GB2142332A - Spirosuccinimide derivatives - Google Patents
Spirosuccinimide derivatives Download PDFInfo
- Publication number
- GB2142332A GB2142332A GB08416172A GB8416172A GB2142332A GB 2142332 A GB2142332 A GB 2142332A GB 08416172 A GB08416172 A GB 08416172A GB 8416172 A GB8416172 A GB 8416172A GB 2142332 A GB2142332 A GB 2142332A
- Authority
- GB
- United Kingdom
- Prior art keywords
- compound
- formula
- acid addition
- addition salt
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 159
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims description 100
- 239000002253 acid Substances 0.000 claims description 97
- 125000000217 alkyl group Chemical group 0.000 claims description 90
- 239000001257 hydrogen Substances 0.000 claims description 85
- 229910052739 hydrogen Inorganic materials 0.000 claims description 85
- -1 tetrahydrobenzocycloheptenyl Chemical group 0.000 claims description 68
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 66
- 239000001301 oxygen Substances 0.000 claims description 66
- 229910052760 oxygen Inorganic materials 0.000 claims description 66
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 36
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 29
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 19
- 125000001589 carboacyl group Chemical group 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 239000005864 Sulphur Substances 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 125000006193 alkinyl group Chemical group 0.000 claims description 8
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- KRDCQZQJIOVAJY-UHFFFAOYSA-N 8-(cyclopropylmethyl)-2-ethyl-2,8-diazaspiro[4.5]decane-1,3-dione Chemical compound O=C1N(CC)C(=O)CC11CCN(CC2CC2)CC1 KRDCQZQJIOVAJY-UHFFFAOYSA-N 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 206010020651 Hyperkinesia Diseases 0.000 claims description 4
- 208000000269 Hyperkinesis Diseases 0.000 claims description 4
- 206010026749 Mania Diseases 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000005358 mercaptoalkyl group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 4
- 206010039966 Senile dementia Diseases 0.000 claims description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- CAHDYNYJWYSNKM-UHFFFAOYSA-N 2-ethyl-2,9-diazaspiro[4.5]decane-1,3-dione Chemical compound O=C1N(CC)C(=O)CC11CNCCC1 CAHDYNYJWYSNKM-UHFFFAOYSA-N 0.000 claims description 2
- NBQDGUQLQLNBOR-UHFFFAOYSA-N 2-ethyl-8-methyl-3-sulfanylidene-2,8-diazaspiro[4.5]decan-1-one Chemical compound C(C)N1C(C2(CC1=S)CCN(CC2)C)=O NBQDGUQLQLNBOR-UHFFFAOYSA-N 0.000 claims description 2
- REUYZVSLTRHIIU-UHFFFAOYSA-N 2-ethyl-8-methyl-8-oxido-2-aza-8-azoniaspiro[4.5]decane-1,3-dione Chemical compound O=C1N(CC)C(=O)CC11CC[N+](C)([O-])CC1 REUYZVSLTRHIIU-UHFFFAOYSA-N 0.000 claims description 2
- JESJDYKIFCIOMN-UHFFFAOYSA-N 8-(cyclopropylmethyl)-2-ethyl-8-oxido-2-aza-8-azoniaspiro[4.5]decane-1,3-dione Chemical compound C(C)N1C(C2(CC1=O)CC[N+](CC2)(CC2CC2)[O-])=O JESJDYKIFCIOMN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 125000004149 thio group Chemical group *S* 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 50
- NSXCSOQOOHVDDY-UHFFFAOYSA-N 2-ethyl-8-methyl-1-sulfanylidene-2,8-diazaspiro[4.5]decan-3-one Chemical compound C(C)N1C(C2(CC1=O)CCN(CC2)C)=S NSXCSOQOOHVDDY-UHFFFAOYSA-N 0.000 claims 1
- VOCAHHVQSGLVRD-UHFFFAOYSA-N 2-ethyl-8-methyl-2,8-diazaspiro[4.5]decane-1,3-dithione Chemical compound C(C)N1C(C2(CC1=S)CCN(CC2)C)=S VOCAHHVQSGLVRD-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 239000003814 drug Substances 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 239000000243 solution Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 239000002775 capsule Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229960001866 silicon dioxide Drugs 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- FWWOWPGPERBCNJ-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)-4-oxobutanoic acid Chemical compound OCCOC(=O)CC(O)C(O)=O FWWOWPGPERBCNJ-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- 238000004587 chromatography analysis Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- VRYALKFFQXWPIH-PBXRRBTRSA-N (3r,4s,5r)-3,4,5,6-tetrahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)CC=O VRYALKFFQXWPIH-PBXRRBTRSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000003727 cerebral blood flow Effects 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000008203 oral pharmaceutical composition Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 1
- OODAUJSHKGCQSF-UHFFFAOYSA-N 2-ethyl-2,8-diazaspiro[4.5]decane-1,3-dione Chemical compound O=C1N(CC)C(=O)CC11CCNCC1 OODAUJSHKGCQSF-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- LURVRIQOFCDNOU-UHFFFAOYSA-N Cl.C(C)N1C(C2(CC1=O)CCN(CC2)C)=S Chemical compound Cl.C(C)N1C(C2(CC1=O)CCN(CC2)C)=S LURVRIQOFCDNOU-UHFFFAOYSA-N 0.000 description 1
- QVTHUOAQPIBAOT-UHFFFAOYSA-N Cl.C(C)N1C(C2(CC1=S)CCN(CC2)C)=O Chemical compound Cl.C(C)N1C(C2(CC1=S)CCN(CC2)C)=O QVTHUOAQPIBAOT-UHFFFAOYSA-N 0.000 description 1
- DIEUAKCNUGAYCF-UHFFFAOYSA-N Cl.C(C)N1C(C2(CC1=S)CCN(CC2)C)=S Chemical compound Cl.C(C)N1C(C2(CC1=S)CCN(CC2)C)=S DIEUAKCNUGAYCF-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical group Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 229910003844 NSO2 Inorganic materials 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000019568 aromas Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- AXFBWIDRWVXXLY-UHFFFAOYSA-N diethyl 2-(3-cyano-1-ethoxycarbonylpiperidin-3-yl)propanedioate Chemical compound C(C)OC(C(C(=O)OCC)C1(CN(CCC1)C(=O)OCC)C#N)=O AXFBWIDRWVXXLY-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- AQANJZHCWMIUHG-UHFFFAOYSA-N ethyl 3-(2-ethoxy-2-oxoethyl)piperidine-3-carboxylate Chemical compound CCOC(=O)CC1(C(=O)OCC)CCCNC1 AQANJZHCWMIUHG-UHFFFAOYSA-N 0.000 description 1
- VWQXCLBFGRMQJC-UHFFFAOYSA-N ethyl 3-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCCC(=O)C1 VWQXCLBFGRMQJC-UHFFFAOYSA-N 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 210000003715 limbic system Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 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
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000036385 rapid eye movement (rem) sleep Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH350483 | 1983-06-27 | ||
| CH350583 | 1983-06-27 | ||
| CH350383 | 1983-06-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| GB8416172D0 GB8416172D0 (en) | 1984-08-01 |
| GB2142332A true GB2142332A (en) | 1985-01-16 |
Family
ID=27174377
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08416172A Withdrawn GB2142332A (en) | 1983-06-27 | 1984-06-25 | Spirosuccinimide derivatives |
Country Status (16)
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0273659A1 (en) * | 1986-12-27 | 1988-07-06 | Takeda Chemical Industries, Ltd. | Azaspiro compounds, their production and use |
| RU2182983C2 (ru) * | 1997-04-16 | 2002-05-27 | Ман Б Энд В Диесель А/С | Поршневой двигатель внутреннего сгорания |
| WO2004005293A3 (en) * | 2002-07-05 | 2004-05-13 | Targacept Inc | N-aryl diazaspiracyclic compounds and methods of preparation and use thereof |
| WO2005023809A1 (en) * | 2003-09-10 | 2005-03-17 | Virochem Pharma Inc. | Spiro compounds and methods for the modulation of chemokine receptor activity |
| US7612056B2 (en) | 2004-04-06 | 2009-11-03 | Jenssen Pharmaceutica N.V. | Substituted diaza-spiro-[4.5]-decane derivatives and their use as neurokinin antagonists |
| US8604200B2 (en) | 2005-03-08 | 2013-12-10 | Janssen Pharmaceutica N.V. | Diaza-spiro-{4,4}-nonane derivatives as neurokinin (NK1) antagonists |
| US9005578B2 (en) | 2008-03-21 | 2015-04-14 | Fluoropharma, Inc. | Compounds and compositions for the detection and treatment of Alzheimer's disease and related disorders |
| US10058625B2 (en) | 2004-02-24 | 2018-08-28 | The General Hospital Corporation | Catalytic radiofluorination |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3431195A1 (de) * | 1984-08-24 | 1986-03-06 | Troponwerke GmbH & Co KG, 5000 Köln | Neue benzodiazepine, verfahren zu ihrer herstellung sowie ihre verwendung |
| US5407938A (en) * | 1990-04-10 | 1995-04-18 | Israel Institute For Biological Research | Certain 1-methyl-piperidine-4-spiro-4'-(1'-3'-oxazolines) and corresponding -(1',3' thiazolines) |
| JP2800953B2 (ja) * | 1990-07-06 | 1998-09-21 | 住友製薬株式会社 | 新規なイミド誘導体 |
| BE1007765A5 (fr) | 1994-06-27 | 1995-10-17 | Blagden Ind Plc | Fut metallique a ouverture totale. |
| AU2206699A (en) * | 1997-12-23 | 1999-07-12 | Alcon Laboratories, Inc. | Muscarinic agents and use thereof to treat glaucoma, myopia and various other conditions |
| US8257680B1 (en) | 2004-02-24 | 2012-09-04 | The General Hospital Corporation | Catalytic radiofluorination |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1211646B (de) * | 1959-03-25 | 1966-03-03 | Sandoz Ag | Verfahren zur Herstellung von Spirosuccinimiden und deren Salzen |
| GB936477A (en) * | 1959-03-25 | 1963-09-11 | Sandoz Ltd | Improvements in or relating to substituted succinimides |
| US3198800A (en) * | 1964-05-07 | 1965-08-03 | Sandoz Ltd | 2, 8-(para-f-4-oxo-butyl)-diazaspiro[4, 5]-decane-1, 3-diones |
| BE897058A (fr) * | 1982-06-25 | 1983-12-16 | Sandoz Sa | Utilisation d'un derive du spiro-succinimide dans le traitement de la demence du type alzheimer |
-
1984
- 1984-06-15 HU HU842326A patent/HUT36793A/hu unknown
- 1984-06-15 NL NL8401907A patent/NL8401907A/nl not_active Application Discontinuation
- 1984-06-16 DE DE3422411A patent/DE3422411A1/de not_active Withdrawn
- 1984-06-18 WO PCT/CH1984/000099 patent/WO1985000171A1/de unknown
- 1984-06-22 FR FR8410017A patent/FR2549061A1/fr active Pending
- 1984-06-25 FI FI842547A patent/FI842547A7/fi not_active Application Discontinuation
- 1984-06-25 IL IL72218A patent/IL72218A0/xx unknown
- 1984-06-25 GR GR75100A patent/GR82274B/el unknown
- 1984-06-25 DK DK310184A patent/DK310184A/da not_active Application Discontinuation
- 1984-06-25 SE SE8403376A patent/SE8403376L/xx not_active Application Discontinuation
- 1984-06-25 GB GB08416172A patent/GB2142332A/en not_active Withdrawn
- 1984-06-25 PT PT78787A patent/PT78787B/pt unknown
- 1984-06-25 AU AU29833/84A patent/AU2983384A/en not_active Abandoned
- 1984-06-26 IT IT48458/84A patent/IT1199148B/it active
- 1984-06-26 ES ES533735A patent/ES8601202A1/es not_active Expired
- 1984-06-27 LU LU85434A patent/LU85434A1/fr unknown
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0273659A1 (en) * | 1986-12-27 | 1988-07-06 | Takeda Chemical Industries, Ltd. | Azaspiro compounds, their production and use |
| US4804665A (en) * | 1986-12-27 | 1989-02-14 | Takeda Chemical Industries, Ltd. | Azaspiro compounds and their use |
| RU2182983C2 (ru) * | 1997-04-16 | 2002-05-27 | Ман Б Энд В Диесель А/С | Поршневой двигатель внутреннего сгорания |
| KR101052287B1 (ko) * | 2002-07-05 | 2011-07-27 | 타가셉트 인코포레이티드 | Ｎ-아릴 디아자스피로시클릭 화합물, 그 제조방법, 및 그용도 |
| US6956042B2 (en) | 2002-07-05 | 2005-10-18 | Targacept, Inc. | N-aryl diazaspiracyclic compounds and methods of preparation and use thereof |
| US7291731B2 (en) | 2002-07-05 | 2007-11-06 | Targacept, Inc. | N-aryl diazaspiracyclic compounds and methods of preparation and use thereof |
| EA009789B1 (ru) * | 2002-07-05 | 2008-04-28 | Таргасепт, Инк. | N-арилдиазаспирациклические соединения и способы их получения и применения |
| US7375110B2 (en) | 2002-07-05 | 2008-05-20 | Targacept, Inc. | N-aryl diazaspiracyclic compounds and methods of preparation and use thereof |
| US7923559B2 (en) | 2002-07-05 | 2011-04-12 | Targacept, Inc. | N-aryl diazaspirocyclic compounds and methods of preparation and use thereof |
| WO2004005293A3 (en) * | 2002-07-05 | 2004-05-13 | Targacept Inc | N-aryl diazaspiracyclic compounds and methods of preparation and use thereof |
| US7288548B2 (en) | 2003-09-10 | 2007-10-30 | Virochem Pharma, Inc. | Spiro compounds and methods for the modulation of chemokine receptor activity |
| WO2005023809A1 (en) * | 2003-09-10 | 2005-03-17 | Virochem Pharma Inc. | Spiro compounds and methods for the modulation of chemokine receptor activity |
| US10058625B2 (en) | 2004-02-24 | 2018-08-28 | The General Hospital Corporation | Catalytic radiofluorination |
| US10695449B2 (en) | 2004-02-24 | 2020-06-30 | The General Hospital Corporation | Catalytic radiofluorination |
| US7612056B2 (en) | 2004-04-06 | 2009-11-03 | Jenssen Pharmaceutica N.V. | Substituted diaza-spiro-[4.5]-decane derivatives and their use as neurokinin antagonists |
| US8604200B2 (en) | 2005-03-08 | 2013-12-10 | Janssen Pharmaceutica N.V. | Diaza-spiro-{4,4}-nonane derivatives as neurokinin (NK1) antagonists |
| US9005578B2 (en) | 2008-03-21 | 2015-04-14 | Fluoropharma, Inc. | Compounds and compositions for the detection and treatment of Alzheimer's disease and related disorders |
| US10857247B2 (en) | 2008-03-21 | 2020-12-08 | The General Hospital Corporation | Compounds and compositions for the detection and treatment of Alzheimer's disease and related disorders |
Also Published As
| Publication number | Publication date |
|---|---|
| DK310184D0 (da) | 1984-06-25 |
| HUT36793A (en) | 1985-10-28 |
| SE8403376L (sv) | 1984-12-28 |
| IT8448458A0 (it) | 1984-06-26 |
| LU85434A1 (fr) | 1985-03-26 |
| IT1199148B (it) | 1988-12-30 |
| DK310184A (da) | 1984-12-28 |
| PT78787B (en) | 1986-06-05 |
| AU2983384A (en) | 1985-01-03 |
| IL72218A0 (en) | 1984-10-31 |
| FI842547A0 (fi) | 1984-06-25 |
| SE8403376D0 (sv) | 1984-06-25 |
| ES533735A0 (es) | 1985-10-16 |
| WO1985000171A1 (en) | 1985-01-17 |
| GB8416172D0 (en) | 1984-08-01 |
| FI842547A7 (fi) | 1984-12-28 |
| NL8401907A (nl) | 1985-01-16 |
| PT78787A (en) | 1984-07-01 |
| FR2549061A1 (fr) | 1985-01-18 |
| GR82274B (enrdf_load_stackoverflow) | 1984-12-13 |
| DE3422411A1 (de) | 1985-01-03 |
| ES8601202A1 (es) | 1985-10-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| GB2142332A (en) | Spirosuccinimide derivatives | |
| EP0054951A1 (en) | Dibenz(b,f)(1,4)oxazepine derivatives, process for preparing the same, and pharmaceutical compositions comprising the same | |
| US4746655A (en) | Fused aromatic-spiropiperidine oxazepinones(and thiones) | |
| US4888335A (en) | 3-alkoxy-2-aminopropyl heterocyclic amines and their use as cardiovascular agents | |
| EP0003016B1 (en) | Pyrazino-benzoxazepine and -benzthiazepine derivatives, processes for their production and pharmaceutical compositions containing them | |
| EP0357126B1 (en) | Tetracyclic antidepressants | |
| IE49788B1 (en) | 6-substituted 11-alkylene-morphanthridines,their preparation and therapeutic agents containing these compounds | |
| JPH05132477A (ja) | 三環式化合物およびその中間体 | |
| KR920005827B1 (ko) | 벤조티아디아제핀 유도체 | |
| US4616023A (en) | Pharmaceutical compositions of 4-(dibenzo-[a,d]cycloalkenyl)piperazine compounds and methods | |
| NZ204893A (en) | Benzothiopyranopyridinones and pharmaceutical compositions containing such | |
| US4728649A (en) | 3-oxo-piperazin-1-yl-ergolines exhibiting antidopaminergic activity | |
| US4929616A (en) | Novel basic-substituted 5-halo-thienoisothiazol-3(2H)-one 1,1-dioxides, a process for the preparation thereof, and pharmaceutical preparations containing these compounds | |
| EP0136736B1 (en) | 1-(4'-alkylthiophenyl)-2-amino-1,3-propanediol n-substituted derivatives | |
| US4031223A (en) | Trifluoromethylthio derivatives of cyproheptadine | |
| HK24194A (en) | Pyrrolo[1,2-a][4,1]benzoxazepines, process for their preparation, pharmaceutical compositions containing these compounds and therapeutical use | |
| AU600588B2 (en) | Naphthothiazepine derivatives and preparation thereof | |
| US4235895A (en) | Substituted 5H-dibenz[b,f]azepine | |
| NZ197392A (en) | 5-diazacycloalkyl-imidazo(2,1-b) (1,3,5)- benzothiadiazepines | |
| US5547961A (en) | Method of treatment of intestinal diseases | |
| JPS6036487A (ja) | スピロスクシンイミド誘導体 | |
| US5336679A (en) | Tetrahydroimidazopyridine derivatives and salts thereof | |
| US3294638A (en) | Method and compositions employing 2-alkyl-3-piperidinopyrazines | |
| EP0465191B1 (en) | Bicyclic sulfur-containing compounds | |
| US4639457A (en) | Benzocycloheptapyridone compounds for treating congestive heart failure |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| WAP | Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1) |