CA2769203A1 - Liver x receptor agonists - Google Patents
Liver x receptor agonists Download PDFInfo
- Publication number
- CA2769203A1 CA2769203A1 CA2769203A CA2769203A CA2769203A1 CA 2769203 A1 CA2769203 A1 CA 2769203A1 CA 2769203 A CA2769203 A CA 2769203A CA 2769203 A CA2769203 A CA 2769203A CA 2769203 A1 CA2769203 A1 CA 2769203A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- hydroxyl
- deleted
- independently
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000000766 liver X receptor agonist Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 53
- 238000000034 method Methods 0.000 claims abstract description 24
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 20
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 9
- 201000011510 cancer Diseases 0.000 claims abstract description 9
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 6
- 201000000351 arcus senilis Diseases 0.000 claims abstract description 6
- 239000008280 blood Substances 0.000 claims abstract description 6
- 210000004369 blood Anatomy 0.000 claims abstract description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- -1 amino, carboxyl Chemical group 0.000 claims description 16
- 125000001475 halogen functional group Chemical group 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 102000004311 liver X receptors Human genes 0.000 description 24
- 108090000865 liver X receptors Proteins 0.000 description 24
- 239000000203 mixture Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 13
- 201000010099 disease Diseases 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 229940125904 compound 1 Drugs 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000007832 Na2SO4 Substances 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000556 agonist Substances 0.000 description 8
- 150000001841 cholesterols Chemical class 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 6
- 108060001084 Luciferase Proteins 0.000 description 5
- 239000005089 Luciferase Substances 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 108090000331 Firefly luciferases Proteins 0.000 description 4
- DGABKXLVXPYZII-UHFFFAOYSA-N Hyodeoxycholic acid Natural products C1C(O)C2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 DGABKXLVXPYZII-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- DGABKXLVXPYZII-SIBKNCMHSA-N hyodeoxycholic acid Chemical compound C([C@H]1[C@@H](O)C2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 DGABKXLVXPYZII-SIBKNCMHSA-N 0.000 description 4
- 208000027866 inflammatory disease Diseases 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000242743 Renilla reniformis Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 210000002376 aorta thoracic Anatomy 0.000 description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
- 210000002168 brachiocephalic trunk Anatomy 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002270 dispersing agent Substances 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- FHUDAMLDXFJHJE-UHFFFAOYSA-N 1,1,1-trifluoropropan-2-one Chemical compound CC(=O)C(F)(F)F FHUDAMLDXFJHJE-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 101150037123 APOE gene Proteins 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
- 101000603962 Homo sapiens Oxysterols receptor LXR-alpha Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 102100038476 Oxysterols receptor LXR-alpha Human genes 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
- 238000005462 in vivo assay Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- JEHCHYAKAXDFKV-UHFFFAOYSA-J lead tetraacetate Chemical compound CC(=O)O[Pb](OC(C)=O)(OC(C)=O)OC(C)=O JEHCHYAKAXDFKV-UHFFFAOYSA-J 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000003571 reporter gene assay Methods 0.000 description 2
- 238000005055 short column chromatography Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- DKPMWHFRUGMUKF-UHFFFAOYSA-N (3alpha,5alpha,6alpha,7alpha)-3,6,7-Trihydroxycholan-24-oic acid Natural products OC1C(O)C2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 DKPMWHFRUGMUKF-UHFFFAOYSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- JOYGXTIHTHBSOA-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-thiophen-2-ylprop-2-en-1-one Chemical compound C1=CC(Cl)=CC=C1C(=O)C=CC1=CC=CS1 JOYGXTIHTHBSOA-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- OHXPGWPVLFPUSM-KLRNGDHRSA-N 3,7,12-trioxo-5beta-cholanic acid Chemical compound C1CC(=O)C[C@H]2CC(=O)[C@H]3[C@@H]4CC[C@H]([C@@H](CCC(O)=O)C)[C@@]4(C)C(=O)C[C@@H]3[C@]21C OHXPGWPVLFPUSM-KLRNGDHRSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- HOSGXJWQVBHGLT-UHFFFAOYSA-N 6-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical group N1C(=O)CCC2=CC(O)=CC=C21 HOSGXJWQVBHGLT-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- 241000254158 Lampyridae Species 0.000 description 1
- SMEROWZSTRWXGI-UHFFFAOYSA-N Lithocholsaeure Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 SMEROWZSTRWXGI-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010065673 Nephritic syndrome Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- NPGIHFRTRXVWOY-UHFFFAOYSA-N Oil red O Chemical compound Cc1ccc(C)c(c1)N=Nc1cc(C)c(cc1C)N=Nc1c(O)ccc2ccccc12 NPGIHFRTRXVWOY-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000007568 Proto-Oncogene Proteins c-fos Human genes 0.000 description 1
- 108010071563 Proto-Oncogene Proteins c-fos Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000000453 Skin Neoplasms Diseases 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 108010069201 VLDL Cholesterol Proteins 0.000 description 1
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 238000005865 alkene metathesis reaction Methods 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000000923 atherogenic effect Effects 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- RPKLZQLYODPWTM-KBMWBBLPSA-N cholanoic acid Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCC(O)=O)C)[C@@]1(C)CC2 RPKLZQLYODPWTM-KBMWBBLPSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000000975 co-precipitation Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- RFKZUAOAYVHBOY-UHFFFAOYSA-M copper(1+);acetate Chemical compound [Cu+].CC([O-])=O RFKZUAOAYVHBOY-UHFFFAOYSA-M 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229960002997 dehydrocholic acid Drugs 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- DAKIDYQCFJQMDF-UHFFFAOYSA-N dichloromethane;pyridine Chemical compound ClCCl.C1=CC=NC=C1 DAKIDYQCFJQMDF-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000010710 hepatitis C virus infection Diseases 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- MNPASXFANXKFQJ-UHFFFAOYSA-N lithium N-[bis(dimethylamino)phosphoryl]-N-methylmethanamine di(propan-2-yl)azanide Chemical compound [Li+].CC(C)[N-]C(C)C.CN(C)P(=O)(N(C)C)N(C)C MNPASXFANXKFQJ-UHFFFAOYSA-N 0.000 description 1
- SMEROWZSTRWXGI-HVATVPOCSA-N lithocholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 SMEROWZSTRWXGI-HVATVPOCSA-N 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 102000006255 nuclear receptors Human genes 0.000 description 1
- 108020004017 nuclear receptors Proteins 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- LCEFEIBEOBPPSJ-UHFFFAOYSA-N phenyl selenohypobromite Chemical compound Br[Se]C1=CC=CC=C1 LCEFEIBEOBPPSJ-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 208000030925 respiratory syncytial virus infectious disease Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 150000003962 selenoxides Chemical class 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 210000003291 sinus of valsalva Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 230000008410 smoothened signaling pathway Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- WZCZNEGTXVXAAS-UHFFFAOYSA-N trifluoromethanol Chemical compound OC(F)(F)F WZCZNEGTXVXAAS-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 229960001661 ursodiol Drugs 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 108010002139 very low density lipoprotein triglyceride Proteins 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic 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
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22938609P | 2009-07-29 | 2009-07-29 | |
| US61/229,386 | 2009-07-29 | ||
| PCT/US2010/043719 WO2011014661A2 (en) | 2009-07-29 | 2010-07-29 | Liver x receptor agonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2769203A1 true CA2769203A1 (en) | 2011-02-03 |
Family
ID=43529941
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2769203A Abandoned CA2769203A1 (en) | 2009-07-29 | 2010-07-29 | Liver x receptor agonists |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8829213B2 (https=) |
| EP (1) | EP2459581A4 (https=) |
| JP (1) | JP2013500986A (https=) |
| CN (1) | CN102482315A (https=) |
| CA (1) | CA2769203A1 (https=) |
| WO (1) | WO2011014661A2 (https=) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2848212C (en) | 2011-09-08 | 2022-03-29 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| CN103360453B (zh) * | 2012-04-04 | 2015-10-07 | 浙江大学 | 四环三萜类化合物的制备和抗衰老应用 |
| CN103360456B (zh) * | 2012-04-04 | 2015-07-29 | 浙江大学 | 三萜类化合物及制备和应用 |
| EP2759295A1 (en) | 2013-01-29 | 2014-07-30 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Foam cell specific Liver X Receptor (LXR) alpha agonist, SIRT1 inhibitors as well as p300 inhibitors as pharmaceutically active agents |
| PT2968369T (pt) | 2013-03-13 | 2018-12-05 | Sage Therapeutics Inc | Esteroides neuroativos e métodos para o seu uso |
| CN104072564B (zh) | 2013-03-28 | 2016-08-17 | 广州市赛普特医药科技股份有限公司 | 2β,3α,5α-三羟基-雄甾-6-酮及其制备方法与用途 |
| JP6320861B2 (ja) * | 2013-10-16 | 2018-05-09 | 株式会社ファンケル | コレステロール吸収阻害剤 |
| WO2015106164A1 (en) | 2014-01-10 | 2015-07-16 | Rgenix, Inc. | Lxr agonists and uses thereof |
| US10259840B2 (en) | 2014-06-18 | 2019-04-16 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| KR102526631B1 (ko) | 2014-11-19 | 2023-04-27 | 엔제트피 유케이 리미티드 | 스테로이드 fxr 조절인자를 제조하기 위한 중간체로서의 6-알킬-7-하이드록시-4-엔-3-온 스테로이드 |
| TWI688571B (zh) | 2014-11-19 | 2020-03-21 | 英商Ｎｚｐ英國有限公司 | 化合物（四） |
| US10131688B2 (en) | 2014-11-19 | 2018-11-20 | NZP UK Limited | 5.beta.-6-alkyl-7-hydroxy-3-one steroids as intermediates for the production of steroidal FXR modulators |
| US10538550B2 (en) | 2014-11-19 | 2020-01-21 | NZP UK Limited | 6.alpha.-alkyl-3,7-dione steroids as intermediates for the production of steroidal FXR modulators |
| CA2991311C (en) | 2015-07-06 | 2025-05-06 | Sage Therapeutics, Inc. | OXYSTEROLS AND THEIR METHODS OF USE |
| EP3828194B1 (en) | 2015-07-06 | 2025-04-16 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| HUE071964T2 (hu) | 2015-07-06 | 2025-10-28 | Sage Therapeutics Inc | Oxiszterolok és alkalmazási eljárásaik |
| US20190365784A1 (en) * | 2015-12-30 | 2019-12-05 | Raúl Enrique MASSONE | Use of brassinosteroid analogs for the treatment of dermal disorders by selectively modulating liver x receptors (lxr) and dermal disease treatment by brassinosteroid analogs acting as selective liver x receptor (lxr) modulators |
| EP3402477A4 (en) | 2016-01-11 | 2019-08-21 | The Rockefeller University | METHOD FOR THE TREATMENT OF DISEASES RELATED TO MYELOID-DERIVED SUPPRESSOR CELLS |
| SMT202200300T1 (it) | 2016-04-01 | 2022-09-14 | Sage Therapeutics Inc | Ossisteroli e relativi metodi d'uso |
| WO2017193046A1 (en) | 2016-05-06 | 2017-11-09 | Sage Therapeutics, Inc. | Oxysterols and methods of use thereof |
| CN106188205B (zh) * | 2016-05-06 | 2017-08-25 | 深圳以诺生物制药有限公司 | 一种罗汉果醇衍生物单体及其组合物的用途 |
| GB201608777D0 (en) | 2016-05-18 | 2016-06-29 | Dextra Lab Ltd | Compounds |
| GB201608776D0 (en) | 2016-05-18 | 2016-06-29 | Dextra Lab Ltd | Methods and compounds |
| IT201600068742A1 (it) * | 2016-07-01 | 2018-01-01 | Bar Pharmaceuticals Soc A Responsabilita Limitata | Derivati dell'acido iodesossicolico e loro uso |
| ES2884071T3 (es) | 2016-07-07 | 2021-12-10 | Sage Therapeutics Inc | 24-hidroxiesteroles sustituidos en 11 para el tratamiento de afecciones relacionadas con NMDA |
| ES2935057T3 (es) | 2016-09-30 | 2023-03-01 | Sage Therapeutics Inc | C7 oxisteroles sustituidos y estos compuestos para su uso como moduladores de la NMDA |
| RU2019115113A (ru) | 2016-10-18 | 2020-11-24 | Сейдж Терапьютикс, Инк. | Оксистеролы и способы их применения |
| KR20230051723A (ko) | 2016-10-18 | 2023-04-18 | 세이지 테라퓨틱스, 인크. | 옥시스테롤 및 그의 사용 방법 |
| CA3078981A1 (en) | 2017-11-21 | 2019-05-31 | Rgenix, Inc. | Polymorphs and uses thereof |
| US12186329B2 (en) | 2018-08-23 | 2025-01-07 | President And Fellows Of Harvard College | Compositions and methods related to cholic acid 7-sulfate as a treatment for diabetes |
| EP3890745B1 (en) | 2018-12-04 | 2025-11-19 | President and Fellows of Harvard College | Synthetic derivatives of cholic acid 7-sulfate and uses thereof |
| JP2022514257A (ja) * | 2018-12-13 | 2022-02-10 | アイノス，インコーポレイテッド | ドライアイ疾患の治療のための局所点眼製剤におけるｌｘｒアゴニスト |
| KR20250171471A (ko) | 2019-05-10 | 2025-12-08 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 장 박테리아 담즙산 대사의 소분자 조정제 |
| TWI888447B (zh) | 2019-12-13 | 2025-07-01 | 美商因思博納公司 | 金屬鹽及其用途 |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2698853A (en) * | 1951-08-11 | 1955-01-04 | Monsanto Chemicals | Oxidation of steroids |
| FR1482102A (fr) * | 1966-03-31 | 1967-05-26 | Centre Nat Rech Scient | Nouveaux dérivés de stéroïdes et procédé de préparation |
| US3784598A (en) * | 1972-01-20 | 1974-01-08 | Ciba Geigy Corp | Process for the conversion of a 3-hydroxy-5,6-oxido group of a steroid into a delta4-3-oxo group |
| JPS4976857A (https=) | 1972-12-06 | 1974-07-24 | ||
| US3963765A (en) * | 1973-04-01 | 1976-06-15 | Yehuda Mazur | Preparation of derivatives of cholesterol |
| US3887545A (en) * | 1973-11-12 | 1975-06-03 | Hoffmann La Roche | Synthesis of 1{60 -hydroxylated cholesterol derivatives |
| US4006172A (en) * | 1976-04-26 | 1977-02-01 | The Upjohn Company | Process for 7-keto-Δ5 -steroids |
| US4125544A (en) * | 1977-06-09 | 1978-11-14 | G. D. Searle | 20/22/23/24-Oxa-7-oxocholesterols and esters thereof |
| IT1106121B (it) | 1977-08-29 | 1985-11-11 | Searle & Co | Derivati 25-alchilcolesterolici e relativo procedimento di produzione |
| US4193930A (en) * | 1977-08-29 | 1980-03-18 | G. D. Searle & Co. | 25-Alkyl-3β-hydroxycholest-5-en-7-ones and esters thereof |
| JPS563000A (en) * | 1979-06-20 | 1981-01-13 | Green Cross Corp:The | Water-soluble cholesterol derivative |
| US4639420A (en) * | 1984-11-21 | 1987-01-27 | Schaffner Carl P | Method for the immunoanalysis of cholesterol epoxides |
| US4917998A (en) * | 1986-05-06 | 1990-04-17 | Epitope, Inc. | Method of detecting AIDS virus infection |
| IT1212141B (it) * | 1987-06-03 | 1989-11-08 | So Ri Far S R L | Composizioni farmaceutiche per la prevenzione e terapia della calcolosi delle vie biliari e della dispepsia biliare. |
| US5151545A (en) * | 1987-10-13 | 1992-09-29 | Pfizer Inc. | 3,5-dihydroxy-6,8-nonadienoic acids and derivatives as hypocholesterolemic agents |
| US5562910A (en) * | 1989-09-25 | 1996-10-08 | University Of Utah Research Foundation | Vaccine compositions and method for enhancing an immune response |
| US5506223A (en) * | 1990-08-29 | 1996-04-09 | Humanetics Corporation | Δ5-androstenes useful for promoting weight maintenance or weight loss and treatment process |
| JPH0749438B2 (ja) | 1990-10-31 | 1995-05-31 | 東京田辺製薬株式会社 | タウリン抱合型胆汁酸の精製方法 |
| IL105050A0 (en) | 1992-03-27 | 1993-07-08 | Lilly Co Eli | Steroid derivatives |
| IT1255241B (it) | 1992-07-22 | 1995-10-20 | Simos Contos | Derivato di acido biliare e suo uso in terapia |
| IT1255486B (it) * | 1992-08-04 | 1995-11-06 | Erregierre Ind Chim | Processo per preparare gli acidi biliari coniugati con la taurina |
| US5482935A (en) * | 1993-01-05 | 1996-01-09 | American Home Product Corporation | Anti-atherosclerotic use of 17 alpha-dihydroequilin |
| TW289757B (https=) * | 1993-05-08 | 1996-11-01 | Hoechst Ag | |
| IT1270853B (it) * | 1993-05-20 | 1997-05-13 | Sanofi Elf | Procedimento per la preparazione di derivati taurocolanici |
| CN1055929C (zh) | 1993-09-20 | 2000-08-30 | 中国科学院上海有机化学研究所 | 三氟甲基甾体化合物及其制备方法 |
| IT1274000B (it) * | 1994-04-06 | 1997-07-14 | Alfa Wassermann Spa | Derivati di acidi biliari utili nella terapia della calcolosi biliare da colesterolo e nelle patologie indotte da colestasi |
| CN1152316A (zh) * | 1994-05-19 | 1997-06-18 | 麦克公司 | 具有烯丙基的甾族化合物的氧化 |
| US5583239A (en) * | 1995-05-30 | 1996-12-10 | Lehigh University | Antimicrobial sterol conjugates |
| CN1248916A (zh) | 1997-01-24 | 2000-03-29 | 加利福尼亚大学董事会 | FXR、PPARα和LXRα激活剂恢复屏障功能、促进表皮分化和抑制增生的用途 |
| US6060465A (en) * | 1997-02-06 | 2000-05-09 | Miljkovic; Dusan | Bile acids and their derivatives as glycoregulatory agents |
| JP2002532729A (ja) * | 1998-12-23 | 2002-10-02 | グラクソ グループ リミテッド | 核内受容体のリガンドのアッセイ |
| WO2000040965A1 (en) * | 1999-01-07 | 2000-07-13 | Tularik, Inc. | Fxr receptor-mediated modulation of cholesterol metabolism |
| CN1187364C (zh) * | 1999-04-30 | 2005-02-02 | 亚其发展公司 | 类固醇衍生物 |
| JP2002030097A (ja) * | 2000-07-11 | 2002-01-29 | Kyorin Pharmaceut Co Ltd | ステロイド誘導体の製造方法 |
| JP2002030096A (ja) * | 2000-07-11 | 2002-01-29 | Kyorin Pharmaceut Co Ltd | 神経細胞突起再生剤及びその製造方法 |
| DE10105041A1 (de) | 2001-02-05 | 2002-08-14 | Tell Pharm Ag Hergiswil | Tripeptide und Tripeptid-Derivate für die Behandlung neurodegenerativer Krankheiten |
| EP1385868A4 (en) | 2001-02-08 | 2004-12-08 | Univ Chicago | STEROID DERIVATIVE |
| JP4309661B2 (ja) * | 2001-05-03 | 2009-08-05 | ザ ユニバーシティー オブ シカゴ | 肝臓ｘ受容体 |
| US7078396B2 (en) * | 2001-05-03 | 2006-07-18 | Arch Development Corporation | Method of treating disorder related to high cholesterol concentration |
| WO2003039480A2 (en) | 2001-11-08 | 2003-05-15 | The University Of Chicago | Method of treating disorder related to high cholesterol concentration |
| WO2003086303A2 (en) | 2002-04-12 | 2003-10-23 | The University Of Chicago | Farnesoid x-activated receptor agonists |
| US20070032464A1 (en) * | 2004-10-08 | 2007-02-08 | Shutsung Liao | Methods of treating cancers |
-
2010
- 2010-07-29 US US12/846,326 patent/US8829213B2/en not_active Expired - Fee Related
- 2010-07-29 CA CA2769203A patent/CA2769203A1/en not_active Abandoned
- 2010-07-29 JP JP2012523043A patent/JP2013500986A/ja active Pending
- 2010-07-29 EP EP10805047A patent/EP2459581A4/en not_active Withdrawn
- 2010-07-29 WO PCT/US2010/043719 patent/WO2011014661A2/en not_active Ceased
- 2010-07-29 CN CN2010800336173A patent/CN102482315A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN102482315A (zh) | 2012-05-30 |
| EP2459581A2 (en) | 2012-06-06 |
| EP2459581A4 (en) | 2012-12-26 |
| JP2013500986A (ja) | 2013-01-10 |
| WO2011014661A2 (en) | 2011-02-03 |
| WO2011014661A3 (en) | 2011-06-09 |
| US8829213B2 (en) | 2014-09-09 |
| US20110059932A1 (en) | 2011-03-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8829213B2 (en) | Liver X receptor agonists | |
| CA2716095C (en) | Steroid analogues for neuroprotection | |
| ES2313305T3 (es) | Nuevo agonista esteroide de fxr. | |
| JP4309661B2 (ja) | 肝臓ｘ受容体 | |
| JP3333210B2 (ja) | 新規プレドニソロン誘導体および該化合物を含有する薬剤 | |
| EA003392B1 (ru) | Производные желчных кислот | |
| TW200400837A (en) | Novel formulations of anti-inflammatory androstane derivatives and β 2-adrenoreceptor agonists | |
| JP2005508368A (ja) | 高コレステロール濃度に関連した疾患の治療方法 | |
| CN101906039A (zh) | 取代苯酚的羟基酸酯化合物、制备方法及在药物中的应用 | |
| EP3243829A1 (en) | Steroid anionic compounds, method for their production, use and pharmaceutical preparation containing them | |
| JP2014012657A (ja) | 抗炎症剤及び抗癌剤であるグルココルチコイドの脂肪酸エステル | |
| US20120309728A1 (en) | New steroid inhibitors of pgp for use for inhibiting multidrug resistance | |
| US7078396B2 (en) | Method of treating disorder related to high cholesterol concentration | |
| CN113620969A (zh) | 带桥环的环己烷二羧酸衍生物及其药物组合物和应用 | |
| CN102186874A (zh) | 新的释放no的类固醇衍生物 | |
| NZ256796A (en) | Estrene steroid-containing medicament for nasal administration | |
| JP6437636B2 (ja) | 神経保護特性を有する両親媒性化合物 | |
| JP6356218B2 (ja) | 抗腫瘍活性を有する７−α−［９−（４，４，５，５，５−ペンタフルオロペンチルスルフィニル）ノニル］−エストラ−１，３，５（１０）−トリエン−３，１７β−ジオールのエステル誘導体及びその調製方法 | |
| CZ92697A3 (en) | Novel estrenes intended for inducing hypothalamus effects | |
| WO2001030803A1 (en) | B-homoestra-1,3,5(10)-trienes as modulators of tubulin polymerization | |
| AU2005281640A1 (en) | Novel derivatives of 3,5-seco-4-norcholestane and use thereof | |
| JP2005535611A (ja) | アスコルビン酸を伴った新規アンドロスタン及びアンドロステン誘導体並びに種々の病気、疾患及び障害の治療または予防におけるそれらの使用 | |
| US6696436B1 (en) | B-homoestra-1,3,5(10)-trienes as modulators of tubulin polymerization | |
| JP2024528569A (ja) | プラダー・ウィリー症候群を治療するためのカンナビジオール酸エステル | |
| WO2006059768A1 (ja) | ９，１０－セコプレグナン誘導体及び医薬 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20150729 |