Compounds co-inducing cholinergic up-regulation and inflammation down-regulation and uses thereof
AssigneeIsrael Institute for Biological Research
InventorsGabriel Amitai, Rachel Adani, Ishai Rabinovitz, Gali Sod-Moriah, Haim Meshulam
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Abstract
Chimeric compounds are disclosed which are covalent conjugates of reversible or irreversible cholinergic up-regulators and non-steroidal anti-inflammatory drugs (NSAIDs), methods for their synthesis and use thereof for treatment and/or prevention of central nervous system (CNS) disorders and diseases.
Claims133
A chimeric compound comprising a cholinergic up-regulator moiety and a non-steroidal anti-inflammatory moiety being covalently linked thereto.
A chimeric compound of a general formula:
- A-S-B
- wherein:
- A is a cholinergic up-regulator moiety selected from the group consisting of a cholinesterase inhibitor residue, a nicotinic receptor agonist residue and a muscarinic receptor agonist residue;
- B is a non-steroidal anti-inflammatory moiety characterized by a functional group selected from the group consisting of a free carboxylic acid group and a free amine group;
- and
- S is a hydrocarbon spacer being covalently linked to B via a —C(═X)Y— bond, where X is a non-substituted or substituted oxygen, sulfur or nitrogen atom and Y is a substituted or non-substituted carbon, oxygen, nitrogen, sulfur, silicon or phosphor atom linked to said C via a single covalent bond.
A reversible cholinesterase inhibitor having a general formula A:
- 11
- wherein,
- R1 is C(═Q)Z-R3;
- R2 is selected from the group consisting of hydrogen, an alkyl, a hydroxyalkyl, a haloalkyl, an alkylamine, a cycloalkyl and an aryl;
- X is a halide.
- Q and Z are each independently selected from the group consisting of oxygen and sulfur;
- and
- R3 is selected from the group consisting of an alkyl, a cycloalkyl and an aryl.
A reversible cholinesterase inhibitor having a general formula B:
- 12
- wherein,
- R1 is C(═Q)Z-R3;
- R2 is selected from the group consisting of hydrogen, an alkyl, a hydroxyalkyl, a haloalkyl, an alkylamine, a cycloalkyl and an aryl;
- Q and Z are each independently selected from the group consisting of oxygen or sulfur;
- and
- R3 is selected from the group consisting of an alkyl, a cycloalkyl and an aryl.
Dependencies are inferred from the claim text.