DE3209534C2 - - Google Patents
Info
- Publication number
- DE3209534C2 DE3209534C2 DE3209534A DE3209534A DE3209534C2 DE 3209534 C2 DE3209534 C2 DE 3209534C2 DE 3209534 A DE3209534 A DE 3209534A DE 3209534 A DE3209534 A DE 3209534A DE 3209534 C2 DE3209534 C2 DE 3209534C2
- Authority
- DE
- Germany
- Prior art keywords
- formula
- azaspiro
- butyl
- compounds
- dione
- 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.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 12
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 239000002243 precursor Substances 0.000 claims description 6
- 238000006297 dehydration reaction Methods 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 230000018044 dehydration Effects 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 231100000252 nontoxic Toxicity 0.000 claims description 4
- 230000003000 nontoxic effect Effects 0.000 claims description 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical compound C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 claims description 3
- XPIWMQNQOHSVEG-UHFFFAOYSA-N 8-[4-[4-hydroxy-4-(2-methoxyphenyl)piperidin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione Chemical compound COC1=CC=CC=C1C1(O)CCN(CCCCN2C(CC3(CCCC3)CC2=O)=O)CC1 XPIWMQNQOHSVEG-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- BHLNCZXOZOWOMI-UHFFFAOYSA-N 8-[4-(4-phenyl-3,6-dihydro-2h-pyridin-1-yl)butyl]-8-azaspiro[4.5]decane-7,9-dione Chemical compound C1C(=O)N(CCCCN2CC=C(CC2)C=2C=CC=CC=2)C(=O)CC21CCCC2 BHLNCZXOZOWOMI-UHFFFAOYSA-N 0.000 claims 2
- VBUTZUWNFLDUSX-UHFFFAOYSA-N 8-[4-[4-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione Chemical compound C1=CC(Cl)=CC=C1C(CC1)=CCN1CCCCN1C(=O)CC2(CCCC2)CC1=O VBUTZUWNFLDUSX-UHFFFAOYSA-N 0.000 claims 2
- DCQXKOYNTMQDEB-UHFFFAOYSA-N 8-[4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCCN(C(C1)=O)C(=O)CC21CCCC2 DCQXKOYNTMQDEB-UHFFFAOYSA-N 0.000 claims 2
- WTVNFKVGGUWHQC-UHFFFAOYSA-N decane-2,4-dione Chemical compound CCCCCCC(=O)CC(C)=O WTVNFKVGGUWHQC-UHFFFAOYSA-N 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical group [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- -1 4-phenyl-1,2,3,6-tetrahydro pyridin-1-yl Chemical group 0.000 description 5
- QQCVFKSWYYHXMA-UHFFFAOYSA-N 8-(4-bromobutyl)-8-azaspiro[4.5]decane-7,9-dione Chemical compound C1C(=O)N(CCCCBr)C(=O)CC11CCCC1 QQCVFKSWYYHXMA-UHFFFAOYSA-N 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000701 neuroleptic effect Effects 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical class CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- KNCYXPMJDCCGSJ-UHFFFAOYSA-N piperidine-2,6-dione Chemical compound O=C1CCCC(=O)N1 KNCYXPMJDCCGSJ-UHFFFAOYSA-N 0.000 description 3
- 230000000506 psychotropic effect Effects 0.000 description 3
- 239000012429 reaction media Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 3
- 230000002936 tranquilizing effect Effects 0.000 description 3
- OMPXTQYWYRWWPH-UHFFFAOYSA-N 4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1NCCC(C=2C=CC=CC=2)=C1 OMPXTQYWYRWWPH-UHFFFAOYSA-N 0.000 description 2
- KQKFQBTWXOGINC-UHFFFAOYSA-N 4-phenylpiperidin-4-ol Chemical class C=1C=CC=CC=1C1(O)CCNCC1 KQKFQBTWXOGINC-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000000164 antipsychotic agent Substances 0.000 description 2
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 2
- 229960004046 apomorphine Drugs 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 229940125725 tranquilizer Drugs 0.000 description 2
- 239000003204 tranquilizing agent Substances 0.000 description 2
- 125000005943 1,2,3,6-tetrahydropyridyl group Chemical group 0.000 description 1
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- RQKOZXQKXHODOQ-UHFFFAOYSA-N 4-(2-methoxyphenyl)piperidin-4-ol Chemical compound COC1=CC=CC=C1C1(O)CCNCC1 RQKOZXQKXHODOQ-UHFFFAOYSA-N 0.000 description 1
- LZAYOZUFUAMFLD-UHFFFAOYSA-N 4-(4-chlorophenyl)-4-hydroxypiperidine Chemical compound C=1C=C(Cl)C=CC=1C1(O)CCNCC1 LZAYOZUFUAMFLD-UHFFFAOYSA-N 0.000 description 1
- VJUSRPDMTASJPL-UHFFFAOYSA-N 8-[4-(4-phenyl-3,6-dihydro-2h-pyridin-1-yl)butyl]-8-azaspiro[4.5]decane-7,9-dione;hydrochloride Chemical compound Cl.C1C(=O)N(CCCCN2CC=C(CC2)C=2C=CC=CC=2)C(=O)CC21CCCC2 VJUSRPDMTASJPL-UHFFFAOYSA-N 0.000 description 1
- XAEXIIFIUFOZIY-UHFFFAOYSA-N 8-[4-[4-(2-methoxyphenyl)-3,6-dihydro-2h-pyridin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione;hydrochloride Chemical compound Cl.COC1=CC=CC=C1C(CC1)=CCN1CCCCN1C(=O)CC2(CCCC2)CC1=O XAEXIIFIUFOZIY-UHFFFAOYSA-N 0.000 description 1
- GSZGGGNXBKDVTJ-UHFFFAOYSA-N 8-[4-[4-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione;hydrochloride Chemical compound Cl.C1=CC(Cl)=CC=C1C(CC1)=CCN1CCCCN1C(=O)CC2(CCCC2)CC1=O GSZGGGNXBKDVTJ-UHFFFAOYSA-N 0.000 description 1
- YXGRRIYIZLIVIW-UHFFFAOYSA-N 8-[4-[4-hydroxy-4-(2-methoxyphenyl)piperidin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione;hydrochloride Chemical compound Cl.COC1=CC=CC=C1C1(O)CCN(CCCCN2C(CC3(CCCC3)CC2=O)=O)CC1 YXGRRIYIZLIVIW-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- YRTHJMQKDCXPAY-UHFFFAOYSA-N azaspirodecanedione Chemical compound C1C(=O)NC(=O)CC11CCCC1 YRTHJMQKDCXPAY-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical compound CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 229940082150 encore Drugs 0.000 description 1
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- VANNPISTIUFMLH-UHFFFAOYSA-N glutaric anhydride Chemical class O=C1CCCC(=O)O1 VANNPISTIUFMLH-UHFFFAOYSA-N 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000012430 organic reaction media Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000005942 tetrahydropyridyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Anesthesiology (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/244,426 US4320131A (en) | 1981-03-16 | 1981-03-16 | N-[(4-Phenyl-1,2,3,6-tetrahydropyridin-1-yl)alkylene]azaspiroalkanediones and N-[(4-hydroxy-4-phenylpiperidin-1-yl)alkylene]azaspiroalkanediones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3209534A1 DE3209534A1 (de) | 1982-09-23 |
| DE3209534C2 true DE3209534C2 (en, 2012) | 1993-03-11 |
Family
ID=22922718
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19823209534 Granted DE3209534A1 (de) | 1981-03-16 | 1982-03-16 | Azaspiroalkandione, verfahren zu ihrer herstellung und pharmazeutische mittel, die diese verbindungen enthalten |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US4320131A (en, 2012) |
| JP (1) | JPS57165384A (en, 2012) |
| KR (1) | KR880001557B1 (en, 2012) |
| AT (1) | AT381939B (en, 2012) |
| AU (1) | AU535385B2 (en, 2012) |
| BE (1) | BE892502A (en, 2012) |
| CA (1) | CA1192556A (en, 2012) |
| CH (2) | CH657365A5 (en, 2012) |
| CY (1) | CY1372A (en, 2012) |
| DE (1) | DE3209534A1 (en, 2012) |
| DK (1) | DK161322C (en, 2012) |
| ES (1) | ES510448A0 (en, 2012) |
| FI (1) | FI71317C (en, 2012) |
| FR (1) | FR2501689B1 (en, 2012) |
| GB (1) | GB2094801B (en, 2012) |
| GR (1) | GR76113B (en, 2012) |
| HK (1) | HK4688A (en, 2012) |
| HU (2) | HU193379B (en, 2012) |
| IE (1) | IE52789B1 (en, 2012) |
| IL (1) | IL65254A0 (en, 2012) |
| IT (1) | IT1148145B (en, 2012) |
| KE (1) | KE3710A (en, 2012) |
| LU (1) | LU84012A1 (en, 2012) |
| NL (1) | NL8201022A (en, 2012) |
| NZ (1) | NZ199944A (en, 2012) |
| PH (1) | PH18182A (en, 2012) |
| PT (1) | PT74584B (en, 2012) |
| SE (2) | SE449100B (en, 2012) |
| SG (1) | SG30887G (en, 2012) |
| YU (1) | YU43789B (en, 2012) |
| ZA (1) | ZA821541B (en, 2012) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2660407B2 (ja) * | 1986-09-26 | 1997-10-08 | 住友製薬株式会社 | 新規なイミド誘導体 |
| US5153206A (en) * | 1988-12-02 | 1992-10-06 | Pfizer Inc. | Arylpiperidine derivatives |
| US5137894A (en) * | 1991-12-05 | 1992-08-11 | New James S | 4-(4-Piperidinyl-thieno[3,2-c]pyridine derivatives of n-alkylglutarimides |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US355877A (en) * | 1887-01-11 | Waltee n | ||
| FR3013E (fr) * | 1902-04-03 | 1904-08-12 | William Henry Hoyle | Perfectionnements au procédé et aux machines pour la fabrication de matières fibreuses connues sous le nom de fils "frottés" |
| US3106552A (en) * | 1960-07-19 | 1963-10-08 | Geschickter Fund Med Res | Nu-substituted azaspiranes and azaspirane-diones and processes for their preparation |
| US3432499A (en) * | 1965-04-02 | 1969-03-11 | Geschickter Fund Med Res | Trifluoromethylazaspiranes and azaspirane diones |
| US3398151A (en) * | 1966-02-01 | 1968-08-20 | Mead Johnson & Co | Azaspirodecanediones and azaspiroundecanediones |
| US3558777A (en) * | 1968-06-21 | 1971-01-26 | Mead Johnson & Co | Pharmacologic processes and compositions containing azaspirodecanediones and azaspiroundecanediones |
| BE759371A (fr) * | 1969-11-24 | 1971-05-24 | Bristol Myers Co | Azaspirodecanediones heterocycliques et procedes pour leur preparation |
| CH547802A (de) * | 1970-06-19 | 1974-04-11 | Hoffmann La Roche | Verfahren zur herstellung von tetrahydropyridinderivaten. |
| US3976776A (en) * | 1972-12-06 | 1976-08-24 | Mead Johnson & Company | Tranquilizer process employing N-(heteroarcyclic)piperazinylalkylazaspiroalkanediones |
| US4250175A (en) * | 1977-10-31 | 1981-02-10 | Mccall John M | Methods of treating psychosis |
| US4179510A (en) * | 1977-10-31 | 1979-12-18 | The Upjohn Company | Methods of treating psychosis |
| US4218456A (en) * | 1978-07-10 | 1980-08-19 | Warner-Lambert Company | 1-(4-Fluorophenyl)-4-(1,2,3,6-tetrahydro-4-phenoxy-1-pyridinyl)-butanones |
| US4261990A (en) * | 1979-03-09 | 1981-04-14 | Ciba-Geigy Corporation | N-alkyleneiminoalkyl-dicarboximides as antiallergics and antiasthmatics |
| US4221714A (en) * | 1979-08-03 | 1980-09-09 | American Cyanamid Company | 11-(1,2,3,6-Tetrahydro-substituted-4-pyridyl)-dibenz[b,f][1,4]oxazepines |
| US4305944A (en) * | 1980-09-08 | 1981-12-15 | Mead Johnson & Company | N-[(4-[3-cyano substituted pyridyl]piperazino)alkyl]-azaspirodecanediones |
-
1981
- 1981-03-16 US US06/244,426 patent/US4320131A/en not_active Expired - Fee Related
-
1982
- 1982-03-08 NZ NZ199944A patent/NZ199944A/en unknown
- 1982-03-09 ZA ZA821541A patent/ZA821541B/xx unknown
- 1982-03-11 FR FR8204101A patent/FR2501689B1/fr not_active Expired
- 1982-03-11 GR GR67561A patent/GR76113B/el unknown
- 1982-03-11 NL NL8201022A patent/NL8201022A/nl not_active Application Discontinuation
- 1982-03-12 AU AU81335/82A patent/AU535385B2/en not_active Ceased
- 1982-03-12 DK DK112682A patent/DK161322C/da not_active IP Right Cessation
- 1982-03-12 FI FI820855A patent/FI71317C/fi not_active IP Right Cessation
- 1982-03-15 IT IT47992/82A patent/IT1148145B/it active
- 1982-03-15 IL IL65254A patent/IL65254A0/xx not_active IP Right Cessation
- 1982-03-15 HU HU86477A patent/HU193379B/hu not_active IP Right Cessation
- 1982-03-15 HU HU82780A patent/HU190793B/hu not_active IP Right Cessation
- 1982-03-15 IE IE590/82A patent/IE52789B1/en not_active IP Right Cessation
- 1982-03-15 PH PH26997A patent/PH18182A/en unknown
- 1982-03-15 YU YU558/82A patent/YU43789B/xx unknown
- 1982-03-15 LU LU84012A patent/LU84012A1/fr unknown
- 1982-03-15 BE BE0/207573A patent/BE892502A/fr not_active IP Right Cessation
- 1982-03-15 CA CA000398330A patent/CA1192556A/en not_active Expired
- 1982-03-15 SE SE8201630A patent/SE449100B/sv not_active IP Right Cessation
- 1982-03-15 ES ES510448A patent/ES510448A0/es active Granted
- 1982-03-15 PT PT74584A patent/PT74584B/pt not_active IP Right Cessation
- 1982-03-16 CH CH4177/85A patent/CH657365A5/de not_active IP Right Cessation
- 1982-03-16 DE DE19823209534 patent/DE3209534A1/de active Granted
- 1982-03-16 AT AT0104682A patent/AT381939B/de not_active IP Right Cessation
- 1982-03-16 JP JP57040316A patent/JPS57165384A/ja active Granted
- 1982-03-16 GB GB8207580A patent/GB2094801B/en not_active Expired
- 1982-03-16 KR KR8201128A patent/KR880001557B1/ko not_active Expired
- 1982-03-16 CY CY137282A patent/CY1372A/en unknown
- 1982-03-16 CH CH1654/82A patent/CH652123A5/de not_active IP Right Cessation
- 1982-07-31 KE KE3710A patent/KE3710A/xx unknown
-
1986
- 1986-07-21 SE SE8603177A patent/SE460606B/sv not_active IP Right Cessation
-
1987
- 1987-03-27 SG SG308/87A patent/SG30887G/en unknown
-
1988
- 1988-01-21 HK HK46/88A patent/HK4688A/xx unknown
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Owner name: BRISTOL-MYERS SQUIBB CO. (N.D.GES.D.STAATES DELAWA |
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Representative=s name: KINZEBACH, W., DIPL.-CHEM. DR.PHIL. RIEDL, P., DIP |
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