AU746991B2 - Selective thyroid hormone analogs - Google Patents
Selective thyroid hormone analogs Download PDFInfo
- Publication number
- AU746991B2 AU746991B2 AU78234/98A AU7823498A AU746991B2 AU 746991 B2 AU746991 B2 AU 746991B2 AU 78234/98 A AU78234/98 A AU 78234/98A AU 7823498 A AU7823498 A AU 7823498A AU 746991 B2 AU746991 B2 AU 746991B2
- Authority
- AU
- Australia
- Prior art keywords
- formula
- compound
- hydrogen
- compounds
- lower 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.)
- Ceased
Links
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 41
- 239000005495 thyroid hormone Substances 0.000 claims abstract description 19
- 229940036555 thyroid hormone Drugs 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 239000000556 agonist Substances 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 178
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 60
- 239000001257 hydrogen Substances 0.000 claims description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 35
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 201000010099 disease Diseases 0.000 claims description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 206010003119 arrhythmia Diseases 0.000 claims description 3
- 125000001072 heteroaryl group Chemical group 0.000 claims description 3
- 208000003532 hypothyroidism Diseases 0.000 claims description 3
- 230000002989 hypothyroidism Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 2
- 208000001132 Osteoporosis Diseases 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 66
- 230000027455 binding Effects 0.000 abstract description 7
- 108010071769 Thyroid Hormone Receptors beta Proteins 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- 238000006243 chemical reaction Methods 0.000 description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 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 description 28
- -1 hydrocarbon radical Chemical class 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 229940093499 ethyl acetate Drugs 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 21
- 108090000721 thyroid hormone receptors Proteins 0.000 description 21
- 102000004217 thyroid hormone receptors Human genes 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- IAWVKQXSGXUIOY-UHFFFAOYSA-N (4-methoxy-2,6-dimethylphenyl)-(4-methoxy-3-propan-2-ylphenyl)methanone Chemical compound CC1=CC(OC)=CC(C)=C1C(=O)C1=CC=C(OC)C(C(C)C)=C1 IAWVKQXSGXUIOY-UHFFFAOYSA-N 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 239000012442 inert solvent Substances 0.000 description 10
- 239000004615 ingredient Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- LWFGSQIPMQSROI-UHFFFAOYSA-N 4-[(4-hydroxy-3-propan-2-ylphenyl)methyl]-3,5-dimethylphenol Chemical compound C1=C(O)C(C(C)C)=CC(CC=2C(=CC(O)=CC=2C)C)=C1 LWFGSQIPMQSROI-UHFFFAOYSA-N 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 101000904460 Encephalitozoon cuniculi (strain GB-M1) Probable glycerol-3-phosphate dehydrogenase Proteins 0.000 description 7
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 102000006255 nuclear receptors Human genes 0.000 description 7
- 108020004017 nuclear receptors Proteins 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 230000000747 cardiac effect Effects 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 6
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 5
- RLBVVOLDXFINKU-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-3-propan-2-ylphenyl)methoxy]-1,3-dimethylbenzene Chemical compound CC1=CC(OC)=CC(C)=C1OCC1=CC=C(OC)C(C(C)C)=C1 RLBVVOLDXFINKU-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 235000012000 cholesterol Nutrition 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 230000037323 metabolic rate Effects 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- ZAXBNAISKUFTMD-UHFFFAOYSA-N 1-(4-methoxy-2,6-dimethylphenyl)-1-(4-methoxy-3-propan-2-ylphenyl)ethanol Chemical compound CC1=CC(OC)=CC(C)=C1C(C)(O)C1=CC=C(OC)C(C(C)C)=C1 ZAXBNAISKUFTMD-UHFFFAOYSA-N 0.000 description 4
- CRBJBYGJVIBWIY-UHFFFAOYSA-N 2-isopropylphenol Chemical compound CC(C)C1=CC=CC=C1O CRBJBYGJVIBWIY-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
- 108010010234 HDL Lipoproteins Proteins 0.000 description 4
- 102000015779 HDL Lipoproteins Human genes 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- VYLVYHXQOHJDJL-UHFFFAOYSA-K cerium trichloride Chemical compound Cl[Ce](Cl)Cl VYLVYHXQOHJDJL-UHFFFAOYSA-K 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 229940088597 hormone Drugs 0.000 description 4
- 239000005556 hormone Substances 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 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
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 210000001685 thyroid gland Anatomy 0.000 description 4
- 230000000929 thyromimetic effect Effects 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- LGJVLQBOZGJNFD-UHFFFAOYSA-N (2-butyl-4-methoxy-5-propan-2-ylphenyl)-(4-methoxy-2,6-dimethylphenyl)methanone Chemical compound CCCCC1=CC(OC)=C(C(C)C)C=C1C(=O)C1=C(C)C=C(OC)C=C1C LGJVLQBOZGJNFD-UHFFFAOYSA-N 0.000 description 3
- GQRGGTFCTKGZJL-UHFFFAOYSA-N (4-hydroxy-2,6-dimethylphenyl)-(4-methoxy-3-propan-2-ylphenyl)methanone Chemical compound C1=C(C(C)C)C(OC)=CC=C1C(=O)C1=C(C)C=C(O)C=C1C GQRGGTFCTKGZJL-UHFFFAOYSA-N 0.000 description 3
- NNZRVXTXKISCGS-UHFFFAOYSA-N 1-methoxy-2-propan-2-ylbenzene Chemical compound COC1=CC=CC=C1C(C)C NNZRVXTXKISCGS-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- RAWZVIWEDAGMPW-UHFFFAOYSA-N 2-bromo-5-methoxy-1,3-dimethylbenzene Chemical compound COC1=CC(C)=C(Br)C(C)=C1 RAWZVIWEDAGMPW-UHFFFAOYSA-N 0.000 description 3
- CFNMTRKNNCKHBM-UHFFFAOYSA-N 4-bromo-1-methoxy-2-propan-2-ylbenzene Chemical compound COC1=CC=C(Br)C=C1C(C)C CFNMTRKNNCKHBM-UHFFFAOYSA-N 0.000 description 3
- ZFINNXSRPCWLHX-UHFFFAOYSA-N 4-methoxy-2,6-dimethylbenzaldehyde Chemical compound COC1=CC(C)=C(C=O)C(C)=C1 ZFINNXSRPCWLHX-UHFFFAOYSA-N 0.000 description 3
- YTNWKTGXDCFJAQ-UHFFFAOYSA-N 5-methoxy-2-[(4-methoxy-3-propan-2-ylphenyl)methyl]-1,3-dimethylbenzene Chemical compound CC1=CC(OC)=CC(C)=C1CC1=CC=C(OC)C(C(C)C)=C1 YTNWKTGXDCFJAQ-UHFFFAOYSA-N 0.000 description 3
- DKMJKHDQZRIMRB-UHFFFAOYSA-N 5-methoxy-2-[1-(4-methoxy-3-propan-2-ylphenyl)ethyl]-1,3-dimethylbenzene Chemical compound CC1=CC(OC)=CC(C)=C1C(C)C1=CC=C(OC)C(C(C)C)=C1 DKMJKHDQZRIMRB-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 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 3
- 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 3
- 108010028554 LDL Cholesterol Proteins 0.000 description 3
- 238000008214 LDL Cholesterol Methods 0.000 description 3
- 108010007622 LDL Lipoproteins Proteins 0.000 description 3
- 102000007330 LDL Lipoproteins Human genes 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 229960004132 diethyl ether Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- ATKZDAIUKACDKV-UHFFFAOYSA-N 4-[1-(4-hydroxy-3-propan-2-ylphenyl)ethyl]-3,5-dimethylphenol Chemical compound C1=C(O)C(C(C)C)=CC(C(C)C=2C(=CC(O)=CC=2C)C)=C1 ATKZDAIUKACDKV-UHFFFAOYSA-N 0.000 description 2
- WMUWDPLTTLJNPE-UHFFFAOYSA-N 4-bromo-3,5-dimethylphenol Chemical compound CC1=CC(O)=CC(C)=C1Br WMUWDPLTTLJNPE-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010089254 Cholesterol oxidase Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 108010023302 HDL Cholesterol Proteins 0.000 description 2
- 206010062767 Hypophysitis Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
- 108090001030 Lipoproteins Proteins 0.000 description 2
- 102000004895 Lipoproteins Human genes 0.000 description 2
- 108060001084 Luciferase Proteins 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 208000009453 Thyroid Nodule Diseases 0.000 description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 239000012888 bovine serum Substances 0.000 description 2
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 150000003857 carboxamides Chemical class 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000001010 compromised effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- YMAWOPBAYDPSLA-UHFFFAOYSA-N glycylglycine Chemical compound [NH3+]CC(=O)NCC([O-])=O YMAWOPBAYDPSLA-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 230000004217 heart function Effects 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 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 2
- 230000006698 induction Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 210000003635 pituitary gland Anatomy 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- KUYMVWXKHQSIAS-UHFFFAOYSA-N tert-butyl 2-chloroacetate Chemical compound CC(C)(C)OC(=O)CCl KUYMVWXKHQSIAS-UHFFFAOYSA-N 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- 201000002510 thyroid cancer Diseases 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 235000013311 vegetables Nutrition 0.000 description 2
- PHKHVRIRSWKUHM-UHFFFAOYSA-N (2-butyl-4-hydroxy-5-propan-2-ylphenyl)-(4-hydroxy-2,6-dimethylphenyl)methanone Chemical compound CCCCC1=CC(O)=C(C(C)C)C=C1C(=O)C1=C(C)C=C(O)C=C1C PHKHVRIRSWKUHM-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- NIBFJPXGNVPNHK-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-4-carbaldehyde Chemical group C1=CC(C=O)=C2OC(F)(F)OC2=C1 NIBFJPXGNVPNHK-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- 239000004821 Contact adhesive Substances 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 108010008488 Glycylglycine Proteins 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- RDATWFFCODFLLB-SEPHDYHBSA-M [Na+].[Cl-].OC(=O)\C=C\C(O)=O Chemical compound [Na+].[Cl-].OC(=O)\C=C\C(O)=O RDATWFFCODFLLB-SEPHDYHBSA-M 0.000 description 1
- 229940022682 acetone Drugs 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000005431 alkyl carboxamide group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
- 230000000326 anti-hypercholesterolaemic effect Effects 0.000 description 1
- 230000001315 anti-hyperlipaemic effect Effects 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000004097 bone metabolism Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 230000003913 calcium metabolism Effects 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- FKZLAFQXOCKZOC-UHFFFAOYSA-N cerium lithium Chemical compound [Li][Ce] FKZLAFQXOCKZOC-UHFFFAOYSA-N 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- QSGFBPQQGVJVPU-UHFFFAOYSA-N chloroform N,N-dimethylformamide oxolane Chemical compound C(Cl)(Cl)Cl.O1CCCC1.C(=O)N(C)C QSGFBPQQGVJVPU-UHFFFAOYSA-N 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000019197 fats Nutrition 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
- 230000008175 fetal development Effects 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229940043257 glycylglycine Drugs 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 229960002885 histidine Drugs 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000003871 intestinal function Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 238000003819 low-pressure liquid chromatography Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- QXUAFCKBYYPTPQ-ZWKAXHIPSA-L magnesium (2R,3R,4S,5R,6S)-2-(hydroxymethyl)-6-[(2R,3S,4R,5R)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxane-3,4,5-triol octadecanoate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O QXUAFCKBYYPTPQ-ZWKAXHIPSA-L 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 229940032007 methylethyl ketone Drugs 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/84—Unsaturated compounds containing keto groups containing six membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
- C07C59/70—Ethers of hydroxy-acetic acid, e.g. substitutes on the ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Compounds Of Unknown Constitution (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/877,792 US5883294A (en) | 1997-06-18 | 1997-06-18 | Selective thyroid hormone analogs |
| US08/877792 | 1997-06-18 | ||
| PCT/US1998/011758 WO1998057919A1 (en) | 1997-06-18 | 1998-06-08 | Selective thyroid hormone analogs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU7823498A AU7823498A (en) | 1999-01-04 |
| AU746991B2 true AU746991B2 (en) | 2002-05-09 |
Family
ID=25370738
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU78234/98A Ceased AU746991B2 (en) | 1997-06-18 | 1998-06-08 | Selective thyroid hormone analogs |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5883294A (https=) |
| EP (1) | EP0991618B1 (https=) |
| JP (1) | JP2002511084A (https=) |
| KR (1) | KR20010013999A (https=) |
| AT (1) | ATE254095T1 (https=) |
| AU (1) | AU746991B2 (https=) |
| CA (1) | CA2290622C (https=) |
| DE (1) | DE69819726T2 (https=) |
| WO (1) | WO1998057919A1 (https=) |
Families Citing this family (51)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6266622B1 (en) * | 1995-12-13 | 2001-07-24 | Regents Of The University Of California | Nuclear receptor ligands and ligand binding domains |
| AU717743B2 (en) | 1995-12-13 | 2000-03-30 | Regents Of The University Of California, The | Nuclear receptor ligands and ligand binding domains |
| US6017958A (en) * | 1996-06-04 | 2000-01-25 | Octamer, Inc. | Method of treating malignant tumors with thyroxine analogues having no significant hormonal activity |
| US6217598B1 (en) * | 1997-11-25 | 2001-04-17 | Linvatec Corporation | End-cutting shaver blade |
| DE69924846T2 (de) * | 1998-06-30 | 2006-04-27 | The Regents Of The University Of California, Oakland | Thyroidhormon-analoga und verfahren zu ihrer herstellung |
| US6723717B1 (en) | 1999-06-01 | 2004-04-20 | The University Of Texas Southwestern Medical Center | Sulfur-containing thyroxane derivatives and their use as hair growth promotors |
| CA2374260A1 (en) | 1999-06-01 | 2000-12-07 | The University Of Texas Southwestern Medical Center | Method of treating hair loss using sulfonyl thyromimetic compounds |
| US6680344B1 (en) | 1999-06-01 | 2004-01-20 | The University Of Texas Southwestern Medical Center | Method of treating hair loss using diphenylmethane derivatives |
| CA2374266A1 (en) * | 1999-06-01 | 2000-12-07 | The University Of Texas Southwestern Medical Center | Method of treating hair loss using diphenylmethane derivatives |
| CA2374263A1 (en) | 1999-06-01 | 2000-12-07 | The University Of Texas Southwestern Medical Center | Method of treating hair loss using diphenylether derivatives |
| US6516294B1 (en) | 1999-07-01 | 2003-02-04 | The Regents Of The University Of California | Nuclear receptor for 1α,25-dihydroxyvitamin D3 useful for selection of vitamin D3 ligands and a method therefor |
| DE10024939A1 (de) | 2000-05-19 | 2001-11-29 | Bayer Ag | Neue Diphenylmethanderivate für Arzneimittel |
| GB0015205D0 (en) * | 2000-06-21 | 2000-08-09 | Karobio Ab | Bioisosteric thyroid receptor ligands and method |
| DE10046029A1 (de) | 2000-09-18 | 2002-03-28 | Bayer Ag | Indazole |
| WO2002051805A1 (de) * | 2000-12-27 | 2002-07-04 | Bayer Aktiengesellschaft | Indol-derivate |
| US7504435B2 (en) * | 2001-01-31 | 2009-03-17 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Method for stimulating weight loss and/or for lowering triglycerides in patients |
| US6534676B2 (en) | 2001-01-31 | 2003-03-18 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Method to treat chronic heart failure and/or elevated cholesterol levels using 3,5-diiodothyropropionic acid and method to prepare same |
| US6716877B2 (en) | 2001-01-31 | 2004-04-06 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Method to treat chronic heart failure and/or elevated cholesterol levels |
| US6777442B2 (en) | 2001-03-12 | 2004-08-17 | Bayer Aktiengesellschaft | Diphenyl derivatives |
| US7302347B2 (en) * | 2002-12-10 | 2007-11-27 | The Regents Of The University Of California | Method for creating specific, high affinity nuclear receptor pharmaceuticals |
| AU2003300852A1 (en) * | 2002-12-10 | 2004-06-30 | The Regents Of The University Of California | A method for creating specific, high affinity nuclear receptor pharmaceuticals |
| WO2006128058A2 (en) | 2005-05-26 | 2006-11-30 | Metabasis Therapeutics, Inc. | Thyromimetics for the treatment of fatty liver diseases |
| CN1882327A (zh) * | 2003-11-19 | 2006-12-20 | 症变治疗公司 | 含磷的新的拟甲状腺素药 |
| WO2005085865A2 (en) * | 2004-03-09 | 2005-09-15 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with thyroid hormone receptor beta (thrb) |
| WO2006128056A2 (en) * | 2005-05-26 | 2006-11-30 | Metabasis Therapeutics, Inc. | Novel phosphinic acid-containing thyromimetics |
| WO2007002036A1 (en) * | 2005-06-24 | 2007-01-04 | Thomas Lavin | Tyroid hormone in burn and adipose deposites |
| PL1919878T3 (pl) | 2005-07-21 | 2011-03-31 | Hoffmann La Roche | Pochodne pirydazynonu jako agoniści receptora hormonu tarczycy |
| GB0606212D0 (en) * | 2006-03-28 | 2006-05-10 | Karobio Ab | Pharmaceutical compositions |
| WO2008106213A1 (en) * | 2007-02-27 | 2008-09-04 | Titan Pharmaceuticals, Inc. | Administration of 3,5-diiodothyropropionic acid for stimulating weight loss, and/or lowering triglyceride levels, and/or treatment of metabolic syndrome. |
| US8076334B2 (en) | 2007-09-20 | 2011-12-13 | Hoffmann-La Roche Inc. | Prodrugs of thyroid hormone analogs |
| WO2009089093A1 (en) * | 2008-01-04 | 2009-07-16 | Quatrx Pharmaceuticals Company | Thyroid hormone receptor agonists |
| WO2014178892A1 (en) | 2013-05-03 | 2014-11-06 | Scanlan Thomas S | Use of sobetirome in the treatment of x-linked adrenolenoleukodystrophy |
| EP3259246B1 (en) | 2015-02-20 | 2023-03-22 | Oregon Health & Science University | Derivatives of sobetirome |
| WO2017106974A1 (en) | 2015-12-24 | 2017-06-29 | Mcmaster University | Compounds for targeting thyroid hormone receptor alpha isoforms and methods of use thereof |
| US11872207B2 (en) | 2015-12-24 | 2024-01-16 | Mcmaster University | Dronedarone and derivatives thereof for treating cancer |
| CN109475121B (zh) | 2016-05-18 | 2021-06-25 | 俄勒冈健康科学大学 | 苏比替罗衍生物 |
| US11325886B2 (en) | 2016-08-12 | 2022-05-10 | Oregon Health & Science University | Amide compounds, pharmaceutical compositions thereof, and methods of using the same |
| CA3044059A1 (en) | 2016-11-21 | 2018-05-24 | Viking Therapeutics, Inc. | Method of treating glycogen storage disease |
| US11707472B2 (en) | 2017-06-05 | 2023-07-25 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis |
| US11660281B2 (en) * | 2017-06-29 | 2023-05-30 | Yale University | Compositions and methods of treating or preventing fibrotic lung diseases |
| IL276592B2 (en) | 2018-02-14 | 2023-11-01 | Univ Oregon Health & Science | History of Subtirum |
| ES3053674T3 (en) | 2018-03-22 | 2026-01-23 | Viking Therapeutics Inc | Crystalline forms and methods of producing crystalline forms of a compound |
| WO2020117962A1 (en) | 2018-12-05 | 2020-06-11 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis and inflammation |
| EP3894383A1 (en) | 2018-12-12 | 2021-10-20 | Autobahn Therapeutics, Inc. | Novel thyromimetics |
| CA3130371A1 (en) | 2019-03-01 | 2020-09-10 | Autobahn Therapeutics, Inc. | Novel thyromimetics |
| IT201900006923A1 (it) * | 2019-05-16 | 2020-11-16 | International Soc For Drug Development S R L | Nuovi tiromimetici con uno scaffold bifenilmetano e loro uso |
| KR20220121239A (ko) | 2019-11-29 | 2022-08-31 | 아우토반 쎄라퓨틱스, 인크. | 신규한 갑상선 호르몬 모방제 |
| CN111116684B (zh) | 2019-12-31 | 2020-09-25 | 厦门甘宝利生物医药有限公司 | 一种具有甲状腺激素受体激动剂特性的肝靶向化合物及其药物组合物 |
| US20230242473A1 (en) * | 2020-06-17 | 2023-08-03 | Autobahn Therapeutics, Inc. | Thyromimetics |
| JP7813730B2 (ja) | 2020-06-17 | 2026-02-13 | オートバーン セラピューティクス，インク． | 甲状腺様作用剤 |
| WO2021257851A1 (en) * | 2020-06-17 | 2021-12-23 | Autobahn Therapeutics, Inc. | Thyromimetics |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1149803A (en) * | 1979-10-09 | 1983-07-12 | Carroll W. Ours | HYDROXYAMINOMETHYL DERIVATIVES OF BENZOYL DI-SUBSTITUTED .alpha.-PHENOXY ALKANOYL ESTERS |
| US4323691A (en) * | 1979-10-09 | 1982-04-06 | Abbott Laboratories | Hydroxyaminomethyl derivatives of benzoyl di-substituted α-phenoxyalkanoyl esters |
| IT1218855B (it) * | 1984-12-28 | 1990-04-24 | Ates Componenti Elettron | Stadio amplificatore di segnali, integrato monoliticamente, ad alta dinamica di uscita |
| GB8501372D0 (en) * | 1985-01-18 | 1985-02-20 | Smith Kline French Lab | Chemical compounds |
| JPH05170690A (ja) * | 1991-12-20 | 1993-07-09 | Mitsui Toatsu Chem Inc | ジフェニル炭化水素誘導体を有効成分として含有する血栓溶解促進剤 |
| DE4327365A1 (de) * | 1993-08-14 | 1995-02-16 | Boehringer Mannheim Gmbh | Verwendung von Phenolen und Phenolderivaten als Arzneimittel mit fibrinogensenkender Wirkung |
| DE69924846T2 (de) * | 1998-06-30 | 2006-04-27 | The Regents Of The University Of California, Oakland | Thyroidhormon-analoga und verfahren zu ihrer herstellung |
-
1997
- 1997-06-18 US US08/877,792 patent/US5883294A/en not_active Expired - Lifetime
-
1998
- 1998-06-08 KR KR19997012027A patent/KR20010013999A/ko not_active Withdrawn
- 1998-06-08 AT AT98926384T patent/ATE254095T1/de not_active IP Right Cessation
- 1998-06-08 WO PCT/US1998/011758 patent/WO1998057919A1/en not_active Ceased
- 1998-06-08 EP EP98926384A patent/EP0991618B1/en not_active Expired - Lifetime
- 1998-06-08 AU AU78234/98A patent/AU746991B2/en not_active Ceased
- 1998-06-08 CA CA002290622A patent/CA2290622C/en not_active Expired - Fee Related
- 1998-06-08 JP JP50453099A patent/JP2002511084A/ja not_active Ceased
- 1998-06-08 DE DE69819726T patent/DE69819726T2/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| ATE254095T1 (de) | 2003-11-15 |
| JP2002511084A (ja) | 2002-04-09 |
| EP0991618A1 (en) | 2000-04-12 |
| CA2290622A1 (en) | 1998-12-23 |
| DE69819726T2 (de) | 2004-09-30 |
| AU7823498A (en) | 1999-01-04 |
| EP0991618A4 (en) | 2000-09-27 |
| KR20010013999A (ko) | 2001-02-26 |
| DE69819726D1 (de) | 2003-12-18 |
| EP0991618B1 (en) | 2003-11-12 |
| WO1998057919A1 (en) | 1998-12-23 |
| CA2290622C (en) | 2008-08-05 |
| US5883294A (en) | 1999-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU746991B2 (en) | Selective thyroid hormone analogs | |
| US6107517A (en) | Thyroid hormone analogues and methods for their preparation | |
| WO2000063196A1 (en) | New compounds, their preparation and use | |
| US7932290B2 (en) | Method for the treatment of metabolic disorders | |
| EP1285908B9 (en) | Substituted phenylpropionic acid derivatives | |
| US4576758A (en) | Anti-inflammatory lipoxin B analogs | |
| WO2000063189A1 (en) | Crystalline r- guanidines, arginine or (l) -arginine (2s) -2- ethoxy -3-{4- [2-(10h -phenoxazin -10-yl)ethoxy]phenyl}propanoate | |
| JP5240927B2 (ja) | 代謝障害の処置のための化合物 | |
| JP3373198B2 (ja) | アリールチアゾリジンジオン誘導体 | |
| JP2004501076A (ja) | 新規化合物、それらの製造及び使用 | |
| CZ50593A3 (en) | Steroid derivative, process of its preparation and a pharmaceutical preparation in which said derivative is comprised | |
| US6274608B1 (en) | Compounds, their preparation and use | |
| EP1657233A1 (en) | Lipoxin compounds | |
| US7019034B2 (en) | Compositions and methods for reducing serum glucose and triglyceride levels in diabetic mammals | |
| JPH0379336B2 (https=) | ||
| US4713486A (en) | Novel compounds | |
| US20080015253A1 (en) | Pentenoic Acid Derivatives, Processes For The Preparation Thereof, Pharmaceutical Compositions Comprising Them, And Therapeutic Applications Thereof | |
| US20020022656A1 (en) | New compounds, their preparation and use | |
| WO2003004484A1 (en) | Novel aliphatic compounds, synthesis method and method of using the same | |
| US4954520A (en) | 1,3-dioxolane derivatives useful in the treatment of inflammation | |
| US7414128B2 (en) | Crystalline R-guanidines, Arginine or (L)-Arginine (2S)-2-Ethoxy-3-{4-[2-(10H -phenoxazin-10-yl)ethoxy]phenyl}propanoate | |
| Yoshihara | Studies of antagonists and selective agonists of the thyroid hormone receptors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |