ZA200200939B - RAR selective retinoid agonists. - Google Patents

RAR selective retinoid agonists. Download PDF

Info

Publication number: ZA200200939B
Authority: ZA; South Africa
Prior art keywords: methyl; tetrahydrobenzo; benzoic acid; methoxymethyl; compound
Prior art date: 1999-08-25

Application number

ZA200200939A

Other languages

English (en)

Inventor

Paula Nanette Belloni

Peter Mohr

Original Assignee

Hoffmann La Roche

Priority date (The priority date 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 date listed.)

1999-08-25

Filing date

2002-02-01

Publication date

2003-07-30

2002-02-01 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2003-07-30 Publication of ZA200200939B publication Critical patent/ZA200200939B/en

Links

239000000556 agonist Substances 0.000 title description 14
150000004492 retinoid derivatives Chemical class 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims description 86
239000000203 mixture Substances 0.000 claims description 35
239000005711 Benzoic acid Substances 0.000 claims description 22
238000000034 method Methods 0.000 claims description 14
238000011282 treatment Methods 0.000 claims description 14
239000003814 drug Substances 0.000 claims description 13
206010014561 Emphysema Diseases 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 12
229920002554 vinyl polymer Polymers 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 8
WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 7
239000002585 base Substances 0.000 claims description 7
235000010233 benzoic acid Nutrition 0.000 claims description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 7
208000019693 Lung disease Diseases 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
150000001735 carboxylic acids Chemical class 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 5
VOFMOBJODDPURX-AATRIKPKSA-N 4-[(e)-2-[5-(ethoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzothiepin-8-yl]ethenyl]benzoic acid Chemical compound C=1C=C2C(COCC)(C)CCCSC2=CC=1\C=C\C1=CC=C(C(O)=O)C=C1 VOFMOBJODDPURX-AATRIKPKSA-N 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
239000011593 sulfur Chemical group 0.000 claims description 4
229910052717 sulfur Chemical group 0.000 claims description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 3
150000002431 hydrogen Chemical group 0.000 claims description 3
150000003863 ammonium salts Chemical class 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
239000000126 substance Substances 0.000 claims 5
CTURAYFRAMCQLH-BJILWQEISA-N COCC1(CCOC2=CC=C(C=C12)/C=C/C1=CC=C(C(=O)O)C=C1)C.COCC1(CCOC2=CC=C(C=C12)C#CC1=CC=C(C(=O)O)C=C1)C Chemical compound COCC1(CCOC2=CC=C(C=C12)/C=C/C1=CC=C(C(=O)O)C=C1)C.COCC1(CCOC2=CC=C(C=C12)C#CC1=CC=C(C(=O)O)C=C1)C CTURAYFRAMCQLH-BJILWQEISA-N 0.000 claims 1
239000003513 alkali Substances 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 108
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 102
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 99
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 42
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 37
229940093499 ethyl acetate Drugs 0.000 description 36
235000019439 ethyl acetate Nutrition 0.000 description 36
239000012074 organic phase Substances 0.000 description 34
229960004132 diethyl ether Drugs 0.000 description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
239000002904 solvent Substances 0.000 description 29
238000006243 chemical reaction Methods 0.000 description 28
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
238000003818 flash chromatography Methods 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
238000004817 gas chromatography Methods 0.000 description 21
229910052943 magnesium sulfate Inorganic materials 0.000 description 21
235000019341 magnesium sulphate Nutrition 0.000 description 21
239000000243 solution Substances 0.000 description 21
239000012230 colorless oil Substances 0.000 description 20
108090000064 retinoic acid receptors Proteins 0.000 description 20
102000003702 retinoic acid receptors Human genes 0.000 description 19
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
238000001914 filtration Methods 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
239000013078 crystal Substances 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
-1 tert.-butyl Chemical group 0.000 description 15
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 14
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
238000002360 preparation method Methods 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 14
229910052938 sodium sulfate Inorganic materials 0.000 description 14
235000011152 sodium sulphate Nutrition 0.000 description 14
238000003756 stirring Methods 0.000 description 14
238000001035 drying Methods 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
238000001704 evaporation Methods 0.000 description 12
230000008020 evaporation Effects 0.000 description 12
238000000605 extraction Methods 0.000 description 12
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
238000005406 washing Methods 0.000 description 11
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 10
229930002330 retinoic acid Natural products 0.000 description 10
229910000104 sodium hydride Inorganic materials 0.000 description 10
229940096885 Retinoic acid receptor agonist Drugs 0.000 description 9
239000012043 crude product Substances 0.000 description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 9
210000004072 lung Anatomy 0.000 description 9
239000002775 capsule Substances 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
238000002425 crystallisation Methods 0.000 description 7
230000008025 crystallization Effects 0.000 description 7
229940079593 drug Drugs 0.000 description 7
239000002480 mineral oil Substances 0.000 description 7
235000010446 mineral oil Nutrition 0.000 description 7
239000011734 sodium Substances 0.000 description 7
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
229910052681 coesite Inorganic materials 0.000 description 6
238000001816 cooling Methods 0.000 description 6
229910052906 cristobalite Inorganic materials 0.000 description 6
230000005595 deprotonation Effects 0.000 description 6
238000010537 deprotonation reaction Methods 0.000 description 6
201000010099 disease Diseases 0.000 description 6
238000009472 formulation Methods 0.000 description 6
239000004615 ingredient Substances 0.000 description 6
239000003921 oil Substances 0.000 description 6
229910052682 stishovite Inorganic materials 0.000 description 6
229910052905 tridymite Inorganic materials 0.000 description 6
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
208000027418 Wounds and injury Diseases 0.000 description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
230000003197 catalytic effect Effects 0.000 description 5
230000007062 hydrolysis Effects 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
239000011591 potassium Substances 0.000 description 5
229910052700 potassium Inorganic materials 0.000 description 5
239000000843 powder Substances 0.000 description 5
150000003138 primary alcohols Chemical class 0.000 description 5
239000000047 product Substances 0.000 description 5
230000008439 repair process Effects 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
235000012239 silicon dioxide Nutrition 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000003826 tablet Substances 0.000 description 5
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
102000016387 Pancreatic elastase Human genes 0.000 description 4
108010067372 Pancreatic elastase Proteins 0.000 description 4
102000034527 Retinoid X Receptors Human genes 0.000 description 4
108010038912 Retinoid X Receptors Proteins 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
239000012267 brine Substances 0.000 description 4
238000013270 controlled release Methods 0.000 description 4
125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 4
239000008101 lactose Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
239000011159 matrix material Substances 0.000 description 4
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 4
238000000746 purification Methods 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
239000007787 solid Substances 0.000 description 4
229960001727 tretinoin Drugs 0.000 description 4
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 4
OMHQJHQNQVNLEV-UHFFFAOYSA-N (4-methyl-2,3-dihydrochromen-4-yl)methanol Chemical compound C1=CC=C2C(C)(CO)CCOC2=C1 OMHQJHQNQVNLEV-UHFFFAOYSA-N 0.000 description 3
BRTQCMQWIFSHAN-UHFFFAOYSA-N (8-bromo-5-methyl-3,4-dihydro-2h-1-benzothiepin-5-yl)methanol Chemical compound OCC1(C)CCCSC2=CC(Br)=CC=C12 BRTQCMQWIFSHAN-UHFFFAOYSA-N 0.000 description 3
SOHIYESEPVZKHS-UHFFFAOYSA-N 2,3,4,5-tetrahydrooxepine Chemical class C1CCC=COC1 SOHIYESEPVZKHS-UHFFFAOYSA-N 0.000 description 3
GIANSFFRJWVAIK-UHFFFAOYSA-N 4-[2-[4-(methoxymethyl)-4-methyl-2,3-dihydrochromen-6-yl]ethynyl]benzoic acid Chemical compound C1=C2C(COC)(C)CCOC2=CC=C1C#CC1=CC=C(C(O)=O)C=C1 GIANSFFRJWVAIK-UHFFFAOYSA-N 0.000 description 3
DOOAJHWQKPGEHC-UHFFFAOYSA-N 8-bromo-5-(ethoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzothiepine Chemical compound CCOCC1(C)CCCSC2=CC(Br)=CC=C12 DOOAJHWQKPGEHC-UHFFFAOYSA-N 0.000 description 3
SHGAZHPCJJPHSC-ZVCIMWCZSA-N 9-cis-retinoic acid Chemical compound OC(=O)/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-ZVCIMWCZSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
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 3
241000124008 Mammalia Species 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
206010052428 Wound Diseases 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
229960001445 alitretinoin Drugs 0.000 description 3
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 3
230000015572 biosynthetic process Effects 0.000 description 3
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 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
238000000262 chemical ionisation mass spectrometry Methods 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
230000000694 effects Effects 0.000 description 3
230000009786 epithelial differentiation Effects 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
208000014674 injury Diseases 0.000 description 3
239000003446 ligand Substances 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
SJFNDMHZXCUXSA-UHFFFAOYSA-M methoxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SJFNDMHZXCUXSA-UHFFFAOYSA-M 0.000 description 3
230000002685 pulmonary effect Effects 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
238000000926 separation method Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000007910 systemic administration Methods 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
BZQJORBFRHWNDM-UHFFFAOYSA-N (4-methyl-2,3-dihydrochromen-4-yl)methyl acetate Chemical compound C1=CC=C2C(COC(=O)C)(C)CCOC2=C1 BZQJORBFRHWNDM-UHFFFAOYSA-N 0.000 description 2
GICWOWRUIGCEEE-UHFFFAOYSA-N (6-bromo-4-methyl-2,3-dihydrochromen-4-yl)methyl acetate Chemical compound C1=C(Br)C=C2C(COC(=O)C)(C)CCOC2=C1 GICWOWRUIGCEEE-UHFFFAOYSA-N 0.000 description 2
FEAAKHIPVPHDGC-UHFFFAOYSA-N (6-ethynyl-4-methyl-2,3-dihydrochromen-4-yl)methyl acetate Chemical compound C1=C(C#C)C=C2C(COC(=O)C)(C)CCOC2=C1 FEAAKHIPVPHDGC-UHFFFAOYSA-N 0.000 description 2
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 2
MICTUIBIFKCHCY-UHFFFAOYSA-N 2-[4-(methoxymethyl)-4-methyl-2,3-dihydrochromen-6-yl]ethynyl-trimethylsilane Chemical compound C1=C(C#C[Si](C)(C)C)C=C2C(COC)(C)CCOC2=C1 MICTUIBIFKCHCY-UHFFFAOYSA-N 0.000 description 2
GSEOHUUQFIJCPA-UHFFFAOYSA-N 4-(methoxymethyl)-4-methyl-2,3-dihydrochromene Chemical compound C1=CC=C2C(COC)(C)CCOC2=C1 GSEOHUUQFIJCPA-UHFFFAOYSA-N 0.000 description 2
IXBTUGFYHVZLLP-AATRIKPKSA-N 4-[(e)-2-[5-methyl-5-(propoxymethyl)-3,4-dihydro-2h-1-benzoxepin-8-yl]ethenyl]benzoic acid Chemical compound C=1C=C2C(COCCC)(C)CCCOC2=CC=1\C=C\C1=CC=C(C(O)=O)C=C1 IXBTUGFYHVZLLP-AATRIKPKSA-N 0.000 description 2
SEDHSETVCZKXNR-UHFFFAOYSA-N 4-[2-[5-(methoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzothiepin-8-yl]ethynyl]benzoic acid Chemical compound C=1C=C2C(COC)(C)CCCSC2=CC=1C#CC1=CC=C(C(O)=O)C=C1 SEDHSETVCZKXNR-UHFFFAOYSA-N 0.000 description 2
XUNWKZCNCGPGOP-UHFFFAOYSA-N 4-methyl-2,3-dihydrochromene-4-carbaldehyde Chemical compound C1=CC=C2C(C)(C=O)CCOC2=C1 XUNWKZCNCGPGOP-UHFFFAOYSA-N 0.000 description 2
MFSOSUFMFBDJRW-UHFFFAOYSA-N 5-(ethoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzothiepine-8-carbaldehyde Chemical compound CCOCC1(C)CCCSC2=CC(C=O)=CC=C12 MFSOSUFMFBDJRW-UHFFFAOYSA-N 0.000 description 2
XSOVIAWIIMVIGI-UHFFFAOYSA-N 5-(methoxymethyl)-5-propyl-3,4-dihydro-2h-1-benzoxepine-8-carbaldehyde Chemical compound CCCC1(COC)CCCOC2=CC(C=O)=CC=C12 XSOVIAWIIMVIGI-UHFFFAOYSA-N 0.000 description 2
WYSQKJSUCVWCPP-UHFFFAOYSA-N 6-bromo-4-(methoxymethyl)-4-methyl-2,3-dihydrochromene Chemical compound C1=C(Br)C=C2C(COC)(C)CCOC2=C1 WYSQKJSUCVWCPP-UHFFFAOYSA-N 0.000 description 2
WYOZOOHMOLFSDJ-UHFFFAOYSA-N 6-ethynyl-4-(methoxymethyl)-4-methyl-2,3-dihydrochromene Chemical compound C1=C(C#C)C=C2C(COC)(C)CCOC2=C1 WYOZOOHMOLFSDJ-UHFFFAOYSA-N 0.000 description 2
AKSLKUOXOIRZBA-UHFFFAOYSA-N 8-bromo-2,3,4,5-tetrahydro-1-benzoxepine-5-carbaldehyde Chemical compound O=CC1CCCOC2=CC(Br)=CC=C21 AKSLKUOXOIRZBA-UHFFFAOYSA-N 0.000 description 2
QNLKNFSEQSCQRR-UHFFFAOYSA-N 8-bromo-3,4-dihydro-2h-1-benzothiepin-5-one Chemical compound S1CCCC(=O)C=2C1=CC(Br)=CC=2 QNLKNFSEQSCQRR-UHFFFAOYSA-N 0.000 description 2
VUIYYTWSPPVDTD-UHFFFAOYSA-N 8-bromo-5-(methoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzothiepine Chemical compound COCC1(C)CCCSC2=CC(Br)=CC=C12 VUIYYTWSPPVDTD-UHFFFAOYSA-N 0.000 description 2
VNXJGYRDJDBASA-UHFFFAOYSA-N 8-bromo-5-(methoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzoxepine Chemical compound COCC1(C)CCCOC2=CC(Br)=CC=C12 VNXJGYRDJDBASA-UHFFFAOYSA-N 0.000 description 2
NWDCESXTFQUVNX-UHFFFAOYSA-N 8-bromo-5-(methoxymethyl)-5-propyl-3,4-dihydro-2h-1-benzoxepine Chemical compound CCCC1(COC)CCCOC2=CC(Br)=CC=C12 NWDCESXTFQUVNX-UHFFFAOYSA-N 0.000 description 2
SFRQRFWLXBBTFR-UHFFFAOYSA-N 8-ethynyl-5-(methoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzoxepine Chemical compound COCC1(C)CCCOC2=CC(C#C)=CC=C12 SFRQRFWLXBBTFR-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
208000002874 Acne Vulgaris Diseases 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
102000016942 Elastin Human genes 0.000 description 2
108010014258 Elastin Proteins 0.000 description 2
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
108010007979 Glycocholic Acid Proteins 0.000 description 2
WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
201000004681 Psoriasis Diseases 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
206010000496 acne Diseases 0.000 description 2
150000001351 alkyl iodides Chemical class 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000012876 carrier material Substances 0.000 description 2
229940125890 compound Ia Drugs 0.000 description 2
230000006378 damage Effects 0.000 description 2
KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
230000008034 disappearance Effects 0.000 description 2
229920002549 elastin Polymers 0.000 description 2
150000002084 enol ethers Chemical class 0.000 description 2
230000009841 epithelial lesion Effects 0.000 description 2
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 2
OFUCEQWVGVURAS-UHFFFAOYSA-N ethyl 4-(diethoxyphosphorylmethyl)benzoate Chemical compound CCOC(=O)C1=CC=C(CP(=O)(OCC)OCC)C=C1 OFUCEQWVGVURAS-UHFFFAOYSA-N 0.000 description 2
MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
RFDAIACWWDREDC-FRVQLJSFSA-N glycocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 RFDAIACWWDREDC-FRVQLJSFSA-N 0.000 description 2
239000008187 granular material Substances 0.000 description 2
229940088597 hormone Drugs 0.000 description 2
239000005556 hormone Substances 0.000 description 2
239000007972 injectable composition Substances 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
239000002502 liposome Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000006193 liquid solution Substances 0.000 description 2
239000006194 liquid suspension Substances 0.000 description 2
GOUOELTUEQQRRT-UHFFFAOYSA-N methyl 4-[2-[4-(methoxymethyl)-4-methyl-2,3-dihydrochromen-6-yl]ethynyl]benzoate Chemical compound C1=C2C(COC)(C)CCOC2=CC=C1C#CC1=CC=C(C(=O)OC)C=C1 GOUOELTUEQQRRT-UHFFFAOYSA-N 0.000 description 2
HOSOOSDBTVRIGX-UHFFFAOYSA-N methyl 4-[2-[5-(methoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzoxepin-8-yl]ethynyl]benzoate Chemical compound C=1C=C2C(COC)(C)CCCOC2=CC=1C#CC1=CC=C(C(=O)OC)C=C1 HOSOOSDBTVRIGX-UHFFFAOYSA-N 0.000 description 2
DYUWQWMXZHDZOR-UHFFFAOYSA-N methyl 4-iodobenzoate Chemical compound COC(=O)C1=CC=C(I)C=C1 DYUWQWMXZHDZOR-UHFFFAOYSA-N 0.000 description 2
150000004702 methyl esters Chemical class 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
239000000693 micelle Substances 0.000 description 2
210000004400 mucous membrane Anatomy 0.000 description 2
PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 2
239000007923 nasal drop Substances 0.000 description 2
229940100662 nasal drops Drugs 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
239000006187 pill Substances 0.000 description 2
230000004983 pleiotropic effect Effects 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
229920001515 polyalkylene glycol Polymers 0.000 description 2
230000001737 promoting effect Effects 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
230000009467 reduction Effects 0.000 description 2
239000011369 resultant mixture Substances 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
238000003860 storage Methods 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
238000010792 warming Methods 0.000 description 2
BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
DLAXCQFAFHBMJY-UHFFFAOYSA-N (8-bromo-5-methyl-3,4-dihydro-2h-1-benzoxepin-5-yl)methanol Chemical compound OCC1(C)CCCOC2=CC(Br)=CC=C12 DLAXCQFAFHBMJY-UHFFFAOYSA-N 0.000 description 1
JPHAQKNEDMRMFM-UHFFFAOYSA-N (8-bromo-5-propyl-3,4-dihydro-2h-1-benzoxepin-5-yl)methanol Chemical compound CCCC1(CO)CCCOC2=CC(Br)=CC=C12 JPHAQKNEDMRMFM-UHFFFAOYSA-N 0.000 description 1
108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
CIJBRVFURVUXMM-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1-benzothiepin-2-ylmethanol Chemical compound S1C(CO)CCCC2=CC=CC=C21 CIJBRVFURVUXMM-UHFFFAOYSA-N 0.000 description 1
XNMYBTLKAQPVQT-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1-benzoxepin-2-ylmethanol Chemical compound O1C(CO)CCCC2=CC=CC=C21 XNMYBTLKAQPVQT-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
RUHDMIRVAFTNRL-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-4-carbaldehyde Chemical compound C1=CC=C2C(C=O)CCOC2=C1 RUHDMIRVAFTNRL-UHFFFAOYSA-N 0.000 description 1
OHXPGWPVLFPUSM-KLRNGDHRSA-N 3,7,12-trioxo-5beta-cholanic acid Chemical compound C1CC(=O)C[C@H]2CC(=O)[C@H]3[C@@H]4CC[C@H]([C@@H](CCC(O)=O)C)[C@@]4(C)C(=O)C[C@@H]3[C@]21C OHXPGWPVLFPUSM-KLRNGDHRSA-N 0.000 description 1
HNGQQUDFJDROPY-UHFFFAOYSA-N 3-bromobenzenethiol Chemical compound SC1=CC=CC(Br)=C1 HNGQQUDFJDROPY-UHFFFAOYSA-N 0.000 description 1
MNOJRWOWILAHAV-UHFFFAOYSA-N 3-bromophenol Chemical compound OC1=CC=CC(Br)=C1 MNOJRWOWILAHAV-UHFFFAOYSA-N 0.000 description 1
ZDIBKEWYZLHOJX-ONEGZZNKSA-N 4-[(e)-2-[4-(methoxymethyl)-4-methyl-2,3-dihydrochromen-6-yl]ethenyl]benzoic acid Chemical compound C1=C2C(COC)(C)CCOC2=CC=C1\C=C\C1=CC=C(C(O)=O)C=C1 ZDIBKEWYZLHOJX-ONEGZZNKSA-N 0.000 description 1
AQRRFBSTUODWOG-SNAWJCMRSA-N 4-[(e)-2-[5-(methoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzoxepin-8-yl]ethenyl]benzoic acid Chemical compound C=1C=C2C(COC)(C)CCCOC2=CC=1\C=C\C1=CC=C(C(O)=O)C=C1 AQRRFBSTUODWOG-SNAWJCMRSA-N 0.000 description 1
SXVOHIMDGSABTF-AATRIKPKSA-N 4-[(e)-2-[5-(methoxymethyl)-5-propyl-3,4-dihydro-2h-1-benzothiepin-8-yl]ethenyl]benzoic acid Chemical compound C=1C=C2C(CCC)(COC)CCCSC2=CC=1\C=C\C1=CC=C(C(O)=O)C=C1 SXVOHIMDGSABTF-AATRIKPKSA-N 0.000 description 1
ZMAXJHXSMOYDIW-AATRIKPKSA-N 4-[(e)-2-[5-(methoxymethyl)-5-propyl-3,4-dihydro-2h-1-benzoxepin-8-yl]ethenyl]benzoic acid Chemical compound C=1C=C2C(CCC)(COC)CCCOC2=CC=1\C=C\C1=CC=C(C(O)=O)C=C1 ZMAXJHXSMOYDIW-AATRIKPKSA-N 0.000 description 1
FDCUAHFXAPNSJR-UHFFFAOYSA-N 4-[2-[4-(acetyloxymethyl)-4-methyl-2,3-dihydrochromen-6-yl]ethynyl]benzoic acid Chemical compound C1=C2C(COC(=O)C)(C)CCOC2=CC=C1C#CC1=CC=C(C(O)=O)C=C1 FDCUAHFXAPNSJR-UHFFFAOYSA-N 0.000 description 1
CZZRYJSFDKYTRX-UHFFFAOYSA-N 4-[2-[4-(hydroxymethyl)-4-methyl-2,3-dihydrochromen-6-yl]ethynyl]benzoic acid Chemical compound C1=C2C(C)(CO)CCOC2=CC=C1C#CC1=CC=C(C(O)=O)C=C1 CZZRYJSFDKYTRX-UHFFFAOYSA-N 0.000 description 1
OZCNOMNNLZGXAG-UHFFFAOYSA-N 4-[2-[5-(ethoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzoxepin-8-yl]ethynyl]benzoic acid Chemical compound C=1C=C2C(COCC)(C)CCCOC2=CC=1C#CC1=CC=C(C(O)=O)C=C1 OZCNOMNNLZGXAG-UHFFFAOYSA-N 0.000 description 1
PTAKZNJIEZJKPN-UHFFFAOYSA-N 4-[2-[5-methyl-5-(propoxymethyl)-3,4-dihydro-2h-1-benzoxepin-8-yl]ethynyl]benzoic acid Chemical compound C=1C=C2C(COCCC)(C)CCCOC2=CC=1C#CC1=CC=C(C(O)=O)C=C1 PTAKZNJIEZJKPN-UHFFFAOYSA-N 0.000 description 1
LPAYXXMXEJUGQM-UHFFFAOYSA-N 5-(methoxymethyl)-5-propyl-3,4-dihydro-2h-1-benzothiepine-8-carbaldehyde Chemical compound CCCC1(COC)CCCSC2=CC(C=O)=CC=C12 LPAYXXMXEJUGQM-UHFFFAOYSA-N 0.000 description 1
RYBRYYPJUGXFCY-UHFFFAOYSA-N 6-bromo-4-(methoxymethyl)-4-methyl-2,3-dihydrochromene;8-bromo-5-(methoxymethyl)-5-propyl-3,4-dihydro-2h-1-benzoxepine Chemical compound C1=C(Br)C=C2C(COC)(C)CCOC2=C1.CCCC1(COC)CCCOC2=CC(Br)=CC=C12 RYBRYYPJUGXFCY-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
PCPUAZRWCCHSFF-UHFFFAOYSA-N 8-bromo-2,3,4,5-tetrahydro-1-benzothiepine-5-carbaldehyde Chemical compound O=CC1CCCSC2=CC(Br)=CC=C21 PCPUAZRWCCHSFF-UHFFFAOYSA-N 0.000 description 1
LXKQMHNFHKVGAZ-UHFFFAOYSA-N 8-bromo-3,4-dihydro-2h-1-benzoxepin-5-one Chemical compound O1CCCC(=O)C=2C1=CC(Br)=CC=2 LXKQMHNFHKVGAZ-UHFFFAOYSA-N 0.000 description 1
MMZHELJAIITTFP-UHFFFAOYSA-N 8-bromo-5-(methoxymethylidene)-3,4-dihydro-2h-1-benzothiepine Chemical compound COC=C1CCCSC2=CC(Br)=CC=C12 MMZHELJAIITTFP-UHFFFAOYSA-N 0.000 description 1
HALFPIJMTYSADV-UHFFFAOYSA-N 8-bromo-5-methyl-3,4-dihydro-2h-1-benzothiepine-5-carbaldehyde Chemical compound O=CC1(C)CCCSC2=CC(Br)=CC=C12 HALFPIJMTYSADV-UHFFFAOYSA-N 0.000 description 1
YIZLHAVMCHAQOP-UHFFFAOYSA-N 8-bromo-5-methyl-3,4-dihydro-2h-1-benzoxepine-5-carbaldehyde Chemical compound O=CC1(C)CCCOC2=CC(Br)=CC=C12 YIZLHAVMCHAQOP-UHFFFAOYSA-N 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
239000004380 Cholic acid Substances 0.000 description 1
208000032544 Cicatrix Diseases 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
229920002785 Croscarmellose sodium Polymers 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
206010015719 Exsanguination Diseases 0.000 description 1
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
108010035713 Glycodeoxycholic Acid Proteins 0.000 description 1
WVULKSPCQVQLCU-UHFFFAOYSA-N Glycodeoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCC(O)=O)C)C1(C)C(O)C2 WVULKSPCQVQLCU-UHFFFAOYSA-N 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
206010019668 Hepatic fibrosis Diseases 0.000 description 1
238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
RFDAIACWWDREDC-UHFFFAOYSA-N Na salt-Glycocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCC(O)=O)C)C1(C)C(O)C2 RFDAIACWWDREDC-UHFFFAOYSA-N 0.000 description 1
108020005497 Nuclear hormone receptor Proteins 0.000 description 1
206010035664 Pneumonia Diseases 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
208000033826 Promyelocytic Acute Leukemia Diseases 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
102100022941 Retinol-binding protein 1 Human genes 0.000 description 1
108050008744 Retinol-binding protein 1 Proteins 0.000 description 1
238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
208000002847 Surgical Wound Diseases 0.000 description 1
WBWWGRHZICKQGZ-UHFFFAOYSA-N Taurocholic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(=O)NCCS(O)(=O)=O)C)C1(C)C(O)C2 WBWWGRHZICKQGZ-UHFFFAOYSA-N 0.000 description 1
102000040945 Transcription factor Human genes 0.000 description 1
108091023040 Transcription factor Proteins 0.000 description 1
FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
238000007239 Wittig reaction Methods 0.000 description 1
XCTPTRZUUVGEAP-UHFFFAOYSA-N [4-methyl-6-(2-trimethylsilylethynyl)-2,3-dihydrochromen-4-yl]methyl acetate Chemical compound C1=C(C#C[Si](C)(C)C)C=C2C(COC(=O)C)(C)CCOC2=C1 XCTPTRZUUVGEAP-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-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
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
238000012387 aerosolization Methods 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000005210 alkyl ammonium group Chemical group 0.000 description 1
SYESMXTWOAQFET-YCNIQYBTSA-N all-trans-3,4-didehydroretinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C=CCC1(C)C SYESMXTWOAQFET-YCNIQYBTSA-N 0.000 description 1
GGCUJPCCTQNTJF-FRCNGJHJSA-N all-trans-4-oxoretinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C(=O)CCC1(C)C GGCUJPCCTQNTJF-FRCNGJHJSA-N 0.000 description 1
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
230000008382 alveolar damage Effects 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
230000019552 anatomical structure morphogenesis Effects 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229940072107 ascorbate Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
125000001743 benzylic group Chemical group 0.000 description 1
239000003833 bile salt Substances 0.000 description 1
229940093761 bile salts Drugs 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
235000013539 calcium stearate Nutrition 0.000 description 1
239000008116 calcium stearate Substances 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000007963 capsule composition Substances 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
210000003679 cervix uteri Anatomy 0.000 description 1
RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 1
229960001091 chenodeoxycholic acid Drugs 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
235000019416 cholic acid Nutrition 0.000 description 1
229960002471 cholic acid Drugs 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
238000004040 coloring Methods 0.000 description 1
239000012050 conventional carrier Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
229940099112 cornstarch Drugs 0.000 description 1
229960001681 croscarmellose sodium Drugs 0.000 description 1
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
GOHCTCOGYKAJLZ-UHFFFAOYSA-N ctep Chemical compound CC=1N(C=2C=CC(OC(F)(F)F)=CC=2)C(C)=NC=1C#CC1=CC=NC(Cl)=C1 GOHCTCOGYKAJLZ-UHFFFAOYSA-N 0.000 description 1
229940097362 cyclodextrins Drugs 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
229960002997 dehydrocholic acid Drugs 0.000 description 1
KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 1
229960003964 deoxycholic acid Drugs 0.000 description 1
230000008021 deposition Effects 0.000 description 1
238000001212 derivatisation Methods 0.000 description 1
238000005828 desilylation reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical group C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
230000008556 epithelial cell proliferation Effects 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
238000006266 etherification reaction Methods 0.000 description 1
WPSFEXSPQCXGAB-BQYQJAHWSA-N ethyl 4-[(e)-2-[5-(methoxymethyl)-5-propyl-3,4-dihydro-2h-1-benzoxepin-8-yl]ethenyl]benzoate Chemical compound C=1C=C2C(CCC)(COC)CCCOC2=CC=1\C=C\C1=CC=C(C(=O)OCC)C=C1 WPSFEXSPQCXGAB-BQYQJAHWSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
210000002744 extracellular matrix Anatomy 0.000 description 1
239000000284 extract Substances 0.000 description 1
230000003328 fibroblastic effect Effects 0.000 description 1
239000000834 fixative Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
229940099347 glycocholic acid Drugs 0.000 description 1
WVULKSPCQVQLCU-BUXLTGKBSA-N glycodeoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 WVULKSPCQVQLCU-BUXLTGKBSA-N 0.000 description 1
235000021552 granulated sugar Nutrition 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
239000007887 hard shell capsule Substances 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
230000001969 hypertrophic effect Effects 0.000 description 1
210000002865 immune cell Anatomy 0.000 description 1
239000007943 implant Substances 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
210000004969 inflammatory cell Anatomy 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
210000000867 larynx Anatomy 0.000 description 1
238000000670 ligand binding assay Methods 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
230000004807 localization Effects 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
239000000463 material Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
108020004999 messenger RNA Proteins 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
RTTDYMSMJLCBQD-VOTSOKGWSA-N methyl 4-[(e)-2-[5-(ethoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzothiepin-8-yl]ethenyl]benzoate Chemical compound C=1C=C2C(COCC)(C)CCCSC2=CC=1\C=C\C1=CC=C(C(=O)OC)C=C1 RTTDYMSMJLCBQD-VOTSOKGWSA-N 0.000 description 1
KQYMRQNQBWEOLO-UHFFFAOYSA-N methyl 4-[2-[4-(acetyloxymethyl)-4-methyl-2,3-dihydrochromen-6-yl]ethynyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C#CC1=CC=C(OCCC2(COC(C)=O)C)C2=C1 KQYMRQNQBWEOLO-UHFFFAOYSA-N 0.000 description 1
LXTTYXBNOVPKKY-UHFFFAOYSA-N methyl 4-[2-[5-(methoxymethyl)-5-methyl-3,4-dihydro-2h-1-benzothiepin-8-yl]ethynyl]benzoate Chemical compound C=1C=C2C(COC)(C)CCCSC2=CC=1C#CC1=CC=C(C(=O)OC)C=C1 LXTTYXBNOVPKKY-UHFFFAOYSA-N 0.000 description 1
JPGRSTBIEYGVNO-UHFFFAOYSA-N methyl 4-ethynylbenzoate Chemical compound COC(=O)C1=CC=C(C#C)C=C1 JPGRSTBIEYGVNO-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
239000003094 microcapsule Substances 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
238000007491 morphometric analysis Methods 0.000 description 1
JJYKJUXBWFATTE-UHFFFAOYSA-N mosher's acid Chemical compound COC(C(O)=O)(C(F)(F)F)C1=CC=CC=C1 JJYKJUXBWFATTE-UHFFFAOYSA-N 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000002790 naphthalenes Chemical class 0.000 description 1
238000002663 nebulization Methods 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
102000006255 nuclear receptors Human genes 0.000 description 1
108020004017 nuclear receptors Proteins 0.000 description 1
230000000771 oncological effect Effects 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
ATYBXHSAIOKLMG-UHFFFAOYSA-N oxepin Chemical compound O1C=CC=CC=C1 ATYBXHSAIOKLMG-UHFFFAOYSA-N 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
QJPQVXSHYBGQGM-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 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
238000012545 processing Methods 0.000 description 1
239000003380 propellant Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
210000003456 pulmonary alveoli Anatomy 0.000 description 1
210000004879 pulmonary tissue Anatomy 0.000 description 1
238000011552 rat model Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
231100000916 relative toxicity Toxicity 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
102000027483 retinoid hormone receptors Human genes 0.000 description 1
108091008679 retinoid hormone receptors Proteins 0.000 description 1
229960003471 retinol Drugs 0.000 description 1
235000020944 retinol Nutrition 0.000 description 1
239000011607 retinol Substances 0.000 description 1
WWDMJSSVVPXVSV-YCNIQYBTSA-N retinyl ester Chemical compound CC1CCCC(C)(C)C1\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O WWDMJSSVVPXVSV-YCNIQYBTSA-N 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
231100000241 scar Toxicity 0.000 description 1
230000037387 scars Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000007974 sodium acetate buffer Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
JAJWGJBVLPIOOH-IZYKLYLVSA-M sodium taurocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 JAJWGJBVLPIOOH-IZYKLYLVSA-M 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
102000005969 steroid hormone receptors Human genes 0.000 description 1
108020003113 steroid hormone receptors Proteins 0.000 description 1
150000003431 steroids Chemical class 0.000 description 1
210000002536 stromal cell Anatomy 0.000 description 1
210000003537 structural cell Anatomy 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
150000003463 sulfur Chemical class 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000007916 tablet composition Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
WBWWGRHZICKQGZ-GIHLXUJPSA-N taurocholic acid Chemical compound C([C@@H]1C[C@H]2O)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@H](O)C1 WBWWGRHZICKQGZ-GIHLXUJPSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
102000004217 thyroid hormone receptors Human genes 0.000 description 1
108090000721 thyroid hormone receptors Proteins 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000008733 trauma Effects 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
210000003932 urinary bladder Anatomy 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
235000019155 vitamin A Nutrition 0.000 description 1
239000011719 vitamin A Substances 0.000 description 1
229940045997 vitamin a Drugs 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
230000029663 wound healing Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/08—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/20—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 hydrogenated in the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
- C07D337/02—Seven-membered rings
- C07D337/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D337/08—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with one six-membered ring

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Pyrane Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

ZA200200939A 1999-08-25 2002-02-01 RAR selective retinoid agonists. ZA200200939B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP99116603		1999-08-25

Publications (1)

Publication Number	Publication Date
ZA200200939B true ZA200200939B (en)	2003-07-30

Family

ID=8238844

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200200939A ZA200200939B (en)	1999-08-25	2002-02-01	RAR selective retinoid agonists.

Country Status (18)

Country	Link
US (1)	US6479670B1 (de)
EP (1)	EP1212316B1 (de)
JP (1)	JP3795394B2 (de)
KR (1)	KR100470500B1 (de)
CN (1)	CN1151144C (de)
AR (1)	AR025351A1 (de)
AT (1)	ATE252093T1 (de)
AU (1)	AU769784B2 (de)
BR (1)	BR0013582A (de)
CA (1)	CA2382527A1 (de)
DE (1)	DE60005980T2 (de)
DK (1)	DK1212316T3 (de)
ES (1)	ES2207548T3 (de)
MX (1)	MXPA02001939A (de)
PT (1)	PT1212316E (de)
TR (1)	TR200200473T2 (de)
WO (1)	WO2001014360A2 (de)
ZA (1)	ZA200200939B (de)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2373073A1 (en) *	1999-05-07	2000-11-16	Takeda Chemical Industries, Ltd.	Cyclic compounds and uses thereof
JO2178B1 (en) *	1999-10-19	2003-04-23	اف . هوفمان لاروش ايه جي	Treatment of emphysema using rar selective retinoid antagonists
US6552069B1 (en) *	1999-12-13	2003-04-22	Chugai Seiyaku Kabushiki Kaisha	3-methyl-chroman and -thiochroman derivatives
BR0213501A (pt) *	2001-11-02	2004-08-24	Searle Llc	Compostos de benzotiepina mono- e di-fluorada como inibidores de transporte de ácido biliar co-dependente de sódio apical (asbt) e captação de taurocolato
US7101565B2 (en)	2002-02-05	2006-09-05	Corpak Medsystems, Inc.	Probiotic/prebiotic composition and delivery method
AU2003286245A1 (en) *	2002-11-25	2004-06-18	Amedis Pharmaceuticals Ltd.	Silicon compounds to be used as ligands for retinoid receptors
EP1771124B1 (de) *	2004-03-30	2010-12-29	Proxy Biomedical Limited	Behandeltes chirurgisches mesh aus monofilen fasern
US9119777B2 (en)	2008-05-30	2015-09-01	Microdose Therapeutx, Inc.	Methods and compositions for administration of oxybutynin
US8415390B2 (en)	2008-05-30	2013-04-09	Microdose Therapeutx, Inc.	Methods and compositions for administration of oxybutynin
US10500232B2 (en)	2013-08-26	2019-12-10	The J. David Gladstone Ins., a testamentary trust established under the Will of J. David Gladstone	Small molecule cellular reprogramming to generate neuronal cells
EP3348279B1 (de) *	2015-09-10	2021-08-04	National University Corporation Okayama University	Medizinische zusammensetzung zur prävention oder behandlung von entzündlichen atemwegserkrankungen
CN107176945B (zh)	2016-03-11	2021-06-08	中国科学院上海有机化学研究所	一种视黄酸类化合物、其制备方法、中间体及应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5958954A (en)	1995-09-01	1999-09-28	Allergan Sales, Inc.	Synthesis and use of retinoid compounds having negative hormone and/or antagonist activities

2000
- 2000-07-12 US US09/614,331 patent/US6479670B1/en not_active Expired - Fee Related
- 2000-08-18 DK DK00958468T patent/DK1212316T3/da active
- 2000-08-18 TR TR2002/00473T patent/TR200200473T2/xx unknown
- 2000-08-18 ES ES00958468T patent/ES2207548T3/es not_active Expired - Lifetime
- 2000-08-18 AU AU69971/00A patent/AU769784B2/en not_active Ceased
- 2000-08-18 KR KR10-2002-7002458A patent/KR100470500B1/ko not_active Expired - Fee Related
- 2000-08-18 PT PT00958468T patent/PT1212316E/pt unknown
- 2000-08-18 CN CNB00811899XA patent/CN1151144C/zh not_active Expired - Fee Related
- 2000-08-18 WO PCT/EP2000/008065 patent/WO2001014360A2/en not_active Ceased
- 2000-08-18 MX MXPA02001939A patent/MXPA02001939A/es active IP Right Grant
- 2000-08-18 CA CA002382527A patent/CA2382527A1/en not_active Abandoned
- 2000-08-18 JP JP2001518447A patent/JP3795394B2/ja not_active Expired - Fee Related
- 2000-08-18 EP EP00958468A patent/EP1212316B1/de not_active Expired - Lifetime
- 2000-08-18 BR BR0013582-8A patent/BR0013582A/pt not_active IP Right Cessation
- 2000-08-18 AT AT00958468T patent/ATE252093T1/de not_active IP Right Cessation
- 2000-08-18 DE DE60005980T patent/DE60005980T2/de not_active Expired - Fee Related
- 2000-08-23 AR ARP000104344A patent/AR025351A1/es not_active Application Discontinuation
2002
- 2002-02-01 ZA ZA200200939A patent/ZA200200939B/en unknown

Also Published As

Publication number	Publication date
ES2207548T3 (es)	2004-06-01
JP2003507465A (ja)	2003-02-25
EP1212316A2 (de)	2002-06-12
US6479670B1 (en)	2002-11-12
TR200200473T2 (tr)	2002-05-21
PT1212316E (pt)	2004-02-27
MXPA02001939A (es)	2002-08-20
BR0013582A (pt)	2002-05-07
ATE252093T1 (de)	2003-11-15
CN1370156A (zh)	2002-09-18
AR025351A1 (es)	2002-11-20
DE60005980T2 (de)	2004-08-12
WO2001014360A3 (en)	2001-05-17
DE60005980D1 (de)	2003-11-20
DK1212316T3 (da)	2004-02-23
JP3795394B2 (ja)	2006-07-12
KR20020039335A (ko)	2002-05-25
AU6997100A (en)	2001-03-19
WO2001014360A2 (en)	2001-03-01
CA2382527A1 (en)	2001-03-01
CN1151144C (zh)	2004-05-26
AU769784B2 (en)	2004-02-05
EP1212316B1 (de)	2003-10-15
KR100470500B1 (ko)	2005-02-07

Publication	Publication Date	Title
AU772551B2 (en)	2004-04-29	New selective retinoid agonists
EP1280757B1 (de)	2005-08-17	Gamma-selektive retinoide
EP1212316B1 (de)	2003-10-15	Benzopyran und benzothiopyran, verwendbar als selektive retinoid-agonisten
US6596758B1 (en)	2003-07-22	Benzopyrans and benzoxepines, pharmaceutical compositions comprising them and preparation process
AU2001289619B2 (en)	2006-07-13	Thiophene retinoids
AU2001289619A1 (en)	2002-04-18	Thiophene retinoids