JP2011527699A - ２−メチレン−１９，２６−ジノル−（２０ｓ，２２ｅ，２５ｒ）−ビタミンｄ類似物質 - Google Patents
２−メチレン−１９，２６−ジノル−（２０ｓ，２２ｅ，２５ｒ）−ビタミンｄ類似物質 Download PDFInfo
- Publication number
- JP2011527699A JP2011527699A JP2011517621A JP2011517621A JP2011527699A JP 2011527699 A JP2011527699 A JP 2011527699A JP 2011517621 A JP2011517621 A JP 2011517621A JP 2011517621 A JP2011517621 A JP 2011517621A JP 2011527699 A JP2011527699 A JP 2011527699A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- administered
- day
- formula
- methylene
- 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.)
- Pending
Links
- 239000011710 vitamin D Substances 0.000 title abstract description 20
- 229940046008 vitamin d Drugs 0.000 title abstract description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 132
- 239000011612 calcitriol Substances 0.000 claims abstract description 27
- 230000004069 differentiation Effects 0.000 claims abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 11
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 208000013725 Chronic Kidney Disease-Mineral and Bone disease Diseases 0.000 claims abstract description 8
- 201000006409 renal osteodystrophy Diseases 0.000 claims abstract description 8
- 208000008589 Obesity Diseases 0.000 claims abstract description 7
- 235000020824 obesity Nutrition 0.000 claims abstract description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 5
- 210000002374 sebum Anatomy 0.000 claims abstract description 5
- 230000028327 secretion Effects 0.000 claims abstract description 5
- 230000037303 wrinkles Effects 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 85
- 239000000203 mixture Substances 0.000 claims description 35
- 241001465754 Metazoa Species 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 108090000623 proteins and genes Proteins 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 13
- 238000013518 transcription Methods 0.000 claims description 13
- 230000035897 transcription Effects 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 210000001789 adipocyte Anatomy 0.000 claims description 8
- 210000000577 adipose tissue Anatomy 0.000 claims description 8
- AEDMQUAPBVOJNN-UHFFFAOYSA-N [3-[2-[4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl]-1,3-thiazol-5-yl]-1,2,4-oxadiazol-5-yl]methanol Chemical compound O1C(CO)=NC(C=2SC(=NC=2)N2CCC(CC2)OC=2C(=CC=CC=2)C(F)(F)F)=N1 AEDMQUAPBVOJNN-UHFFFAOYSA-N 0.000 claims description 6
- 208000032839 leukemia Diseases 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 206010009944 Colon cancer Diseases 0.000 claims description 5
- 206010060862 Prostate cancer Diseases 0.000 claims description 5
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 5
- 208000029742 colonic neoplasm Diseases 0.000 claims description 5
- 201000000849 skin cancer Diseases 0.000 claims description 5
- 230000037393 skin firmness Effects 0.000 claims description 4
- 206010052779 Transplant rejections Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 206010025135 lupus erythematosus Diseases 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 48
- 239000011575 calcium Substances 0.000 abstract description 38
- 229910052791 calcium Inorganic materials 0.000 abstract description 38
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 34
- 210000000988 bone and bone Anatomy 0.000 abstract description 19
- 210000004027 cell Anatomy 0.000 abstract description 18
- 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 abstract description 14
- 230000000968 intestinal effect Effects 0.000 abstract description 14
- 239000003814 drug Substances 0.000 abstract description 12
- 239000005556 hormone Substances 0.000 abstract description 10
- 229940088597 hormone Drugs 0.000 abstract description 10
- 238000001727 in vivo Methods 0.000 abstract description 6
- 239000002246 antineoplastic agent Substances 0.000 abstract description 5
- 230000002103 transcriptional effect Effects 0.000 abstract description 5
- 206010013786 Dry skin Diseases 0.000 abstract description 4
- 230000037336 dry skin Effects 0.000 abstract description 4
- 238000007665 sagging Methods 0.000 abstract description 4
- 210000001616 monocyte Anatomy 0.000 abstract description 3
- 208000037979 autoimmune inflammatory disease Diseases 0.000 abstract 1
- 230000001939 inductive effect Effects 0.000 abstract 1
- 230000035755 proliferation Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 63
- 101100203600 Caenorhabditis elegans sor-1 gene Proteins 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 238000005481 NMR spectroscopy Methods 0.000 description 31
- 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 28
- 239000000243 solution Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 230000024245 cell differentiation Effects 0.000 description 19
- 239000011734 sodium Substances 0.000 description 18
- -1 vitamin D compounds Chemical class 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 15
- JKNVNYIZDQXTQP-ZYWSVXDBSA-N (8R,9R,10S,13R,14R,17S)-17-ethyl-10,13-dimethyl-1,2,3,4,5,6,7,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-8-ol Chemical compound O[C@@]12[C@@H]3CC[C@H](CC)[C@]3(CC[C@@H]2[C@]2(CCCCC2CC1)C)C JKNVNYIZDQXTQP-ZYWSVXDBSA-N 0.000 description 14
- JWMFYGXQPXQEEM-NUNROCCHSA-N 5β-pregnane Chemical compound C([C@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](CC)[C@@]2(C)CC1 JWMFYGXQPXQEEM-NUNROCCHSA-N 0.000 description 14
- 229930003316 Vitamin D Natural products 0.000 description 13
- 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 13
- 230000027455 binding Effects 0.000 description 13
- 235000019166 vitamin D Nutrition 0.000 description 13
- 102000009310 vitamin D receptors Human genes 0.000 description 13
- 108050000156 vitamin D receptors Proteins 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 230000002829 reductive effect Effects 0.000 description 12
- 238000010898 silica gel chromatography Methods 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 230000037213 diet Effects 0.000 description 7
- 235000005911 diet Nutrition 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 150000003710 vitamin D derivatives Chemical class 0.000 description 7
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 230000033001 locomotion Effects 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- 239000000725 suspension Substances 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
- PKFBWEUIKKCWEW-WEZTXPJVSA-N (1r,3r)-5-[(2e)-2-[(1r,3as,7ar)-1-[(2r)-6-hydroxy-6-methylheptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]cyclohexane-1,3-diol Chemical class C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](CCCC(C)(C)O)C)=C\C=C1C[C@@H](O)C[C@H](O)C1 PKFBWEUIKKCWEW-WEZTXPJVSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 101000573199 Homo sapiens Protein PML Proteins 0.000 description 4
- 208000001132 Osteoporosis Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 208000005770 Secondary Hyperparathyroidism Diseases 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 102000054896 human PML Human genes 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 210000000936 intestine Anatomy 0.000 description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 150000003722 vitamin derivatives Chemical class 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- IYWFYZSFLYICJP-MRXNPFEDSA-N [(3r)-3-triethylsilyloxybutyl] 4-methylbenzenesulfonate Chemical compound CC[Si](CC)(CC)O[C@H](C)CCOS(=O)(=O)C1=CC=C(C)C=C1 IYWFYZSFLYICJP-MRXNPFEDSA-N 0.000 description 3
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 208000017520 skin disease Diseases 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 230000005758 transcription activity Effects 0.000 description 3
- DNQHWLRVTGAQJN-SNVBAGLBSA-N triethyl-[(2r)-4-iodobutan-2-yl]oxysilane Chemical compound CC[Si](CC)(CC)O[C@H](C)CCI DNQHWLRVTGAQJN-SNVBAGLBSA-N 0.000 description 3
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000015943 Coeliac disease Diseases 0.000 description 2
- 206010009900 Colitis ulcerative Diseases 0.000 description 2
- 208000011231 Crohn disease Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 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
- 244000089409 Erythrina poeppigiana Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-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
- 241000286209 Phasianidae Species 0.000 description 2
- 235000009776 Rathbunia alamosensis Nutrition 0.000 description 2
- 229910004161 SiNa Inorganic materials 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 description 2
- 206010000496 acne Diseases 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000001118 alkylidene group Chemical group 0.000 description 2
- 231100000360 alopecia Toxicity 0.000 description 2
- 239000003963 antioxidant agent 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
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000002449 bone cell Anatomy 0.000 description 2
- LWQQLNNNIPYSNX-UROSTWAQSA-N calcipotriol Chemical compound C1([C@H](O)/C=C/[C@@H](C)[C@@H]2[C@]3(CCCC(/[C@@H]3CC2)=C\C=C\2C([C@@H](O)C[C@H](O)C/2)=C)C)CC1 LWQQLNNNIPYSNX-UROSTWAQSA-N 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- 208000035475 disorder Diseases 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
- 239000003995 emulsifying agent Substances 0.000 description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 2
- 208000026278 immune system disease Diseases 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 230000001483 mobilizing effect Effects 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 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
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 150000004714 phosphonium salts Chemical class 0.000 description 2
- 239000006187 pill Substances 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
- 230000000069 prophylactic effect Effects 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
- 230000008591 skin barrier function Effects 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (1R)-1,3-butanediol Natural products CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- PUPZLCDOIYMWBV-SCSAIBSYSA-N (R)-butane-1,3-diol Chemical compound C[C@@H](O)CCO PUPZLCDOIYMWBV-SCSAIBSYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-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
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- WSNMPAVSZJSIMT-UHFFFAOYSA-N COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 Chemical compound COc1c(C)c2COC(=O)c2c(O)c1CC(O)C1(C)CCC(=O)O1 WSNMPAVSZJSIMT-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 241001198387 Escherichia coli BL21(DE3) Species 0.000 description 1
- 206010064503 Excessive skin Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- FNJSWIPFHMKRAT-UHFFFAOYSA-N Monomethyl phthalate Chemical compound COC(=O)C1=CC=CC=C1C(O)=O FNJSWIPFHMKRAT-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000007984 Tris EDTA buffer Substances 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
- 201000006035 X-linked dominant hypophosphatemic rickets Diseases 0.000 description 1
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 230000009471 action Effects 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
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 230000035563 calcemia Effects 0.000 description 1
- 229960002882 calcipotriol Drugs 0.000 description 1
- 230000004094 calcium homeostasis Effects 0.000 description 1
- 150000001721 carbon 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
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 150000003997 cyclic ketones Chemical class 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 125000005345 deuteroalkyl group Chemical group 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960002061 ergocalciferol Drugs 0.000 description 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 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
- 238000002474 experimental method Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005843 halogen 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
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
- 208000011111 hypophosphatemic rickets Diseases 0.000 description 1
- 210000000987 immune system Anatomy 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
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion 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
- 150000002500 ions Chemical class 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
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- DBYQHFPBWKKZAT-UHFFFAOYSA-N lithium;benzene Chemical compound [Li+].C1=CC=[C-]C=C1 DBYQHFPBWKKZAT-UHFFFAOYSA-N 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 125000000346 malonyl group Chemical group C(CC(=O)*)(=O)* 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000002503 metabolic effect 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
- 239000011707 mineral 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
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 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
- 231100000989 no adverse effect Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 125000003452 oxalyl group Chemical group *C(=O)C(*)=O 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 210000002990 parathyroid gland Anatomy 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet 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
- 239000002244 precipitate Substances 0.000 description 1
- 108010091624 preproparathormone Proteins 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 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
- 238000000159 protein binding assay Methods 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000012925 reference material Substances 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
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 208000024891 symptom Diseases 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
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- ZHSKFONQCREGOG-UHFFFAOYSA-N triethyl(trifluoromethyl)silane Chemical compound CC[Si](CC)(CC)C(F)(F)F ZHSKFONQCREGOG-UHFFFAOYSA-N 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
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000011653 vitamin D2 Substances 0.000 description 1
- 235000001892 vitamin D2 Nutrition 0.000 description 1
- 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 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
-
- 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
- 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
- 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
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P37/02—Immunomodulators
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Child & Adolescent Psychology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports 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 |
|---|---|---|---|
| US12/171,120 US8399439B2 (en) | 2008-07-10 | 2008-07-10 | 2-methylene-19,26-dinor-(20S,22E,25R)-vitamin D analogs |
| US12/171,120 | 2008-07-10 | ||
| PCT/US2009/050106 WO2010006169A2 (en) | 2008-07-10 | 2009-07-09 | 2-methylene-19, 26-dinor-(20s, 22e, 25r)-vitamin d analogs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011527699A true JP2011527699A (ja) | 2011-11-04 |
| JP2011527699A5 JP2011527699A5 (enExample) | 2012-08-23 |
Family
ID=41382534
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011517621A Pending JP2011527699A (ja) | 2008-07-10 | 2009-07-09 | ２−メチレン−１９，２６−ジノル−（２０ｓ，２２ｅ，２５ｒ）−ビタミンｄ類似物質 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8399439B2 (enExample) |
| EP (1) | EP2315745A2 (enExample) |
| JP (1) | JP2011527699A (enExample) |
| AU (1) | AU2009268505B2 (enExample) |
| CA (1) | CA2730257A1 (enExample) |
| WO (1) | WO2010006169A2 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8575136B2 (en) * | 2006-04-06 | 2013-11-05 | Wisconsin Alumni Research Foundation | 2-methylene-1α-hydroxy-18,19,21-trinorvitamin D3 analogs and uses thereof |
| US20110237557A1 (en) * | 2010-03-23 | 2011-09-29 | Deluca Hector F | Diastereomers of 2-methylene-19-nor-22-methyl-1alpha,25-dihydroxyvitamin 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 |
| US8604009B2 (en) * | 2010-03-23 | 2013-12-10 | Wisconsin Alumni Research Foundation | (20S)-2-methylene-19-nor-22-dimethyl-1α,25-dihydroxyvitamin D3 and (20R)-2-methylene-19-nor-22-dimethyl-1α,25-hydroxyvitamin D3 |
| CA2824870C (en) * | 2011-06-14 | 2018-08-14 | Wisconsin Alumni Research Foundation | 3-desoxy-2-methylene-19-nor-vitamin d analogs and their uses |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007512376A (ja) * | 2003-11-25 | 2007-05-17 | ウイスコンシン アラムニ リサーチ ファンデーション | 肥満症の予防及び治療用ビタミンｄ類似体 |
| WO2008039751A2 (en) * | 2006-09-28 | 2008-04-03 | Wisconsin Alumni Research Foundation | 2-methylene-(20s,25s)-19,27-dinor-(22e)-vitamin d analogs |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4666634A (en) * | 1984-12-05 | 1987-05-19 | Chugai Seiyaku Kabushiki Kaisha | vitamin D3 derivatives having a substituent at 2-position |
| US5086191A (en) * | 1991-05-28 | 1992-02-04 | Wisconsin Alumni Research Foundation | Intermediates for the synthesis of 19-nor vitamin D compounds |
| GB9214202D0 (en) * | 1992-07-03 | 1992-08-12 | Leo Pharm Prod Ltd | Chemical compounds |
| JP2898882B2 (ja) * | 1993-04-05 | 1999-06-02 | ウイスコンシン アラムナイ リサーチ フオンデーシヨン | ２−位に置換基を有する１９−ノル−ビタミンｄ３ 化合物 |
| DK0717034T3 (da) * | 1994-12-14 | 1999-10-18 | Duphar Int Res | Vitamin D-forbindelser og fremgangsmåde til fremstilling af disse forbindelser |
| US5843928A (en) * | 1997-03-17 | 1998-12-01 | Wisconsin Alumni Research Foundation | 2-alkylidene-19-nor-vitamin D compounds |
| US5945410A (en) * | 1997-03-17 | 1999-08-31 | Wisconsin Alumni Research Foundation | 2-alkyl-19-nor-vitamin D compounds |
| GB9721156D0 (en) * | 1997-10-06 | 1997-12-03 | Leo Pharm Prod Ltd | Novel vitamin d analogues |
| AU7544501A (en) * | 2000-09-08 | 2002-03-22 | Wisconsin Alumni Res Found | 1alpha-hydroxy-2-methylene-19-nor-homopregnacalciferol and its therapeutic applications |
| 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 |
| NZ545862A (en) * | 2003-08-20 | 2010-01-29 | Wisconsin Alumni Res Found | 2-Methylene-19-nor-vitamin D2 compounds |
| DE602005021245D1 (de) * | 2004-11-22 | 2010-06-24 | Wisconsin Alumni Res Found | 2-methylen-19,26,27-trinor-(20s)-1-alpha-hydroxyvitamin d3 and dessen verwendungen |
| WO2006057884A2 (en) * | 2004-11-22 | 2006-06-01 | Wisconsin Alumni Research Foundation | 2α-METHYL AND 2ß-METHYL ANALOGS OF 19,26,27-TRINOR-(20S)-1α-HYDROXYVITAMIN D3 AND THEIR USES |
| AU2005309804B9 (en) * | 2004-11-22 | 2011-12-08 | Wisconsin Alumni Research Foundation | 2alpha-methyl-19-nor-(20S)-1alpha-hydroxy-bishomopregnacalciferol and its uses |
| US7528122B2 (en) * | 2006-02-02 | 2009-05-05 | Wisconsin Alumni Research Foundation | Vitamin D analog—NEL, methods and uses thereof |
| US7803789B2 (en) * | 2006-02-02 | 2010-09-28 | Wisconsin Alumni Research Foundation | Vitamin D analog—RAK, methods and uses thereof |
| JP2009532460A (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−置換−１α，２５−ジヒドロキシ−１９，２６，２７−トリノルビタミンＤ類縁体およびその使用 |
| AU2007300214A1 (en) * | 2006-09-28 | 2008-04-03 | Wisconsin Alumni Research Foundation | 2-methylene-(20R,25S)-19,27-dinor-(22E)-vitamin D analogs |
| EP2240440A2 (en) * | 2007-12-28 | 2010-10-20 | Wisconsin Alumni Research Foundation | 2-methylene-(20s,25s)-19,26-dinor-vitamin d analogs |
-
2008
- 2008-07-10 US US12/171,120 patent/US8399439B2/en not_active Expired - Fee Related
-
2009
- 2009-07-09 AU AU2009268505A patent/AU2009268505B2/en not_active Ceased
- 2009-07-09 EP EP09790222A patent/EP2315745A2/en not_active Withdrawn
- 2009-07-09 JP JP2011517621A patent/JP2011527699A/ja active Pending
- 2009-07-09 WO PCT/US2009/050106 patent/WO2010006169A2/en not_active Ceased
- 2009-07-09 CA CA2730257A patent/CA2730257A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007512376A (ja) * | 2003-11-25 | 2007-05-17 | ウイスコンシン アラムニ リサーチ ファンデーション | 肥満症の予防及び治療用ビタミンｄ類似体 |
| WO2008039751A2 (en) * | 2006-09-28 | 2008-04-03 | Wisconsin Alumni Research Foundation | 2-methylene-(20s,25s)-19,27-dinor-(22e)-vitamin d analogs |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2010006169A2 (en) | 2010-01-14 |
| WO2010006169A3 (en) | 2010-04-15 |
| US20100009947A1 (en) | 2010-01-14 |
| AU2009268505A1 (en) | 2010-01-14 |
| US8399439B2 (en) | 2013-03-19 |
| CA2730257A1 (en) | 2010-01-14 |
| EP2315745A2 (en) | 2011-05-04 |
| AU2009268505B2 (en) | 2014-01-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| 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 | |
| US7741314B2 (en) | 2-Methylene-(20R,25S)-19,27-Dinor-(22E)-Vitamin D Analogs | |
| JP5161582B2 (ja) | １７，２０（ｚ）−デヒドロビタミンｄ類似体およびそれらの使用 | |
| US8609643B2 (en) | 2-methylene-(20S,25R)-19,26-dinor-vitamin D analogs | |
| 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 | |
| JP2011527699A (ja) | ２−メチレン−１９，２６−ジノル−（２０ｓ，２２ｅ，２５ｒ）−ビタミンｄ類似物質 | |
| US8445468B2 (en) | (20S,22E)-2-methylene-19-nor-22-ene-1α,25-dihydroxyvitamin D3 | |
| JP2011527695A (ja) | ２−メチレン−１９，２６−ジノル−（２０ｒ，２２ｅ，２５ｒ）−ビタミンｄ類似物質 | |
| US8114859B2 (en) | 2-methylene-(20S,25S)-19,27-dinor-(22E)-vitamin D analogs | |
| 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 | |
| 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 | |
| JP2011527698A (ja) | ２−メチレン−（２０ｅ）−２０（２２）−デヒドロ−１９−ノル−ビタミンｄ類似物質 | |
| US7947666B2 (en) | 2-methylene-(20S,25S)-19,26-dinor-vitamin D analogs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120706 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120706 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140218 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140225 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140318 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140326 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140624 |