Ciba-geigy Corporation

Damian Pharma Ag

Ronald E Steele

Robert M Bowman

Leslie J Browne

Christoph Schumacher

Walter Fuhrer

Bruce H Ewald

Leslie Browne

Robert Diener

The present invention relates to a compound selected from (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine and a pharmaceutically acceptable salt thereof, and in particular to the phosphate salt of (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine, both having preferably an enantiomeric excess of the (R) form higher than or equal to 97%. Furthermore, the present invention relates to pharmaceutical compositions comprising the same, their use as a medicament and in methods of treatment of diseases and disorders in humans including women of child bearing potential and pediatric patients in which aldosterone over-exposure contributes to the deleterious effects of said diseases or disorders, as well as processes for preparing said inventive compounds.

Aldosterone synthase inhibitor

The present invention relates to a composition for use in the treatment of a disease or disorder, wherein said disease or disorder is preferably a disease or disorder in which aldosterone overexposure contributes to the symptoms of said disease or disorder, said composition comprises a compound which is (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine or a pharmaceutically acceptable salt thereof, wherein preferably said compound is (R)-(+)-5-(p-cyanophenyl)-5,6,7,8-tetrahydroimidazolium[1,5-a]pyridine dihydrogen phosphate, and wherein said compound has an enantiomeric excess (ee) of the (R) form higher than or equal to 97%, and wherein said composition is administered once daily to a subject in need thereof. The invention further relates to a pharmaceutical composition comprising a daily dosage of said compound in a fixed-unit dosage form and to a combination comprising (i) said pharmaceutical composition or said compound; and (ii) instructions for administration of said pharmaceutical composition or said compound once per day.

R-fadrozole for use in the treatment of aldostonerism

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

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-heterocyclc substituted tolunitriles

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.

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Long Valley, NJ, United States of America

Ronald E Steele