AU2002329276B2 - Alkyl urea retinoid agonists I - Google Patents
Alkyl urea retinoid agonists I Download PDFInfo
- Publication number
- AU2002329276B2 AU2002329276B2 AU2002329276A AU2002329276A AU2002329276B2 AU 2002329276 B2 AU2002329276 B2 AU 2002329276B2 AU 2002329276 A AU2002329276 A AU 2002329276A AU 2002329276 A AU2002329276 A AU 2002329276A AU 2002329276 B2 AU2002329276 B2 AU 2002329276B2
- Authority
- AU
- Australia
- Prior art keywords
- compound
- acid
- emphysema
- alkyl
- compounds
- 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
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- -1 Alkyl urea retinoid Chemical class 0.000 title claims description 85
- 239000000556 agonist Substances 0.000 title description 21
- 239000004202 carbamide Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 153
- 206010014561 Emphysema Diseases 0.000 claims description 56
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 52
- 239000000203 mixture Substances 0.000 claims description 51
- 210000004072 lung Anatomy 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 41
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 201000011510 cancer Diseases 0.000 claims description 33
- 206010028980 Neoplasm Diseases 0.000 claims description 32
- 238000011282 treatment Methods 0.000 claims description 30
- 208000035475 disorder Diseases 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 23
- 241000124008 Mammalia Species 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 239000000651 prodrug Substances 0.000 claims description 13
- 229940002612 prodrug Drugs 0.000 claims description 13
- 239000012453 solvate Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 239000013543 active substance Substances 0.000 claims description 8
- 230000009885 systemic effect Effects 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 238000009472 formulation Methods 0.000 description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 125000000753 cycloalkyl group Chemical group 0.000 description 18
- 201000010099 disease Diseases 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 102000003702 retinoic acid receptors Human genes 0.000 description 18
- 108090000064 retinoic acid receptors Proteins 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 17
- 241000700159 Rattus Species 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 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 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 150000003254 radicals Chemical class 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000000443 aerosol Substances 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
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- 229910004298 SiO 2 Inorganic materials 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 150000004492 retinoid derivatives Chemical class 0.000 description 11
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 125000003710 aryl alkyl group Chemical group 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 230000008439 repair process Effects 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 9
- AMDKYPNODLTUMY-UHFFFAOYSA-N 5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-amine Chemical compound NC1=CC=C2C(C)(C)CCC(C)(C)C2=C1 AMDKYPNODLTUMY-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000004615 ingredient Substances 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- 125000000623 heterocyclic group Chemical group 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000005711 Benzoic acid Substances 0.000 description 6
- 102000016387 Pancreatic elastase Human genes 0.000 description 6
- 108010067372 Pancreatic elastase Proteins 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000013270 controlled release Methods 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 231100000419 toxicity Toxicity 0.000 description 6
- 230000001988 toxicity Effects 0.000 description 6
- QNWYDHIBRDOIQK-UHFFFAOYSA-N 4-[[hexyl-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)carbamoyl]amino]benzoic acid Chemical compound C=1C=C(C(CCC2(C)C)(C)C)C2=CC=1N(CCCCCC)C(=O)NC1=CC=C(C(O)=O)C=C1 QNWYDHIBRDOIQK-UHFFFAOYSA-N 0.000 description 5
- 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 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 125000002252 acyl group Chemical group 0.000 description 5
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- 229940112141 dry powder inhaler Drugs 0.000 description 5
- 239000003995 emulsifying agent Substances 0.000 description 5
- DAMAIUQNBVXKGF-UHFFFAOYSA-N ethyl 4-[[butyl-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)carbamoyl]amino]benzoate Chemical compound C=1C=C(C(CCC2(C)C)(C)C)C2=CC=1N(CCCC)C(=O)NC1=CC=C(C(=O)OCC)C=C1 DAMAIUQNBVXKGF-UHFFFAOYSA-N 0.000 description 5
- DFFXYEXIVDWJJD-UHFFFAOYSA-N ethyl 4-[[hexyl-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)carbamoyl]amino]benzoate Chemical compound C=1C=C(C(CCC2(C)C)(C)C)C2=CC=1N(CCCCCC)C(=O)NC1=CC=C(C(=O)OCC)C=C1 DFFXYEXIVDWJJD-UHFFFAOYSA-N 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- RQXZYQVRTXXPIA-UHFFFAOYSA-N n-hexyl-5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-amine Chemical compound CC1(C)CCC(C)(C)C=2C1=CC(NCCCCCC)=CC=2 RQXZYQVRTXXPIA-UHFFFAOYSA-N 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 230000029058 respiratory gaseous exchange Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- HMEZBVXXKPGBGC-UHFFFAOYSA-N 2,2,2-trifluoro-n-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)acetamide Chemical compound FC(F)(F)C(=O)NC1=CC=C2C(C)(C)CCC(C)(C)C2=C1 HMEZBVXXKPGBGC-UHFFFAOYSA-N 0.000 description 4
- ZHYOLRKOHJNRBF-UHFFFAOYSA-N 5,5,8,8-tetramethyl-n-pentyl-6,7-dihydronaphthalen-2-amine Chemical compound CC1(C)CCC(C)(C)C=2C1=CC(NCCCCC)=CC=2 ZHYOLRKOHJNRBF-UHFFFAOYSA-N 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
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- 229940096885 Retinoic acid receptor agonist Drugs 0.000 description 4
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- NRDBJQVWJNLNDF-UHFFFAOYSA-N ethyl 4-[[pentyl-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)carbamoyl]amino]benzoate Chemical compound C=1C=C(C(CCC2(C)C)(C)C)C2=CC=1N(CCCCC)C(=O)NC1=CC=C(C(=O)OCC)C=C1 NRDBJQVWJNLNDF-UHFFFAOYSA-N 0.000 description 4
- 125000004404 heteroalkyl group Chemical group 0.000 description 4
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- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 3
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- 239000012188 paraffin wax Substances 0.000 description 1
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
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- 239000006187 pill Substances 0.000 description 1
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- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])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
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 230000009979 protective mechanism Effects 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
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- 238000009613 pulmonary function test Methods 0.000 description 1
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- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
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- 150000004508 retinoic acid derivatives Chemical class 0.000 description 1
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- 108091011071 retinoid binding proteins Proteins 0.000 description 1
- 102000027483 retinoid hormone receptors Human genes 0.000 description 1
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- 239000000779 smoke Substances 0.000 description 1
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- 239000000661 sodium alginate Substances 0.000 description 1
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- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000003195 sodium channel blocking agent Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
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- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Chemical group 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 102000005969 steroid hormone receptors Human genes 0.000 description 1
- 108020003113 steroid hormone receptors Proteins 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
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- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 230000000153 supplemental effect Effects 0.000 description 1
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- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
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- 238000010189 synthetic method Methods 0.000 description 1
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- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
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- 102000004217 thyroid hormone receptors Human genes 0.000 description 1
- 108090000721 thyroid hormone receptors Proteins 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US32296301P | 2001-09-18 | 2001-09-18 | |
| US60/332,963 | 2001-09-18 | ||
| PCT/EP2002/010179 WO2003024921A1 (en) | 2001-09-18 | 2002-09-11 | Alkyl urea retinoid agonists i |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2002329276A1 AU2002329276A1 (en) | 2003-06-05 |
| AU2002329276B2 true AU2002329276B2 (en) | 2008-04-24 |
Family
ID=33130243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2002329276A Ceased AU2002329276B2 (en) | 2001-09-18 | 2002-09-11 | Alkyl urea retinoid agonists I |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US6844466B2 (enExample) |
| EP (1) | EP1430024A1 (enExample) |
| JP (1) | JP4421293B2 (enExample) |
| KR (1) | KR100896550B1 (enExample) |
| CN (1) | CN1283621C (enExample) |
| AR (1) | AR036533A1 (enExample) |
| AU (1) | AU2002329276B2 (enExample) |
| BR (1) | BR0212583A (enExample) |
| CA (1) | CA2460693C (enExample) |
| MX (1) | MXPA04002590A (enExample) |
| PL (1) | PL370361A1 (enExample) |
| RU (1) | RU2299877C2 (enExample) |
| WO (1) | WO2003024921A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1636160A4 (en) * | 2003-06-23 | 2006-09-27 | Auspex Pharmaceuticals | NEW THERAPEUTIC AGENTS FOR THE TREATMENT OF CANCER, METABOLISM AND SKIN DISEASES |
| WO2005108338A1 (en) * | 2004-05-03 | 2005-11-17 | Auspex Pharmaceuticals | Novel therapeutic agents for the treatment of cancer, metabolic diseases and skin disorders |
| AU2006229904A1 (en) * | 2005-03-30 | 2006-10-05 | Merck Sharp & Dohme Corp. | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| TW200821284A (en) * | 2006-10-03 | 2008-05-16 | Merck & Co Inc | Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use |
| DK3721880T3 (da) | 2010-09-01 | 2022-05-09 | Univ Jefferson | Sammensætning og fremgangsmåde til muskelreparation og regenerering |
| SG10201704687YA (en) | 2012-11-08 | 2017-07-28 | Univ Yamaguchi | Therapeutic agent for keratoconjunctive disorders |
| KR101426197B1 (ko) * | 2013-02-20 | 2014-08-01 | 여윤영 | 주먹밥틀 |
| CN105377258B (zh) | 2013-05-22 | 2020-08-28 | 国立大学法人山口大学 | 视网膜脉络膜病症的抑制剂 |
| CN105294567B (zh) * | 2015-10-29 | 2018-10-09 | 湖北新烯王生物科技有限公司 | 取代的3-氟苯基甲醇类化合物、药物组合物及用途 |
| MX390115B (es) | 2016-06-08 | 2025-03-20 | Clementia Pharmaceuticals Inc | Metodos para tratar la osificacion heterotopica. |
| AU2017359673B2 (en) | 2016-11-16 | 2021-10-21 | Clementia Pharmaceuticals Inc. | Methods for treating multiple osteochondroma (MO) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LU87821A1 (fr) | 1990-10-12 | 1992-05-25 | Cird Galderma | Composes bi-aromatiques,et leur utilisation en medecine humaine et veterinaire et en cosmetique |
| EP0983991B1 (en) * | 1992-04-22 | 2003-12-17 | Ligand Pharmaceuticals, Inc. | Compounds having selectivity for retinoid x receptors |
| US6093742A (en) | 1997-06-27 | 2000-07-25 | Vertex Pharmaceuticals, Inc. | Inhibitors of p38 |
| JO2178B1 (en) | 1999-10-19 | 2003-04-23 | اف . هوفمان لاروش ايه جي | Treatment of invasive diseases, using selected anti-PAR materials |
-
2002
- 2002-09-11 EP EP02764881A patent/EP1430024A1/en not_active Withdrawn
- 2002-09-11 JP JP2003528769A patent/JP4421293B2/ja not_active Expired - Fee Related
- 2002-09-11 WO PCT/EP2002/010179 patent/WO2003024921A1/en not_active Ceased
- 2002-09-11 RU RU2004111787/04A patent/RU2299877C2/ru not_active IP Right Cessation
- 2002-09-11 AU AU2002329276A patent/AU2002329276B2/en not_active Ceased
- 2002-09-11 CN CNB028181522A patent/CN1283621C/zh not_active Expired - Fee Related
- 2002-09-11 PL PL02370361A patent/PL370361A1/xx not_active IP Right Cessation
- 2002-09-11 MX MXPA04002590A patent/MXPA04002590A/es active IP Right Grant
- 2002-09-11 CA CA2460693A patent/CA2460693C/en not_active Expired - Fee Related
- 2002-09-11 KR KR1020047003931A patent/KR100896550B1/ko not_active Expired - Fee Related
- 2002-09-11 BR BR0212583-8A patent/BR0212583A/pt not_active Application Discontinuation
- 2002-09-16 AR ARP020103490A patent/AR036533A1/es unknown
- 2002-09-17 US US10/245,133 patent/US6844466B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP2005505571A (ja) | 2005-02-24 |
| BR0212583A (pt) | 2004-10-13 |
| CA2460693C (en) | 2010-12-07 |
| CN1555359A (zh) | 2004-12-15 |
| AR036533A1 (es) | 2004-09-15 |
| KR100896550B1 (ko) | 2009-05-07 |
| JP4421293B2 (ja) | 2010-02-24 |
| CA2460693A1 (en) | 2003-03-27 |
| KR20040035809A (ko) | 2004-04-29 |
| US6844466B2 (en) | 2005-01-18 |
| MXPA04002590A (es) | 2004-06-18 |
| US20030158226A1 (en) | 2003-08-21 |
| EP1430024A1 (en) | 2004-06-23 |
| CN1283621C (zh) | 2006-11-08 |
| RU2004111787A (ru) | 2005-10-20 |
| PL370361A1 (en) | 2005-05-16 |
| WO2003024921A1 (en) | 2003-03-27 |
| RU2299877C2 (ru) | 2007-05-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |