SK142495A3 - Carbazole derivatives, process for preparing the same, pharmaceutical compositions containing the same and their use - Google Patents

Carbazole derivatives, process for preparing the same, pharmaceutical compositions containing the same and their use Download PDF

Info

Publication number: SK142495A3
Authority: SK; Slovakia
Prior art keywords: group; carbazole; ylmethyl; formula; compound according
Prior art date: 1993-05-21

Application number

SK1424-95A

Other languages

English (en)

Slovak (sk)

Inventor

Peter C Cherry

John D Cocker

Andrew D Searle

Original Assignee

Glaxo Group Ltd

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.)

1993-05-21

Filing date

1994-05-19

Publication date

1996-06-05

1994-05-19 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1996-06-05 Publication of SK142495A3 publication Critical patent/SK142495A3/sk

Links

239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 15
238000004519 manufacturing process Methods 0.000 title claims description 4
125000000609 carbazolyl group Chemical class C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 title abstract 2
150000001875 compounds Chemical class 0.000 claims abstract description 151
150000003839 salts Chemical class 0.000 claims abstract description 31
238000000034 method Methods 0.000 claims abstract description 27
239000012453 solvate Substances 0.000 claims abstract description 21
238000002360 preparation method Methods 0.000 claims abstract description 17
239000003098 androgen Substances 0.000 claims abstract description 13
239000003814 drug Substances 0.000 claims abstract description 12
239000000262 estrogen Substances 0.000 claims abstract description 12
125000006575 electron-withdrawing group Chemical group 0.000 claims abstract description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
125000005843 halogen group Chemical group 0.000 claims abstract description 5
230000008569 process Effects 0.000 claims abstract description 5
239000004480 active ingredient Substances 0.000 claims description 21
-1 2-fluoro-7- [1,2,4] triazol-l-ylmethyl-9H-carbazole 2-fluoro-7-pyridin-3-ylmethyl-9H-carbazole 2-fluoro-7-pyridin-4-ylmethyl-9H-carbazole Chemical compound 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
238000011282 treatment Methods 0.000 claims description 12
229940011871 estrogen Drugs 0.000 claims description 11
229910052731 fluorine Inorganic materials 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
125000001153 fluoro group Chemical group F* 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
229940124597 therapeutic agent Drugs 0.000 claims description 7
LFCQNAOJQWIHSR-UHFFFAOYSA-N 2-fluoro-7-(pyridin-3-ylmethyl)-9h-carbazole Chemical compound C=1C(F)=CC=C(C2=CC=3)C=1NC2=CC=3CC1=CC=CN=C1 LFCQNAOJQWIHSR-UHFFFAOYSA-N 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
206010060862 Prostate cancer Diseases 0.000 claims description 5
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 5
229940030486 androgens Drugs 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
241000124008 Mammalia Species 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
125000002560 nitrile group Chemical group 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
239000000460 chlorine Substances 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
239000002552 dosage form Substances 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
238000011200 topical administration Methods 0.000 claims description 3
GJYDAAIUCZMZGI-UHFFFAOYSA-N 1,7-difluoro-2-(1,2,4-triazol-1-ylmethyl)-9h-carbazole Chemical compound C=1C(F)=CC=C(C2=CC=3)C=1NC2=C(F)C=3CN1C=NC=N1 GJYDAAIUCZMZGI-UHFFFAOYSA-N 0.000 claims description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
125000003172 aldehyde group Chemical group 0.000 claims description 2
125000002843 carboxylic acid group Chemical group 0.000 claims description 2
125000004185 ester group Chemical group 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
125000000468 ketone group Chemical group 0.000 claims 1
239000000825 pharmaceutical preparation Substances 0.000 claims 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
239000000243 solution Substances 0.000 description 82
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
239000000203 mixture Substances 0.000 description 56
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 43
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
239000007787 solid Substances 0.000 description 32
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
239000003054 catalyst Substances 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 26
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
229910052757 nitrogen Inorganic materials 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 19
229910000041 hydrogen chloride Inorganic materials 0.000 description 19
239000002904 solvent Substances 0.000 description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
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 description 18
239000012267 brine Substances 0.000 description 17
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
239000000284 extract Substances 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 14
239000000725 suspension Substances 0.000 description 14
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
102000001854 Steroid 17-alpha-Hydroxylase Human genes 0.000 description 12
108010015330 Steroid 17-alpha-Hydroxylase Proteins 0.000 description 12
235000019441 ethanol Nutrition 0.000 description 12
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
239000004615 ingredient Substances 0.000 description 11
239000003921 oil Substances 0.000 description 11
235000019198 oils Nutrition 0.000 description 11
239000000047 product Substances 0.000 description 11
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
239000000706 filtrate Substances 0.000 description 10
238000005406 washing Methods 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
239000000543 intermediate Substances 0.000 description 9
229910052763 palladium Inorganic materials 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
238000003756 stirring Methods 0.000 description 9
239000003826 tablet Substances 0.000 description 9
229960003604 testosterone Drugs 0.000 description 9
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
239000002585 base Substances 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
230000005764 inhibitory process Effects 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
239000000843 powder Substances 0.000 description 7
125000006239 protecting group Chemical group 0.000 description 7
XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 6
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
235000019270 ammonium chloride Nutrition 0.000 description 6
229960004125 ketoconazole Drugs 0.000 description 6
239000010410 layer Substances 0.000 description 6
235000019359 magnesium stearate Nutrition 0.000 description 6
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
229910052700 potassium Inorganic materials 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
102000011022 Chorionic Gonadotropin Human genes 0.000 description 5
108010062540 Chorionic Gonadotropin Proteins 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
244000166102 Eucalyptus leucoxylon Species 0.000 description 5
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 5
241000700159 Rattus Species 0.000 description 5
UMYBPELCCZPPOD-UHFFFAOYSA-N [4-[[tert-butyl(dimethyl)silyl]oxymethyl]phenyl]boronic acid Chemical compound CC(C)(C)[Si](C)(C)OCC1=CC=C(B(O)O)C=C1 UMYBPELCCZPPOD-UHFFFAOYSA-N 0.000 description 5
125000004429 atom Chemical group 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
238000001816 cooling Methods 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000009472 formulation Methods 0.000 description 5
229940084986 human chorionic gonadotropin Drugs 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
238000010992 reflux Methods 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
241000282412 Homo Species 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
239000003125 aqueous solvent Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000006071 cream Substances 0.000 description 4
SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 4
238000001035 drying Methods 0.000 description 4
239000006260 foam Substances 0.000 description 4
239000008101 lactose Substances 0.000 description 4
239000001267 polyvinylpyrrolidone Substances 0.000 description 4
229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
235000010288 sodium nitrite Nutrition 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 4
239000003981 vehicle Substances 0.000 description 4
CDFBRMQNNCVRSY-UHFFFAOYSA-N 2-fluoro-7-(1,2,4-triazol-1-ylmethyl)-9h-carbazole Chemical compound C=1C(F)=CC=C(C2=CC=3)C=1NC2=CC=3CN1C=NC=N1 CDFBRMQNNCVRSY-UHFFFAOYSA-N 0.000 description 3
CJKAHOZICMOBTA-UHFFFAOYSA-N 2-fluoro-7-(pyridin-4-ylmethyl)-9h-carbazole Chemical compound C=1C(F)=CC=C(C2=CC=3)C=1NC2=CC=3CC1=CC=NC=C1 CJKAHOZICMOBTA-UHFFFAOYSA-N 0.000 description 3
AXUGYCMGYYRNSE-UHFFFAOYSA-N 2-fluoro-7-[(3-fluoropyridin-4-yl)methyl]-9h-carbazole Chemical compound C=1C(F)=CC=C(C2=CC=3)C=1NC2=CC=3CC1=CC=NC=C1F AXUGYCMGYYRNSE-UHFFFAOYSA-N 0.000 description 3
BEEQFMQHLNPVKA-UHFFFAOYSA-N 2-fluoro-7-[(3-methoxypyridin-4-yl)methyl]-9h-carbazole Chemical compound COC1=CN=CC=C1CC1=CC=C2C3=CC=C(F)C=C3NC2=C1 BEEQFMQHLNPVKA-UHFFFAOYSA-N 0.000 description 3
LXCHEUMJSPFNAY-UHFFFAOYSA-N 2-fluoro-7-[(3-methylpyridin-4-yl)methyl]-9h-carbazole Chemical compound CC1=CN=CC=C1CC1=CC=C2C3=CC=C(F)C=C3NC2=C1 LXCHEUMJSPFNAY-UHFFFAOYSA-N 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
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206010028980 Neoplasm Diseases 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
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DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
239000002246 antineoplastic agent Substances 0.000 description 3
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238000000338 in vitro Methods 0.000 description 3
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229910000510 noble metal Inorganic materials 0.000 description 3
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 3
229910052697 platinum Inorganic materials 0.000 description 3
229910003446 platinum oxide Inorganic materials 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
235000019333 sodium laurylsulphate Nutrition 0.000 description 3
229940079832 sodium starch glycolate Drugs 0.000 description 3
239000008109 sodium starch glycolate Substances 0.000 description 3
229920003109 sodium starch glycolate Polymers 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
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239000000375 suspending agent Substances 0.000 description 3
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NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 3
239000008096 xylene Substances 0.000 description 3
KLGLTKXJZOYKJB-UHFFFAOYSA-N (7-fluoro-9h-carbazol-2-yl)-pyridin-3-ylmethanol Chemical compound C=1C=C(C2=CC=C(F)C=C2N2)C2=CC=1C(O)C1=CC=CN=C1 KLGLTKXJZOYKJB-UHFFFAOYSA-N 0.000 description 2
SSPREYNSXYGGTR-UHFFFAOYSA-N 1,4,7-trifluoro-2-(1,2,4-triazol-1-ylmethyl)-9h-carbazole Chemical compound C=1C(F)=CC=C(C2=C(F)C=3)C=1NC2=C(F)C=3CN1C=NC=N1 SSPREYNSXYGGTR-UHFFFAOYSA-N 0.000 description 2
OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 2
XRXNWKIKQFEOGO-UHFFFAOYSA-N 1-bromo-4-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(F)=CC=C1Br XRXNWKIKQFEOGO-UHFFFAOYSA-N 0.000 description 2
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239000003456 ion exchange resin Substances 0.000 description 1
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JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
229940011051 isopropyl acetate Drugs 0.000 description 1
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AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
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VEDDBHYQWFOITD-UHFFFAOYSA-N para-bromobenzyl alcohol Chemical compound OCC1=CC=C(Br)C=C1 VEDDBHYQWFOITD-UHFFFAOYSA-N 0.000 description 1
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239000011591 potassium Substances 0.000 description 1
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229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
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238000007493 shaping process Methods 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
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229910052708 sodium Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
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238000010254 subcutaneous injection Methods 0.000 description 1
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239000000126 substance Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000003900 succinic acid esters Chemical class 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
USFPINLPPFWTJW-UHFFFAOYSA-N tetraphenylphosphonium Chemical compound C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 USFPINLPPFWTJW-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
231100001274 therapeutic index Toxicity 0.000 description 1
230000008719 thickening Effects 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
229940100640 transdermal system Drugs 0.000 description 1
150000003852 triazoles 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
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
238000005550 wet granulation Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

SK1424-95A 1993-05-21 1994-05-19 Carbazole derivatives, process for preparing the same, pharmaceutical compositions containing the same and their use SK142495A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB939310635A GB9310635D0 (en)	1993-05-21	1993-05-21	Chemical compounds
PCT/EP1994/001613 WO1994027989A1 (en)	1993-05-21	1994-05-19	Carbazole derivatives with 17,20-lyase-inhibiting activity

Publications (1)

Publication Number	Publication Date
SK142495A3 true SK142495A3 (en)	1996-06-05

Family

ID=10736007

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1424-95A SK142495A3 (en)	1993-05-21	1994-05-19	Carbazole derivatives, process for preparing the same, pharmaceutical compositions containing the same and their use

Country Status (19)

Country	Link
EP (1)	EP0699196A1 (2)
JP (1)	JPH08510455A (2)
CN (1)	CN1126473A (2)
AU (1)	AU6928794A (2)
BG (1)	BG100154A (2)
CA (1)	CA2162921A1 (2)
CZ (1)	CZ305195A3 (2)
FI (1)	FI955587A7 (2)
GB (1)	GB9310635D0 (2)
HU (1)	HUT73790A (2)
IL (1)	IL109703A0 (2)
NO (1)	NO954681L (2)
OA (1)	OA10195A (2)
PE (1)	PE31195A1 (2)
PL (1)	PL311702A1 (2)
SK (1)	SK142495A3 (2)
TW (1)	TW279866B (2)
WO (1)	WO1994027989A1 (2)
ZA (1)	ZA943494B (2)

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CN1131944A (zh) *	1993-09-30	1996-09-25	山之内制药株式会社	唑类衍生物和它的药物组合物
WO1996014090A1 (en) *	1994-11-07	1996-05-17	Janssen Pharmaceutica N.V.	Compositions comprising carbazoles and cyclodextrins
PL322028A1 (en) *	1995-03-01	1998-01-05	Yamanouchi Pharma Co Ltd	Derivatives of imidazoles and pharmaceutic composition containing them
EP0974584B1 (en) *	1997-02-21	2003-01-15	Takeda Chemical Industries, Ltd.	Fused ring compounds, process for producing the same and use thereof
EP1334106B1 (en)	2000-11-17	2006-05-24	Takeda Pharmaceutical Company Limited	Imidazole derivatives, production method thereof and use thereof
ATE502030T1 (de)	2000-11-20	2011-04-15	Takeda Pharmaceutical	Imidazolderivate, verfahren zu deren herstellung und deren verwendung
WO2002046186A1 (en)	2000-12-08	2002-06-13	Takeda Chemical Industries, Ltd.	Substituted thiazole derivatives bearing 3-pyridyl groups, process for preparing the same and use thereof
MX2007015905A (es) *	2005-06-24	2008-03-06	Lilly Co Eli	Derivados de tetrahidrocarbazol utiles como moduladores de receptor de androgeno (sarm).
GB0525323D0 (en)	2005-12-13	2006-01-18	Sterix Ltd	Compound
US8093279B2 (en)	2005-12-13	2012-01-10	Gillian Reed, legal representative	Compound
CN100586932C (zh) *	2007-01-26	2010-02-03	中国医学科学院医药生物技术研究所	抗肿瘤化合物及其制备方法
MA33451B1 (fr)	2009-06-26	2012-07-03	Novartis Ag	Dérivés d'imidazolidin-2-one 1,3-disubstitués en tant qu'inhibiteurs de cyp 17
CA2788907A1 (en) *	2010-02-04	2011-08-11	Radius Health, Inc.	Selective androgen receptor modulators
PT2568806T (pt)	2010-05-12	2016-08-05	Radius Health Inc	Regimes terapêuticos
US9132105B2 (en)	2010-08-04	2015-09-15	Pellficure Pharmaceuticals, Inc.	Treatment of prostate carcinoma
JP2013537210A (ja)	2010-09-16	2013-09-30	ノバルティスアーゲー	１７α−ヒドロキシラーゼ／Ｃ１７，２０−リアーゼ阻害剤
ES2550319T3 (es)	2010-09-28	2015-11-06	Radius Health, Inc	Moduladores selectivos del receptor de andrógenos
EA023064B1 (ru)	2011-04-28	2016-04-29	Новартис Аг	ИНГИБИТОРЫ 17α-ГИДРОКСИЛАЗЫ/C-ЛИАЗЫ
US9492460B2 (en) *	2013-02-27	2016-11-15	Bristol-Myers Squibb Company	Carbazole compounds useful as bromodomain inhibitors
AU2014241816B9 (en)	2013-03-14	2019-02-14	Pellficure Pharmaceuticals Inc.	Novel therapy for prostate carcinoma
RS67458B1 (sr)	2014-03-28	2025-12-31	Univ Duke	Lečenje kancera dojke pozitivnog na receptor estrogena upotrebom selektivnih modulatora receptora estrogena
US9421264B2 (en)	2014-03-28	2016-08-23	Duke University	Method of treating cancer using selective estrogen receptor modulators
CA2960750A1 (en)	2014-09-12	2016-03-17	Pellficure Pharmaceuticals, Inc.	Compositions and methods for treatment of prostate carcinoma
RS63311B1 (sr)	2016-06-22	2022-07-29	Ellipses Pharma Ltd	Ar+ metode lečenja raka dojke
WO2018080933A1 (en)	2016-10-24	2018-05-03	Pellficure Pharmaceuticals Inc.	Pharmaceutical compositions of 5-hydroxy-2-methylnaphthalene-1, 4-dione
KR102881465B1 (ko)	2017-01-05	2025-11-04	래디어스 파마슈티컬스, 인코포레이티드	Rad1901-2hcl의 다형 형태

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GB8518743D0 (en) *	1985-07-24	1985-08-29	Glaxo Group Ltd	Heterocyclic compounds

1993
- 1993-05-21 GB GB939310635A patent/GB9310635D0/en active Pending
1994
- 1994-05-02 ZA ZA943494A patent/ZA943494B/xx unknown
- 1994-05-17 TW TW083104441A patent/TW279866B/zh active
- 1994-05-19 PL PL94311702A patent/PL311702A1/xx unknown
- 1994-05-19 SK SK1424-95A patent/SK142495A3/sk unknown
- 1994-05-19 EP EP94917647A patent/EP0699196A1/en not_active Withdrawn
- 1994-05-19 CA CA002162921A patent/CA2162921A1/en not_active Abandoned
- 1994-05-19 JP JP7500181A patent/JPH08510455A/ja active Pending
- 1994-05-19 HU HU9503321A patent/HUT73790A/hu unknown
- 1994-05-19 CN CN94192683A patent/CN1126473A/zh active Pending
- 1994-05-19 WO PCT/EP1994/001613 patent/WO1994027989A1/en not_active Ceased
- 1994-05-19 AU AU69287/94A patent/AU6928794A/en not_active Abandoned
- 1994-05-19 CZ CZ953051A patent/CZ305195A3/cs unknown
- 1994-05-20 IL IL10970394A patent/IL109703A0/xx unknown
- 1994-11-18 PE PE1994255110A patent/PE31195A1/es not_active Application Discontinuation
1995
- 1995-11-17 OA OA60742A patent/OA10195A/en unknown
- 1995-11-20 FI FI955587A patent/FI955587A7/fi not_active Application Discontinuation
- 1995-11-20 NO NO954681A patent/NO954681L/no unknown
- 1995-11-21 BG BG100154A patent/BG100154A/xx unknown

Also Published As

Publication number	Publication date
EP0699196A1 (en)	1996-03-06
OA10195A (en)	1996-12-18
JPH08510455A (ja)	1996-11-05
NO954681D0 (no)	1995-11-20
IL109703A0 (en)	1994-08-26
PE31195A1 (es)	1995-10-18
CA2162921A1 (en)	1994-12-08
CN1126473A (zh)	1996-07-10
FI955587A0 (fi)	1995-11-20
PL311702A1 (en)	1996-03-04
CZ305195A3 (en)	1996-06-12
WO1994027989A1 (en)	1994-12-08
FI955587A7 (fi)	1995-11-20
HU9503321D0 (en)	1996-01-29
BG100154A (en)	1996-07-31
GB9310635D0 (en)	1993-07-07
TW279866B (2)	1996-07-01
HUT73790A (en)	1996-09-30
ZA943494B (en)	1995-01-23
AU6928794A (en)	1994-12-20
NO954681L (no)	1995-11-20

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