FI66587C - Foerfarande foer framstaellning av nya terapeutiskt anvaendbara polyenfoereningar - Google Patents
Foerfarande foer framstaellning av nya terapeutiskt anvaendbara polyenfoereningar Download PDFInfo
- Publication number
- FI66587C FI66587C FI781227A FI781227A FI66587C FI 66587 C FI66587 C FI 66587C FI 781227 A FI781227 A FI 781227A FI 781227 A FI781227 A FI 781227A FI 66587 C FI66587 C FI 66587C
- Authority
- FI
- Finland
- Prior art keywords
- formula
- alkylcarbamoyl
- carboxylic acid
- alkoxycarbonyl
- ether
- Prior art date
Links
- 229940126601 medicinal product Drugs 0.000 title 1
- 230000001225 therapeutic effect Effects 0.000 title 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 73
- -1 polyene compounds Chemical class 0.000 claims description 60
- 150000001875 compounds Chemical class 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 150000002576 ketones Chemical class 0.000 claims description 14
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 9
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 9
- 239000007858 starting material Substances 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 5
- 150000002085 enols Chemical class 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003086 colorant Substances 0.000 claims 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims 1
- 150000007860 aryl ester derivatives Chemical group 0.000 claims 1
- 229910002091 carbon monoxide Inorganic materials 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 61
- 239000000243 solution Substances 0.000 description 41
- 239000002253 acid Substances 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 125000004494 ethyl ester group Chemical group 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000005457 ice water Substances 0.000 description 9
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000012259 ether extract Substances 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 229910052987 metal hydride Inorganic materials 0.000 description 5
- 239000002674 ointment Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 150000004714 phosphonium salts Chemical class 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 150000004681 metal hydrides Chemical class 0.000 description 4
- 208000017520 skin disease Diseases 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 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 4
- WYSORZHDPDKQIX-UHFFFAOYSA-N 1,3-bis(1,1,3,3-tetramethyl-2h-inden-5-yl)propan-2-one Chemical compound C1=C2C(C)(C)CC(C)(C)C2=CC(CC(=O)CC=2C=C3C(C)(C)CC(C3=CC=2)(C)C)=C1 WYSORZHDPDKQIX-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CTZQMJMQRYPMPJ-UHFFFAOYSA-N 3-methyl-7-(1,1,3,3-tetramethyl-2H-inden-5-yl)octa-2,4,6-trien-1-ol Chemical compound CC(=CCO)C=CC=C(C)C=1C=C2C(CC(C2=CC=1)(C)C)(C)C CTZQMJMQRYPMPJ-UHFFFAOYSA-N 0.000 description 3
- OWPGCBIZBSGSLX-UHFFFAOYSA-N 5-methoxy-1,1,3,3-tetramethyl-2h-indene Chemical compound COC1=CC=C2C(C)(C)CC(C)(C)C2=C1 OWPGCBIZBSGSLX-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 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
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- WMXCPQZEPYDIFZ-UHFFFAOYSA-N ethyl 3-methyl-6-oxohexa-2,4-dienoate Chemical compound CCOC(=O)C=C(C)C=CC=O WMXCPQZEPYDIFZ-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- FYPPFNIHEQRSSA-UHFFFAOYSA-M triphenyl-[1-(1,1,3,3-tetramethyl-2h-inden-5-yl)ethyl]phosphanium;bromide Chemical compound [Br-].C=1C=C(C(CC2(C)C)(C)C)C2=CC=1C(C)[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 FYPPFNIHEQRSSA-UHFFFAOYSA-M 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- OJCRKGPORQMMRN-UHFFFAOYSA-N 1,1,3,3-tetramethyl-2h-inden-5-ol Chemical compound OC1=CC=C2C(C)(C)CC(C)(C)C2=C1 OJCRKGPORQMMRN-UHFFFAOYSA-N 0.000 description 2
- FZHYDVCIRXMJRY-UHFFFAOYSA-N 5-(1-bromoethyl)-1,1,3,3-tetramethyl-2h-indene Chemical compound CC(Br)C1=CC=C2C(C)(C)CC(C)(C)C2=C1 FZHYDVCIRXMJRY-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000006052 Horner reaction Methods 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 2
- 239000002841 Lewis acid Substances 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 238000007239 Wittig reaction Methods 0.000 description 2
- 206010000496 acne Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical group CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 150000001989 diazonium salts Chemical class 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 208000003154 papilloma Diseases 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 239000005051 trimethylchlorosilane Substances 0.000 description 2
- CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 2
- BIUFXBHZCYSMPU-UHFFFAOYSA-N (3-methoxy-5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)methanol Chemical compound CC1(C)CCC(C)(C)C2=C1C=C(CO)C(OC)=C2 BIUFXBHZCYSMPU-UHFFFAOYSA-N 0.000 description 1
- IWIWGFMIKABCFO-UHFFFAOYSA-N 1,1,3,3-tetramethyl-2h-indene Chemical compound C1=CC=C2C(C)(C)CC(C)(C)C2=C1 IWIWGFMIKABCFO-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- KDVZUARNRGKIKF-UHFFFAOYSA-N 1-(7-methoxy-1,1,3,3-tetramethyl-2h-inden-5-yl)ethanone Chemical compound COC1=CC(C(C)=O)=CC2=C1C(C)(C)CC2(C)C KDVZUARNRGKIKF-UHFFFAOYSA-N 0.000 description 1
- 125000006083 1-bromoethyl group Chemical group 0.000 description 1
- UWLHSHAHTBJTBA-UHFFFAOYSA-N 1-iodooctane Chemical compound CCCCCCCCI UWLHSHAHTBJTBA-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- PTIHUMXZQYCPNN-UHFFFAOYSA-N 4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1-carbonitrile Chemical compound ClC1=C(Cl)C(=O)C(C#N)=CC1=O PTIHUMXZQYCPNN-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- QVYTWTDUAISYFX-UHFFFAOYSA-N 4-methylhexa-2,4-dienal Chemical compound CC=C(C)C=CC=O QVYTWTDUAISYFX-UHFFFAOYSA-N 0.000 description 1
- JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 description 1
- OQSPYEBPVLTVFG-UHFFFAOYSA-N 6-(2-bromoethyl)-1,1,4,4-tetramethyl-2,3-dihydronaphthalene Chemical compound BrCCC1=CC=C2C(C)(C)CCC(C)(C)C2=C1 OQSPYEBPVLTVFG-UHFFFAOYSA-N 0.000 description 1
- ARSRBNBHOADGJU-UHFFFAOYSA-N 7,12-dimethyltetraphene Chemical compound C1=CC2=CC=CC=C2C2=C1C(C)=C(C=CC=C1)C1=C2C ARSRBNBHOADGJU-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- LBRDJIFLQLITAV-UHFFFAOYSA-N C(C)(=O)OCC=C(C=CC=C(C)C=1C=C2C(CC(C2=CC1)(C)C)(C)C)C Chemical compound C(C)(=O)OCC=C(C=CC=C(C)C=1C=C2C(CC(C2=CC1)(C)C)(C)C)C LBRDJIFLQLITAV-UHFFFAOYSA-N 0.000 description 1
- DDIVHJFPPUPPHF-UHFFFAOYSA-N CC(=CCOCC=C(C=CC=C(C)C=1C=C2C(CC(C2=CC=1)(C)C)(C)C)C)C=CC=C(C)C=1C=C2C(CC(C2=CC=1)(C)C)(C)C Chemical compound CC(=CCOCC=C(C=CC=C(C)C=1C=C2C(CC(C2=CC=1)(C)C)(C)C)C)C=CC=C(C)C=1C=C2C(CC(C2=CC=1)(C)C)(C)C DDIVHJFPPUPPHF-UHFFFAOYSA-N 0.000 description 1
- QIZPRSPKZBTDNX-UHFFFAOYSA-N CC(=O)C1=CC=2C(CCC(C2C=C1)(C)C)(C)C.CC1(C=2C=CC=CC2C(CC1)(C)C)C Chemical compound CC(=O)C1=CC=2C(CCC(C2C=C1)(C)C)(C)C.CC1(C=2C=CC=CC2C(CC1)(C)C)C QIZPRSPKZBTDNX-UHFFFAOYSA-N 0.000 description 1
- KWLPYDHVDPSFTK-UHFFFAOYSA-N CC(=O)C1=CC=2C(CCC(C2C=C1OC)(C)C)(C)C.COC=1C=CC=2C(CCC(C2C1)(C)C)(C)C Chemical compound CC(=O)C1=CC=2C(CCC(C2C=C1OC)(C)C)(C)C.COC=1C=CC=2C(CCC(C2C1)(C)C)(C)C KWLPYDHVDPSFTK-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- QZKRHPLGUJDVAR-UHFFFAOYSA-K EDTA trisodium salt Chemical compound [Na+].[Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O QZKRHPLGUJDVAR-UHFFFAOYSA-K 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241001302806 Helogenes Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- YEDTWOLJNQYBPU-UHFFFAOYSA-N [Na].[Na].[Na] Chemical compound [Na].[Na].[Na] YEDTWOLJNQYBPU-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000005036 alkoxyphenyl group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000005037 alkyl phenyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000005998 bromoethyl group Chemical group 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229940117173 croton oil Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical compound NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- VOACVYSPZBBHFY-UHFFFAOYSA-N ethyl 6-diethoxyphosphoryl-3-methylhexa-2,4-dienoate Chemical compound CCOC(=O)C=C(C)C=CCP(=O)(OCC)OCC VOACVYSPZBBHFY-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- FPVGTPBMTFTMRT-NSKUCRDLSA-L fast yellow Chemical compound [Na+].[Na+].C1=C(S([O-])(=O)=O)C(N)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 FPVGTPBMTFTMRT-NSKUCRDLSA-L 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000002035 hexane extract Substances 0.000 description 1
- 201000006122 hypervitaminosis A Diseases 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 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
- 230000003780 keratinization Effects 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000012958 reprocessing Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000009121 systemic therapy Methods 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
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/132—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group
- C07C29/136—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH
- C07C29/143—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by reduction of an oxygen containing functional group of >C=O containing groups, e.g. —COOH of ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/38—Alcohols containing six-membered aromatic rings and other rings and having unsaturation outside the aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C33/00—Unsaturated compounds having hydroxy or O-metal groups bound to acyclic carbon atoms
- C07C33/40—Halogenated unsaturated alcohols
- C07C33/50—Halogenated unsaturated alcohols containing six-membered aromatic rings and other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/46—Friedel-Crafts reactions
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/782—Ketones containing a keto group bound to a six-membered aromatic ring polycyclic
- C07C49/792—Ketones containing a keto group bound to a six-membered aromatic ring polycyclic containing rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5456—Arylalkanephosphonium compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| LU77254A LU77254A1 (ja) | 1977-05-04 | 1977-05-04 | |
| LU77254 | 1977-05-04 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI781227A FI781227A (fi) | 1978-11-05 |
| FI66587B FI66587B (fi) | 1984-07-31 |
| FI66587C true FI66587C (fi) | 1984-11-12 |
Family
ID=19728555
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI781227A FI66587C (fi) | 1977-05-04 | 1978-04-20 | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara polyenfoereningar |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US4193931A (ja) |
| JP (1) | JPS53137940A (ja) |
| AR (1) | AR220704A1 (ja) |
| AT (1) | AT356647B (ja) |
| AU (1) | AU522598B2 (ja) |
| BE (1) | BE866651A (ja) |
| BR (1) | BR7802807A (ja) |
| CA (1) | CA1114830A (ja) |
| CH (2) | CH641755A5 (ja) |
| CS (1) | CS214853B2 (ja) |
| CU (1) | CU21105A (ja) |
| DE (1) | DE2819213A1 (ja) |
| DK (1) | DK155730C (ja) |
| ES (2) | ES469394A1 (ja) |
| FI (1) | FI66587C (ja) |
| FR (1) | FR2390428A1 (ja) |
| GB (2) | GB1600915A (ja) |
| GR (1) | GR74426B (ja) |
| HU (1) | HU183088B (ja) |
| IE (1) | IE46946B1 (ja) |
| IL (2) | IL54590A (ja) |
| IT (1) | IT1096278B (ja) |
| LU (1) | LU77254A1 (ja) |
| MC (1) | MC1193A1 (ja) |
| MY (1) | MY8500250A (ja) |
| NL (1) | NL7804773A (ja) |
| NO (1) | NO148290C (ja) |
| NZ (1) | NZ187114A (ja) |
| PH (1) | PH14216A (ja) |
| PT (1) | PT67988B (ja) |
| SE (1) | SE436644B (ja) |
| ZA (1) | ZA782415B (ja) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4216312A (en) * | 1978-08-24 | 1980-08-05 | Hoffmann-La Roche Inc. | Furyl substituted polyenes |
| FI67386C (fi) * | 1979-06-21 | 1985-03-11 | Hoffmann La Roche | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara sockerderivat |
| CH651007A5 (de) * | 1982-06-24 | 1985-08-30 | Hoffmann La Roche | Polyenverbindungen. |
| DK158947C (da) * | 1982-07-06 | 1991-01-21 | Hoffmann La Roche | Tetrahydronaphthalin-,benzofuran- og benzothiophenderivater, fremstilling og anvendelse deraf samt rodenticid indeholdende saadanne derivater |
| US4529600A (en) * | 1982-09-09 | 1985-07-16 | Sri International | Pentadeuterioretinoids |
| US4439614A (en) * | 1982-09-22 | 1984-03-27 | Sri International | 5,6-Methano-5,6-dihydroretinoids |
| US4464389A (en) * | 1982-10-20 | 1984-08-07 | Sri International | Esters of retinoic acid and pentaerythritol and monobenzal acetals thereof |
| US4539154A (en) * | 1983-06-15 | 1985-09-03 | Hoffmann-La Roche Inc. | Polyene compounds |
| CH661516A5 (de) * | 1983-12-08 | 1987-07-31 | Hoffmann La Roche | Phenylnonatetraenoylzuckerderivate. |
| FR2569689B1 (fr) * | 1984-09-05 | 1990-11-16 | Oreal | Nouveaux derives du benzonorbornene, leurs procedes de preparation et compositions medicamenteuse et cosmetique les contenant |
| FR2580277B1 (fr) * | 1985-04-15 | 1988-06-10 | Oreal | Nouveaux derives naphtaleniques a action retinoique, le ur procede de preparation et compositions medicamenteuse et cosmetique les contenant |
| ZW7487A1 (en) * | 1986-05-23 | 1987-12-16 | Hoffmann La Roche | Tetrahydronaphthaline and indane derivatives |
| US5030765A (en) * | 1986-05-23 | 1991-07-09 | Hoffmann-La Roche Inc. | Novel tetrahydronaphthalene and indane derivatives |
| US5030764A (en) * | 1986-05-23 | 1991-07-09 | Hoffmann-La Roche Inc. | Novel tetrahydronaphthalene and indane derivatives |
| AT388728B (de) * | 1987-03-17 | 1989-08-25 | Hoffmann La Roche | Neue tetrahydronaphthalin- und indanderivate |
| US5250562A (en) * | 1988-02-24 | 1993-10-05 | Hoffmann-La Roche Inc. | Stilbene derivatives |
| US5248696A (en) * | 1991-04-18 | 1993-09-28 | World Research Institute For Science And Technology, Inc. | Composition and method for treating tumors |
| US7655699B1 (en) | 1992-04-22 | 2010-02-02 | Eisai Inc. | Compounds having selective activity for retinoid X receptors, and means for modulation of processes mediated by retinoid X receptors |
| US5780676A (en) * | 1992-04-22 | 1998-07-14 | Ligand Pharmaceuticals Incorporated | Compounds having selective activity for Retinoid X Receptors, and means for modulation of processes mediated by Retinoid X Receptors |
| CA2129773C (en) * | 1993-09-02 | 2007-05-01 | Michael Klaus | Aromatic carboxylic acid derivatives |
| FR2719041B1 (fr) * | 1994-04-26 | 1996-05-31 | Cird Galderma | Nouveaux composés polyéniques, compositions pharmaceutiques et cosmétiques les contenant et utilisations. |
| AU712187B2 (en) * | 1994-12-30 | 1999-10-28 | Ligand Pharmaceuticals Incorporated | Novel trienoic retinoid compounds and methods |
| US7115728B1 (en) * | 1995-01-30 | 2006-10-03 | Ligand Pharmaceutical Incorporated | Human peroxisome proliferator activated receptor γ |
| CA2233888A1 (en) * | 1995-10-06 | 1997-04-10 | Ligand Pharmaceuticals Incorporated | Dimer-selective rxr modulators and methods for their use |
| US6112489A (en) * | 1995-12-12 | 2000-09-05 | Monotech International, Inc. | Monocoque concrete structures |
| WO1998007716A2 (en) * | 1996-08-23 | 1998-02-26 | The Board Of Regents For Oklahoma State University | Heteroarotinoids-anticancer agents with receptor specificity and tgase activity |
| FR2752837B1 (fr) * | 1996-09-02 | 1999-11-12 | Cird Galderma | Nouveaux composes modulateurs des recepteurs hormonaux, les compositions les comprenant et leur utilisation en therapie |
| WO1999005161A1 (en) | 1997-07-25 | 1999-02-04 | Ligand Pharmaceuticals Incorporated | HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA (PPARη) GENE REGULATORY SEQUENCES AND USES THEREFOR |
| US6534545B1 (en) | 1997-09-25 | 2003-03-18 | Galderma Research & Development | Unsaturated derivatives at the 4-position of 6-tert-butyl-1,1-dimethylindane and their use in human and veterinary medicine and cosmetics |
| FR2768731B1 (fr) | 1997-09-25 | 1999-12-10 | Cird Galderma | Derives insatures en position -4 du 6-tert-butyl-1,1- dimethylindane et leur utilisation en medecine humaine ou veterinaire ainsi qu'en cosmetique |
| EP1093362A1 (en) * | 1998-06-12 | 2001-04-25 | Ligand Pharmaceuticals Incorporated | Treatment of anti-estrogen resistant breast cancer using rxr modulators |
| US6566372B1 (en) * | 1999-08-27 | 2003-05-20 | Ligand Pharmaceuticals Incorporated | Bicyclic androgen and progesterone receptor modulator compounds and methods |
| EP1212322A2 (en) | 1999-08-27 | 2002-06-12 | Ligand Pharmaceuticals Incorporated | 8-substituted-6-trifluoromethyl-9-pyrido[3,2-g]quinoline compounds as androgen receptor modulators |
| TR200200507T2 (tr) * | 1999-08-27 | 2002-10-21 | Ligand Pharmaceuticals Inc | Androjen reseptörü modülatör bileşikleri ve metotları |
| PE20010647A1 (es) * | 1999-09-14 | 2001-06-23 | Lilly Co Eli | Moduladores de receptores de retinoide x (rxr) con perfil farmacologico mejorado |
| US7312247B2 (en) | 2001-03-27 | 2007-12-25 | Errant Gene Therapeutics, Llc | Histone deacetylase inhibitors |
| US6495719B2 (en) * | 2001-03-27 | 2002-12-17 | Circagen Pharmaceutical | Histone deacetylase inhibitors |
| US8026280B2 (en) | 2001-03-27 | 2011-09-27 | Errant Gene Therapeutics, Llc | Histone deacetylase inhibitors |
| US7842727B2 (en) * | 2001-03-27 | 2010-11-30 | Errant Gene Therapeutics, Llc | Histone deacetylase inhibitors |
| US6586460B1 (en) | 2001-04-02 | 2003-07-01 | The Board Of Regents For Oklahoma State University | Heteroarotinoids containing urea or thiourea linker |
| AU2003243272A1 (en) * | 2002-05-22 | 2003-12-12 | Errant Gene Therapeutics, Llc | Histone deacetylase inhibitors based on alpha-ketoepoxide compounds |
| EP1567142A4 (en) * | 2002-11-20 | 2005-12-14 | Errant Gene Therapeutics Llc | TREATMENT OF PULMONARY CELLS WITH HISTONE DEACETYLASE INHIBITORS |
| US9050310B2 (en) * | 2004-06-25 | 2015-06-09 | Minas Theodore Coroneo | Treatment of ocular lesions |
| EP1817020A4 (en) * | 2004-11-08 | 2012-11-21 | Errant Gene Therapeutics Inc | INHIBITORS OF HISTONATE ACETYLASE |
| US20060204474A1 (en) * | 2005-02-25 | 2006-09-14 | Coroneo Minas T | Treatment of epithelial layer lesions |
| WO2012076842A1 (en) * | 2010-12-09 | 2012-06-14 | University Of Durham | Synthetic retinoids for control of cell differentiation |
| US11045441B2 (en) | 2015-10-13 | 2021-06-29 | Wisconsin Alumni Research Foundation | Use of retinoic acid and analogs thereof to treat central neural apneas |
| MX2020003762A (es) * | 2017-09-28 | 2022-05-03 | Johnson & Johnson Consumer Inc | Composiciones cosmeticas y metodo para tratar la piel. |
| US10966948B2 (en) | 2019-07-23 | 2021-04-06 | Johnson & Johnson Surgical Vision, Inc. | Compositions and methods for treating the eye |
| KR20210038636A (ko) * | 2018-07-27 | 2021-04-07 | 존슨 앤드 존슨 서지컬 비전, 인코포레이티드 | 눈 치료용 조성물 및 방법 |
| US11197841B2 (en) | 2019-07-23 | 2021-12-14 | Johnson & Johnson Surgical Vision, Inc. | Compositions and methods for treating the eye |
| US11969454B2 (en) | 2019-11-19 | 2024-04-30 | Johnson & Johnson Surgical Vision, Inc. | Compositions and methods for treating the eye |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3452085A (en) * | 1966-02-11 | 1969-06-24 | Carbo Erba Spa | Alpha-(5-indanyl)-butyric acid |
| US3781314A (en) * | 1971-07-14 | 1973-12-25 | Hoffmann La Roche | Polyene compounds |
| BE793108A (fr) * | 1971-12-22 | 1973-06-21 | Hoffmann La Roche | Derives polyeniques |
| FR2235679B1 (ja) * | 1973-07-02 | 1978-07-21 | Takeda Chemical Industries Ltd | |
| CH582668A5 (ja) * | 1973-08-10 | 1976-12-15 | Hoffmann La Roche | |
| CH585709A5 (ja) * | 1973-08-24 | 1977-03-15 | Hoffmann La Roche | |
| CH592598A5 (ja) * | 1973-10-30 | 1977-10-31 | Hexachimie | |
| AR206620A1 (es) * | 1974-02-07 | 1976-08-06 | Hexachimie | Procedimiento para preparar acidos 5-indanilaceticos |
| FR2276035A1 (fr) * | 1974-06-28 | 1976-01-23 | Lipha | Nouveaux derives de l'indane |
| US4054589A (en) * | 1974-09-26 | 1977-10-18 | Hoffmann-La Roche Inc. | Novel 9-substituted phenyl-3,7-dimethyl-nona-2,4,6,8-tetraene esters |
| JPS51125235A (en) * | 1974-09-26 | 1976-11-01 | Hoffmann La Roche | Preparation of polyene compounds |
-
1977
- 1977-05-04 LU LU77254A patent/LU77254A1/xx unknown
-
1978
- 1978-03-30 CH CH340578A patent/CH641755A5/de not_active IP Right Cessation
- 1978-04-13 CA CA301,052A patent/CA1114830A/en not_active Expired
- 1978-04-20 FI FI781227A patent/FI66587C/fi not_active IP Right Cessation
- 1978-04-24 US US05/899,427 patent/US4193931A/en not_active Expired - Lifetime
- 1978-04-27 ZA ZA00782415A patent/ZA782415B/xx unknown
- 1978-04-27 IL IL54590A patent/IL54590A/xx unknown
- 1978-04-28 NZ NZ187714A patent/NZ187114A/xx unknown
- 1978-05-01 IE IE864/78A patent/IE46946B1/en unknown
- 1978-05-02 DE DE19782819213 patent/DE2819213A1/de active Granted
- 1978-05-02 JP JP5241878A patent/JPS53137940A/ja active Granted
- 1978-05-02 FR FR7812933A patent/FR2390428A1/fr active Granted
- 1978-05-02 MC MC781300A patent/MC1193A1/xx unknown
- 1978-05-03 GB GB5961/80A patent/GB1600915A/en not_active Expired
- 1978-05-03 PT PT67988A patent/PT67988B/pt unknown
- 1978-05-03 HU HU78HO2072A patent/HU183088B/hu not_active IP Right Cessation
- 1978-05-03 AT AT320478A patent/AT356647B/de not_active IP Right Cessation
- 1978-05-03 BE BE187341A patent/BE866651A/xx not_active IP Right Cessation
- 1978-05-03 DK DK195378A patent/DK155730C/da not_active IP Right Cessation
- 1978-05-03 NL NL7804773A patent/NL7804773A/xx not_active Application Discontinuation
- 1978-05-03 NO NO781586A patent/NO148290C/no unknown
- 1978-05-03 PH PH21098A patent/PH14216A/en unknown
- 1978-05-03 GB GB17478/78A patent/GB1600914A/en not_active Expired
- 1978-05-03 SE SE7805136A patent/SE436644B/sv not_active IP Right Cessation
- 1978-05-03 ES ES469394A patent/ES469394A1/es not_active Expired
- 1978-05-04 CU CU7834913A patent/CU21105A/es unknown
- 1978-05-04 IT IT23003/78A patent/IT1096278B/it active
- 1978-05-04 BR BR7802807A patent/BR7802807A/pt unknown
- 1978-05-04 AU AU35762/78A patent/AU522598B2/en not_active Expired
- 1978-05-04 CS CS782858A patent/CS214853B2/cs unknown
- 1978-05-04 GR GR56136A patent/GR74426B/el unknown
- 1978-05-04 AR AR272036A patent/AR220704A1/es active
- 1978-11-20 ES ES475240A patent/ES475240A1/es not_active Expired
-
1980
- 1980-12-12 IL IL61697A patent/IL61697A0/xx unknown
-
1983
- 1983-02-11 CH CH78683A patent/CH642380A5/de not_active IP Right Cessation
-
1985
- 1985-12-30 MY MY250/85A patent/MY8500250A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI66587C (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara polyenfoereningar | |
| US4326055A (en) | Stilbene derivatives | |
| FI84908C (fi) | Foerfarande foer framstaellning av diarylacetylener, som aer anvaendbara saosom laekemedel. | |
| FI68804C (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara stilbenderivat | |
| JPH01157934A (ja) | 新規なベンゾシクロヘプテン誘導体 | |
| US3931257A (en) | Polyene compounds | |
| CA1123442A (en) | Fluorinated polyenes | |
| FI66835B (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara polyenfoereningar samt salter daerav | |
| US5256694A (en) | Diarylacetylenes, their preparation and their use | |
| GB1563732A (en) | Polyene compounds | |
| JPS63501288A (ja) | １，４−ナフタレンジオ−ルおよび１，４−ヒドロキノン誘導体 | |
| CA1276032C (en) | Polyene compounds | |
| KR820000457B1 (ko) | 폴리엔 화합물의 제조 방법 | |
| KR820002075B1 (ko) | 스틸벤유도체의 제조방법 | |
| KR820000458B1 (ko) | 폴리엔화합물의 제조 방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: F. HOFFMANN-LA ROCHE AG |