NO311215B1 - Benzodiazepinderivater egnet til bruk som CCK- reseptorantagonister - Google Patents
Benzodiazepinderivater egnet til bruk som CCK- reseptorantagonister Download PDFInfo
- Publication number
- NO311215B1 NO311215B1 NO19943133A NO943133A NO311215B1 NO 311215 B1 NO311215 B1 NO 311215B1 NO 19943133 A NO19943133 A NO 19943133A NO 943133 A NO943133 A NO 943133A NO 311215 B1 NO311215 B1 NO 311215B1
- Authority
- NO
- Norway
- Prior art keywords
- benzodiazepine
- dihydro
- oxo
- urea
- phenyl
- Prior art date
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- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 title claims abstract description 4
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 title abstract description 8
- 229940122623 CCK receptor antagonist Drugs 0.000 title 1
- 108010089448 Cholecystokinin B Receptor Proteins 0.000 claims abstract description 20
- 102100036016 Gastrin/cholecystokinin type B receptor Human genes 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 12
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 claims abstract description 11
- 229940079593 drug Drugs 0.000 claims abstract description 10
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 211
- 150000001875 compounds Chemical class 0.000 claims description 158
- 239000004202 carbamide Substances 0.000 claims description 118
- 239000000203 mixture Substances 0.000 claims description 93
- -1 NHCHO where c is 0-2 Chemical group 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 150000001557 benzodiazepines Chemical class 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- WQULYWDOIINWGJ-UHFFFAOYSA-N 1-[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(=O)C(C)(C)C)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 WQULYWDOIINWGJ-UHFFFAOYSA-N 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical group 0.000 claims description 9
- 102100021022 Gastrin Human genes 0.000 claims description 8
- 108010052343 Gastrins Proteins 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- MAXKXPNYSHCJHW-SANMLTNESA-N 1-[(3r)-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-[3-(methylamino)phenyl]urea Chemical compound CNC1=CC=CC(NC(=O)N[C@H]2C(N(CC(=O)C(C)(C)C)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 MAXKXPNYSHCJHW-SANMLTNESA-N 0.000 claims description 5
- FSFFUAFLXQLAQX-UHFFFAOYSA-N 1-[3-(dimethylamino)phenyl]-3-[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]urea Chemical compound CN(C)C1=CC=CC(NC(=O)NC2C(N(CC(=O)C(C)(C)C)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 FSFFUAFLXQLAQX-UHFFFAOYSA-N 0.000 claims description 5
- WFNOPNJYCVFERE-UHFFFAOYSA-N 3-[[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]carbamoylamino]benzoic acid Chemical compound O=C1N(CC(=O)C(C)(C)C)C2=CC=CC=C2C(C=2C=CC=CC=2)=NC1NC(=O)NC1=CC=CC(C(O)=O)=C1 WFNOPNJYCVFERE-UHFFFAOYSA-N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 230000035790 physiological processes and functions Effects 0.000 claims description 5
- QGOXRTGPIJTFEY-UHFFFAOYSA-N 1-[1-(2-cyclopentyl-2-hydroxyethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(O)C3CCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 QGOXRTGPIJTFEY-UHFFFAOYSA-N 0.000 claims description 4
- GABUALDOFIACFO-UHFFFAOYSA-N 1-[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-pyridin-2-yl-3h-1,4-benzodiazepin-3-yl]-3-[3-[ethyl(methyl)amino]phenyl]urea Chemical compound CCN(C)C1=CC=CC(NC(=O)NC2C(N(CC(=O)C(C)(C)C)C3=CC=CC=C3C(C=3N=CC=CC=3)=N2)=O)=C1 GABUALDOFIACFO-UHFFFAOYSA-N 0.000 claims description 4
- BLLORHYVWFCDES-UHFFFAOYSA-N 1-[1-(3,3-dimethyl-2-oxobutyl)-5-(4-methylphenyl)-2-oxo-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound C1=CC(C)=CC=C1C(C1=CC=CC=C1N(CC(=O)C(C)(C)C)C1=O)=NC1NC(=O)NC1=CC=CC(C)=C1 BLLORHYVWFCDES-UHFFFAOYSA-N 0.000 claims description 4
- VOPNRSWFTFKUAX-QUWDGAPNSA-N 1-[1-[2-[(2s)-1-acetylpyrrolidin-2-yl]-2-oxoethyl]-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC(=O)N1CCC[C@H]1C(=O)CN1C(=O)C(NC(=O)NC=2C=C(C)C=CC=2)N=C(C=2C=CC=CC=2)C2=CC=CC=C21 VOPNRSWFTFKUAX-QUWDGAPNSA-N 0.000 claims description 4
- INMWFCCMIFVEPO-UHFFFAOYSA-N 1-[3-(dimethylamino)phenyl]-3-[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-pyridin-2-yl-3h-1,4-benzodiazepin-3-yl]urea Chemical compound CN(C)C1=CC=CC(NC(=O)NC2C(N(CC(=O)C(C)(C)C)C3=CC=CC=C3C(C=3N=CC=CC=3)=N2)=O)=C1 INMWFCCMIFVEPO-UHFFFAOYSA-N 0.000 claims description 4
- MUMCKBQXVLFNBF-UHFFFAOYSA-N 1-[7-chloro-5-(2-chlorophenyl)-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(=O)C(C)(C)C)C3=CC=C(Cl)C=C3C(C=3C(=CC=CC=3)Cl)=N2)=O)=C1 MUMCKBQXVLFNBF-UHFFFAOYSA-N 0.000 claims description 4
- 239000003743 cholecystokinin B receptor antagonist Substances 0.000 claims description 4
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- JZENZFTVQRCUBC-BRIWLPCBSA-N 1-(3-methylphenyl)-3-[2-oxo-1-[2-oxo-2-[(2r)-pyrrolidin-2-yl]ethyl]-5-phenyl-3h-1,4-benzodiazepin-3-yl]urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(=O)[C@@H]3NCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 JZENZFTVQRCUBC-BRIWLPCBSA-N 0.000 claims description 3
- YRDCVSLWPXSVMY-UHFFFAOYSA-N 1-[1-(2-cyclobutyl-2-oxoethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(=O)C3CCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 YRDCVSLWPXSVMY-UHFFFAOYSA-N 0.000 claims description 3
- YLGSFAOEFWUIKO-UHFFFAOYSA-N 1-[1-(2-cyclopentyl-2-oxoethyl)-2-oxo-5-pyridin-4-yl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(=O)C3CCCC3)C3=CC=CC=C3C(C=3C=CN=CC=3)=N2)=O)=C1 YLGSFAOEFWUIKO-UHFFFAOYSA-N 0.000 claims description 3
- LNHBBGWNSQZZEL-UHFFFAOYSA-N 1-[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-nitrophenyl)urea Chemical compound O=C1N(CC(=O)C(C)(C)C)C2=CC=CC=C2C(C=2C=CC=CC=2)=NC1NC(=O)NC1=CC=CC([N+]([O-])=O)=C1 LNHBBGWNSQZZEL-UHFFFAOYSA-N 0.000 claims description 3
- DARHABFSCSRGOG-UHFFFAOYSA-N 3-[[1-(3,3-dimethyl-2-oxopentyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]carbamoylamino]benzoic acid Chemical compound O=C1N(CC(=O)C(C)(C)CC)C2=CC=CC=C2C(C=2C=CC=CC=2)=NC1NC(=O)NC1=CC=CC(C(O)=O)=C1 DARHABFSCSRGOG-UHFFFAOYSA-N 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 3
- 208000007107 Stomach Ulcer Diseases 0.000 claims description 3
- 201000008629 Zollinger-Ellison syndrome Diseases 0.000 claims description 3
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- 208000000718 duodenal ulcer Diseases 0.000 claims description 3
- 201000000052 gastrinoma Diseases 0.000 claims description 3
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- XBDKUDLNLTTYKW-UHFFFAOYSA-N n-[3-[[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]carbamoylamino]phenyl]formamide Chemical compound O=C1N(CC(=O)C(C)(C)C)C2=CC=CC=C2C(C=2C=CC=CC=2)=NC1NC(=O)NC1=CC=CC(NC=O)=C1 XBDKUDLNLTTYKW-UHFFFAOYSA-N 0.000 claims description 3
- ABJHMASUFPDZRW-DEOSSOPVSA-N 1-(3-aminophenyl)-3-[(3r)-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-pyridin-2-yl-3h-1,4-benzodiazepin-3-yl]urea Chemical compound N([C@@H]1N=C(C2=CC=CC=C2N(C1=O)CC(=O)C(C)(C)C)C=1N=CC=CC=1)C(=O)NC1=CC=CC(N)=C1 ABJHMASUFPDZRW-DEOSSOPVSA-N 0.000 claims description 2
- CNBCNQRFXCKGJF-NDEPHWFRSA-N 1-[(3r)-1-(2-cyclopentyl-2-oxoethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)N[C@H]2C(N(CC(=O)C3CCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 CNBCNQRFXCKGJF-NDEPHWFRSA-N 0.000 claims description 2
- DVXKDSWTEKGMCH-RSXGOPAZSA-N 1-[(3r)-1-[(2s)-2-hydroxy-3,3-dimethylbutyl]-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)N[C@H]2C(N(C[C@@H](O)C(C)(C)C)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 DVXKDSWTEKGMCH-RSXGOPAZSA-N 0.000 claims description 2
- CNBCNQRFXCKGJF-MUUNZHRXSA-N 1-[(3s)-1-(2-cyclopentyl-2-oxoethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)N[C@@H]2C(N(CC(=O)C3CCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 CNBCNQRFXCKGJF-MUUNZHRXSA-N 0.000 claims description 2
- IOYYZMHBESBQRA-UHFFFAOYSA-N 1-[1-(2-cycloheptyl-2-oxoethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(=O)C3CCCCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 IOYYZMHBESBQRA-UHFFFAOYSA-N 0.000 claims description 2
- GSTYQWQSRHNRNN-UHFFFAOYSA-N 1-[1-(2-cyclohexyl-2-oxoethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(=O)C3CCCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 GSTYQWQSRHNRNN-UHFFFAOYSA-N 0.000 claims description 2
- IMSUILBIZGRXLR-UHFFFAOYSA-N 1-[1-(2-cyclopentyl-2-oxoethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methoxyphenyl)urea Chemical compound COC1=CC=CC(NC(=O)NC2C(N(CC(=O)C3CCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 IMSUILBIZGRXLR-UHFFFAOYSA-N 0.000 claims description 2
- TUCVLWXPVRMGPL-UHFFFAOYSA-N 1-[1-(2-cyclopentyl-2-oxoethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-nitrophenyl)urea Chemical compound [O-][N+](=O)C1=CC=CC(NC(=O)NC2C(N(CC(=O)C3CCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 TUCVLWXPVRMGPL-UHFFFAOYSA-N 0.000 claims description 2
- GNMVNUZRQLYQHI-UHFFFAOYSA-N 1-[1-(2-cyclopentyl-2-oxoethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-[3-(dimethylamino)phenyl]urea Chemical compound CN(C)C1=CC=CC(NC(=O)NC2C(N(CC(=O)C3CCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 GNMVNUZRQLYQHI-UHFFFAOYSA-N 0.000 claims description 2
- PPWNCSOHCNHQDD-UHFFFAOYSA-N 1-[1-(3-ethyl-2-oxopentyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound O=C1N(CC(=O)C(CC)CC)C2=CC=CC=C2C(C=2C=CC=CC=2)=NC1NC(=O)NC1=CC=CC(C)=C1 PPWNCSOHCNHQDD-UHFFFAOYSA-N 0.000 claims description 2
- YTOIZHIOIUMYEL-UHFFFAOYSA-N 1-[1-(3-methyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound O=C1N(CC(=O)C(C)C)C2=CC=CC=C2C(C=2C=CC=CC=2)=NC1NC(=O)NC1=CC=CC(C)=C1 YTOIZHIOIUMYEL-UHFFFAOYSA-N 0.000 claims description 2
- DZSWOHKLBJAPQM-UHFFFAOYSA-N 3-[[1-(2-cyclopentyl-2-oxoethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]carbamoylamino]benzoic acid Chemical compound OC(=O)C1=CC=CC(NC(=O)NC2C(N(CC(=O)C3CCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 DZSWOHKLBJAPQM-UHFFFAOYSA-N 0.000 claims description 2
- 208000007882 Gastritis Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 235000021229 appetite regulation Nutrition 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000000468 ketone group Chemical group 0.000 claims description 2
- YDZYKNJZCVIKPP-VWLOTQADSA-N netazepide Chemical compound CNC1=CC=CC(NC(=O)N[C@H]2C(N(CC(=O)C(C)(C)C)C3=CC=CC=C3C(C=3N=CC=CC=3)=N2)=O)=C1 YDZYKNJZCVIKPP-VWLOTQADSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
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- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- BCKBRPCMBQSENO-VWLOTQADSA-N 1-(3-aminophenyl)-3-[(3r)-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]urea Chemical compound N([C@@H]1N=C(C2=CC=CC=C2N(C1=O)CC(=O)C(C)(C)C)C=1C=CC=CC=1)C(=O)NC1=CC=CC(N)=C1 BCKBRPCMBQSENO-VWLOTQADSA-N 0.000 claims 1
- BCKBRPCMBQSENO-UHFFFAOYSA-N 1-(3-aminophenyl)-3-[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]urea Chemical compound O=C1N(CC(=O)C(C)(C)C)C2=CC=CC=C2C(C=2C=CC=CC=2)=NC1NC(=O)NC1=CC=CC(N)=C1 BCKBRPCMBQSENO-UHFFFAOYSA-N 0.000 claims 1
- AEFWSJIJISUSSZ-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[1-(2-cycloheptyl-2-oxoethyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]urea Chemical compound ClC1=CC=CC(NC(=O)NC2C(N(CC(=O)C3CCCCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 AEFWSJIJISUSSZ-UHFFFAOYSA-N 0.000 claims 1
- JZENZFTVQRCUBC-DCCUJTHKSA-N 1-(3-methylphenyl)-3-[2-oxo-1-[2-oxo-2-[(2s)-pyrrolidin-2-yl]ethyl]-5-phenyl-3h-1,4-benzodiazepin-3-yl]urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(=O)[C@H]3NCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 JZENZFTVQRCUBC-DCCUJTHKSA-N 0.000 claims 1
- AUPDOGKZFGQZFV-NDEPHWFRSA-N 1-[(3r)-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-[3-[ethyl(methyl)amino]phenyl]urea Chemical compound CCN(C)C1=CC=CC(NC(=O)N[C@H]2C(N(CC(=O)C(C)(C)C)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 AUPDOGKZFGQZFV-NDEPHWFRSA-N 0.000 claims 1
- MAXKXPNYSHCJHW-UHFFFAOYSA-N 1-[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-[3-(methylamino)phenyl]urea Chemical compound CNC1=CC=CC(NC(=O)NC2C(N(CC(=O)C(C)(C)C)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 MAXKXPNYSHCJHW-UHFFFAOYSA-N 0.000 claims 1
- YTVYYUWEMFMKIX-UHFFFAOYSA-N 1-[1-[2-(1-methylcyclopentyl)-2-oxoethyl]-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(=O)C3(C)CCCC3)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 YTVYYUWEMFMKIX-UHFFFAOYSA-N 0.000 claims 1
- KYWXZMQXYWPUPN-UHFFFAOYSA-N 1-[3-[(dimethylamino)methyl]phenyl]-3-[1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]urea Chemical compound CN(C)CC1=CC=CC(NC(=O)NC2C(N(CC(=O)C(C)(C)C)C3=CC=CC=C3C(C=3C=CC=CC=3)=N2)=O)=C1 KYWXZMQXYWPUPN-UHFFFAOYSA-N 0.000 claims 1
- HTUODNDFSPBESN-UHFFFAOYSA-N 1-[5-(2-chlorophenyl)-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-3h-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea Chemical compound CC1=CC=CC(NC(=O)NC2C(N(CC(=O)C(C)(C)C)C3=CC=CC=C3C(C=3C(=CC=CC=3)Cl)=N2)=O)=C1 HTUODNDFSPBESN-UHFFFAOYSA-N 0.000 claims 1
- IIDJGAJSTDDBOY-UHFFFAOYSA-N 1-[7-chloro-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-5-phenyl-3h-1,4-benzodiazepin-3-yl]-3-[3-(dimethylamino)phenyl]urea Chemical compound CN(C)C1=CC=CC(NC(=O)NC2C(N(CC(=O)C(C)(C)C)C3=CC=C(Cl)C=C3C(C=3C=CC=CC=3)=N2)=O)=C1 IIDJGAJSTDDBOY-UHFFFAOYSA-N 0.000 claims 1
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- 229910052740 iodine Inorganic materials 0.000 description 1
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- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 235000013847 iso-butane Nutrition 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
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- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
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- BVKGNQRDVFGNIW-UHFFFAOYSA-N methyl 2-(3-aminophenyl)acetate Chemical compound COC(=O)CC1=CC=CC(N)=C1 BVKGNQRDVFGNIW-UHFFFAOYSA-N 0.000 description 1
- WITYUUTUSPKOAB-UHFFFAOYSA-N methyl 2-methyl-2-phenylpropanoate Chemical compound COC(=O)C(C)(C)C1=CC=CC=C1 WITYUUTUSPKOAB-UHFFFAOYSA-N 0.000 description 1
- ZQITUIHFLCKDMR-UHFFFAOYSA-N methyl 3-[ethyl(methyl)amino]benzoate Chemical compound CCN(C)C1=CC=CC(C(=O)OC)=C1 ZQITUIHFLCKDMR-UHFFFAOYSA-N 0.000 description 1
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- 235000005985 organic acids Nutrition 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
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- 239000000546 pharmaceutical excipient Substances 0.000 description 1
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- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
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- 239000011736 potassium bicarbonate Substances 0.000 description 1
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- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
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- 239000002464 receptor antagonist Substances 0.000 description 1
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- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
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- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
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- 239000005720 sucrose Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
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- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YTZKOQUCBOVLHL-UHFFFAOYSA-N tert-butylbenzene Chemical compound CC(C)(C)C1=CC=CC=C1 YTZKOQUCBOVLHL-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
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- NNPPMTNAJDCUHE-UHFFFAOYSA-N trimethylmethane Natural products CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
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Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
-
- 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
- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9204221A GB2264492B (en) | 1992-02-27 | 1992-02-27 | Benzodiazepine derivatives |
| GB929212740A GB9212740D0 (en) | 1992-02-27 | 1992-06-16 | Benzodiazephine derivatives |
| PCT/GB1993/000404 WO1993016999A1 (en) | 1992-02-27 | 1993-02-26 | Benzodiazepin derivatives useful as cck-receptor antagonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO943133L NO943133L (no) | 1994-08-24 |
| NO943133D0 NO943133D0 (no) | 1994-08-24 |
| NO311215B1 true NO311215B1 (no) | 2001-10-29 |
Family
ID=26300386
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19943133A NO311215B1 (no) | 1992-02-27 | 1994-08-24 | Benzodiazepinderivater egnet til bruk som CCK- reseptorantagonister |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US5688943A (ru) |
| EP (1) | EP0628033B1 (ru) |
| JP (1) | JP2571344B2 (ru) |
| CN (1) | CN1051079C (ru) |
| AT (1) | ATE245632T1 (ru) |
| AU (1) | AU672390B2 (ru) |
| CA (1) | CA2129990C (ru) |
| DE (1) | DE69333108T2 (ru) |
| DK (1) | DK0628033T3 (ru) |
| ES (1) | ES2203616T3 (ru) |
| FI (1) | FI121234B (ru) |
| HU (1) | HU224012B1 (ru) |
| IL (1) | IL104853A (ru) |
| NO (1) | NO311215B1 (ru) |
| PT (1) | PT628033E (ru) |
| RU (1) | RU2139282C1 (ru) |
| TW (1) | TW438783B (ru) |
| WO (1) | WO1993016999A1 (ru) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0539170A1 (en) * | 1991-10-24 | 1993-04-28 | Merck Sharp & Dohme Ltd. | Benzodiazepine derivatives and their use as antagonists of cholecystokinin and/or gastrin receptors |
| GB2282595A (en) * | 1993-08-25 | 1995-04-12 | Yamanouchi Pharma Co Ltd | Benzodiazepine derivatives |
| GB2282594A (en) * | 1993-08-25 | 1995-04-12 | Yamanouchi Pharma Co Ltd | Benzodiazepine derivatives |
| US5556969A (en) * | 1994-12-07 | 1996-09-17 | Merck Sharp & Dohme Ltd. | Benzodiazepine derivatives |
| AUPO284396A0 (en) * | 1996-10-08 | 1996-10-31 | Fujisawa Pharmaceutical Co., Ltd. | Benzodiazepine derivatives |
| US6100254A (en) * | 1997-10-10 | 2000-08-08 | Board Of Regents, The University Of Texas System | Inhibitors of protein tyrosine kinases |
| EP1391203A4 (en) * | 2001-05-11 | 2005-09-14 | Astellas Pharma Inc | ANTITUMORAL AGENTS |
| WO2004101533A1 (en) * | 2003-05-12 | 2004-11-25 | Janssen Pharmaceutica, N.V. | 1, 3, 4-benzotriazepin-2-one salts and their use as cck receptor ligands |
| US8053413B2 (en) * | 2005-06-06 | 2011-11-08 | The Board Of Trustees Of The University Of Illinois | Methods for treating sleep disorders by cholecystokinin (CCK) receptor B antagonists |
| CN101669557B (zh) * | 2009-08-20 | 2012-07-25 | 杭州六易科技有限公司 | 一种清热解毒凉茶的制作方法 |
| KR101435729B1 (ko) * | 2009-09-28 | 2014-09-01 | 닛뽕소다 가부시키가이샤 | 함질소 헤테로 고리 화합물 및 그의 염, 그리고 농원예용 살균제 |
| PL3071206T3 (pl) | 2013-11-22 | 2022-01-17 | CL BioSciences LLC | Antagoniści gastryny (eg yf476, netazepid) do leczenia i zapobiegania osteoporozie |
| GB201414116D0 (en) * | 2014-08-08 | 2014-09-24 | Trio Medicines Ltd | Benzodiazepine derivatives |
| GB201513979D0 (en) | 2015-08-07 | 2015-09-23 | Trio Medicines Ltd | Synthesis of benzodiazepine derivatives |
| CN110177565A (zh) * | 2016-09-09 | 2019-08-27 | 目标实验室有限责任公司 | 胆囊收缩素2受体靶向近红外成像及其用途 |
| US10881667B2 (en) * | 2018-10-30 | 2021-01-05 | City University Of Hong Kong | Method and composition for treating epilepsy |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4820834A (en) * | 1984-06-26 | 1989-04-11 | Merck & Co., Inc. | Benzodiazepine analogs |
| CA2026856A1 (en) * | 1989-10-05 | 1991-04-06 | Mark G. Bock | 3-substituted-1,4-benzodiazepines useful as oxytocin |
| CA2032226A1 (en) * | 1989-12-18 | 1991-06-19 | Mark G. Bock | Benzodiazepine analogs |
| IL96613A0 (en) * | 1989-12-18 | 1991-09-16 | Merck & Co Inc | Pharmaceutical compositions containing benzodiazepine analogs |
| IE904560A1 (en) * | 1989-12-18 | 1991-06-19 | Merck & Co Inc | New benzodiazepine analogs |
| US4994258A (en) * | 1990-03-05 | 1991-02-19 | Merck & Co., Inc. | Gamma emitting, CCK-A antagonists for pancreatic imaging |
| US5206234A (en) * | 1990-10-22 | 1993-04-27 | Merck & Co., Inc. | Benzolactam analogs as antagonists of cck |
| US5218115A (en) * | 1991-04-10 | 1993-06-08 | Merck & Co., Inc. | Cholecystokinin antagonists |
| US5218114A (en) * | 1991-04-10 | 1993-06-08 | Merck & Co., Inc. | Cholecystokinin antagonists |
-
1993
- 1993-02-25 IL IL104853A patent/IL104853A/xx not_active IP Right Cessation
- 1993-02-26 HU HU9402212A patent/HU224012B1/hu active IP Right Grant
- 1993-02-26 PT PT93905480T patent/PT628033E/pt unknown
- 1993-02-26 AT AT93905480T patent/ATE245632T1/de not_active IP Right Cessation
- 1993-02-26 RU RU94038255A patent/RU2139282C1/ru active
- 1993-02-26 WO PCT/GB1993/000404 patent/WO1993016999A1/en active IP Right Grant
- 1993-02-26 EP EP93905480A patent/EP0628033B1/en not_active Expired - Lifetime
- 1993-02-26 CA CA002129990A patent/CA2129990C/en not_active Expired - Lifetime
- 1993-02-26 JP JP5506433A patent/JP2571344B2/ja not_active Expired - Lifetime
- 1993-02-26 DE DE69333108T patent/DE69333108T2/de not_active Expired - Fee Related
- 1993-02-26 DK DK93905480T patent/DK0628033T3/da active
- 1993-02-26 ES ES93905480T patent/ES2203616T3/es not_active Expired - Lifetime
- 1993-02-26 US US08/284,462 patent/US5688943A/en not_active Expired - Lifetime
- 1993-02-26 AU AU36391/93A patent/AU672390B2/en not_active Expired
- 1993-02-27 CN CN93101848A patent/CN1051079C/zh not_active Expired - Lifetime
- 1993-03-24 TW TW082102213A patent/TW438783B/zh not_active IP Right Cessation
-
1994
- 1994-08-24 NO NO19943133A patent/NO311215B1/no not_active IP Right Cessation
- 1994-08-26 FI FI943941A patent/FI121234B/fi not_active IP Right Cessation
-
1997
- 1997-06-06 US US08/867,422 patent/US5962451A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| IL104853A (en) | 1997-11-20 |
| US5688943A (en) | 1997-11-18 |
| FI943941A (fi) | 1994-10-26 |
| DE69333108T2 (de) | 2004-04-15 |
| FI121234B (fi) | 2010-08-31 |
| FI943941A0 (fi) | 1994-08-26 |
| HU224012B1 (hu) | 2005-04-28 |
| AU3639193A (en) | 1993-09-13 |
| DE69333108D1 (de) | 2003-08-28 |
| EP0628033A1 (en) | 1994-12-14 |
| TW438783B (en) | 2001-06-07 |
| AU672390B2 (en) | 1996-10-03 |
| RU2139282C1 (ru) | 1999-10-10 |
| ES2203616T3 (es) | 2004-04-16 |
| NO943133L (no) | 1994-08-24 |
| PT628033E (pt) | 2003-12-31 |
| HUT67963A (en) | 1995-05-29 |
| HU9402212D0 (en) | 1994-09-28 |
| RU94038255A (ru) | 1996-07-10 |
| CN1075717A (zh) | 1993-09-01 |
| JPH07505121A (ja) | 1995-06-08 |
| IL104853A0 (en) | 1993-06-10 |
| ATE245632T1 (de) | 2003-08-15 |
| EP0628033B1 (en) | 2003-07-23 |
| WO1993016999A1 (en) | 1993-09-02 |
| US5962451A (en) | 1999-10-05 |
| JP2571344B2 (ja) | 1997-01-16 |
| CA2129990A1 (en) | 1993-09-02 |
| NO943133D0 (no) | 1994-08-24 |
| CA2129990C (en) | 2006-01-10 |
| DK0628033T3 (da) | 2003-11-10 |
| CN1051079C (zh) | 2000-04-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |