CA1268179C - Derives .beta.-carboline-3-oxadiazolyliques; methode de preparation et utilisation - Google Patents

Derives .beta.-carboline-3-oxadiazolyliques; methode de preparation et utilisation

Info

Publication number: CA1268179C
Authority: CA; Canada
Prior art keywords: compound; carboline; set forth; forth above; ethyl
Prior art date: 1984-05-15
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

Application number

CA486598

Other languages

English (en)

Inventor

Mogens Engelstoft

Tage Honore

Frank Watjen

Erling Niels Petersen

Andreas Huth

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bayer Pharma AG

Original Assignee

Schering AG

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.)

1984-05-15

Filing date

1985-05-14

Publication date

1990-04-25

1985-05-14 Application filed by Schering AG filed Critical Schering AG

1990-04-25 Application granted granted Critical

1990-04-25 Publication of CA1268179C publication Critical patent/CA1268179C/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 5
150000001875 compounds Chemical class 0.000 claims abstract description 45
125000000217 alkyl group Chemical group 0.000 claims description 14
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
239000000825 pharmaceutical preparation Substances 0.000 claims description 3
101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000001715 oxadiazolyl group Chemical group 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 2
229910017912 NH2OH Inorganic materials 0.000 claims 2
125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
125000000392 cycloalkenyl group Chemical group 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
230000000506 psychotropic effect Effects 0.000 abstract description 3
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
239000000203 mixture Substances 0.000 description 9
238000012360 testing method Methods 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
229960002200 flunitrazepam Drugs 0.000 description 6
238000003756 stirring Methods 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
-1 3-ethyl-1, 2, 4-oxadiazole-5-yl Chemical group 0.000 description 5
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
238000006073 displacement reaction Methods 0.000 description 4
239000000126 substance Substances 0.000 description 4
VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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239000011541 reaction mixture Substances 0.000 description 3
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FBAOVPVVMDOHPK-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfinyl)-1h-imidazole Chemical compound N=1C=CNC=1S(=O)C1=NC=CN1 FBAOVPVVMDOHPK-UHFFFAOYSA-N 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
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PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 2
230000027455 binding Effects 0.000 description 2
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239000012043 crude product Substances 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
239000008101 lactose Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000003345 scintillation counting Methods 0.000 description 2
230000009870 specific binding Effects 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
239000008096 xylene Substances 0.000 description 2
RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
ZVAPWJGRRUHKGP-UHFFFAOYSA-N 1h-1,5-benzodiazepine Chemical class N1C=CC=NC2=CC=CC=C12 ZVAPWJGRRUHKGP-UHFFFAOYSA-N 0.000 description 1
BPMFPOGUJAAYHL-UHFFFAOYSA-N 9H-Pyrido[2,3-b]indole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=N1 BPMFPOGUJAAYHL-UHFFFAOYSA-N 0.000 description 1
229920000856 Amylose Polymers 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
241000448280 Elates Species 0.000 description 1
239000001828 Gelatine Substances 0.000 description 1
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 1
239000007836 KH2PO4 Substances 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
235000003846 Ricinus Nutrition 0.000 description 1
241000322381 Ricinus <louse> Species 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
241000251539 Vertebrata <Metazoa> Species 0.000 description 1
239000002253 acid Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
239000012752 auxiliary agent Substances 0.000 description 1
229940049706 benzodiazepine Drugs 0.000 description 1
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
229960003529 diazepam Drugs 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
239000008298 dragée Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000009472 formulation Methods 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
RLZPCFQNZGINRP-UHFFFAOYSA-N n'-hydroxypropanimidamide Chemical compound CCC(N)=NO RLZPCFQNZGINRP-UHFFFAOYSA-N 0.000 description 1
239000003921 oil Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 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
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

CA486598 1984-05-15 1985-05-14 Derives .beta.-carboline-3-oxadiazolyliques; methode de preparation et utilisation Expired CA1268179C (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DK2400/84		1984-05-15

Publications (1)

Publication Number	Publication Date
CA1268179C true CA1268179C (fr)	1990-04-25

Publication	Publication Date	Title
US4507313A (en)	1985-03-26	Oxadiazolyl-imidazo-[1,4]benzodiazepines and their use in treatment of diseases of the central nervous system
US5656629A (en)	1997-08-12	6-substituted pyrazolo (3,4-d)pyrimidin-4-ones and compositions and methods of use thereof
US4886797A (en)	1989-12-12	Heterocyclic compounds and their preparation and use
IE58115B1 (en)	1993-07-14	New beta -carboline-3-oxadiazolyl derivatives,method of preparing the same and their use
EP0283162B1 (fr)	1993-08-11	Composés hétérocycliques, leur préparation et utilisation
CA1264748A (fr)	1990-01-23	Derives de .beta.-carboline-3-oxadiazolyl; preparation et utilisation
US5183822A (en)	1993-02-02	Substituted 3,4-annelated benzimidazol-2(1h)-ones
EP0226282B1 (fr)	1989-07-05	Composés hétérocycliques, leur préparation et leur utilisation
CA1269377A (fr)	1990-05-22	DERIVES DE SUBSTITUTION PHENOXYLES DE .beta.-CARBOLINE; PREPARATION ET UTILISATION COMME MEDICAMENTS
DK159150B (da)	1990-09-10	Isocyanomethylforbindelse samt fremgangsmaade til fremstilling af et oxadiazolimidazobenzodiazepinderivat
WO1997049708A1 (fr)	1997-12-31	Les benzazepines: des antagonistes tricycliques de la vasopressine
CA1268179C (fr)	1990-04-25	Derives .beta.-carboline-3-oxadiazolyliques; methode de preparation et utilisation
HU195814B (en)	1988-07-28	Process for the production of derivatives of tetrahydrobeta-carbolins and medical preparatives containing thereof
AU634736B2 (en)	1993-03-04	New annelated indole derivatives
US8541440B2 (en)	2013-09-24	Derivatives of 5-pyridinyl-1-azabicyclo[3.2.1]octane, preparation method thereof and use of same in therapeutics
US5198437A (en)	1993-03-30	1,7-annelated indolecarboxylic acid esters and amides
CA2074601A1 (fr)	1993-01-27	Derives pyrazole
CA2104267A1 (fr)	1994-03-03	Derives d'oxadiazolyl-1,6-naphthyridine
JPH05503082A (ja)	1993-05-27	イミダゾキノキサリン化合物、その製造及び使用
US20090088440A1 (en)	2009-04-02	Derivatives of 5-pyridazinyl-1-azabicyclo[3.2.1]octane, preparation method thereof and use of same in therapeutics
HU201759B (en)	1990-12-28	Process for producing new condensed diazepinones and pharmaceutical compositions comprising same
DK151964B (da)	1988-01-18	Beta-carbolin-3-carboxylsyrederivater og fremgangsmaade til fremstilling af samme samt farmaceutisk praeparat
HK1125929A (en)	2009-08-21	Novel diazabicyclic aryl derivatives and their medical use
DK151963B (da)	1988-01-18	Beta-carbolin-3-oxadiazolylderivater og farmaceutiske praeparater indeholdende disse
DK151809B (da)	1988-01-04	Analogifremgangsmaade til fremstilling af oxadiazolylimidazo-oe1,4aa-benzodiazepinderivater

CA1268179C - Derives .beta.-carboline-3-oxadiazolyliques; methode de preparation et utilisation - Google Patents

Info

Links

Applications Claiming Priority (1)

Publications (1)

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