Oxazolidin-2-one and thiazolidin-2-one derivatives for use as ep4 receptor agonists in the treatment of glaucoma

A compound having the structural formula I:

• or a pharmaceutically acceptable salt thereof, wherein,
• X is O or S;
• Y1 is
• 1) CH2CH2,
• 2) CHCH, or
• Y is C(O) or CH(OH);
• A and W are independently selected from the group consisting of
• 1) a bond, and
• 2) C1-6 alkylene, unsubstituted or substituted with 1, 2, 3, or 4 halogen atoms;
• Z is
• 1) O,
• 2) S,
• 4) CH2
• 5) HC═CH,
• 6) C≡C, or
• 7) a disubstituted aryl or heteroaryl ring, wherein one ring atom of the ring is attached to the moiety
• —W—R1
• and another ring atom is attached to the moiety
• with the proviso that when Z is O or S, then A and W are independently selected from the group consisting of C1-6 alkylene, unsubstituted or substituted with 1, 2, 3, or 4 halogen atoms;
• R1 is
• COR5,
• OH,
• CN,
• (CH2)1-3 CO2R6,
• (CH2)0-4SO3R6,
• CF2SO2NH2,
• SO2NH2,
• SO2NHCOR8,
• PO(OH)2,
• C1-4 alkoxy,
• hydroxymethylketone,
• (CH2)0-4 heterocyclyl, wherein heterocyclyl is unsubstituted or substituted with 1 to 3 groups of Ra, or
• tetrazole;
• R2 is
• 1) C1-6alkyl, provided that R2 is not n-pentyl,
• 2) (CH2)0-8C6-10aryl,
• 3) (CH2)0-8C5-10heteroaryl,
• 4) (CH2)0-8C3-10heterocycloalkyl,
• 5) (CH2)0-8C3-8cycloalkyl,
• 6) O—C1-10alkyl,
• 7) O—C6-10aryl,
• 8) O—C5-10heteroaryl,
• 9) O—C5-10heterocycloalkyl,
• 10) O—C3-10cycloalkyl
• wherein aryl, heteroaryl, heterocycloalkyl, and cycloalkyl are unsubstituted or substituted with 1-3 groups of Rb;
• R3 and R4 are independently selected from the group consisting of
• 1) hydrogen,
• 2) halogen, and
• 3) C1-6 alkyl, or
• R3 and R4, together with the carbon atom to which they are attached, form a C3-7 cycloalkyl ring;
• R5 is
• 1) hydrogen,
• 2) OH,
• 3) CH2OH,
• 4) C1-6 alkoxy,
• 5) NHPO2R6,
• 6) NHR9,
• 7) NHSO2R8, or
• 8) NR6R7;
• R6 and R7 are independently selected from the group consisting of hydrogen and C1-6 alkyl;
• R8 is selected from the group consisting of hydrogen, C6-10aryl, and C1-4alkyl;
• R9 is acyl or sulfonyl;
• and
• Ra and Rb are independently selected from the group consisting of
• 1) C1-6alkoxy,
• 2) C1-6alkyl, unsubstituted or substituted with
• a) C1-6 alkoxy,
• b) C1-6 alkylthio,
• c) CN,
• d) OH, or
• e) CF3,
• 3) CF3,
• 4) nitro,
• 5) amino,
• 6) cyano,
• 7) C1-6alkylamino,
• 8) halogen
• 9) ORc,
• 10) OCH2Rc, and
• 11) CH2ORc;
• Rc is
• 1) C6-10aryl,
• 2) C5-10heteroaryl,
• 3) C3-10heterocycloalkyl, or
• 4) C3-8cycloalkyl.