Metabolic stabilization of substituted adamantane
OwnerJeffrey Rohde, Liping Pan +2inventors
InventorsJeffrey Rohde, Liping Pan, Marina Pliushchev, James Link
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Abstract
The present invention is directed to the method of increasing the metabolic stability of adamantane containing compounds that are inhibitors of the 11-beta-hydroxysteroid dehydrogenase Type 1 (11-beta-HSD-1) enzyme. The stability is achieved by substitutions of the adamantane ring.
Claims5
A method of increasing the metabolic stability of a pharmaceutically active adamantane compound by incorporating a substituted adamantane ring of formula (I),
- wherein
- one or more of A1, A2, A3, A4, B1, B2, B3 and B4 are individually selected from the group consisting of carboxy, alkyl-S(O)2NHC(O)—, tetrazolyl, carboxyalkyl, R1C(O)—N(R2)—, R1S(O)2N(R2)—, R1R2N-alkyl, R1R2NC(O)—, and R1R2NC(O)-alkyl, and the remainder of A1, A2, A3, A4, B1, B2, B3 and B4 are individually selected from the group consisting of hydrogen, carboxy, alkyl-S(O)2NHC(O)—, tetrazolyl, carboxyalkyl, R1C(O)—N(R2)—, R1S(O)2N(R2)—, R1R2N-alkyl, R1R2NC(O)—, and R1R2NC(O)-alkyl;
- R1 and R2 are each individually selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylcarbonyl, arylsulfonyl;
- and
- Z is a residue which imparts 11-beta-HSD-1 activity when attached to the adamantane ring system.
A method of increasing the metabolic stability of a pharmaceutically active adamantane compound that inhibits 11-beta-hydroxysteroid dehydrogenase Type 1 (11-beta-HSD-1) enzyme by incorporating a substituted adamantane ring of formula (I),
- wherein
- one or more of A1, A2, A3, A4, B1, B2, B3 and B4 are individually selected from the group consisting of carboxy, alkyl-S(O)2NHC(O)—, tetrazolyl, carboxyalkyl, R1C(O)—N(R2)—, R1S(O)2N(R2)—, R1R2N-alkyl, R1R2NC(O)—, and R1R2NC(O)-alkyl, and the remainder of A1, A2, A3, A4, B1, B2, B3 and B4 are individually selected from the group consisting of hydrogen, carboxy, alkyl-S(O)2NHC(O)—, tetrazolyl, carboxyalkyl, R1C(O)—N(R2)—, R1S(O)2N(R2)—, R1R2N-alkyl, R1R2NC(O)—, and R1R2NC(O)-alkyl;
- R1 and R2 are each individually selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylcarbonyl, and arylsulfonyl;
- and
- Z is a residue which imparts 11-beta-HSD-1 activity when attached to the adamantane ring system.
A method of increasing metabolic stability of a pharmaceutically active adamantane compound by substituting the adamantane compound with a group that can participate in hydrogen bonding.
Dependencies are inferred from the claim text.