N.v. Organon

Brad Sherborne

John Richard Morphy

Koc-Kan Ho

Simon James Anthony Grove

Steven G Kultgen

Celia Kingsbury

Niall Morton Hamilton

Peter Christopher Ray

Michael John Kiczun

Peter Thomas Albert Littlewood

Angus Richard Brown

Michael Ohhlmeyer

Steven Laats

The invention provides for compounds having the structure according to the formula I wherein: X is a carbon or nitrogen atom; Ar is phenyl or heteroaromatic ring; Ris hydrogen, halogen, CN or (1C-4C)alkyl; Ris hydrogen, halogen or optionally fluorinated (1C-3C)alkoxy; Rand Rare independently hydrogen, optionally halogenated (1C-4C)alkyl, optionally halogenated (1C-4C)alkoxy, optionally halogenated aryl(1C-4C)alkoxy, optionally halogenated (1C-4C)alkenyl or hydroxylmethyl; Ris hydrogen, halogen, optionally halogenated (1C-4C)alkoxy or optionally halogenated aryl(1C-4C)alkoxy; Ris hydrogen, benzyl, optionally substituted with one or more halogens or (1C-4C)alkyl, or Ris optionally halogenated (1C-4C)alkyl; each Rindependently is hydrogen, halogen, optionally halogenated (1C-4C)alkyl or optionally halogenated (1C-4C)alkoxy and pharmaceutically suitable acid addition salts thereof for use as glucocorticoid receptor modulators, in particular for treatment of central nervous system disorders.

Compounds with medicinal effects due to interaction with the glucocorticoid receptor

The present invention relates to 6-substituted isoquinoline derivatives having the general Formula I wherein X is O, S or NH; Y is OH or NH; m is 0, 1 or 2; n is 0 or 1; o is 0 or 1; Ris H, when Y is NH; or Ris H, (C)alkyl or halogen, when Y is OH; Rand Rare independently H, (C)alkyl or halogen; Ris H or (C)alkyl, optionally substituted with halogen, (C)cycloalkyl, (C)aryl or a saturated 5- or 6-membered heterocyclic ring comprising 1-3 heteroatoms independently selected from O, S and N, the (C)aryl and heterocyclic ring being optionally substituted with (C)alkyl, (C)alkyloxy or halogen; Ris H or (C)alkyl; or a pharmaceutically acceptable salt thereof, with the proviso that the compounds of Formula I wherein X is O, Y is OH , n is 0 and m+o=2 are excluded, to pharmaceutical compositions comprising the same, as well as to the use of said 6-substituted isoquinoline derivatives for the preparation of a medicament for the treatment of ROCK-I related disorders such as glaucoma, hypertension and atherosclerosis.

6-substituted isoquinoline derivatives

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Newhouse, United Kingdom

Brad Sherborne