ES2338428T3 - Tratamiento de la enfermedad inflamatoria del intestino con compuestos de 2-metilen-19-nor-vitamina d. - Google Patents
Tratamiento de la enfermedad inflamatoria del intestino con compuestos de 2-metilen-19-nor-vitamina d. Download PDFInfo
- Publication number
- ES2338428T3 ES2338428T3 ES04778892T ES04778892T ES2338428T3 ES 2338428 T3 ES2338428 T3 ES 2338428T3 ES 04778892 T ES04778892 T ES 04778892T ES 04778892 T ES04778892 T ES 04778892T ES 2338428 T3 ES2338428 T3 ES 2338428T3
- Authority
- ES
- Spain
- Prior art keywords
- methylene
- dihydroxyvitamin
- dehydrovitamin
- dihydroxy
- vitamin
- 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.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 42
- 238000011282 treatment Methods 0.000 title claims description 16
- 208000027866 inflammatory disease Diseases 0.000 title description 3
- 210000000936 intestine Anatomy 0.000 title description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 41
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 208000011231 Crohn disease Diseases 0.000 claims abstract description 7
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 4
- 229930003316 Vitamin D Natural products 0.000 claims description 46
- 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 description 46
- 235000019166 vitamin D Nutrition 0.000 claims description 46
- 239000011710 vitamin D Substances 0.000 claims description 46
- 229940046008 vitamin d Drugs 0.000 claims description 46
- 229960005084 calcitriol Drugs 0.000 claims description 24
- -1 vitamin D compound Chemical class 0.000 claims description 19
- 229960003783 24-homo-1,25-dihydroxyvitamin d3 Drugs 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 208000003099 inflammatory bowel disease 2 Diseases 0.000 claims 1
- 238000011161 development Methods 0.000 abstract description 10
- 238000000034 method Methods 0.000 abstract description 9
- 239000011612 calcitriol Substances 0.000 abstract description 6
- 230000001934 delay Effects 0.000 abstract 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 38
- 241000699670 Mus sp. Species 0.000 description 19
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 16
- 108090000174 Interleukin-10 Proteins 0.000 description 15
- 102000003814 Interleukin-10 Human genes 0.000 description 15
- 239000000203 mixture Substances 0.000 description 13
- GMRQFYUYWCNGIN-UHFFFAOYSA-N 1,25-Dihydroxy-vitamin D3' Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CC(O)C1=C GMRQFYUYWCNGIN-UHFFFAOYSA-N 0.000 description 12
- GMRQFYUYWCNGIN-ZVUFCXRFSA-N 1,25-dihydroxy vitamin D3 Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=CC=C1C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-ZVUFCXRFSA-N 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 238000009472 formulation Methods 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 229910052791 calcium Inorganic materials 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000010171 animal model Methods 0.000 description 5
- 210000000988 bone and bone Anatomy 0.000 description 5
- 239000003246 corticosteroid Substances 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- 229940088594 vitamin Drugs 0.000 description 5
- 239000011782 vitamin Substances 0.000 description 5
- 102000009310 vitamin D receptors Human genes 0.000 description 5
- 108050000156 vitamin D receptors Proteins 0.000 description 5
- 208000037147 Hypercalcaemia Diseases 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 206010047626 Vitamin D Deficiency Diseases 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 150000002431 hydrogen Chemical group 0.000 description 4
- 230000000148 hypercalcaemia Effects 0.000 description 4
- 210000000987 immune system Anatomy 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 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 4
- 229960004618 prednisone Drugs 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 230000009469 supplementation Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 229930003231 vitamin Natural products 0.000 description 4
- 235000013343 vitamin Nutrition 0.000 description 4
- KJKIIUAXZGLUND-ICCVIKJNSA-N 25-hydroxyvitamin 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)CCC1=C KJKIIUAXZGLUND-ICCVIKJNSA-N 0.000 description 3
- 206010065687 Bone loss Diseases 0.000 description 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- 210000001744 T-lymphocyte Anatomy 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 230000000125 calcaemic effect Effects 0.000 description 3
- 235000020964 calcitriol Nutrition 0.000 description 3
- GMRQFYUYWCNGIN-NKMMMXOESA-N calcitriol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C GMRQFYUYWCNGIN-NKMMMXOESA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 206010009887 colitis Diseases 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 229910052805 deuterium Inorganic materials 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 208000010227 enterocolitis Diseases 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 208000030915 hypercalcemia disease Diseases 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 150000003722 vitamin derivatives Chemical class 0.000 description 3
- ATMUYWZMPLKPEJ-XLMAVXFVSA-N (1r,3ar,7ar)-7a-methyl-1-[(2r)-6-methylheptan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-one Chemical compound O=C1CCC[C@]2(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@H]21 ATMUYWZMPLKPEJ-XLMAVXFVSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 2
- 125000001118 alkylidene group Chemical group 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000018678 bone mineralization Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 125000005345 deuteroalkyl group Chemical group 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 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 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229940079322 interferon Drugs 0.000 description 2
- 238000007737 ion beam deposition Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 206010041569 spinal fracture Diseases 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 235000020799 vitamin D status Nutrition 0.000 description 2
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 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)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- VJIOBQLKFJUZJB-IBOOZMTFSA-N (1r,3ar,7ar)-1-[(e,2r,5r)-5,6-dimethylhept-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-one Chemical compound O=C1CCC[C@]2(C)[C@@H]([C@H](C)/C=C/[C@H](C)C(C)C)CC[C@H]21 VJIOBQLKFJUZJB-IBOOZMTFSA-N 0.000 description 1
- OQANPHBRHBJGNZ-FYJGNVAPSA-N (3e)-6-oxo-3-[[4-(pyridin-2-ylsulfamoyl)phenyl]hydrazinylidene]cyclohexa-1,4-diene-1-carboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=C\C1=N\NC1=CC=C(S(=O)(=O)NC=2N=CC=CC=2)C=C1 OQANPHBRHBJGNZ-FYJGNVAPSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- 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 description 1
- JWUBBDSIWDLEOM-UHFFFAOYSA-N 25-Hydroxycholecalciferol Natural products C1CCC2(C)C(C(CCCC(C)(C)O)C)CCC2C1=CC=C1CC(O)CCC1=C JWUBBDSIWDLEOM-UHFFFAOYSA-N 0.000 description 1
- JWUBBDSIWDLEOM-DCHLRESJSA-N 25-Hydroxyvitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C/C=C1\C[C@@H](O)CCC1=C JWUBBDSIWDLEOM-DCHLRESJSA-N 0.000 description 1
- JWUBBDSIWDLEOM-NQZHSCJISA-N 25-hydroxy-3 epi cholecalciferol Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=CC=C1C[C@H](O)CCC1=C JWUBBDSIWDLEOM-NQZHSCJISA-N 0.000 description 1
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
- 241001149231 Arachnis x Vanda Species 0.000 description 1
- 208000000412 Avitaminosis Diseases 0.000 description 1
- 208000013725 Chronic Kidney Disease-Mineral and Bone disease Diseases 0.000 description 1
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 241001125048 Sardina Species 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 description 1
- 206010047627 Vitamin deficiencies Diseases 0.000 description 1
- 201000006035 X-linked dominant hypophosphatemic rickets Diseases 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 125000005466 alkylenyl group Chemical group 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 230000004094 calcium homeostasis Effects 0.000 description 1
- OKTJSMMVPCPJKN-YPZZEJLDSA-N carbon-10 atom Chemical compound [10C] OKTJSMMVPCPJKN-YPZZEJLDSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000001721 carboxyacetyl group Chemical group 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 229960002061 ergocalciferol Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 208000011111 hypophosphatemic rickets Diseases 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000031261 interleukin-10 production Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 244000005706 microflora Species 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- QHJWOSHIGFDANE-UHFFFAOYSA-N prop-2-enylphosphane Chemical compound PCC=C QHJWOSHIGFDANE-UHFFFAOYSA-N 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 201000006409 renal osteodystrophy Diseases 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000032349 type 2B vitamin D-dependent rickets Diseases 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000001892 vitamin D2 Nutrition 0.000 description 1
- 239000011653 vitamin D2 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound 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-YRZJJWOYSA-N 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K31/59—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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/680,881 US7704980B2 (en) | 2003-10-08 | 2003-10-08 | Treatment of inflammatory bowel disease with 2-methylene-19-nor-vitamin D compounds |
| US680881 | 2003-10-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2338428T3 true ES2338428T3 (es) | 2010-05-07 |
Family
ID=34422197
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES04778892T Expired - Lifetime ES2338428T3 (es) | 2003-10-08 | 2004-07-23 | Tratamiento de la enfermedad inflamatoria del intestino con compuestos de 2-metilen-19-nor-vitamina d. |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US7704980B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1673095B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2007508298A (cg-RX-API-DMAC7.html) |
| AT (1) | ATE448788T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2004283073B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2541991A1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE602004024221D1 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2338428T3 (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ546440A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2005039592A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011017165A1 (en) * | 2009-08-03 | 2011-02-10 | Wisconsin Alumni Research Foundation | Method of preventing renal disease and treating symptoms thereof |
| ES2545403T3 (es) * | 2010-03-23 | 2015-09-10 | Wisconsin Alumni Research Foundation | (20S)-2-metilen-19-nor-22-dimetil-1alfa,25-dihidroxivitamina D3 y (20R)-2-metilen-19-nor-22-dimetil-1alfa,25-hidroxivitamina D3 |
| US8664206B2 (en) | 2010-03-23 | 2014-03-04 | Wisconsin Alumni Research Foundation | Diastereomers of 2-methylene-19-nor-22-methyl-1α,25-dihydroxyvitamin D3 |
| WO2011119622A1 (en) * | 2010-03-23 | 2011-09-29 | Wisconsin Alumni Research Foundation | DIASTEREOMERS OF 2-METHYLENE-19-NOR-22-METHYL-1α,25- DIHYDROXYVITAMIN D3 |
| FR2961401B1 (fr) * | 2010-06-17 | 2013-04-05 | Laetitia Mathez | Composition anti-inflammatoire |
| CN102631354B (zh) * | 2011-02-11 | 2015-01-21 | 广东泰禾医药科技有限公司 | 含维生素d3和二甲双胍的药物组合物 |
| US9834512B2 (en) | 2011-06-03 | 2017-12-05 | Wisconsin Alumni Research Foundation | (22E)-2-methylene-26,27-cyclo-22-dehydro-1α-hydroxy-19-norvitamin D3 derivatives |
| US20130295083A1 (en) * | 2012-05-02 | 2013-11-07 | Wisconsin Alumni Research Foundation | 2a-Methyl-19-nor-(20S)-1a,25-dihydroxyvitamin D3 (2AMD) or 2 methylene-19-nor-(20S)-1a,25-dihydroxyvitamin D3 (2MD) Support Survival and Function of Transplanted Islet Cells In Type 1 Diabetes |
| RU2666995C2 (ru) | 2012-06-29 | 2018-09-13 | Висконсин Алюмни Рисерч Фаундейшн | ПРИМЕНЕНИЕ 2-МЕТИЛЕН-19-НОР-(20S)-1α,25-ДИГИДРОКСИВИТАМИНА D3 ДЛЯ ЛЕЧЕНИЯ ВТОРИЧНОГО ГИПЕРПАРАТИРЕОЗА |
| US9370527B2 (en) | 2012-12-28 | 2016-06-21 | The Regents Of The University Of Michigan | Amelioration of intestinal fibrosis and treatment of Crohn's disease |
| US9539264B2 (en) | 2014-12-30 | 2017-01-10 | Wisconsin Alumni Research Foundation | Use of 2-methylene-19-nor-(20S)-1-alpha,25-dihydroxyvitamin D3 to treat secondary hyperparathyroidism in patients previously treated with calcimimetics |
| US10369161B2 (en) | 2014-12-30 | 2019-08-06 | Wisconsin Alumni Research Foundation | Use of 2-methylene-19-NOR-(20S)-1-alpha,25-dihydroxyvitamin D3 to treat primary hyperparathyroidism |
| WO2017184262A1 (en) * | 2016-04-18 | 2017-10-26 | Wisconsin Alumni Research Foundation | Use of 2amd and 2md to treat fibrosis |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4221961A1 (de) * | 1992-06-30 | 1994-01-05 | Schering Ag | 22-En-25-oxa-Derivate in der Vitamin D-Reihe, Verfahren zu ihrer Herstellung, diese Derivate enthaltenen pharmazeutische Präparate sowie deren Verwendung als Arzneimittel |
| IL107185A (en) * | 1992-10-06 | 1998-02-22 | Schering Ag | Vitamin d, 25-carboxylic acid derivatives and pharmaceutical compositions containing the same |
| US5981597A (en) * | 1995-02-13 | 1999-11-09 | Trustees Of The University Of Pennsylvania | Differentiating agents for the treatment of inflammatory intestinal diseases |
| US6392071B1 (en) * | 1997-03-17 | 2002-05-21 | Wisconsin Alumni: Research Foundation | 26,27-homologated-20-EPI-2-alkylidene-19-nor-vitamin D compounds |
| US5843928A (en) * | 1997-03-17 | 1998-12-01 | Wisconsin Alumni Research Foundation | 2-alkylidene-19-nor-vitamin D compounds |
| US6989377B2 (en) * | 1999-12-21 | 2006-01-24 | Wisconsin Alumni Research Foundation | Treating vitamin D responsive diseases |
| US6358939B1 (en) * | 1999-12-21 | 2002-03-19 | Northern Lights Pharmaceuticals, Llc | Use of biologically active vitamin D compounds for the prevention and treatment of inflammatory bowel disease |
| AU2001265272B2 (en) * | 2000-05-31 | 2006-08-17 | Wisconsin Alumni Research Foundation | 2-ethyl and 2-ethylidene-19-nor-vitamin d compounds |
| BR0113703A (pt) * | 2000-09-08 | 2003-07-22 | Wisconsin Alumni Researcg Foun | Compostos e métodos de tratamento de psorìase, leucemia, câncer do cólon, do seio ou da próstata, osteodistrofia renal, de doenças auto-imune, inflamatória e de condição de pele |
| ES2315426T3 (es) * | 2001-12-13 | 2009-04-01 | Wisconsin Alumni Research Foundation | (20s)-1alfa-hidroxi-2-metileno-19-nor-bishomopregnacalciferol y sus usos. |
| US6566352B1 (en) * | 2002-02-18 | 2003-05-20 | Wisconsin Alumni Research Foudation | 1 α-hydroxy-2-methylene-19-nor-pregnacalciferol and its uses |
| US7259143B2 (en) * | 2002-09-05 | 2007-08-21 | Wisconsin Alumni Research Foundation | Method of extending the dose range of vitamin D compounds |
-
2003
- 2003-10-08 US US10/680,881 patent/US7704980B2/en not_active Expired - Fee Related
-
2004
- 2004-07-23 CA CA002541991A patent/CA2541991A1/en not_active Abandoned
- 2004-07-23 AT AT04778892T patent/ATE448788T1/de not_active IP Right Cessation
- 2004-07-23 JP JP2006533831A patent/JP2007508298A/ja not_active Ceased
- 2004-07-23 EP EP04778892A patent/EP1673095B1/en not_active Expired - Lifetime
- 2004-07-23 WO PCT/US2004/023586 patent/WO2005039592A1/en not_active Ceased
- 2004-07-23 DE DE602004024221T patent/DE602004024221D1/de not_active Expired - Lifetime
- 2004-07-23 NZ NZ546440A patent/NZ546440A/xx not_active IP Right Cessation
- 2004-07-23 ES ES04778892T patent/ES2338428T3/es not_active Expired - Lifetime
- 2004-07-23 AU AU2004283073A patent/AU2004283073B2/en not_active Expired
-
2010
- 2010-02-17 US US12/707,358 patent/US20100160267A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20100160267A1 (en) | 2010-06-24 |
| AU2004283073B2 (en) | 2010-05-27 |
| CA2541991A1 (en) | 2005-05-06 |
| NZ546440A (en) | 2009-08-28 |
| EP1673095B1 (en) | 2009-11-18 |
| DE602004024221D1 (de) | 2009-12-31 |
| ATE448788T1 (de) | 2009-12-15 |
| AU2004283073A1 (en) | 2005-05-06 |
| JP2007508298A (ja) | 2007-04-05 |
| EP1673095A1 (en) | 2006-06-28 |
| US20050080059A1 (en) | 2005-04-14 |
| US7704980B2 (en) | 2010-04-27 |
| WO2005039592A1 (en) | 2005-05-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1250225C (zh) | 2α－甲基－19－去甲－20(S)－1α,25－二羟维生素D3生产用于增加骨强度的药物的用途 | |
| ES2274116T3 (es) | 1-alfa-hidroxi-2-metilenj-19-nor-pregnacalciferol y sus usos. | |
| ES2227215T3 (es) | 1 alfa-hidroxi.2.metilen-19-nor-homopregnacalciferol y sus aplicaciones terapeuticas. | |
| US20100160267A1 (en) | Treatment of Inflammatory Bowel Disease With 2-Methylene-19-Nor-Vitamin D Compounds | |
| US7259143B2 (en) | Method of extending the dose range of vitamin D compounds | |
| US7115594B2 (en) | Use of 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3 to increase bone strength | |
| US20080249068A1 (en) | Method of Extending the Dose Range of Vitamin D Compounds | |
| ES2399328T3 (es) | Uso de 2-metilen-19-nor-20(S)-1a,25-dihidroxivitamina D3 para la profilaxis de enfermedades óseas | |
| ES2249013T3 (es) | Compuestos de 19-nor-vitamina d3 con actividad calcemica. | |
| AU4510001A (en) | Treatment of inflammatory bowel disease with vitamin d compounds | |
| MXPA06003974A (en) | Treatment of inflammatory bowel disease with 2-methylene-19-nor-vitamin d compounds | |
| MXPA06009640A (en) | USE OF 2-METHYLENE-19-NOR-20(S)-1alpha,25-DIHYDROXYVITAMIN D3 |