TH41482A - Tetracycline tetrahydrofuran derivatives replaced with halogens. - Google Patents

Abstract

DC60 (06/06/49) This invention concerns a compound with the formula (I) (chemical formula) (I), an N-oxide, a pharmaceutically accepted addition salt, and a stereochemical isomer of such compounds, where n is 0, 1, 2, 3, 4, 5, or 6, X is CH2 or O, and R1 and R2 independently are hydrogen C1-6 alkyl, C1-6 alkyl carbonyl, halomethyl carbonyl, or C1-6 alkyl substituted with hydroxyl, C1-6 alkyloxy, carboxyl, C1-6 alkyl carbonyloxy, C1-6 alkyloxycarbonyl or aryl, or R1 and R2 may be associated with a nitrogen atom to which it is attached to form a morpholinyl ring. or select a substituted heterocycle at R3 and R4 either halogen or R3 is a halogen and R4 is hydrogen or R3 is hydrogen and R4 is a halogen and aryl is phenyl or phenyl substituted by 1, 2 or 3 substituents chosen from halo, hydroxyl, C1-6 alkyl and halomethyl compounds. Compounds formulated (I) may be used as therapeutic agents. This invention concerns compounds formulated (I) (chemical formula), N-oxide forms, pharmaceutically acceptable addition salts and stereochemical isomers of them, where n is 0, 1, 2, 3, 4, 5 or 6, X is CH2 or O, R1 and R2 independently are hydrogen, C1-6 alkyl, C1-6 alkyl carbonyl, halomethyl carbonyl or substituted C1-6 alkyl. With hydroxyl C1-6 alkyl carboxyl C1-6 alkyl carboxyl C1-6 alkyloxycarbonyl or aryl, or R1 and R2 may, together with a nitrogen atom, form a morpholinyl ring or selectively form a heterocycle substituted at R3 and R4, either halogen or R3 is halogen and R4 is hydrogen, or R3 is hydrogen and R4 is halogen and aryl is phenyl or phenyl substituted by a 1, 2 or 3 substituted group from a halohydroxy C1-6 alkyl and halomethyl, compounds with the formula (I) may be used as therapeutic agents.

Claims (11)

1. Compound according to formula (I) (chemical formula) 2. The compound claims claim 1, where X is CH2. 3. A compound that meets claim 1 or 2, in which the hydrogen atoms on carbon atoms 3a and 12b lie on opposite sides of the intermediate plane as analyzed by the tetracyclic ring system. 4. The compound claims one of three claims, where R3 is a halo and R4 is a hydrogen. 5. The compound claims one of four claims, where n is 1. 6. A compound that claims any of the claims 1 through 5, in which both R1 and R2 independently are chosen from hydrogen or C1-6 alkyl or together with the nitrogen atom to which it is bound to form a morpholinyl ring or radical according to the formula (c) or (e). 7. The compounds entitled under claim I, whereby the compounds are 11-fluoro3,3a,812b-tetrahydro-N,N-dimethyl-2H-dibenzo(3,4:6,7)furan-2-methanines, their stereochemical isomers, or their pharmaceutically acceptable addition salts, or their N-oxides. 8. A mixture containing a pharmacodynamically recognized carrier and therapeuticly effective amounts of the active ingredient as claimed in claim one of claims 1 through 7. 9. The compound is entitled to one of the claims under claims 1 through 7 for use as a pharmaceutical product. 10. The use of the compound as entitled under any one of the claims in Claims 1 through 7 in the manufacture of pharmaceuticals for the treatment of anxiety, psychosis, schizophrenia, depression, migraine, sleep disorders, and the addictive properties of drugs used in excess. 11. The procedure for preparing compounds as claimed in Patent 1, which is characterized as follows: a) An intermediate of formula (II) is N-alkylated by an intermediate of formula (III) (chemical formula) in which R1 to R4, n and X are the same as those specified in Patent 1, and W is the appropriate living group, in an inert solvent and selectably containing an appropriate base; b) Compounds of formula (I) can be transformed into individual compounds according to known transformations, and if desired, compounds of formula (I) can be transformed into non-toxic, therapeutic acid salts by acid action, or into non-toxic, therapeutic alkali salts by alkali action, or conversely, the acid salts can be transformed into free bases by alkali action, or the base salts can be transformed into free acids by additional acid action, and if desired, stoichiometric isomers can be prepared. The teriochemical or N-oxide forms of those substances (11 claims, 4 pages, 0 images).