JP5770261B2 - （２０Ｓ）−２−メチレン−１９−ノル−２２−ジメチル−１α，２５−ジヒドロキシビタミンＤ３および（２０Ｒ）−２−メチレン−１９−ノル−２２−ジメチル−１α，２５−ヒドロキシビタミンＤ３ - Google Patents
（２０Ｓ）−２−メチレン−１９−ノル−２２−ジメチル−１α，２５−ジヒドロキシビタミンＤ３および（２０Ｒ）−２−メチレン−１９−ノル−２２−ジメチル−１α，２５−ヒドロキシビタミンＤ３ Download PDFInfo
- Publication number
- JP5770261B2 JP5770261B2 JP2013501398A JP2013501398A JP5770261B2 JP 5770261 B2 JP5770261 B2 JP 5770261B2 JP 2013501398 A JP2013501398 A JP 2013501398A JP 2013501398 A JP2013501398 A JP 2013501398A JP 5770261 B2 JP5770261 B2 JP 5770261B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- pharmaceutical composition
- mmol
- biological condition
- dimethyl
- 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 - Fee Related
Links
- 239000011612 calcitriol Substances 0.000 title description 32
- 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 title 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 title 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 title 1
- 150000001875 compounds Chemical class 0.000 claims description 102
- 239000000203 mixture Substances 0.000 claims description 45
- -1 t-butyldimethylsilyl groups Chemical group 0.000 claims description 39
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 7
- 206010060862 Prostate cancer Diseases 0.000 claims description 7
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 7
- 201000004681 Psoriasis Diseases 0.000 claims description 7
- 206010052779 Transplant rejections Diseases 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 201000006417 multiple sclerosis Diseases 0.000 claims description 7
- 210000000056 organ Anatomy 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 208000032839 leukemia Diseases 0.000 claims description 6
- 206010025135 lupus erythematosus Diseases 0.000 claims description 6
- 210000002374 sebum Anatomy 0.000 claims description 6
- 230000028327 secretion Effects 0.000 claims description 6
- 208000029742 colonic neoplasm Diseases 0.000 claims description 5
- 208000013725 Chronic Kidney Disease-Mineral and Bone disease Diseases 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 201000006409 renal osteodystrophy Diseases 0.000 claims description 4
- 230000037303 wrinkles Effects 0.000 claims description 4
- 208000015943 Coeliac disease Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 3
- 238000011200 topical administration Methods 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 122
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 122
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
- 239000011734 sodium Substances 0.000 description 45
- 239000000243 solution Substances 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 41
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 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 31
- 239000011575 calcium Substances 0.000 description 28
- 229910052791 calcium Inorganic materials 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000000034 method Methods 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 22
- 230000000694 effects Effects 0.000 description 22
- 238000005516 engineering process Methods 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 101000931108 Mus musculus DNA (cytosine-5)-methyltransferase 1 Proteins 0.000 description 18
- 101000798092 Mus musculus tRNA (cytosine(38)-C(5))-methyltransferase Proteins 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 239000000377 silicon dioxide Substances 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 210000000988 bone and bone Anatomy 0.000 description 12
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000003643 water by type Substances 0.000 description 12
- 239000012230 colorless oil Substances 0.000 description 11
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 11
- 230000003389 potentiating effect Effects 0.000 description 11
- 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 10
- 201000010099 disease Diseases 0.000 description 10
- 238000009472 formulation Methods 0.000 description 10
- 150000002576 ketones Chemical class 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 108090000623 proteins and genes Proteins 0.000 description 10
- 230000032258 transport Effects 0.000 description 10
- TXTGPWLZHZYCQV-YFOXLAJYSA-N (8s,9s,10s,13r,14s,17s)-10,13-dimethyl-17-propyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthrene Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CCC)[C@@]1(C)CC2 TXTGPWLZHZYCQV-YFOXLAJYSA-N 0.000 description 9
- 230000004069 differentiation Effects 0.000 description 9
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 9
- 230000000968 intestinal effect Effects 0.000 description 9
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 229930003316 Vitamin D Natural products 0.000 description 8
- 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 description 8
- 230000027455 binding Effects 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 8
- 239000011710 vitamin D Substances 0.000 description 8
- 235000019166 vitamin D Nutrition 0.000 description 8
- 229940046008 vitamin d Drugs 0.000 description 8
- 241000700159 Rattus Species 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 230000024245 cell differentiation Effects 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 150000002009 diols Chemical class 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 6
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- STMPXDBGVJZCEX-UHFFFAOYSA-N triethylsilyl trifluoromethanesulfonate Chemical compound CC[Si](CC)(CC)OS(=O)(=O)C(F)(F)F STMPXDBGVJZCEX-UHFFFAOYSA-N 0.000 description 6
- 150000003722 vitamin derivatives Chemical class 0.000 description 6
- NEEJBPZVIFKIMU-WTCULTLOSA-N CCC[C@H]1CC[C@H]2[C@@]3(CCC4CCCC[C@]4(C)[C@H]3CC[C@]12C)O Chemical compound CCC[C@H]1CC[C@H]2[C@@]3(CCC4CCCC[C@]4(C)[C@H]3CC[C@]12C)O NEEJBPZVIFKIMU-WTCULTLOSA-N 0.000 description 5
- 244000089409 Erythrina poeppigiana Species 0.000 description 5
- 235000009776 Rathbunia alamosensis Nutrition 0.000 description 5
- 229910004161 SiNa Inorganic materials 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 229940088597 hormone Drugs 0.000 description 5
- 239000005556 hormone Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 229940088594 vitamin Drugs 0.000 description 5
- 229930003231 vitamin Natural products 0.000 description 5
- 235000013343 vitamin Nutrition 0.000 description 5
- 239000011782 vitamin Substances 0.000 description 5
- 150000003710 vitamin D derivatives Chemical class 0.000 description 5
- 102000009310 vitamin D receptors Human genes 0.000 description 5
- 108050000156 vitamin D receptors Proteins 0.000 description 5
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 4
- 235000020964 calcitriol Nutrition 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 229940043279 diisopropylamine Drugs 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 108091008039 hormone receptors Proteins 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000004305 normal phase HPLC Methods 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 4
- 230000035897 transcription Effects 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 4
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 3
- 101000573199 Homo sapiens Protein PML Proteins 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229940126543 compound 14 Drugs 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 102000054896 human PML Human genes 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 230000005758 transcription activity Effects 0.000 description 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- 102100027518 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial Human genes 0.000 description 2
- 101710191280 1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial Proteins 0.000 description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229940126657 Compound 17 Drugs 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- COHYTHOBJLSHDF-UHFFFAOYSA-N Indigo Chemical compound N1C2=CC=CC=C2C(=O)C1=C1C(=O)C2=CC=CC=C2N1 COHYTHOBJLSHDF-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 208000005770 Secondary Hyperparathyroidism Diseases 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000003118 aryl group Chemical group 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
- 230000008033 biological extinction Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000002449 bone cell Anatomy 0.000 description 2
- 229960005084 calcitriol Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 230000009137 competitive binding Effects 0.000 description 2
- 229940125846 compound 25 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125898 compound 5 Drugs 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 2
- 229940074439 potassium sodium tartrate Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 238000004007 reversed phase HPLC Methods 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-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
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-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
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- MDKIZGHFZJHYNK-UCQQBFDRSA-N CC(C(CC1)[C@@](C)(CCC2)C1/C2=C/C=C(C[C@H](C1=C)O)C[C@H]1O)C(C)(C)CCC(C)(C)O Chemical compound CC(C(CC1)[C@@](C)(CCC2)C1/C2=C/C=C(C[C@H](C1=C)O)C[C@H]1O)C(C)(C)CCC(C)(C)O MDKIZGHFZJHYNK-UCQQBFDRSA-N 0.000 description 1
- MDKIZGHFZJHYNK-LWUDMKPESA-N C[C@@H](C(CC1)[C@@](C)(CCC2)C1/C2=C/C=C(C[C@H](C1=C)O)C[C@H]1O)C(C)(C)CCC(C)(C)O Chemical compound C[C@@H](C(CC1)[C@@](C)(CCC2)C1/C2=C/C=C(C[C@H](C1=C)O)C[C@H]1O)C(C)(C)CCC(C)(C)O MDKIZGHFZJHYNK-LWUDMKPESA-N 0.000 description 1
- GHPLEKNBRWIYBF-ROQCGBJPSA-N C[C@@H]([C@@H](CC1)[C@@](C)(CCC2)C1/C2=C/C=C(\C[C@H](C1=C)O)/C[C@H]1[O]#C)C(C)(C)CCC(C)(C)O Chemical compound C[C@@H]([C@@H](CC1)[C@@](C)(CCC2)C1/C2=C/C=C(\C[C@H](C1=C)O)/C[C@H]1[O]#C)C(C)(C)CCC(C)(C)O GHPLEKNBRWIYBF-ROQCGBJPSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 238000005718 Kornblum oxidation reaction Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 241000282458 Ursus sp. Species 0.000 description 1
- 201000006035 X-linked dominant hypophosphatemic rickets Diseases 0.000 description 1
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 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 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 125000000746 allylic group Chemical group 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000005784 autoimmunity Effects 0.000 description 1
- 230000004888 barrier function Effects 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
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000000125 calcaemic effect Effects 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 230000004094 calcium homeostasis Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000001721 carboxyacetyl group Chemical group 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- UMCMPZBLKLEWAF-UHFFFAOYSA-N chaps detergent Chemical compound OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)C1(C)C(O)C2 UMCMPZBLKLEWAF-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 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 1
- 230000037336 dry skin Effects 0.000 description 1
- 230000000668 effect on calcium Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 150000002137 ergosterols 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
- 239000012894 fetal calf serum Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 208000011111 hypophosphatemic rickets Diseases 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography 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
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000002540 macrophage Anatomy 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
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical group 0.000 description 1
- JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 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
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 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
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000004765 promyelocyte Anatomy 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000007665 sagging Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 239000001962 taste-modifying agent 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
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000002103 transcriptional 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
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C401/00—Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/24—All rings being cycloaliphatic the ring system containing nine carbon atoms, e.g. perhydroindane
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Toxicology (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US31663110P | 2010-03-23 | 2010-03-23 | |
| US61/316,631 | 2010-03-23 | ||
| PCT/US2011/029432 WO2011119610A2 (en) | 2010-03-23 | 2011-03-22 | (20S)-2-METHYLENE-19-NOR-22-DIMETHYL-1α,25- DIHYDROXYVITAMIN D3 AND (20R)-2-METHYLENE-19-NOR-22- DIMETHYL-1α,25-HYDROXYVITAMIN D3 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013522369A JP2013522369A (ja) | 2013-06-13 |
| JP2013522369A5 JP2013522369A5 (enExample) | 2014-05-08 |
| JP5770261B2 true JP5770261B2 (ja) | 2015-08-26 |
Family
ID=44170321
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013501398A Expired - Fee Related JP5770261B2 (ja) | 2010-03-23 | 2011-03-22 | （２０Ｓ）−２−メチレン−１９−ノル−２２−ジメチル−１α，２５−ジヒドロキシビタミンＤ３および（２０Ｒ）−２−メチレン−１９−ノル−２２−ジメチル−１α，２５−ヒドロキシビタミンＤ３ |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8604009B2 (enExample) |
| EP (1) | EP2556053B1 (enExample) |
| JP (1) | JP5770261B2 (enExample) |
| AU (1) | AU2011232633B2 (enExample) |
| CA (1) | CA2794006C (enExample) |
| ES (1) | ES2545403T3 (enExample) |
| WO (1) | WO2011119610A2 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8884039B2 (en) | 2012-05-30 | 2014-11-11 | Wisconsin Alumni Research Foundation | Crystallization of (20R) and (20S) analogs of 2-methylene-19-nor-24-dimethyl-1α,25-dihydroxyvitamin D3 |
| US9205096B2 (en) | 2012-06-29 | 2015-12-08 | Wisconsin Alumni Research Foundation | Use of 2-methylene-19-nor-(20S)-1α,25-dihydroxyvitamin D3 to treat secondary hyperparathyroidism |
| US9539231B2 (en) | 2014-01-17 | 2017-01-10 | The Regents Of The University Of Colorado, A Body Corporate | Method for treating triple-negative breast cancer using AMPI-109 |
| 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 |
| 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 |
Family Cites Families (64)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1333616C (en) | 1989-03-09 | 1994-12-20 | Hector F. Deluca | 19-nor-vitamin d compounds |
| US5246925A (en) | 1989-03-09 | 1993-09-21 | Wisconsin Alumni Research Foundation | 19-nor-vitamin D compounds for use in treating hyperparathyroidism |
| JPH0695892B2 (ja) | 1990-01-12 | 1994-11-30 | 伊藤忠飼料株式会社 | 体脂肪の畜積量を減少させる飼料 |
| US5086191A (en) | 1991-05-28 | 1992-02-04 | Wisconsin Alumni Research Foundation | Intermediates for the synthesis of 19-nor vitamin D compounds |
| EP0619306B1 (en) | 1993-04-05 | 1996-09-11 | Wisconsin Alumni Research Foundation | 19-Nor-vitamin D3 compounds with substituent at 2-position |
| JP3210156B2 (ja) | 1993-10-18 | 2001-09-17 | マツダ株式会社 | 自動車の前部車体構造 |
| US5552392A (en) | 1993-11-03 | 1996-09-03 | Wisconsin Alumni Research Foundation | Method of treating hypoparathyroidism with (20S) vitamin D compounds |
| US5843928A (en) | 1997-03-17 | 1998-12-01 | Wisconsin Alumni Research Foundation | 2-alkylidene-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 |
| US6316642B1 (en) | 1997-03-17 | 2001-11-13 | Wisconsin Alumni Research Foundation | 26,27-Homologated-20-EPI-2alkyl-19-nor-vitamin D compounds |
| US5945410A (en) | 1997-03-17 | 1999-08-31 | Wisconsin Alumni Research Foundation | 2-alkyl-19-nor-vitamin D compounds |
| US6306844B1 (en) | 1997-03-17 | 2001-10-23 | Wisconsin Alumni Research Foundation | Use of 2α-methyl-19-nor-20(S)-1α, 25-dihydroxyvitamin D3 to increase bone strength |
| US6114317A (en) | 1998-05-21 | 2000-09-05 | Wisconsin Alumni Research Foundation | Method of locking 1α-OH of vitamin D compounds in axial orientation |
| DE60031666T2 (de) | 1999-04-01 | 2007-08-30 | The Johns Hopkins University | NICHT-CALCEMISCHE, TRANSKRIPTIONELL-AKTIVE, SCHWEFELHALTIGE ANALOGA VON 1-alpha, 25-DIHYDROXYVITAMIN D3 MIT ANTIPROLIFERATIVER WIRKUNG |
| DE60134549D1 (de) | 2000-05-31 | 2008-08-07 | Wisconsin Alumni Res Found | 2-ethyl und 2-ethyliden-19-nor-vitamin d-verbindungen |
| WO2002005823A2 (en) | 2000-07-14 | 2002-01-24 | Wisconsin Alumni Research Foundation | USE OF 2-METHYLENE-19-NOR-20(S)-1α,25-DIHYDROXYVITAMIN D3 TO INCREASE BONE STRENGTH |
| US6384087B1 (en) | 2000-09-01 | 2002-05-07 | University Of Tennesseee Research Corporation, Inc. | Materials and methods for the treatment or prevention of obesity |
| KR100672886B1 (ko) | 2000-09-08 | 2007-01-24 | 위스콘신 얼럼나이 리서어치 화운데이션 | 1α-히드록시-2-메틸렌-19-노르-호모프레그나칼시페롤 및그의 치료적 용도 |
| US6835723B2 (en) | 2001-12-13 | 2004-12-28 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-20(S)-1α-hydroxy-bis-homo-pregnacalciferol in crystalline form |
| US6627622B2 (en) | 2002-02-18 | 2003-09-30 | Wisconsin Alumni Research Foundation | (20S)-1α-hydroxy-2-methylene-19-nor-bishomopregnacalciferol and its uses |
| US6566352B1 (en) | 2002-02-18 | 2003-05-20 | Wisconsin Alumni Research Foudation | 1 α-hydroxy-2-methylene-19-nor-pregnacalciferol and its uses |
| CN1277817C (zh) | 2002-03-29 | 2006-10-04 | 威斯康星校友研究基金会 | 合成1α－羟基－2－亚甲基－19－去甲－高孕钙化醇的方法 |
| US6846811B2 (en) | 2002-04-22 | 2005-01-25 | Wisconsin Alumni Research Foundation | (20S) 1α-hydroxy-2α-methyl and 2β-methyl-19-nor-vitamin D3 and their uses |
| US20080249068A1 (en) | 2002-09-05 | 2008-10-09 | Deluca Hector F | Method of Extending the Dose Range of Vitamin D Compounds |
| US6894037B2 (en) | 2003-07-03 | 2005-05-17 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-20(S)-25-methyl-1α-hydroxycalciferol and its uses |
| ATE537834T1 (de) | 2003-08-20 | 2012-01-15 | Wisconsin Alumni Res Found | 2-methylen-19-nor-vitamin d2-verbindungen |
| WO2005027913A1 (en) | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and a growth hormone secretagogue |
| WO2005027915A1 (en) | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and parathyroid hormone |
| WO2005027931A1 (en) | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and an ep2 or ep4 selective agonist |
| WO2005027924A1 (en) | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and an estrogen agonist/antagonist |
| WO2005027929A1 (en) | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Pharmaceutical compositions and methods comprising combinations of 2-alkylidene-19-nor-vitamin d derivatives and an estrogen |
| US7214670B2 (en) | 2003-09-24 | 2007-05-08 | Wisconsin Alumni Research Foundation | Use of 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3 to increase the life expectancy of human beings |
| US7704980B2 (en) | 2003-10-08 | 2010-04-27 | Wisconsin Alumni Research Foundation | Treatment of inflammatory bowel disease with 2-methylene-19-nor-vitamin D compounds |
| EP1689412A4 (en) | 2003-11-25 | 2009-03-11 | Wisconsin Alumni Res Found | VITAMIN D ANALOGUE FOR THE PREVENTION AND TREATMENT OF ADIPOSITAS |
| US7053075B2 (en) | 2003-11-25 | 2006-05-30 | Deluca Hector F | Methods for reducing body fat using vitamin D compounds |
| US7915242B2 (en) | 2004-02-17 | 2011-03-29 | Wisconsin Alumni Research Foundation | Vitamin D receptor antagonists and their use in treating asthma |
| US7214671B2 (en) | 2004-02-19 | 2007-05-08 | Wisconsin Alumni Research Foundation | Use of 2-methylene-19-nor-20(S)-1α,25-dihydroxyvitamin D3 for the prophylaxis of bone diseases |
| US7713951B2 (en) | 2004-04-09 | 2010-05-11 | Wisconsin Alumni Research Foundation | 2-alkylidene-18,19-dinor-vitamin D compounds |
| ES2349662T3 (es) | 2004-11-22 | 2011-01-10 | Wisconsin Alumni Research Foundation | 2-metileno-18,19-dinor-1alfa-hidroxi-homopregnacalciferol y sus usos. |
| AU2005309791A1 (en) | 2004-11-22 | 2006-06-01 | Wisconsin Alumni Research Foundation | 2-methylene-19,26,27-trinor-(20S)-1alpha-hydroxyvitamin D3 and its uses |
| AU2005309819A1 (en) | 2004-11-22 | 2006-06-01 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-(20S)-1alpha-hydroxy-trishomopregnacalciferol |
| MX2007006263A (es) | 2004-11-22 | 2007-07-10 | Wisconsin Alumni Res Found | Analogos 2a-metil y 2??-metil de 19,26,27-trinor-(20s)-1a- hidroxivitamina d3 y sus usos. |
| EP1846369A2 (en) | 2004-11-22 | 2007-10-24 | Wisconsin Alumni Research Foundation | 2alpha-methyl-19-nor-(20s)-1alpha-hydroxy-bishomopregnacalciferol and its uses |
| ES2344989T3 (es) | 2004-11-22 | 2010-09-13 | Wisconsin Alumni Research Foundation | Analogos de 17,20(e)-deshidro vitamina d y sus usos. |
| MX2007009726A (es) | 2005-02-11 | 2007-09-26 | Wisconsin Alumni Res Found | 2-metilen-19-nor-(20s-24s)-1a, 25-dihidroxivitamina-d2. |
| AU2006213722B2 (en) | 2005-02-11 | 2011-09-22 | Wisconsin Alumni Research Foundation | 2-methylene-19-nor-(20S-24epi)-1alpha,25-dihydroxyvitamin-D2 |
| MX2007011919A (es) | 2005-03-29 | 2007-11-22 | Wisconsin Alumni Res Found | 2-metilen-19-nor-(23s)-25-deshidro-1a-hidroxivitamina d3-26,23-lactona y 2-metilen19-nor-(23r)-25-deshidro-1a- hidroxivitamina d3-26,23-lactona. |
| CA2605727A1 (en) | 2005-05-03 | 2006-11-09 | Wisconsin Alumni Research Foundation | 19,26,27-trinor-1.alpha.,25-dihydroxyvitamin d3 compounds |
| NZ571773A (en) | 2006-04-06 | 2011-11-25 | Wisconsin Alumni Res Found | 2-Methylene-1alpha,25-dihydroxy-18,19,21-trinorvitamin D3 and uses thereof |
| JP2009532458A (ja) | 2006-04-06 | 2009-09-10 | ウイスコンシン アラムニ リサーチ ファンデーション | ２−メチレン−１α−ヒドロキシ−１９，２１−ジノルビタミンＤ３類縁体およびその使用 |
| JP2010505739A (ja) | 2006-04-06 | 2010-02-25 | ウイスコンシン アラムニ リサーチ ファンデーション | ２−メチレン−１α，２５−ジヒドロキシ−１９，２１−ジノルビタミンＤ３類縁体およびその使用 |
| NZ575111A (en) | 2006-09-28 | 2012-02-24 | Wisconsin Alumni Res Found | 2-methylene-(20r,25s)-19,27-dinor-(22e)-vitamin d analogs |
| US8377913B2 (en) * | 2007-11-20 | 2013-02-19 | Abbvie Inc. | Vitamin D receptor activators and methods of making |
| US7718638B2 (en) | 2007-12-28 | 2010-05-18 | Wisconsin Alumni Research Foundation | (20R)-23,23-difluoro-2-methylene-19-nor-bishomopregnacalciferol-vitamin D analogs |
| MX2010007266A (es) | 2007-12-28 | 2010-11-30 | Wisconsin Alumni Res Found | Análogos de vitamina d, (20s)-23, 23-difluoro-2-metilen-19-nor-bis homopregnacalciferol. |
| CA2710970A1 (en) | 2007-12-28 | 2009-07-09 | Wisconsin Alumni Research Foundation | 2-methylene-(20s,25r)-19,26-dinor-vitamin d analogs |
| US8143238B2 (en) | 2008-03-06 | 2012-03-27 | Wisconsin Alumni Research Foundation | Methods of increasing epidermal skin thickness by topical administration of a 19-nor containing vitamin D compound |
| CA2717362A1 (en) | 2008-03-10 | 2009-09-17 | Wisconsin Alumni Research Foundation | Vitamin d compounds and methods for reducing ocular hypertension (oht) |
| US8399439B2 (en) | 2008-07-10 | 2013-03-19 | Wisconsin Alumni Research Foundation | 2-methylene-19,26-dinor-(20S,22E,25R)-vitamin D analogs |
| US8193170B2 (en) | 2008-07-10 | 2012-06-05 | Wisconsin Alumni Research Foundation | 2-methylene-19,26-dinor-(20R,22E,25R)-vitamin D analogs |
| US7893043B2 (en) | 2008-07-10 | 2011-02-22 | Wisconsin Alumni Research Foundation | 2-methylene-(17Z)-17(20)-dehydro-19,21-dinor-vitamin D analogs |
| US7888339B2 (en) | 2008-07-10 | 2011-02-15 | Wisconsin Alumni Research Foundation | 2-methylene-20(21)-dehydro-19-nor-vitamin D analogs |
| JP5908402B2 (ja) | 2009-08-03 | 2016-04-26 | ウィスコンシン・アルムニ・リサーチ・ファウンデーションＷｉｓｃｏｎｓｉｎ Ａｌｕｍｎｉ Ｒｅｓｅａｒｃｈ Ｆｏｕｎｄａｔｉｏｎ | 腎疾患の予防方法およびその症状を処置する方法 |
| US8445468B2 (en) | 2009-10-02 | 2013-05-21 | Wisconsin Alumni Research Foundation | (20S,22E)-2-methylene-19-nor-22-ene-1α,25-dihydroxyvitamin D3 |
-
2011
- 2011-03-22 EP EP11711237.5A patent/EP2556053B1/en not_active Not-in-force
- 2011-03-22 JP JP2013501398A patent/JP5770261B2/ja not_active Expired - Fee Related
- 2011-03-22 US US13/053,844 patent/US8604009B2/en active Active
- 2011-03-22 CA CA2794006A patent/CA2794006C/en not_active Expired - Fee Related
- 2011-03-22 WO PCT/US2011/029432 patent/WO2011119610A2/en not_active Ceased
- 2011-03-22 AU AU2011232633A patent/AU2011232633B2/en not_active Ceased
- 2011-03-22 ES ES11711237.5T patent/ES2545403T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2011232633B2 (en) | 2014-05-29 |
| AU2011232633A1 (en) | 2012-10-18 |
| CA2794006C (en) | 2017-11-28 |
| CA2794006A1 (en) | 2011-09-29 |
| JP2013522369A (ja) | 2013-06-13 |
| ES2545403T3 (es) | 2015-09-10 |
| WO2011119610A2 (en) | 2011-09-29 |
| US20110237556A1 (en) | 2011-09-29 |
| AU2011232633A8 (en) | 2012-11-01 |
| WO2011119610A3 (en) | 2012-11-29 |
| EP2556053B1 (en) | 2015-07-29 |
| US8604009B2 (en) | 2013-12-10 |
| EP2556053A2 (en) | 2013-02-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5113766B2 (ja) | ビタミンｄ類似体：ｒａｋ、その方法および使用 | |
| JP2009525980A (ja) | ビタミンｄ類似体：ｎｅｌ、その方法および使用 | |
| JP6383365B2 (ja) | （２２Ｅ）−２−メチレン−２２−デヒドロ−１α，２４，２５−トリヒドロキシ−１９−ノル−ビタミンＤ３類似体 | |
| JP2008520689A (ja) | １９，２６，２７−トリノル−（２０Ｓ）−１α−ヒドロキシビタミンＤ３の２α−メチルおよび２β−メチル類似体およびそれらの使用 | |
| JP2009532458A (ja) | ２−メチレン−１α−ヒドロキシ−１９，２１−ジノルビタミンＤ３類縁体およびその使用 | |
| JP2011507966A (ja) | ２−メチレン−２０−メチル−１９，２４，２５，２６，２７−ペンタノル−ビタミンｄ類縁体 | |
| JP5770261B2 (ja) | （２０Ｓ）−２−メチレン−１９−ノル−２２−ジメチル−１α，２５−ジヒドロキシビタミンＤ３および（２０Ｒ）−２−メチレン−１９−ノル−２２−ジメチル−１α，２５−ヒドロキシビタミンＤ３ | |
| JP5043673B2 (ja) | １７，２０（ｅ）−デヒドロビタミンｄ類似体およびそれらの使用 | |
| JP2010504995A (ja) | ２−メチレン−（２０ｒ，２５ｓ）−１９，２７−ジノル−（２２ｅ）−ビタミンｄ類縁体 | |
| JP2008520691A (ja) | ２−メチレン−１９，２６，２７−トリノル−（２０Ｓ）−１α−ヒドロキシビタミンＤ３およびその使用 | |
| JP5036566B2 (ja) | ２−メチレン−１９−ノル−（２０Ｓ−２４Ｓ）−１α，２５−ジヒドロキシビタミン−Ｄ２ | |
| JP2011508744A (ja) | （２０ｒ）−２３，２３−ジフルオロ−２−メチレン−１９−ノル−ビスホモプレグナカルシフェロール−ビタミンｄ類縁体 | |
| JP2008520709A (ja) | ２−メチレン−１９−ノル−（２０Ｓ）−１α−ヒドロキシ−トリスホモプレグナカルシフェロール | |
| JP5629682B2 (ja) | ２−メチレン−（１７ｚ）−１７（２０）−デヒドロ−１９，２１−ジノル−ビタミンｄ類似物質 | |
| JP2008520708A (ja) | ２−メチレン−１９−ノル−（２０Ｒ）−１α−ヒドロキシ−ビスホモプレグナカルシフェロール | |
| JP2010504994A (ja) | ２−メチレン−（２０ｓ，２５ｓ）−１９，２７−ジノル−（２２ｅ）−ビタミンｄ類縁体 | |
| JP5036565B2 (ja) | ２−メチレン−１９−ノル−（２０Ｓ−２４エピ）−１α，２５−ジヒドロキシビタミン−Ｄ２ | |
| JP5043674B2 (ja) | ２−メチレン−１８，１９−ジノル−１α−ヒドロキシ−ホモプレグナカルシフェロール及びその使用 | |
| JP2008538214A (ja) | ２−メチレン−１９−ノル−（２３Ｓ）−２５−デヒドロ−１α−ヒドロキシビタミンＤ３−２６，２３−ラクトンおよび２−メチレン−１９−ノル−（２３Ｒ）−２５−デヒドロ−１α−ヒドロキシビタミンＤ３−２６，２３−ラクトン | |
| JP2011527700A (ja) | ２−メチレン−２０（２１）−デヒドロ−１９−ノル−ビタミンｄ類似物質 | |
| JP5931845B2 (ja) | ２−メチレン−１９−ノル−２２−メチル−１α，２５−ジヒドロキシビタミンＤ３のジアステレオマー | |
| JP2013512259A (ja) | ２−メチレン−１９，２６−ノル−（２０Ｓ）−１α−ヒドロキシビタミンＤ３ | |
| JP5036548B2 (ja) | ２−メチレン−１９，２１−ジノル−１α−ヒドロキシ−ビスホモプレグナカルシフェロール | |
| JP2009533418A (ja) | １，１−ジメチルプロピル側鎖を持つ１α−ヒドロキシ−２−（３’−ヒドロキシプロピリデン）−１９−ノル−ビタミンＤ化合物 | |
| JP2009532457A (ja) | ２−メチレン−１α−ヒドロキシ−１８，１９，２１−トリノルビタミンＤ３類縁体およびその使用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140319 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140319 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20141224 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150316 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20150514 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20150603 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20150624 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5770261 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |