CA2420869A1 - Compounds having activity as inhibitors of cytochrome p450rai - Google Patents
Compounds having activity as inhibitors of cytochrome p450rai Download PDFInfo
- Publication number
- CA2420869A1 CA2420869A1 CA002420869A CA2420869A CA2420869A1 CA 2420869 A1 CA2420869 A1 CA 2420869A1 CA 002420869 A CA002420869 A CA 002420869A CA 2420869 A CA2420869 A CA 2420869A CA 2420869 A1 CA2420869 A1 CA 2420869A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- carbons
- alkyl
- accordance
- 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.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 559
- 239000003112 inhibitor Substances 0.000 title abstract description 13
- 230000000694 effects Effects 0.000 title description 21
- 102100039282 Cytochrome P450 26A1 Human genes 0.000 title description 12
- 101710130818 Cytochrome P450 26A1 Proteins 0.000 title description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 189
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 101
- -1 3,4-dihydro-4,4-dimethylspiro[2H-1-benzopyran-2,1'-cyclopropane]-6-yl Chemical group 0.000 claims description 99
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 87
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 56
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 46
- 229910052794 bromium Inorganic materials 0.000 claims description 44
- 229910052736 halogen Chemical group 0.000 claims description 44
- 229910052801 chlorine Inorganic materials 0.000 claims description 43
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 40
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 39
- 229910052731 fluorine Inorganic materials 0.000 claims description 38
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
- 239000005711 Benzoic acid Substances 0.000 claims description 34
- 150000002367 halogens Chemical class 0.000 claims description 34
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 32
- 229910052740 iodine Inorganic materials 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 125000004414 alkyl thio group Chemical group 0.000 claims description 31
- 125000002541 furyl group Chemical group 0.000 claims description 25
- 125000001624 naphthyl 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
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 24
- 150000001768 cations Chemical class 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 235000010233 benzoic acid Nutrition 0.000 claims description 18
- 125000002883 imidazolyl group Chemical group 0.000 claims description 18
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 18
- 125000002971 oxazolyl 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
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 15
- 229960003424 phenylacetic acid Drugs 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- NSTREUWFTAOOKS-UHFFFAOYSA-N 2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1F NSTREUWFTAOOKS-UHFFFAOYSA-N 0.000 claims description 4
- 239000003279 phenylacetic acid Substances 0.000 claims description 3
- RKSQOVLLZSFLAE-UHFFFAOYSA-N 2-[4-[2-[3-methyl-4-(1-propan-2-yloxycyclopropyl)phenyl]ethynyl]phenyl]acetic acid Chemical compound C=1C=C(C#CC=2C=CC(CC(O)=O)=CC=2)C=C(C)C=1C1(OC(C)C)CC1 RKSQOVLLZSFLAE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 40
- 125000005843 halogen group Chemical group 0.000 claims 10
- 125000002619 bicyclic group Chemical group 0.000 claims 5
- 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 2
- FRFBANPMURAGSX-UHFFFAOYSA-N spiro[chromene-2,1'-cyclopropane]-6-carboxylic acid Chemical compound C1=CC2=CC(C(=O)O)=CC=C2OC21CC2 FRFBANPMURAGSX-UHFFFAOYSA-N 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- XMNHGDPCBNIWFV-UHFFFAOYSA-N 2-[2-fluoro-4-[2-(2,2,4,4-tetramethyl-3h-chromen-6-yl)ethynyl]phenyl]acetic acid Chemical compound C=1C=C2OC(C)(C)CC(C)(C)C2=CC=1C#CC1=CC=C(CC(O)=O)C(F)=C1 XMNHGDPCBNIWFV-UHFFFAOYSA-N 0.000 claims 1
- UUDHDRXYERWKTE-UHFFFAOYSA-N 2-[4-(2,2,4,4-tetramethyl-3h-chromene-6-carbonyl)oxyphenyl]acetic acid Chemical compound C=1C=C2OC(C)(C)CC(C)(C)C2=CC=1C(=O)OC1=CC=C(CC(O)=O)C=C1 UUDHDRXYERWKTE-UHFFFAOYSA-N 0.000 claims 1
- JBKIUXYXZUSWPS-UHFFFAOYSA-N 2-[4-(8,8-dimethyl-5-oxo-6,7-dihydronaphthalene-2-carbonyl)oxyphenyl]acetic acid Chemical compound C1=C2C(C)(C)CCC(=O)C2=CC=C1C(=O)OC1=CC=C(CC(O)=O)C=C1 JBKIUXYXZUSWPS-UHFFFAOYSA-N 0.000 claims 1
- ITXFQVKXIVKNHH-UHFFFAOYSA-N 2-[4-[2-(2,2,4,4-tetramethyl-3h-chromen-6-yl)ethynyl]phenyl]acetic acid Chemical compound C=1C=C2OC(C)(C)CC(C)(C)C2=CC=1C#CC1=CC=C(CC(O)=O)C=C1 ITXFQVKXIVKNHH-UHFFFAOYSA-N 0.000 claims 1
- AZLHHZTWOKNMGH-UHFFFAOYSA-N 2-[4-[2-(2-cyclopropyl-4,4-dimethyl-1,3-dihydroisoquinolin-6-yl)ethynyl]-2-fluorophenyl]acetic acid Chemical compound C1=C2C(C)(C)CN(C3CC3)CC2=CC=C1C#CC1=CC=C(CC(O)=O)C(F)=C1 AZLHHZTWOKNMGH-UHFFFAOYSA-N 0.000 claims 1
- ZLYPJYBYWIRJKY-UHFFFAOYSA-N 2-[4-[2-(2-cyclopropyl-4,4-dimethyl-1,3-dihydroisoquinolin-6-yl)ethynyl]phenyl]acetic acid Chemical compound C1=C2C(C)(C)CN(C3CC3)CC2=CC=C1C#CC1=CC=C(CC(O)=O)C=C1 ZLYPJYBYWIRJKY-UHFFFAOYSA-N 0.000 claims 1
- OHXOJSLDGUQQAS-UHFFFAOYSA-N 2-[4-[2-(3,5-ditert-butyl-4-methoxyphenyl)ethynyl]-2-fluorophenyl]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(F)=C1 OHXOJSLDGUQQAS-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
- GNPNJKBHUSKWND-UHFFFAOYSA-N 2-[4-[2-(4-imidazol-1-yl-2,3-dimethylphenyl)ethynyl]phenyl]acetic acid Chemical compound CC1=C(C)C(N2C=NC=C2)=CC=C1C#CC1=CC=C(CC(O)=O)C=C1 GNPNJKBHUSKWND-UHFFFAOYSA-N 0.000 claims 1
- ZPLGNBCEQJWHPT-UHFFFAOYSA-N 2-[4-[2-(4-imidazol-1-yl-2-methyl-3-propan-2-ylphenyl)ethynyl]phenyl]acetic acid Chemical compound CC(C)C1=C(C)C(C#CC=2C=CC(CC(O)=O)=CC=2)=CC=C1N1C=CN=C1 ZPLGNBCEQJWHPT-UHFFFAOYSA-N 0.000 claims 1
- RABWFFBPJKCGCA-UHFFFAOYSA-N 2-[4-[2-(4-imidazol-1-yl-2-methyl-3-propan-2-ylphenyl)ethynyl]phenyl]benzoic acid Chemical compound CC(C)C1=C(C)C(C#CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C(O)=O)=CC=C1N1C=CN=C1 RABWFFBPJKCGCA-UHFFFAOYSA-N 0.000 claims 1
- DGFTWCCCWFYBFB-UHFFFAOYSA-N 2-[4-[2-(5-imidazol-1-yl-8,8-dimethyl-6,7-dihydro-5h-naphthalen-2-yl)ethynyl]phenyl]acetic acid Chemical compound C1=C2C(C)(C)CCC(N3C=NC=C3)C2=CC=C1C#CC1=CC=C(CC(O)=O)C=C1 DGFTWCCCWFYBFB-UHFFFAOYSA-N 0.000 claims 1
- LWCBOTGILHXRHK-UHFFFAOYSA-N 2-[4-[2-(8,8-dimethyl-5-oxo-6,7-dihydronaphthalen-2-yl)ethynyl]-2-fluorophenyl]acetic acid Chemical compound C1=C2C(C)(C)CCC(=O)C2=CC=C1C#CC1=CC=C(CC(O)=O)C(F)=C1 LWCBOTGILHXRHK-UHFFFAOYSA-N 0.000 claims 1
- LYOAHZUZZNMLNC-UHFFFAOYSA-N 2-[4-[2-(8-cyclopropyl-2,2,4,4-tetramethyl-3h-chromen-6-yl)ethynyl]-2-fluorophenyl]acetic acid Chemical compound C=12OC(C)(C)CC(C)(C)C2=CC(C#CC=2C=C(F)C(CC(O)=O)=CC=2)=CC=1C1CC1 LYOAHZUZZNMLNC-UHFFFAOYSA-N 0.000 claims 1
- FKURZNWAFOUMKK-UHFFFAOYSA-N 2-[4-[2-(8-cyclopropyl-2,2,4,4-tetramethyl-3h-chromen-6-yl)ethynyl]phenyl]acetic acid Chemical compound C=12OC(C)(C)CC(C)(C)C2=CC(C#CC=2C=CC(CC(O)=O)=CC=2)=CC=1C1CC1 FKURZNWAFOUMKK-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- UBXQMNPDZOGDSY-UHFFFAOYSA-N 2-[4-[2-(8-ethyl-2,2,4,4-tetramethyl-3h-chromen-6-yl)ethynyl]phenyl]acetic acid Chemical compound C=1C(C(CC(C)(C)O2)(C)C)=C2C(CC)=CC=1C#CC1=CC=C(CC(O)=O)C=C1 UBXQMNPDZOGDSY-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
- FNIQAQQYKWQMEP-UHFFFAOYSA-N 2-[4-[2-[3-methyl-4-(1-phenylmethoxycyclopropyl)phenyl]ethynyl]phenyl]acetic acid Chemical compound CC1=CC(C#CC=2C=CC(CC(O)=O)=CC=2)=CC=C1C1(OCC=2C=CC=CC=2)CC1 FNIQAQQYKWQMEP-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
- HQOZXBGCEKMVTO-UHFFFAOYSA-N 2-[4-[2-[4-(1-propan-2-yloxycyclopropyl)phenyl]ethynyl]phenyl]acetic acid Chemical compound C=1C=C(C#CC=2C=CC(CC(O)=O)=CC=2)C=CC=1C1(OC(C)C)CC1 HQOZXBGCEKMVTO-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
- ZFDGDSDFJCLIBX-UHFFFAOYSA-N 2-[4-[2-[5-[cyclopropyl(methyl)amino]-8,8-dimethyl-6,7-dihydro-5h-naphthalen-2-yl]ethynyl]-2-fluorophenyl]acetic acid Chemical compound C1CC(C)(C)C2=CC(C#CC=3C=C(F)C(CC(O)=O)=CC=3)=CC=C2C1N(C)C1CC1 ZFDGDSDFJCLIBX-UHFFFAOYSA-N 0.000 claims 1
- WNJLJQKQEKVIJT-UHFFFAOYSA-N 2-fluoro-4-[2-(2,2,4,4-tetramethyl-3h-chromen-6-yl)ethynyl]benzoic acid Chemical compound C=1C=C2OC(C)(C)CC(C)(C)C2=CC=1C#CC1=CC=C(C(O)=O)C(F)=C1 WNJLJQKQEKVIJT-UHFFFAOYSA-N 0.000 claims 1
- HFSKVLVQPKQVFD-UHFFFAOYSA-N 4-[2-(1-cyclopropyl-4,4-dimethyl-2,3-dihydroquinolin-6-yl)ethynyl]benzoic acid Chemical compound C12=CC=C(C#CC=3C=CC(=CC=3)C(O)=O)C=C2C(C)(C)CCN1C1CC1 HFSKVLVQPKQVFD-UHFFFAOYSA-N 0.000 claims 1
- YNJIMZKUXOYINQ-UHFFFAOYSA-N 4-[2-(4-imidazol-1-yl-2,3-dimethylphenyl)ethynyl]benzoic acid Chemical compound CC1=C(C)C(N2C=NC=C2)=CC=C1C#CC1=CC=C(C(O)=O)C=C1 YNJIMZKUXOYINQ-UHFFFAOYSA-N 0.000 claims 1
- VSHLPGYGJSORKV-UHFFFAOYSA-N 4-[2-(8,8-dimethyl-5-oxo-6,7-dihydronaphthalen-2-yl)ethynyl]-2-fluorobenzoic acid Chemical compound C1=C2C(C)(C)CCC(=O)C2=CC=C1C#CC1=CC=C(C(O)=O)C(F)=C1 VSHLPGYGJSORKV-UHFFFAOYSA-N 0.000 claims 1
- QELVCKRITXHFTQ-UHFFFAOYSA-N 4-[2-(8-cyclopropyl-2,2,4,4-tetramethyl-3h-chromen-6-yl)ethynyl]benzoic acid Chemical compound C=12OC(C)(C)CC(C)(C)C2=CC(C#CC=2C=CC(=CC=2)C(O)=O)=CC=1C1CC1 QELVCKRITXHFTQ-UHFFFAOYSA-N 0.000 claims 1
- APJKXYNFLYDWJW-UHFFFAOYSA-N 4-[2-(8-cyclopropyl-4,4-dimethylspiro[3h-chromene-2,1'-cyclopropane]-6-yl)ethynyl]-2-fluorobenzoic acid Chemical compound O1C2=C(C3CC3)C=C(C#CC=3C=C(F)C(C(O)=O)=CC=3)C=C2C(C)(C)CC21CC2 APJKXYNFLYDWJW-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- IVAZIDXFVDVVCY-UHFFFAOYSA-N 4-[2-[3-methyl-4-(1-phenylmethoxycyclopropyl)phenyl]ethynyl]benzoic acid Chemical compound CC1=CC(C#CC=2C=CC(=CC=2)C(O)=O)=CC=C1C1(OCC=2C=CC=CC=2)CC1 IVAZIDXFVDVVCY-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
- 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 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
- LTWKGLUJOILBLP-UHFFFAOYSA-N 4-[2-[4-[1-(2-phenylethylamino)cyclopropyl]phenyl]ethynyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C#CC1=CC=C(C2(CC2)NCCC=2C=CC=CC=2)C=C1 LTWKGLUJOILBLP-UHFFFAOYSA-N 0.000 claims 1
- QICQZRSZHVZUNX-UHFFFAOYSA-N 4-[2-[4-[1-(benzylamino)cyclopropyl]phenyl]ethynyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C#CC1=CC=C(C2(CC2)NCC=2C=CC=CC=2)C=C1 QICQZRSZHVZUNX-UHFFFAOYSA-N 0.000 claims 1
- ZTHZFYAFRKPOFL-UHFFFAOYSA-N 4-[2-[4-[1-(dibenzylamino)cyclopropyl]phenyl]ethynyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C#CC1=CC=C(C2(CC2)N(CC=2C=CC=CC=2)CC=2C=CC=CC=2)C=C1 ZTHZFYAFRKPOFL-UHFFFAOYSA-N 0.000 claims 1
- ODDUJFDAXPFOJC-UHFFFAOYSA-N 4-[2-[4-[1-(dipropylamino)cyclopropyl]phenyl]ethynyl]benzoic acid Chemical compound C=1C=C(C#CC=2C=CC(=CC=2)C(O)=O)C=CC=1C1(N(CCC)CCC)CC1 ODDUJFDAXPFOJC-UHFFFAOYSA-N 0.000 claims 1
- PBMNEISYXMSEQQ-UHFFFAOYSA-N 4-[2-[4-[1-(propylamino)cyclopropyl]phenyl]ethynyl]benzoic acid Chemical compound C=1C=C(C#CC=2C=CC(=CC=2)C(O)=O)C=CC=1C1(NCCC)CC1 PBMNEISYXMSEQQ-UHFFFAOYSA-N 0.000 claims 1
- ZNNVLFPXIQFABK-UHFFFAOYSA-N 4-[2-[4-[[cyclopropyl(ethyl)amino]methyl]-3-propan-2-ylphenyl]ethynyl]benzoic acid Chemical compound C1CC1N(CC)CC(C(=C1)C(C)C)=CC=C1C#CC1=CC=C(C(O)=O)C=C1 ZNNVLFPXIQFABK-UHFFFAOYSA-N 0.000 claims 1
- CVJNXBWYODEEOO-UHFFFAOYSA-N 4-[2-[5-[cyclopropyl(methyl)amino]-8,8-dimethyl-6,7-dihydro-5h-naphthalen-2-yl]ethynyl]-2-fluorobenzoic acid Chemical compound C1CC(C)(C)C2=CC(C#CC=3C=C(F)C(C(O)=O)=CC=3)=CC=C2C1N(C)C1CC1 CVJNXBWYODEEOO-UHFFFAOYSA-N 0.000 claims 1
- SKHRLBFJAYNUQC-UHFFFAOYSA-N methyl 2-[4-[2-(1-cyclopropyl-4,4-dimethyl-2,3-dihydroquinolin-6-yl)ethynyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1C#CC1=CC=C(N(CCC2(C)C)C3CC3)C2=C1 SKHRLBFJAYNUQC-UHFFFAOYSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 27
- 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 26
- 229930002330 retinoic acid Natural products 0.000 abstract description 26
- 201000010099 disease Diseases 0.000 abstract description 25
- 229960001727 tretinoin Drugs 0.000 abstract description 23
- 102000004190 Enzymes Human genes 0.000 abstract description 8
- 108090000790 Enzymes Proteins 0.000 abstract description 8
- 102000018832 Cytochromes Human genes 0.000 abstract description 4
- 108010052832 Cytochromes Proteins 0.000 abstract description 4
- 230000001939 inductive effect Effects 0.000 abstract description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 325
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 320
- 239000000543 intermediate Substances 0.000 description 257
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 244
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 208
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 194
- 238000000034 method Methods 0.000 description 173
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
- 239000000243 solution Substances 0.000 description 166
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 144
- 238000005481 NMR spectroscopy Methods 0.000 description 117
- 235000019439 ethyl acetate Nutrition 0.000 description 112
- 101150041968 CDC13 gene Proteins 0.000 description 108
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 105
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 104
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 100
- 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 97
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
- 239000007787 solid Substances 0.000 description 77
- 239000003153 chemical reaction reagent Substances 0.000 description 76
- 239000000741 silica gel Substances 0.000 description 76
- 229910002027 silica gel Inorganic materials 0.000 description 76
- 239000003480 eluent Substances 0.000 description 75
- 239000003921 oil Substances 0.000 description 75
- 235000019198 oils Nutrition 0.000 description 75
- 238000005160 1H NMR spectroscopy Methods 0.000 description 74
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 69
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 68
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 68
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 63
- 238000003818 flash chromatography Methods 0.000 description 62
- 239000011541 reaction mixture Substances 0.000 description 62
- 229910001868 water Inorganic materials 0.000 description 62
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 58
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 58
- 229940086542 triethylamine Drugs 0.000 description 57
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 54
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 39
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 37
- 238000004440 column chromatography Methods 0.000 description 36
- 229910052786 argon Inorganic materials 0.000 description 34
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 150000002148 esters Chemical class 0.000 description 28
- 239000000203 mixture Substances 0.000 description 25
- 229910000027 potassium carbonate Inorganic materials 0.000 description 25
- 229940022663 acetate Drugs 0.000 description 24
- 229960000583 acetic acid Drugs 0.000 description 24
- 238000004587 chromatography analysis Methods 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 24
- 239000012071 phase Substances 0.000 description 24
- 229920006395 saturated elastomer Polymers 0.000 description 24
- 239000002253 acid Substances 0.000 description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 22
- 239000003039 volatile agent Substances 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 21
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical class C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 238000010626 work up procedure Methods 0.000 description 18
- 239000012267 brine Substances 0.000 description 17
- 239000011734 sodium Substances 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 16
- 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 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 238000005299 abrasion Methods 0.000 description 16
- 239000000284 extract Substances 0.000 description 16
- 125000001153 fluoro group Chemical group F* 0.000 description 16
- KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 16
- 229910052708 sodium Inorganic materials 0.000 description 16
- 238000003556 assay Methods 0.000 description 15
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- 239000012230 colorless oil Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 13
- 230000002265 prevention Effects 0.000 description 13
- 230000001988 toxicity Effects 0.000 description 13
- 231100000419 toxicity Toxicity 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- 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 12
- 238000004007 reversed phase HPLC Methods 0.000 description 12
- 229940094989 trimethylsilane Drugs 0.000 description 12
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical class C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 11
- 230000000699 topical effect Effects 0.000 description 11
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 10
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 10
- IYIVBGQBEMSRLO-UHFFFAOYSA-N methyl 2-(4-iodophenyl)acetate Chemical compound COC(=O)CC1=CC=C(I)C=C1 IYIVBGQBEMSRLO-UHFFFAOYSA-N 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- PDCBSXRDMMRWRF-UHFFFAOYSA-N 5,6,7,8-tetramethyl-3,4-dihydro-2h-chromene Chemical compound O1CCCC2=C(C)C(C)=C(C)C(C)=C21 PDCBSXRDMMRWRF-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 238000005886 esterification reaction Methods 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 125000005647 linker group Chemical group 0.000 description 9
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 9
- 150000004492 retinoid derivatives Chemical class 0.000 description 9
- 125000003003 spiro group Chemical group 0.000 description 9
- 125000000547 substituted alkyl group Chemical group 0.000 description 9
- WPWNEKFMGCWNPR-UHFFFAOYSA-N 3,4-dihydro-2h-thiochromene Chemical compound C1=CC=C2CCCSC2=C1 WPWNEKFMGCWNPR-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000032050 esterification Effects 0.000 description 8
- YCBJOQUNPLTBGG-UHFFFAOYSA-N ethyl 4-iodobenzoate Chemical compound CCOC(=O)C1=CC=C(I)C=C1 YCBJOQUNPLTBGG-UHFFFAOYSA-N 0.000 description 8
- 230000007794 irritation Effects 0.000 description 8
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 8
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical class NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 7
- 241000282412 Homo Species 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 7
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 7
- 150000001345 alkine derivatives Chemical class 0.000 description 7
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 230000037396 body weight Effects 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 6
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 6
- QFNABHBYVSJWLO-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-2h-naphthalen-1-one Chemical class C1C=CC=C2C(=O)CCCC21 QFNABHBYVSJWLO-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- 241000124008 Mammalia Species 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 235000019502 Orange oil Nutrition 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 239000002131 composite material Substances 0.000 description 6
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 6
- UGFHIPBXIWJXNA-UHFFFAOYSA-N liarozole Chemical compound ClC1=CC=CC(C(C=2C=C3NC=NC3=CC=2)N2C=NC=C2)=C1 UGFHIPBXIWJXNA-UHFFFAOYSA-N 0.000 description 6
- 229950007056 liarozole Drugs 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 239000010502 orange oil Substances 0.000 description 6
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 5
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 5
- 201000004681 Psoriasis Diseases 0.000 description 5
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- ZINVXYJYHMFSCJ-UHFFFAOYSA-N ethyl 2-(2-fluoro-4-iodophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(I)C=C1F ZINVXYJYHMFSCJ-UHFFFAOYSA-N 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 238000004305 normal phase HPLC Methods 0.000 description 5
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
- 229940049953 phenylacetate Drugs 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 239000010936 titanium Substances 0.000 description 5
- 229910052719 titanium Inorganic materials 0.000 description 5
- IPSRAFUHLHIWAR-UHFFFAOYSA-N zinc;ethane Chemical compound [Zn+2].[CH2-]C.[CH2-]C IPSRAFUHLHIWAR-UHFFFAOYSA-N 0.000 description 5
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 4
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- JVIOPGPPUFQCFR-UHFFFAOYSA-N 2',3'-dimethylspiro[chromene-2,1'-cyclopropane] Chemical compound CC1C(C12OC1=C(C=C2)C=CC=C1)C JVIOPGPPUFQCFR-UHFFFAOYSA-N 0.000 description 4
- NHDVFXNUAUYRHR-UHFFFAOYSA-N 2,2,4,4-tetramethyl-3h-chromene Chemical compound C1=CC=C2OC(C)(C)CC(C)(C)C2=C1 NHDVFXNUAUYRHR-UHFFFAOYSA-N 0.000 description 4
- YIOBTWJWUAFQHJ-UHFFFAOYSA-N 4,4-dimethylspiro[3H-chromene-2,1'-cyclopropane] Chemical compound CC1(CC2(OC3=C1C=CC=C3)CC2)C YIOBTWJWUAFQHJ-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 4
- 241000701806 Human papillomavirus Species 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 4
- 108010022037 Retinoic Acid 4-Hydroxylase Proteins 0.000 description 4
- 206010038934 Retinopathy proliferative Diseases 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 4
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 230000006907 apoptotic process Effects 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
- 238000004364 calculation method Methods 0.000 description 4
- 229940126543 compound 14 Drugs 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- 150000002084 enol ethers Chemical class 0.000 description 4
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 4
- 229940058172 ethylbenzene Drugs 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000003463 hyperproliferative effect Effects 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 125000006303 iodophenyl group Chemical group 0.000 description 4
- 229960004125 ketoconazole Drugs 0.000 description 4
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 4
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 4
- SCHHLHKOJRWALP-UHFFFAOYSA-N methyl 2-fluoro-4-iodobenzoate Chemical compound COC(=O)C1=CC=C(I)C=C1F SCHHLHKOJRWALP-UHFFFAOYSA-N 0.000 description 4
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 4
- 150000002829 nitrogen Chemical class 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 4
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 4
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 4
- 208000017520 skin disease Diseases 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 229960000187 tissue plasminogen activator Drugs 0.000 description 4
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 4
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 3
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 3
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 3
- 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
- IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 description 3
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 3
- XQXPVVBIMDBYFF-UHFFFAOYSA-N 4-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C=C1 XQXPVVBIMDBYFF-UHFFFAOYSA-N 0.000 description 3
- HCCNBKFJYUWLEX-UHFFFAOYSA-N 7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one Chemical compound O=C1N(CCOCCC)C2=CC(C=3C=NC(OC)=CC=3)=NC=C2N=C1NCC1=CN=CC=N1 HCCNBKFJYUWLEX-UHFFFAOYSA-N 0.000 description 3
- 208000002874 Acne Vulgaris Diseases 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 229940126639 Compound 33 Drugs 0.000 description 3
- 229940127007 Compound 39 Drugs 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 101150102856 POU2F1 gene Proteins 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 229910006124 SOCl2 Inorganic materials 0.000 description 3
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 3
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 3
- IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 3
- 206010000496 acne Diseases 0.000 description 3
- 150000001263 acyl chlorides Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 229940126142 compound 16 Drugs 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 229940125846 compound 25 Drugs 0.000 description 3
- 229940125851 compound 27 Drugs 0.000 description 3
- 229940125877 compound 31 Drugs 0.000 description 3
- 229940126545 compound 53 Drugs 0.000 description 3
- 229920001577 copolymer Chemical group 0.000 description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000011905 homologation Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000001294 propane Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 239000012049 topical pharmaceutical composition Substances 0.000 description 3
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 2
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 2
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 2
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 2
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 2
- 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 2
- RDOXILXISZRPFQ-UHFFFAOYSA-N (4-bromophenyl) 3-methylbut-2-enoate Chemical compound CC(C)=CC(=O)OC1=CC=C(Br)C=C1 RDOXILXISZRPFQ-UHFFFAOYSA-N 0.000 description 2
- IOQORVDNYPOZPL-VQTJNVASSA-N (5S,6R)-5-(4-chlorophenyl)-6-cyclopropyl-3-[6-methoxy-5-(4-methylimidazol-1-yl)pyridin-2-yl]-5,6-dihydro-2H-1,2,4-oxadiazine Chemical compound ClC1=CC=C(C=C1)[C@@H]1NC(=NO[C@@H]1C1CC1)C1=NC(=C(C=C1)N1C=NC(=C1)C)OC IOQORVDNYPOZPL-VQTJNVASSA-N 0.000 description 2
- ZXMGHDIOOHOAAE-UHFFFAOYSA-N 1,1,1-trifluoro-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)NS(=O)(=O)C(F)(F)F ZXMGHDIOOHOAAE-UHFFFAOYSA-N 0.000 description 2
- MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 description 2
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 2
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 2
- ALWAKZAFAKRUNG-UHFFFAOYSA-N 2-(2-fluoro-4-iodophenyl)acetonitrile Chemical compound FC1=CC(I)=CC=C1CC#N ALWAKZAFAKRUNG-UHFFFAOYSA-N 0.000 description 2
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 2
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 2
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 2
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 2
- DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- BDUBTLFQHNYXPC-UHFFFAOYSA-N 3-methylbut-2-enoyl chloride Chemical compound CC(C)=CC(Cl)=O BDUBTLFQHNYXPC-UHFFFAOYSA-N 0.000 description 2
- QOWZBQAJZICMKD-UHFFFAOYSA-N 4,4-dimethyl-2,3-dihydro-1h-isoquinoline Chemical compound C1=CC=C2C(C)(C)CNCC2=C1 QOWZBQAJZICMKD-UHFFFAOYSA-N 0.000 description 2
- WDLBKPHWHMIYNG-UHFFFAOYSA-N 4,4-dimethyl-2,3-dihydro-1h-quinoline Chemical compound C1=CC=C2C(C)(C)CCNC2=C1 WDLBKPHWHMIYNG-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 2
- TUXYZHVUPGXXQG-UHFFFAOYSA-N 4-bromobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1 TUXYZHVUPGXXQG-UHFFFAOYSA-N 0.000 description 2
- DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 2
- VQJNJGBSRXLRSA-UHFFFAOYSA-N 5-methoxy-3,3-dimethyl-2h-inden-1-one Chemical compound COC1=CC=C2C(=O)CC(C)(C)C2=C1 VQJNJGBSRXLRSA-UHFFFAOYSA-N 0.000 description 2
- ZMEGAKQYQYQIHK-UHFFFAOYSA-N 6-bromo-4,4-dimethyl-3h-chromen-2-one Chemical compound C1=C(Br)C=C2C(C)(C)CC(=O)OC2=C1 ZMEGAKQYQYQIHK-UHFFFAOYSA-N 0.000 description 2
- GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 2
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 2
- 206010059313 Anogenital warts Diseases 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 229940126657 Compound 17 Drugs 0.000 description 2
- 208000000907 Condylomata Acuminata Diseases 0.000 description 2
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 2
- 101100202237 Danio rerio rxrab gene Proteins 0.000 description 2
- 101100309320 Danio rerio rxrga gene Proteins 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 2
- 206010013774 Dry eye Diseases 0.000 description 2
- 208000032928 Dyslipidaemia Diseases 0.000 description 2
- 206010058314 Dysplasia Diseases 0.000 description 2
- 102000018997 Growth Hormone Human genes 0.000 description 2
- 108010051696 Growth Hormone Proteins 0.000 description 2
- 206010021197 Ichthyoses Diseases 0.000 description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 description 2
- 208000001126 Keratosis Diseases 0.000 description 2
- 206010054949 Metaplasia Diseases 0.000 description 2
- 101100189356 Mus musculus Papolb gene Proteins 0.000 description 2
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 2
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 101150050070 RXRA gene Proteins 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- 208000000260 Warts Diseases 0.000 description 2
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 2
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 2
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 2
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 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 2
- 150000001408 amides Chemical class 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- 208000025009 anogenital human papillomavirus infection Diseases 0.000 description 2
- 201000004201 anogenital venereal wart Diseases 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 229910052785 arsenic Inorganic materials 0.000 description 2
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 2
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- URAOANIJEFDBLH-UHFFFAOYSA-N benzyl 4-bromo-2-ethylbenzoate Chemical compound CCC1=CC(Br)=CC=C1C(=O)OCC1=CC=CC=C1 URAOANIJEFDBLH-UHFFFAOYSA-N 0.000 description 2
- CKXJOUQTHOVDON-UHFFFAOYSA-N benzyl 4-bromobenzoate Chemical compound C1=CC(Br)=CC=C1C(=O)OCC1=CC=CC=C1 CKXJOUQTHOVDON-UHFFFAOYSA-N 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000003679 cervix uteri Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 108700010039 chimeric receptor Proteins 0.000 description 2
- 229940117975 chromium trioxide Drugs 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 2
- 206010009887 colitis Diseases 0.000 description 2
- 210000001072 colon Anatomy 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940126086 compound 21 Drugs 0.000 description 2
- 229940126208 compound 22 Drugs 0.000 description 2
- 229940125833 compound 23 Drugs 0.000 description 2
- 229940125961 compound 24 Drugs 0.000 description 2
- 229940127204 compound 29 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940125807 compound 37 Drugs 0.000 description 2
- 229940127573 compound 38 Drugs 0.000 description 2
- 229940126540 compound 41 Drugs 0.000 description 2
- 229940125936 compound 42 Drugs 0.000 description 2
- 229940127271 compound 49 Drugs 0.000 description 2
- 229940127113 compound 57 Drugs 0.000 description 2
- 229940125900 compound 59 Drugs 0.000 description 2
- 229940126179 compound 72 Drugs 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- AXAZMDOAUQTMOW-UHFFFAOYSA-N dimethylzinc Chemical compound C[Zn]C AXAZMDOAUQTMOW-UHFFFAOYSA-N 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 2
- GAQVJPBRDCFXHW-UHFFFAOYSA-N ethyl 4-ethynyl-2-fluorobenzoate Chemical compound CCOC(=O)C1=CC=C(C#C)C=C1F GAQVJPBRDCFXHW-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 239000000122 growth hormone Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 230000003779 hair growth Effects 0.000 description 2
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 2
- 206010021198 ichthyosis Diseases 0.000 description 2
- 208000009326 ileitis Diseases 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- 229960001438 immunostimulant agent Drugs 0.000 description 2
- 239000003022 immunostimulating agent Substances 0.000 description 2
- 230000003308 immunostimulating effect Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 230000006882 induction of apoptosis Effects 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- AMZMQXJQIYKBJU-UHFFFAOYSA-N iodo benzoate Chemical compound IOC(=O)C1=CC=CC=C1 AMZMQXJQIYKBJU-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000003780 keratinization Effects 0.000 description 2
- 210000000867 larynx Anatomy 0.000 description 2
- 201000011486 lichen planus Diseases 0.000 description 2
- 238000000670 ligand binding assay Methods 0.000 description 2
- 230000037356 lipid metabolism Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 2
- 229910001623 magnesium bromide Inorganic materials 0.000 description 2
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 230000015689 metaplastic ossification Effects 0.000 description 2
- DZYKILFYVRVLFU-UHFFFAOYSA-N methyl 2-(2-fluoro-4-iodophenyl)acetate Chemical compound COC(=O)CC1=CC=C(I)C=C1F DZYKILFYVRVLFU-UHFFFAOYSA-N 0.000 description 2
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 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 2
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 2
- 230000009826 neoplastic cell growth Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 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 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].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.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 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 208000003154 papilloma Diseases 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 230000008832 photodamage Effects 0.000 description 2
- 230000001817 pituitary effect Effects 0.000 description 2
- 229920000333 poly(propyleneimine) Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 102000027478 retinoid receptor subtypes Human genes 0.000 description 2
- 108091008678 retinoid receptor subtypes Proteins 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 201000010153 skin papilloma Diseases 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- KEAYESYHFKHZAL-OUBTZVSYSA-N sodium-24 Chemical compound [24Na] KEAYESYHFKHZAL-OUBTZVSYSA-N 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- WQUCQEYAGIYKSV-UHFFFAOYSA-N trimethyl-[2-(2,2,4,4-tetramethyl-3H-chromen-3-yl)ethynyl]silane Chemical compound C[Si](C)(C)C#CC1C(OC2=CC=CC=C2C1(C)C)(C)C WQUCQEYAGIYKSV-UHFFFAOYSA-N 0.000 description 2
- 210000003932 urinary bladder Anatomy 0.000 description 2
- 210000004291 uterus Anatomy 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
- DQTRDMFDRUMQHG-UHFFFAOYSA-N (2-cyclopropyl-4,4-dimethyl-1,3-dihydroisoquinolin-6-yl) trifluoromethanesulfonate Chemical compound C1C2=CC=C(OS(=O)(=O)C(F)(F)F)C=C2C(C)(C)CN1C1CC1 DQTRDMFDRUMQHG-UHFFFAOYSA-N 0.000 description 1
- ISBSSBGEYIBVTO-TYKWNDPBSA-N (20R,22R)-20,22-dihydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@](C)(O)[C@H](O)CCC(C)C)[C@@]1(C)CC2 ISBSSBGEYIBVTO-TYKWNDPBSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
- FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 1
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- MXHYFISNECFQHA-UHFFFAOYSA-N (4-iodophenyl) acetate Chemical compound CC(=O)OC1=CC=C(I)C=C1 MXHYFISNECFQHA-UHFFFAOYSA-N 0.000 description 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
- OIIOPWHTJZYKIL-PMACEKPBSA-N (5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one Chemical compound C1(=C(N=C(C2=C(C(C3=CC=CC(=C3Cl)C3=NC(OC)=C(N=C3)CNC[C@H]3NC(=O)CC3)=CC=C2)Cl)C=N1)OC)CNC[C@H]1NC(=O)CC1 OIIOPWHTJZYKIL-PMACEKPBSA-N 0.000 description 1
- SRKGZXIJDGWVAI-GVAVTCRGSA-M (e,3r)-7-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)C1=NC(C(C)(C)C)=CC(C=2C=CC(F)=CC=2)=C1\C=C\C(O)C[C@@H](O)CC([O-])=O SRKGZXIJDGWVAI-GVAVTCRGSA-M 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- LMWFCQBHWSLJHM-UHFFFAOYSA-N 1,1-dimethyl-3,4-dihydro-2H-isoquinoline-6-carbaldehyde Chemical compound CC1(NCCC2=CC(=CC=C12)C=O)C LMWFCQBHWSLJHM-UHFFFAOYSA-N 0.000 description 1
- SPASUAZZYDHFPM-UHFFFAOYSA-N 1,1-dimethyl-3,4-dihydroisoquinoline-2-carbaldehyde Chemical compound C1=CC=C2C(C)(C)N(C=O)CCC2=C1 SPASUAZZYDHFPM-UHFFFAOYSA-N 0.000 description 1
- NTAGXJQHJQUOOA-UHFFFAOYSA-N 1,2,3,4-tetrahydronaphthalene-2-carboxylic acid Chemical compound C1=CC=C2CC(C(=O)O)CCC2=C1 NTAGXJQHJQUOOA-UHFFFAOYSA-N 0.000 description 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- HTVBVYGZKUSMHF-UHFFFAOYSA-N 1,2-dimethyl-3,4-dihydro-2h-quinoline Chemical compound C1=CC=C2N(C)C(C)CCC2=C1 HTVBVYGZKUSMHF-UHFFFAOYSA-N 0.000 description 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
- VDARUWWMXLYABC-UHFFFAOYSA-N 1-(bromomethyl)-2-fluoro-4-iodobenzene Chemical compound FC1=CC(I)=CC=C1CBr VDARUWWMXLYABC-UHFFFAOYSA-N 0.000 description 1
- LSHNHBIMENYOQK-UHFFFAOYSA-N 1-bromo-4-(1-methoxycyclopropyl)benzene Chemical compound C=1C=C(Br)C=CC=1C1(OC)CC1 LSHNHBIMENYOQK-UHFFFAOYSA-N 0.000 description 1
- FYJFFDDXEGFRLK-UHFFFAOYSA-N 1-bromo-4-(1-methoxyethenyl)benzene Chemical compound COC(=C)C1=CC=C(Br)C=C1 FYJFFDDXEGFRLK-UHFFFAOYSA-N 0.000 description 1
- SZRMBIPVRWIUOJ-UHFFFAOYSA-N 1-bromo-4-(1-phenylmethoxyethenyl)benzene Chemical compound C1=CC(Br)=CC=C1C(=C)OCC1=CC=CC=C1 SZRMBIPVRWIUOJ-UHFFFAOYSA-N 0.000 description 1
- JCMRUUQLLHHWSW-UHFFFAOYSA-N 1-bromo-4-(1-propan-2-yloxyethenyl)benzene Chemical compound CC(C)OC(=C)C1=CC=C(Br)C=C1 JCMRUUQLLHHWSW-UHFFFAOYSA-N 0.000 description 1
- RKTLSSSSKADLBN-UHFFFAOYSA-N 1-cyclopropyl-4,4-dimethyl-2,3-dihydro-1H-isoquinoline-6-carbaldehyde Chemical compound C1(CC1)C1NCC(C2=CC(=CC=C12)C=O)(C)C RKTLSSSSKADLBN-UHFFFAOYSA-N 0.000 description 1
- 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 1
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 1
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- QXJWKKXKURVOMU-UHFFFAOYSA-N 2-(2-fluoro-4-iodophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(I)C=C1F QXJWKKXKURVOMU-UHFFFAOYSA-N 0.000 description 1
- YNTJKQDWYXUTLZ-UHFFFAOYSA-N 2-(3-chlorophenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=CC=CC(Cl)=C1 YNTJKQDWYXUTLZ-UHFFFAOYSA-N 0.000 description 1
- XTHBCPJTMVZTPE-UHFFFAOYSA-N 2-(4,4-dimethyl-2,3-dihydroquinolin-1-yl)ethynyl-trimethylsilane Chemical compound C1=CC=C2C(C)(C)CCN(C#C[Si](C)(C)C)C2=C1 XTHBCPJTMVZTPE-UHFFFAOYSA-N 0.000 description 1
- FJSHTWVDFAUNCO-UHFFFAOYSA-N 2-(4-iodophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(I)C=C1 FJSHTWVDFAUNCO-UHFFFAOYSA-N 0.000 description 1
- PAYROHWFGZADBR-UHFFFAOYSA-N 2-[[4-amino-5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidin-2-yl]amino]propane-1,3-diol Chemical compound C1=C(I)C(OC)=CC(C(C)C)=C1OC1=CN=C(NC(CO)CO)N=C1N PAYROHWFGZADBR-UHFFFAOYSA-N 0.000 description 1
- ADHGKAMLCVLWLS-UHFFFAOYSA-N 2-ethynyl-1,2,3,4-tetrahydronaphthalene Chemical compound C1=CC=C2CC(C#C)CCC2=C1 ADHGKAMLCVLWLS-UHFFFAOYSA-N 0.000 description 1
- ZSNZFDAZLLRCEL-UHFFFAOYSA-N 2-fluoro-2-iodo-2-phenylacetic acid Chemical compound OC(=O)C(F)(I)C1=CC=CC=C1 ZSNZFDAZLLRCEL-UHFFFAOYSA-N 0.000 description 1
- NXWTWYULZRDBSA-UHFFFAOYSA-N 2-fluoro-4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1F NXWTWYULZRDBSA-UHFFFAOYSA-N 0.000 description 1
- QZLWTFTXGKKCHZ-UHFFFAOYSA-N 2-fluoro-4-iodo-1-methylbenzene Chemical compound CC1=CC=C(I)C=C1F QZLWTFTXGKKCHZ-UHFFFAOYSA-N 0.000 description 1
- ZUKTUEOOOXEFML-UHFFFAOYSA-N 2-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=CC=C2C(=O)C(OC)CCC2=C1 ZUKTUEOOOXEFML-UHFFFAOYSA-N 0.000 description 1
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 1
- 101150098072 20 gene Proteins 0.000 description 1
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical group [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 1
- RJAYWHRDCHVZQC-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-1H-isoquinoline-2-carbaldehyde Chemical compound C1C=CC=C2CN(C=O)CCC21 RJAYWHRDCHVZQC-UHFFFAOYSA-N 0.000 description 1
- CHOVRXRQUYRLHZ-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-2h-quinoline-1-carbaldehyde Chemical compound C1C=CC=C2N(C=O)CCCC21 CHOVRXRQUYRLHZ-UHFFFAOYSA-N 0.000 description 1
- WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 1
- DVGCDEKJXRBYOC-UHFFFAOYSA-N 3-bromo-1,4,4-trimethyl-3H-quinolin-2-one Chemical compound BrC1C(N(C2=CC=CC=C2C1(C)C)C)=O DVGCDEKJXRBYOC-UHFFFAOYSA-N 0.000 description 1
- FVMDYYGIDFPZAX-UHFFFAOYSA-N 3-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=CC(O)=C1 FVMDYYGIDFPZAX-UHFFFAOYSA-N 0.000 description 1
- ZLUJQEVPPFXWGW-UHFFFAOYSA-N 4,4-dimethyl-2-methylidene-3H-chromene Chemical compound CC1(C)CC(=C)Oc2ccccc12 ZLUJQEVPPFXWGW-UHFFFAOYSA-N 0.000 description 1
- SJHPCNCNNSSLPL-UHFFFAOYSA-N 4-(ethoxymethylene)-2-phenyloxazol-5-one Chemical compound O1C(=O)C(=COCC)N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-UHFFFAOYSA-N 0.000 description 1
- IFGLFRBENZAFPT-UHFFFAOYSA-N 4-[1-(2,2-dimethylpropoxy)cyclopropyl]-1-ethynyl-2-methylbenzene Chemical compound C1=C(C#C)C(C)=CC(C2(CC2)OCC(C)(C)C)=C1 IFGLFRBENZAFPT-UHFFFAOYSA-N 0.000 description 1
- DAXQCSQIJIHHBU-UHFFFAOYSA-N 4-bromo-2-(4-hydroxy-2,4-dimethylpentan-2-yl)phenol Chemical compound CC(C)(O)CC(C)(C)C1=CC(Br)=CC=C1O DAXQCSQIJIHHBU-UHFFFAOYSA-N 0.000 description 1
- YTTOXYJBLIMLQL-UHFFFAOYSA-N 4-bromo-2-ethyl-1-(1-phenylmethoxycyclopropyl)benzene Chemical compound CCC1=CC(Br)=CC=C1C1(OCC=2C=CC=CC=2)CC1 YTTOXYJBLIMLQL-UHFFFAOYSA-N 0.000 description 1
- AXVMOWPQXSKSHL-UHFFFAOYSA-N 4-bromo-2-ethyl-1-(1-phenylmethoxyethenyl)benzene Chemical compound CCC1=CC(Br)=CC=C1C(=C)OCC1=CC=CC=C1 AXVMOWPQXSKSHL-UHFFFAOYSA-N 0.000 description 1
- QICLFMFOLSIPOD-UHFFFAOYSA-N 4-bromo-2-ethylbenzoic acid Chemical compound CCC1=CC(Br)=CC=C1C(O)=O QICLFMFOLSIPOD-UHFFFAOYSA-N 0.000 description 1
- RVCJOGNLYVNRDN-UHFFFAOYSA-N 4-bromo-2-methylbenzoic acid Chemical compound CC1=CC(Br)=CC=C1C(O)=O RVCJOGNLYVNRDN-UHFFFAOYSA-N 0.000 description 1
- KWVXDZLVCISXIB-UHFFFAOYSA-N 4-bromo-3-methylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC=C1Br KWVXDZLVCISXIB-UHFFFAOYSA-N 0.000 description 1
- AYVPVDWQZAAZCM-UHFFFAOYSA-N 4-bromo-n-methylaniline Chemical compound CNC1=CC=C(Br)C=C1 AYVPVDWQZAAZCM-UHFFFAOYSA-N 0.000 description 1
- TUXYZHVUPGXXQG-UHFFFAOYSA-M 4-bromobenzoate Chemical compound [O-]C(=O)C1=CC=C(Br)C=C1 TUXYZHVUPGXXQG-UHFFFAOYSA-M 0.000 description 1
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- GSDQYSSLIKJJOG-UHFFFAOYSA-N 4-chloro-2-(3-chloroanilino)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1NC1=CC=CC(Cl)=C1 GSDQYSSLIKJJOG-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
- WJRKNLONLOMALV-UHFFFAOYSA-N 5-chloropyridine Chemical compound ClC1=C=NC=C[CH]1 WJRKNLONLOMALV-UHFFFAOYSA-N 0.000 description 1
- HADAVSLDWIFQNY-UHFFFAOYSA-N 5-methoxy-3,3-dimethyl-1,2-dihydroindene Chemical compound COC1=CC=C2CCC(C)(C)C2=C1 HADAVSLDWIFQNY-UHFFFAOYSA-N 0.000 description 1
- IJRKLHTZAIFUTB-UHFFFAOYSA-N 5-nitro-2-(2-phenylethylamino)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NCCC1=CC=CC=C1 IJRKLHTZAIFUTB-UHFFFAOYSA-N 0.000 description 1
- QXHDUBVENJRQSR-UHFFFAOYSA-N 6-(2-trimethylsilylethynyl)-3,4-dihydro-1H-naphthalen-2-one Chemical compound C[Si](C)(C)C#CC=1C=C2CCC(CC2=CC1)=O QXHDUBVENJRQSR-UHFFFAOYSA-N 0.000 description 1
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
- QGBXGWZCNVMPQB-UHFFFAOYSA-N 6-bromo-2,2,4,4-tetramethyl-3h-thiochromene Chemical compound BrC1=CC=C2SC(C)(C)CC(C)(C)C2=C1 QGBXGWZCNVMPQB-UHFFFAOYSA-N 0.000 description 1
- WBOOAXJWGJAIMB-UHFFFAOYSA-N 6-bromo-4,4-dimethyl-2,3-dihydro-1h-quinoline Chemical compound C1=C(Br)C=C2C(C)(C)CCNC2=C1 WBOOAXJWGJAIMB-UHFFFAOYSA-N 0.000 description 1
- WMFWCNYKBAYFGA-UHFFFAOYSA-N 6-bromo-8-cyclopropyl-4,4-dimethylspiro[3h-chromene-2,1'-cyclopropane] Chemical compound O1C2=C(C3CC3)C=C(Br)C=C2C(C)(C)CC21CC2 WMFWCNYKBAYFGA-UHFFFAOYSA-N 0.000 description 1
- MFJYBRBHKROOPH-UHFFFAOYSA-N 6-ethynyl-n,4,4-trimethyl-n-propan-2-yl-2,3-dihydro-1h-naphthalen-1-amine Chemical compound C#CC1=CC=C2C(N(C)C(C)C)CCC(C)(C)C2=C1 MFJYBRBHKROOPH-UHFFFAOYSA-N 0.000 description 1
- UJGDLLGKMWVCPT-UHFFFAOYSA-N 6-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2CCC(=O)C2=C1 UJGDLLGKMWVCPT-UHFFFAOYSA-N 0.000 description 1
- FFSDUEDAAQFMHC-UHFFFAOYSA-N 6-methoxy-4,4-dimethyl-2,3-dihydro-1h-isoquinoline Chemical compound C1NCC(C)(C)C2=CC(OC)=CC=C21 FFSDUEDAAQFMHC-UHFFFAOYSA-N 0.000 description 1
- ZCWLXIWJQXVJKO-UHFFFAOYSA-N 6-methoxy-4,4-dimethyl-2,3-dihydro-1h-naphthalene Chemical compound C1CCC(C)(C)C2=CC(OC)=CC=C21 ZCWLXIWJQXVJKO-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- KXTPWCBWIATUET-UHFFFAOYSA-N 8-ethenyl-4,4-dimethylspiro[3H-chromene-2,1'-cyclopropane] Chemical compound CC1(CC2(OC3=C1C=CC=C3C=C)CC2)C KXTPWCBWIATUET-UHFFFAOYSA-N 0.000 description 1
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
- 206010000503 Acne cystic Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 241000182988 Assa Species 0.000 description 1
- 229910015845 BBr3 Inorganic materials 0.000 description 1
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
- OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 101710160472 Carbon monoxide dehydrogenase 1 Proteins 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 1
- 101100456896 Drosophila melanogaster metl gene Proteins 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 101000745891 Homo sapiens Cytochrome P450 26A1 Proteins 0.000 description 1
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical group COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
- AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 1
- POFVJRKJJBFPII-UHFFFAOYSA-N N-cyclopentyl-5-[2-[[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1(CCCC1)NC=1SC(=C(N=1)C)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)CC POFVJRKJJBFPII-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 101100513046 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) eth-1 gene Proteins 0.000 description 1
- 241001442654 Percnon planissimum Species 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 101100482117 Saimiri sciureus THBD gene Proteins 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- HJSWGKDSNMUBRY-UHFFFAOYSA-N [4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]phenyl] 2,2,4,4-tetramethyl-3h-chromene-6-carboxylate Chemical compound C1=CC(CC(=O)OC(C)(C)C)=CC=C1OC(=O)C1=CC=C(OC(C)(C)CC2(C)C)C2=C1 HJSWGKDSNMUBRY-UHFFFAOYSA-N 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 229960005339 acitretin Drugs 0.000 description 1
- 208000009621 actinic keratosis Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- IHUNBGSDBOWDMA-AQFIFDHZSA-N all-trans-acitretin Chemical compound COC1=CC(C)=C(\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O)C(C)=C1C IHUNBGSDBOWDMA-AQFIFDHZSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 150000001500 aryl chlorides Chemical class 0.000 description 1
- 150000007860 aryl ester derivatives Chemical class 0.000 description 1
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 1
- 229940090012 bentyl Drugs 0.000 description 1
- QEZVRJNTXBDINZ-UHFFFAOYSA-N benzyl 4-bromo-2-methylbenzoate Chemical compound CC1=CC(Br)=CC=C1C(=O)OCC1=CC=CC=C1 QEZVRJNTXBDINZ-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- FBCNRCVXBGRPQU-UHFFFAOYSA-N bromo benzoate Chemical compound BrOC(=O)C1=CC=CC=C1 FBCNRCVXBGRPQU-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- TUFGVZMNGTYAQD-UHFFFAOYSA-N comins' reagent Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=C(Cl)C=N1 TUFGVZMNGTYAQD-UHFFFAOYSA-N 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940125878 compound 36 Drugs 0.000 description 1
- 229940125844 compound 46 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- GUBNMFJOJGDCEL-UHFFFAOYSA-N dicyclomine hydrochloride Chemical group [Cl-].C1CCCCC1C1(C(=O)OCC[NH+](CC)CC)CCCCC1 GUBNMFJOJGDCEL-UHFFFAOYSA-N 0.000 description 1
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- ORVACBDINATSAR-UHFFFAOYSA-N dimethylaluminum Chemical compound C[Al]C ORVACBDINATSAR-UHFFFAOYSA-N 0.000 description 1
- WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- NDRMKYGXPVSWMV-UHFFFAOYSA-N ethyl 2-fluoro-4-(2-trimethylsilylethynyl)benzoate Chemical compound CCOC(=O)C1=CC=C(C#C[Si](C)(C)C)C=C1F NDRMKYGXPVSWMV-UHFFFAOYSA-N 0.000 description 1
- WNKIKZLKALPNKP-UHFFFAOYSA-N ethyl 2-fluoro-4-(trifluoromethylsulfonyloxy)benzoate Chemical compound CCOC(=O)C1=CC=C(OS(=O)(=O)C(F)(F)F)C=C1F WNKIKZLKALPNKP-UHFFFAOYSA-N 0.000 description 1
- MWKPJOZJIAQHTB-UHFFFAOYSA-N ethyl 2-fluoro-4-hydroxybenzoate Chemical compound CCOC(=O)C1=CC=C(O)C=C1F MWKPJOZJIAQHTB-UHFFFAOYSA-N 0.000 description 1
- ZYZGFQIQZUBVPT-UHFFFAOYSA-N ethyl 4-[2-(8-cyclopropyl-2,2,4,4-tetramethyl-3h-chromen-6-yl)ethynyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C#CC1=CC(C2CC2)=C(OC(C)(C)CC2(C)C)C2=C1 ZYZGFQIQZUBVPT-UHFFFAOYSA-N 0.000 description 1
- XMGXMUKCUANNLV-UHFFFAOYSA-N ethyl 4-[2-[4-(1-phenylmethoxycyclopropyl)phenyl]ethynyl]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(C2(CC2)OCC=2C=CC=CC=2)C=C1 XMGXMUKCUANNLV-UHFFFAOYSA-N 0.000 description 1
- UKMMYQIWPFZQIS-UHFFFAOYSA-N ethyl 5-iodofuran-3-carboxylate Chemical compound CCOC(=O)C1=COC(I)=C1 UKMMYQIWPFZQIS-UHFFFAOYSA-N 0.000 description 1
- OMVRJXZNKOPMRA-UHFFFAOYSA-N ethyl 5-iodothiophene-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(I)S1 OMVRJXZNKOPMRA-UHFFFAOYSA-N 0.000 description 1
- KWUIVKFNXQGVSY-UHFFFAOYSA-N ethyl 5-iodothiophene-3-carboxylate Chemical compound CCOC(=O)C1=CSC(I)=C1 KWUIVKFNXQGVSY-UHFFFAOYSA-N 0.000 description 1
- KKKHZZOMDYNIKE-UHFFFAOYSA-N ethyl 6-iodopyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC=C(I)N=C1 KKKHZZOMDYNIKE-UHFFFAOYSA-N 0.000 description 1
- 229960002199 etretinate Drugs 0.000 description 1
- HQMNCQVAMBCHCO-DJRRULDNSA-N etretinate Chemical compound CCOC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C=C(OC)C(C)=C1C HQMNCQVAMBCHCO-DJRRULDNSA-N 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000002035 hexane extract Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- HBMCQTHGYMTCOF-UHFFFAOYSA-N hydroquinone monoacetate Natural products CC(=O)OC1=CC=C(O)C=C1 HBMCQTHGYMTCOF-UHFFFAOYSA-N 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-M hydroxide;hydrate Chemical compound O.[OH-] JEGUKCSWCFPDGT-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910001410 inorganic ion Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 1
- ADAHADRJWVCICR-UHFFFAOYSA-N isoquinoline-6-carboxylic acid Chemical compound C1=NC=CC2=CC(C(=O)O)=CC=C21 ADAHADRJWVCICR-UHFFFAOYSA-N 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 208000002741 leukoplakia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- XEPQADIWKRDGOM-UHFFFAOYSA-N methyl 2-[4-[2-(2,2,4,4-tetramethyl-3h-chromen-6-yl)ethynyl]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1C#CC1=CC=C(OC(C)(C)CC2(C)C)C2=C1 XEPQADIWKRDGOM-UHFFFAOYSA-N 0.000 description 1
- CZNGTXVOZOWWKM-UHFFFAOYSA-N methyl 4-bromobenzoate Chemical compound COC(=O)C1=CC=C(Br)C=C1 CZNGTXVOZOWWKM-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 229940073584 methylene chloride Drugs 0.000 description 1
- XYDYWTJEGDZLTH-UHFFFAOYSA-N methylenetriphenylphosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=C)C1=CC=CC=C1 XYDYWTJEGDZLTH-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- MTKBKHIRLNIYGX-UHFFFAOYSA-N n-(4-bromophenyl)-n,3-dimethylbut-2-enamide Chemical compound CC(C)=CC(=O)N(C)C1=CC=C(Br)C=C1 MTKBKHIRLNIYGX-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
- KPSSIOMAKSHJJG-UHFFFAOYSA-N neopentyl alcohol Chemical compound CC(C)(C)CO KPSSIOMAKSHJJG-UHFFFAOYSA-N 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
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- IKNCGYCHMGNBCP-UHFFFAOYSA-N propan-1-olate Chemical compound CCC[O-] IKNCGYCHMGNBCP-UHFFFAOYSA-N 0.000 description 1
- HTZUIGNAYGHEGG-UHFFFAOYSA-N propan-2-yl 4-bromo-2-methylbenzoate Chemical compound CC(C)OC(=O)C1=CC=C(Br)C=C1C HTZUIGNAYGHEGG-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
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000030541 receptor transactivation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 230000036620 skin dryness Effects 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 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
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 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
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 150000003530 tetrahydroquinolines Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- TUMGRIOPKPEFCZ-UHFFFAOYSA-N trimethyl-[2-[4-(1-propan-2-yloxycyclopropyl)phenyl]ethynyl]silane Chemical compound C=1C=C(C#C[Si](C)(C)C)C=CC=1C1(OC(C)C)CC1 TUMGRIOPKPEFCZ-UHFFFAOYSA-N 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- 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
- 229960000281 trometamol Drugs 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 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 |
| US09/651,001 | 2000-08-29 | ||
| US09/651,234 US6387951B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US09/651,235 US6252090B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US09/651,234 | 2000-08-29 | ||
| US09/651,003 | 2000-08-29 | ||
| US09/651,003 US6303785B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US09/651,564 | 2000-08-29 | ||
| US09/651,235 | 2000-08-29 | ||
| US09/651,564 US6380256B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US09/651,004 | 2000-08-29 | ||
| US09/651,004 US6369261B1 (en) | 2000-08-29 | 2000-08-29 | Compounds having activity as inhibitors of cytochrome P450RAI |
| US09/651,566 | 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 |
|---|---|
| CA2420869A1 true CA2420869A1 (en) | 2002-03-07 |
Family
ID=27569871
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002420869A Abandoned CA2420869A1 (en) | 2000-08-29 | 2001-08-14 | Compounds having activity as inhibitors of cytochrome 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) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8575134B2 (en) | 2004-12-13 | 2013-11-05 | Ono Pharmaceutical Co., Ltd. | Aminocarboxylic acid derivative and medicinal use thereof |
| US8791159B2 (en) | 2003-08-29 | 2014-07-29 | Ono Pharmaceutical Co., Ltd. | Compound capable of binding S1P receptor and pharmaceutical use thereof |
Families Citing this family (18)
| 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 |
| 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 |
| 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
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8791159B2 (en) | 2003-08-29 | 2014-07-29 | Ono Pharmaceutical Co., Ltd. | Compound capable of binding S1P receptor and pharmaceutical use thereof |
| US8575134B2 (en) | 2004-12-13 | 2013-11-05 | Ono Pharmaceutical Co., Ltd. | Aminocarboxylic acid derivative and medicinal use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1366036A2 (en) | 2003-12-03 |
| WO2002018361A3 (en) | 2003-07-31 |
| 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 |
| ES2256288T3 (es) | 2006-07-16 |
| EP1366036B1 (en) | 2006-01-11 |
| AU8647101A (en) | 2002-03-13 |
| DE60116642T2 (de) | 2006-11-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6495552B2 (en) | Methods of providing and using compounds having activity as inhibitors of cytochrome P450RAI | |
| US6291677B1 (en) | Compounds having activity as inhibitors of cytochrome P450RAI | |
| AU2001286478A1 (en) | Methods of providing and using compounds (retinoids) having activity as inhibitors of cytochrome P450RAI | |
| EP1366036B1 (en) | Compounds having activity as inhibitors of cytochrome p450rai | |
| CA2550123A1 (en) | Compounds having selective cytochrome p450rai-1 or selective cytochrome p450rai-2 inhibitory activity and methods of obtaining the same | |
| AU2001286471A1 (en) | Compounds having activity as inhibitors of cytochrome P450RAI | |
| US6252090B1 (en) | Compounds having activity as inhibitors of cytochrome P450RAI | |
| AU649124B2 (en) | 7-chromanyl esters of phenols and benzoic acids having retinoid-like activity | |
| US6303785B1 (en) | Compounds having activity as inhibitors of cytochrome P450RAI | |
| US6387951B1 (en) | Compounds having activity as inhibitors of cytochrome P450RAI | |
| US6369261B1 (en) | Compounds having activity as inhibitors of cytochrome P450RAI | |
| US7351737B2 (en) | 4-[(8-substituted)-6-chromanoyl]-and 4-[8-substituted)-chroman-6-YL-ethynyl]-benzoic and phenylacetic acids, their esters and salts having cytochrome P450RAI inhibitory activity | |
| US6603019B2 (en) | 1-imidazolyl substituted tetrahydronaphthalene derivatives as inhibitors of eytochrome P450RAI | |
| US6369225B1 (en) | Compounds having activity as inhibitors of cytochrome P450RAI | |
| HK1059439B (en) | Compounds having activity as inhibitors of cytochrome p450rai | |
| US20040077721A1 (en) | Compositions and methods using compounds having cytochrome P450RAI inhibitory activity co-administered with vitamin A | |
| AU2006249248A1 (en) | Pharmaceutical compositions having activity as inhibitors of cytochrome P450RAI |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |