ES2207339T3 - Derivados del acido 2,4-pentadienoico que tienen actividad selectiva hacia los receptores retinoides x(rxr). - Google Patents
Derivados del acido 2,4-pentadienoico que tienen actividad selectiva hacia los receptores retinoides x(rxr).Info
- Publication number
- ES2207339T3 ES2207339T3 ES99970078T ES99970078T ES2207339T3 ES 2207339 T3 ES2207339 T3 ES 2207339T3 ES 99970078 T ES99970078 T ES 99970078T ES 99970078 T ES99970078 T ES 99970078T ES 2207339 T3 ES2207339 T3 ES 2207339T3
- Authority
- ES
- Spain
- Prior art keywords
- carbons
- compound
- alkyl
- formula
- group
- 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
- 102000034527 Retinoid X Receptors Human genes 0.000 title claims description 26
- 108010038912 Retinoid X Receptors Proteins 0.000 title claims description 26
- 230000000694 effects Effects 0.000 title description 44
- SDVVLIIVFBKBMG-UHFFFAOYSA-N penta-2,4-dienoic acid Chemical class OC(=O)C=CC=C SDVVLIIVFBKBMG-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 242
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 81
- -1 alkyl radical Chemical class 0.000 claims abstract description 78
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 125000003118 aryl group Chemical group 0.000 claims abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 15
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 12
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 12
- 125000005037 alkyl phenyl group Chemical group 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical group 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 6
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical group O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract description 5
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 3
- 125000002252 acyl group Chemical group 0.000 claims abstract description 3
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims abstract description 3
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
- 239000011737 fluorine Substances 0.000 claims abstract description 3
- 125000005020 hydroxyalkenyl group Chemical group 0.000 claims abstract description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 3
- 125000005016 hydroxyalkynyl group Chemical group 0.000 claims abstract description 3
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims abstract description 3
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 3
- 229910003204 NH2 Inorganic materials 0.000 claims abstract 2
- 125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 claims abstract 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims abstract 2
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 28
- 238000002360 preparation method Methods 0.000 claims description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 208000030533 eye disease Diseases 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
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- 230000001817 pituitary effect Effects 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 2
- 208000030159 metabolic disease Diseases 0.000 claims description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 abstract 1
- 125000006725 C1-C10 alkenyl group Chemical group 0.000 abstract 1
- 101100134927 Gallus gallus COR8 gene Proteins 0.000 abstract 1
- 125000001326 naphthylalkyl group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 74
- 239000002253 acid Substances 0.000 description 55
- 239000000556 agonist Substances 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 45
- 238000000034 method Methods 0.000 description 42
- 239000000203 mixture Substances 0.000 description 40
- 239000002904 solvent Substances 0.000 description 37
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 31
- 150000004492 retinoid derivatives Chemical class 0.000 description 31
- 239000000243 solution Substances 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 239000005557 antagonist Substances 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- 239000003153 chemical reaction reagent Substances 0.000 description 23
- 102000005962 receptors Human genes 0.000 description 23
- 108020003175 receptors Proteins 0.000 description 23
- 102000003702 retinoic acid receptors Human genes 0.000 description 22
- 108090000064 retinoic acid receptors Proteins 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 16
- 150000002148 esters Chemical class 0.000 description 15
- 210000003491 skin Anatomy 0.000 description 14
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- 230000000875 corresponding effect Effects 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 239000012267 brine Substances 0.000 description 11
- 229940079593 drug Drugs 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 102000052812 Ornithine decarboxylases Human genes 0.000 description 10
- 108700005126 Ornithine decarboxylases Proteins 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000001704 evaporation Methods 0.000 description 10
- 230000008020 evaporation Effects 0.000 description 10
- KEIFWROAQVVDBN-UHFFFAOYSA-N 1,2-dihydronaphthalene Chemical compound C1=CC=C2C=CCCC2=C1 KEIFWROAQVVDBN-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 230000003287 optical effect Effects 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 8
- 150000001298 alcohols Chemical class 0.000 description 8
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 230000002441 reversible effect Effects 0.000 description 8
- 230000001988 toxicity Effects 0.000 description 8
- 231100000419 toxicity Toxicity 0.000 description 8
- 239000011719 vitamin A Substances 0.000 description 8
- 235000019155 vitamin A Nutrition 0.000 description 8
- 229940045997 vitamin a Drugs 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 125000004122 cyclic group Chemical group 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 102000027483 retinoid hormone receptors Human genes 0.000 description 7
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- 239000000741 silica gel Substances 0.000 description 7
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- 239000000126 substance Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 229930002330 retinoic acid Natural products 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 229960001727 tretinoin Drugs 0.000 description 6
- QPQXCZGFJJMKHH-OWOJBTEDSA-N (e)-3-iodoprop-2-en-1-ol Chemical class OC\C=C\I QPQXCZGFJJMKHH-OWOJBTEDSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
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- 229940125773 compound 10 Drugs 0.000 description 5
- 125000002897 diene group Chemical group 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 5
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 5
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- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 4
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Classifications
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- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
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- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
- C07C57/48—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid having unsaturation outside the aromatic rings
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- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
- C07C57/50—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid containing condensed ring systems
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/612—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
- C07C69/618—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety having unsaturation outside the six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/56—Ring systems containing bridged rings
- C07C2603/58—Ring systems containing bridged rings containing three rings
- C07C2603/70—Ring systems containing bridged rings containing three rings containing only six-membered rings
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
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- Toxicology (AREA)
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US164950 | 1998-10-01 | ||
| US09/164,950 US6147224A (en) | 1998-10-01 | 1998-10-01 | 2,4-pentadienoic acid derivatives having selective activity for retinoid X (RXR) receptors |
Publications (1)
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| ES2207339T3 true ES2207339T3 (es) | 2004-05-16 |
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| ES99970078T Expired - Lifetime ES2207339T3 (es) | 1998-10-01 | 1999-09-20 | Derivados del acido 2,4-pentadienoico que tienen actividad selectiva hacia los receptores retinoides x(rxr). |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US6147224A (https=) |
| EP (2) | EP1117628B1 (https=) |
| JP (1) | JP2002526516A (https=) |
| KR (2) | KR20010075457A (https=) |
| CN (1) | CN1328538A (https=) |
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| AT (1) | ATE254593T1 (https=) |
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| DE (1) | DE69912973T2 (https=) |
| ES (1) | ES2207339T3 (https=) |
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| TR200200507T2 (tr) | 1999-08-27 | 2002-10-21 | Ligand Pharmaceuticals Inc | Androjen reseptörü modülatör bileşikleri ve metotları |
| EP1212322A2 (en) | 1999-08-27 | 2002-06-12 | Ligand Pharmaceuticals Incorporated | 8-substituted-6-trifluoromethyl-9-pyrido[3,2-g]quinoline compounds as androgen receptor modulators |
| AU7586600A (en) * | 1999-09-14 | 2001-04-17 | Ligand Pharmaceuticals Incorporated | Rxr modulators with improved pharmacologic profile |
| US6906046B2 (en) | 2000-12-22 | 2005-06-14 | Celltech R & D Inc. | Pharmaceutical uses and synthesis of benzobicyclooctanes |
| US6495719B2 (en) | 2001-03-27 | 2002-12-17 | Circagen Pharmaceutical | Histone deacetylase inhibitors |
| WO2002076941A2 (en) * | 2001-03-27 | 2002-10-03 | Circagen Pharmaceutical | Histone deacetylase inhibitors |
| US7842727B2 (en) | 2001-03-27 | 2010-11-30 | Errant Gene Therapeutics, Llc | Histone deacetylase inhibitors |
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| GB8826760D0 (en) * | 1988-11-16 | 1988-12-21 | Wellcome Found | Pesticides |
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| US5455265A (en) * | 1993-02-11 | 1995-10-03 | Allergan, Inc. | Method of treatment with compounds having selective agonist-like activity on RXR retinoid receptors |
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| US5675033A (en) * | 1995-06-06 | 1997-10-07 | Allergan | 2,4-pentadienoic acid derivatives having retinoid-like biological activity |
| US5776699A (en) * | 1995-09-01 | 1998-07-07 | Allergan, Inc. | Method of identifying negative hormone and/or antagonist activities |
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| AU762492B2 (en) * | 1999-03-08 | 2003-06-26 | Basilea Pharmaceutica Ag | Retinoid antagonists and use thereof |
-
1998
- 1998-10-01 US US09/164,950 patent/US6147224A/en not_active Expired - Fee Related
-
1999
- 1999-09-20 KR KR1020017004018A patent/KR20010075457A/ko not_active Abandoned
- 1999-09-20 CA CA002346034A patent/CA2346034A1/en not_active Abandoned
- 1999-09-20 NZ NZ510528A patent/NZ510528A/xx unknown
- 1999-09-20 EP EP99970078A patent/EP1117628B1/en not_active Expired - Lifetime
- 1999-09-20 ES ES99970078T patent/ES2207339T3/es not_active Expired - Lifetime
- 1999-09-20 CN CN99813787A patent/CN1328538A/zh active Pending
- 1999-09-20 JP JP2000574489A patent/JP2002526516A/ja active Pending
- 1999-09-20 EP EP03025774A patent/EP1388534A3/en not_active Withdrawn
- 1999-09-20 AU AU60513/99A patent/AU757932B2/en not_active Ceased
- 1999-09-20 DE DE69912973T patent/DE69912973T2/de not_active Expired - Fee Related
- 1999-09-20 WO PCT/US1999/021712 patent/WO2000020370A1/en not_active Ceased
- 1999-09-20 AT AT99970078T patent/ATE254593T1/de not_active IP Right Cessation
- 1999-09-20 BR BR9914256-2A patent/BR9914256A/pt not_active Application Discontinuation
- 1999-10-01 AR ARP990104996A patent/AR020691A1/es not_active Application Discontinuation
- 1999-10-12 TW TW088116960A patent/TW580494B/zh not_active IP Right Cessation
-
2001
- 2001-03-30 ZA ZA200102635A patent/ZA200102635B/en unknown
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2006
- 2006-09-20 KR KR1020060091029A patent/KR20060118367A/ko not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| DE69912973T2 (de) | 2004-07-22 |
| TW580494B (en) | 2004-03-21 |
| US6147224A (en) | 2000-11-14 |
| WO2000020370A1 (en) | 2000-04-13 |
| ATE254593T1 (de) | 2003-12-15 |
| AR020691A1 (es) | 2002-05-22 |
| HK1039477A1 (en) | 2002-04-26 |
| JP2002526516A (ja) | 2002-08-20 |
| AU757932B2 (en) | 2003-03-13 |
| KR20060118367A (ko) | 2006-11-23 |
| CN1328538A (zh) | 2001-12-26 |
| NZ510528A (en) | 2003-04-29 |
| EP1388534A3 (en) | 2004-02-25 |
| CA2346034A1 (en) | 2000-04-13 |
| EP1388534A2 (en) | 2004-02-11 |
| BR9914256A (pt) | 2001-07-03 |
| EP1117628B1 (en) | 2003-11-19 |
| EP1117628A1 (en) | 2001-07-25 |
| KR20010075457A (ko) | 2001-08-09 |
| ZA200102635B (en) | 2002-10-18 |
| AU6051399A (en) | 2000-04-26 |
| DE69912973D1 (de) | 2003-12-24 |
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