NO321361B1 - Cyklokarbamatderivater, deres bruk som medikament, et farmasoytisk preparat, samt anvendelse av derivatene for fremstilling av medikamenter. - Google Patents

Info

Publication number

NO321361B1

NO321361B1 NO20015378A NO20015378A NO321361B1 NO 321361 B1 NO321361 B1 NO 321361B1 NO 20015378 A NO20015378 A NO 20015378A NO 20015378 A NO20015378 A NO 20015378A NO 321361 B1 NO321361 B1 NO 321361B1

Authority

NO

Norway

Prior art keywords

dihydro

benzo

oxazin

dimethyl

oxo

Prior art date

1999-05-04

Links

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• 239000003814 drug Substances 0.000 title claims description 18
• 238000004519 manufacturing process Methods 0.000 title claims description 14
• 239000000825 pharmaceutical preparation Substances 0.000 title claims description 8
• 150000001875 compounds Chemical class 0.000 claims description 195
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 69
• 125000000217 alkyl group Chemical group 0.000 claims description 59
• 229910052736 halogen Inorganic materials 0.000 claims description 51
• 150000002367 halogens Chemical class 0.000 claims description 51
• 125000001424 substituent group Chemical group 0.000 claims description 47
• 125000003545 alkoxy group Chemical group 0.000 claims description 42
• -1 6-(3-cyano-5-fluorophenyl)-4,4-dimethyl-2-oxo-4H-benzo[d] [ 1,3]oxazin-1 - carboxylic acid Chemical compound 0.000 claims description 36
• 229910052799 carbon Inorganic materials 0.000 claims description 35
• 150000003839 salts Chemical class 0.000 claims description 35
• 125000005842 heteroatom Chemical group 0.000 claims description 30
• 125000003118 aryl group Chemical group 0.000 claims description 29
• 238000011282 treatment Methods 0.000 claims description 29
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 28
• 241000124008 Mammalia Species 0.000 claims description 25
• 125000003342 alkenyl group Chemical group 0.000 claims description 24
• 125000000304 alkynyl group Chemical group 0.000 claims description 24
• 229920006395 saturated elastomer Polymers 0.000 claims description 24
• 229910052760 oxygen Inorganic materials 0.000 claims description 23
• 125000000623 heterocyclic group Chemical group 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
• 229910052739 hydrogen Inorganic materials 0.000 claims description 18
• 125000003107 substituted aryl group Chemical group 0.000 claims description 14
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
• 238000002360 preparation method Methods 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 12
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 12
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 11
• 229940088597 hormone Drugs 0.000 claims description 11
• 239000005556 hormone Substances 0.000 claims description 11
• 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 10
• KVMSWMUZFCLLFV-UHFFFAOYSA-N 3-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)-5-fluorobenzonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(F)=CC(C#N)=C1 KVMSWMUZFCLLFV-UHFFFAOYSA-N 0.000 claims description 9
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 9
• 150000001555 benzenes Chemical group 0.000 claims description 9
• 230000001419 dependent effect Effects 0.000 claims description 9
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• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
• BVPSAWJCIXNPDT-UHFFFAOYSA-N 6-(3-chlorophenyl)-4,4-bis(prop-1-ynyl)-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C#CC)(C#CC)OC(=O)NC2=CC=C1C1=CC=CC(Cl)=C1 BVPSAWJCIXNPDT-UHFFFAOYSA-N 0.000 claims description 7
• OVZBDRQFIYMAJF-UHFFFAOYSA-N 6-(3-chlorophenyl)-4-ethynyl-4-methyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C#C)OC(=O)NC2=CC=C1C1=CC=CC(Cl)=C1 OVZBDRQFIYMAJF-UHFFFAOYSA-N 0.000 claims description 7
• 125000002541 furyl group Chemical group 0.000 claims description 7
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 6
• HZDVGBZUSRBRKH-UHFFFAOYSA-N 6-(3-chlorophenyl)-4-methyl-4-prop-1-ynyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C#CC)(C)OC(=O)NC2=CC=C1C1=CC=CC(Cl)=C1 HZDVGBZUSRBRKH-UHFFFAOYSA-N 0.000 claims description 6
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
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• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
• 230000001613 neoplastic effect Effects 0.000 claims description 6
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 6
• 150000003536 tetrazoles Chemical class 0.000 claims description 6
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 6
• 229930192474 thiophene Natural products 0.000 claims description 6
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
• HVXMMYUSBANZAI-UHFFFAOYSA-N 3-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)benzonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC(C#N)=C1 HVXMMYUSBANZAI-UHFFFAOYSA-N 0.000 claims description 5
• 201000009273 Endometriosis Diseases 0.000 claims description 5
• 206010046798 Uterine leiomyoma Diseases 0.000 claims description 5
• 230000012173 estrus Effects 0.000 claims description 5
• 201000010260 leiomyoma Diseases 0.000 claims description 5
• 125000004426 substituted alkynyl group Chemical group 0.000 claims description 5
• PPDYGKBOJSGKBD-UHFFFAOYSA-N 6-(3-bromophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC(Br)=C1 PPDYGKBOJSGKBD-UHFFFAOYSA-N 0.000 claims description 4
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
• 210000000481 breast Anatomy 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 238000002657 hormone replacement therapy Methods 0.000 claims description 4
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
• IDIRENXOSJYSCR-UHFFFAOYSA-N 2-[3-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)phenyl]acetonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC(CC#N)=C1 IDIRENXOSJYSCR-UHFFFAOYSA-N 0.000 claims description 3
• JGYMUYVJOIEFFQ-UHFFFAOYSA-N 3-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)-5-methoxybenzonitrile Chemical compound COC1=CC(C#N)=CC(C=2C=C3C(C)(C)OC(=O)NC3=CC=2)=C1 JGYMUYVJOIEFFQ-UHFFFAOYSA-N 0.000 claims description 3
• PNEKYSUBNQXRHM-UHFFFAOYSA-N 4,4-dimethyl-6-(1-methylpyrrol-2-yl)-1h-3,1-benzoxazin-2-one Chemical compound CN1C=CC=C1C1=CC=C(NC(=O)OC2(C)C)C2=C1 PNEKYSUBNQXRHM-UHFFFAOYSA-N 0.000 claims description 3
• QWIQKRAABPUAGQ-UHFFFAOYSA-N 4,4-dimethyl-6-[2-(1,2,4-thiadiazol-3-yl)phenyl]-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC=C1C=1N=CSN=1 QWIQKRAABPUAGQ-UHFFFAOYSA-N 0.000 claims description 3
• RHSCGZFJZHKZNC-UHFFFAOYSA-N 4,4-dimethyl-6-[3-(2h-tetrazol-5-yl)phenyl]-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C(C=1)=CC=CC=1C1=NN=NN1 RHSCGZFJZHKZNC-UHFFFAOYSA-N 0.000 claims description 3
• SAEGXQBZONVMAM-UHFFFAOYSA-N 4-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)furan-2-carbaldehyde Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=COC(C=O)=C1 SAEGXQBZONVMAM-UHFFFAOYSA-N 0.000 claims description 3
• JXNHGWCUOXLKRL-UHFFFAOYSA-N 4-benzyl-6-(3-chlorophenyl)-4-methyl-1h-3,1-benzoxazin-2-one Chemical compound O1C(=O)NC2=CC=C(C=3C=C(Cl)C=CC=3)C=C2C1(C)CC1=CC=CC=C1 JXNHGWCUOXLKRL-UHFFFAOYSA-N 0.000 claims description 3
• WRAWKFUWOAFTDQ-UHFFFAOYSA-N 5-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)furan-2-carbonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=C(C#N)O1 WRAWKFUWOAFTDQ-UHFFFAOYSA-N 0.000 claims description 3
• LGLOOLWMNDHTKN-UHFFFAOYSA-N 6-(3-bromo-5-fluorophenyl)-4,4-dicyclopropyl-1h-3,1-benzoxazin-2-one Chemical compound FC1=CC(Br)=CC(C=2C=C3C(C4CC4)(C4CC4)OC(=O)NC3=CC=2)=C1 LGLOOLWMNDHTKN-UHFFFAOYSA-N 0.000 claims description 3
• UWIIXWIVGXAFAN-UHFFFAOYSA-N 6-(3-bromo-5-fluorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(F)=CC(Br)=C1 UWIIXWIVGXAFAN-UHFFFAOYSA-N 0.000 claims description 3
• JRDFVXBVDLMFJH-UHFFFAOYSA-N 6-(3-bromo-5-methylphenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound CC1=CC(Br)=CC(C=2C=C3C(C)(C)OC(=O)NC3=CC=2)=C1 JRDFVXBVDLMFJH-UHFFFAOYSA-N 0.000 claims description 3
• PRCXSDHAGJJCKC-UHFFFAOYSA-N 6-(3-chloro-4-fluorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=C(F)C(Cl)=C1 PRCXSDHAGJJCKC-UHFFFAOYSA-N 0.000 claims description 3
• VMPIROWONHUKCP-UHFFFAOYSA-N 6-(3-chlorophenyl)-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC(Cl)=C1 VMPIROWONHUKCP-UHFFFAOYSA-N 0.000 claims description 3
• UNTRVRJHIUBUIT-UHFFFAOYSA-N 6-(3-chlorophenyl)-4-methyl-1,4-dihydro-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)OC(=O)NC2=CC=C1C1=CC=CC(Cl)=C1 UNTRVRJHIUBUIT-UHFFFAOYSA-N 0.000 claims description 3
• QBIGFWOGRAVJFF-UHFFFAOYSA-N 6-[3-bromo-5-(trifluoromethoxy)phenyl]-4,4-dimethyl-1h-3,1-benzoxazin-2-one Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC(Br)=CC(OC(F)(F)F)=C1 QBIGFWOGRAVJFF-UHFFFAOYSA-N 0.000 claims description 3
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 3
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
• 201000009030 Carcinoma Diseases 0.000 claims description 3
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 3
• 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 3
• 208000009956 adenocarcinoma Diseases 0.000 claims description 3
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• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
• WBRVELFLQXWPBG-UHFFFAOYSA-N 2-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)thiophene-3-carbonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C=1SC=CC=1C#N WBRVELFLQXWPBG-UHFFFAOYSA-N 0.000 claims description 2
• AJDVWADIJRNVOJ-UHFFFAOYSA-N 2-[2-(4,4-dimethyl-2-oxo-1h-3,1-benzoxazin-6-yl)phenyl]acetonitrile Chemical compound C1=C2C(C)(C)OC(=O)NC2=CC=C1C1=CC=CC=C1CC#N AJDVWADIJRNVOJ-UHFFFAOYSA-N 0.000 claims description 2
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• PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
• SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
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• 229940046008 vitamin d Drugs 0.000 description 1
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• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1