Oxazolidine and Morpholine Carboxamide Derivatives as P2X7 Modulators

A compound of formula (I):

• wherein:
• R1 represents C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkylmethyl-, pyridinylmethyl- or benzyl, any of which is optionally substituted with 1, 2 or 3 halogen atoms;
• or an unsubstituted phenyl;
• X represents O or —(CR2R3)—;
• Y represents a bond or O;
• such that when X is O, Y represents a bond;
• and when X is —(CR2R3)—, Y represents O;
• R2 and R3 independently represent hydrogen, C1-6 alkyl, C6-10 arylmethyl- or C3-6 cycloalkylmethyl-;
• and any of said C1-6 alkyl, C6-10 arylmethyl- or C3-6 cycloalkylmethyl- is optionally substituted with 1, 2 or 3 halogen atoms;
• R4, R5 and R6 independently represent hydrogen, fluorine or methyl;
• and
• R7, R8, R9, R10 and R11 independently represent hydrogen, halogen, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl or phenyl, and any of said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl or phenyl is optionally substituted with 1, 2 or 3 halogen atoms;
• or R10 and R11 together with the carbon atoms to which they are attached form a benzene ring which is optionally substituted with 1, 2 or 3 halogen atoms;
• with the proviso that when R7 and R11 are both selected from hydrogen or fluorine, at least one of R8, R9 and R10 is a halogen atom.

A compound which is:

• (4R)-N-[(2-chloro-4-fluorophenyl)methyl]-3-ethyl-2-oxo-1,3-oxazolidine-4-carboxamide;
• N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1,3-oxazolidine-4-carboxamide;
• (4R)-N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1,3-oxazolidine-4-carboxamide;
• N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-5-oxo-4-(phenylmethyl)-3-morpholinecarboxamide;
• N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-5-oxo-4-(phenylmethyl)-3-morpholinecarboxamide;
• N-[(2,4-dichlorophenyl)methyl]-5-oxo-4-(phenylmethyl)-3-morpholinecarboxamide;
• N-(1-naphthalenylmethyl)-5-oxo-4-(phenylmethyl)-3-morpholinecarboxamide;
• or
• N-[(2-chloro-4-fluorophenyl)methyl]-5-oxo-4-(phenylmethyl)-3-morpholinecarboxamide.

A compound which is:

• (4S)-N-[(2-chloro-4-fluorophenyl)methyl]-3-ethyl-2-oxo-1,3-oxazolidine-4-carboxamide;
• (4S)-N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-3-methyl-2-oxo-1,3-oxazolidine-4-carboxamide;
• or
• N-{[2-chloro-3-(trifluoromethyl)phenyl]methyl}-4-methyl-5-oxo-3-morpholinecarboxamide.

A compound of formula (IB):

• wherein:
• R1 represents methyl or ethyl;
• X represents O or —(CR2R3)—;
• Y represents a bond or O;
• such that when X is O, Y represents a bond;
• and when X is —(CR2R3)—, Y represents O;
• R2, R3, R4, R5 and R6 all represent hydrogen;
• and
• R7, R8, R9, R10 and R11 independently represent hydrogen, halogen, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl or phenyl, and any of said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl or phenyl is optionally substituted with 1, 2 or 3 halogen atoms;
• or R10 and R11 together with the carbon atoms to which they are attached form a benzene ring which is optionally substituted with 1, 2 or 3 halogen atoms;
• with the proviso that when R7 and R11 are both selected from hydrogen or fluorine, at least one of R8, R9 and R10 is a halogen atom;
• and wherein more than 50% by molarity of the compound of formula (IB) has the indicated stereochemistry at the ring-carbon atom bonded to R6.