HRP940980A2 - Epi-epidatidine derivatives - Google Patents

Epi-epidatidine derivatives Download PDF

Info

Publication number: HRP940980A2
Authority: HR; Croatia
Prior art keywords: general formula; lower alkyl; compound; compounds; mixture
Prior art date: 1993-12-09

Application number

HRP9303507A

Other languages

English (en)

Croatian (hr)

Inventor

Csaba Szantay

Zsuzsana Balogh

Istvan Moldvai

Eszter Temesvari

Attila Mandi

Gabor Blasko

Gyula Simig

Gyorgyi Lax

Sandor Drabant

Margit Csorgo

Maria Somogyi

Blanka Lady

Marton Fekete

Katalin Szemeredi

Istvan Gyertyan

Gabor Gigler

Tamas Szallasi

Original Assignee

Egyt Gyogyszervegyeszeti Gyar

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.)

1993-12-09

Filing date

1994-12-09

Publication date

1997-06-30

1993-12-09 Priority claimed from HU9303506A external-priority patent/HUT69382A/hu

1993-12-09 Priority claimed from HU9303507A external-priority patent/HUT69389A/hu

1994-12-09 Application filed by Egyt Gyogyszervegyeszeti Gyar filed Critical Egyt Gyogyszervegyeszeti Gyar

1997-06-30 Publication of HRP940980A2 publication Critical patent/HRP940980A2/hr

Links

150000001875 compounds Chemical class 0.000 claims description 148
239000000203 mixture Substances 0.000 claims description 104
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 66
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 43
150000003839 salts Chemical class 0.000 claims description 42
125000000217 alkyl group Chemical group 0.000 claims description 41
-1 hydroxy, phenoxy Chemical group 0.000 claims description 39
239000002253 acid Substances 0.000 claims description 37
238000000034 method Methods 0.000 claims description 24
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 16
229910052739 hydrogen Inorganic materials 0.000 claims description 16
238000006722 reduction reaction Methods 0.000 claims description 16
239000000825 pharmaceutical preparation Substances 0.000 claims description 15
125000003118 aryl group Chemical group 0.000 claims description 14
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 11
125000000304 alkynyl group Chemical group 0.000 claims description 11
125000001072 heteroaryl group Chemical group 0.000 claims description 11
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
230000000202 analgesic effect Effects 0.000 claims description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 9
239000003054 catalyst Substances 0.000 claims description 9
239000003638 chemical reducing agent Substances 0.000 claims description 9
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238000007363 ring formation reaction Methods 0.000 claims description 9
150000007513 acids Chemical class 0.000 claims description 8
230000010933 acylation Effects 0.000 claims description 8
238000005917 acylation reaction Methods 0.000 claims description 8
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125000002252 acyl group Chemical group 0.000 claims description 5
239000000010 aprotic solvent Substances 0.000 claims description 5
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 5
150000008282 halocarbons Chemical class 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
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HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
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125000005843 halogen group Chemical group 0.000 claims 2
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239000003937 drug carrier Substances 0.000 claims 1
238000010438 heat treatment Methods 0.000 claims 1
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238000004440 column chromatography Methods 0.000 description 30
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238000004587 chromatography analysis Methods 0.000 description 21
239000012044 organic layer Substances 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
239000002904 solvent Substances 0.000 description 20
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239000008346 aqueous phase Substances 0.000 description 18
239000000047 product Substances 0.000 description 18
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 18
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238000009835 boiling Methods 0.000 description 15
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XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
239000012279 sodium borohydride Substances 0.000 description 13
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WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
239000012043 crude product Substances 0.000 description 11
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235000019341 magnesium sulphate Nutrition 0.000 description 11
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238000002425 crystallisation Methods 0.000 description 9
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239000012359 Methanesulfonyl chloride Substances 0.000 description 8
125000004432 carbon atom Chemical group C* 0.000 description 8
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BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 8
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230000015572 biosynthetic process Effects 0.000 description 6
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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 6
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125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
HNBSRFNIRTUFTB-UHFFFAOYSA-N 5-nitropentan-2-one;triphenylphosphanium;bromide Chemical compound [Br-].CC(=O)CCC[N+]([O-])=O.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 HNBSRFNIRTUFTB-UHFFFAOYSA-N 0.000 description 1
UAWMVMPAYRWUFX-UHFFFAOYSA-N 6-Chloronicotinic acid Chemical compound OC(=O)C1=CC=C(Cl)N=C1 UAWMVMPAYRWUFX-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
NLPRAJRHRHZCQQ-UHFFFAOYSA-N Epibatidine Natural products C1=NC(Cl)=CC=C1C1C(N2)CCC2C1 NLPRAJRHRHZCQQ-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
RFMMMVDNIPUKGG-YFKPBYRVSA-N N-acetyl-L-glutamic acid Chemical compound CC(=O)N[C@H](C(O)=O)CCC(O)=O RFMMMVDNIPUKGG-YFKPBYRVSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229960004909 aminosalicylic acid Drugs 0.000 description 1
230000003042 antagnostic effect Effects 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000000872 buffer Substances 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
RCTFHBWTYQOVGJ-UHFFFAOYSA-N chloroform;dichloromethane Chemical compound ClCCl.ClC(Cl)Cl RCTFHBWTYQOVGJ-UHFFFAOYSA-N 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
238000005352 clarification Methods 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
239000012059 conventional drug carrier Substances 0.000 description 1
239000011549 crystallization solution Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
ZHGASCUQXLPSDT-UHFFFAOYSA-N cyclohexanesulfonic acid Chemical compound OS(=O)(=O)C1CCCCC1 ZHGASCUQXLPSDT-UHFFFAOYSA-N 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
KOGOBKOHQTZGIS-UHFFFAOYSA-N cyclohexyl methanesulfonate Chemical compound CS(=O)(=O)OC1CCCCC1 KOGOBKOHQTZGIS-UHFFFAOYSA-N 0.000 description 1
229960004132 diethyl ether Drugs 0.000 description 1
125000005805 dimethoxy phenyl group Chemical group 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
QDYBCIWLGJMJGO-UHFFFAOYSA-N dinitromethanone Chemical compound [O-][N+](=O)C(=O)[N+]([O-])=O QDYBCIWLGJMJGO-UHFFFAOYSA-N 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
230000001804 emulsifying effect Effects 0.000 description 1
NLPRAJRHRHZCQQ-IVZWLZJFSA-N epibatidine Chemical compound C1=NC(Cl)=CC=C1[C@@H]1[C@H](N2)CC[C@H]2C1 NLPRAJRHRHZCQQ-IVZWLZJFSA-N 0.000 description 1
238000006345 epimerization reaction Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
229940052303 ethers for general anesthesia Drugs 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
210000004744 fore-foot Anatomy 0.000 description 1
238000005194 fractionation Methods 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000000499 gel Substances 0.000 description 1
125000004446 heteroarylalkyl group Chemical group 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-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
125000005956 isoquinolyl group Chemical group 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
238000013421 nuclear magnetic resonance imaging Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
230000004526 pharmaceutical effect Effects 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000004151 quinonyl group Chemical group 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
238000012216 screening Methods 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000010972 statistical evaluation Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
229950000244 sulfanilic acid Drugs 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur 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
235000002906 tartaric acid Nutrition 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000009736 wetting Methods 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
- C07D487/08—Bridged 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
- A61P25/04—Centrally acting analgesics, e.g. opioids

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
Pain & Pain Management (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

HRP9303507A 1993-12-09 1994-12-09 Epi-epidatidine derivatives HRP940980A2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
HU9303506A HUT69382A (en)	1993-12-09	1993-12-09	7-azabicyclo [2.2.1]heptane derivatives and pharmaceutical compositions containing the same and process for the production thereof
HU9303507A HUT69389A (en)	1993-12-09	1993-12-09	Amino-ciklohexane-derivatives and process for their production

Publications (1)

Publication Number	Publication Date
HRP940980A2 true HRP940980A2 (en)	1997-06-30

Family

ID=26318171

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HRP9303507A HRP940980A2 (en)	1993-12-09	1994-12-09	Epi-epidatidine derivatives

Country Status (15)

Country	Link
EP (1)	EP0657455A1 (de)
JP (1)	JPH07291974A (de)
KR (1)	KR950017996A (de)
CN (1)	CN1112118A (de)
BE (1)	BE1008622A3 (de)
BG (1)	BG99253A (de)
CA (1)	CA2137611A1 (de)
CZ (1)	CZ308494A3 (de)
ES (1)	ES2095186B1 (de)
FR (1)	FR2713641B1 (de)
GR (1)	GR1002598B (de)
HR (1)	HRP940980A2 (de)
IT (1)	ITMI942483A1 (de)
PL (1)	PL306204A1 (de)
YU (1)	YU71994A (de)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE1008622A3 (fr) *	1993-12-09	1996-06-04	Egyt Gyogyszervegyeszeti Gyar	Derives de l'epi-epibatidine.
HUT69381A (en) *	1993-12-09	1995-09-28	Egyt Gyogyszervegyeszeti Gyar	Process for producing (2-chloro pyridyl)-7-azabicyclo [2.2.1.]heptane
CA2196979A1 (en) *	1994-08-25	1996-02-29	T. Y. Shen	7-azabicyclo¬2.2.1\|-heptane and -heptene derivatives as cholinergic receptor ligands
EP0955301A3 (de) *	1998-04-27	2001-04-18	Pfizer Products Inc.	7-Aza-bicyclo[2.2.1]-heptan Derivate, deren Herstellung und Verwendung aufgrund ihrer Affinität für neuronale nikotinische Acetylcholin Rezeptoren
CN101084211A (zh) *	2004-09-20	2007-12-05	泽农医药公司	杂环衍生物及其作为治疗剂的用途
US7884125B2 (en)	2008-04-30	2011-02-08	Universiteit Gent	Straightforward entry to 7-azabicyclo[2.2.1]heptane-1-carbonitriles and subsequent synthesis of epibatidine analogues
US8389561B2 (en)	2008-04-30	2013-03-05	Universiteit Gent	Substituted 7-azabicyclo[2.2.1]heptyl derivatives useful for making pharmaceutical compositions
US8809365B2 (en)	2009-11-04	2014-08-19	Universiteit Gent	1-substituted 2-azabicyclo [3.1.1] heptyl derivatives useful as nicotinic acetylcholine receptor modulators for treating neurologic disorders
CN101863892B (zh) *	2010-06-13	2012-05-09	华东理工大学	地棘蛙素及其类似物的制备方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0513174B1 (de) *	1990-02-02	1995-08-16	Schering Corporation	4,5-cycloalkano-3-benzazepin-7-ol-derivate und ihre verwendung
US5314899A (en) *	1992-03-03	1994-05-24	The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services	Epibatidine and derivatives, compositions and methods of treating pain
WO1994022868A1 (en) *	1993-04-01	1994-10-13	University Of Virginia	7-azabicyclo-[2.2.1]-heptane and -heptene derivatives as analgesics and anti-inflammatory agents
BE1008622A3 (fr) *	1993-12-09	1996-06-04	Egyt Gyogyszervegyeszeti Gyar	Derives de l'epi-epibatidine.
EP0664293A1 (de) *	1993-12-24	1995-07-26	Duphar International Research B.V	2-Phenyl-7-azabicycloheptane und 6-Phenyl-8-azabicyclo-octane

1994
- 1994-12-06 BE BE9401109A patent/BE1008622A3/fr not_active IP Right Cessation
- 1994-12-06 FR FR9414632A patent/FR2713641B1/fr not_active Expired - Fee Related
- 1994-12-07 CZ CZ943084A patent/CZ308494A3/cs unknown
- 1994-12-08 CA CA002137611A patent/CA2137611A1/en not_active Abandoned
- 1994-12-08 YU YU71994A patent/YU71994A/sh unknown
- 1994-12-09 ES ES09402520A patent/ES2095186B1/es not_active Expired - Lifetime
- 1994-12-09 GR GR940100548A patent/GR1002598B/el unknown
- 1994-12-09 EP EP94119481A patent/EP0657455A1/de not_active Withdrawn
- 1994-12-09 IT IT94MI002483A patent/ITMI942483A1/it unknown
- 1994-12-09 HR HRP9303507A patent/HRP940980A2/hr not_active Application Discontinuation
- 1994-12-09 KR KR1019940033414A patent/KR950017996A/ko not_active Withdrawn
- 1994-12-09 JP JP6306738A patent/JPH07291974A/ja active Pending
- 1994-12-09 CN CN94119383A patent/CN1112118A/zh active Pending
- 1994-12-09 BG BG99253A patent/BG99253A/bg unknown
- 1994-12-09 PL PL94306204A patent/PL306204A1/xx unknown

Also Published As

Publication number	Publication date
ITMI942483A0 (it)	1994-12-09
GR1002598B (el)	1997-02-12
CZ308494A3 (en)	1995-07-12
PL306204A1 (en)	1995-06-12
FR2713641B1 (fr)	1997-04-11
BE1008622A3 (fr)	1996-06-04
FR2713641A1 (fr)	1995-06-16
ES2095186A1 (es)	1997-02-01
EP0657455A1 (de)	1995-06-14
CA2137611A1 (en)	1995-06-10
YU71994A (sh)	1997-12-05
CN1112118A (zh)	1995-11-22
ITMI942483A1 (it)	1995-06-09
BG99253A (en)	1995-09-29
JPH07291974A (ja)	1995-11-07
KR950017996A (ko)	1995-07-22
ES2095186B1 (es)	1997-09-01

Legal Events

Date	Code	Title	Description
1997-06-30	A1OB	Publication of a patent application
1998-04-16	ODBC	Application rejected

Publication	Publication Date	Title
Evans et al.	1992	Orally active, nonpeptide oxytocin antagonists
Campiani et al.	1993	A palladium-catalyzed route to huperzine A and its analogs and their anticholinesterase activity
DE60109960T2 (de)	2006-02-16	8-substituierte 2,6-methano-3-benzazocine und 3-substituierte morphinane als opioidrezeptorbindende agenzien
DE69125099T2 (de)	1997-06-19	Indolderivate
DE60016566T2 (de)	2005-12-15	Triazolopyridazinderivate als liganden für gaba-rezeptoren
SK15612002A3 (sk)	2003-04-01	Azabicyklické karbamáty, spôsob ich prípravy a farmaceutické prostriedky, ktoré ich obsahujú ako účinné látky
FR2786769A1 (fr)	2000-06-09	Derives de 2,5-diazabicyclo[2.2.1]heptane, leur preparation et leur application en therapeutique
US4929614A (en)	1990-05-29	Benzodiazepines, process and intermediates for the preparation thereof and their application in therapy
CA2519372A1 (en)	2004-09-30	Substituted cyclohexyl and piperidinyl derivates as melanocortin-4 receptor modulators
CH637956A5 (de)	1983-08-31	In 11-stellung substituierte 5,11-dihydro-6h-pyrido-(2,3-b)(1,4)benzodiazepin-6-one, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel.
US5639751A (en)	1997-06-17	N-acyl-2,3-benzodiazepine derivatives for treating acute and chronic neurodegenerative disorders
DE69914594T2 (de)	2004-12-09	Aryl-annellierte azapolycyclische verbindungen
WO1997030983A1 (en)	1997-08-28	Tetrahydro-n,n-dimethyl-2,2-diphenyl-3-feranemethanamine, its enantiomers, and their pharmaceutically acceptable acid addition salts
HRP940980A2 (en)	1997-06-30	Epi-epidatidine derivatives
DE69011547T2 (de)	1995-03-09	1,2-Ethandiolderivate und ihre Salze, Verfahren zu ihrer Herstellung und sie enthaltende gehirnfunktionsverbessernde Mittel.
US5521174A (en)	1996-05-28	N-acyl-2,3-benzodiazepine derivatives and a method of treating spasms of the skeletal musculature therewith
DE69420310T2 (de)	2000-04-13	Substituierte Pyrrole
Chorev et al.	1984	Retro-inverso isomerization of peptides: side reactions in the synthesis of N, N'-diacyl-1, 1-diamino-2-phenylethane derivatives
Awaya et al.	1984	Racemic and optically active 2, 9-dimethyl-5-(m-hydroxyphenyl) morphans and pharmacological comparison with the 9-demethyl homologs
EP0326106B1 (de)	1994-07-27	Alkylen-diamine
WO2004081005A1 (en)	2004-09-23	Melanin-concentrating hormone receptor antagonists and compositions and methods related thereto
PL154813B1 (en)	1991-09-30	Method of obtaining s enantiomeric derivatives of glutar amide
PL191091B1 (pl)	2006-03-31	Nowe związki indanolowe, zawierające je kompozycje farmaceutyczne oraz ich zastosowanie
JP4110579B2 (ja)	2008-07-02	インドロモルヒナン誘導体および脳障害治療・予防剤
JPH0142952B2 (de)	1989-09-18