Halogen substituted tetracyclic tetrahydrofuran derivatives, process of their preparation and use as well as compositions containing thereof

• Main Authors: ANDRUS-GIL JOSU IGNACIO, FERNANDEZ-GADEA FRANCISCO JAVIER, DIAZ-MARTINEZ ADOLFO, GIL-LOPETEGUI PILAR
• Format: Patent
• Language: Czech; English
• Published: 12.07.2006
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

Tetracyklické deriváty tetrahydrofuranu substituované halogenem vzorce I, jejich N-oxidy, farmaceuticky prijatelné soli a stereochemicky izomerní formy, kde n znamená císlo nula, 1, 2, 3, 4, 5 nebo 6; X je CH.sub.2.n. nebo kyslík; R.sup.1.n. a R.sup.2.n. jsou kazdý nezávisle vodík, C.sub.1-6.n.alkyl, C.sub.1-6.n.alkylkarbonyl, halogenmethylkarbonyl nebo C.sub.1-6.n.alkyl substituovaný hydroxylem,C.sub.1-6.n.alkyloxy, karboxylem, C.sub.1-6.n.alkylkarbonyloxy, C.sub.1-6.n.alkyloxykarbonylem neboarylem; nebo R.sup.1.n. a R.sup.2.n. spolecne s atomem dusíku, ke kterému jsou pripojeny, mohou tvorit morfolinyl nebo poprípade substituovaný heterocyklus; R.sup.3.n. a R.sup.4.n. jsou oba halogen; nebo R.sup.3.n. je halogen a R.sup.4.n. je vodík; nebo R.sup.3.n. je vodík a R.sup.4.n. je halogen; a aryl je fenyl nebo fenyl substituovaný 1, 2 nebo3 substituenty vybranými ze skupiny, kterou tvoríhalogen, hydroxyl, C.sub.1-6.n.alkyl a halogenmethyl. Deriváty vzorce I se hodí pro lécení úzkosti,psychózy, schizofrenie, deprese, poruch spánku a návykových vlastností zneuzívaných léciv. In the present invention, there are disclosed halogen substituted tetracyclic tetrahydrofuran derivatives of the general formula I, N-oxide forms, pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein n is zero, 1, 2, 3, 4, 5 or 6; X represents CHi2 or oxygen; Re1 and Re2 each independently represents hydrogen, alkyl containing 1 to 6 carbon atoms, alkylcarbonyl having 1 to 6 carbon atoms in the alkyl moiety, halomethylcarbonyl or alkyl containing 1 to 6 carbon atoms and being substituted with hydroxy, alkyloxy containing 1 to 6 carbon atoms, carboxyl, C1-6 alkylcarbonyloxy having 1 to 6 carbon atoms in the alkyl moiety, C1-6 alkyloxycarbonyl with 1 to 6 carbon atoms in the alkyl moiety or aryl; or Re1 and Re2 taken together with a nitrogen atom to which they are attached may form a morpholinyl ring or an optionally substituted heterocycle; Re3 and Re4 represent both halogen; or Re3 represent halogen and Re4 denotes hydrogen ; or Re3 represents hydrogen and Re4 denotes halogen; and aryl is phenyl or phenyl substituted with 1, 2 or 3 substituents being selected from the group consisting of halo, hydroxy, alkyl containing 1 to 6 carbon atoms and halomethyl. The above-described derivatives of the general formula I are useful in the treatment of anxiety, psychosis, schizophrenia, depression, sleep disorders and addictive properties of drugs of abuse.