Piperidinic Derivatives, Pharmaceutic Compositions Containing the Same and Preparation Processes

Piperidinic derivatives, inhibitors of acetylcholinesterase and/or its isoforms having:

• the general formula (II):
• wherein:
• n corresponds to an integer number from 2 to 16.
• R1 is hydrogen, acyl, alkyl, alcoxyl, cycloalkyl;
• furyl, tiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl, isoquinolyl or Phenyl-W;
• wherein W is hydrogen, ortho-alkyl, ortho-cycloalkyl, ortho-alcoxyl, ortho-cycloalcoxyl, ortho-thioxy, ortho-aryloxy, ortho-sulfones, ortho-sulfides, ortho-sulfoxides, ortho-sulfonates, ortho-sulfonamides, ortho-amino, ortho-amido, ortho-halo, ortho-carboalkoxy, ortho-carbothioalkoxy, ortho-trihaloalkane, ortho-cyano, ortho-nitro, meta-alkyl, meta-cycloalkyl, meta-alcoxyl, meta-cycloalcoxyl, meta-thioxy, meta-aryloxy, meta-sulfones, meta-sulfides, meta-sulfoxides, meta-sulfonates, meta-sulfonamides, meta-amino, meta-amido, meta-halo, meta-carboalkoxy, meta-carbothioalkoxy, meta-trihaloalkane, meta-cyano, meta-nitro, para-alkyl, para-cycloalkyl, para-alcoxyl, para-cycloalcoxyl, para-thioxy, para-aryloxy, para-sulfones, para-sulfides, para-sulfoxides, para-sulfonates, para-sulfonamides, para-amino, para-amido, para-halo, para-carboalkoxy, para-carbothioalkoxy, para-trihaloalkane, para-cyano or para-nitro;
• R2 is either -hydrogen or alkyl with 1 to 9 carbon atoms, and
• X is halogen;
• or a pharmaceutically acceptable salt thereof.

Piperidinic derivatives, inhibitors of acetylcholinesterase and/or its isoforms comprising:

• the general formula (III):
• wherein:
• n corresponds to an integer number from 2 to 16.
• R1 is hydrogen, acyl, alkyl, alcoxyl, cycloalkyl;
• furyl, tiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl, isoquinolyl or Phenyl-W;
• wherein W is hydrogen, ortho-alkyl, ortho-cycloalkyl, ortho-alcoxyl, ortho-cycloalcoxyl, ortho-thioxy, ortho-aryloxy, ortho-sulfones, ortho-sulfides, ortho-sulfoxides, ortho-sulfonates, ortho-sulfonamides, ortho-amino, ortho-amido, ortho-halo, ortho-carboalkoxy, ortho-carbothioalkoxy, ortho-trihaloalkane, ortho-cyano, ortho-nitro, meta-alkyl, meta-cycloalkyl, meta-alcoxyl, meta-cycloalcoxyl, meta-thioxy, meta-aryloxy, meta-sulfones, meta-sulfides, meta-sulfoxides, meta-sulfonates, meta-sulfonamides, meta-amino, meta-amido, meta-halo, meta-carboalkoxy, meta-carbothioalkoxy, meta-trihaloalkane, meta-cyano, meta-nitro, para-alkyl, para-cycloalkyl, para-alcoxyl, para-cycloalcoxyl, para-thioxy, para-aryloxy, para-sulfones, para-sulfides, para-sulfoxides, para-sulfonates, para-sulfonamides, para-amino, para-amido, para-halo, para-carboalkoxy, para-carbothioalkoxy, para-trihaloalkane, para-cyano or para-nitro-.
• R2 is either -hydrogen or alkyl with 1 to 9 carbon atoms, and
• X is halogen;
• or a pharmaceutically acceptable salt thereof.

Pharmaceutical composition for the treatment of pathologies associated with cholinergic transmission, comprising:

• a pharmaceutically acceptable vehicle and at least-one compound of general formula (I):
• wherein:
• n corresponds to an integer number from 2 to 16;
• R1 is hydrogen, acyl, alkyl, alcoxyl, cycloalkyl;
• furyl, tiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl, isoquinolyl or Phenyl-W;
• wherein W is hydrogen, ortho-alkyl, ortho-cycloalkyl, ortho-alcoxyl, ortho-cycloalcoxyl, ortho-thioxy, ortho-aryloxy, ortho-sulfones, ortho-sulfides, ortho-sulfoxides, ortho-sulfonates, ortho-sulfonamides, ortho-amino, ortho-amido, ortho-halo, ortho-carboalkoxy, ortho-carbothioalkoxy, ortho-trihaloalkane, ortho-cyano, ortho-nitro, meta-alkyl, meta-cycloalkyl, meta-alcoxyl, meta-cycloalcoxyl, meta-thioxy, meta-aryloxy, meta-sulfones, meta-sulfides, meta-sulfoxides, meta-sulfonates, meta-sulfonamides, meta-amino, meta-amido, meta-halo, meta-carboalkoxy, meta-carbothioalkoxy, meta-trihaloalkane, meta-cyano, meta-nitro, para-alkyl, para-cycloalkyl, para-alcoxyl, para-cycloalcoxyl, para-thioxy, para-aryloxy, para-sulfones, para-sulfides, para-sulfoxides, para-sulfonates, para-sulfonamides, para-amino, para-amido, para-halo, para-carboalkoxy, para-carbothioalkoxy, para-trihaloalkane, para-cyano or para-nitro;
• or a pharmaceutically acceptable salt thereof.

Pharmaceutical composition for the treatment of pathologies associated to cholinergic transmission, comprising:

• a pharmaceutically acceptable vehicle and at least-one compound of general formula (II):
• wherein:
• n corresponds to an integer number from 2 to 16;
• R1 is hydrogen, acyl, alkyl, alcoxyl, cycloalkyl;
• furyl, tiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl, isoquinolyl or Phenyl-W;
• wherein W is hydrogen, ortho-alkyl, ortho-cycloalkyl, ortho-alcoxyl, ortho-cycloalcoxyl, ortho-thioxy, ortho-aryloxy, ortho-sulfones, ortho-sulfides, ortho-sulfoxides, ortho-sulfonates, ortho-sulfonamides, ortho-amino, ortho-amido, ortho-halo, ortho-carboalkoxy, ortho-carbothioalkoxy, ortho-trihaloalkane, ortho-cyano, ortho-nitro, meta-alkyl, meta-cycloalkyl, meta-alcoxyl, meta-cycloalcoxyl, meta-thioxy, meta-aryloxy, meta-sulfones, meta-sulfides, meta-sulfoxides, meta-sulfonates, meta-sulfonamides, meta-amino, meta-amido, meta-halo, meta-carboalkoxy, meta-carbothioalkoxy, meta-trihaloalkane, meta-cyano, meta-nitro, para-alkyl, para-cycloalkyl, para-alcoxyl, para-cycloalcoxyl, para-thioxy, para-aryloxy, para-sulfones, para-sulfides, para-sulfoxides, para-sulfonates, para-sulfonamides, para-amino, para-amido, para-halo, para-carboalkoxy, para-carbothioalkoxy, para-trihaloalkane, para-cyano or para-nitro;
• R2 is either -hydrogen or alkyl with 1 to 9 carbon atoms, and
• X is halogen;
• or a pharmaceutically acceptable salt thereof.

Pharmaceutical composition for the treatment of pathologies associated to cholinergic transmission, comprising:

• a pharmaceutically acceptable vehicle and at least-one compound of general formula (III):
• wherein:
• n corresponds to an integer number from 2 to 16.
• R1 is hydrogen, acyl, alkyl, alcoxyl, cycloalkyl;
• furyl, tiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl, isoquinolyl or Phenyl-W;
• wherein W is hydrogen, ortho-alkyl, ortho-cycloalkyl, ortho-alcoxyl, ortho-cycloalcoxyl, ortho-thioxy, ortho-aryloxy, ortho-sulfones, ortho-sulfides, ortho-sulfoxides, ortho-sulfonates, ortho-sulfonamides, ortho-amino, ortho-amido, ortho-halo, ortho-carboalkoxy, ortho-carbothioalkoxy, ortho-trihaloalkane, ortho-cyano, ortho-nitro, meta-alkyl, meta-cycloalkyl, meta-alcoxyl, meta-cycloalcoxyl, meta-thioxy, meta-aryloxy, meta-sulfones, meta-sulfides, meta-sulfoxides, meta-sulfonates, meta-sulfonamides, meta-amino, meta-amido, meta-halo, meta-carboalkoxy, meta-carbothioalkoxy, meta-trihaloalkane, meta-cyano, meta-nitro, para-alkyl, para-cycloalkyl, para-alcoxyl, para-cycloalcoxyl, para-thioxy, para-aryloxy, para-sulfones, para-sulfides, para-sulfoxides, para-sulfonates, para-sulfonamides, para-amino, para-amido, para-halo, para-carboalkoxy, para-carbothioalkoxy, para-trihaloalkane, para-cyano or para-nitro;
• R2 is either -hydrogen or alkyl with 1 to 9 carbon atoms, and
• X is halogen;
• or a pharmaceutically acceptable salt thereof.

Process for the preparation of piperidinic derivatives of general formula (I):

• wherein:
• n corresponds to an integer number from 2 to 16, and
• R1 is hydrogen, acyl, alkyl, alcoxyl, cycloalkyl;
• furyl, tiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl, isoquinolyl or Phenyl-W;
• wherein W is hydrogen, ortho-alkyl, ortho-cycloalkyl, ortho-alcoxyl, ortho-cycloalcoxyl, ortho-thioxy, ortho-aryloxy, ortho-sulfones, ortho-sulfides, ortho-sulfoxides, ortho-sulfonates, ortho-sulfonamides, ortho-amino, ortho-amido, ortho-halo, ortho-carboalkoxy, ortho-carbothioalkoxy, ortho-trihaloalkane, ortho-cyano, ortho-nitro, meta-alkyl, meta-cycloalkyl, meta-alcoxyl, meta-cycloalcoxyl, meta-thioxy, meta-aryloxy, meta-sulfones, meta-sulfides, meta-sulfoxides, meta-sulfonates, meta-sulfonamides, meta-amino, meta-amido, meta-halo, meta-carboalkoxy, meta-carbothioalkoxy, meta-trihaloalkane, meta-cyano, meta-nitro, para-alkyl, para-cycloalkyl, para-alcoxyl, para-cycloalcoxyl, para-thioxy, para-aryloxy, para-sulfones, para-sulfides, para-sulfoxides, para-sulfonates, para-sulfonamides, para-amino, para-amido, para-halo, para-carboalkoxy, para-carbothioalkoxy, para-trihaloalkane, para-cyano or para-nitro;
• or a pharmaceutically acceptable salt thereof,
• comprising at least one step of alcoholic and/or hydroalcoholic extraction of flowers and/or buds from plants of the Cassia genus.

Process for the preparation of piperidinic derivatives of general formula (II).

• wherein:
• n corresponds to an integer number from 2 to 16.
• R1 is hydrogen, acyl, alkyl, alcoxyl, cycloalkyl;
• furyl, tiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl, isoquinolyl or Phenyl-W;
• wherein W is hydrogen, ortho-alkyl, ortho-cycloalkyl, ortho-alcoxyl, ortho-cycloalcoxyl, ortho-thioxy, ortho-aryloxy, ortho-sulfones, ortho-sulfides, ortho-sulfoxides, ortho-sulfonates, ortho-sulfonamides, ortho-amino, ortho-amido, ortho-halo, ortho-carboalkoxy, ortho-carbothioalkoxy, ortho-trihaloalkane, ortho-cyano, ortho-nitro, meta-alkyl, meta-cycloalkyl, meta-alcoxyl, meta-cycloalcoxyl, meta-thioxy, meta-aryloxy, meta-sulfones, meta-sulfides, meta-sulfoxides, meta-sulfonates, meta-sulfonamides, meta-amino, meta-amido, meta-halo, meta-carboalkoxy, meta-carbothioalkoxy, meta-trihaloalkane, meta-cyano, meta-nitro, para-alkyl, para-cycloalkyl, para-alcoxyl, para-cycloalcoxyl, para-thioxy, para-aryloxy, para-sulfones, para-sulfides, para-sulfoxides, para-sulfonates, para-sulfonamides, para-amino, para-amido, para-halo, para-carboalkoxy, para-carbothioalkoxy, para-trihaloalkane, para-cyano or para-nitro;
• R2 is either hydrogen or alkyl with 1 to 9 carbon atoms, and
• X is halogen;
• or a pharmaceutically acceptable salt thereof;
• comprising the step of submitting the respective starting compounds to a reaction of acidification with strong acids.

Process for the preparation of piperidinic derivatives of general formula (III)

• wherein
• n corresponds to an integer number from 2 to 16.
• R1 is hydrogen, acyl, alkyl, alcoxyl, cycloalkyl;
• furyl, tiophenyl, pyridinyl, pyrimidinyl, pyrrolyl, thiazolyl, quinazolyl, isoquinolyl or Phenyl-W;
• wherein W is hydrogen, ortho-alkyl, ortho-cycloalkyl, ortho-alcoxyl, ortho-cycloalcoxyl, ortho-thioxy, ortho-aryloxy, ortho-sulfones, ortho-sulfides, ortho-sulfoxides, ortho-sulfonates, ortho-sulfonamides, ortho-amino, ortho-amido, ortho-halo, ortho-carboalkoxy, ortho-carbothioalkoxy, ortho-trihaloalkane, ortho-cyano, ortho-nitro, meta-alkyl, meta-cycloalkyl, meta-alcoxyl, meta-cycloalcoxyl, meta-thioxy, meta-aryloxy, meta-sulfones, meta-sulfides, meta-sulfoxides, meta-sulfonates, meta-sulfonamides, meta-amino, meta-amido, meta-halo, meta-carboalkoxy, meta-carbothioalkoxy, meta-trihaloalkane, meta-cyano, meta-nitro, para-alkyl, para-cycloalkyl, para-alcoxyl, para-cycloalcoxyl, para-thioxy, para-aryloxy, para-sulfones, para-sulfides, para-sulfoxides, para-sulfonates, para-sulfonamides, para-amino, para-amido, para-halo, para-carboalkoxy, para-carbothioalkoxy, para-trihaloalkane, para-cyano or para-nitro;
• R2 is either hydrogen or alkyl with 1 to 9 carbon atoms, and
• X is halogen;
• or a pharmaceutically acceptable salt thereof;
• comprising the step of submitting the respective starting compounds to a reduction reaction.