CS414091A3 - Condensed benzazepines - Google Patents

Condensed benzazepines Download PDF

Info

Publication number: CS414091A3
Authority: CS; Czechoslovakia
Prior art keywords: hydrogen; alkyl; hydroxy; methyl; benzo
Prior art date: 1986-01-16

Application number

CS914140A

Other languages

Czech (cs)

English (en)

Inventor

Joel G Berger

Wei K Chang

Elijah H Gold

John W Clader

Original Assignee

Schering Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1986-01-16

Filing date

1991-12-30

Publication date

1992-05-13

1991-12-30 Application filed by Schering Corp filed Critical Schering Corp

1992-05-13 Publication of CS414091A3 publication Critical patent/CS414091A3/cs

Links

150000008038 benzoazepines Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 142
229910052739 hydrogen Inorganic materials 0.000 claims description 98
239000001257 hydrogen Substances 0.000 claims description 98
125000000217 alkyl group Chemical group 0.000 claims description 76
-1 Y is C3 Substances 0.000 claims description 59
150000002431 hydrogen Chemical group 0.000 claims description 53
239000000203 mixture Substances 0.000 claims description 49
150000003839 salts Chemical class 0.000 claims description 45
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 32
125000003545 alkoxy group Chemical group 0.000 claims description 30
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
FBABDBSOFPUQMW-UHFFFAOYSA-N 5h-benzo[g][1]benzazepine Chemical compound N1C=CC=CC2=C1C=CC1=CC=CC=C21 FBABDBSOFPUQMW-UHFFFAOYSA-N 0.000 claims description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
238000000034 method Methods 0.000 claims description 22
125000003118 aryl group Chemical group 0.000 claims description 17
125000003710 aryl alkyl group Chemical group 0.000 claims description 16
125000000753 cycloalkyl group Chemical group 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 11
229910052736 halogen Inorganic materials 0.000 claims description 11
150000002367 halogens Chemical group 0.000 claims description 11
229910052757 nitrogen Inorganic materials 0.000 claims description 11
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 9
239000008194 pharmaceutical composition Substances 0.000 claims description 9
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
239000003937 drug carrier Substances 0.000 claims description 8
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
238000009833 condensation Methods 0.000 claims description 7
230000005494 condensation Effects 0.000 claims description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 6
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 6
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
125000004414 alkyl thio group Chemical group 0.000 claims description 6
239000003638 chemical reducing agent Substances 0.000 claims description 6
125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 6
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
125000001309 chloro group Chemical group Cl* 0.000 claims description 5
125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 5
YGLDQFWPUCURIP-UHFFFAOYSA-N 3h-3-benzazepine Chemical compound C1=CNC=CC2=CC=CC=C21 YGLDQFWPUCURIP-UHFFFAOYSA-N 0.000 claims description 4
208000028017 Psychotic disease Diseases 0.000 claims description 4
125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 4
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 4
125000004104 aryloxy group Chemical group 0.000 claims description 4
230000036407 pain Effects 0.000 claims description 4
229930192474 thiophene Natural products 0.000 claims description 4
125000001246 bromo group Chemical group Br* 0.000 claims description 3
229910052796 boron Inorganic materials 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
229940124550 renal vasodilator Drugs 0.000 claims description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 4
125000003277 amino group Chemical group 0.000 claims 3
YEUFVOFLAMBYQF-UHFFFAOYSA-N 4-methoxy-10-methyl-10-azatetracyclo[9.9.0.02,7.015,20]icosa-2,4,6,15,17,19-hexaen-5-ol Chemical compound C1CCC2=CC=CC=C2C2C(C=C(C(=C3)O)OC)=C3CCN(C)C12 YEUFVOFLAMBYQF-UHFFFAOYSA-N 0.000 claims 1
208000020401 Depressive disease Diseases 0.000 claims 1
150000001335 aliphatic alkanes Chemical class 0.000 claims 1
125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
125000002947 alkylene group Chemical group 0.000 claims 1
125000005605 benzo group Chemical group 0.000 claims 1
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims 1
230000001419 dependent effect Effects 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
239000000243 solution Substances 0.000 description 37
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 20
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
239000007787 solid Substances 0.000 description 18
238000012360 testing method Methods 0.000 description 17
239000002904 solvent Substances 0.000 description 16
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
241000700159 Rattus Species 0.000 description 13
229960000583 acetic acid Drugs 0.000 description 13
239000010410 layer Substances 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
102000005962 receptors Human genes 0.000 description 12
108020003175 receptors Proteins 0.000 description 12
239000003054 catalyst Substances 0.000 description 11
239000003814 drug Substances 0.000 description 11
230000000694 effects Effects 0.000 description 11
238000001704 evaporation Methods 0.000 description 11
230000008020 evaporation Effects 0.000 description 11
239000003921 oil Substances 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
229940079593 drug Drugs 0.000 description 10
238000003756 stirring Methods 0.000 description 10
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
241000699670 Mus sp. Species 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
239000007983 Tris buffer Substances 0.000 description 8
239000000463 material Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
230000004044 response Effects 0.000 description 8
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
229910052799 carbon Inorganic materials 0.000 description 7
238000001816 cooling Methods 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
239000000047 product Substances 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
GOTMKOSCLKVOGG-OAHLLOKOSA-N (5R)-8-chloro-3-methyl-5-phenyl-1,2,4,5-tetrahydro-3-benzazepin-7-ol Chemical compound C1([C@@H]2C3=CC(O)=C(Cl)C=C3CCN(C2)C)=CC=CC=C1 GOTMKOSCLKVOGG-OAHLLOKOSA-N 0.000 description 6
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 6
241000282693 Cercopithecidae Species 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
239000002585 base Substances 0.000 description 6
230000027455 binding Effects 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
239000000284 extract Substances 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
206010015995 Eyelid ptosis Diseases 0.000 description 5
239000002253 acid Substances 0.000 description 5
XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000007788 liquid Substances 0.000 description 5
201000003004 ptosis Diseases 0.000 description 5
230000009467 reduction Effects 0.000 description 5
238000006722 reduction reaction Methods 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
239000000908 ammonium hydroxide Substances 0.000 description 4
238000003556 assay Methods 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 4
239000007924 injection Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
230000003470 muricidal effect Effects 0.000 description 4
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
229950001675 spiperone Drugs 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 3
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
229940126062 Compound A Drugs 0.000 description 3
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
230000001430 anti-depressive effect Effects 0.000 description 3
239000000935 antidepressant agent Substances 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
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150000001721 carbon Chemical group 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000036461 convulsion Effects 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
DNJIEGIFACGWOD-UHFFFAOYSA-N ethanethiol Chemical compound CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 3
239000007789 gas Substances 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
229940098779 methanesulfonic acid Drugs 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
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DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 3
229910052717 sulfur Inorganic materials 0.000 description 3
239000003826 tablet Substances 0.000 description 3
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RPANAEVOUHFJGH-UHFFFAOYSA-N 1-(3-methoxyphenyl)-3,4-dihydro-1h-naphthalen-2-one Chemical compound COC1=CC=CC(C2C3=CC=CC=C3CCC2=O)=C1 RPANAEVOUHFJGH-UHFFFAOYSA-N 0.000 description 2
XYEADBDMDKNORF-UHFFFAOYSA-N 12-azatricyclo[9.5.0.02,7]hexadeca-1(16),2,4,6,8,10,12,14-octaene Chemical compound C1=C2C(N=CC=C1)=CC=CC1=C2C=CC=C1 XYEADBDMDKNORF-UHFFFAOYSA-N 0.000 description 2
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BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
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UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
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GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
239000000872 buffer Substances 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000018044 dehydration Effects 0.000 description 2
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239000003480 eluent Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
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239000012458 free base Substances 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
239000005457 ice water Substances 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
239000007928 intraperitoneal injection Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
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Classifications

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- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
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Heart & Thoracic Surgery (AREA)
Endocrinology (AREA)
Reproductive Health (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Other In-Based Heterocyclic Compounds (AREA)
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CS914140A 1986-01-16 1991-12-30 Condensed benzazepines CS414091A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US82047186A	1986-01-16	1986-01-16

Publications (1)

Publication Number	Publication Date
CS414091A3 true CS414091A3 (en)	1992-05-13

Family

ID=25230864

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS914140A CS414091A3 (en)	1986-01-16	1991-12-30	Condensed benzazepines

Country Status (19)

Country	Link
EP (2)	EP0254737B1 (fr)
JP (1)	JPH0681745B2 (fr)
KR (1)	KR900007781B1 (fr)
AU (1)	AU588080B2 (fr)
CA (1)	CA1333485C (fr)
CS (1)	CS414091A3 (fr)
DK (1)	DK164161C (fr)
ES (1)	ES2031834T3 (fr)
FI (1)	FI83512C (fr)
GR (1)	GR3000994T3 (fr)
HU (1)	HU199805B (fr)
IE (1)	IE59651B1 (fr)
IL (2)	IL81268A0 (fr)
NZ (1)	NZ218953A (fr)
OA (1)	OA08660A (fr)
PT (1)	PT84109B (fr)
SG (1)	SG128692G (fr)
WO (1)	WO1987004430A2 (fr)
ZA (1)	ZA87291B (fr)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4973586A (en) *	1986-01-16	1990-11-27	Schering Corporation	Fused benzazepines, compositions of, and medical use thereof
JPH0678317B2 (ja) *	1987-07-15	1994-10-05	シェリング・コーポレーション	縮合ベンズアゼピン
DK325188D0 (da) *	1988-06-15	1988-06-15	Novo Industri As	Hidtil ukendte benzazepinderivater
HUT58035A (en) *	1988-07-29	1992-01-28	Schering Corp	Process for enanthiospecific synthesis of intermediates of hexahydrobenzo(d)naphtno(2,1-b)azepines
US5091526A (en) *	1988-07-29	1992-02-25	Schering Corporation	Process for the enantiospecific synthesis of intermediates for hexahydro-benzo[d]-naphtho[2,1-b]azepines
US5104814A (en) *	1988-11-22	1992-04-14	Schering Corporation	Assay kit and methods for neuroleptic drugs
FR2642065B1 (fr) *	1989-01-24	1991-05-24	Lipha	Derives d'acides benzocycloalcenyl dihydroxy alcanoiques, procede de preparation et medicaments les contenant
EP0513174B1 (fr) *	1990-02-02	1995-08-16	Schering Corporation	Derives de 4,5-cycloalcano-3-benzazepin-7-ol et leurs utilisations
US5461147A (en) *	1993-09-27	1995-10-24	Schering Corporation	Process for preparing benzazepine intermediates for the synthesis of D1 antagonists
US5463051A (en) *	1993-09-27	1995-10-31	Schering Corporation	Process for preparing benzazepine intermediates for the synthesis of D1 antagonists
US5461148A (en) *	1993-09-27	1995-10-24	Schering Corporation	Process for preparing benzazepine intermediates for the synthesis of D1 antagonists
AR027687A1 (es) *	2000-03-22	2003-04-09	Yakult Honsha Kk	Procedimiento para preparar camptotecina
EP2316468A1 (fr)	2002-02-22	2011-05-04	Shire LLC	Système de distribution et méthodes de protection et d'administration de dextroamphetamine
DE60321354D1 (de) *	2002-08-29	2008-07-10	Schering Corp	Selektive d1/d5 rezeptorantagonisten zur behandlung von fettleibigkeit und von zns störungen
WO2005035504A2 (fr) *	2003-05-22	2005-04-21	Schering Corporation	Antagonistes selectifs des recepteurs d1/d5 utilises dans le traitement de l'obesite et des troubles du systeme nerveux central
EP2164324B1 (fr) *	2007-06-15	2014-08-13	University Of Florida Research Foundation	Composés thérapeutiques

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3393192A (en) *	1965-04-26	1968-07-16	Schering Corp	Novel benzazepines
GB1118688A (en)	1967-02-17	1968-07-03	Scherico Ltd	Novel benzazepines and process for making same
CH481110A (de) *	1967-02-17	1969-11-15	Geigy Ag J R	Verfahren zur Herstellung von 1,2,4,5-Tetrahydro-3-azepinen
US3609138A (en)	1967-12-22	1971-09-28	Ciba Geigy Corp	1-aryl-3-benzazepines
NL7206204A (fr) *	1971-05-10	1972-11-14
US3939165A (en) *	1974-11-14	1976-02-17	Morton-Norwich Products, Inc.	5,6,6A,6B,7,8-Hexahydrobenz[a]phenanthridine hydrochloride
US4011319A (en)	1975-07-02	1977-03-08	Smithkline Corporation	Pharmaceutical compositions and methods involving benzazepine derivatives
US4284555A (en)	1979-04-27	1981-08-18	Schering Corporation	7-Chloro-8(substituted amino carbonyloxy)-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines
US4477378A (en)	1980-02-05	1984-10-16	Schering Corp.	Esters of substituted 8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines

1987
- 1987-01-14 AU AU68920/87A patent/AU588080B2/en not_active Ceased
- 1987-01-14 HU HU87914A patent/HU199805B/hu not_active IP Right Cessation
- 1987-01-14 WO PCT/US1987/000042 patent/WO1987004430A2/fr not_active Ceased
- 1987-01-14 JP JP62500944A patent/JPH0681745B2/ja not_active Expired - Lifetime
- 1987-01-14 EP EP87900939A patent/EP0254737B1/fr not_active Expired - Lifetime
- 1987-01-14 KR KR1019870700836A patent/KR900007781B1/ko not_active Expired
- 1987-01-15 ZA ZA87291A patent/ZA87291B/xx unknown
- 1987-01-15 IL IL81268A patent/IL81268A0/xx not_active IP Right Cessation
- 1987-01-15 EP EP87100446A patent/EP0230270B1/fr not_active Expired - Lifetime
- 1987-01-15 ES ES198787100446T patent/ES2031834T3/es not_active Expired - Lifetime
- 1987-01-15 PT PT84109A patent/PT84109B/pt not_active IP Right Cessation
- 1987-01-15 CA CA000527422A patent/CA1333485C/fr not_active Expired - Fee Related
- 1987-01-15 NZ NZ218953A patent/NZ218953A/xx unknown
- 1987-01-15 IL IL103007A patent/IL103007A/xx not_active IP Right Cessation
- 1987-01-20 IE IE11287A patent/IE59651B1/en not_active IP Right Cessation
- 1987-09-14 DK DK479087A patent/DK164161C/da not_active IP Right Cessation
- 1987-09-15 OA OA59194A patent/OA08660A/xx unknown
- 1987-09-15 FI FI874006A patent/FI83512C/fi not_active IP Right Cessation
1990
- 1990-10-29 GR GR90400833T patent/GR3000994T3/el unknown
1991
- 1991-12-30 CS CS914140A patent/CS414091A3/cs unknown
1992
- 1992-12-17 SG SG1286/92A patent/SG128692G/en unknown

Also Published As

Publication number	Publication date
IE870112L (en)	1987-07-16
IL81268A0 (en)	1987-08-31
ZA87291B (en)	1987-11-25
NZ218953A (en)	1990-03-27
HUT48600A (en)	1989-06-28
EP0230270B1 (fr)	1990-08-01
PT84109B (pt)	1989-07-31
SG128692G (en)	1993-03-12
AU6892087A (en)	1987-08-14
GR3000994T3 (en)	1991-12-10
DK479087A (da)	1987-09-14
FI83512B (fi)	1991-04-15
DK479087D0 (da)	1987-09-14
AU588080B2 (en)	1989-09-07
FI874006A0 (fi)	1987-09-15
WO1987004430A3 (fr)	1988-03-24
DK164161C (da)	1992-10-26
WO1987004430A2 (fr)	1987-07-30
EP0254737A1 (fr)	1988-02-03
EP0254737B1 (fr)	1990-07-25
ES2031834T3 (es)	1993-01-01
KR900007781B1 (ko)	1990-10-20
PT84109A (en)	1987-02-01
JPH0681745B2 (ja)	1994-10-19
IL103007A (en)	1993-07-08
FI874006L (fi)	1987-09-15
CA1333485C (fr)	1994-12-13
HU199805B (en)	1990-03-28
JPS63502348A (ja)	1988-09-08
EP0230270A2 (fr)	1987-07-29
EP0230270A3 (en)	1987-10-21
KR880700794A (ko)	1988-04-12
IE59651B1 (en)	1994-03-09
OA08660A (en)	1988-11-30
FI83512C (fi)	1991-07-25
DK164161B (da)	1992-05-18

Publication	Publication Date	Title
CS414091A3 (en)	1992-05-13	Condensed benzazepines
EP0170213B1 (fr)	1990-01-10	Agents à base de glutarimide ayant des propriétés anxiolytiques et antihypertensives
US5296482A (en)	1994-03-22	(Benzocycloalkyl) alkylamines
US5530125A (en)	1996-06-25	Synthesis of α-substituted-aryl ethylamines
JPH0819065B2 (ja)	1996-02-28	ベンゾ融合シクロアルカンおよびオキサ‐およびチア‐シクロアルカントランス‐１，２‐ジアミン誘導体
EP0096838A1 (fr)	1983-12-28	Aryloxy-1 tétrahydro-2,3,4,5 benzazépines-3, leur procédé de préparation et leur application comme médicaments
US4973586A (en)	1990-11-27	Fused benzazepines, compositions of, and medical use thereof
IE912031A1 (en)	1991-12-18	8-lower alkyl-5-cycloalkyl or 5-cycloalkenyl substituted¹benzazepines and pharmaceutical compositions containing them
KR100213531B1 (ko)	1999-08-02	헥사히드로아제핀 유도체, 그것들의 제법과 그것들을 함유하는 약학 조성물
US4612312A (en)	1986-09-16	Glutarimide antianxiety and antihypertensive agents
EP0513174A1 (fr)	1992-11-19	Derives de 4,5-cycloalcano-3-benzazepin-7-ol et leurs utilisations.
US5302716A (en)	1994-04-12	Fused benzazepines
KOJIMA et al.	1985	Syntheses of (±)-2-[(inden-7-yloxy) methyl] morpholine hydrochloride (YM-08054, indeloxazine hydrochloride) and its derivatives with potential cerebral-activating and antidepressive properties
FI88800B (fi)	1993-03-31	Foerfarande foer framstaellning av farmakologiskt vaerdefulla 2,3,4,5,6,7-hexahydro-2,7-metano-1,5-bensoxazonin- eller -1,4-bensoxazonin-foereningar samt mellanprodukter
EP0363353B1 (fr)	1992-07-22	Benzazepines fusionnees
JP2007509094A (ja)	2007-04-12	Ｍａｏ−ｂ阻害物質としてのベンズアゼピン誘導体
FI64142C (fi)	1983-10-10	Foerfarande foer framstaellning av nya terapeutiskt aktiva benso(c)kinolinonderivat
HK29493A (en)	1993-04-02	Fused benzazepines
IE60925B1 (en)	1994-09-07	Fused benzazepines