CA2118697A1 - Derives de l'indole, inhibiteurs de la 5-alpha-reductase - Google Patents

Derives de l'indole, inhibiteurs de la 5-alpha-reductase

Info

Publication number: CA2118697A1
Authority: CA; Canada
Prior art keywords: compound; salt; alkyl; nmr; formula
Prior art date: 1991-09-11
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002118697A

Other languages

English (en)

Inventor

Satoshi Okada

Kozo Sawada

Natsuko Kayakiri

Yuki Saitoh

Hirokazu Tanaka

Masashi Hashimoto

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Fujisawa Pharmaceutical Co Ltd

Original Assignee

Individual

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.)

1991-09-11

Filing date

1992-09-09

Publication date

1993-03-18

1991-09-11 Priority claimed from US07/757,522 external-priority patent/US5212320A/en

1992-09-09 Application filed by Individual filed Critical Individual

1993-03-18 Publication of CA2118697A1 publication Critical patent/CA2118697A1/fr

Status Abandoned legal-status Critical Current

Links

229940054051 antipsychotic indole derivative Drugs 0.000 title abstract description 10
150000002475 indoles Chemical class 0.000 title abstract description 9
229940113178 5 Alpha reductase inhibitor Drugs 0.000 title 1
239000002677 5-alpha reductase inhibitor Substances 0.000 title 1
150000003839 salts Chemical class 0.000 claims abstract description 68
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims abstract description 34
229940123934 Reductase inhibitor Drugs 0.000 claims abstract description 6
150000001875 compounds Chemical class 0.000 claims description 76
125000000217 alkyl group Chemical group 0.000 claims description 31
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
238000000034 method Methods 0.000 claims description 20
239000002253 acid Substances 0.000 claims description 15
238000003379 elimination reaction Methods 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 9
125000006239 protecting group Chemical group 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 6
FISRBTUJXHCGAM-UHFFFAOYSA-N 4-[3-[4-[1-[4-(2-methylpropyl)phenyl]hexoxy]benzoyl]indol-1-yl]butanoic acid Chemical compound C=1C=C(C(=O)C=2C3=CC=CC=C3N(CCCC(O)=O)C=2)C=CC=1OC(CCCCC)C1=CC=C(CC(C)C)C=C1 FISRBTUJXHCGAM-UHFFFAOYSA-N 0.000 claims description 5
201000010099 disease Diseases 0.000 claims description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000005037 alkyl phenyl group Chemical group 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
239000003814 drug Substances 0.000 claims description 3
230000001404 mediated effect Effects 0.000 claims description 3
231100000252 nontoxic Toxicity 0.000 claims description 3
230000003000 nontoxic effect Effects 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 3
241001465754 Metazoa Species 0.000 claims description 2
UAIBWZSWIOHVNZ-UHFFFAOYSA-N 4-[3-[4-[1-[4-(2-methylpropyl)phenyl]pentoxy]benzoyl]indol-1-yl]butanoic acid Chemical compound C=1C=C(C(=O)C=2C3=CC=CC=C3N(CCCC(O)=O)C=2)C=CC=1OC(CCCC)C1=CC=C(CC(C)C)C=C1 UAIBWZSWIOHVNZ-UHFFFAOYSA-N 0.000 claims 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 119
-1 alkaline earth metal salt Chemical class 0.000 description 69
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 62
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 51
239000000203 mixture Substances 0.000 description 47
238000002360 preparation method Methods 0.000 description 42
101150041968 CDC13 gene Proteins 0.000 description 38
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 26
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 24
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 21
150000002148 esters Chemical group 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 18
239000000243 solution Substances 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
239000002904 solvent Substances 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
229910052943 magnesium sulfate Inorganic materials 0.000 description 13
235000019341 magnesium sulphate Nutrition 0.000 description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 12
229960003604 testosterone Drugs 0.000 description 12
239000012267 brine Substances 0.000 description 10
125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 9
229960000443 hydrochloric acid Drugs 0.000 description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
125000005907 alkyl ester group Chemical group 0.000 description 8
230000008030 elimination Effects 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
235000011167 hydrochloric acid Nutrition 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
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 8
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
239000005457 ice water Substances 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
239000000725 suspension Substances 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
239000012230 colorless oil Substances 0.000 description 5
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 5
238000006722 reduction reaction Methods 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
201000004384 Alopecia Diseases 0.000 description 4
239000002841 Lewis acid Substances 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 4
239000013078 crystal Substances 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
150000007517 lewis acids Chemical class 0.000 description 4
239000007788 liquid Substances 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
235000011181 potassium carbonates Nutrition 0.000 description 4
239000007787 solid Substances 0.000 description 4
HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
LYTGASAOAHKORG-UHFFFAOYSA-N 1-[4-(2-methylpropyl)phenyl]pentan-1-one Chemical compound CCCCC(=O)C1=CC=C(CC(C)C)C=C1 LYTGASAOAHKORG-UHFFFAOYSA-N 0.000 description 3
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
206010000496 acne Diseases 0.000 description 3
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
PSEHHVRCDVOTID-NAVXHOJHSA-N chloro-bis[(1s,3s,4r,5s)-4,6,6-trimethyl-3-bicyclo[3.1.1]heptanyl]borane Chemical compound C([C@@H]([C@H]1C)B(Cl)[C@@H]2[C@@H](C)[C@@]3(C[C@](C2)(C3(C)C)[H])[H])[C@]2([H])C(C)(C)[C@@]1([H])C2 PSEHHVRCDVOTID-NAVXHOJHSA-N 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
125000004356 hydroxy functional group Chemical group O* 0.000 description 3
230000002401 inhibitory effect Effects 0.000 description 3
KXUHSQYYJYAXGZ-UHFFFAOYSA-N isobutylbenzene Chemical compound CC(C)CC1=CC=CC=C1 KXUHSQYYJYAXGZ-UHFFFAOYSA-N 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000000843 powder Substances 0.000 description 3
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
238000003756 stirring Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
LQGMXKXKTHJGAI-OAHLLOKOSA-N (1r)-1-[4-(2-methylpropyl)phenyl]pentan-1-ol Chemical compound CCCC[C@@H](O)C1=CC=C(CC(C)C)C=C1 LQGMXKXKTHJGAI-OAHLLOKOSA-N 0.000 description 2
GGFQGSUQOGVNBQ-UHFFFAOYSA-N 1-(1-bromohexyl)-4-(2-methylpropyl)benzene Chemical compound CCCCCC(Br)C1=CC=C(CC(C)C)C=C1 GGFQGSUQOGVNBQ-UHFFFAOYSA-N 0.000 description 2
LILNXNJUTKZRTF-UHFFFAOYSA-N 1-[4-(2-methylpropyl)phenyl]hexan-1-ol Chemical compound CCCCCC(O)C1=CC=C(CC(C)C)C=C1 LILNXNJUTKZRTF-UHFFFAOYSA-N 0.000 description 2
DGNYSNMYAQGDJL-UHFFFAOYSA-N 1-[4-(2-methylpropyl)phenyl]hexan-1-one Chemical compound CCCCCC(=O)C1=CC=C(CC(C)C)C=C1 DGNYSNMYAQGDJL-UHFFFAOYSA-N 0.000 description 2
LQGMXKXKTHJGAI-UHFFFAOYSA-N 1-[4-(2-methylpropyl)phenyl]pentan-1-ol Chemical compound CCCCC(O)C1=CC=C(CC(C)C)C=C1 LQGMXKXKTHJGAI-UHFFFAOYSA-N 0.000 description 2
CEYBCWUOMMOBMH-UHFFFAOYSA-N 1h-indol-3-yl-(3-nitrophenyl)methanone Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)C=2C3=CC=CC=C3NC=2)=C1 CEYBCWUOMMOBMH-UHFFFAOYSA-N 0.000 description 2
TYKFEQBRBNHOJM-UHFFFAOYSA-N 2,2-dimethyl-1-[4-(2-methylpropyl)phenyl]propan-1-ol Chemical compound CC(C)CC1=CC=C(C(O)C(C)(C)C)C=C1 TYKFEQBRBNHOJM-UHFFFAOYSA-N 0.000 description 2
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
208000002874 Acne Vulgaris Diseases 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
206010020112 Hirsutism Diseases 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
206010036976 Prostatism Diseases 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
125000004423 acyloxy group Chemical group 0.000 description 2
230000002411 adverse Effects 0.000 description 2
229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
150000008041 alkali metal carbonates Chemical class 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
231100000360 alopecia Toxicity 0.000 description 2
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
239000002775 capsule Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000001816 cooling Methods 0.000 description 2
125000002592 cumenyl group Chemical group C1(=C(C=CC=C1)*)C(C)C 0.000 description 2
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 2
DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 2
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
QUGIIPDRGIDZIC-UHFFFAOYSA-N ethyl 4-[3-(4-hydroxybenzoyl)indol-1-yl]butanoate Chemical compound C12=CC=CC=C2N(CCCC(=O)OCC)C=C1C(=O)C1=CC=C(O)C=C1 QUGIIPDRGIDZIC-UHFFFAOYSA-N 0.000 description 2
125000004494 ethyl ester group Chemical group 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
125000005446 heptyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 2
125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 2
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
125000002346 iodo group Chemical group I* 0.000 description 2
FGKJLKRYENPLQH-UHFFFAOYSA-N isocaproic acid Chemical compound CC(C)CCC(O)=O FGKJLKRYENPLQH-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
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
150000004702 methyl esters Chemical class 0.000 description 2
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BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
150000002169 ethanolamines Chemical class 0.000 description 1
SKXOUWSGVVVQBY-UHFFFAOYSA-N ethyl 3-[3-(3-nitrobenzoyl)indol-1-yl]propanoate Chemical compound C12=CC=CC=C2N(CCC(=O)OCC)C=C1C(=O)C1=CC=CC([N+]([O-])=O)=C1 SKXOUWSGVVVQBY-UHFFFAOYSA-N 0.000 description 1
ZXOINWVSTHVXNE-UHFFFAOYSA-N ethyl 4-[3-(3-nitrobenzoyl)indol-1-yl]butanoate Chemical compound C12=CC=CC=C2N(CCCC(=O)OCC)C=C1C(=O)C1=CC=CC([N+]([O-])=O)=C1 ZXOINWVSTHVXNE-UHFFFAOYSA-N 0.000 description 1
AZWFHHNTXZIPFS-UHFFFAOYSA-N ethyl 4-[3-[3-[1-[4-(2-methylpropyl)phenyl]butylamino]benzoyl]indol-1-yl]butanoate Chemical compound C=1C=CC(C(=O)C=2C3=CC=CC=C3N(CCCC(=O)OCC)C=2)=CC=1NC(CCC)C1=CC=C(CC(C)C)C=C1 AZWFHHNTXZIPFS-UHFFFAOYSA-N 0.000 description 1
RSJHGGMTXCQVRR-UHFFFAOYSA-N ethyl 4-[3-[3-[1-[4-(2-methylpropyl)phenyl]hexylamino]benzoyl]indol-1-yl]butanoate Chemical compound C=1C=CC(C(=O)C=2C3=CC=CC=C3N(CCCC(=O)OCC)C=2)=CC=1NC(CCCCC)C1=CC=C(CC(C)C)C=C1 RSJHGGMTXCQVRR-UHFFFAOYSA-N 0.000 description 1
FVEGKSVWFUOTMU-UHFFFAOYSA-N ethyl 4-[3-[3-[1-[4-(2-methylpropyl)phenyl]propylamino]benzoyl]indol-1-yl]butanoate Chemical compound C12=CC=CC=C2N(CCCC(=O)OCC)C=C1C(=O)C(C=1)=CC=CC=1NC(CC)C1=CC=C(CC(C)C)C=C1 FVEGKSVWFUOTMU-UHFFFAOYSA-N 0.000 description 1
JNGRFTLFHPNRLI-XMMPIXPASA-N ethyl 4-[3-[4-[(1r)-1-[4-(2-methylpropyl)phenyl]ethoxy]benzoyl]indol-1-yl]butanoate Chemical compound C1([C@@H](C)OC2=CC=C(C=C2)C(=O)C2=CN(C3=CC=CC=C32)CCCC(=O)OCC)=CC=C(CC(C)C)C=C1 JNGRFTLFHPNRLI-XMMPIXPASA-N 0.000 description 1
JNGRFTLFHPNRLI-DEOSSOPVSA-N ethyl 4-[3-[4-[(1s)-1-[4-(2-methylpropyl)phenyl]ethoxy]benzoyl]indol-1-yl]butanoate Chemical compound C1([C@H](C)OC2=CC=C(C=C2)C(=O)C2=CN(C3=CC=CC=C32)CCCC(=O)OCC)=CC=C(CC(C)C)C=C1 JNGRFTLFHPNRLI-DEOSSOPVSA-N 0.000 description 1
MEHAIXNJPBTCER-UHFFFAOYSA-N ethyl 4-[3-[4-[1-[4-(2-methylpropyl)phenyl]octoxy]benzoyl]indol-1-yl]butanoate Chemical compound C=1C=C(C(=O)C=2C3=CC=CC=C3N(CCCC(=O)OCC)C=2)C=CC=1OC(CCCCCCC)C1=CC=C(CC(C)C)C=C1 MEHAIXNJPBTCER-UHFFFAOYSA-N 0.000 description 1
XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
238000000605 extraction Methods 0.000 description 1
235000019253 formic acid Nutrition 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
239000011521 glass Substances 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000008187 granular material Substances 0.000 description 1
125000003106 haloaryl group Chemical group 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
125000005059 halophenyl group Chemical group 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
150000002431 hydrogen Chemical group 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
201000010066 hyperandrogenism Diseases 0.000 description 1
238000011534 incubation Methods 0.000 description 1
229910003480 inorganic solid Inorganic materials 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
239000008101 lactose Substances 0.000 description 1
235000015122 lemonade Nutrition 0.000 description 1
239000006210 lotion Substances 0.000 description 1
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
239000001095 magnesium carbonate Substances 0.000 description 1
229910000021 magnesium carbonate Inorganic materials 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
239000004137 magnesium phosphate Substances 0.000 description 1
229910000157 magnesium phosphate Inorganic materials 0.000 description 1
229960002261 magnesium phosphate Drugs 0.000 description 1
235000010994 magnesium phosphates Nutrition 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000000463 material Substances 0.000 description 1
239000003863 metallic catalyst Substances 0.000 description 1
STEPQTYSZVCJPV-UHFFFAOYSA-N metazachlor Chemical compound CC1=CC=CC(C)=C1N(C(=O)CCl)CN1N=CC=C1 STEPQTYSZVCJPV-UHFFFAOYSA-N 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
125000004971 nitroalkyl group Chemical group 0.000 description 1
MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
229940099990 ogen Drugs 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
239000008188 pellet Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000012071 phase Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
125000006308 propyl amino group Chemical group 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
201000004240 prostatic hypertrophy Diseases 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical class [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet 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
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
PUGUQINMNYINPK-UHFFFAOYSA-N tert-butyl 4-(2-chloroacetyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(C(=O)CCl)CC1 PUGUQINMNYINPK-UHFFFAOYSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
LTSUHJWLSNQKIP-UHFFFAOYSA-J tin(iv) bromide Chemical compound Br[Sn](Br)(Br)Br LTSUHJWLSNQKIP-UHFFFAOYSA-J 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
UBZYKBZMAMTNKW-UHFFFAOYSA-J titanium tetrabromide Chemical compound Br[Ti](Br)(Br)Br UBZYKBZMAMTNKW-UHFFFAOYSA-J 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000003944 tolyl group Chemical group 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
125000005270 trialkylamine group Chemical group 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
229920001567 vinyl ester resin Polymers 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
125000005023 xylyl group Chemical group 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (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)
Dermatology (AREA)
Urology & Nephrology (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)

CA002118697A 1991-09-11 1992-09-09 Derives de l'indole, inhibiteurs de la 5-alpha-reductase Abandoned CA2118697A1 (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US07/757,522 US5212320A (en)	1990-05-21	1991-09-11	Indole derivatives and their use for testosterone 5-alpha-reductase-mediated diseases
US07/757,522		1991-09-11
US79259591A	1991-11-15	1991-11-15
US07/792,595		1991-11-15

Publications (1)

Publication Number	Publication Date
CA2118697A1 true CA2118697A1 (fr)	1993-03-18

Family

ID=27116395

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002118697A Abandoned CA2118697A1 (fr)	1991-09-11	1992-09-09	Derives de l'indole, inhibiteurs de la 5-alpha-reductase

Country Status (4)

Country	Link
EP (1)	EP0603278A1 (fr)
JP (1)	JPH07501790A (fr)
CA (1)	CA2118697A1 (fr)
WO (1)	WO1993005019A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9302577D0 (en) *	1993-02-10	1993-03-24	Fujisawa Pharmaceutical Co	Indole derivatives
GB9310092D0 (en) *	1993-05-17	1993-06-30	Fujisawa Pharmaceutical Co	Indole derivatives
DE69521687T2 (de) *	1994-03-30	2001-10-25	Zeria Pharmaceutical Co., Ltd.	4-indol-1-yl-buttersäure derivate, deren herstellung und deren verwendung als inhibitoren für alpha1-adrenerge rezeptoren und testosteron 5alpha-reduktasen
US5543417A (en) *	1994-10-21	1996-08-06	Merck & Co., Inc.	Combination method of treating acne using 4-AZA-5α-cholestan-ones and 4-AZA-5α-androstan-ones as selective 5α-reductase inhibitors with anti-bacterial, keratolytic, or anti-inflammatory agents
KR100368297B1 (ko) *	2000-05-31	2003-01-24	이승기	양성 전립선 비대증 치료용 메나퀴논 7

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR1492929A (fr) *	1966-05-11	1967-08-25	Roussel Uclaf	Nouveaux 1-(omega-carboxyalcoyl) indoles substitués et procédé de préparation
FR7337M (fr) *	1968-01-11	1969-10-13
US3557142A (en) *	1968-02-20	1971-01-19	Sterling Drug Inc	4,5,6,7-tetrahydro-indole-lower-alkanoic acids and esters
AU574383B2 (en) *	1983-09-28	1988-07-07	Nippon Zoki Pharmaceutical Co., Ltd.	Acylindole derivatives
GB9011335D0 (en) *	1990-05-21	1990-07-11	Fujisawa Pharmaceutical Co	Indolebutyric acid derivatives and process for preparation thereof

1992
- 1992-09-09 JP JP5505114A patent/JPH07501790A/ja active Pending
- 1992-09-09 CA CA002118697A patent/CA2118697A1/fr not_active Abandoned
- 1992-09-09 EP EP92919507A patent/EP0603278A1/fr not_active Ceased
- 1992-09-09 WO PCT/JP1992/001152 patent/WO1993005019A1/fr not_active Ceased

Also Published As

Publication number	Publication date
JPH07501790A (ja)	1995-02-23
WO1993005019A1 (fr)	1993-03-18
EP0603278A1 (fr)	1994-06-29

Legal Events

Date	Code	Title	Description
1998-09-09	FZDE	Dead

Publication	Publication Date	Title
EP0458207B1 (fr)	1997-03-26	Dérivés d'indole
JPS61191683A (ja)	1986-08-26	新規な酸性インド−ル化合物
EP0552552A2 (fr)	1993-07-28	Dérivés de l'acide 5-déazafolique et leur utilisation comme agents antinéoplastiques
NZ332640A (en)	2001-03-30	Optionally fused phenyl methyl substituted indole derivatives useful as endothelin receptor antagonists
US5530019A (en)	1996-06-25	Indole derivatives useful as testosterone 5α-reductase inhibitors
EP0620818A1 (fr)	1994-10-26	CETONES D'ARYLE UTILISEES COMME INHIBITEURS DE TESTOSTERONE 5$g(a)-REDUCTASE
WO1991009598A1 (fr)	1991-07-11	Derives de l'azaoxindole
US5811432A (en)	1998-09-22	Azaoxindole derivatives
EP0516849B1 (fr)	1995-01-25	Derives d'indole
NZ224240A (en)	1991-03-26	Indole and isoindoline derivatives, preparation and pharmaceutical compositions thereof
CA2118697A1 (fr)	1993-03-18	Derives de l'indole, inhibiteurs de la 5-alpha-reductase
JP3465827B2 (ja)	2003-11-10	アザインドール誘導体およびこれを有効成分とする抗潰瘍薬
JP2663794B2 (ja)	1997-10-15	複素環誘導体
ES2322260T3 (es)	2009-06-18	Nuevos derivados de acetona sustituidos con heteroarilo en calidad de inhibidores de la fosfolipasa a2.
AU735516B2 (en)	2001-07-12	Process for preparing 4-substituted-1H-indole-3-glyoxamides
US5780633A (en)	1998-07-14	Process for the preparation of indolizine derivatives
JPS60202877A (ja)	1985-10-14	ω‐アリール‐アルキルチエニル化合物、それらの製法およびこれら化合物を含有する医薬生成物
JPH07503969A (ja)	1995-04-27	テストステロン５α−還元酵素阻害剤としてのインドール誘導体
US5283251A (en)	1994-02-01	Indole derivatives
US5212320A (en)	1993-05-18	Indole derivatives and their use for testosterone 5-alpha-reductase-mediated diseases
GB2287706A (en)	1995-09-27	Indolizine derivatives
US3535337A (en)	1970-10-20	1-p-chlorobenzoyl-2-methyl-3-metallo-methyl indoles
WO1994018168A1 (fr)	1994-08-18	Derives d'indole utilises comme inhibiteurs de 5-alpha-reductase
WO1994026710A1 (fr)	1994-11-24	DERIVES D'INDOLE UTILES COMME INHIBITEURS DE LA TESTOSTERONE 5α-REDUCTASE