IL98588A - Pharmaceutical preparations containing octahydro derivatives - 2 - [shafts) water (dinil [- 7 - converted - H1 - pyridines] a, 1,2 [pyrisines for the treatment of overdose and addiction to substances - Google Patents

Pharmaceutical preparations containing octahydro derivatives - 2 - [shafts) water (dinil [- 7 - converted - H1 - pyridines] a, 1,2 [pyrisines for the treatment of overdose and addiction to substances

Info

Publication number: IL98588A
Authority: IL; Israel
Prior art keywords: compound; composition; pyrido; calcd; hrms
Prior art date: 1990-06-29

Application number

IL9858891A

Other languages

English (en)

Hebrew (he)

Other versions

IL98588A0 (en

Original Assignee

Pfizer

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.)

1990-06-29

Filing date

1991-06-23

Publication date

1995-06-29

1991-06-23 Application filed by Pfizer filed Critical Pfizer

1992-07-15 Publication of IL98588A0 publication Critical patent/IL98588A0/xx

1995-06-29 Publication of IL98588A publication Critical patent/IL98588A/en

Links

201000009032 substance abuse Diseases 0.000 title claims abstract description 12
208000011117 substance-related disease Diseases 0.000 title claims description 20
231100000736 substance abuse Toxicity 0.000 title claims description 9
239000008194 pharmaceutical composition Substances 0.000 title claims description 5
MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 49
239000000203 mixture Substances 0.000 claims description 33
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
239000002253 acid Substances 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 6
241000124008 Mammalia Species 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
239000003814 drug Substances 0.000 claims description 4
101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 14
SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 abstract description 4
206010012335 Dependence Diseases 0.000 abstract description 4
229960002715 nicotine Drugs 0.000 abstract description 4
SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 abstract description 4
239000000126 substance Substances 0.000 abstract description 3
239000004081 narcotic agent Substances 0.000 abstract description 2
PJEAHOHAPYWSEB-UHFFFAOYSA-N 4h-pyrido[1,2-a]pyrazine Chemical class C1=CC=CN2CC=NC=C21 PJEAHOHAPYWSEB-UHFFFAOYSA-N 0.000 abstract 1
125000004122 cyclic group Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 83
239000000047 product Substances 0.000 description 52
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
238000002360 preparation method Methods 0.000 description 47
238000004809 thin layer chromatography Methods 0.000 description 44
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 43
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 41
238000000034 method Methods 0.000 description 38
-1 4, 4 -dimethylpiperidine- 2, 6-dion-l-yl Chemical group 0.000 description 35
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 19
238000006243 chemical reaction Methods 0.000 description 17
239000003921 oil Substances 0.000 description 17
229940093499 ethyl acetate Drugs 0.000 description 16
235000019439 ethyl acetate Nutrition 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000007787 solid Substances 0.000 description 15
239000000243 solution Substances 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
239000012258 stirred mixture Substances 0.000 description 12
239000013078 crystal Substances 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
101150041968 CDC13 gene Proteins 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
239000000284 extract Substances 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
239000002904 solvent Substances 0.000 description 8
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 8
GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical class CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
239000012071 phase Substances 0.000 description 6
229920006395 saturated elastomer Polymers 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
238000003756 stirring Methods 0.000 description 5
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
230000000694 effects Effects 0.000 description 4
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
230000008569 process Effects 0.000 description 4
229960002317 succinimide Drugs 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
239000008096 xylene Substances 0.000 description 4
150000003738 xylenes Chemical class 0.000 description 4
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
238000006073 displacement reaction Methods 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
239000010410 layer Substances 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
239000002002 slurry Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 description 2
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
206010013654 Drug abuse Diseases 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
230000009471 action Effects 0.000 description 2
238000010171 animal model Methods 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000010828 elution Methods 0.000 description 2
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 2
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000006260 foam Substances 0.000 description 2
238000007429 general method Methods 0.000 description 2
QOIGKGMMAGJZNZ-UHFFFAOYSA-N gepirone Chemical compound O=C1CC(C)(C)CC(=O)N1CCCCN1CCN(C=2N=CC=CN=2)CC1 QOIGKGMMAGJZNZ-UHFFFAOYSA-N 0.000 description 2
229960000647 gepirone Drugs 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
150000003949 imides Chemical class 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
239000000463 material Substances 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
239000000376 reactant Substances 0.000 description 2
238000010992 reflux Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
229940014800 succinic anhydride Drugs 0.000 description 2
238000000967 suction filtration Methods 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
TZJUVVIWVWFLCD-UHFFFAOYSA-N 1,1-dioxo-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-1,2-benzothiazol-3-one Chemical compound O=S1(=O)C2=CC=CC=C2C(=O)N1CCCCN(CC1)CCN1C1=NC=CC=N1 TZJUVVIWVWFLCD-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
UXWBIYCPUVWKHP-KBPBESRZSA-N 1-[[(7s,9as)-2-pyrimidin-2-yl-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-7-yl]methyl]pyrrolidine-2,5-dione Chemical compound O=C1CCC(=O)N1C[C@@H]1CN2CCN(C=3N=CC=CN=3)C[C@@H]2CC1 UXWBIYCPUVWKHP-KBPBESRZSA-N 0.000 description 1
ONHPOXROAPYCGT-UHFFFAOYSA-N 2,3,4,6,7,8,9,9a-octahydro-1h-pyrido[1,2-a]pyrazine Chemical compound C1CNCC2CCCCN21 ONHPOXROAPYCGT-UHFFFAOYSA-N 0.000 description 1
MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 1
IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
YUJCWMGBRDBPDL-UHFFFAOYSA-N 4,4-dimethylpiperidine-2,6-dione Chemical compound CC1(C)CC(=O)NC(=O)C1 YUJCWMGBRDBPDL-UHFFFAOYSA-N 0.000 description 1
GFWLMILMVMCJDI-UHFFFAOYSA-N 8-oxaspiro[4.5]decane-7,9-dione Chemical compound C1C(=O)OC(=O)CC11CCCC1 GFWLMILMVMCJDI-UHFFFAOYSA-N 0.000 description 1
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
206010020710 Hyperphagia Diseases 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
241000208125 Nicotiana Species 0.000 description 1
235000002637 Nicotiana tabacum Nutrition 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
241000700159 Rattus Species 0.000 description 1
241000906446 Theraps Species 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
159000000021 acetate salts Chemical class 0.000 description 1
PNDCJFQBXPVFGX-UYXJWNHNSA-N acetic acid;(2r,5s)-piperidine-2,5-dicarboxylic acid Chemical compound CC(O)=O.OC(=O)[C@H]1CC[C@H](C(O)=O)NC1 PNDCJFQBXPVFGX-UYXJWNHNSA-N 0.000 description 1
230000002411 adverse Effects 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
230000004075 alteration Effects 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
239000000935 antidepressant agent Substances 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
239000002249 anxiolytic agent Substances 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
239000002585 base Substances 0.000 description 1
239000003637 basic solution Substances 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000012267 brine Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 1
229960002495 buspirone Drugs 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
230000000994 depressogenic effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
TUGSJNQAIMFEDY-UHFFFAOYSA-N dimethyl pyridine-2,5-dicarboxylate Chemical compound COC(=O)C1=CC=C(C(=O)OC)N=C1 TUGSJNQAIMFEDY-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
230000003291 dopaminomimetic effect Effects 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000007689 inspection Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
229950003599 ipsapirone Drugs 0.000 description 1
OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 1
LVPMIMZXDYBCDF-UHFFFAOYSA-N isocinchomeronic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)N=C1 LVPMIMZXDYBCDF-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
238000003760 magnetic stirring Methods 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
229940043265 methyl isobutyl ketone Drugs 0.000 description 1
ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
208000008013 morphine dependence Diseases 0.000 description 1
DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 1
229960003086 naltrexone Drugs 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
229940127240 opiate Drugs 0.000 description 1
235000020830 overeating Nutrition 0.000 description 1
MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
229910003446 platinum oxide Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
229940001470 psychoactive drug Drugs 0.000 description 1
239000004089 psychotropic agent Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
150000003216 pyrazines Chemical class 0.000 description 1
238000011160 research Methods 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000000825 ultraviolet detection Methods 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Addiction (AREA)
Psychiatry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

IL9858891A 1990-06-29 1991-06-23 Pharmaceutical preparations containing octahydro derivatives - 2 - [shafts) water (dinil [- 7 - converted - H1 - pyridines] a, 1,2 [pyrisines for the treatment of overdose and addiction to substances IL98588A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
PCT/US1990/003708 WO1992000075A1 (fr)	1990-06-29	1990-06-29	Derives de pyridopyrazine utilises dans le traitement de l'abus et de la dependance de substances

Publications (2)

Publication Number	Publication Date
IL98588A0 IL98588A0 (en)	1992-07-15
IL98588A true IL98588A (en)	1995-06-29

Family

ID=22220931

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9858891A IL98588A (en)	1990-06-29	1991-06-23	Pharmaceutical preparations containing octahydro derivatives - 2 - [shafts) water (dinil [- 7 - converted - H1 - pyridines] a, 1,2 [pyrisines for the treatment of overdose and addiction to substances

Country Status (17)

Country	Link
US (1)	US5616585A (fr)
EP (1)	EP0536173B1 (fr)
JP (1)	JPH05507274A (fr)
KR (1)	KR930701171A (fr)
AT (1)	ATE116545T1 (fr)
AU (1)	AU651977B2 (fr)
CA (1)	CA2086335C (fr)
DE (1)	DE69106516T2 (fr)
DK (1)	DK0536173T3 (fr)
ES (1)	ES2066447T3 (fr)
HU (1)	HUT62797A (fr)
IE (1)	IE64467B1 (fr)
IL (1)	IL98588A (fr)
MY (1)	MY106553A (fr)
NZ (1)	NZ238750A (fr)
WO (2)	WO1992000075A1 (fr)
ZA (1)	ZA915012B (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6231833B1 (en)	1999-08-05	2001-05-15	Pfizer Inc	2,7-substituted octahydro-1H-pyrido[1,2-A]pyrazine derivatives as ligands for serotonin receptors
HN1999000146A (es) *	1998-09-21	2000-11-11	Pfizer Prod Inc	Agentes farmaceuticos para el tratamiento de la enfermedad de parkinson, adhd y microadenomas.
EP1177792A3 (fr) *	2000-07-27	2002-10-23	Pfizer Products Inc.	Ligands dopamine d4 destines au traitement des troubles associees a la cherche de la nouveaute
UA110688C2 (uk)	2012-09-21	2016-01-25	Пфайзер Інк.	Біциклічні піридинони
MX368391B (es)	2015-02-03	2019-09-30	Pfizer	Ciclopropabenzofuranil-piridopirazindionas novedosas.

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK144213C (da) *	1979-06-20	1982-06-21	H B Nielsen	Hylster til garnspole
US4777173A (en) *	1987-03-25	1988-10-11	Bristol-Myers Company	Method for treatment of alcohol abuse
DE3727879A1 (de) *	1987-08-21	1989-03-02	Troponwerke Gmbh & Co Kg	Verwendung von 2-pyrimidinyl-1-piperazin-derivaten
DE3736974A1 (de) *	1987-10-31	1989-05-11	Troponwerke Gmbh & Co Kg	Verwendung von 2-pyrimidinyl-1-piperazin-derivaten
IL91451A0 (en) *	1988-08-30	1990-04-29	Bristol Myers Co	Pharmaceutical compositions comprising azapiron compounds and their use in the treatment of addiction
WO1990008148A1 (fr) *	1989-01-23	1990-07-26	Pfizer Inc.	Agents anxiolytiques bis-aza-bicycliques

1990
- 1990-06-29 WO PCT/US1990/003708 patent/WO1992000075A1/fr not_active Ceased
1991
- 1991-05-28 DE DE69106516T patent/DE69106516T2/de not_active Expired - Fee Related
- 1991-05-28 HU HU924138D patent/HUT62797A/hu unknown
- 1991-05-28 EP EP91910566A patent/EP0536173B1/fr not_active Expired - Lifetime
- 1991-05-28 DK DK91910566.8T patent/DK0536173T3/da active
- 1991-05-28 AT AT91910566T patent/ATE116545T1/de not_active IP Right Cessation
- 1991-05-28 AU AU79094/91A patent/AU651977B2/en not_active Ceased
- 1991-05-28 CA CA002086335A patent/CA2086335C/fr not_active Expired - Fee Related
- 1991-05-28 ES ES91910566T patent/ES2066447T3/es not_active Expired - Lifetime
- 1991-05-28 WO PCT/US1991/003749 patent/WO1992000074A2/fr not_active Ceased
- 1991-05-28 JP JP91510300A patent/JPH05507274A/ja active Pending
- 1991-06-23 IL IL9858891A patent/IL98588A/en not_active IP Right Cessation
- 1991-06-27 NZ NZ238750A patent/NZ238750A/xx not_active IP Right Cessation
- 1991-06-28 MY MYPI91001174A patent/MY106553A/en unknown
- 1991-06-28 ZA ZA915012A patent/ZA915012B/xx unknown
- 1991-06-28 IE IE225991A patent/IE64467B1/en not_active IP Right Cessation
1992
- 1992-12-28 KR KR1019920703374A patent/KR930701171A/ko not_active Ceased
1995
- 1995-01-25 US US08/377,874 patent/US5616585A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
WO1992000074A3 (fr)	1992-03-05
AU651977B2 (en)	1994-08-11
IE912259A1 (en)	1992-01-01
CA2086335A1 (fr)	1991-12-30
KR930701171A (ko)	1993-06-11
EP0536173B1 (fr)	1995-01-04
JPH05507274A (ja)	1993-10-21
NZ238750A (en)	1999-09-29
IE64467B1 (en)	1995-08-09
ATE116545T1 (de)	1995-01-15
DE69106516D1 (de)	1995-02-16
IL98588A0 (en)	1992-07-15
CA2086335C (fr)	1996-01-02
ZA915012B (en)	1993-02-24
MY106553A (en)	1995-06-30
US5616585A (en)	1997-04-01
DE69106516T2 (de)	1995-05-11
HUT62797A (en)	1993-06-28
DK0536173T3 (da)	1995-05-01
WO1992000075A1 (fr)	1992-01-09
EP0536173A1 (fr)	1993-04-14
WO1992000074A2 (fr)	1992-01-09
AU7909491A (en)	1992-01-23
HU9204138D0 (en)	1993-04-28
ES2066447T3 (es)	1995-03-01

Legal Events

Date	Code	Title
1997-11-20	KB	Patent renewed
2001-07-24	KB	Patent renewed
2006-03-12	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
EP0380217B1 (fr)	1992-11-19	Agents bis-aza-bicycliques anxiolytiques et antidépresseurs
JPH07504676A (ja)	1995-05-25	ホスホジエステラーゼ阻害因子としてのピリド［２，３−ｄ］ピリミジン誘導体類
JPH11501925A (ja)	1999-02-16	置換Ｎ−アリールメチルおよびヘテロシクリルメチル−１Ｈ−ピラゾロ〔３，４−ｂ〕キノリン−４−アミン並びにそれらを含有する組成物
CN102712589A (zh)	2012-10-03	作为醛固酮合酶抑制剂的芳基-吡啶衍生物
AU2023248084B2 (en)	2025-06-19	Compounds
US6150524A (en)	2000-11-21	Morphine derivatives with analgesic activity
KR100262762B1 (ko)	2000-08-01	중추신경계 질환의 치료에 유용한 3-옥소-피리도(1,2-알파)벤즈이미다졸-4-카복실 및 4-옥소-아제디노(1,2-알파)벤즈이미다졸-5-카복실 유도체
US5616585A (en)	1997-04-01	Pyridopyrazine derivatives for treating alcohol and nicotine abuse and addiction
EP0222474B1 (fr)	1990-10-03	Gamma-carbolines
JP2001501949A (ja)	2001-02-13	中枢神経系疾患を処置することに有用な５―ヘテロ原子を含有するアルキル置換された―３―オキソ―ピリド（１，２―ａ）ベンゾイミダゾール―４―カルボキサミド誘導体
HU190448B (en)	1986-09-29	Process for preparing 11h-pyrido /2,3-b/ /1,4/ benzodiazepine-derivatives
EP0220282A1 (fr)	1987-05-06	Derives de pyrimidine ayant une activite antiallergique, anti-inflammatoire et immunosuppressive
WO1993024501A1 (fr)	1993-12-09	Composes heterocycliques contenant du phosphore, utilises comme antagonistes d'angiotensines
WO1993024487A1 (fr)	1993-12-09	Composes heterocycliques contenant de l'azote utiles comme antagonistes de l'angiotensine ii
JP2001131153A (ja)	2001-05-15	ジヒドロキノリン誘導体