US 8,138,206 B2 · Piperidine derivative

Abstract

Disclosed is a substance having an antagonistic effect on the binding of histamine to a histamine H3 receptor or an inhibitory effect on the activity which a histamine H3 receptor constantly exhibits. A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof; (I) wherein R1 represents a phenyl group which may be substituted or the like and R2 represents a cyano group which may be substituted or the like, or R1 and R2 together form an aliphatic heterocylic ring which may be substituted; R3 represents a group represented by the formula (II-1) below; and all of X1 to X4 represent a carbon atom or the like: (II-1) where R4 and R5 represent a lower alkyl group or the like; and m1 represents an integer of 2 to 4.

A compound of the formula (I):

wherein:
R1 is selected from the group consisting of:
an aryl group optionally having from 1 to 3 substituents selected from a substituent group α;
a 5- or 6-membered heteroaryl group having from 1 to 3 hetero atoms selected from a group consisting of a nitrogen atom, a sulfur atom and an oxygen atom, and optionally having from 1 to 3 substituents selected from the substituent group α;
a heteroarylalkyl group optionally having from 1 to 3 substituents selected from the substituent group α;
an aralkyl group optionally having from 1 to 3 substituents selected from the substituent group α;
an arylcarbonyl group optionally having from 1 to 3 substituents selected from the substituent group α;
and wherein the heteroaryl group may form a condensed ring with a phenyl group or a pyridyl group;
R2 is selected from the group consisting of:
an aryl group;
a heteroaryl group having from 1 to 3 hetero atoms selected from a group consisting of a nitrogen atom, a sulfur atom and an oxygen atom;
a cyano group;
a lower alkyl group;
a lower alkoxy group;
or a hydroxy group;
or
R1 and R2, taken together, may form a 5- or 6-membered aliphatic heterocyclic group having from 1 to 3 hetero atoms selected from a group consisting of a nitrogen atom, a sulfur atom and an oxygen atom, the aliphatic heterocyclic group may further form a condensed ring with a phenyl group or a pyridyl group, the aliphatic heterocyclic group may have 1 or 2, the same or different substituents selected from a substituent group β, the phenyl group or the pyridyl group that may be condensed with the aliphatic heterocyclic group to form a condensed ring may have 1 or 2, the same or different substituents selected from a substituent group γ;
R3 is selected from the group consisting of:
a) a group of a formula (II-1):
wherein R4 and R5 may be the same or different, each representing a lower alkyl group optionally substituted with a halogen atom, or a cycloalkyl group optionally substituted with a halogen atom;
or R4 and R5, taken together with the nitrogen atom, form a 5- to 8-membered monocyclic ring, or 6- to 8-membered bicyclic ring, and the monocyclic ring may have, as a substituent, a lower alkyl group optionally substituted with a halogen atom, or a halogen atom or an oxo group;
m 1 indicates an integer of from 2 to 4;
the hydrogen atom in —(CH2)m1— may be substituted with a lower alkyl group having from 1 to 3 carbon atoms;
b) a group of a formula (II-2):
wherein R6 represents a lower alkyl group or a cycloalkyl group;
m2 indicates an integer of from 0 to 4;
or
c) a group of a formula (II-3):
wherein R7 and R8 may be the same or different, each representing a lower alkyl group optionally substituted with a halogen atom, or a cycloalkyl group optionally substituted with a halogen atom;
or R7 and R8, taken together with the nitrogen atom, form a 5- to 8-membered monocyclic ring, or 6- to 8-membered bicyclic ring, and the monocyclic ring may have, as a substituent, a lower alkyl group optionally substituted with a halogen atom, or a halogen atom or an oxo group;
m3 indicates an integer of from 0 to 4;
X1 to X4 are all carbon atoms, wherein X1 to X4 are carbon atoms, then X1 to X4 may be substituted with a lower alkyl group optionally substituted with a halogen atom or a lower alkoxy group, a cycloalkyl group optionally substituted with a halogen atom or a lower alkoxy group, a lower alkoxy group optionally substituted with a halogen atom or a lower alkoxy group, or a cyano group or a halogen atom,
substituent group α is selected from the group consisting of:
a lower alkyl group optionally substituted with a halogen atom, a lower alkoxy group optionally substituted with a halogen atom, and a halogen atom;
substituent group β is selected from the group consisting of:
a halogen atom;
an oxo group;
a lower alkyl group optionally substituted with a halogen atom or a lower alkoxy group;
a lower alkoxy group optionally substituted with a halogen atom or a lower alkoxy group;
a 5- or 6-membered, nitrogen-containing aliphatic hetero ring optionally substituted with an oxo group or a lower alkyl group, and optionally having 1 or 2 double bonds in the ring;
an aralkyl group;
a heteroarylalkyl group;
a lower alkylsulfonyl group;
a cycloalkylsulfonyl group;
an aryl group;
and a heteroaryl group;
wherein the aralkyl group, the heteroarylalkyl group, the lower alkylsulfonyl group, the cycloalkylsulfonyl group, the aryl group and the heteroaryl group may be substituted with a lower alkyl group optionally substituted with a lower alkoxy group or a halogen atom, a cycloalkyl group optionally substituted with a lower alkoxy group or a halogen atom, a lower alkoxy group optionally substituted with a halogen atom (when the group has two such lower alkoxy groups, they may form, taken together, a 5- or 6-membered ring), a halogen atom, a cyano group, a hydroxyl group, an alkylsulfonyl group, a cycloalkylsulfonyl group, an aryl group, a heteroaryl group, an alkylaminocarbonyl group, an alkanoylamino group, an alkylamino group or a dialkylamino group;
substituent group γ is selected from the group consisting of:
a lower alkyl group optionally substituted with a lower alkoxy group or a halogen atom, a lower alkoxy group optionally substituted with a halogen atom, and a halogen atom;
or a pharmaceutically acceptable salt thereof.

47 more elements

Piperidine derivative

Life of this patent

Piperidine derivative

Life of this patent

Abstract

Claims20