Ciba-geigy Corporation

Jan W Wasley

Karl O Gelotte

Harold Meckler

Jon Norman

Disclosed are the pyrrolylphenyl-substituted hydroxamic acid derivatives of the formula ##STR1## wherein R represents hydrogen, lower alkyl, halogen or lower alkoxy; R.sub.1 and R.sub.2 independently represent hydrogen, lower alkyl or aryl; Y represents a direct bond, lower alkylene, lower alkenylene, lower alkadienylene, (thio, sulfinyl or sulfonyl)-lower alkylene or oxy-lower alkylene; Z represents ##STR2## wherein R.sub.3 represents hydrogen or acyl; R.sub.4 represents lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, aryl or aryl-lower alkyl; or Z represents ##STR3## wherein R.sub.3 represents hydrogen or acyl; R.sub.5 represents lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, aryl, aryl-lower alkyl, amino or N-(mono- or di-lower alkyl)-amino; R.sub.6 and R.sub.7 represent hydrogen or lower alkyl; and pharmaceutically acceptable salts thereof provided that R.sub.3 represents hydrogen; which are useful as selective lipoxygenase inhibitors, methods for preparation thereof, pharmaceutical compositions comprising said compounds, and a method of inhibiting lipoxygenase and of treating diseases in mammals which are responsive to lipoxygenase inhibition using said compounds and pharmaceutical compositions comprising said compounds of the invention.

Pyrrolylphenyl-substituted hydroxamic acid derivatives

Disclosed are the compounds of formula I ##STR1## wherein R and R.sub.1 -R.sub.3 independently represent hydrogen or lower alkyl, and m represents the integer 2 or 3; their methods of preparation; pharmaceutical compositions thereof, and their use for treating cognitive disorders in mammals.

Tetracyclic pyrrole lactam derivatives

Disclosed are the compounds of formula I ##STR1## wherein R.sub.1 -R.sub.3 represent hy drogen or lower alkyl; m represents the integer 2 or 3; n represents the integer 1 or 2; Het represents a pyrrole or imidazole ring bonded at any two adjacent positions and optionally substituted by one or two of lower alkyl; and pharmaceutically acceptable salts of compounds of formula I wherein Het represents optionally substituted imidazole; their methods of preparation; pharmaceutical compositions thereof, and their use for treating cognitive disorders in mammals.

Heterotetracyclic lactam derivatives

The invention relates to the pyrrolyl-substituted hydroxamic acid derivatives of the formula ##STR1## wherein R represents aryl, aryl-lower alkyl, cycloalkyl, bicycloalkyl or adamantyl; R.sub.1 and R.sub.2 represent hydrogen or lower alkyl; Y represents a direct bond, lower alkylene, lower alkenylene or lower alkadienylene; Z represents ##STR2## wherein R.sub.3 represents hydrogen or acyl; R.sub.4 represents lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, aryl or aryl-lower alkyl; or Z represents ##STR3## wherein R.sub.3 represents hydrogen or acyl; R.sub.5 represents lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, aryl, aryl-lower alkyl, amino or N-(mono- or di-lower alkyl)-amino; R.sub.6 and R.sub.7 represent hydrogen or lower alkyl; and pharmaceutically acceptable salts thereof provided that R.sub.3 represents hydrogen; which are useful as lipoxygenase inhibitors.

Certain pyrrolyl-substituted hydroxamic acid derivatives

Disclosed are the compounds of formula I: ##STR1## wherein R.sub.1 -R.sub.3 represent hydrogen or lower alkyl; m represents the integer 2 or 3; n represents the integer 1 or 2; Het represents a pyrrole or imidazole ring bonded at any two adjacent positions and optionally substituted by one or two or lower alkyl; and pharmaceutically acceptable salts of compounds of formula I wherein Het represents optionally substituted imidazole; their methods of preparation; pharmaceutical compositions thereof, and their use for treating cognitive disorders in mammals.

Heterotertracyclic lactam derivatives, pharmaceutical compositions, and

Disclosed are compounds of the formula ##STR1## wherein R.sub.1 represents unsubstituted or lower alkyl-substituted C.sub.3 -C.sub.7 -cycloalkyl, unsubstituted or lower alkyl substituted C.sub.7 -or C.sub.8 -bicycloalkyl, unsubstituted or lower alkyl-substituted adamantyl, 4-piperidinyl or N-lower alkyl or aryl-lower alkyl-substituted piperidinyl, 1- or 2-indanyl, 1- or 2-tetrahydronaphthyl, 1- or 2-perhydroindanyl, 1- or 2-perhydronaphthyl; R.sub.2 represents hydrogen, lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl, aryl-lower alkyl, C.sub.3 -C.sub.7 -cycloalkyl-lower alkyl, lower alkanoyl or aryl-lower alkanoyl; or R.sub.1 and R.sub.2 combined with the nitrogen to which they are attached represent pyrrolidino, piperidino, perhydroazepino, morpholino, thiomorpholino, tetrahydro- or perhydro-(isoquinolinyl or quinolinyl), dihydro- or perhydroindolyl, piperazino or N-lower alkyl-piperazino; R.sub.3 represents hydrogen, lower alkyl, halogen or lower alkoxy; pharmaceutically acceptable ester and ether derivatives thereof; and pharmaceutically acceptable acid-addition salts of any said basic compounds of formula I and derivatives thereof; as 5-lipoxygenase inhibitors.

4-Amino-substituted 1,2-dihydroxynaphthalene derivatives useful in

Disclosed are the compound of the formula ##STR1## wherein n represents zero, 1 or 2; Ar represents a carbocyclic or heterocyclic aryl radical; R and R.sub.1 independently represent hydrogen, lower alkyl or Ar-lower alkyl; R.sub.2 and R.sub.3 independently represent hydrogen, lower alkyl, halogen, trifluoromethyl or lower alkoxy; or R.sub.2 and R.sub.3 together on adjacent carbon atoms represent lower alkylenedioxy; R.sub.4 represents hydroxy or NR.sub.5 R.sub.6 wherein R.sub.5 and R.sub.6 independently represent hydrogen, lower alkyl or AR-lower alkyl,; or R.sub.5 and R.sub.6 together with the nitrogen to which they are attached represent pyrrolidino or piperidino; pharmaceutically acceptable salts thereof; lower alkyl enol ethers and lower alkanoyl enol esters of compounds of formual I wherein R.sub.4 represents hydroxy; as e.g. antiinflammatory agents; methods for preparing said compounds and pharmaceutical compositions comprising said compounds.

2,1-benzothiazepine-2,2-dioxide-5-carboxylic acid derivatives

Disclosed are the compounds of the formula ##STR1## wherein n represents the integer 1,2,3 or 4; R.sub.1 represents hydrogen, lower alkyl, halogen, trifluoromethyl, hydroxy or lower alkoxy; R.sub.2 represents hydrogen or lower alkyl; R.sub.3 represents hydrogen, lower alkyl or halogen; R.sub.4 represents amino, lower alkylamino, di-lower alkylamino, morpholino, N-lower alkyl or N-aryl piperazino, pyrrolidino, piperidino or substituted piperidino selected from ##STR2## in which R.sub.5 represents hydrogen, halogen or lower alkyl; and pharmaceutically acceptable salts thereof; which are useful in mammals as calmodulin antagonists for the treatments of gastrointestinal disorders.

Pyrrolo[1,2-a] [4,1]benzoxazepine derivatives useful as calmodulin and

The invention relates to 1,3,4,16b-tetrahydro-2H,10H-indolo[2,1-c]pyrazino[1,2-a][1,4]benzodiazepin e derivatives of the formula I, ##STR1## wherein R.sup.1 is hydrogen, lower alkyl, C.sub.3-7 -alkenyl, C.sub.3-7 -alkynyl, 3 to 7 ring-membered cycloalkyl, C.sub.2-7 -alkyl substituted by a substituent selected from hydroxy, amino, N-mono-lower alkyl-amino and N,N-di-lower alkyl-amino; or R.sup.1 is lower alkyl substituted by a substituent selected from 3 to 7 ring-membered cycloalkyl, carboxy, lower alkoxycarbonyl, carbamoyl, N-mono-lower alkyl-carbamoyl, N,N-di-lower alkyl-carbamoyl and lower alkanoyl; or R.sup.1 is lower alkyl substituted by either phenyl or benzoyl each of said phenyl or benzoyl radicals being unsubstituted or substituted by up to three members selected from lower alkyl, lower alkoxy, lower alkylthio, halogen and trifluoromethyl; R.sup.2 and R.sup.3 represent hydrogen, lower alkyl, hydroxy, lowr alkoxy, halogen or trifluoromethyl; and R.sup.4 represents hydrogen, lower alkyl, hydroxy-lower alkyl, carboxy, lower alkoxycarbonyl, carbamoyl, N-mono- or N,N-di-lower alkyl-carbamoyl, or formyl; salts and 2N-oxides; which are useful as serotonin-2 receptor antagonists.

1,3,4,16b-tetra

Disclosed are the novel compounds of formula I ##STR1## wherein ring A is unsubstituted or substituted by one or two identical or different substituents selected from lower alkyl, halogen, trifluoromethyl, lower alkoxy, hydroxy and acyloxy; or ring A is substituted on adjacent carbon atoms by lower alkylenedioxy; R represents hydrogen, halogen or lower alkyl; and Ar represents carbocyclic aryl or heteroaryl; which are useful as benzodiazepine receptor agonists, processes for preparing the same, pharmaceutical compositions comprising said compounds and methods of treating nervous system disorders, such as anxiety and epilepsy, by administration of said compounds and pharmaceutical compositions to mammals.

9H-pyrrolo[2,1-c]-1,2,4-triazolo[4,3-a][1,4]benzodiazepines

Certain 1,3,4,14b-tetrahydro-2H,10H-pyrazino�1,2-a!pyrrolo-�2,1-c!�1,4!benzodiazep ines e.g. those of the formula ##STR1## wherein R.sub.1 is lower alkyl or hydroxy(lower)alkyl; R.sub.2 is hydrogen, chloro or trifluoromethyl; pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising said compounds, are useful for the treatment of anxiety in mammals.

Method of treating anxiety

1,3,4,14b-Tetrahydro-2H,10H-pyrazino[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepin es, e.g. those of the formula ##STR1## R.sub.6 .dbd.H, alkyl, alkenyl, alkynyl, (cycloalkyl or HO)-alkyl

Diazepinopyrrolobenzodiazepines

1,3,4,14b-Tetrahydro-2H,10H-pyrazino[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepin es, e.g. those of the formula ##STR1## R.sub.6 =H, alkyl, alkenyl, alkynyl, (cycloalkyl or HO)-alkyl R.sub.7 =H, halo or CF.sub.3 acyl derivatives, N-oxides, quaternaries and acid addition salts thereof are antidepressants.

Growing community of inventors

Chatham, NJ, United States of America

Jan W Wasley