Anti-obesity 1,2,3,4,10,10a-hexahydropyrazino[1,2-a] indoles
AssigneesHoffmann-La Roche Inc., Vernalis Research Limited
InventorsJonathan Bentley, Paul Hebeisen, Patrizio Mattei, Marc Muller, Hans Richter, Stephan Roever, Sven Taylor
Life of this patent
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Abstract
The present invention is directed to 1,2,3,4,10,10a,-hexahydropyrazino[1,2-a]indole derivatives as well as pharmaceutically acceptable salts, solvates and esters thereof, wherein R1 to R8 have the significance given in claim 1 be used in the form of pharmaceutical preparations for the treatment or prevention of disorders of the central nervous system, damage to the central nervous system, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, obesity and sleep apnea.
Claims118
A compound of formula (I):
- wherein
- R1, R2, R3 and R4 are independently hydrogen, halogen, hydroxy, alkyl, cycloalkyl, aralkyl, aryl, alkoxy, alkoxy alkyl, hydroxy alkyl, alkoxy alkoxy alkyl, hydroxyalkoxy alkyl, halo alkyl, halo alkoxy, aryloxy, alkylcarbonyl, arylcarbonyl, alkylthio, arylthio, alkylsulfoxyl, arylsulfoxyl, alkylsulfonyl, arylsulfonyl, amino, nitro, cyano, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylcarbonylamino, carboxy, heterocyclyl or R3 and R4 form together with the carbon atoms to which they are attached form a 5- to 7-membered carbocyclic ring which ring is unsubstituted or alkyl substituted;
- R5 is hydrogen, alkyl or cycloalkyl;
- R6 is hydrogen, alkyl, hydroxy alkyl, carbamoyl alkyl, alkoxycarbonyl alkyl, aryloxycarbonyl alkyl or —(CH2)n-A;
- R7 is hydrogen, alkyl, cycloalkyl, hydroxyalkyl or alkoxyalkyl, whereby R7 is not hydrogen when R6 is hydrogen, alkyl, cycloalkyl or 1H-pyrrolo(2,3-b)pyridin-3-ylmethyl;
- R8 is hydrogen, alkyl or cycloalkyl;
- A is a heterocyclyl or cycloalkyl ring which ring can be unsubstituted or substituted on a ring carbon atom with a hydroxy, carboxy, oxo, alkanoyloxy alkyl, aryloxycarbonyl or alkylcarbamoyl substituent;
- n is 0, 1, 2 or 3;
- or pharmaceutically acceptable salts, solvates or esters thereof.
(canceled)
32-33. (canceled)
42-50. (canceled)
57-58. (canceled)
(canceled)
110-115. (canceled)
The compound of claim 115 wherein said compound is (4R,10aR)-N-(4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indol-7-yl)-acetamide;
- hydrochloride.
The compound of claim 115 wherein said compound is (4R,10aR)-(4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indol-7-yl)-methanol;
- hydrochloride.
The compound of claim 115 wherein said compound is (4R,10aR)-4-methyl-1,2,3,4,10,10a-hexahydro-pyrazino[1,2-a]indole-7-carboxylic acid butylamide;
- hydrochloride.
119-121. (canceled)
Dependencies are inferred from the claim text.