Ciba-geigy Corporation

Leslie J Browne

Robert M Bowman

Ronald E Steele

Robert Diener

Bruce H Ewald

The invention is concerned with aromatase inhibiting compounds of formula I ##STR1## wherein R and Ro represent hydrogen or lower alkyl; or R and Ro located on adjacent carbon atoms and together when combined with the benzene ring to which they are attached form a naphthalene or tetrahydronaphthalene ring; R.sub.1 and R.sub.2 independently represent hydrogen, lower alkyl, (lower alkyl, aryl or aryl-lower alkyl)-thio, lower alkenyl, aryl, aryl-lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl, or C.sub.3 -C.sub.6 -cycloalkyl-lower alkyl; or R.sub.1 and R.sub.2 combined represent lower alkylidene, mono- or di-aryl-lower alkylidene; R.sub.1 and R.sub.2 combined also represent C.sub.4 -C.sub.6 -straight chain alkylene, lower alkyl-substituted straight chain alkylene or ortho-phenylene bridged-C.sub.2 -C.sub.4 -straight chain alkylene, each forming with the carbon atom attached thereto a corresponding optionally substituted or benzo-fused 5, 6 or 7-membered ring; W represents 1-imidazolyl, 1-(1,2,4- or 1,3,4)-triazolyl or 3-pyridyl; or W represents 1-imidazolyl, 1-(1,2,4 or 1,3,4)-triazolyl or 3-pyridyl substituted by lower alkyl; and pharmaceutically acceptable salts thereof.

Alpha-heterocycle substituted tolunitriles

Disclosed are compounds of formula I ##STR1## wherein R.sub.1 represents hydrogen, lower alkyl, substituted lower alkyl, nitro, halogen, free, etherified or esterified hydroxy, free, etherified, oxidised etherified or esterified mercapto, unsubstituted, mono- or disubstituted amino, ammonio, free or functionally modified sulfo, free or functionally modified formyl, C.sub.2 -C.sub.20 -acyl, cyano, free or functionally modified carboxy; and R.sub.2 represents hydrogen, lower alkyl, substituted lower alkyl, halogen; free, etherified or esterified hydroxy; free, etherified, oxidised etherified or esterified mercapto; free or functionally modified carboxy, or acyl; the 7,8-dihydro derivatives thereof; and compounds of the formula I* ##STR2## wherein n denotes 0, 1, 2, 3, or 4, and R.sub.1 and R.sub.2 are as defined above under formula I and salts thereof; e.g. as aromatase inhibitors; pharmaceutical compositions containing these compounds; the use of these compounds for the treatment of conditions responsive to e.g. aromatase inhibition in mammals; processes and intermediates for preparing these compounds.

Substituted imidazo[5-a]pyridine derviatives and other substituted

The invention is concerned with aromatase inhibiting compounds of formula I ##STR1## wherein R and Ro represent hydrogen or lower alkyl; or R and Ro located on adjacent carbon atoms and together when combined with the benzene ring to which they are attached form a naphthalene or tetrahydronaphthalene ring; R.sub.1 and R.sub.2 independently represent hydrogen, lower alkyl, (lower alkyl, aryl or aryl-lower alkyl)-thio, lower alkenyl, aryl, aryl-lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl, or C.sub.3 -C.sub.6 -cycloalkyl-lower alkyl; or R.sub.1 and R.sub.2 combined represent lower alkylidene, mono-or di-aryl-lower alkylidene; R.sub.1 and R.sub.2 combined also represent C.sub.4 -C.sub.6 -straight chain alkylene, lower alkyl-substituted straight chain alkylene or ortho-phenylene bridged-C.sub.2 -C.sub.4 -straight chain alkylene, each forming with the carbon atom attached thereto a corresponding optionally substituted or benzo-fused 5, 6 or 7-membered ring; W represents 1-imidazolyl, 1-(1,2,4- or 1,3,4)-triazolyl or 3-pyridyl; or W represents 1-imidazolyl, 1-( 1,2,4 or 1,3,4)-triazolyl or 3-pyridyl substituted by lower alkyl; and pharmaceutically acceptable salts thereof.

The invention is concerned with aromatase inhibiting compounds of formula I ##STR1## wherein R and Ro represent hydrogen or lower alkyl; or R and Ro located on adjacent carbon atoms and together when combined with the benzene ring to which they are attached form a naphthalene or tetrahydronaphthalene ring; R.sub.1 and R.sub.2 independently represent hydrogen, lower alkyl, (lower alkyl, aryl or aryl-lower alkyl)-thio, lower alkenyl, aryl, aryl-lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl, or C.sub.3 -C.sub.6 -cycloalkyl-lower alkyl; or R.sub.1 and R.sub.2 combined represent lower alkylidene, mono- or di-aryl-lower alkylidene; R.sub.1 and R.sub.2 combined also represent C.sub.4 -C.sub.6 -straight chain alkylene, lower alkyl-substituted straight chain alkylene or ortho-phenylene bridged-C.sub.2 -C.sub.4 -straight chain alkylene, each forming with the carbon atom attached thereto a corresponding optionally substituted or benzo-fused 5, 6 or 7-membered ring; W represents 1-imidazolyl, 1-(1,2,4- or 1,3,4-triazolyl or 3-pyridyl; or W represents 1-imidazolyl, (1-1,2,4 or 1,3,4)-triazolyl or 3-pyridyl substituted by lower alkyl; and pharmaceutically acceptable salts thereof.

Disclosed are compounds of formula I ##STR1## wherein R.sub.1 represents hydrogen, lower alkyl, substituted lower alkyl, nitro, halogen, free, etherified or esterified hydroxy, free, etherified, oxidized etherified or esterified mercapto, unsubstituted, mono- or disubstituted amino, ammonio, free or functionally modified sulfo, free or functionally modified formyl, C.sub.2 --C.sub.20 -acyl, cyano, free or functionally modified carboxy; and R.sub.2 represents hydrogen, lower alkyl, substituted lower alkyl, halogen; free, etherified or esterified hydroxy; free, etherified, oxidized etherified or esterified mercapto; free or functionally modified carboxy, or acyl; the 7,8-dihydro derivatives thereof; and compounds of the formula I* ##STR2## wherein n denotes 0, 1, 2, 3 or 4, and R.sub.1 and R.sub.2 are as defined above under formula I and salts thereof; e.g. as aromatase inhibitors; pharmaceutical compositions containing these compounds; the use of these compounds for the treatment of conditions responsive to e.g. aromatase inhibition in mammals; processes and intermediates for preparing these compounds.

Substituted imidazo[1,5-a]pyridine derivatives and other substituted

The invention is concerned with aromatase inhibiting compounds of formula I ##STR1## where R and Ro represent hydrogen or lower alkyl; or R and Ro located on adjacent carbon atoms and together when combined with the benzene ring to which they are attached form a naphthalene or tetrahydronaphthalene ring; R.sub.1 and R.sub.2 independently represent hydrogen, lower alkyl, (lower alkyl, aryl or aryl-lower alkyl)-thio, lower alkenyl, aryl, aryl-lower alkyl, C.sub.3 -C.sub.6 -cycloalkyl, or C.sub.3 -C.sub.6 -cycloalkyl-lower alkyl; or R.sub.1 and R.sub.2 combined represent lower alkylidene, mono- or di-aryl-lower alkylidene; R.sub.1 and R.sub.2 combined also represent C.sub.4 -C.sub.6 -straight chain alkylene, lower alkyl-substituted straight chain alkylene or ortho-phenylene bridged-C.sub.2 -C.sub.4 -straight chain alkylene, each forming with the carbon atom attached thereto a corresponding optionally substituted or benzo-fused 5, 6 or 7-membered ring; W represents 1-imidazolyl, 1-(1,2,4- or 1,3,4)-triazolyl or 3-pyridyl; or W represents 1-imidazolyl, 1-(1,2,4 or 1,3,4)-triazolyl or 3-pyridyl substituted by lower alkyl; and pharmaceutically acceptable salts thereof.

Disclosed are compounds of formula I ##STR1## wherein R.sub.1 represents hydrogen, lower alkyl, substituted lower alkyl, nitro, halogen, free, etherified or esterified hydroxy, free, etherified, oxidized etherified or esterified mercapto, unsubstituted, mono- or disubstituted amino, ammonio, free or functionally modified sulfo, free or functionally modified formyl, C.sub.2 -C.sub.20 -acyl, cyano, free or functionally modified carboxy; and R.sub.2 represents hydrogen, lower alkyl, substituted lower alkyl, halogen; free, etherified or esterified hydroxy; free, etherified, oxidized etherified or esterified mercapto; free or functionally modified carboxy, or acyl; the 7,8-dihydro derivatives thereof; and compounds of the formula I* ##STR2## wherein n denotes 0, 1, 2, 3 or 4, and R.sub.1 and R.sub.2 are as defined above under formula I and salts thereof; e.g. as aromatase inhibitors; pharmaceutical compositions containing these compounds; the use of these compounds for the treatment of conditions responsive to e.g. aromatase inhibition in mammals; processes and intermediates for preparing these compounds.

Substituted imidazo[1,5-A]pyridine derivatives and other substituted

Compounds of the formula ##STR1## wherein R.sub.1 represents cyano, nitro or C.sub.1 -C.sub.4 -alkyl or the 7,8-dihydro derivative thereof or the 5,6,7,8 tetrahydro derivative of the formula ##STR2## wherein R.sub.1 is as defined under formula Ia and R.sub.2 is hydrogen, C.sub.1 -C.sub.4 -alkyl, halogen etherified or esterified hydroxy or mercapto, carboxy-C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxycarbonyl-C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkanoyl, to stereoisomers, mixtures of these stereoisomers and salts of these compounds are disclosed as well as their preparation, pharmaceutical compositions containing the same and the use thereof as inhibitors of aromatase activity.

Substituted imidazo[1,5-A]pyridine derivatives as aromatase inhibitors

Disclosed are compounds of the formula I ##STR1## or a 5,6,7,8-tetrahydro derivative thereof, wherein R.sub.1 is hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy, or aryl-lower alkoxy in which aryl represents phenyl or phenyl substituted by lower alkoxy, lower alkyl, halogen or trifluoromethyl; R.sub.2 represents hydrogen, halogen, or lower alkyl; C represents carboxy, lower alkoxycarbonyl, unsubstituted or mono- or di-(lower alkyl) substituted carbamoyl, cyano, formyl, hydroxymethyl, 5-tetrazolyl, dihydro-2-oxazolyl, dihydro-2-oxazolyl substituted by lower alkyl, or hydroxycarbamoyl; and

Certain imidazo(1,5-a)pyridine derivatives and their use as thromboxane

Disclosed are compounds of formula I ##STR1## wherein Ar is 3- or 4-pyridyl or 3- or 4-pyridyl substituted by lower alkyl;

Certain N-(pyridyl) indoles

Disclosed are e.g. 5-(tetrazolylalkyl, hydroxycarbamoylalkyl)imidazo[1,5-a]-pyridines, and methods of synthesis. Said compounds are useful as selective thromboxane synthetase inhibitors for the treatment of diseases such as cerebral ischaemia, shock, thrombosis and ischaemic heart disease.

Certain imidazo (1,5-A) pyridine aliphatic carboxylic acid derivatives

Secondary hydroxypyridylalkylamines, e.g., those of the formula ##STR1## and acid addition salts thereof are cardioprotective, e.g., antiischemic agents.

Growing community of inventors

Morristown, NJ, United States of America

Leslie J Browne