CA2112678A1 - Indoles - Google Patents
IndolesInfo
- Publication number
- CA2112678A1 CA2112678A1 CA002112678A CA2112678A CA2112678A1 CA 2112678 A1 CA2112678 A1 CA 2112678A1 CA 002112678 A CA002112678 A CA 002112678A CA 2112678 A CA2112678 A CA 2112678A CA 2112678 A1 CA2112678 A1 CA 2112678A1
- Authority
- CA
- Canada
- Prior art keywords
- formula
- alkyl
- compound
- aryl
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000002475 indoles Chemical class 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 244
- 238000000034 method Methods 0.000 claims abstract description 83
- 125000003118 aryl group Chemical group 0.000 claims abstract description 76
- 150000003839 salts Chemical class 0.000 claims abstract description 73
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 57
- -1 nitro, amino Chemical group 0.000 claims abstract description 44
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims abstract description 37
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 34
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 31
- 238000002360 preparation method Methods 0.000 claims abstract description 30
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 25
- 125000006732 (C1-C15) alkyl group Chemical group 0.000 claims abstract description 22
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 22
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 21
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 14
- 125000004419 alkynylene group Chemical group 0.000 claims abstract description 13
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims abstract description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 7
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims abstract description 6
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract 3
- 238000006243 chemical reaction Methods 0.000 claims description 58
- 125000005843 halogen group Chemical group 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 29
- 241000282414 Homo sapiens Species 0.000 claims description 25
- 239000000203 mixture Substances 0.000 claims description 25
- 230000007062 hydrolysis Effects 0.000 claims description 23
- 238000006460 hydrolysis reaction Methods 0.000 claims description 23
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- 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 17
- 150000002148 esters Chemical class 0.000 claims description 17
- 150000001412 amines Chemical class 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 12
- 150000003431 steroids Chemical class 0.000 claims description 12
- 201000004384 Alopecia Diseases 0.000 claims description 11
- 229910052708 sodium Inorganic materials 0.000 claims description 11
- 239000011734 sodium Substances 0.000 claims description 11
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical class C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 claims description 9
- 201000005825 prostate adenocarcinoma Diseases 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 230000002378 acidificating effect Effects 0.000 claims description 8
- 125000001246 bromo group Chemical group Br* 0.000 claims description 8
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 7
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 7
- 239000012024 dehydrating agents Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 230000032050 esterification Effects 0.000 claims description 7
- 238000005886 esterification reaction Methods 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 208000002874 Acne Vulgaris Diseases 0.000 claims description 6
- 206010020112 Hirsutism Diseases 0.000 claims description 6
- 206010039792 Seborrhoea Diseases 0.000 claims description 6
- 206010000496 acne Diseases 0.000 claims description 6
- 230000029936 alkylation Effects 0.000 claims description 6
- 238000005804 alkylation reaction Methods 0.000 claims description 6
- 206010068168 androgenetic alopecia Diseases 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 231100000360 alopecia Toxicity 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 5
- 238000009109 curative therapy Methods 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 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 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 3
- 238000003776 cleavage reaction Methods 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 230000007017 scission Effects 0.000 claims description 3
- DKKAQRYCCROADB-QHCPKHFHSA-N 4-[3-[2-[4-[(1s)-1-[4-(2-methylpropyl)phenyl]ethoxy]phenyl]acetyl]indol-1-yl]butanoic acid Chemical compound C1=CC(CC(C)C)=CC=C1[C@H](C)OC(C=C1)=CC=C1CC(=O)C1=CN(CCCC(O)=O)C2=CC=CC=C12 DKKAQRYCCROADB-QHCPKHFHSA-N 0.000 claims 2
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 53
- 239000002585 base Substances 0.000 description 38
- 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 36
- 239000000243 solution Substances 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- OBNCKNCVKJNDBV-UHFFFAOYSA-N ethyl butyrate Chemical compound CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 23
- 102000004316 Oxidoreductases Human genes 0.000 description 22
- 108090000854 Oxidoreductases Proteins 0.000 description 22
- 239000002253 acid Substances 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- 229960003604 testosterone Drugs 0.000 description 20
- 239000002904 solvent Substances 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 14
- 210000002307 prostate Anatomy 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 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 11
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 11
- 229960003473 androstanolone Drugs 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- 238000010626 work up procedure Methods 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 230000008020 evaporation Effects 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000020477 pH reduction Effects 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 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
- 239000003098 androgen Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000005119 centrifugation Methods 0.000 description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 5
- 159000000001 potassium salts Chemical class 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 101100279860 Caenorhabditis elegans epg-2 gene Proteins 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 239000002841 Lewis acid Substances 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 150000007517 lewis acids Chemical class 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000001117 sulphuric acid Substances 0.000 description 4
- 235000011149 sulphuric acid Nutrition 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-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
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001347 alkyl bromides Chemical class 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 230000035479 physiological effects, processes and functions Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 2
- 101150041968 CDC13 gene Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 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
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 229940030486 androgens Drugs 0.000 description 2
- 229940054051 antipsychotic indole derivative Drugs 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
- 239000012267 brine Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 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
- XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 2
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- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
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- 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
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
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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)
- Indole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB919115951A GB9115951D0 (en) | 1991-07-24 | 1991-07-24 | Indoles |
| GB9115951.7 | 1991-07-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2112678A1 true CA2112678A1 (en) | 1993-02-04 |
Family
ID=10698873
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002112678A Abandoned CA2112678A1 (en) | 1991-07-24 | 1992-07-20 | Indoles |
| CA002112689A Abandoned CA2112689A1 (en) | 1991-07-24 | 1992-07-20 | Indoles |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002112689A Abandoned CA2112689A1 (en) | 1991-07-24 | 1992-07-20 | Indoles |
Country Status (20)
Families Citing this family (15)
| 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 |
| ES2160158T3 (es) | 1994-03-30 | 2001-11-01 | Zeria Pharm Co Ltd | Derivados de 4-indol-1-il acido butirico, su preparacion y su utilizacion como inhibidores de receptores alfa1-adrenergicos y testosterona 5alfa-reductasas. |
| 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 |
| KR100953990B1 (ko) | 1997-05-14 | 2010-04-21 | 아테로제닉스, 인코포레이티드 | Ｖｃａｍ-1의 발현을 억제하기 위한 화합물 및 억제방법 |
| 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 |
| US8252840B2 (en) | 2007-03-26 | 2012-08-28 | Salutria Pharmaceuticals Llc | Methods of derivatives of probucol for the treatment of type II 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)
| 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 CA CA002112678A patent/CA2112678A1/en not_active Abandoned
- 1992-07-20 CZ CS94136A patent/CZ13694A3/cs unknown
- 1992-07-20 EP EP92915891A patent/EP0598754A1/en not_active Withdrawn
- 1992-07-20 SK SK84-94A patent/SK8494A3/sk unknown
- 1992-07-20 JP JP5502591A patent/JPH06509336A/ja active Pending
- 1992-07-20 AU AU23270/92A patent/AU655662B2/en not_active Expired - Fee Related
- 1992-07-20 WO PCT/EP1992/001625 patent/WO1993002050A1/en not_active Application Discontinuation
- 1992-07-20 CA CA002112689A patent/CA2112689A1/en not_active Abandoned
- 1992-07-20 HU HU9400199A patent/HU9400199D0/hu unknown
- 1992-07-20 BR BR9206306A patent/BR9206306A/pt not_active Application Discontinuation
- 1992-07-20 JP JP5502592A patent/JPH06511483A/ja active Pending
- 1992-07-20 EP EP92915417A patent/EP0598750A1/en not_active Withdrawn
- 1992-07-20 AU AU23271/92A patent/AU2327192A/en not_active Abandoned
- 1992-07-20 WO PCT/EP1992/001626 patent/WO1993002051A1/en not_active Application Discontinuation
- 1992-07-22 PT PT100717A patent/PT100717A/pt not_active Application Discontinuation
- 1992-07-22 PT PT100718A patent/PT100718A/pt not_active Application Discontinuation
- 1992-07-23 ZA ZA925546A patent/ZA925546B/xx unknown
- 1992-07-23 IE IE238792A patent/IE922387A1/en not_active Application Discontinuation
- 1992-07-23 IE IE238692A patent/IE922386A1/en not_active Application Discontinuation
- 1992-07-23 NZ NZ243687A patent/NZ243687A/en unknown
- 1992-07-23 ZA ZA925547A patent/ZA925547B/xx unknown
- 1992-07-23 MX MX9204342A patent/MX9204342A/es 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 FI940311A patent/FI940311A7/fi not_active Application Discontinuation
- 1994-01-21 FI FI940310A patent/FI940310A7/fi not_active Application Discontinuation
- 1994-01-24 NO NO940237A patent/NO940237L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NZ243687A (en) | 1994-12-22 |
| IL102545A0 (en) | 1993-01-14 |
| FI940310A0 (fi) | 1994-01-21 |
| CA2112689A1 (en) | 1993-02-04 |
| CN1068816A (zh) | 1993-02-10 |
| WO1993002051A1 (en) | 1993-02-04 |
| AU2327192A (en) | 1993-02-23 |
| HU9400199D0 (en) | 1994-05-30 |
| EP0598750A1 (en) | 1994-06-01 |
| FI940311A0 (fi) | 1994-01-21 |
| FI940311A7 (fi) | 1994-01-21 |
| WO1993002050A1 (en) | 1993-02-04 |
| AU655662B2 (en) | 1995-01-05 |
| AU2327092A (en) | 1993-02-23 |
| ZA925546B (en) | 1994-01-24 |
| CZ13694A3 (en) | 1994-07-13 |
| SK8494A3 (en) | 1994-11-09 |
| TW223060B (enrdf_load_stackoverflow) | 1994-05-01 |
| ZA925547B (en) | 1994-01-24 |
| PT100717A (pt) | 1993-08-31 |
| BR9206306A (pt) | 1994-11-08 |
| NO940237D0 (no) | 1994-01-24 |
| EP0598754A1 (en) | 1994-06-01 |
| PT100718A (pt) | 1993-08-31 |
| IE922387A1 (en) | 1993-01-27 |
| JPH06511483A (ja) | 1994-12-22 |
| NO940237L (no) | 1994-01-24 |
| IE922386A1 (en) | 1993-01-27 |
| IL102544A0 (en) | 1993-01-14 |
| JPH06509336A (ja) | 1994-10-20 |
| CN1068817A (zh) | 1993-02-10 |
| MX9204342A (es) | 1994-03-31 |
| FI940310A7 (fi) | 1994-01-21 |
| GB9115951D0 (en) | 1991-09-11 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |