 0.000 claims 2
- 102000009310 vitamin D receptors Human genes 0.000 claims 2
- 108050000156 vitamin D receptors Proteins 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical group FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 claims 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 claims 1
- 229930192392 Mitomycin Natural products 0.000 claims 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 229930012538 Paclitaxel Natural products 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- HFVNWDWLWUCIHC-GUPDPFMOSA-N Prednimustine Chemical compound O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 HFVNWDWLWUCIHC-GUPDPFMOSA-N 0.000 claims 1
- 208000024313 Testicular Neoplasms Diseases 0.000 claims 1
- 206010057644 Testis cancer Diseases 0.000 claims 1
- 101710183280 Topoisomerase Proteins 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 1
- 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 1
- 229940009456 adriamycin Drugs 0.000 claims 1
- 229940100198 alkylating agent Drugs 0.000 claims 1
- 239000002168 alkylating agent Substances 0.000 claims 1
- 230000036765 blood level Effects 0.000 claims 1
- 210000000481 breast Anatomy 0.000 claims 1
- 229960004562 carboplatin Drugs 0.000 claims 1
- 190000008236 carboplatin Chemical compound 0.000 claims 1
- 201000010881 cervical cancer Diseases 0.000 claims 1
- 210000003679 cervix uteri Anatomy 0.000 claims 1
- 229960004316 cisplatin Drugs 0.000 claims 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims 1
- 210000001072 colon Anatomy 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 229960000975 daunorubicin Drugs 0.000 claims 1
- 230000004069 differentiation Effects 0.000 claims 1
- 229960003668 docetaxel Drugs 0.000 claims 1
- 210000004696 endometrium Anatomy 0.000 claims 1
- 230000002708 enhancing effect Effects 0.000 claims 1
- 230000001667 episodic effect Effects 0.000 claims 1
- 229960004750 estramustine phosphate Drugs 0.000 claims 1
- ADFOJJHRTBFFOF-RBRWEJTLSA-N estramustine phosphate Chemical group ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)OP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 ADFOJJHRTBFFOF-RBRWEJTLSA-N 0.000 claims 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical group 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 claims 1
- 229960005420 etoposide Drugs 0.000 claims 1
- 229960000390 fludarabine Drugs 0.000 claims 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims 1
- 229960002949 fluorouracil Drugs 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 230000002440 hepatic effect Effects 0.000 claims 1
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 229960001330 hydroxycarbamide Drugs 0.000 claims 1
- 229960000908 idarubicin Drugs 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 208000032839 leukemia Diseases 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 208000003747 lymphoid leukemia Diseases 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 229960001924 melphalan Drugs 0.000 claims 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims 1
- 229960000485 methotrexate Drugs 0.000 claims 1
- 229960004857 mitomycin Drugs 0.000 claims 1
- 208000025113 myeloid leukemia Diseases 0.000 claims 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims 1
- 230000002611 ovarian Effects 0.000 claims 1
- 210000001672 ovary Anatomy 0.000 claims 1
- 229960001756 oxaliplatin Drugs 0.000 claims 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims 1
- 229960001592 paclitaxel Drugs 0.000 claims 1
- 210000000496 pancreas Anatomy 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 229960004694 prednimustine Drugs 0.000 claims 1
- 206010041823 squamous cell carcinoma Diseases 0.000 claims 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 201000003120 testicular cancer Diseases 0.000 claims 1
- 238000012360 testing method Methods 0.000 claims 1
- 210000001550 testis Anatomy 0.000 claims 1
- 229960003048 vinblastine Drugs 0.000 claims 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound 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 1
- 229960004528 vincristine Drugs 0.000 claims 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical group 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 claims 1
- 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 claims 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
- A61K31/59—Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring 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
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/891,814 | 2001-06-26 | ||
| US09/891,814 US6503893B2 (en) | 1996-12-30 | 2001-06-26 | Method of treating hyperproliferative diseases using active vitamin D analogues |
| PCT/US2002/020475 WO2003000023A2 (en) | 2001-06-26 | 2002-06-26 | Method of treating hyperproliferative diseases using active vitamin d analogues |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2450942A1 true CA2450942A1 (en) | 2003-01-03 |
Family
ID=25398862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002450942A Abandoned CA2450942A1 (en) | 2001-06-26 | 2002-06-26 | Method of treating hyperproliferative diseases using active vitamin d analogues |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US6503893B2 (enExample) |
| EP (1) | EP1408983A4 (enExample) |
| JP (1) | JP2004535429A (enExample) |
| KR (1) | KR20040015753A (enExample) |
| CN (1) | CN1234366C (enExample) |
| AU (1) | AU2002322346B2 (enExample) |
| CA (1) | CA2450942A1 (enExample) |
| IL (1) | IL159068A0 (enExample) |
| MX (1) | MXPA03011307A (enExample) |
| WO (1) | WO2003000023A2 (enExample) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040009958A1 (en) * | 1991-01-08 | 2004-01-15 | Bone Care International, Inc. | Methods for preparation and use of 1alpha,24(S)-dihydroxyvitamin D2 |
| US5763429A (en) * | 1993-09-10 | 1998-06-09 | Bone Care International, Inc. | Method of treating prostatic diseases using active vitamin D analogues |
| US6566353B2 (en) * | 1996-12-30 | 2003-05-20 | Bone Care International, Inc. | Method of treating malignancy associated hypercalcemia using active vitamin D analogues |
| US20020128240A1 (en) * | 1996-12-30 | 2002-09-12 | Bone Care International, Inc. | Treatment of hyperproliferative diseases using active vitamin D analogues |
| US6316642B1 (en) * | 1997-03-17 | 2001-11-13 | Wisconsin Alumni Research Foundation | 26,27-Homologated-20-EPI-2alkyl-19-nor-vitamin D compounds |
| US6392071B1 (en) * | 1997-03-17 | 2002-05-21 | Wisconsin Alumni: Research Foundation | 26,27-homologated-20-EPI-2-alkylidene-19-nor-vitamin D compounds |
| US6087350A (en) * | 1997-08-29 | 2000-07-11 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Use of pretreatment chemicals to enhance efficacy of cytotoxic agents |
| EP2340840B1 (en) * | 1998-03-27 | 2012-08-29 | Oregon Health Sciences University | Pulse dose Vitamin D drug for the treatment of hyperproliferative skin diseases |
| GB9920548D0 (en) * | 1999-08-31 | 1999-11-03 | Rhone Poulenc Rorer Sa | Treatment of hepatocellular carcinoma |
| JP2005515996A (ja) * | 2001-12-03 | 2005-06-02 | ノバセア インコーポレイティッド | 活性型ビタミンｄ化合物を含む薬学的組成物 |
| US7259143B2 (en) * | 2002-09-05 | 2007-08-21 | Wisconsin Alumni Research Foundation | Method of extending the dose range of vitamin D compounds |
| US20080249068A1 (en) * | 2002-09-05 | 2008-10-09 | Deluca Hector F | Method of Extending the Dose Range of Vitamin D Compounds |
| US20040058895A1 (en) * | 2002-09-18 | 2004-03-25 | Bone Care International, Inc. | Multi-use vessels for vitamin D formulations |
| US7148211B2 (en) * | 2002-09-18 | 2006-12-12 | Genzyme Corporation | Formulation for lipophilic agents |
| US20040053895A1 (en) * | 2002-09-18 | 2004-03-18 | Bone Care International, Inc. | Multi-use vessels for vitamin D formulations |
| US20050026877A1 (en) * | 2002-12-03 | 2005-02-03 | Novacea, Inc. | Pharmaceutical compositions comprising active vitamin D compounds |
| US20050020546A1 (en) * | 2003-06-11 | 2005-01-27 | Novacea, Inc. | Pharmaceutical compositions comprising active vitamin D compounds |
| US20050222190A1 (en) * | 2004-03-30 | 2005-10-06 | Curd John G | 1,4-bis-N-oxide azaanthracenediones and the use thereof |
| US7094775B2 (en) * | 2004-06-30 | 2006-08-22 | Bone Care International, Llc | Method of treating breast cancer using a combination of vitamin D analogues and other agents |
| US20060003950A1 (en) * | 2004-06-30 | 2006-01-05 | Bone Care International, Inc. | Method of treating prostatic diseases using a combination of vitamin D analogues and other agents |
| US20060189543A1 (en) * | 2005-02-23 | 2006-08-24 | Rosenbloom Richard A | Compositions and methods for the treatment of leukemia |
| US7914810B2 (en) * | 2005-05-06 | 2011-03-29 | Synthes Usa, Llc | Methods for the in situ treatment of bone cancer |
| EP1993559B1 (en) | 2006-02-03 | 2016-06-22 | OPKO Renal, LLC | Treating vitamin d insufficiency and deficiency with 25-hydroxyvitamin d2 and 25-hydroxyvitamin d3 |
| ES2670029T3 (es) | 2006-06-21 | 2018-05-29 | Opko Ireland Global Holdings, Ltd. | Terapia usando agente de repleción de la vitamina D y agente de reemplazo de la hormona de la vitamina D |
| TW200833345A (en) * | 2006-11-01 | 2008-08-16 | Novacea Inc | Use of vitamin D compounds and mimics thereof to enhance delivery of therapeutics and oxygen to tumors and other tissues |
| US8501717B2 (en) * | 2007-02-09 | 2013-08-06 | Merck, Sharp & Dohme Corp. | Methods to treat and/or prevent mucositis |
| CA2683628C (en) | 2007-04-25 | 2018-03-06 | Cytochroma Inc. | Method of treating vitamin d insufficiency and deficiency |
| HRP20231142T3 (hr) | 2007-04-25 | 2024-01-05 | Eirgen Pharma Ltd. | Kontrolirano oslobađanje 25-hidroksivitamina d |
| JP2010525080A (ja) * | 2007-04-25 | 2010-07-22 | プロヴェンティヴ セラピュティックス リミテッド ライアビリティ カンパニー | 慢性腎臓病における続発性副甲状腺機能亢進症の安全かつ効果的な治療および予防方法 |
| ES2954932T3 (es) | 2008-04-02 | 2023-11-27 | Eirgen Pharma Ltd | Métodos, composiciones, usos y kits útiles para la deficiencia de vitamina D y trastornos relacionados |
| US20100009934A1 (en) * | 2008-06-09 | 2010-01-14 | Combinatorx, Incorporated | Beta adrenergic receptor agonists for the treatment of b-cell proliferative disorders |
| CA2750659C (en) | 2009-01-27 | 2017-11-21 | Berg Biosystems, Llc | Vitamin d3 and analogs thereof for alleviating side effects associated with chemotherapy |
| EA201270226A1 (ru) | 2009-08-14 | 2012-09-28 | БЕРГ БАЙОСИСТЕМЗ, ЭлЭлСи | Витамин d3 и его аналогии для лечения алопеции |
| WO2011123476A1 (en) | 2010-03-29 | 2011-10-06 | Cytochroma Inc. | Methods and compositions for reducing parathyroid levels |
| KR101847947B1 (ko) | 2013-03-15 | 2018-05-28 | 옵코 아이피 홀딩스 Ⅱ 인코포레이티드 | 안정화되고 변형된 비타민 ｄ 방출 제형 |
| HK1222819A1 (zh) | 2013-05-29 | 2017-07-14 | 博格有限责任公司 | 使用维生素d预防或减轻化疗诱发的脱发 |
| US10220047B2 (en) | 2014-08-07 | 2019-03-05 | Opko Ireland Global Holdings, Ltd. | Adjunctive therapy with 25-hydroxyvitamin D and articles therefor |
| CN104710485B (zh) * | 2015-01-13 | 2017-06-27 | 南京理工大学 | 维生素d2糖苷类似物、合成及应用 |
| CN108883120A (zh) | 2016-03-28 | 2018-11-23 | 欧普科爱尔兰环球控股有限公司 | 维生素d治疗方法 |
Family Cites Families (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2383446A (en) | 1941-06-04 | 1945-08-28 | Du Pont | Antirachitic materials and processes for their production |
| US3697559A (en) | 1971-02-25 | 1972-10-10 | Wisconsin Alumni Res Found | 1,25-dihydroxycholecalciferol |
| US3741996A (en) | 1971-12-02 | 1973-06-26 | Wisconsin Alumni Res Found | 1{60 -hydroxycholecalciferol |
| US4670190A (en) | 1973-01-10 | 1987-06-02 | Hesse Robert H | 1-α-hydroxy vitamin D compounds and process for preparing same |
| US3907843A (en) | 1974-06-14 | 1975-09-23 | Wisconsin Alumni Res Found | 1{60 -Hydroxyergocalciferol and processes for preparing same |
| US4202829A (en) | 1978-01-05 | 1980-05-13 | Wisconsin Alumni Research Foundation | Process for preparing 1α-hydroxylated compounds |
| FR2446278A2 (en) | 1978-01-16 | 1980-08-08 | Wisconsin Alumni Res Found | 1-alpha-hydroxy-vitamin=D deriv. preparation - by solvolysis of 1-alpha-hydroxy-cyclo-vitamin=D using carboxylic acid e.g. acetic to give 3 O-acyl cpd. which is hydrolysed or reduced |
| US4260549A (en) | 1979-05-21 | 1981-04-07 | Wisconsin Alumni Research Foundation | Process for preparing 1α-hydroxylated compounds |
| US4195027A (en) | 1978-01-16 | 1980-03-25 | Wisconsin Alumni Research Foundation | Process for preparing 1α-hydroxylated compounds |
| US4225596A (en) | 1978-10-13 | 1980-09-30 | Wisconsin Alumni Research Foundation | Method for treating calcium imbalance and improving calcium absorption in mammals |
| US4234495A (en) | 1979-09-10 | 1980-11-18 | Wisconsin Alumni Research Foundation | Process for preparing 1α-hydroxyvitamin D compounds from 1α-hydroxy-3,5-cyclovitamin D compounds |
| US4362710A (en) | 1980-07-04 | 1982-12-07 | Nissan Gosei Kogyo Co., Ltd. | Feeds for baby pigs, process for preparing the same and method of breeding baby pigs |
| JPS57149224A (en) | 1981-03-13 | 1982-09-14 | Chugai Pharmaceut Co Ltd | Tumor-suppressing agent |
| CH655396B (enExample) | 1981-11-11 | 1986-04-15 | ||
| US4508651A (en) | 1983-03-21 | 1985-04-02 | Hoffmann-La Roche Inc. | Synthesis of 1α,25-dihydroxyergocalciferol |
| AU568549B2 (en) | 1983-05-09 | 1988-01-07 | Wisconsin Alumni Research Foundation | Process for the preparation of 1a, 25-dihydroxylated vitamin d2 and related compounds |
| US4689180A (en) | 1984-01-30 | 1987-08-25 | Wisconsin Alumni Research Foundation | 1α,25-dihydroxy-22Z-dehydroxyvitamin D compound |
| US4588716A (en) | 1984-05-04 | 1986-05-13 | Wisconsin Alumni Research Foundation | Method for treating metabolic bone disease in mammals |
| US4554106A (en) | 1984-11-01 | 1985-11-19 | Wisconsin Alumni Research Foundation | Method for preparing 1α-hydroxyvitamin D compounds |
| US4555364A (en) | 1984-11-01 | 1985-11-26 | Wisconsin Alumni Research Foundation | Method for preparing 1-hydroxyvitamin D compounds |
| US4661294A (en) | 1985-03-18 | 1987-04-28 | The General Hospital Corporation | Biologically active 1-thio derivatives of vitamin D |
| IL78342A (en) | 1985-04-04 | 1991-06-10 | Gen Hospital Corp | Pharmaceutical composition for treatment of osteoporosis in humans comprising a parathyroid hormone or a fragment thereof |
| JPH07100685B2 (ja) | 1985-08-02 | 1995-11-01 | レオ・ファ−マシュ−ティカル・プロダクツ・リミテッド・エイ／エス（レ−ベンス・ケミスケ・ファブリック・プロデュクチオンスアクチ−セルスカブ） | 新規ビタミンｄ類似体 |
| US4833125A (en) | 1986-12-05 | 1989-05-23 | The General Hospital Corporation | Method of increasing bone mass |
| JP2550391B2 (ja) | 1988-06-30 | 1996-11-06 | 日清製粉株式会社 | １β−ヒドロキシビタミンＤ▲下２▼およびＤ▲下３▼の製造方法 |
| US5602116A (en) | 1988-08-02 | 1997-02-11 | Bone Care International, Inc. | Method for treating and preventing secondary hyperparathyroidism |
| US5104864A (en) | 1988-08-02 | 1992-04-14 | Bone Care International, Inc. | Method for treating and preventing loss of bone mass |
| CA1333616C (en) | 1989-03-09 | 1994-12-20 | Hector F. Deluca | 19-nor-vitamin d compounds |
| US5372996A (en) | 1989-03-10 | 1994-12-13 | Endorecherche, Inc. | Method of treatment of androgen-related diseases |
| JP2645130B2 (ja) | 1989-03-31 | 1997-08-25 | 日清製粉株式会社 | ステロイド誘導体 |
| GB2229921B (en) | 1989-04-05 | 1992-12-16 | Chugai Pharmaceutical Co Ltd | Treatment for hyperparathyroidism with use of vitamin d derivatives |
| US5801164A (en) | 1990-09-21 | 1998-09-01 | Bone Care International, Inc. | Methods of treating osteoporosis prophylactically or therapeutically |
| US6025346A (en) | 1990-09-21 | 2000-02-15 | Bone Care International, Inc. | 1α-hydroxy vitamin D4 and novel intermediates and analogues |
| ES2169023T3 (es) | 1990-09-21 | 2002-07-01 | Bone Care Int Inc | Nueva 1alfa-hidroxi vitaminada d4 y nuevos intermedios y analogos. |
| US5798345A (en) | 1990-09-21 | 1998-08-25 | Bone Care International, Inc. | Method of inhibiting the hyperproliferation of malignant cells |
| US5763428A (en) | 1990-09-21 | 1998-06-09 | Bone Care International, Inc. | Methods of treating skin disorders with novel 1a-hydroxy vitamin D4 compounds and derivatives thereof |
| US6538037B2 (en) * | 1991-01-08 | 2003-03-25 | Bone Care International, Inc. | Methods for preparation and use of 1α,24(S)-dihydroxyvitamin D2 |
| US5789397A (en) | 1991-01-08 | 1998-08-04 | Bone Care International, Inc. | Methods for preparation and use of 1A,24(S)-dihydroxy vitamin D2 |
| US6166000A (en) | 1991-01-08 | 2000-12-26 | Bone Care International, Inc. | Methods for preparation and use of 1α,24(S)-Dihydroxy vitamin . D.sub2 |
| DK0550702T3 (da) | 1991-01-08 | 1999-11-01 | Bone Care Int Inc | Fremgangsmåde til fremstilling og anvendelse af 1alfa,24-dihydroxy-vitamin D2 |
| JP3030157B2 (ja) | 1991-03-13 | 2000-04-10 | 株式会社クラレ | シクロヘキサントリオール誘導体 |
| HUT66379A (en) | 1991-05-28 | 1994-11-28 | Procter & Gamble | Calcium, trace mineral, vitamin d and drug therapy combinations |
| AU650751B2 (en) | 1991-05-28 | 1994-06-30 | Wisconsin Alumni Research Foundation | Novel synthesis of 19-nor vitamin D compounds |
| EP0541852B1 (en) | 1991-11-14 | 1997-04-23 | Digital Equipment International Limited | Spindle and hub assembly |
| AU682817B2 (en) | 1992-01-29 | 1997-10-23 | Bone Care International, Inc. | 1alpha-hydroxy-24-(epi)-vitamin D4 |
| EP0562497A1 (en) | 1992-03-27 | 1993-09-29 | Nisshin Flour Milling Co., Ltd. | 1 alpha-hydroxy vitamins D7 and D4' processes for the preparation thereof and pharmaceutical compositions |
| AU4841193A (en) | 1992-08-28 | 1994-03-29 | Lunar Corporation | 1alpha,24(S)-dihydroxy vitamin D2, its formation and use |
| US5350745A (en) | 1993-01-29 | 1994-09-27 | Lunar Corporation | Treatment of myocardial failure |
| US5763429A (en) | 1993-09-10 | 1998-06-09 | Bone Care International, Inc. | Method of treating prostatic diseases using active vitamin D analogues |
| EP0664287B1 (en) | 1994-01-20 | 1998-07-15 | Duphar International Research B.V | Vitamin D compounds and method of preparing these compounds |
| US5763427A (en) * | 1995-03-31 | 1998-06-09 | Hamilton Civic Hospitals Research Development Inc. | Compositions and methods for inhibiting thrombogenesis |
| DE19549243A1 (de) | 1995-12-21 | 1997-06-26 | Schering Ag | Pharmazeutische Präparate enthaltend Clathrate von Cyclodextrinen und nichtnatürliche Vitamin D-Analoga |
| US6034074A (en) | 1996-09-13 | 2000-03-07 | New Life Pharmaceuticals Inc. | Prevention of ovarian cancer by administration of a Vitamin D compound |
| WO1998020123A2 (en) * | 1996-11-04 | 1998-05-14 | Institut Curie | Stable cell lines expressing the cftr protein or a mutant of this protein, tool for selecting molecules having an effect on the intracellular transport of these proteins |
| AUPO727097A0 (en) | 1997-06-10 | 1997-07-03 | Unisearch Limited | Method of treatment of hepatoma and pharmaceutical compositions for use therein |
| US6087350A (en) | 1997-08-29 | 2000-07-11 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Use of pretreatment chemicals to enhance efficacy of cytotoxic agents |
| WO1999049027A1 (en) | 1998-03-25 | 1999-09-30 | Cutanogen, Inc. | Methods for prevention and treatment of cancer |
| EP2340840B1 (en) * | 1998-03-27 | 2012-08-29 | Oregon Health Sciences University | Pulse dose Vitamin D drug for the treatment of hyperproliferative skin diseases |
| US20010002396A1 (en) | 1998-07-16 | 2001-05-31 | Charles Achkar | Compositions and methods of treating skin conditions |
| CA2385755C (en) | 1999-09-29 | 2007-02-06 | Colotech A/S | Prevention of colorectal cancer |
| DK1276482T3 (da) | 2000-03-02 | 2008-05-26 | Univ Pittsburgh | Kombinationskemoterapi |
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2001
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| IL159068A0 (en) | 2004-05-12 |
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| JP2004535429A (ja) | 2004-11-25 |
| US20030130242A1 (en) | 2003-07-10 |
| CN1234366C (zh) | 2006-01-04 |
| US6680309B2 (en) | 2004-01-20 |
| WO2003000023A3 (en) | 2003-07-31 |
| KR20040015753A (ko) | 2004-02-19 |
| EP1408983A4 (en) | 2007-05-09 |
| US20020025950A1 (en) | 2002-02-28 |
| MXPA03011307A (es) | 2004-06-08 |
| US6503893B2 (en) | 2003-01-07 |
| WO2003000023A2 (en) | 2003-01-03 |
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