DK1731511T3 - Bicykliske heterocykliske strukturer, lægemidler indeholdende disse forbindelser, anvendelse deraf og fremgangsmåde til fremstilling deraf - Google Patents

Bicykliske heterocykliske strukturer, lægemidler indeholdende disse forbindelser, anvendelse deraf og fremgangsmåde til fremstilling deraf Download PDF

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DK1731511T3
DK1731511T3 DK06116986.8T DK06116986T DK1731511T3 DK 1731511 T3 DK1731511 T3 DK 1731511T3 DK 06116986 T DK06116986 T DK 06116986T DK 1731511 T3 DK1731511 T3 DK 1731511T3
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amino
quinazoline
oxo
fluorophenyl
chloro
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Frank Himmelsbach
Elke Langkopf
Birgit Jung
Anke Baum
Flavio Solca
Thomas Metz
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Boehringer Ingelheim Pharma
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/94—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Gastroenterology & Hepatology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Claims (7)

1. Bicykliske heterocykliske strukturer ifølge den generelle formel
, (I) hvor Ra repræsenterer et hydrogenatom, Rb repræsenterer en 1-phenylethylgruppe eller en phenylgruppe, hvor phenylkernen er substitueret med resterne Ri og R2, hvor Ri og R2, som kan være ens eller forskellige, hhv. repræsenterer et hydrogen-, fluor-, chlor- eller bromatom, X betyder et nitrogenatom, A betyder en iminogruppe, B betyder en carbonylgruppe, C betyder en 1,2-vinylen- eller ethinylengruppe, D betyder en methylengruppe, E betyder en dimethylamino-, diethylamino-, bis-(2-methoxy-ethyl)-amino-, N-methyl-N-(2-methoxy-ethyl)-amino-, N-ethyl-N-(2-methoxy-ethyl)-amino-, N-methyl-N-cyklopropyl-amino-, N-methyl-N-cyklopropylmethyl-amino-, N-methyl-N-(l-methoxy-2-propyl)-amino-, N-methyl-N-(2-methoxy-propyl)-amino- eller N-methyl-N-(3-methoxy-propyl)-amino-gruppe, en pyrrolidino-, piperidino- eller morpholinogruppe, som eventuelt er substitueret med én eller to methylgrupper, og Rc betyder en cyklopropylmethoxy-, cyklobutyloxy- eller cyklopentyloxygruppe, en tetrahydrofuran-3-yloxy-, tetrahydropyran-4-yloxy- eller tetrahydrofuran-2-ylmethoxygruppe, tautomere, stereoisomere og salte deraf.
2. Følgende forbindelse ifølge den generelle formel I ifølge krav 1: (1) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(N,N-diethylamino)-l-oxo-2-buten-l-yl]amino}-7-cyklopropylmethoxy-quinazolin, (2) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(morpholin-4-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklopropylmethoxy-quinazolin, (3) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(2,6-dimethyl-morpholin-4-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklopropylmethoxy-quinazolin, (4) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(dimethylamino)-l-oxo-2-buten-l-yl]amino}-7-cyklopropylmethoxy-quinazolin, (5) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(morpholin-4-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklobutyloxy-quinazolin, (6) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(morpholin-4-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklopentyloxy-quinazolin, (7) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(diethylamino)-l-oxo-2-buten-l-yl]amino>-7-cyklobutyloxy-quinazolin, (8) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(diethylamino)-l-oxo-2-buten-l-yl]amino>-7-cyklopentyloxy-quinazolin, (9) 4-[(R)-(l-phenyl-ethyl)amino]-6-{[4-(morpholin-4-yl)-l-oxo-2-buten-l-yl]amino>-7-cyklobutyloxy-quinazolin, (10) 4-[(R)-(l-phenyl-ethyl)amino]-6-{[4-(morpholin-4-yl)-l-oxo-2-buten-l-yl]amino>-7-cyklopropylmethoxy-quinazolin, (11) 4-[(R)-(l-phenyl-ethyl)anninol-6-{[4-(morpholin-4-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklopentyloxy-quinazolin, (12) 4-[(R)-(l-phenyl-ethyl)amino]-6-{[4-(diethylannino)-l-oxo-2-buten-l-yl]amino}-7-cyklobutyloxy-quinazolin, (13) 4-[(R)-(l-phenyl-ethyl)amino]-6-{[4-(diethylannino)-l-oxo-2-buten-l-yl]amino>-7-cyklopentyloxy-quinazolin, (14) 4-[(R)-(l-phenyl-ethyl)amino]-6-{[4-(diethylamino)-l-oxo-2-buten-l-yl]amino}-7-cyklopropylmethoxy-quinazolin, (15) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[bis-(2-methoxy-ethyl)-amino]-l-oxo-2-buten-l-yl>amino)-7-cyklopropylmethoxy-quinazolin, (16) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-ethyl-N-(2-methoxyethyl)-amino]-l-oxo-2-buten-l-yl>amino)-7-cyklopropyl-methoxy-quinazolin, (17) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(piperidin-l-yl)-l-oxo-2-buten-l-yl]amino>-7-cyklopropylmethoxy-quinazolin, (18) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(2-methyl-piperidin-l-yl)-l-oxo-2-buten-l-yl]amino>-7-cyklopropylmethoxy-quinazolin, (19) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(pyrrolidin-l-yl) - l-oxo-2-buten-l-yl]amino>-7-cyklopropylmethoxy-quinazolin, (20) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(2-methyl-pyrrolidin-l-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklopropylmethoxy-quinazolin, (21) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(cis-2,6-dimethyl-piperidin-l-yl)-l-oxo-2-buten-l-yl]amino>-7-cyklopropylmethoxy-quinazolin, (22) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(2,5-dimethyl-pyrrolidin-l-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklopropyl-methoxy-quinazolin, (23) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(diethylamino)-l-oxo-2-buten-l-yl]amino}-7-[(tetrahydrofuran-2-yl)methoxy]-quinazolin, (24) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(diethylamino)-l-oxo-2-buten-l- yl]amino}-7-[(S)-(tetrahydrofuran-3-yl)oxy]-quinazolin, (25) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(4-diethylamino-methyl-piperidin-l-yl)- 1- oxo-2-buten-l-yl]amino>-7-cyklo-propylmethoxy-quinazolin, (26) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(N-methyl-N-cyklo-propylmethyl-annino)-l-oxo-2-buten-l-yl]annino>-7-cyklopropylmethoxy-quinazolin, (27) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-methyl-N-(2-methoxypropyl)-amino]-l-oxo-2-buten-l-yl>annino)-7-cyklopropylmethoxy-quinazoliri, (28) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-methyl-N-(3-methoxypropyl)-annino]-l-oxo-2-buten-l-yl>annino)-7-cyklopropylmethoxy-quinazolin, (29) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(diethylamino)-l-oxo-2-buten-l-yl]amino>-7-[(tetrahydropyran-4-yl)oxy]-quinazolin, (30) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-methyl-N-(l-methoxy-2-propyl)-amino]-l-oxo-2-buten-l-yl>amino)-7-cyklopropylmethoxy-quinazolin, (31) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(N,N-dimethylamino)-l-oxo-2-butin-l-yl]amino>-7-cyklopropylmethoxy-quinazolin, (32) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(N,N-diethylamino)-l-oxo-2-butin-l-yl]amino>-7-cyklopropylmethoxy-quinazolin, (33) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(piperidin-l-yl)-l-oxo-2-butin-l-yl]amino>-7-cyklopropylmethoxy-quinazolin, (34) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(morpholin-4-yl)-l-oxo-2-butin-l-yl]amino>-7-cyklopropylmethoxy-quinazolin, (35) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(N,N-dimethylamino)-l-oxo-2-buten-l-yl]amino>-7-(2-cyklopropyl-ethoxy)-quinazolin, (36) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[bis-(2-methoxy-ethyl)-annino]-l-oxo- 2- buten-l-yl>amino)-7-cyklobutyloxy-quinazolin, (37) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-methyl-N-(2-methoxyethyl)-annino]-l-oxo-2-buten-l-yl>amino)-7-cyklobutyloxy-quinazolin, (38) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[(S)-N-methyl-N-(l-methoxy-2-propyl)-amino]-l-oxo-2-buten-l-yl>annino)-7-cyklobutyloxy-quinazolin, (39) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[(R)-N-methyl-N-(l-methoxy-2-propyl)-amino]-l-oxo-2-buten-l-yl>annino)-7-cyklobutyloxy-quinazolin, (40) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-methyl-N-(l-methoxy-2-propyl)-amino]-l-oxo-2-buten-l-yl>amino)-7-cyklopropylmethoxy-quinazolin, (41) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-methyl-N-(2-methoxypropyl)-amino]-l-oxo-2-buten-l-yl>amino)-7-cyklopropylmethoxy-quinazolin, (42) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-methyl-N-(3-methoxypropyl)-amino]-l-oxo-2-buten-l-yl>amino)-7-cyklopropyl-methoxy-quinazolin, (43) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(N-cyklopropyl-N-methyl-amino)-l-oxo-2-buten-l-yl]amino>-7-cyklobutyloxy-quinazolin, (44) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(N-cyklopropylmethyl-N-methyl-amino)-l-oxo-2-buten-l-yl]amino}-7-cyklobutyloxy-quinazolin, (45) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(pyrrolidin-l-yl)-l-oxo-2-buten-l-yllaminol-7-cyklobutyloxy-quinazolin, (46) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(2-methyl-pyrrolidin-l-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklobutyloxy-quinazolin, (47) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(2,5-dimethyl-pyrrolidin-l-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklobutyloxy-quinazolin, (48) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(piperidin-l-yl) - l-oxo-2-buten-l-yl]amino>-7-cyklobutyloxy-quinazolin, (49) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(2-methyl-piperidin-l-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklobutyloxy-quinazolin, (50) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(2,6-dimethyl-piperidin-l-yl)-l-oxo-2-buten-l-yl]amino>-7-cyklobutyloxy-quinazolin, (51) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(3-methyl-morpholin-4-yl)-l-oxo-2-buten-l-yl]amino}-7-cyklobutyloxy-quinazolin, (52) 4-[(3-chlor-4-fluorphenyl)amino]-6-{[4-(3,5-dimethyl-morpholin-4-yl)-l-oxo-2-buten-l-yl]amino>-7-cyklobutyloxy-quinazolin, (53) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-methyl-N-(2-methoxyethyl)-amino]-l-oxo-2-buten-l-yl>amino)-7-(tetrahydrofuran-3-yl-oxy)-quinazolin, (54) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-methyl-N-(2-methoxyethyl)-annino]-l-oxo-2-buten-l-yl>amino)-7-(tetrahydropyran-4-yl-oxy)-quinazolin og (55) 4-[(3-chlor-4-fluorphenyl)amino]-6-({4-[N-methyl-N-(2-methoxyethyl)-annino]-l-oxo-2-buten-l-yl>amino)-7-(tetrahydrofuran-2-yl-methoxy)-quinazolin, samt salte deraf.
3. Fysiologisk acceptable salte af forbindelsen ifølge krav 1 eller 2 med uorganiske eller organiske syrer eller baser.
4. Lægemiddel, indeholdende en forbindelse ifølge krav 1 eller 2 eller et fysiologisk acceptabelt salt ifølge krav 3, samt eventuelt ét eller flere inerte bærestoffer og/eller fortyndingsmidler.
5. Anvendelse af en forbindelse ifølge mindst ét af kravene 1 til 3, til fremstilling af et lægemiddel, som er egnet til behandling af benigne eller maligne tumorer, til forebyggelse og behandling af sygdomme i luftvejene og lungerne, samt til behandling af sygdomme i mave-tarmkanalen og galdegangene og -blæren.
6. Fremgangsmåde til fremstilling af et lægemiddel ifølge krav 4, kendetegnet ved, at en forbindelse ifølge mindst et af kravene 1 til 3 inkorporeres gennem ikke-kemiske veje i et eller flere inerte hjælpestoffer og/eller fortyndingsmidler.
7. Fremgangsmåde til fremstilling af forbindelsen ifølge den generelle formel I ifølge kravene ltil 3, kendetegnet ved, at a) en forbindelse ifølge den generelle formel
, (II) hvor Ra til Rc, A og X er defineret som nævnt i kravene 1 eller 2, reageres med en forbindelse ifølge den generelle formel
(III) hvor B til E er defineret som nævnt i kravene 1 eller 2, og Zi repræsenterer en fraspaltningsgruppe, eller b) til fremstilling af forbindelser ifølge den generelle formel I, hvor resten E er forbundet over et nitrogenatom med resten D, at en forbindelse ifølge den generelle formel
, (IV) hvor Ra til Rc, A til D og X er defineret som nævnt i kravene 1 eller 2, og Z2 repræsenterer en fraspaltningsgruppe, reageres med en forbindelse ifølge den generelle formel H - E’ , (V) hvor E' repræsenterer en rest, som nævnt for E i kravene 1 eller 2, som er forbundet over et nitrogenatom med resten D, og eventuelt omdannes en således opnået forbindelse ifølge den generelle formel I, som indeholder en amino-, alkylamino- eller iminogruppe, ved acylering eller sulfonylering, til en tilsvarende acyl- eller sulfonylforbindelse ifølge den generelle formel I, og/eller omdannes en således opnået forbindelse ifølge den generelle formel I, som indeholder en amino-, alkylamino- eller iminogruppe, ved alkylering eller reduktiv alkylering, til en tilsvarende alkylforbindelse ifølge den generelle formel I, og/eller omdannes en således opnået forbindelse ifølge den generelle formel I, som indeholder en carboxy- eller hydro-xyphosphorylgruppe, ved forestring, til en tilsvarende ester ifølge den generelle formel I, og/eller omdannes en således opnået forbindelse ifølge den generelle formel I, som indehol- der en carboxy- eller estergruppe, ved reaktion med en tilsvarende amin, til et tilsvarende amid ifølge den generelle formel I, og/eller om nødvendigt fraspaltes en beskyttelsesgruppe anvendt i ovennævnte reaktion, og/eller eventuelt fraktioneres en således opnået forbindelse ifølge den generelle formel I, i stereoisomerer deraf og/eller omdannes en således opnået forbindelse ifølge den generelle formel I til salte deraf, i særdeleshed, for den farmaceutiske anvendelse, til fysiologisk acceptable salte deraf.
DK06116986.8T 1999-06-21 2000-06-16 Bicykliske heterocykliske strukturer, lægemidler indeholdende disse forbindelser, anvendelse deraf og fremgangsmåde til fremstilling deraf DK1731511T3 (da)

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Application Number Priority Date Filing Date Title
DE1999128281 DE19928281A1 (de) 1999-06-21 1999-06-21 Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
US14664499P 1999-07-30 1999-07-30
DE2000123085 DE10023085A1 (de) 2000-05-11 2000-05-11 Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
EP00936888A EP1194418A1 (de) 1999-06-21 2000-06-16 Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung

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