CN1068816A - 吲哚类衍生物 - Google Patents

吲哚类衍生物 Download PDF

Info

Publication number: CN1068816A
Authority: CN; China
Prior art keywords: formula; compound; alkyl; defined above; cooh
Prior art date: 1991-07-24
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.): Pending

Application number

CN92108675A

Other languages

English (en)

Chinese (zh)

Inventor

J·布拉格

K·库珀

P·L·施帕戈

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.)

Pfizer Inc

Original Assignee

Pfizer Inc

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.)

1991-07-24

Filing date

1992-07-24

Publication date

1993-02-10

1992-07-24 Application filed by Pfizer Inc filed Critical Pfizer Inc

1993-02-10 Publication of CN1068816A publication Critical patent/CN1068816A/zh

Status Pending legal-status Critical Current

Links

150000002475 indoles Chemical class 0.000 title description 5
229940054051 antipsychotic indole derivative Drugs 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 278
238000002360 preparation method Methods 0.000 claims abstract description 61
150000003839 salts Chemical class 0.000 claims abstract description 57
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
238000000034 method Methods 0.000 claims description 72
-1 nitro, amino Chemical group 0.000 claims description 60
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
238000006243 chemical reaction Methods 0.000 claims description 46
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 46
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 41
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 41
239000002585 base Substances 0.000 claims description 39
229910052739 hydrogen Inorganic materials 0.000 claims description 39
125000003118 aryl group Chemical group 0.000 claims description 35
239000000203 mixture Substances 0.000 claims description 32
229910052736 halogen Inorganic materials 0.000 claims description 28
150000002367 halogens Chemical class 0.000 claims description 28
229910052799 carbon Inorganic materials 0.000 claims description 26
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 24
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
230000007062 hydrolysis Effects 0.000 claims description 21
238000006460 hydrolysis reaction Methods 0.000 claims description 21
239000002253 acid Substances 0.000 claims description 20
150000001447 alkali salts Chemical class 0.000 claims description 14
150000002148 esters Chemical class 0.000 claims description 14
229910052727 yttrium Inorganic materials 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
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 claims description 9
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
229910052794 bromium Inorganic materials 0.000 claims description 9
239000012024 dehydrating agents‎ Substances 0.000 claims description 9
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
230000002378 acidificating effect Effects 0.000 claims description 8
239000000460 chlorine Substances 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
229910052708 sodium Inorganic materials 0.000 claims description 8
239000011734 sodium Substances 0.000 claims 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 claims description 8
125000001475 halogen functional group Chemical group 0.000 claims description 7
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 6
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims description 6
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 claims description 6
238000007254 oxidation reaction Methods 0.000 claims description 6
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
238000005886 esterification reaction Methods 0.000 claims description 5
238000002156 mixing Methods 0.000 claims description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
238000005804 alkylation reaction Methods 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
238000003776 cleavage reaction Methods 0.000 claims description 3
230000007017 scission Effects 0.000 claims description 3
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 2
SMSOYFGWXDACGL-QFIPXVFZSA-N 4-[3-[4-[(1s)-1-[4-(2-methylpropyl)phenyl]ethoxy]benzoyl]indol-1-yl]butanoic acid Chemical compound C1=CC(CC(C)C)=CC=C1[C@H](C)OC1=CC=C(C(=O)C=2C3=CC=CC=C3N(CCCC(O)=O)C=2)C=C1 SMSOYFGWXDACGL-QFIPXVFZSA-N 0.000 claims description 2
125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 2
238000005904 alkaline hydrolysis reaction Methods 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 109
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
239000000047 product Substances 0.000 description 41
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
239000000243 solution Substances 0.000 description 36
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 29
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 28
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
238000005160 1H NMR spectroscopy Methods 0.000 description 26
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
239000002904 solvent Substances 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 21
238000010992 reflux Methods 0.000 description 21
239000012044 organic layer Substances 0.000 description 20
238000003756 stirring Methods 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
239000000741 silica gel Substances 0.000 description 17
229910002027 silica gel Inorganic materials 0.000 description 17
229960003604 testosterone Drugs 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
238000001704 evaporation Methods 0.000 description 15
230000008020 evaporation Effects 0.000 description 14
210000002307 prostate Anatomy 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
229910052943 magnesium sulfate Inorganic materials 0.000 description 12
235000019341 magnesium sulphate Nutrition 0.000 description 12
239000003921 oil Substances 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
239000000872 buffer Substances 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 10
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 10
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 10
108010029908 3-oxo-5-alpha-steroid 4-dehydrogenase Proteins 0.000 description 9
102000001779 3-oxo-5-alpha-steroid 4-dehydrogenase Human genes 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
238000003818 flash chromatography Methods 0.000 description 9
239000007787 solid Substances 0.000 description 9
239000007858 starting material Substances 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
201000004384 Alopecia Diseases 0.000 description 8
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
230000002401 inhibitory effect Effects 0.000 description 8
239000000725 suspension Substances 0.000 description 8
108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 7
206010060862 Prostate cancer Diseases 0.000 description 7
208000000236 Prostatic Neoplasms Diseases 0.000 description 7
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
230000020477 pH reduction Effects 0.000 description 7
238000010626 work up procedure Methods 0.000 description 7
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
238000000746 purification Methods 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
239000000758 substrate Substances 0.000 description 6
239000002677 5-alpha reductase inhibitor Substances 0.000 description 5
206010004446 Benign prostatic hyperplasia Diseases 0.000 description 5
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
208000004403 Prostatic Hyperplasia Diseases 0.000 description 5
XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000003098 androgen Substances 0.000 description 5
OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
238000001914 filtration Methods 0.000 description 5
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 5
159000000001 potassium salts Chemical class 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 4
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 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
208000002874 Acne Vulgaris Diseases 0.000 description 4
206010020112 Hirsutism Diseases 0.000 description 4
241000282412 Homo Species 0.000 description 4
239000002841 Lewis acid Substances 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
206010039793 Seborrhoeic dermatitis Diseases 0.000 description 4
206010000496 acne Diseases 0.000 description 4
125000000217 alkyl group Chemical group 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
206010068168 androgenetic alopecia Diseases 0.000 description 4
150000001735 carboxylic acids Chemical class 0.000 description 4
230000032050 esterification Effects 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
150000007517 lewis acids Chemical class 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000007800 oxidant agent Substances 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
239000002245 particle Substances 0.000 description 4
150000002989 phenols Chemical class 0.000 description 4
239000000843 powder Substances 0.000 description 4
208000008742 seborrheic dermatitis Diseases 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
238000012360 testing method Methods 0.000 description 4
244000166102 Eucalyptus leucoxylon Species 0.000 description 3
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
KZENBFUSKMWCJF-UHFFFAOYSA-N [5-[5-[5-(hydroxymethyl)-2-thiophenyl]-2-furanyl]-2-thiophenyl]methanol Chemical compound S1C(CO)=CC=C1C1=CC=C(C=2SC(CO)=CC=2)O1 KZENBFUSKMWCJF-UHFFFAOYSA-N 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
229910052783 alkali metal Inorganic materials 0.000 description 3
150000001347 alkyl bromides Chemical class 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 3
231100000673 dose–response relationship Toxicity 0.000 description 3
239000003814 drug Substances 0.000 description 3
XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 3
229940088597 hormone Drugs 0.000 description 3
239000005556 hormone Substances 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
238000011065 in-situ storage Methods 0.000 description 3
238000011534 incubation Methods 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
150000007529 inorganic bases Chemical class 0.000 description 3
229910052500 inorganic mineral Inorganic materials 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
235000010755 mineral Nutrition 0.000 description 3
239000011707 mineral Substances 0.000 description 3
210000000056 organ Anatomy 0.000 description 3
230000035479 physiological effects, processes and functions Effects 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
238000011160 research Methods 0.000 description 3
230000003637 steroidlike Effects 0.000 description 3
239000000126 substance Substances 0.000 description 3
229940095585 testosterone-5-alpha reductase inhibitors for benign prostatic hypertrophy Drugs 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
VLVILBSSXMZZCB-SNVBAGLBSA-N (1r)-1-[4-(2-methylpropyl)phenyl]ethanol Chemical compound CC(C)CC1=CC=C([C@@H](C)O)C=C1 VLVILBSSXMZZCB-SNVBAGLBSA-N 0.000 description 2
RKOJQNXAYJLAQM-UHFFFAOYSA-N 1h-indol-3-yl-(4-phenylmethoxyphenyl)methanone Chemical compound C=1NC2=CC=CC=C2C=1C(=O)C(C=C1)=CC=C1OCC1=CC=CC=C1 RKOJQNXAYJLAQM-UHFFFAOYSA-N 0.000 description 2
SIHXYIBHFFOXMF-UHFFFAOYSA-N 2,3-dimethyl-4-phenylmethoxybenzoyl chloride Chemical compound CC1=C(C)C(C(Cl)=O)=CC=C1OCC1=CC=CC=C1 SIHXYIBHFFOXMF-UHFFFAOYSA-N 0.000 description 2
QWBBPBRQALCEIZ-UHFFFAOYSA-N 2,3-dimethylphenol Chemical compound CC1=CC=CC(O)=C1C QWBBPBRQALCEIZ-UHFFFAOYSA-N 0.000 description 2
OHSBJNMOJFJZGI-AWEZNQCLSA-N 4-[(1s)-1-[4-(2-methylpropyl)phenyl]ethoxy]benzoyl chloride Chemical compound C1=CC(CC(C)C)=CC=C1[C@H](C)OC1=CC=C(C(Cl)=O)C=C1 OHSBJNMOJFJZGI-AWEZNQCLSA-N 0.000 description 2
ICEKEZSKMGHZNT-UHFFFAOYSA-N 4-phenylmethoxybenzoyl chloride Chemical compound C1=CC(C(=O)Cl)=CC=C1OCC1=CC=CC=C1 ICEKEZSKMGHZNT-UHFFFAOYSA-N 0.000 description 2
MAUCRURSQMOFGV-UHFFFAOYSA-N 4-propylbenzaldehyde Chemical compound CCCC1=CC=C(C=O)C=C1 MAUCRURSQMOFGV-UHFFFAOYSA-N 0.000 description 2
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
239000005977 Ethylene Substances 0.000 description 2
241000400611 Eucalyptus deanei Species 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-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
238000005903 acid hydrolysis reaction Methods 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
231100000360 alopecia Toxicity 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
229960003473 androstanolone Drugs 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000012267 brine Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
238000004296 chiral HPLC Methods 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
239000006185 dispersion Substances 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
239000003480 eluent Substances 0.000 description 2
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 2
239000006260 foam Substances 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
208000024963 hair loss Diseases 0.000 description 2
230000003676 hair loss Effects 0.000 description 2
125000001188 haloalkyl group Chemical group 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
150000002460 imidazoles Chemical class 0.000 description 2
VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 2
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
238000001819 mass spectrum Methods 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000002674 ointment Substances 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000008188 pellet Substances 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000012071 phase Substances 0.000 description 2
239000008363 phosphate buffer Substances 0.000 description 2
230000002265 prevention Effects 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
239000012679 serum free medium Substances 0.000 description 2
239000002002 slurry Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
239000001488 sodium phosphate Substances 0.000 description 2
229910000162 sodium phosphate Inorganic materials 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
210000001550 testis Anatomy 0.000 description 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
238000001665 trituration Methods 0.000 description 2
OELWYQGRQUQQPD-IOMDMTNGSA-N (+)-(3R)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol Chemical compound C([C@@H](O)CCC=1C=C(O)C(O)=CC=1)C\C=C\C1=CC=CC=C1 OELWYQGRQUQQPD-IOMDMTNGSA-N 0.000 description 1
VLVILBSSXMZZCB-JTQLQIEISA-N (1s)-1-[4-(2-methylpropyl)phenyl]ethanol Chemical compound CC(C)CC1=CC=C([C@H](C)O)C=C1 VLVILBSSXMZZCB-JTQLQIEISA-N 0.000 description 1
KWGRBVOPPLSCSI-PSASIEDQSA-N (1s,2r)-2-(methylamino)-1-phenylpropan-1-ol Chemical compound CN[C@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-PSASIEDQSA-N 0.000 description 1
TZZUWLNIZBCCGL-UHFFFAOYSA-N (4-propylphenyl)methanol Chemical compound CCCC1=CC=C(CO)C=C1 TZZUWLNIZBCCGL-UHFFFAOYSA-N 0.000 description 1
YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
WHSROYYJBJDRBV-UHFFFAOYSA-N 1-(1-bromoethyl)-4-(2-methylpropyl)benzene Chemical compound CC(C)CC1=CC=C(C(C)Br)C=C1 WHSROYYJBJDRBV-UHFFFAOYSA-N 0.000 description 1
VZTGSONNNMGQNQ-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)ethanol Chemical compound CC(O)C1=CC=C(Cl)C(Cl)=C1 VZTGSONNNMGQNQ-UHFFFAOYSA-N 0.000 description 1
WBPAOUHWPONFEQ-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C(Cl)=C1 WBPAOUHWPONFEQ-UHFFFAOYSA-N 0.000 description 1
OKDVJTURSCLUBA-UHFFFAOYSA-N 1-(4-acetylphenyl)-2-methylpropan-1-one Chemical compound CC(C)C(=O)C1=CC=C(C(C)=O)C=C1 OKDVJTURSCLUBA-UHFFFAOYSA-N 0.000 description 1
HZFBZEOPUXCNHK-UHFFFAOYSA-N 1-(4-ethylphenyl)ethanol Chemical compound CCC1=CC=C(C(C)O)C=C1 HZFBZEOPUXCNHK-UHFFFAOYSA-N 0.000 description 1
GULNUIVHBYSTNR-UHFFFAOYSA-N 1-(4-propylphenyl)butan-1-ol Chemical compound CCCC(O)C1=CC=C(CCC)C=C1 GULNUIVHBYSTNR-UHFFFAOYSA-N 0.000 description 1
UOAIQCAHLUIZHW-UHFFFAOYSA-N 1-(bromomethyl)-4-(2-methylpropyl)benzene Chemical compound CC(C)CC1=CC=C(CBr)C=C1 UOAIQCAHLUIZHW-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
KUKQHKRFGDNZJY-UHFFFAOYSA-N 1-bromo-2,3-dimethyl-4-phenylmethoxybenzene Chemical compound C1=C(Br)C(C)=C(C)C(OCC=2C=CC=CC=2)=C1 KUKQHKRFGDNZJY-UHFFFAOYSA-N 0.000 description 1
NUPWGLKBGVNSJX-UHFFFAOYSA-N 1-bromo-4-propylbenzene Chemical compound CCCC1=CC=C(Br)C=C1 NUPWGLKBGVNSJX-UHFFFAOYSA-N 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
RMRXHCMHTCMERT-UHFFFAOYSA-N 2,3-dimethyl-4-phenylmethoxybenzoic acid Chemical compound CC1=C(C)C(C(O)=O)=CC=C1OCC1=CC=CC=C1 RMRXHCMHTCMERT-UHFFFAOYSA-N 0.000 description 1
GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 1
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
CTQBGYOLHHOVPE-AWEZNQCLSA-N 4-[(1s)-1-[4-(2-methylpropyl)phenyl]ethoxy]benzoic acid Chemical compound C1=CC(CC(C)C)=CC=C1[C@H](C)OC1=CC=C(C(O)=O)C=C1 CTQBGYOLHHOVPE-AWEZNQCLSA-N 0.000 description 1
CTQBGYOLHHOVPE-UHFFFAOYSA-N 4-[1-[4-(2-methylpropyl)phenyl]ethoxy]benzoic acid Chemical compound C1=CC(CC(C)C)=CC=C1C(C)OC1=CC=C(C(O)=O)C=C1 CTQBGYOLHHOVPE-UHFFFAOYSA-N 0.000 description 1
OHSBJNMOJFJZGI-UHFFFAOYSA-N 4-[1-[4-(2-methylpropyl)phenyl]ethoxy]benzoyl chloride Chemical compound C1=CC(CC(C)C)=CC=C1C(C)OC1=CC=C(C(Cl)=O)C=C1 OHSBJNMOJFJZGI-UHFFFAOYSA-N 0.000 description 1
CSGLAKQYXAWANW-UHFFFAOYSA-N 4-[1-[tert-butyl(dimethyl)silyl]oxyethyl]benzoyl chloride Chemical compound CC(C)(C)[Si](C)(C)OC(C)C1=CC=C(C(Cl)=O)C=C1 CSGLAKQYXAWANW-UHFFFAOYSA-N 0.000 description 1
MOKFDXJOXUHQNO-UHFFFAOYSA-N 4-bromo-2,3-dimethylphenol Chemical compound CC1=C(C)C(Br)=CC=C1O MOKFDXJOXUHQNO-UHFFFAOYSA-N 0.000 description 1
AQSCHALQLXXKKC-UHFFFAOYSA-N 4-phenylmethoxybenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OCC1=CC=CC=C1 AQSCHALQLXXKKC-UHFFFAOYSA-N 0.000 description 1
102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
229940122815 Aromatase inhibitor Drugs 0.000 description 1
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
IQKUFJQLTVJRCV-UHFFFAOYSA-N C12=CC=CC=C2N(CCCC(=O)OCC)C=C1C(=O)C1=CC=C(C(C)O)C=C1 Chemical compound C12=CC=CC=C2N(CCCC(=O)OCC)C=C1C(=O)C1=CC=C(C(C)O)C=C1 IQKUFJQLTVJRCV-UHFFFAOYSA-N 0.000 description 1
HWKWFRHWDBQDHJ-UHFFFAOYSA-N C12=CC=CC=C2N(CCCC(=O)OCC)C=C1C(=O)C1=CC=C(C(C)O[Si](C)(C)C(C)(C)C)C=C1 Chemical compound C12=CC=CC=C2N(CCCC(=O)OCC)C=C1C(=O)C1=CC=C(C(C)O[Si](C)(C)C(C)(C)C)C=C1 HWKWFRHWDBQDHJ-UHFFFAOYSA-N 0.000 description 1
JYNXFEOISCRASD-IBGZPJMESA-N C1=CC(CC(C)C)=CC=C1[C@H](C)OC1=CC=C(C(=O)C=2C3=CC=CC=C3NC=2)C=C1 Chemical compound C1=CC(CC(C)C)=CC=C1[C@H](C)OC1=CC=C(C(=O)C=2C3=CC=CC=C3NC=2)C=C1 JYNXFEOISCRASD-IBGZPJMESA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
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 1
239000004367 Lipase Substances 0.000 description 1
108090001060 Lipase Proteins 0.000 description 1
102000004882 Lipase Human genes 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
238000007126 N-alkylation reaction Methods 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
229930040373 Paraformaldehyde Natural products 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical class OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical class [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
238000006859 Swern oxidation reaction Methods 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
OQMJVIPISXBCIE-UHFFFAOYSA-N [4-[1-[tert-butyl(dimethyl)silyl]oxyethyl]phenyl]-(1h-indol-3-yl)methanone Chemical compound C1=CC(C(O[Si](C)(C)C(C)(C)C)C)=CC=C1C(=O)C1=CNC2=CC=CC=C12 OQMJVIPISXBCIE-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000005041 acyloxyalkyl group Chemical group 0.000 description 1
125000005236 alkanoylamino group Chemical group 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
230000001548 androgenic effect Effects 0.000 description 1
229940030486 androgens Drugs 0.000 description 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000002280 anti-androgenic effect Effects 0.000 description 1
239000000051 antiandrogen Substances 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
239000003886 aromatase inhibitor Substances 0.000 description 1
125000003710 aryl alkyl group Chemical group 0.000 description 1
PEPMWUSGRKINHX-TXTPUJOMSA-N atamestane Chemical compound C1C[C@@H]2[C@@]3(C)C(C)=CC(=O)C=C3CC[C@H]2[C@@H]2CCC(=O)[C@]21C PEPMWUSGRKINHX-TXTPUJOMSA-N 0.000 description 1
229950004810 atamestane Drugs 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
229940117975 chromium trioxide Drugs 0.000 description 1
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
VTHIKKVKIVQWHV-UHFFFAOYSA-N chromium(6+) oxygen(2-) pyridine Chemical compound [O-2].[O-2].[O-2].[Cr+6].C1=CC=NC=C1 VTHIKKVKIVQWHV-UHFFFAOYSA-N 0.000 description 1
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical group [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000006184 cosolvent Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 1
230000006806 disease prevention Effects 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000004495 emulsifiable concentrate Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
230000007071 enzymatic hydrolysis Effects 0.000 description 1
238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
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 1
PEOXIBQVNCENPT-UHFFFAOYSA-N ethyl 4-[3-(4-phenylmethoxybenzoyl)indol-1-yl]butanoate Chemical compound C12=CC=CC=C2N(CCCC(=O)OCC)C=C1C(=O)C(C=C1)=CC=C1OCC1=CC=CC=C1 PEOXIBQVNCENPT-UHFFFAOYSA-N 0.000 description 1
BBWMASBANDIFMV-UHFFFAOYSA-N ethyl 4-phenylpiperidine-4-carboxylate;hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C1(C(=O)OCC)CC[NH2+]CC1 BBWMASBANDIFMV-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
229940043351 ethyl-p-hydroxybenzoate Drugs 0.000 description 1
NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
159000000011 group IA salts Chemical class 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical class OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
235000013847 iso-butane Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000010410 layer Substances 0.000 description 1
235000019421 lipase Nutrition 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000006210 lotion Substances 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
238000010907 mechanical stirring Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
ZKUUVVYMPUDTGJ-UHFFFAOYSA-N methyl 5-hydroxy-4-methoxy-2-nitrobenzoate Chemical compound COC(=O)C1=CC(O)=C(OC)C=C1[N+]([O-])=O ZKUUVVYMPUDTGJ-UHFFFAOYSA-N 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
239000004570 mortar (masonry) Substances 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
239000004533 oil dispersion Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
238000007248 oxidative elimination reaction Methods 0.000 description 1
238000005949 ozonolysis reaction Methods 0.000 description 1
NODGRWCMFMEGJH-UHFFFAOYSA-N p-ethylacetophenone Chemical compound CCC1=CC=C(C(C)=O)C=C1 NODGRWCMFMEGJH-UHFFFAOYSA-N 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
229920002866 paraformaldehyde Polymers 0.000 description 1
150000002960 penicillins Chemical class 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000004344 phenylpropyl group Chemical group 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical class [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Chemical class 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
229960001289 prazosin Drugs 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
150000003254 radicals Chemical group 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
238000012552 review Methods 0.000 description 1
238000009738 saturating Methods 0.000 description 1
210000001732 sebaceous gland Anatomy 0.000 description 1
238000000926 separation method Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
229940001584 sodium metabisulfite Drugs 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
239000012064 sodium phosphate buffer Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 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
239000010959 steel Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
AVBGNFCMKJOFIN-UHFFFAOYSA-N triethylammonium acetate Chemical compound CC(O)=O.CCN(CC)CC AVBGNFCMKJOFIN-UHFFFAOYSA-N 0.000 description 1
NNPPMTNAJDCUHE-UHFFFAOYSA-N trimethylmethane Natural products CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 1
239000000052 vinegar Chemical class 0.000 description 1
235000021419 vinegar Nutrition 0.000 description 1
229940045860 white wax Drugs 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- 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)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Urology & Nephrology (AREA)
Dermatology (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Saccharide Compounds (AREA)

CN92108675A 1991-07-24 1992-07-24 吲哚类衍生物 Pending CN1068816A (zh)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US9115951.7		1991-07-24
GB919115951A GB9115951D0 (en)	1991-07-24	1991-07-24	Indoles

Publications (1)

Publication Number	Publication Date
CN1068816A true CN1068816A (zh)	1993-02-10

Family

ID=10698873

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CN92108675A Pending CN1068816A (zh)	1991-07-24	1992-07-24	吲哚类衍生物
CN92108665A Pending CN1068817A (zh)	1991-07-24	1992-07-24	吲哚类衍生物

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CN92108665A Pending CN1068817A (zh)	1991-07-24	1992-07-24	吲哚类衍生物

Country Status (20)

Country	Link
EP (2)	EP0598750A1 (no)
JP (2)	JPH06511483A (no)
CN (2)	CN1068816A (no)
AU (2)	AU2327192A (no)
BR (1)	BR9206306A (no)
CA (2)	CA2112689A1 (no)
CZ (1)	CZ13694A3 (no)
FI (2)	FI940310A (no)
GB (1)	GB9115951D0 (no)
HU (1)	HU9400199D0 (no)
IE (2)	IE922387A1 (no)
IL (2)	IL102544A0 (no)
MX (1)	MX9204342A (no)
NO (1)	NO940237L (no)
NZ (1)	NZ243687A (no)
PT (2)	PT100718A (no)
SK (1)	SK8494A3 (no)
TW (1)	TW223060B (no)
WO (2)	WO1993002050A1 (no)
ZA (2)	ZA925546B (no)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9204024D0 (en) *	1992-02-25	1992-04-08	Fujisawa Pharmaceutical Co	Indole derivatives
GB9302577D0 (en) *	1993-02-10	1993-03-24	Fujisawa Pharmaceutical Co	Indole derivatives
US5530019A (en) *	1993-04-05	1996-06-25	Fujisawa Pharmaceutical Co., Ltd.	Indole derivatives useful as testosterone 5α-reductase inhibitors
GB9310092D0 (en) *	1993-05-17	1993-06-30	Fujisawa Pharmaceutical Co	Indole derivatives
GB9317096D0 (en) *	1993-08-17	1993-09-29	Pfizer Ltd	Indoles
KR100349634B1 (ko) *	1994-03-30	2003-01-08	제리아 신야쿠 고교 가부시키 가이샤	인돌유도체및이를함유하는제제
GB9409583D0 (en) *	1994-05-13	1994-07-06	Pfizer Ltd	Indoles
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
PL207885B1 (pl)	1997-05-14	2011-02-28	Atherogenics Inc	Pochodna probukolu i kompozycja zawierająca pochodną probukolu
US6670398B2 (en)	1997-05-14	2003-12-30	Atherogenics, Inc.	Compounds and methods for treating transplant rejection
US7417063B2 (en)	2004-04-13	2008-08-26	Bristol-Myers Squibb Company	Bicyclic heterocycles useful as serine protease inhibitors
FR2893615B1 (fr) *	2005-11-18	2008-03-07	Sanofi Aventis Sa	Derives de 3-acylindole, leur preparation et leur application en therapeutique
PE20090159A1 (es)	2007-03-08	2009-02-21	Plexxikon Inc	COMPUESTOS DERIVADOS DE ACIDO INDOL-PROPIONICO COMO MODULADORES PPARs
EP2139320A4 (en)	2007-03-26	2010-09-08	Salutria Pharmaceuticals Llc	METHODS AND COMPOSITIONS OF PROBUCOL DERIVATIVES FOR THE TREATMENT OF DIABETES
US10703969B2 (en) *	2016-09-27	2020-07-07	Kaohsiung Medical University	Detection method for quaternary ammonium compound having γ-carboxyl group

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9011335D0 (en) *	1990-05-21	1990-07-11	Fujisawa Pharmaceutical Co	Indolebutyric acid derivatives and process for preparation thereof
WO1993005020A1 (en) *	1991-09-06	1993-03-18	Merck & Co., Inc.	Indoles as inhibitors of hiv reverse transcriptase

1991
- 1991-07-24 GB GB919115951A patent/GB9115951D0/en active Pending
1992
- 1992-06-30 TW TW081105178A patent/TW223060B/zh active
- 1992-07-17 IL IL102544A patent/IL102544A0/xx unknown
- 1992-07-17 IL IL102545A patent/IL102545A0/xx unknown
- 1992-07-20 AU AU23271/92A patent/AU2327192A/en not_active Abandoned
- 1992-07-20 JP JP5502592A patent/JPH06511483A/ja active Pending
- 1992-07-20 CA CA002112689A patent/CA2112689A1/en not_active Abandoned
- 1992-07-20 BR BR9206306A patent/BR9206306A/pt not_active Application Discontinuation
- 1992-07-20 HU HU9400199A patent/HU9400199D0/hu unknown
- 1992-07-20 SK SK84-94A patent/SK8494A3/sk unknown
- 1992-07-20 AU AU23270/92A patent/AU655662B2/en not_active Expired - Fee Related
- 1992-07-20 JP JP5502591A patent/JPH06509336A/ja active Pending
- 1992-07-20 CZ CS94136A patent/CZ13694A3/cs unknown
- 1992-07-20 CA CA002112678A patent/CA2112678A1/en not_active Abandoned
- 1992-07-20 EP EP92915417A patent/EP0598750A1/en not_active Withdrawn
- 1992-07-20 WO PCT/EP1992/001625 patent/WO1993002050A1/en not_active Application Discontinuation
- 1992-07-20 EP EP92915891A patent/EP0598754A1/en not_active Withdrawn
- 1992-07-20 WO PCT/EP1992/001626 patent/WO1993002051A1/en not_active Application Discontinuation
- 1992-07-22 PT PT100718A patent/PT100718A/pt not_active Application Discontinuation
- 1992-07-22 PT PT100717A patent/PT100717A/pt not_active Application Discontinuation
- 1992-07-23 IE IE238792A patent/IE922387A1/en not_active Application Discontinuation
- 1992-07-23 ZA ZA925546A patent/ZA925546B/xx unknown
- 1992-07-23 IE IE238692A patent/IE922386A1/en not_active Application Discontinuation
- 1992-07-23 MX MX9204342A patent/MX9204342A/es unknown
- 1992-07-23 ZA ZA925547A patent/ZA925547B/xx unknown
- 1992-07-23 NZ NZ243687A patent/NZ243687A/en unknown
- 1992-07-24 CN CN92108675A patent/CN1068816A/zh active Pending
- 1992-07-24 CN CN92108665A patent/CN1068817A/zh active Pending
1994
- 1994-01-21 FI FI940310A patent/FI940310A/fi not_active Application Discontinuation
- 1994-01-21 FI FI940311A patent/FI940311A0/fi not_active Application Discontinuation
- 1994-01-24 NO NO940237A patent/NO940237L/no unknown

Also Published As

Publication number	Publication date
FI940310A0 (fi)	1994-01-21
CZ13694A3 (en)	1994-07-13
JPH06509336A (ja)	1994-10-20
PT100718A (pt)	1993-08-31
AU655662B2 (en)	1995-01-05
FI940311A (fi)	1994-01-21
FI940311A0 (fi)	1994-01-21
CA2112689A1 (en)	1993-02-04
ZA925546B (en)	1994-01-24
CN1068817A (zh)	1993-02-10
NO940237D0 (no)	1994-01-24
IL102545A0 (en)	1993-01-14
FI940310A (fi)	1994-01-21
WO1993002051A1 (en)	1993-02-04
EP0598750A1 (en)	1994-06-01
EP0598754A1 (en)	1994-06-01
CA2112678A1 (en)	1993-02-04
MX9204342A (es)	1994-03-31
IE922386A1 (en)	1993-01-27
NZ243687A (en)	1994-12-22
NO940237L (no)	1994-01-24
IE922387A1 (en)	1993-01-27
WO1993002050A1 (en)	1993-02-04
AU2327192A (en)	1993-02-23
BR9206306A (pt)	1994-11-08
PT100717A (pt)	1993-08-31
SK8494A3 (en)	1994-11-09
AU2327092A (en)	1993-02-23
HU9400199D0 (en)	1994-05-30
ZA925547B (en)	1994-01-24
JPH06511483A (ja)	1994-12-22
TW223060B (no)	1994-05-01
GB9115951D0 (en)	1991-09-11
IL102544A0 (en)	1993-01-14

Publication	Publication Date	Title
CN1124262C (zh)	2003-10-15	用作内皮缩血管肽受体拮抗剂的吲哚衍生物
CN1193018C (zh)	2005-03-16	杂环衍生物及其医药用途
CN1060841A (zh)	1992-05-06	喹唑啉衍生物及其制备方法
CN1068816A (zh)	1993-02-10	吲哚类衍生物
CN1054771A (zh)	1991-09-25	17β-取代的-4-氮杂-5α-雄甾烷-3-酮衍生物的制备方法
CN1174196A (zh)	1998-02-25	稠杂环吡啶
CN86105309A (zh)	1987-01-14	作为消炎和镇痛药的1-取代的羟吲哚-3-碳酰胺类化合物
CN1072219C (zh)	2001-10-03	二氮杂䓬酮、其生产和用途
CN1046937C (zh)	1999-12-01	木酚素系化合物的制备方法
CN1040986A (zh)	1990-04-04	环烷基取代的戊二酰胺衍生物的制备
CN1039228C (zh)	1998-07-22	叔胺化合物、其盐，及含该类化合物或其盐的药物组合物
CN1085224A (zh)	1994-04-13	氟化17β-取代的4-氮杂-5α-雄甾烷-3-酮衍生物
CN1112786A (zh)	1995-11-29	2-氨基-4-苯基-4-氧代丁酸衍生物
CN1079465A (zh)	1993-12-15	吲哚类
CN1138583A (zh)	1996-12-25	9-取代的2-(2-正烷氧基苯基)-嘌呤-6-酮类化合物
CN1068821A (zh)	1993-02-10	苯并二氢吡喃衍生物
CN1053063A (zh)	1991-07-17	喹唑啉衍生物及其制备方法
CN1423637A (zh)	2003-06-11	新的取代的三环化合物
CN88102538A (zh)	1988-12-07	新的双环化合物、其制备方法以及含这类化合物的药物组合物
CN1323300A (zh)	2001-11-21	制备新的抗糖尿病剂的改进方法
CN1177350A (zh)	1998-03-25	咪唑衍生物及其药学组合物
CN1186344C (zh)	2005-01-26	氨基酸化合物及其作为nep、ace和ece抑制剂的用途
CN1099752A (zh)	1995-03-08	新型酰氨烷基-和亚氨烷基-哌嗪
CN1599717A (zh)	2005-03-23	具有稠环基团的环二胺化合物
CN1199960C (zh)	2005-05-04	新的沉香呋喃衍生物,它们的制备方法,含它们的药物组合物及它们作为药物的用途

Legal Events

Date	Code	Title
1992-12-02	C10	Entry into substantive examination
1992-12-02	SE01	Entry into force of request for substantive examination
1993-02-10	C06	Publication
1993-02-10	PB01	Publication
1996-09-18	C01	Deemed withdrawal of patent application (patent law 1993)
1996-09-18	WD01	Invention patent application deemed withdrawn after publication