Piperidinyl-3-(aryloxy)propanamides and propanoates

A compound of Formula 1,

• or a pharmaceutically acceptable salt thereof in which:
• X1 is selected from N and CR1;
• X2 is selected from N and CR2;
• X3 is selected from N and CR3;
• and
• X4 is selected from N and CR4, provided no more than two of X1, X2, X3, and X4 are N;
• X13 is NR13 and X14 is CR15R16 or X13 is CH2 and X14 is NR14;
• L is selected from NR8 and O;
• r is selected from 0 and 1;
• s is selected from 0 and 1;
• R1, R2, and R3 are each independently selected from
• (a) hydrogen, halo, hydroxy, and cyano;
• and
• (b) C1-4 alkyl, C3-6 cycloalkyl, and C1-4 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo;
• R4 is selected from
• (a) hydrogen, halo, hydroxy, and cyano;
• and
• (b) C1-4 alkyl, C3-6 cycloalkyl, and C1-4 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo;
• R5 is selected from
• (a) hydrogen, halo, hydroxy, and cyano;
• and
• (b) C1-4 alkyl, C3-6 cycloalkyl, and C1-4 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo, oxo, and phenyl which is substituted with 0 to 3 optional substituents independently selected from halo;
• or
• R4 and R5, together with the carbon atoms to which they are attached, form a cyclopent-1-en-1,2-diyl or a furan-2,3-diyl;
• R6 and R7 are each independently selected from halo and C1-3 alkyl, or R6 and R7, together with the carbon atom to which they are attached, form a C3-4 cycloalkan-1,1-diyl;
• R8 is selected from H and C1-4 alkyl;
• R9 and R10 are each independently selected from
• (a) hydrogen, halo, hydroxy, and cyano;
• (b) C1-4 alkyl, C3-6 cycloalkyl, and C1-4 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo;
• and
• (c) phenyl and C1-5 heteroaryl, each substituted with 0 to 3 optional substituents independently selected from halo, C1-4 alkyl, and C1-4 alkoxy, wherein the C1-5 heteroaryl substituent is a monocyclic ring with 5 to 6 ring members in which 1 to 4 ring members are heteroatoms, each of the heteroatoms independently selected from N, O, and S, provided no more than one of the ring members is O or S, and wherein the C1-4 alkyl and C1-4 alkoxy optional substituents on phenyl and C1-5 heteroaryl are each independently substituted with 0 to 3 optional substituents independently selected from halo;
• or
• R9 and R10, together with the carbon atom to which they are attached, form a C3-4 cycloalkan-1,1-diyl;
• R11 and R12 are each independently selected from
• (a) hydrogen, halo, hydroxy, and cyano;
• and
• (b) C1-4 alkyl, C3-6 cycloalkyl, and C1-4 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo;
• or
• R11 and R12, together with the carbon atom to which they are attached, form a C3-4 cycloalkan-1,1-diyl;
• R13 and R14 are each independently selected from
• (a) hydrogen;
• and
• (b) C1-4 alkyl, which is substituted with 0 to 3 optional substituents independently selected from cyano, oxo, and phenyl which is substituted with 0 to 3 optional substituents independently selected from halo;
• and
• R15 and R16 are each independently selected from
• (a) hydrogen, halo, hydroxy, and cyano;
• and
• (b) C1-4 alkyl, C3-6 cycloalkyl, and C1-4 alkoxy, each substituted with 0 to 3 optional substituents independently selected from halo;
• or
• R15 and R16, together with the carbon atom to which they are attached, form a C3-4 cycloalkan-1,1-diyl.