Modulators of trek (twik related k+ channels) channel function

A compound of formula (I):

• or a pharmaceutically acceptable salt thereof,
• wherein:
• L is selected from (1) bond, (2) C2-C4-alkynylene, (3) C2-C4-alkenylene, (4) —(C1-C10-alkylene)-O—, (5) —O—(C1-C10-alkylene)-, (6) -(6 to 15 membered aryl)-, (7) -(5 to 15 membered heteroaryl)-, (8) -(3 to 15 membered heterocycle)-, and (9) —(C3-C10-cycloalkane)-;
• W is selected from (1) CH, (2) CR4, and (3) N
• Z is selected from (1) CH, (2) CR5, and (3) N
• R4 and R5 is each independently selected from (1) cyano, (2) halogen, (3) pentahalosulfanyl, (4) C1-C10-thioalkyl, (5) C1-C10-alkoxy, (6) C1-C10-alkyl, (7) C2-C10-alkenyl, (8) C2-C10-alkynyl, (9) —ORb, (10) 6 to 15 membered aryl, (11) 5 to 15 membered heteroaryl, (12) C3-C10-cycloalkyl, (13) C2-C10-heteroalkyl, (14) 3 to 15 membered heterocycle, and (15) —(CRcRd)n-Q,
• wherein each of (4)-(8) in R4 or R5 may be optionally substituted with 1 to 10 halogen, and each of (10)-(14) in R4 or R5 may be optionally substituted with 1 to 10 substituents selected from (1) halogen, (2) C1-C10-alkyl, and (3) C1-C10-haloalkyl;
• Rb is selected from (1) hydrogen, (2) C1-C10-alkyl, and (3) C1-C10-haloalkyl;
• Rc is selected from (1) hydrogen, (2) halogen, (3) C1-C10-alkyl, and (4) C1-C10-haloalkyl;
• Rd is selected from (1) hydrogen, (2) halogen, (3) C1-C10-alkyl and (4) C1-C10-haloalkyl;
• or when Rc and Rd are C1-C10-alkyl, Rc and Rd may optionally form a C3-C10-cycloalkyl together with the carbon atom to which they are attached;
• n is 0, 1, 2, 3 or 4;
• Q is selected from (1) halogen, (2) cyano, (3) —OR201, (4) —SR202, (5) —C(═O)R203, (6) —C(═O)OR204, (7) —S(═O)R205, (8) —SO2R206, (9) —N(R207)2, (10) —C(═O)N(R20′)2, (11) —SO2N(R209)2, (12) 6 to 15 membered aryl, (13) 5 to 15 membered heteroaryl, (14) C3-C10-cycloalkyl, and (15) 3 to 15 membered heterocycle, wherein each of (12)-(15) in Q may be optionally substituted with 1 to 10 substituents selected from (1) halogen, (2) C1-C10-alkyl, and (3) C1-C10-haloalkyl;
• R201, R202, R203, R204, R205, R206, R207, R208, and R209 are each independently selected from (1) hydrogen, (2) C1-C10-alkyl, and (3) C1-C10-haloalkyl, and multiple R207, R208, and R209 may be the same as or different from each other;
• is selected from (1) 1,2,3-triazole substituted with R3, (2) pyrrole substituted with R3, (3) pyrazole substituted with R3, (4) isoxazole substituted with R3, (5) isothiazole substituted with R3, (6) imidazole substituted with R3, (7) furan substituted with R3, (8) thiophene substituted with R3;
• wherein Y is selected from (1) CH, (2) CR3, (3) N, (4) NH, (5) NR3, (6) O and (7) S,
• U is selected from (1) CH, (2) CR3, (3) CRx, (4) N, (5) NH, (6) NR3, (7) NRx, (8) O and (9) S,
• V is selected from (1) CH, (2) CRx, (3) N, (4) NH, (5) NRx, (6) O, and (7) S,
• one of Y and U is NR3 or CR3, and the other is not NR3 or CR3,
• [Chem. 3]
• is single bond or double bond,
• Rx is selected from (1) NH2, (2) halogen, (3) C1-C4-alkyl, and (4) C1-C4-haloalkyl;
• R is selected from (1) 6 to 15 membered aryl and (2) 5 to 15 membered heteroaryl, each of which may be optionally substituted with 1 to 5 R6;
• wherein multiple R6 may be the same as or different from each other;
• R6 is selected from (1) halogen, (2) cyano, (3) pentahalosulfanyl, (4) C1-C10-alkyl, (5) C1-C10-thioalkyl, (6) C1-C10-alkoxy, (7) C2-C10-alkenyl, (8) C2-C10-alkynyl, and (9) —ORb, wherein each of (4)-(6) in R6 is may be optionally substituted with 1 to 10 halogen;
• R1 is selected from (1) C1-C10-alkyl, (2) halogen, (3) C1-C10-alkoxy, (4) C1-C10-haloalkyl, (5) C1-C10-haloalkoxy and (6) cyano;
• R21 is selected from (1) hydrogen, (2) C1-C10-alkyl, (3) halogen, (4) C1-C10-alkoxy, (5) C1-C10-haloalkyl, (6) C1-C10-haloalkoxy, and (7) cyano;
• R2 is selected from (1) halogen, (2) C1-C10-alkyl, (3) C1-C10-haloalkyl, (4) cyano, and (5) C3-C10-cycloalkyl which may be optionally substituted with 1 to 10 substituents selected from (1) halogen (2) C1-C10-alkyl, and (3) C1-C10-haloalkyl;
• R3 is selected from (1) R7 or
• wherein R7 is selected from (1) C3-C10-alkyl, (2) —(C2-C10-alkylene)-cyano, (3) —(C1-C10-alkylene)-NH—C(═O)—O—(C1-C10-alkyl), (4) —(C1-C10-alkylene)-O—(C1-C10-alkyl), and (5) —(C1-C10-alkylene)-(CR71R72)p—R73—, each of (1)-(5) in R7 is may be optionally substituted with 1 to 10 halogen;
• wherein R71 is selected from (1) hydrogen, (2) halogen, (3) C1-C10-alkyl and (4) C1-C10-haloalkyl;
• R72 is selected from (1) hydrogen, (2) halogen, (3) C1-C10-alkyl, and (4) C1-C10-haloalkyl;
• or when R71 and R72 are C1-C10-alkyl, R71 and R72 may optionally form a C3-C10-cycloalkyl together with the carbon atom to which they are attached, wherein C3-C10-cycloalkyl may be optionally substituted with 1-10 substituents selected from (1) halogen and (2) cyano;
• p is 0, 1, 2, 3 or 4;
• R73 is selected from (1) —OR101, (2) —SR102, (3) —C(═O)R103, (4) —C(═O)OR104, (5) S(═O)R105, (6) —SO2R106, (7) —N(R107)2, (8) —C(═O)N(R108)2, (9) —SO2N(R109)2, (10) 6 to 15 membered aryl, (11) 5 to 15 membered heteroaryl, (12) C3-C10-cycloalkyl, and (13) 3 to 15 membered heterocycle, wherein each of (10)-(13) in R73 may be optionally substituted with 1-10 substituents selected from (1) halogen, (2) C1-C10-alkyl, and (3) C1-C10-haloalkyl;
• R101, R102, R103, R104, R105, R106, R107, R108, and R109 are each independently selected from (1) hydrogen, (2) C1-C10-alkyl, and (3) C1-C10-haloalkyl, and multiple R107, R108, and R109 may be the same as or different from each other;
• M is selected from (1) bond or (2) C1-C10-alkylene which may be optionally substituted with 1 to 3 halogens;
• Ring B is selected from (1) C3-C10-cycloalkyl which may be optionally substituted with 1 to 5 R8, (2) 3 to 15 membered heterocycle which may be optionally substituted with 1 to 5 R9, (3) 6 to 15 membered aryl which may be optionally substituted with 1 to 5 R10, and (4) 5 to 15 membered heteroaryl which may be optionally substituted with 1 to 5 R11;
• wherein multiple R8, R9, R10 or R11 may be the same as or different from each other;
• R8, R9, R10, and R11 are each independently selected from (1) halogen, (2) C1-C10-alkyl, (3) cyano, (4) —C(═O)—(C1-C10-alkyl), (5) —C(═O)—(C3-C10-cycloalkyl), (6) —C(═O)—(3 to 15 membered heterocycle), (7) —C(═O)—O—(C1-C10-alkyl), (8) —C(═O)—O—(C3-C10-cycloalkyl), (9) —C(═O)—O-(3 to 15 membered heterocycle), (10) —C(═O)—NR81—(C1-C10-alkyl), (11) —C(═O)NR82—(C3-C10-cycloalkyl), (12) —C(═O)—NR83-(3 to 15 membered heterocycle), (13) —NR84—C(═O)—(C1-C10-alkyl), (14) —NR85—C(═O)—(C3-C10-cycloalkyl), (15) —NR86—C(═O)—(3 to 15 membered heterocycle), (16) —NR87—C(═O)—O—(C1-C10-alkyl), (17) —NR88—C(═O)—O—(C3-C10-cycloalkyl), (18) —NR89—C(═O)—O-(3 to 15 membered heterocycle), (19) —SO2—(C1-C10-alkyl), and (20) oxo;
• wherein each of (2), (4), (7), (10), (13), (16) and (19) in R8, R9 R10 or R11 may be optionally substituted with 1 to 10 substituents selected from (1) halogen, (2) —OH, and (3) C1-C10-alkoxy, and each of (5), (6), (8), (9), (11), (12), (14), (15), (17), and (18) in R8, R9 R10 or R11 may be optionally substituted with 1 to 10 substituents selected from (1) halogen, (2) OH, (3) C1-C10-alkyl, (4) C1-C10-alkoxy, and (5) C1-C10-haloalkyl;
• and
• R81, R82, R83, R84, R85, R86, R87, R88, and R89 are independently selected from (1) hydrogen and (2) C1-C4-alkyl.