ES2256288T3 - Compuestos con actividad como inhibidores de citocromo p450rai. - Google Patents
Compuestos con actividad como inhibidores de citocromo p450rai.Info
- Publication number
- ES2256288T3 ES2256288T3 ES01965920T ES01965920T ES2256288T3 ES 2256288 T3 ES2256288 T3 ES 2256288T3 ES 01965920 T ES01965920 T ES 01965920T ES 01965920 T ES01965920 T ES 01965920T ES 2256288 T3 ES2256288 T3 ES 2256288T3
- Authority
- ES
- Spain
- Prior art keywords
- carbons
- alkyl
- compound according
- compound
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 598
- 239000003112 inhibitor Substances 0.000 title abstract description 15
- 230000000694 effects Effects 0.000 title description 20
- 108010022037 Retinoic Acid 4-Hydroxylase Proteins 0.000 title description 8
- 102000012211 Retinoic Acid 4-Hydroxylase Human genes 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims description 289
- 239000002253 acid Substances 0.000 claims description 155
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 144
- -1 4 - [(3,4-dihydro-4,4-dimethylspiro [2 H -1-benzopyran-2,1'-cyclopropane] -6-yl) ethynyl] benzeneacetic acid Chemical compound 0.000 claims description 143
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 114
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 76
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 63
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 61
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 57
- 150000002148 esters Chemical class 0.000 claims description 53
- 150000003839 salts Chemical class 0.000 claims description 46
- 229910052801 chlorine Inorganic materials 0.000 claims description 45
- 229910052794 bromium Inorganic materials 0.000 claims description 44
- 229910052736 halogen Inorganic materials 0.000 claims description 44
- 150000002367 halogens Chemical class 0.000 claims description 44
- 229910052740 iodine Inorganic materials 0.000 claims description 44
- 229910052731 fluorine Inorganic materials 0.000 claims description 37
- 125000001072 heteroaryl group Chemical group 0.000 claims description 34
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 125000004414 alkyl thio group Chemical group 0.000 claims description 32
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 29
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 150000001768 cations Chemical class 0.000 claims description 25
- 125000002541 furyl group Chemical group 0.000 claims description 25
- 125000004076 pyridyl group Chemical group 0.000 claims description 25
- 125000001544 thienyl group Chemical group 0.000 claims description 25
- 125000001624 naphthyl group Chemical group 0.000 claims description 24
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 150000004702 methyl esters Chemical class 0.000 claims description 22
- 125000002883 imidazolyl group Chemical group 0.000 claims description 16
- 125000002971 oxazolyl group Chemical group 0.000 claims description 16
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 16
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 16
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
- 125000000335 thiazolyl group Chemical group 0.000 claims description 16
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 8
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- 239000005711 Benzoic acid Substances 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 235000010233 benzoic acid Nutrition 0.000 claims description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- SMSDECBGCWEVPT-UHFFFAOYSA-N 8,8-dimethyl-5-oxo-6,7-dihydronaphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(C)(C)CCC(=O)C2=C1 SMSDECBGCWEVPT-UHFFFAOYSA-N 0.000 claims description 3
- 229960003424 phenylacetic acid Drugs 0.000 claims description 3
- JXKBUOWTZSPVGC-UHFFFAOYSA-N 2,2,4,4-tetramethyl-3h-chromene-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2OC(C)(C)CC(C)(C)C2=C1 JXKBUOWTZSPVGC-UHFFFAOYSA-N 0.000 claims description 2
- YFWAMPGMERJYRF-UHFFFAOYSA-N 2-[4-[2-(8-cyclopropyl-4,4-dimethylspiro[3h-chromene-2,1'-cyclopropane]-6-yl)ethynyl]-2-fluorophenyl]acetic acid Chemical compound O1C2=C(C3CC3)C=C(C#CC=3C=C(F)C(CC(O)=O)=CC=3)C=C2C(C)(C)CC21CC2 YFWAMPGMERJYRF-UHFFFAOYSA-N 0.000 claims description 2
- VRELZWKYSHFKPJ-UHFFFAOYSA-N 2-[4-[2-[3-tert-butyl-4-(1-ethoxycyclopropyl)phenyl]ethynyl]phenyl]acetic acid Chemical compound C=1C=C(C#CC=2C=CC(CC(O)=O)=CC=2)C=C(C(C)(C)C)C=1C1(OCC)CC1 VRELZWKYSHFKPJ-UHFFFAOYSA-N 0.000 claims description 2
- DURFLAAJALTGNB-UHFFFAOYSA-N 4-[2-(8-cyclopropyl-4,4-dimethylspiro[3h-chromene-2,1'-cyclopropane]-6-yl)ethynyl]benzoic acid Chemical compound O1C2=C(C3CC3)C=C(C#CC=3C=CC(=CC=3)C(O)=O)C=C2C(C)(C)CC21CC2 DURFLAAJALTGNB-UHFFFAOYSA-N 0.000 claims description 2
- CODXXKPMKMZJPB-UHFFFAOYSA-N 4-[2-[3-ethyl-4-(1-phenylmethoxycyclopropyl)phenyl]ethynyl]benzoic acid Chemical compound CCC1=CC(C#CC=2C=CC(=CC=2)C(O)=O)=CC=C1C1(OCC=2C=CC=CC=2)CC1 CODXXKPMKMZJPB-UHFFFAOYSA-N 0.000 claims description 2
- KRPFSZDMACMXGP-UHFFFAOYSA-N 4-[2-[3-tert-butyl-4-(1-ethoxycyclopropyl)phenyl]ethynyl]benzoic acid Chemical compound C=1C=C(C#CC=2C=CC(=CC=2)C(O)=O)C=C(C(C)(C)C)C=1C1(OCC)CC1 KRPFSZDMACMXGP-UHFFFAOYSA-N 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims 23
- 230000002378 acidificating effect Effects 0.000 claims 6
- 125000002619 bicyclic group Chemical group 0.000 claims 5
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 claims 1
- ZGWVVSCCYFKFBE-UHFFFAOYSA-N 2-[4-[2-(3,5-ditert-butyl-4-methoxyphenyl)ethynyl]phenyl]acetic acid Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1C#CC1=CC=C(CC(O)=O)C=C1 ZGWVVSCCYFKFBE-UHFFFAOYSA-N 0.000 claims 1
- PGAUVHNCULESQT-UHFFFAOYSA-N 2-[4-[2-[3-ethyl-4-(1-phenylmethoxycyclopropyl)phenyl]ethynyl]phenyl]acetic acid Chemical compound CCC1=CC(C#CC=2C=CC(CC(O)=O)=CC=2)=CC=C1C1(OCC=2C=CC=CC=2)CC1 PGAUVHNCULESQT-UHFFFAOYSA-N 0.000 claims 1
- FZEOKJHZDDAKFQ-UHFFFAOYSA-N 2-[4-[2-[3-ethyl-4-(1-propan-2-yloxycyclopropyl)phenyl]ethynyl]phenyl]acetic acid Chemical compound CCC1=CC(C#CC=2C=CC(CC(O)=O)=CC=2)=CC=C1C1(OC(C)C)CC1 FZEOKJHZDDAKFQ-UHFFFAOYSA-N 0.000 claims 1
- ISZHVGGVKUAHGB-UHFFFAOYSA-N 2-[4-[2-[4-(1-methoxycyclopropyl)phenyl]ethynyl]phenyl]acetic acid Chemical compound C=1C=C(C#CC=2C=CC(CC(O)=O)=CC=2)C=CC=1C1(OC)CC1 ISZHVGGVKUAHGB-UHFFFAOYSA-N 0.000 claims 1
- QBNPHNDDPBUIQE-UHFFFAOYSA-N 2-[4-[2-[4-(1-phenylmethoxycyclopropyl)phenyl]ethynyl]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1C#CC1=CC=C(C2(CC2)OCC=2C=CC=CC=2)C=C1 QBNPHNDDPBUIQE-UHFFFAOYSA-N 0.000 claims 1
- QLUKNAMQMQFMKP-UHFFFAOYSA-N 2-[4-[2-[4-[1-(2,2-dimethylpropoxy)cyclopropyl]-3-methylphenyl]ethynyl]phenyl]acetic acid Chemical compound CC1=CC(C#CC=2C=CC(CC(O)=O)=CC=2)=CC=C1C1(OCC(C)(C)C)CC1 QLUKNAMQMQFMKP-UHFFFAOYSA-N 0.000 claims 1
- JWGMJVCTCINGQN-UHFFFAOYSA-N 2-[4-[2-[4-[[cyclopropyl(ethyl)amino]methyl]-3-methylphenyl]ethynyl]phenyl]acetic acid Chemical compound C1CC1N(CC)CC(C(=C1)C)=CC=C1C#CC1=CC=C(CC(O)=O)C=C1 JWGMJVCTCINGQN-UHFFFAOYSA-N 0.000 claims 1
- ZIUKLJTWFKPKDQ-UHFFFAOYSA-N 4-[2-[3-methyl-4-(1-propan-2-yloxycyclopropyl)phenyl]ethynyl]benzoic acid Chemical compound C=1C=C(C#CC=2C=CC(=CC=2)C(O)=O)C=C(C)C=1C1(OC(C)C)CC1 ZIUKLJTWFKPKDQ-UHFFFAOYSA-N 0.000 claims 1
- VNIVFNHKLXHLGL-UHFFFAOYSA-N 4-[2-[4-(1-methoxycyclopropyl)phenyl]ethynyl]benzoic acid Chemical compound C=1C=C(C#CC=2C=CC(=CC=2)C(O)=O)C=CC=1C1(OC)CC1 VNIVFNHKLXHLGL-UHFFFAOYSA-N 0.000 claims 1
- GYAFAFMCFDHMGV-UHFFFAOYSA-N 4-[2-[4-(1-phenylmethoxycyclopropyl)phenyl]ethynyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C#CC1=CC=C(C2(CC2)OCC=2C=CC=CC=2)C=C1 GYAFAFMCFDHMGV-UHFFFAOYSA-N 0.000 claims 1
- ZLTXPVVWEWNZSO-UHFFFAOYSA-N 4-[2-[4-(1-propan-2-yloxycyclopropyl)phenyl]ethynyl]benzoic acid Chemical compound C=1C=C(C#CC=2C=CC(=CC=2)C(O)=O)C=CC=1C1(OC(C)C)CC1 ZLTXPVVWEWNZSO-UHFFFAOYSA-N 0.000 claims 1
- GGZDTLRYODNTCH-UHFFFAOYSA-N 4-[2-[4-[1-(2,2-dimethylpropoxy)cyclopropyl]-3-methylphenyl]ethynyl]benzoic acid Chemical compound CC1=CC(C#CC=2C=CC(=CC=2)C(O)=O)=CC=C1C1(OCC(C)(C)C)CC1 GGZDTLRYODNTCH-UHFFFAOYSA-N 0.000 claims 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 24
- 201000010099 disease Diseases 0.000 abstract description 22
- 102100039282 Cytochrome P450 26A1 Human genes 0.000 abstract description 16
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 abstract description 14
- 229930002330 retinoic acid Natural products 0.000 abstract description 14
- 229960001727 tretinoin Drugs 0.000 abstract description 12
- 101710130818 Cytochrome P450 26A1 Proteins 0.000 abstract description 9
- 102000004190 Enzymes Human genes 0.000 abstract description 8
- 108090000790 Enzymes Proteins 0.000 abstract description 8
- 230000001939 inductive effect Effects 0.000 abstract description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 338
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 266
- 239000000543 intermediate Substances 0.000 description 261
- 238000005160 1H NMR spectroscopy Methods 0.000 description 229
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 216
- 238000000034 method Methods 0.000 description 203
- 239000000243 solution Substances 0.000 description 181
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 160
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 125
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 124
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 118
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 110
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 101
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
- 239000003921 oil Substances 0.000 description 85
- 235000019198 oils Nutrition 0.000 description 85
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 84
- 239000007787 solid Substances 0.000 description 83
- 239000003480 eluent Substances 0.000 description 75
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 75
- 238000006243 chemical reaction Methods 0.000 description 74
- 239000000741 silica gel Substances 0.000 description 66
- 229910002027 silica gel Inorganic materials 0.000 description 66
- 239000011541 reaction mixture Substances 0.000 description 64
- 239000003153 chemical reaction reagent Substances 0.000 description 63
- 238000003818 flash chromatography Methods 0.000 description 61
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
- 238000004440 column chromatography Methods 0.000 description 49
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 44
- 229910052786 argon Inorganic materials 0.000 description 42
- 239000000203 mixture Substances 0.000 description 42
- 239000012071 phase Substances 0.000 description 41
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 40
- 229920006395 saturated elastomer Polymers 0.000 description 38
- 238000004587 chromatography analysis Methods 0.000 description 35
- 239000007864 aqueous solution Substances 0.000 description 33
- 229960000583 acetic acid Drugs 0.000 description 32
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 31
- 239000012074 organic phase Substances 0.000 description 30
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 28
- 238000012545 processing Methods 0.000 description 28
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 239000012230 colorless oil Substances 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 22
- 229910000027 potassium carbonate Inorganic materials 0.000 description 21
- 230000002829 reductive effect Effects 0.000 description 21
- 239000003039 volatile agent Substances 0.000 description 20
- 238000005299 abrasion Methods 0.000 description 19
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 19
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 19
- 238000005292 vacuum distillation Methods 0.000 description 19
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 17
- 239000012267 brine Substances 0.000 description 17
- 239000000284 extract Substances 0.000 description 17
- 239000000377 silicon dioxide Substances 0.000 description 17
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 239000000499 gel Substances 0.000 description 15
- 210000003491 skin Anatomy 0.000 description 15
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 14
- 229950011148 cyclopropane Drugs 0.000 description 14
- YCBJOQUNPLTBGG-UHFFFAOYSA-N ethyl 4-iodobenzoate Chemical group CCOC(=O)C1=CC=C(I)C=C1 YCBJOQUNPLTBGG-UHFFFAOYSA-N 0.000 description 14
- 238000002953 preparative HPLC Methods 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 238000003556 assay Methods 0.000 description 13
- 238000011156 evaluation Methods 0.000 description 13
- 150000004492 retinoid derivatives Chemical class 0.000 description 13
- 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 12
- 206010040844 Skin exfoliation Diseases 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 230000002265 prevention Effects 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- 229910052708 sodium Inorganic materials 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- VKZHEYVXPIMRCG-UHFFFAOYSA-N (4-iodophenyl)methyl acetate Chemical compound CC(=O)OCC1=CC=C(I)C=C1 VKZHEYVXPIMRCG-UHFFFAOYSA-N 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 150000001345 alkine derivatives Chemical class 0.000 description 10
- 235000019270 ammonium chloride Nutrition 0.000 description 10
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 10
- 238000005886 esterification reaction Methods 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 10
- 230000000699 topical effect Effects 0.000 description 10
- 231100000419 toxicity Toxicity 0.000 description 10
- 230000001988 toxicity Effects 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 9
- JJNHBFYGCSOONU-UHFFFAOYSA-M carbanide;cyclopenta-1,3-diene;dimethylaluminum;titanium(4+);chloride Chemical compound [CH3-].[Ti+3]Cl.C[Al]C.C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 JJNHBFYGCSOONU-UHFFFAOYSA-M 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 230000032050 esterification Effects 0.000 description 9
- 108090000064 retinoic acid receptors Proteins 0.000 description 9
- 102000003702 retinoic acid receptors Human genes 0.000 description 9
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- CZNGTXVOZOWWKM-UHFFFAOYSA-N methyl 4-bromobenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1 CZNGTXVOZOWWKM-UHFFFAOYSA-N 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- QYACUZSEHDNFDN-UHFFFAOYSA-N n,4,4-trimethyl-n-propan-2-yl-6-(2-trimethylsilylethynyl)-2,3-dihydro-1h-naphthalen-1-amine Chemical compound C[Si](C)(C)C#CC1=CC=C2C(N(C)C(C)C)CCC(C)(C)C2=C1 QYACUZSEHDNFDN-UHFFFAOYSA-N 0.000 description 1
- DBNQIOANXZVWIP-UHFFFAOYSA-N n,n-dimethyl-1,1-bis[(2-methylpropan-2-yl)oxy]methanamine Chemical compound CC(C)(C)OC(N(C)C)OC(C)(C)C DBNQIOANXZVWIP-UHFFFAOYSA-N 0.000 description 1
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
- QQZOPKMRPOGIEB-UHFFFAOYSA-N n-butyl methyl ketone Natural products CCCCC(C)=O QQZOPKMRPOGIEB-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
- KPSSIOMAKSHJJG-UHFFFAOYSA-N neopentyl alcohol Chemical compound CC(C)(C)CO KPSSIOMAKSHJJG-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- QTCRCHHNKWSPHB-UHFFFAOYSA-N propan-2-yl 2-bromobenzoate Chemical compound CC(C)OC(=O)C1=CC=CC=C1Br QTCRCHHNKWSPHB-UHFFFAOYSA-N 0.000 description 1
- RTXXREYZBOONJV-UHFFFAOYSA-N propan-2-yl 4-bromobenzoate Chemical compound CC(C)OC(=O)C1=CC=C(Br)C=C1 RTXXREYZBOONJV-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 239000012440 retinoic acid metabolism blocking agent Substances 0.000 description 1
- 108091008726 retinoic acid receptors α Proteins 0.000 description 1
- 108091008761 retinoic acid receptors β Proteins 0.000 description 1
- 108091008760 retinoic acid receptors γ Proteins 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 229960003010 sodium sulfate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 229940056729 sodium sulfate anhydrous Drugs 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 231100000057 systemic toxicity Toxicity 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- FATJQJBKBKEGNL-UHFFFAOYSA-N tert-butyl 2-(3-hydroxyphenyl)acetate Chemical compound CC(C)(C)OC(=O)CC1=CC=CC(O)=C1 FATJQJBKBKEGNL-UHFFFAOYSA-N 0.000 description 1
- NNGDLOYUAYPSNM-UHFFFAOYSA-N tert-butyl 2-(4-hydroxyphenyl)acetate Chemical compound CC(C)(C)OC(=O)CC1=CC=C(O)C=C1 NNGDLOYUAYPSNM-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- C07C59/72—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings and other rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
- C07C65/28—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups having unsaturation outside the aromatic rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Ophthalmology & Optometry (AREA)
- Virology (AREA)
- Cardiology (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines Containing Plant Substances (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Quinoline Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/651,001 US6291677B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US09/651,566 US6369225B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US09/651,234 US6387951B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US651001 | 2000-08-29 | ||
| US09/651,235 US6252090B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US651235 | 2000-08-29 | ||
| US651003 | 2000-08-29 | ||
| US09/651,564 US6380256B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US651566 | 2000-08-29 | ||
| US09/651,003 US6303785B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US651564 | 2000-08-29 | ||
| US651004 | 2000-08-29 | ||
| US09/651,004 US6369261B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US651234 | 2000-08-29 | ||
| PCT/US2001/025443 WO2002018361A2 (en) | 2000-08-29 | 2001-08-14 | Compounds having activity as inhibitors of cytochrome p450rai |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2256288T3 true ES2256288T3 (es) | 2006-07-16 |
Family
ID=27569871
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES01965920T Expired - Lifetime ES2256288T3 (es) | 2000-08-29 | 2001-08-14 | Compuestos con actividad como inhibidores de citocromo p450rai. |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1366036B1 (cg-RX-API-DMAC10.html) |
| JP (1) | JP2004507531A (cg-RX-API-DMAC10.html) |
| AT (1) | ATE315558T1 (cg-RX-API-DMAC10.html) |
| AU (2) | AU2001286471B2 (cg-RX-API-DMAC10.html) |
| CA (1) | CA2420869A1 (cg-RX-API-DMAC10.html) |
| DE (1) | DE60116642T2 (cg-RX-API-DMAC10.html) |
| ES (1) | ES2256288T3 (cg-RX-API-DMAC10.html) |
| WO (1) | WO2002018361A2 (cg-RX-API-DMAC10.html) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6313107B1 (en) * | 2000-08-29 | 2001-11-06 | Allergan Sales, Inc. | Methods of providing and using compounds having activity as inhibitors of cytochrome P450RAI |
| US7482366B2 (en) | 2001-12-21 | 2009-01-27 | X-Ceptor Therapeutics, Inc. | Modulators of LXR |
| US7998986B2 (en) | 2001-12-21 | 2011-08-16 | Exelixis Patent Company Llc | Modulators of LXR |
| US6740676B2 (en) * | 2002-03-19 | 2004-05-25 | Allergan, Inc. | 4-[(8-ethynyl, 8-vinyl or 8-ethynyl-methyl)-6-chromanoyl]-benzoic and 2-[4-[(8-ethynyl, 8-vinyl or 8-ethynyl-methyl)-6-chromanoyl]-phenyl]-acetic acid, their esters and salts having cytochrome p450rai inhibitory activity |
| US7504508B2 (en) | 2002-10-04 | 2009-03-17 | Millennium Pharmaceuticals, Inc. | PGD2 receptor antagonists for the treatment of inflammatory diseases |
| PL376156A1 (en) | 2002-10-04 | 2005-12-27 | Millennium Pharmaceuticals, Inc. | Pgd2 receptor antagonists for the treatment of inflammatory diseases |
| GB0302094D0 (en) | 2003-01-29 | 2003-02-26 | Pharmagene Lab Ltd | EP4 receptor antagonists |
| AU2004268455B2 (en) | 2003-08-29 | 2009-12-17 | Ono Pharmaceutical Co., Ltd. | Compound capable of binding S1P receptor and pharmaceutical use thereof |
| GB0324269D0 (en) | 2003-10-16 | 2003-11-19 | Pharmagene Lab Ltd | EP4 receptor antagonists |
| US7226951B2 (en) * | 2003-12-17 | 2007-06-05 | Allergan, Inc. | Compounds having selective cytochrome P450RAI-1 or selective cytochrome P450RAI-2 inhibitory activity and methods of obtaining the same |
| CA2591399C (en) | 2004-12-13 | 2014-05-20 | Ono Pharmaceutical Co., Ltd. | Aminocarboxylic acid derivative and medicinal use thereof |
| CA2589363A1 (en) | 2004-12-13 | 2006-06-22 | Eli Lilly And Company | Spiro derivatives as lipoxygenase inhibitors |
| BRPI0608553A2 (pt) | 2005-02-24 | 2010-01-12 | Millennium Pharm Inc | antagonistas de receptor de pgd2 para o tratamento de doenças inflamatórias |
| BR112013012836A2 (pt) * | 2010-11-24 | 2019-09-24 | Allergan Inc | moduladores dos receptores s1p" |
| JP2014527083A (ja) | 2011-09-15 | 2014-10-09 | アリゾナ ボード オブ リージェンツ， ア ボディー コーポレイト オブ ザ ステート オブ アリゾナ， アクティング フォー アンド オン ビハーフ オブ アリゾナ ステート ユニバーシティー | 治療用化合物 |
| WO2015109318A2 (en) | 2014-01-17 | 2015-07-23 | Arizona Board Of Regents, A Body Corporate Of The State Of Arizona, Acting For And On Behalf Of Arizona State University | Therapeutic methods |
| WO2016055800A2 (en) * | 2014-10-10 | 2016-04-14 | High Force Research Limited | Fluorescent synthetic retinoids |
| US10238655B2 (en) | 2017-01-23 | 2019-03-26 | Arizona Board Of Regents On Behalf Of Arizona State University | Dihydroindene and tetrahydronaphthalene compounds |
| US10231947B2 (en) | 2017-01-23 | 2019-03-19 | Arizona Board Of Regents On Behalf Of Arizona State University | Isochroman compounds and methods of use thereof |
| US10238626B2 (en) | 2017-01-23 | 2019-03-26 | Arizona Board Of Regents On Behalf Of Arizona State University | Therapeutic compounds |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3475305D1 (en) * | 1983-07-05 | 1988-12-29 | Pfizer | Carboxylic acid derivatives useful for inhibiting the degradation of cartilage |
| JPS6323868A (ja) * | 1986-07-11 | 1988-02-01 | イー・アイ・デュポン・ドゥ・ヌムール・アンド・カンパニー | アンギオテンシン２受容体遮断性イミダゾ−ル |
| US5089509A (en) * | 1988-09-15 | 1992-02-18 | Allergan, Inc. | Disubstituted acetylenes bearing heteroaromatic and heterobicyclic groups having retinoid like activity |
| US5015658A (en) * | 1988-06-29 | 1991-05-14 | Allergan, Inc. | Thiochroman esters of phenols and terephthallates having retinoid-like activity |
| US5045551A (en) * | 1989-09-19 | 1991-09-03 | Allergan, Inc. | Acetylenes disubstituted with a heteroaromatic group and a 2-substituted chromanyl, thiochromanyl or 1,2,3,4-tetrahydroquinolinyl group having retinoid-like activity |
| US5023341A (en) * | 1989-09-19 | 1991-06-11 | Allergan, Inc. | Compounds having a disubstituted acetylene moiety and retinoic acid-like biological activity |
| US5202471A (en) * | 1990-02-06 | 1993-04-13 | Allergan, Inc. | Alkyl, alkoxy and thioalkoxy substituted diphenyl acetylenes having retinoid like activity |
| US5134159A (en) * | 1991-03-26 | 1992-07-28 | Allergan, Inc. | 7-chromanyl esters of phenols and benzoic acids having retinoid-like activity |
| US5489584A (en) * | 1994-12-29 | 1996-02-06 | Allergan, Inc. | Acetylenes disubstituted with a 5-amino or substituted 5-amino substituted tetrahydronaphthyl group and with an aryl or heteroaryl group having retinoid-like biological activity |
| US5498795A (en) * | 1994-12-29 | 1996-03-12 | Allergan, Inc. | Acetylenes disubstituted with hydroxyaryl and aryl or heteroaryl groups having retinoid-like biological activity |
| AU698527B2 (en) * | 1994-12-29 | 1998-10-29 | Allergan, Inc. | Acetylenes disubstituted with a 5 or 8 substituted tetrahydronaphthyl or dihydronaphthyl group and with an aryl or heteroaryl groups having retinoid-like biological activity |
| US5965606A (en) * | 1995-12-29 | 1999-10-12 | Allergan Sales, Inc. | Methods of treatment with compounds having RAR.sub.α receptor specific or selective activity |
| US5739338A (en) * | 1996-11-05 | 1998-04-14 | Allergan | N-aryl substituted tetrahydroquinolines having retinoid agonist, retinoid antagonist or retinoid inverse agonist type biological activity |
-
2001
- 2001-08-14 CA CA002420869A patent/CA2420869A1/en not_active Abandoned
- 2001-08-14 AT AT01965920T patent/ATE315558T1/de not_active IP Right Cessation
- 2001-08-14 EP EP01965920A patent/EP1366036B1/en not_active Expired - Lifetime
- 2001-08-14 ES ES01965920T patent/ES2256288T3/es not_active Expired - Lifetime
- 2001-08-14 AU AU2001286471A patent/AU2001286471B2/en not_active Ceased
- 2001-08-14 JP JP2002523479A patent/JP2004507531A/ja active Pending
- 2001-08-14 WO PCT/US2001/025443 patent/WO2002018361A2/en not_active Ceased
- 2001-08-14 AU AU8647101A patent/AU8647101A/xx active Pending
- 2001-08-14 DE DE60116642T patent/DE60116642T2/de not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP1366036A2 (en) | 2003-12-03 |
| WO2002018361A3 (en) | 2003-07-31 |
| CA2420869A1 (en) | 2002-03-07 |
| AU2001286471B2 (en) | 2006-09-07 |
| HK1059439A1 (en) | 2004-07-02 |
| ATE315558T1 (de) | 2006-02-15 |
| JP2004507531A (ja) | 2004-03-11 |
| DE60116642D1 (de) | 2006-04-06 |
| WO2002018361A2 (en) | 2002-03-07 |
| EP1366036B1 (en) | 2006-01-11 |
| AU8647101A (en) | 2002-03-13 |
| DE60116642T2 (de) | 2006-11-09 |
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