Use of known agonists of the central cannabinoid receptor CB1
AssigneeBayer Aktiengesellschaft
InventorsJoachim Mittendorf, Jürgen Dressel, Michael Matzke, Jürgen Franz, Peter Spreyer, Verena Vöhringer, Joachim Schuhmacher, Arno Friedl, Ervin Horvath, Frank Mauler, Jean-Marie-Viktor De Vry, Reinhard Jork
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Abstract
The present invention relates to the use of known agonists of the central cannabinoid receptor CB1 for the prophylaxis and treatment of neurodegenerative disorders, in particular for the treatment of cerebral apoplexy and craniocerebral trauma.
Claims5
A method of preventing or treating a condition in a patient, said condition being selected from cerebral apoplexy, craniocerebral trauma, and a combination of cerebral apoplexy and craniocerebral trauma, and said method comprising administering to said patient an amount of an agonist of the cannabinoid receptor CB1 which is effective to prevent or treat said condition, wherein said agonist has the formula (I):
- in which
- A and D are identical or different and represent, depending on the position of a single or double bond, a C atom or the CH group;
- E represents, depending on the position of a single or double bond, the CH group, the CH2 group or a sulfur atom;
- G, L and M are identical or different and represent, depending on the position of a single or double bond, a radical of the formula —CR5, —CR6R7 or —NR8;
- in which
- R5, R6, R7 and R8 are identical or different and represent hydrogen, hydroxyl, formyl, C2-6-alkenyl, C2-6-alkinyl or C1-6-alkyl, which alkyl is optionally substituted by hydroxyl or C1-4-alkoxy;
- or
- R6 and R7 together represent a radical of the formula ═O;
- a represents a number 0 or 1;
- R1 represents hydrogen or hydroxyl;
- or
- represents C1-11-alkyl, C1-6-alkoxy, C1-6-alkoxycarbonyl or C1-4-acyloxy, each of which is optionally substituted by hydroxyl, C1-10-alkoxy or by a group of the formula —NR9R10;
- in which
- R9 and P10 are identical or different and represent hydrogen, phenyl or C1-4-alkyl;
- or
- R9 and R10, together with the nitrogen atom to which they are bonded, form a 5- to 7-membered saturated heterocyclic ring which in addition to the nitrogen atom optionally contains in the heterocyclic ring a sulfur atom, an oxygen atom or a radical of the formula —NR11;
- in which
- R11 represents hydrogen, phenyl, C1-6-alkyl or C1-6-acyl;
- R2 represents C1-10-alkyl or C1-10-alkoxy, each of which is optionally substituted by phenyl, halogen, hydroxyl, azido, nitro, trifluoromethyl, trifluoromethoxy, carboxyl, C1-4-alkoxy, C1-4-alkoxycarbonyl or a group of the formula —NR12R13;
- in which
- R12 and R13 are identical or different and represent hydrogen, phenyl or C1-4-alkyl;
- or
- R12 and R13, together with the nitrogen atom to which they are bonded, form a 5- to 7-membered heterocyclic ring which in addition to the nitrogen atom optionally contains in the heterocyclic ring a sulfur atom, an oxygen atom or a radical of the formula —NR11;
- in which
- R11 has the meaning indicated above;
- R3 and R4 are identical or different and represent hydrogen or C1-6-alkyl, which alkyl is optionally substituted by hydroxyl;
- or
- R3 and R4 together represent a radical of the formula H2C═;
- T represents C1-6-alkyl or C2-6-alkenyl;
- and
- V represents hydroxyl;
- or
- T and V together with a ring closure represent an oxygen atom or a radical of the formula —NR14;
- in which
- R14 represents hydrogen or methyl;
- or a salt or stercoisometeric from thereof;
- with the exception of any compound of the following configuration:
- wherein L, R1 and R2 have the meanings indicated above.
A method of preventing or treating a condition in a patient, said condition being selected from cerebral apoplexy, craniocerebral trauma and a combination of cerebral apoplexy and craniocerebral trauma, and said method comprising administering to said patient an amount of an agonist of the cannabinoid receptor CB1 which is effective to prevent or treat said condition, wherein said agonist has the formula (Ia):
- in which
- R1′ represents hydrogen or hydroxyl;
- or
- represents C1-11-alkyl, C1-6-alkoxy, C1-6-alkoxycarbonyl or C1-4-acyloxy, each of which is optionally substituted by hydroxy, C1-10-alkoxy or by a group of the formula —NR9R10;
- in which
- R9 and R10 are identical or different and represent hydrogen, phenyl or C1-4-alkyl;
- or
- R9 and R10, together with the nitrogen atom to which they are bonded, form a 5- to 7-membered saturated heterocyclic ring which in addition to the nitrogen atom optionally contains in the heterocyclic ring a sulfur atom, an oxygen atom or a radical of the formula —NR11;
- in which
- R11 represents hydrogen, phenyl, C1-6-allkyl or C1-6-acyl;
- R2′ represents C1-10-alkyl or C1-10-alkoxy, each of which is optionally substituted by phenyl, halogen, hydroxyl, azido, nitro, trifluoromethyl, trifluoromethoxy, carboxyl, C1-4-alkoxy, C1-4-alkoxycarbonyl or a group of the formula —NR12R13;
- in which
- R12 and R13 are identical or different and represent hydrogen, phenyl or C1-4-alkyl;
- or
- R12 and R13 together with the nitrogen atom to which they are bonded, form a 5- to 7-membered saturated heterocyclic ring which in addition to the nitrogen atom optionally contains in the heterocyclic ring a sulfur atom, an oxygen atom or a radical of the formula —NR11;
- in which
- R11 has the meaning indicated above;
- R15 and R16 are identical or different and represent hydrogen or C1-8-alkyl, which alkyl is optionally substituted by hydroxyl;
- or
- R15 and R16 together with the C—C bond to which they are bonded form a phenyl ring or a 3- to 7-membered carbocyclic ring, which phenyl ring and 3- to 7-membered carbocyclic ring are optionally substituted by C1-6-alkoxycarbonyl or C1-8-alkyl, where the C1-8-alkyl is, in turn, optionally substituted by hydroxyl;
- R17 represents hydrogen;
- or
- R16 and R17 together with a ring closure from a 6-membered saturated, partially saturated or unsaturated heterocyclic ring which contains a sulfur atom, an oxygen atom or a group of the formula —NR18;
- in which
- R18 represents hydrogen or C1-4-alkyl;
- where the 6-membered saturated partially saturated or unsaturated heterocyclic ring is optionally substituted, optionally generally, 1 to 3 times by identical or different C1-8-alkyl groups, where the C1-8-alkyl groups are, in turn, optionally substituted by hydroxyl,
- or a salt or stereoisomeric form thereof.
Dependencies are inferred from the claim text.