The Upjohn Co.

Other

Astra Lakemedel Aktiebolag

Hakan V Wikstrom

Per A Carlsson

Bengt R Andersson

Kjell A Svensson

Nils P Stjernlof

Per L Lindberg

Domingo Sanchez

Folke L Arvidsson

John L Nilsson

Arthur Glenn Romero

Chiu-Hong Lin

Michael D Ennis

Susanne R Haadsma-Svensson

Uli A Hacksell

John S Hjorth

Stig Thomas Elebring

Nils U Svensson

Kjell Anders Svensson

Clas A Sonesson

R Nicholas Waters

Lars O Hansson

Anna M Boije

Anders R Hallberg

Anette M Johansson

Nils A Svensson

Barbro A Ekman

John S Hjort

A compound of Formula I ##STR1## or pharmaceutically acceptable salts of Formula I, where R.sup.1 is H, C.sub.1 -C.sub.3 alkyl, --(CH.sub.2).sub.n CONH.sub.2 where n is 2 to 6, (CH2).sub.n -1-(4,4-dimethylpiperidine-2,6-dione-yl), or cyclopropylmethyl; R.sup.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl or combined with R.sup.1 to form a C.sub.3 -C.sub.8 cycloalkyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 akynyl, (CH.sub.2).sub.n --X--Ar where X is O, S, or NH, 3,3,3-trifluoropropyl, --(CH.sub.2).sub.m --R.sup.9 where m is 2 or 3 and R.sup.9 is phenyl, 2-thiophenyl or 3-thiophenyl; R.sup.3 is hydrogen, C.sub.1 -C.sub.3 alkyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, formyl, CN, halogen, CH.sub.2 OR.sup.2, C(O)C(O)OR.sup.1, C(O)CO NR.sup.1 R.sup.2, --(CH.sub.2).sub.q --NR.sup.1 R.sup.2 where q is 0 to 5, C.dbd.NOR.sup.2, 2(4,5-dihydro)oxazolyl, or COR.sup.10 where R.sup.10 is H, R.sup.1, NR.sup.1 R.sup.2 or CF.sub.3 ; R.sup.4 is hydrogen, C.sub.1 -C.sub.3 alkyl, cyclopropylmethyl, CF.sub.3, 2,2,2-trifluoroethyl, CN, CONR.sup.1 R.sup.2, .dbd.O, 2(4,5-dihydro)imidazolyl, 2(4,5-dihydro)oxazolyl, 2-oxazolyl, 3-oxadiazolyl, or 3,3,3-trifluoropropyl; R.sup.5 is hydrogen, R.sup.1, OCH.sub.3, C(O)CH.sub.3 or C(O)OR.sup.1 ; X is (a) a valence bond, (b) CH.sub.2, or (c) O, S or NR.sup.5 where R.sup.5 is H, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, benzyl, COR.sup.6 where R.sup.6 is a C.sub.1 -C.sub.3 alkyl, phenyl, or CONR.sup.7 R.sup.8 where R.sup.7 and R.sup.8 are independently H or C.sub.1 -C.sub.3 alkyl; and Z is a hydrogen or halogen; provided that when X is CH.sub.2, at least one of R.sub.3 and R.sub.4 is other than hydrogen or C.sub.1 -C.sub.3 alkyl. The compounds of Formula I are suitable for treating disorders of the central nervous system, particularly as 5-HT.sub.1A receptor agonists.

Centrally acting 6,7,8,9-tetrahydro-3H-benz(e) indole heterocyclics

A compound or Formula I ##STR1## or a pharmaceutically acceptable salt thereof wherein n is 1 or 2; R.sup.1 and R.sup.2 are independently H (provided only one is H at the same time), --OH, CN, CH.sub.2 CN, 2- or 4-CF.sub.3, CH.sub.2 CF.sub.3, CH.sub.2 CHF.sub.2, CH.dbd.CF.sub.2, (CH.sub.2).sub.2 CF.sub.3, ethenyl, 2-propenyl, OSO.sub.2 CH.sub.3, OSO.sub.2 CF.sub.3, SSO.sub.2 CF.sub.3, COR, COOR, CON(R).sub.2, SO.sub.x CH.sub.3 (where, x is 0-2), SO.sub.x CF.sub.3, O(CH.sub.2).sub.x CF.sub.3, SO.sub.2 N(R).sub.2, CH.dbd.NOR, COCOOR, COCOON(R).sub.2, C.sub.1-8 alkyls, C.sub.3-8 cycloalkyls, CH.sub.2 OR, CH.sub.2 (R).sub.2, NRSO.sub.2 CF.sub.3, NO.sub.2, halogen, a phenyl at positions 2, 3 or 4, thienyl, furyl, pyrrole, oxazole, thiazole, N-pyrroline, triazole, tetrazole or pyridine; R.sup.3 is hydrogen, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, --(CH.sub.2).sub.m --R.sup.5 (where m is 1-8), CH.sub.2 SCH.sub.3 or a C.sub.4 -C.sub.8 alkylene bonded to said nitrogen and one of its adjacent carbon atoms inclusive whereby a heterocyclic structure is formed; R.sup.4 and R are independently selected from hydrogen, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, --(CH.sub.2).sub.m --R.sup.5 where m is 1-8; R.sup.5 is phenyl, phenyl (substituted with a CN, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl), 2-thiophenyl, 3-thiophenyl, --NR.sup.6 CONR.sup.6 R.sup.7, or --CONR.sup.6 R.sup.7 ; R.sup.6 and R.sup.7 are independently hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkylmethyl, C.sub.2 -C.sub.8 alkenyl or C.sub.2 -C.sub.8 alkynyl; and with the proviso that when R.sup.1 is CN, R.sup.2 and R.sup.4 are H, R.sup.3 is n-Pr and n is 1, then such compound is a pure enantiomer, and when R.sup.1 or R.sup.2 is OH, halogen, CONH.sub.2 or alkyl, then R.sup.4 is not hydrogen. The Formula I compounds possess selective pharmacological properties and are useful in treating central nervous system disorders related to dopamine receptor activity including depression symptoms, geriatric disorders in the improvement of mental and motor functions, schizophrenia, narcolepsy, MBD, obesitas, and disturbances of sexual functions and impotence.

Centrally actig substituted phenylazacycloalkanes

A compound of Formula I ##STR1## or a pharmaceutically acceptable salt thereof wherein n is 1 or 2; R.sup.1 and R.sup.2 are independently H (provided only one is H at the same time), --OH, CN, CH.sub.2 CN, 2-- or 4--CF.sub.3, CH.sub.2 CF.sub.3, CH.sub.2 CHF.sub.2, CH.dbd.CF.sub.2, (CH.sub.2).sub.2 CF.sub.3, ethenyl, 2-propenyl, OSO.sub.2 CH.sub.3, OSO.sub.2 CF.sub.3, SSO.sub.2 CF.sub.3, COR, COOR, CON(R).sub.2, SO.sub.x CH.sub.3 (where, x is 0-2), SO.sub.x CF.sub.3, O(CH.sub.2).sub.x CF.sub.3, SO.sub.2 N(R).sub.2, CH.dbd.NOR, COCOOR, COCOON(R).sub.2, C.sub.1-8 alkyls, C.sub.3-8 cycloalkyls, CH.sub.2 OR, CH.sub.2 (R).sub.2, NRSO.sub.2 CF.sub.3, NO.sub.2, halogen, a phenyl at positions 2, 3 or 4, thienyl, furyl, pyrrole, oxazole, thiazole, N-pyrroline, triazole, tetrazole or pyridine; R.sup.3 is hydrogen, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub. 2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, --(CH.sub.2).sub.m --R.sup.5 (where m is 1-8), CH.sub.2 SCH.sub.3 or a C.sub.4 -C.sub.8 alkylene bonded to said nitrogen and one of its adjacent carbon atoms inclusive whereby a heterocyclic structure is formed; R.sup.4 and R are independently selected from hydrogen, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, --(CH.sub.2).sub.m --R.sup.5 where m is 1-8; R.sup.5 is phenyl, phenyl (substituted with a CN, CF.sub.3, CH.sub.2 CF.sub.3, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkyl-methyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 alkynyl), 2-thiophenyl, 3-thiophenyl, --NR.sup.6 CONR.sup.6 R.sup.7, or --CONR.sup.6 R.sup.7 ; R.sup.6 and R.sup.7 are independently hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.4 -C.sub.9 cycloalkylmethyl, C.sub.2 -C.sub.8 alkenyl or C.sub.2 -C.sub.8 alkynyl; and with the proviso that when R.sup.1 is CN, R.sup.2 and R.sup.4 are H, R.sup.3 is n-Pr and n is 1, then such compound is a pure enantiomer, and when R.sup.1 or R.sup.2 is OH, halogen, CONH.sub.2 or alkyl, then R.sup.4 is not hydrogen. The Formula I compounds possess selective pharmacological properties and are useful in treating central nervous system disorders related to dopamine receptor activity including depression symptoms, geriatric disorders in the improvement of mental and motor functions, schizophrenia, narcolepsy, MBD, obesitas, and disturbances of sexual functions and impotence.

Centrally acting substituted phenylazacycloalkanes

A compound of Formula I ##STR1## or pharmaceutically acceptable salts of Formula I, where R.sup.1 is H, C.sub.1 -C.sub.3 alkyl, --(CH.sub.2).sub.n CONH.sub.2 where n is 2 to 6, (CH2).sub.n -1-(4,4-dimethylpiperidine-2,6-dione-yl), or cyclopropylmethyl;

Centrally acting 6,7,8,9-tetrahydro-3H-benz(E)indole heterocyclics

The present invention is directed to novel chromane derivatives substituted in the 3-position by a substituted amino moiety and substituted on the aromatic ring with one or two substituents. The novel chromane derivatives have useful CNS properties. ##STR1##

Substituted 3-amino chromans

Centrally acting 6,7,8,9-tetrahydro-3H-benz(e)indole heterocyclics

This invention is therapeutically useful tetralins and pharmaceutically acceptable acid addition salts thereof of the formula ##STR1## wherein X.sub.1 is halogen, CF.sub.3, --OR.sub.3, or --SR.sub.4 ; wherein R.sub.3 is alkyl(C.sub.1 -C.sub.8); alkenyl(C.sub.1 -C.sub.8); --CH.sub.2 -cycloalkyl(C.sub.3 -C.sub.8) or benzyl; wherein R.sub.4 is alkyl(C.sub.1 -C.sub.3); wherein X.sub.2 is hydrogen, CF.sub.3 or halogen; wherein R.sub.7 is hydrogen or methyl; wherein R.sub.1 is hydrogen, alkyl(C.sub.1 -C.sub.3), or cyclopropylmethyl; wherein R.sub.2 is --CH.sub.2 -cycloalkyl(C.sub.3 -C.sub.8), alkyl(C.sub.1 -C.sub.8), --(CH.sub.2).sub.q --R.sub.5 or --CH.sub.2 CH.sub.2 --Z--(CH.sub.2).sub.r CH.sub.3 ; wherein R.sub.5 is phenyl, 2-thiophene or 3-thiophene; wherein Z is oxygen or sulfur; and wherein p is one or 2, q is 2 or 3, and r is zero to 3; with the provisos that (1) when X.sub.1 is --OR.sub.3, X.sub.2 is halogen or CF.sub.3 ; and (2) when X.sub.1 is halogen, X.sub.2 is hydrogen, and p is 2, X.sub.1 is in a position other than the 8-position. These compounds are useful to treat central nervous system disorders.

Halo substituted aminotetralins

This invention is therapeutically useful tetralins and pharmaceutically acceptable acid addition salts thereof of the formula ##STR1## wherein YR.sub.1 is OR.sub.1 at the 8 position where R.sub.1 is --CH.sub.2 --(C.sub.3-8 cycloalkyl);

Therapeutically useful tetralin derivatives

Compound of the formula ##STR1## wherein n is 1 or 2, Y is OH, R.sup.1 COO--, R.sup.2 R.sup.3 NCOO-- or R.sup.4 O whereby R.sup.1 is an alkyl group, or a possibly substituted phenyl group, R.sup.2 is an alkyl, phenethyl, or benzyl or phenyl group, R.sup.3 is H or an alkyl group and R.sup.4 is an allyl or benzyl group, and R is an alkyl, hydroxyalkyl, dimethylaminoalkyl or methylthioalkyl group or alkenyl group, processes for their preparations and methods of treatment employing such compounds. The compounds are useful for therapeutic purposes, especially for treatment of disorders in the central nervous system.

Phenyl-azacykloalkanes

Phenyl-azacycloalkanes and use thereof in treatment of central nervous

Compounds of the formula ##STR1## wherein C.sup.1 and N.sup.4 are in trans configuration to each other, wherein R and Y are defined herein below, as bases and pharmaceutically acceptable acid addition salts thereof, processes for their preparation and pharmaceutical preparations and methods of treatment employing such compounds. The compounds are useful for treatment of disorders in the central nervous system.

Tricyclic amines with central dopaminergic activity

Compounds of the formula ##STR1## wherein n is 1 or 2, Y is OH, R.sup.1 COO--, R.sup.2 R.sup.3 NCOO-- or R.sup.4 O whereby R.sup.1 is an alkyl group, or a possibly substituted phenyl group, R.sup.2 is an alkyl, phenethyl, benzyl or phenyl group, R.sup.3 is H or an alkyl group and R.sup.4 is an allyl or benzyl group, and R is an alkyl, hydroxyalkyl, dimethylaminoalkyl or methylthioalkyl group or alkenyl group, processes for their preparation and pharmaceutical preparations and methods of treatment employing such compounds. The compounds are useful for therapeutic purposes, especially for treatment of disorders in the central nervous system.

Substituted phenyl piperidines

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Groningen, Netherlands

Hakan V Wikstrom