N.v. Organon

Merck Sharp + Dohme B.v.

Peter Christopher Ray

John Richard Morphy

Grant Wishart

Ashvinkumar Dhirubhai Mistry

Brad Sherborne

Keneth Davies

Takao Kiyoi

Mark Reid

Steven Laats

The present invention relates to a tricyclic heterocyclic derivative according to Formula (I), wherein the variables are defined as in the specification, or to a pharmaceutically acceptable salt or solvate thereof. The present invention also relates to pharmaceutical compositions comprising said tricyclic heterocyclic derivatives and to their use in therapy, for instance in the treatment or prevention of serotonin mediated disorders, such as obesity. 

Tricyclic heterocyclic derivatives

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

The invention relates to 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 1 or 2; 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; R is H or (C)alkyl, optionally substituted with OH, (C)-alkyloxy, (C)alkyloxycarbonyl, (C)cycloalkyl, which may optionally comprise a heteroatom selected from O and S, (C)aryl, (C)aryloxy or a 5- or 6-membered heteroaryl group comprising 1-3 heteroatoms independently selected from O, N and S, each aryl or heteroaryl group being optionally substituted with 1-3 substituents independently selected from (C)alkyl, (C)alkyloxy, (C)alkylsulfonyl and halogen; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same as well as to the use of the isoquinoline derivatives in the treatment of ROCK-I related disorders such as hypertension, atherosclerosis and glaucoma.

Isoquinoline derivatives

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Newhouse, United Kingdom

Peter Christopher Ray