NO309936B1 - 2,7-Substituerte oktahydro-pyrrol[1,2-a]pyrazin-derivater, anvendelse derav, farmasøytisk preparat, samt mellomprodukter for fremstilling av derivatene - Google Patents

2,7-Substituerte oktahydro-pyrrol[1,2-a]pyrazin-derivater, anvendelse derav, farmasøytisk preparat, samt mellomprodukter for fremstilling av derivatene Download PDF

Info

Publication number: NO309936B1
Authority: NO; Norway
Prior art keywords: octahydro; pyrazine; pyrrole; compound; pharmaceutically acceptable
Prior art date: 1995-12-21

Application number

NO982843A

Other languages

English (en)

Norwegian (no)

Other versions

NO982843L (no

NO982843D0 (no

Inventor

Mark A Sanner

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.)

1995-12-21

Filing date

1998-06-19

Publication date

2001-04-23

1998-06-19 Application filed by Pfizer filed Critical Pfizer

1998-06-19 Publication of NO982843L publication Critical patent/NO982843L/no

1998-06-19 Publication of NO982843D0 publication Critical patent/NO982843D0/no

2001-04-23 Publication of NO309936B1 publication Critical patent/NO309936B1/no

Links

GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical class CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 title claims description 126
238000002360 preparation method Methods 0.000 title claims description 44
239000000825 pharmaceutical preparation Substances 0.000 title claims description 7
239000012450 pharmaceutical intermediate Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 219
-1 -COOR 4 Chemical group 0.000 claims description 57
150000003839 salts Chemical class 0.000 claims description 53
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 48
229960003638 dopamine Drugs 0.000 claims description 24
238000011282 treatment Methods 0.000 claims description 23
238000004519 manufacturing process Methods 0.000 claims description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
208000035475 disorder Diseases 0.000 claims description 17
125000000217 alkyl group Chemical group 0.000 claims description 15
208000028017 Psychotic disease Diseases 0.000 claims description 12
125000004802 cyanophenyl group Chemical group 0.000 claims description 12
125000004212 difluorophenyl group Chemical group 0.000 claims description 12
125000001207 fluorophenyl group Chemical group 0.000 claims description 12
239000000126 substance Substances 0.000 claims description 11
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
230000000694 effects Effects 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
208000016285 Movement disease Diseases 0.000 claims description 8
239000000460 chlorine Substances 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
201000000980 schizophrenia Diseases 0.000 claims description 8
208000019116 sleep disease Diseases 0.000 claims description 8
201000009032 substance abuse Diseases 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 8
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
206010020772 Hypertension Diseases 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
239000011737 fluorine Substances 0.000 claims description 7
239000000543 intermediate Substances 0.000 claims description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
206010007559 Cardiac failure congestive Diseases 0.000 claims description 6
206010019280 Heart failures Diseases 0.000 claims description 6
241000124008 Mammalia Species 0.000 claims description 6
206010028813 Nausea Diseases 0.000 claims description 6
201000005625 Neuroleptic malignant syndrome Diseases 0.000 claims description 6
208000018737 Parkinson disease Diseases 0.000 claims description 6
206010043118 Tardive Dyskinesia Diseases 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
230000008693 nausea Effects 0.000 claims description 6
208000017194 Affective disease Diseases 0.000 claims description 5
208000024172 Cardiovascular disease Diseases 0.000 claims description 5
208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
208000023105 Huntington disease Diseases 0.000 claims description 4
208000022873 Ocular disease Diseases 0.000 claims description 4
208000000323 Tourette Syndrome Diseases 0.000 claims description 4
125000003545 alkoxy group Chemical group 0.000 claims description 4
230000027119 gastric acid secretion Effects 0.000 claims description 4
239000003176 neuroleptic agent Substances 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
231100000736 substance abuse Toxicity 0.000 claims description 4
208000011117 substance-related disease Diseases 0.000 claims description 4
230000002792 vascular Effects 0.000 claims description 4
208000019553 vascular disease Diseases 0.000 claims description 4
201000010099 disease Diseases 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
230000002265 prevention Effects 0.000 claims description 3
125000003373 pyrazinyl group Chemical group 0.000 claims description 2
125000002098 pyridazinyl group Chemical group 0.000 claims description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 122
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 70
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 69
239000000243 solution Substances 0.000 description 61
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 56
239000000203 mixture Substances 0.000 description 56
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 51
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YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
238000006243 chemical reaction Methods 0.000 description 36
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239000000741 silica gel Substances 0.000 description 34
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
239000002904 solvent Substances 0.000 description 29
238000000034 method Methods 0.000 description 28
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
239000012074 organic phase Substances 0.000 description 24
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 24
239000002585 base Substances 0.000 description 23
229910000029 sodium carbonate Inorganic materials 0.000 description 22
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 19
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 19
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 16
239000012442 inert solvent Substances 0.000 description 16
239000002253 acid Substances 0.000 description 14
239000003638 chemical reducing agent Substances 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
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102000015554 Dopamine receptor Human genes 0.000 description 12
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 12
239000010410 layer Substances 0.000 description 12
239000012280 lithium aluminium hydride Substances 0.000 description 12
102000005962 receptors Human genes 0.000 description 12
108020003175 receptors Proteins 0.000 description 12
239000000706 filtrate Substances 0.000 description 11
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 10
150000004678 hydrides Chemical class 0.000 description 10
239000012312 sodium hydride Substances 0.000 description 10
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239000003446 ligand Substances 0.000 description 9
239000002798 polar solvent Substances 0.000 description 9
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 8
239000007900 aqueous suspension Substances 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
229910000510 noble metal Inorganic materials 0.000 description 8
108090000357 Dopamine D4 receptors Proteins 0.000 description 7
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WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 7
230000006870 function Effects 0.000 description 7
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239000002244 precipitate Substances 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
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KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 6
AGYUQBNABXVWMS-UHFFFAOYSA-N 2-chloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1 AGYUQBNABXVWMS-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
206010012335 Dependence Diseases 0.000 description 6
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JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
125000004391 aryl sulfonyl group Chemical group 0.000 description 6
230000027455 binding Effects 0.000 description 6
239000004533 oil dispersion Substances 0.000 description 6
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 5
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AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
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125000004433 nitrogen atom Chemical group N* 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000008183 oral pharmaceutical preparation Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
229940014662 pantothenate Drugs 0.000 description 1
235000019161 pantothenic acid Nutrition 0.000 description 1
239000011713 pantothenic acid Substances 0.000 description 1
239000006072 paste Substances 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
125000005544 phthalimido group Chemical group 0.000 description 1
239000000049 pigment Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
239000012264 purified product Substances 0.000 description 1
150000003233 pyrroles Chemical class 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000036647 reaction Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
230000000698 schizophrenic effect Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
230000009329 sexual behaviour Effects 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
230000007958 sleep Effects 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
229960001790 sodium citrate Drugs 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 1
239000004324 sodium propionate Substances 0.000 description 1
235000010334 sodium propionate Nutrition 0.000 description 1
229960003212 sodium propionate Drugs 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000012360 testing method Methods 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
210000001519 tissue Anatomy 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
230000009466 transformation Effects 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1

Classifications

- 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
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Addiction (AREA)
Anesthesiology (AREA)
Ophthalmology & Optometry (AREA)
Psychology (AREA)
Toxicology (AREA)
Otolaryngology (AREA)
Nutrition Science (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO982843A 1995-12-21 1998-06-19 2,7-Substituerte oktahydro-pyrrol[1,2-a]pyrazin-derivater, anvendelse derav, farmasøytisk preparat, samt mellomprodukter for fremstilling av derivatene NO309936B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US898895P	1995-12-21	1995-12-21
PCT/IB1996/001192 WO1997023482A1 (en)	1995-12-21	1996-11-06	2,7-substituted octahydro-pyrrolo[1,2-a]pyrazine derivatives

Publications (3)

Publication Number	Publication Date
NO982843L NO982843L (no)	1998-06-19
NO982843D0 NO982843D0 (no)	1998-06-19
NO309936B1 true NO309936B1 (no)	2001-04-23

Family

ID=21734893

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO982843A NO309936B1 (no)	1995-12-21	1998-06-19	2,7-Substituerte oktahydro-pyrrol[1,2-a]pyrazin-derivater, anvendelse derav, farmasøytisk preparat, samt mellomprodukter for fremstilling av derivatene

Country Status (33)

Country	Link
US (1)	US5714487A (el)
EP (1)	EP0874849B1 (el)
JP (1)	JP3204456B2 (el)
KR (1)	KR100286786B1 (el)
CN (1)	CN1061350C (el)
AR (1)	AR005102A1 (el)
AT (1)	ATE205846T1 (el)
AU (1)	AU704578B2 (el)
BR (1)	BR9612246A (el)
CA (1)	CA2240594C (el)
CO (1)	CO4480107A1 (el)
CZ (1)	CZ192998A3 (el)
DE (1)	DE69615404T2 (el)
DK (1)	DK0874849T3 (el)
ES (1)	ES2161377T3 (el)
GR (1)	GR3037060T3 (el)
GT (1)	GT199600101A (el)
HU (1)	HUP9900611A3 (el)
IL (1)	IL124453A0 (el)
MA (1)	MA26413A1 (el)
MX (1)	MX9805088A (el)
NO (1)	NO309936B1 (el)
NZ (1)	NZ320537A (el)
PE (1)	PE25998A1 (el)
PL (1)	PL327539A1 (el)
PT (1)	PT874849E (el)
RU (1)	RU2162470C2 (el)
SI (1)	SI0874849T1 (el)
TN (1)	TNSN96164A1 (el)
TR (1)	TR199801161T2 (el)
TW (1)	TW479058B (el)
WO (1)	WO1997023482A1 (el)
ZA (1)	ZA9610781B (el)

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US6281216B1 (en) *	1998-02-09	2001-08-28	Duphar International Research B.V.	2-aminoquinoline derivatives having d4-agonistic activity
EP0982030A3 (en)	1998-08-17	2000-05-10	Pfizer Products Inc.	2,7-substituted octahydro-pyrrolo 1,2-a]pyrazine derivatives as 5ht 1a ligands
IL144670A0 (en) *	1999-02-05	2002-05-23	Upjohn Co	Process to prepare (5r) - (methylamino) -5,6-dihydro-4h-imidazo [4,5,1-ij]-quinolin-2 (1h) -one
DE60011858T2 (de)	1999-09-10	2005-08-25	Mitsubishi Jidosha Kogyo K.K.	Stufenloses Getriebe
US7253165B2 (en)	1999-09-14	2007-08-07	Aventis Pharmaceuticals Inc.	Benzisoxazolyl-, pyridoisoxazolyl-and benzthienyl-phenoxy derivatives useful as D4 antagonists
ATE247110T1 (de) *	1999-09-14	2003-08-15	Aventis Pharma Inc	Benzisoxazolyl-, pyridoisoxazolyl- und benzthienyl-phenoxy derivate als d4 antagonisten
US7091199B1 (en)	1999-09-14	2006-08-15	Aventis Pharmaceuticals Inc.	Thienoisoxazole phenoxy unsubstituted ethyl and propyl derivatives useful as d4 antagonists
US7125903B1 (en)	1999-09-14	2006-10-24	Aventis Pharmaceuticals Inc.	Thienoisoxazolyl-and thienylpyrrazolyl-phenoxy substituted propyl derivatives useful as D4 antagonists
RU2322443C2 (ru) *	2001-09-19	2008-04-20	Мерк Патент Гмбх	Новое применение замещенных аминометилхроманов
TW200801005A (en) *	2005-08-15	2008-01-01	Astrazeneca Ab	Acetylenic piperazines as metabotropic glutamate receptor antagonists
US7728031B2 (en) *	2006-02-24	2010-06-01	Abbott Laboratories	Octahydro-pyrrolo[3,4-b]pyrrole derivatives
US8669255B2 (en) *	2011-09-29	2014-03-11	Abbvie Inc.	Substituted octahydropyrrolo[1,2-a]pyrazines as calcium channel blockers
WO2020051153A1 (en)	2018-09-04	2020-03-12	Pipeline Therapeutics, Inc.	Muscarinic acetylcholine m1 receptor antagonists
US11752149B2 (en)	2019-12-02	2023-09-12	Pipeline Therapeutics, Inc.	Muscarinic acetylcholine M1 receptor antagonists

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US4400511A (en) *	1982-05-07	1983-08-23	American Home Products Corporation	2-Substituted octahydropyrrolo(1,2-A)-pyrazine-3-carboxylic acids
WO1990008148A1 (en) *	1989-01-23	1990-07-26	Pfizer Inc.	Bis-aza-bicyclic anxiolytic agents
US5122515A (en) *	1990-06-19	1992-06-16	Smith Ross C	Nutrient composition containing dipeptides and method for administering the same
JP3058945B2 (ja) *	1990-10-26	2000-07-04	三共株式会社	Ｎ−（３，３−ジ置換アクリロイル）ピペラジン誘導体
CA2146018A1 (en) *	1992-10-23	1994-05-11	Paul David Leeson	Dopamine receptor subtype ligands
CA2146019A1 (en) *	1992-10-23	1994-05-11	Howard B. Broughton	Dopamine receptor subtype ligands
JP3004727B2 (ja) *	1994-08-05	2000-01-31	ファイザー・インコーポレーテッド	ドパミン作動性活性を有するベンゾイミダゾール誘導体
SI9520096A (sl) *	1994-09-30	1998-04-30	Pfizer Inc.	Derivati 2,7-substituiranega oktahidro-1H-pirido /1,2-a/ pirazina
US5576314A (en) *	1994-12-12	1996-11-19	Allelix Biopharmaceuticals Inc.	Bicyclic nonane and decane compounds having dopamine receptor affinity

1996
- 1996-11-06 BR BR9612246A patent/BR9612246A/pt not_active Application Discontinuation
- 1996-11-06 IL IL12445396A patent/IL124453A0/xx unknown
- 1996-11-06 CA CA002240594A patent/CA2240594C/en not_active Expired - Fee Related
- 1996-11-06 TR TR1998/01161T patent/TR199801161T2/xx unknown
- 1996-11-06 AT AT96935226T patent/ATE205846T1/de not_active IP Right Cessation
- 1996-11-06 JP JP52344697A patent/JP3204456B2/ja not_active Expired - Fee Related
- 1996-11-06 HU HU9900611A patent/HUP9900611A3/hu unknown
- 1996-11-06 CZ CZ981929A patent/CZ192998A3/cs unknown
- 1996-11-06 CN CN96199250A patent/CN1061350C/zh not_active Expired - Fee Related
- 1996-11-06 SI SI9630343T patent/SI0874849T1/xx unknown
- 1996-11-06 AU AU73280/96A patent/AU704578B2/en not_active Ceased
- 1996-11-06 NZ NZ320537A patent/NZ320537A/xx unknown
- 1996-11-06 RU RU98111742/04A patent/RU2162470C2/ru not_active IP Right Cessation
- 1996-11-06 DK DK96935226T patent/DK0874849T3/da active
- 1996-11-06 EP EP96935226A patent/EP0874849B1/en not_active Expired - Lifetime
- 1996-11-06 KR KR1019980704718A patent/KR100286786B1/ko not_active Expired - Fee Related
- 1996-11-06 DE DE69615404T patent/DE69615404T2/de not_active Expired - Fee Related
- 1996-11-06 PT PT96935226T patent/PT874849E/pt unknown
- 1996-11-06 WO PCT/IB1996/001192 patent/WO1997023482A1/en not_active Ceased
- 1996-11-06 ES ES96935226T patent/ES2161377T3/es not_active Expired - Lifetime
- 1996-11-06 PL PL96327539A patent/PL327539A1/xx unknown
- 1996-11-08 TW TW085113669A patent/TW479058B/zh not_active IP Right Cessation
- 1996-12-16 AR ARP960105715A patent/AR005102A1/es not_active Application Discontinuation
- 1996-12-16 PE PE1996000913A patent/PE25998A1/es not_active Application Discontinuation
- 1996-12-18 TN TNTNSN96164A patent/TNSN96164A1/fr unknown
- 1996-12-18 MA MA24432A patent/MA26413A1/fr unknown
- 1996-12-19 GT GT199600101A patent/GT199600101A/es unknown
- 1996-12-20 CO CO96066997A patent/CO4480107A1/es unknown
- 1996-12-20 ZA ZA9610781A patent/ZA9610781B/xx unknown
- 1996-12-23 US US08/774,290 patent/US5714487A/en not_active Expired - Fee Related
1998
- 1998-06-19 NO NO982843A patent/NO309936B1/no unknown
- 1998-06-22 MX MX9805088A patent/MX9805088A/es unknown
2001
- 2001-10-30 GR GR20010401932T patent/GR3037060T3/el not_active IP Right Cessation

Also Published As

Publication number	Publication date
KR100286786B1 (ko)	2001-04-16
NO982843L (no)	1998-06-19
KR19990076616A (ko)	1999-10-15
HUP9900611A2 (hu)	1999-08-30
NO982843D0 (no)	1998-06-19
WO1997023482A1 (en)	1997-07-03
TNSN96164A1 (fr)	2005-03-15
EP0874849A1 (en)	1998-11-04
DE69615404D1 (de)	2001-10-25
AR005102A1 (es)	1999-04-14
IL124453A0 (en)	1998-12-06
PE25998A1 (es)	1998-05-19
BR9612246A (pt)	1999-07-13
JPH11508920A (ja)	1999-08-03
US5714487A (en)	1998-02-03
JP3204456B2 (ja)	2001-09-04
CO4480107A1 (es)	1997-07-09
PT874849E (pt)	2002-01-30
GT199600101A (es)	1998-06-12
CA2240594C (en)	2001-07-24
CN1061350C (zh)	2001-01-31
SI0874849T1 (el)	2001-12-31
HUP9900611A3 (en)	2000-09-28
CN1205704A (zh)	1999-01-20
ES2161377T3 (es)	2001-12-01
MA26413A1 (fr)	2004-12-20
PL327539A1 (en)	1998-12-21
MX9805088A (es)	1998-10-31
AU7328096A (en)	1997-07-17
DK0874849T3 (da)	2001-11-19
NZ320537A (en)	1999-03-29
ZA9610781B (en)	1998-06-22
CA2240594A1 (en)	1997-07-03
EP0874849B1 (en)	2001-09-19
DE69615404T2 (de)	2002-06-06
GR3037060T3 (en)	2002-01-31
ATE205846T1 (de)	2001-10-15
AU704578B2 (en)	1999-04-29
TR199801161T2 (xx)	1998-10-21
RU2162470C2 (ru)	2001-01-27
CZ192998A3 (cs)	1999-05-12
TW479058B (en)	2002-03-11

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