1,3,8-triaza-spiro[4,5]decan-4-on derivatives

Details 1,3,8-triaza-spiro[4,5]decan-4-on derivatives 1,3,8-triaza-spiro[4,5]decan-4-on derivatives

C - Chemistry, Metallurgy

07

D

C07D 471/10 (2006.01) A61K 31/435 (2006.01) A61K 31/53 (2006.01) A61K 31/535 (2006.01)

Patent

CA 2255171

The present invention relates to compounds of the general formula (see formula I) wherein R1 is hydrogen, lower alkyl, halogen, lower alkoxy, trifluoromethyl, lower alkyl-phenyl or (C5-7)-cycloalkyl; R2 is hydrogen, lower alkyl, phenyl or lower alkyl-phenyl; R3 is hydrogen, lower alkyl, benzyl, lower alkyl-phenyl, lower alkyl- diphenyl, triazinyl, cyanomethyl, lower alkyl-piperidinyl, lower alkyl-naphthyl, (C5-7)-cycloalkyl, lower alkyl-(C5-7)-cycloalkyl, lower alkyl-pyridinyl, lower alkyl-morpholinyl, lower alkyl- dioxolanyl, lower alkyl-oxazolyl or lower alkyl-2-oxo-oxazolidinyl and wherein the ring systems may be substituted by additional lower alkyl, lower alkoxy, trifluoromethyl or phenyl, or -(CH2)n C(O)O-lower alkyl, -(CH2)n C(O)NH2, -(CH2)n C(O)N(lower alkyl)2, -(CH2)n OH or -(CH2)n C(O)NHCH2C6H5; R4 is hydrogen, lower alkyl or nitrilo; A is a ring system, consisting of (a) (C5-15)-cycloalkyl, which may be in addition to R4 optionally substituted by lower alkyl, trifluoromethyl, phenyl, (C5-7)-cycloalkyl, spiro-undecan- alkyl or by 2-norbornyl, or is one of the following groups (see formula b) (see formula c) (see formula d) dodecahydro-acenaphthylen-1yl (e), bicyclo[6.2.0]dec-9-yl (f) and bicyclononan-9-yl (g); and wherein R5 and R6 are hydrogen, lower alkyl or taken together and with the carbon atoms to which they are attached form a phenyl ring; R7 is hydrogen or lower alkyl; the dotted line represents an optional bond and n is 1 to 4; and to pharmaceutically acceptable acid addition salts thereof. Compounds of the present invention are agonists and/or antagonists of the Orphanin FQ (OFQ) receptor. Consequently they will be useful in the treatment of memory and attention deficits, psychiatric, neurological and physiological disorders, especially, but not limited to, amelioration of symptoms of anxiety and stress disorders, depression, trauma, memory loss due to Alzheimer's disease or other dementias, epilepsy and convulsions, acute and/or chronic pain conditions, symptoms of addictive drug withdrawal, control of water balance, Na+ excretion, arterial blood pressure disorders and metabolic disorders such as obesity.

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