NO327105B1 - Benzimidazolderivater, farmasoytiske preparater inneholdende slike og deres anvendelse for fremstilling av medikamenter for behandling av tilstander - Google Patents
Benzimidazolderivater, farmasoytiske preparater inneholdende slike og deres anvendelse for fremstilling av medikamenter for behandling av tilstander Download PDFInfo
- Publication number
- NO327105B1 NO327105B1 NO20043095A NO20043095A NO327105B1 NO 327105 B1 NO327105 B1 NO 327105B1 NO 20043095 A NO20043095 A NO 20043095A NO 20043095 A NO20043095 A NO 20043095A NO 327105 B1 NO327105 B1 NO 327105B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- formula
- residue
- amino
- optionally substituted
- Prior art date
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- 239000003814 drug Substances 0.000 title claims description 14
- 229940079593 drug Drugs 0.000 title claims description 11
- 238000004519 manufacturing process Methods 0.000 title description 4
- 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title 1
- 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- -1 benzimidazol-2-on-1-yl Chemical group 0.000 claims abstract description 83
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 71
- 125000003118 aryl group Chemical group 0.000 claims abstract description 54
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 51
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 48
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 17
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims abstract description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 10
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 10
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
- 125000005129 aryl carbonyl group Chemical group 0.000 claims abstract description 7
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 113
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 105
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 56
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 150000002367 halogens Chemical class 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 33
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 24
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 24
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 22
- 150000003254 radicals Chemical class 0.000 claims description 21
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 18
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 16
- 125000001624 naphthyl group Chemical group 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
- 229930192474 thiophene Natural products 0.000 claims description 12
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 8
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 8
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 8
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical group C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 6
- 230000001456 gonadotroph Effects 0.000 claims description 6
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 6
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 150000007522 mineralic acids Chemical class 0.000 claims description 5
- 150000007524 organic acids Chemical class 0.000 claims description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 4
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 4
- 206010060862 Prostate cancer Diseases 0.000 claims description 4
- 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 150000005840 aryl radicals Chemical class 0.000 claims description 4
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 4
- 238000000586 desensitisation Methods 0.000 claims description 4
- QPMLSUSACCOBDK-UHFFFAOYSA-N diazepane Chemical compound C1CCNNCC1 QPMLSUSACCOBDK-UHFFFAOYSA-N 0.000 claims description 4
- 125000005959 diazepanyl group Chemical group 0.000 claims description 4
- 206010016629 fibroma Diseases 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 201000009273 Endometriosis Diseases 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 230000001817 pituitary effect Effects 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 2
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 2
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 125000005418 aryl aryl group Chemical group 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 abstract description 5
- 229910052799 carbon Inorganic materials 0.000 abstract description 4
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 abstract description 3
- 125000003342 alkenyl group Chemical group 0.000 abstract description 2
- 125000000304 alkynyl group Chemical group 0.000 abstract description 2
- 150000001602 bicycloalkyls Chemical group 0.000 abstract description 2
- 125000003386 piperidinyl group Chemical group 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 9
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 abstract 4
- 125000005877 1,4-benzodioxanyl group Chemical group 0.000 abstract 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 abstract 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 abstract 1
- 125000003003 spiro group Chemical group 0.000 abstract 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 84
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 239000000203 mixture Substances 0.000 description 50
- 239000000243 solution Substances 0.000 description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
- 229920005990 polystyrene resin Polymers 0.000 description 24
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 18
- 238000000746 purification Methods 0.000 description 17
- 239000000706 filtrate Substances 0.000 description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 238000000605 extraction Methods 0.000 description 15
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 238000010908 decantation Methods 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- 239000003960 organic solvent Substances 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
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- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 10
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- 150000001412 amines Chemical class 0.000 description 9
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- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 239000006260 foam Substances 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- 101100229685 Homo sapiens GNRH1 gene Proteins 0.000 description 8
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- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 8
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- 238000001914 filtration Methods 0.000 description 7
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- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
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- 229960003260 chlorhexidine Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- ARUKYTASOALXFG-UHFFFAOYSA-N cycloheptylcycloheptane Chemical compound C1CCCCCC1C1CCCCCC1 ARUKYTASOALXFG-UHFFFAOYSA-N 0.000 description 1
- NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical compound C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- NSNHWTBQMQIDCF-UHFFFAOYSA-N dihydrate;hydrochloride Chemical compound O.O.Cl NSNHWTBQMQIDCF-UHFFFAOYSA-N 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
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- 239000000839 emulsion Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- LBAQSKZHMLAFHH-UHFFFAOYSA-N ethoxyethane;hydron;chloride Chemical compound Cl.CCOCC LBAQSKZHMLAFHH-UHFFFAOYSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
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- 239000008273 gelatin Substances 0.000 description 1
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- 235000011852 gelatine desserts Nutrition 0.000 description 1
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- 239000003292 glue Substances 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
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- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
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- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- JEGUKCSWCFPDGT-UHFFFAOYSA-M hydroxide;hydrate Chemical compound O.[OH-] JEGUKCSWCFPDGT-UHFFFAOYSA-M 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
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- 238000007912 intraperitoneal administration Methods 0.000 description 1
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- 125000002346 iodo group Chemical group I* 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
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- 238000012417 linear regression Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 1
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- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- WMHIXNUKTHJGSO-UHFFFAOYSA-N methyl 1-[3-[methyl(2-pyridin-2-ylethyl)amino]propyl]-2-sulfanylidene-3h-benzimidazole-5-carboxylate Chemical compound S=C1NC2=CC(C(=O)OC)=CC=C2N1CCCN(C)CCC1=CC=CC=N1 WMHIXNUKTHJGSO-UHFFFAOYSA-N 0.000 description 1
- KOUNRHLZLJYESQ-UHFFFAOYSA-N methyl 2-(3,5-dimethoxyanilino)-1-[3-[methyl(2-pyridin-2-ylethyl)amino]propyl]benzimidazole-5-carboxylate Chemical compound C=1C(OC)=CC(OC)=CC=1NC1=NC2=CC(C(=O)OC)=CC=C2N1CCCN(C)CCC1=CC=CC=N1 KOUNRHLZLJYESQ-UHFFFAOYSA-N 0.000 description 1
- GGDJZPUPOMRZRN-UHFFFAOYSA-N methyl 3-amino-4-[3-[methyl(2-pyridin-2-ylethyl)amino]propylamino]benzoate Chemical compound NC1=CC(C(=O)OC)=CC=C1NCCCN(C)CCC1=CC=CC=N1 GGDJZPUPOMRZRN-UHFFFAOYSA-N 0.000 description 1
- UANPNJKPTBQJPZ-UHFFFAOYSA-N methyl 4-[3-[methyl(2-pyridin-2-ylethyl)amino]propylamino]-3-nitrobenzoate Chemical compound [O-][N+](=O)C1=CC(C(=O)OC)=CC=C1NCCCN(C)CCC1=CC=CC=N1 UANPNJKPTBQJPZ-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- NSBNSZAXNUGWDJ-UHFFFAOYSA-O monopyridin-1-ium tribromide Chemical compound Br[Br-]Br.C1=CC=[NH+]C=C1 NSBNSZAXNUGWDJ-UHFFFAOYSA-O 0.000 description 1
- CJQLLBJIRHNLFE-UHFFFAOYSA-N n'-cyclohexyl-n-methylmethanediimine Chemical compound CN=C=NC1CCCCC1 CJQLLBJIRHNLFE-UHFFFAOYSA-N 0.000 description 1
- RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 150000002924 oxiranes Chemical class 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 210000004258 portal system Anatomy 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
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- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/28—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/30—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
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- Chemical & Material Sciences (AREA)
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- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0116647A FR2833948B1 (fr) | 2001-12-21 | 2001-12-21 | Nouveaux derives de benzimidazole et leur utilisation en tant que medicament |
PCT/FR2002/004477 WO2003053939A1 (fr) | 2001-12-21 | 2002-12-20 | Derives de benzimidazole et leur utilisation comme antagonistes de gnrh |
Publications (2)
Publication Number | Publication Date |
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NO20043095L NO20043095L (no) | 2004-07-19 |
NO327105B1 true NO327105B1 (no) | 2009-04-20 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20043095A NO327105B1 (no) | 2001-12-21 | 2004-07-19 | Benzimidazolderivater, farmasoytiske preparater inneholdende slike og deres anvendelse for fremstilling av medikamenter for behandling av tilstander |
Country Status (19)
Country | Link |
---|---|
US (2) | US7495110B2 (ko) |
EP (1) | EP1467974B1 (ko) |
JP (1) | JP4418679B2 (ko) |
KR (1) | KR100927500B1 (ko) |
CN (1) | CN100334077C (ko) |
AT (1) | ATE370126T1 (ko) |
AU (1) | AU2002365016B2 (ko) |
CA (1) | CA2471044C (ko) |
CZ (1) | CZ2004819A3 (ko) |
DE (1) | DE60221901T2 (ko) |
ES (1) | ES2291544T3 (ko) |
FR (1) | FR2833948B1 (ko) |
HK (1) | HK1070359A1 (ko) |
HU (1) | HU228339B1 (ko) |
NO (1) | NO327105B1 (ko) |
NZ (1) | NZ533558A (ko) |
PL (1) | PL212986B1 (ko) |
RU (1) | RU2294326C2 (ko) |
WO (1) | WO2003053939A1 (ko) |
Families Citing this family (48)
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FR2833948B1 (fr) * | 2001-12-21 | 2004-02-06 | Sod Conseils Rech Applic | Nouveaux derives de benzimidazole et leur utilisation en tant que medicament |
IL164302A0 (en) | 2002-03-29 | 2005-12-18 | Chiron Corp | Substituted benzazoles and use thereof as raf kinase inhibitors |
FR2851563B1 (fr) * | 2003-02-26 | 2005-04-22 | Sod Conseils Rech Applic | Nouveaux derives de benzimidazole et d'imidazo-pyridine et leur utilisation en tant que medicament |
DE10337993A1 (de) * | 2003-08-19 | 2005-03-17 | Bayer Healthcare Ag | Aminobenzimidazole |
FR2862971B1 (fr) * | 2003-11-28 | 2006-03-24 | Sod Conseils Rech Applic | Nouveaux derives de benzimidazole et d'imidazo-pyridine et leur utilisation en tant que medicament |
EP1697343B1 (en) * | 2003-12-18 | 2009-07-01 | Tibotec Pharmaceuticals Ltd. | Aminobenzimidazoles and benzimidazoles as inhibitors of respiratory syncytial virus replication |
WO2005058874A1 (en) * | 2003-12-18 | 2005-06-30 | Tibotec Pharmaceuticals Ltd. | 5- or 6-substituted benzimidazole derivatives as inhibitors of respiratory syncytial virus replication |
US7896927B2 (en) * | 2004-02-12 | 2011-03-01 | össur hf. | Systems and methods for actuating a prosthetic ankle based on a relaxed position |
US7696210B2 (en) * | 2004-06-17 | 2010-04-13 | Wyeth | Gonadotropin releasing hormone receptor antagonists |
CN101048383A (zh) * | 2004-11-23 | 2007-10-03 | 惠氏公司 | 促性腺激素释放激素受体拮抗剂 |
WO2006078907A1 (en) * | 2005-01-20 | 2006-07-27 | Amgen Inc. | 2-substituted benzimidazole derivatives as vanilloid receptor ligands and their use in treatments |
US20060211699A1 (en) * | 2005-03-07 | 2006-09-21 | Wyeth | Quinoxaline dihydrohalide dihydrates and synthetic methods therefor |
JP5066514B2 (ja) * | 2005-03-14 | 2012-11-07 | ハイ ポイント ファーマシューティカルズ,エルエルシー | ベンズアゾール誘導体、組成物及びβ−セクレターゼ阻害剤としての使用方法 |
GB0506133D0 (en) * | 2005-03-24 | 2005-05-04 | Sterix Ltd | Compound |
GB0526042D0 (en) * | 2005-12-21 | 2006-02-01 | Syngenta Participations Ag | Chemical compounds |
CA2641744C (en) | 2006-02-10 | 2012-09-25 | Transtech Pharma, Inc. | Benzazole derivatives, compositions, and methods of use as aurora kinase inhibitors |
CA2660799C (en) * | 2006-08-14 | 2013-03-19 | Council Of Scientific & Industrial Research | Pyrrolo[2,1-c][1,4]benzodiazepine hybrids and a process for the preparation thereof |
WO2008068185A1 (en) | 2006-12-07 | 2008-06-12 | F. Hoffmann-La Roche Ag | Spiro-piperidine derivatives as via receptor antagonists |
KR20090082502A (ko) | 2006-12-22 | 2009-07-30 | 에프. 호프만-라 로슈 아게 | 스피로-피페리딘 유도체 |
GB0706072D0 (en) * | 2007-03-28 | 2007-05-09 | Sterix Ltd | Compound |
WO2008153701A1 (en) * | 2007-05-24 | 2008-12-18 | Schering Corporation | Compounds for inhibiting ksp kinesin activity |
RU2010137300A (ru) | 2008-02-22 | 2012-03-27 | Ф. Хоффманн-Ля Рош Аг (Ch) | Модуляторы бета-амилоида |
GB0808282D0 (en) * | 2008-05-07 | 2008-06-11 | Medical Res Council | Compounds for use in stabilizing p53 mutants |
US20100061976A1 (en) * | 2008-07-24 | 2010-03-11 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Method for treating or preventing osteoporosis by reducing follicle stimulating hormone to cyclic physiological levels in a mammalian subject |
UY32138A (es) * | 2008-09-25 | 2010-04-30 | Boehringer Ingelheim Int | Amidas sustituidas del ácido 2-(2,6-dicloro-fenilamino)-6-fluoro-1-metil-1h-bencimidazol-5-carboxílico y sus sales farmacéuticamente aceptables |
WO2010040661A1 (en) | 2008-10-09 | 2010-04-15 | F. Hoffmann-La Roche Ag | Modulators for amyloid beta |
BRPI0921348A2 (pt) | 2008-11-10 | 2019-09-24 | Hoffmann La Roche | moduladores heterocíclicos da gama secretase |
CN101619058A (zh) * | 2009-01-08 | 2010-01-06 | 上海交通大学 | 一种苯并咪唑-4-酰胺型衍生物 |
MX2011008674A (es) * | 2009-02-18 | 2011-11-04 | Amgen Inc | Compuestos de indol/bencimidazol como inhibidores de quinasa mtor. |
UY32470A (es) * | 2009-03-05 | 2010-10-29 | Boehringer Ingelheim Int | Derivados de 2-{2-cloro-5-[(sustituido) metil]fenilamino} -1-metil]fenilamino}-1-metilbencimidazol-5-carboxamidas-n-(sustituidas) y sus sales fisiológicamente aceptables, composiciones conteniéndolos y aplicaciones |
EP2424533A4 (en) | 2009-04-27 | 2012-10-17 | High Point Pharmaceuticals Llc | SUBSTITUTED ISOQUINOLINE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND THEIR METHODS OF USE AS-SECRETASE INHIBITORS |
CA2766550C (en) * | 2009-06-23 | 2017-04-11 | The Translational Genomics Research Intstitute | Benzamide derivatives |
US8486967B2 (en) | 2010-02-17 | 2013-07-16 | Hoffmann-La Roche Inc. | Heteroaryl substituted piperidines |
CA2792339A1 (en) | 2010-03-23 | 2011-09-29 | High Point Pharmaceuticals, Llc | Substituted imidazo[1,2-b]pyridazine derivatives, pharmaceutical compositions, and methods of use as beta-secretase inhibitors |
US8759537B2 (en) | 2010-08-20 | 2014-06-24 | Boehringer Ingelheim International Gmbh | 3H-imidazo [4, 5-C] pyridine-6-carboxamides as anti-inflammatory agents |
US8586604B2 (en) | 2010-08-20 | 2013-11-19 | Boehringer Ingelheim International Gmbh | Inhibitors of the microsomal prostaglandin E2 synthase-1 |
UY33779A (es) | 2010-12-10 | 2012-07-31 | Boehringer Ingelheim Int | ?2-(fenilamino)-1H-bencimidazol-5-carboxamidas novedosas? |
US8486968B2 (en) | 2010-12-10 | 2013-07-16 | Boehringer Ingelheim International Gmbh | Compounds |
US8466186B2 (en) | 2010-12-10 | 2013-06-18 | Boehringer Ingelheim International Gmbh | Compounds |
AU2013226661B2 (en) * | 2012-02-28 | 2017-08-31 | Tiumbio Co., Ltd | Gonadotropin releasing hormone receptor antagonists, method for the preparation thereof and pharmaceutical composition comprising the same |
CN104230896A (zh) * | 2013-06-17 | 2014-12-24 | 上海汇伦生命科技有限公司 | 苯并咪唑-2-哌嗪杂环类化合物、其药物组合物及其制备方法和用途 |
CN103450093A (zh) * | 2013-09-06 | 2013-12-18 | 中国药科大学 | 2-苄氨基苯并咪唑类化合物及其用途 |
US9796701B2 (en) * | 2013-12-31 | 2017-10-24 | Xuanzhu Pharma Co., Ltd. | Kinase inhibitor and use thereof |
CN107840842A (zh) * | 2016-09-19 | 2018-03-27 | 北京天诚医药科技有限公司 | 炔代杂环化合物、其制备方法及其在医药学上的应用 |
AU2018243749A1 (en) * | 2017-03-31 | 2019-11-21 | Epizyme, Inc. | Methods of using EHMT2 inhibitors |
CN118021814A (zh) | 2017-04-21 | 2024-05-14 | Epizyme股份有限公司 | 用ehmt2抑制剂进行的组合疗法 |
US11384075B2 (en) | 2017-06-27 | 2022-07-12 | Janssen Pharmaceutica Nv | Quinolinone compounds |
CN109796349A (zh) * | 2019-03-01 | 2019-05-24 | 西南石油大学 | 一种还原芳香硝基化合物制备芳胺类化合物的方法 |
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CA2240115A1 (en) * | 1995-12-14 | 1997-06-19 | Wallace T. Ashton | Antagonists of gonadotropin releasing hormone |
US5756507A (en) * | 1995-12-14 | 1998-05-26 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
JP2000095767A (ja) * | 1998-09-28 | 2000-04-04 | Takeda Chem Ind Ltd | 性腺刺激ホルモン放出ホルモン拮抗剤 |
EP1434579B1 (en) * | 2001-10-09 | 2011-06-08 | Amgen Inc. | Imidazole derivatives as antiinflammatory agents |
YU37904A (sh) * | 2001-11-09 | 2006-08-17 | Boehringer Ingelheim Pharmaceuticals Inc. | Benzimidazoli kao korisni inhibitori proteinske kinaze |
FR2833948B1 (fr) * | 2001-12-21 | 2004-02-06 | Sod Conseils Rech Applic | Nouveaux derives de benzimidazole et leur utilisation en tant que medicament |
FR2851563B1 (fr) * | 2003-02-26 | 2005-04-22 | Sod Conseils Rech Applic | Nouveaux derives de benzimidazole et d'imidazo-pyridine et leur utilisation en tant que medicament |
-
2001
- 2001-12-21 FR FR0116647A patent/FR2833948B1/fr not_active Expired - Fee Related
-
2002
- 2002-12-20 KR KR1020047009641A patent/KR100927500B1/ko not_active IP Right Cessation
- 2002-12-20 CA CA2471044A patent/CA2471044C/fr not_active Expired - Fee Related
- 2002-12-20 CN CNB028274091A patent/CN100334077C/zh not_active Expired - Fee Related
- 2002-12-20 WO PCT/FR2002/004477 patent/WO2003053939A1/fr active IP Right Grant
- 2002-12-20 PL PL371085A patent/PL212986B1/pl unknown
- 2002-12-20 JP JP2003554655A patent/JP4418679B2/ja not_active Expired - Fee Related
- 2002-12-20 RU RU2004122102/04A patent/RU2294326C2/ru not_active IP Right Cessation
- 2002-12-20 US US10/499,384 patent/US7495110B2/en not_active Expired - Fee Related
- 2002-12-20 DE DE60221901T patent/DE60221901T2/de not_active Expired - Lifetime
- 2002-12-20 ES ES02805404T patent/ES2291544T3/es not_active Expired - Lifetime
- 2002-12-20 EP EP02805404A patent/EP1467974B1/fr not_active Expired - Lifetime
- 2002-12-20 AU AU2002365016A patent/AU2002365016B2/en not_active Ceased
- 2002-12-20 CZ CZ2004819A patent/CZ2004819A3/cs unknown
- 2002-12-20 HU HU0500183A patent/HU228339B1/hu not_active IP Right Cessation
- 2002-12-20 AT AT02805404T patent/ATE370126T1/de not_active IP Right Cessation
- 2002-12-20 NZ NZ533558A patent/NZ533558A/en not_active IP Right Cessation
-
2004
- 2004-07-19 NO NO20043095A patent/NO327105B1/no not_active IP Right Cessation
-
2005
- 2005-04-11 HK HK05103022A patent/HK1070359A1/xx not_active IP Right Cessation
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- 2008-12-23 US US12/317,470 patent/US8236965B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
FR2833948B1 (fr) | 2004-02-06 |
HUP0500183A2 (hu) | 2005-05-30 |
KR20040068295A (ko) | 2004-07-30 |
NO20043095L (no) | 2004-07-19 |
DE60221901T2 (de) | 2008-04-30 |
AU2002365016A1 (en) | 2003-07-09 |
PL212986B1 (pl) | 2012-12-31 |
EP1467974A1 (fr) | 2004-10-20 |
HU228339B1 (en) | 2013-03-28 |
ES2291544T3 (es) | 2008-03-01 |
CA2471044A1 (fr) | 2003-07-03 |
US20050049290A1 (en) | 2005-03-03 |
AU2002365016B2 (en) | 2008-11-20 |
US8236965B2 (en) | 2012-08-07 |
ATE370126T1 (de) | 2007-09-15 |
FR2833948A1 (fr) | 2003-06-27 |
DE60221901D1 (de) | 2007-09-27 |
JP4418679B2 (ja) | 2010-02-17 |
CA2471044C (fr) | 2012-02-07 |
CN100334077C (zh) | 2007-08-29 |
PL371085A1 (en) | 2005-06-13 |
RU2004122102A (ru) | 2005-06-27 |
US20090170922A1 (en) | 2009-07-02 |
CZ2004819A3 (cs) | 2005-03-16 |
US7495110B2 (en) | 2009-02-24 |
JP2005514397A (ja) | 2005-05-19 |
RU2294326C2 (ru) | 2007-02-27 |
WO2003053939A1 (fr) | 2003-07-03 |
NZ533558A (en) | 2005-12-23 |
HK1070359A1 (en) | 2005-06-17 |
KR100927500B1 (ko) | 2009-11-17 |
EP1467974B1 (fr) | 2007-08-15 |
CN1615300A (zh) | 2005-05-11 |
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