Cyclopropylamines as LSD1 inhibitors
The present invention is directed to cyclopropylamine derivatives which are LSD1 inhibitors useful in the treatment of diseases such as cancer.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein:
ring A is a phenyl ring;
ring B is a piperidinyl ring;
ring C is an azetidinyl ring;
wherein ring C is substituted on any ring-forming atom of ring B except the ring-forming atom of ring B to which R Z is bonded;
each R 1 is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , C(═NR e )R b , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a , SR a , C(O)R b , C(O)NR c R d , C(O)OR a , OC(O)R b , OC(O)NR c R d , C(═NR e )NR c R d , NR c C(═NR e )NR c R d , NR c R d , NR c C(O)R b , NR c C(O)OR a , NR c C(O)NR c R d , NR c S(O)R b , NR c S(O) 2 R b , NR c S(O) 2 NR c R d , S(O)R b , S(O)NR c R d , S(O) 2 R b , and S(O) 2 NR c R d ;
each R 2 is independently selected from halo, C 1-6 alkyl, CN, OR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 , wherein said C 1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, OR a1 , SR a1 , C(O)R b1 , C(O)NR c1 R d1 , C(O)OR a1 , OC(O)R b1 , OC(O)NR c1 R d1 , C(═NR e1 )NR c1 R d1 , NR c1 C(═NR e1 )NR c1 R d1 , NR c1 R d1 , NR c1 C(O)R b1 , NR c1 C(O)OR a1 , NR c1 C(O)NR c1 R d1 , NR c1 S(O)R b1 , NR c1 S(O) 2 R b1 , NR c1 S(O) 2 NR c1 R d1 , S(O)R b1 , S(O)NR c1 R d1 , S(O) 2 R b1 , and S(O) 2 NR c1 R d1 ;
wherein each R 2 is substituted on any ring-forming atom of ring B except the ring-forming atom of ring B to which R Z is bonded;
each R 3 is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , C(═NR e2 )R b2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 ;
R 4 is halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , C(═NR e3 )R b3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , or S(O) 2 NR c3 R d3 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 ;
R 5 and R 6 are each independently selected from H, halo, CN, C 1-4 alkyl, C 1-4 cyanoalkyl, C 1-4 haloalkyl, and —(C 1-4 alkyl)-OR a5 ;
R Z is H, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , C(═NR e4 )R b4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 , NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 , wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a4 , SR a4 , C(O)R b4 , C(O)NR c4 R d4 , C(O)OR a4 , OC(O)R b4 , OC(O)NR c4 R d4 , C(═NR e4 )NR c4 R d4 , NR c4 C(═NR e4 )NR c4 R d4 , NR c4 R d4 , NR c4 C(O)R b4 , NR c4 C(O)OR a4 , NR c4 C(O)NR c4 R d4 , NR c4 S(O)R b4 , NR c4 S(O) 2 R b4 , NR c4 S(O) 2 NR c4 R d4 , S(O)R b4 , S(O)NR c4 R d4 , S(O) 2 R b4 , and S(O) 2 NR c4 R d4 ;
each R a , R b , R c , R d , R a2 , R b2 , R c2 , R d2 , R a3 , R b3 , R c3 , R d3 , R a4 , R b4 , R c4 , and R d4 is independently selected from H, C 1-6 alkyl, C 1-4 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl-, wherein said C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 6-10 aryl, C 3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C 6-10 aryl-C 1-4 alkyl-, C 3-10 cycloalkyl-C 1-4 alkyl-, (5-10 membered heteroaryl)-C 1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C 1-4 alkyl- is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cycanoalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;
or any R c and R d together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;
or any R c2 and R d2 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a5 , SR a5 C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;
or any R c3 and R d3 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;
or any R c4 and R d4 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, 5-6 membered heteroaryl, C 1-6 haloalkyl, halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 , wherein said C 1-6 alkyl, C 3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C 6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 -cyanoalkyl, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;
each R a1 , R b1 , R c1 , R d1 is independently selected from H and C 1-6 alkyl optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from halo, CN, OR a5 , SR a5 , C(O)R b5 , C(O)NR c5 R d5 , C(O)OR a5 , OC(O)R b5 , OC(O)NR c5 R d5 , NR c5 R d5 , NR c5 C(O)R b5 , NR c5 C(O)NR c5 R d5 , NR c5 C(O)OR a5 , C(═NR e5 )NR c5 R d5 , NR c5 C(═NR e5 )NR c5 R d5 , S(O)R b5 , S(O)NR c5 R d5 , S(O) 2 R b5 , NR c5 S(O) 2 R b5 , NR c5 S(O) 2 NR c5 R d5 , and S(O) 2 NR c5 R d5 ;
each R a5 , R b5 , R c5 , and R d5 is independently selected from H, C 1-4 alkyl, C 1-4 haloalkyl, C 2-4 alkenyl, and C 2-4 alkynyl, wherein said C 1-4 alkyl, C 2-4 alkenyl, and C 2-4 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylthio, C 1-4 alkylamino, di(C 1-4 alkyl)amino, C 1-4 haloalkyl, and C 1-4 haloalkoxy; and
each R e , R e1 , R e2 , R e3 , R e4 , and R e5 is independently selected from H, C 1-4 alkyl, and CN;
m is 0, 1, or 2;
n is 0, 1, 2, or 3;
p is 0, 1, 2, 3; and
q is 0, 1, or 2.
2. The compound of claim 1 having Formula IIIb:
or a pharmaceutically acceptable salt thereof, wherein each R 2 is substituted on any ring-forming carbon atom of the piperidine ring depicted in Formula IIIb except the ring-forming carbon atom to which R Z is bonded.
3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, having Formula IVb:
4. The compound of claim 1 having Formula Vb:
or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein q is 0.
6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein q is 1.
7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 0.
8. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 1.
9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is halo.
10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is F.
11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein both R 5 and R 6 are H.
12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , or S(O) 2 R b3 , wherein said C 1-6 alkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a3 , SR a3 , C(O)R b3 , C(O)NR c3 R d3 , C(O)OR a3 , OC(O)R b3 , OC(O)NR c3 R d3 , C(═NR e3 )NR c3 R d3 , NR c3 C(═NR e3 )NR c3 R d3 , NR c3 R d3 , NR c3 C(O)R b3 , NR c3 C(O)OR a3 , NR c3 C(O)NR c3 R d3 , NR c3 S(O)R b3 , NR c3 S(O) 2 R b3 , NR c3 S(O) 2 NR c3 R d3 , S(O)R b3 , S(O)NR c3 R d3 , S(O) 2 R b3 , and S(O) 2 NR c3 R d3 .
13. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is C 1-4 alkyl optionally substituted by CN, C(O)NR c3 R d3 , OR a3 , or C(O)OR a3 .
14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is C 1-4 alkyl optionally substituted by CN, C(O)NR c3 R d3 , or C(O)OR a3 .
15. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is —CH 2 —CN, —CH 2 —C(═O)OH, —CH 2 —C(═O)NH(CH 3 ), —CH 2 —C(═O)N(CH 3 ) 2 , or —CH 2 CH 2 OH.
16. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 3 is independently selected from C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl, 4-10 membered heterocycloalkyl, C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 , wherein said C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 3-10 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 .
17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 3 is independently selected from C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 , wherein said C 1-6 alkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 .
18. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 3 is independently selected from C 1-6 alkyl, C 6-10 aryl, 5-10 membered heteroaryl, C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , and S(O) 2 R b2 , wherein said C 1-6 alkyl, C 6-10 aryl, and 5-10 membered heteroaryl are each optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, CN, NO 2 , OR a2 , SR a2 , C(O)R b2 , C(O)NR c2 R d2 , C(O)OR a2 , OC(O)R b2 , OC(O)NR c2 R d2 , C(═NR e2 )NR c2 R d2 , NR c2 C(═NR e2 )NR c2 R d2 , NR c2 R d2 , NR c2 C(O)R b2 , NR c2 C(O)OR a2 , NR c2 C(O)NR c2 R d2 , NR c2 S(O)R b2 , NR c2 S(O) 2 R b2 , NR c2 S(O) 2 NR c2 R d2 , S(O)R b2 , S(O)NR c2 R d2 , S(O) 2 R b2 , and S(O) 2 NR c2 R d2 .
19. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is H, C 1-4 alkyl, or C 6-10 aryl-C 1-4 alkyl-, wherein said C 1-4 alkyl and C 6-10 aryl-C 1-4 alkyl- are each optionally substituted by halo or OR a4 .
20. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is C 1-4 alkyl.
21. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is C 1-4 alkyl substituted by methoxy.
22. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is C 6-10 aryl-C 1-4 alkyl- substituted by fluoro.
23. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is H, methyl, methoxymethyl, or 4-fluorophenylmethyl.
24. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z is H.
25. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein p is 0.
26. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein p is 1.
27. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein p is 2.
28. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 0.
29. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having a trans configuration with respect to the di-substituted cyclopropyl group depicted in Formula I.
30. The compound of claim 1 selected from:
(1-Methyl-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidin-3-yl)acetonitrile;
(3-{4-[(trans-2-Phenylcyclopropyl)amino]piperidin-1-yl}azetidin-3-yl)acetonitrile;
(1-Benzyl-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidin-3-yl)acetonitrile;
3-(3-(Cyanomethyl)-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidin-1-yl)propanoic acid;
(1-Acetyl-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidin-3-yl)acetonitrile;
(1-Benzoyl-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidin-3-yl)acetonitrile;
Methyl 3-(cyanomethyl)-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidine-1-carboxylate;
(1-(Methylsulfonyl)-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidin-3-yl)acetonitrile;
2-(3-(Cyanomethyl)-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidin-1-yl)nicotinonitrile;
3-Cyano-4-(3-(cyanomethyl)-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidin-1-yl)benzoic acid;
2-(3-(Cyanomethyl)-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidin-1-yl)benzonitrile;
4-(3-(Cyanomethyl)-3-{4-[(trans-2-phenylcyclopropyl)amino]piperidin-1-yl}azetidin-1-yl)benzonitrile;
[1-(Ethylsulfonyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[3-(4-{[(trans-2-Phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-3-yl]acetonitrile;
2-[3-(Cyanomethyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-1-yl]nicotinonitrile;
4-[3-(Cyanomethyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-1-yl]-2,5-difluoro-N-isopropylbenzamide;
{3-(4-{[(trans-2-Phenylcyclopropyl)amino]methyl}piperidin-1-yl)-1-[3-(trifluoromethyl)pyridin-2-yl]azetidin-3-yl}acetonitrile;
{3-(4-{[(trans-2-Phenylcyclopropyl)amino]methyl}piperidin-1-yl)-1-[5-(trifluoromethyl)pyridin-2-yl]azetidin-3-yl}acetonitrile;
2-Chloro-6-[3-(cyanomethyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-1-yl]benzonitrile;
2-[3-(Cyanomethyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-1-yl]benzonitrile;
4-[3-(Cyanomethyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-1-yl]benzonitrile;
Methyl 3-(cyanomethyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidine-1-carboxylate;
3-(Cyanomethyl)-N-(2,4-difluorophenyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidine-1-carboxamide;
N-(3-Chloro-2-fluorophenyl)-3-(cyanomethyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidine-1-carboxamide;
[1-(3,5-Difluorobenzoyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-Benzoyl-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-(2-Fluorobenzoyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-(3-Fluorobenzoyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-(4-Fluorobenzoyl)-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-Methyl-3-(4-{[(trans-2-phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[3-(4-{[(trans-2-Phenylcyclopropyl)amino]methyl}piperidin-1-yl)azetidin-3-yl]acetic acid;
N-Methyl-2-(3-(4-((trans-2-phenylcyclopropylamino)methyl)piperidin-1-yl)azetidin-3-yl)acetamide; and
N,N-Dimethyl-2-(3-(4-((trans-2-phenylcyclopropylamino)methyl)piperidin-1-yl)azetidin-3-yl)acetamide,
or a pharmaceutically acceptable salt of any of the aforementioned.
31. The compound of claim 1 selected from:
[1-(methylsulfonyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-methyl-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1S,2R)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-(ethylsulfonyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
3-(cyanomethyl)-N,N-dimethyl-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide;
3-(cyanomethyl)-N-methyl-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide;
3-(cyanomethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide;
[1-methyl-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetic acid;
[1-ethyl-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetic acid;
2-[1-(ethylsulfonyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]-N,N-dimethylacetamide; and
2-[1-(ethylsulfonyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]-N-methylacetamide;
or a pharmaceutically acceptable salt of any of the aforementioned.
32. The compound of claim 1 selected from:
[1-(1-methyl-1H-pyrazol-4-yl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-(2-hydroxyethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-(3-hydroxycyclobutyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-(cis-4-hydroxycyclohexyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-(isothiazol-5-ylcarbonyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-(morpholin-4-ylcarbonyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-(trans-4-hydroxycyclohexyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-[(1-hydroxycyclopentyl)carbonyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-[(1-hydroxycyclopropyl)carbonyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-[(1-methyl-1H-pyrazol-4-yl)carbonyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-[(1-methyl-1H-pyrazol-4-yl)sulfonyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-[(1-methyl-1H-pyrazol-5-yl)carbonyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-[(3-hydroxyazetidin-1-yl)carbonyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-[(4-hydroxypiperidin-1-yl)carbonyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-[(4-methoxypiperidin-1-yl)carbonyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-[(cis-4-hydroxycyclohexyl)carbonyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[1-[(trans-4-hydroxycyclohexyl)carbonyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]amino}piperidin-1-yl)-1-(4-hydroxycyclohexyl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]amino}piperidin-1-yl)-1-(methylsulfonyl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(1,3-thiazol-5-ylcarbonyl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(1H-pyrazol-4-ylcarbonyl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(pyrazin-2-ylcarbonyl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(tetrahydro-2H-pyran-4-yl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(tetrahydrofuran-3-yl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(tetrahydrofuran-3-ylcarbonyl)azetidin-3-yl]acetonitrile;
2-(3-(4-(((1R,2S)-2-phenylcyclopropyl)amino)piperidin-1-yl)-1-(tetrahydrofuran-2-carbonyl)azetidin-3-yl)acetonitrile;
2-(3-(cyanomethyl)-3-(4-(((1R,2S)-2-phenylcyclopropyl)amino)piperidin-1-yl)azetidin-1-yl)-N,N-dimethylacetamide;
2-[1-(ethylsulfonyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]ethanol;
2-[1-(methylsulfonyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]ethanol;
2-[3-(cyanomethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-1-yl]acetamide;
2-[3-(cyanomethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-1-yl]-N-methylacetamide;
3-(cyanomethyl)-3-(4-{[(1R,2S)-2-(4-fluorophenyl)cyclopropyl]amino}piperidin-1-yl)azetidine-1-sulfonamide;
3-[2-(dimethylamino)-2-oxoethyl]-N,N-dimethyl-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-carboxamide;
methyl 3-[2-(dimethylamino)-2-oxoethyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-carboxylate;
methyl 3-[2-(methylamino)-2-oxoethyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-carboxylate;
N,N-dimethyl-2-(1-(methylsulfonyl)-3-(4-(((1R,2S)-2-phenylcyclopropyl)amino)piperidin-1-yl)azetidin-3-yl)acetamide;
N,N-dimethyl-3-[2-(methylamino)-2-oxoethyl]-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-carboxamide;
N-methyl-2-[1-(methylsulfonyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]acetamide;
tetrahydrofuran-3-yl 3-(cyanomethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidine-1-carboxylate;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(1H-pyrazol-5-ylcarbonyl)azetidin-3-yl]acetonitrile;
{3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-[(3R)-tetrahydrofuran-3-ylcarbonyl]azetidin-3-yl}acetonitrile;
{3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-[(3S)-tetrahydrofuran-3-ylcarbonyl]azetidin-3-yl}acetonitrile;
{3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-[(2S)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}acetonitrile;
{3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-[(2R)-tetrahydrofuran-2-ylcarbonyl]azetidin-3-yl}acetonitrile;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(pyridin-2-ylacetyl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(1,3-thiazol-4-ylcarbonyl)azetidin-3-yl]acetonitrile;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(1,3-thiazol-2-ylcarbonyl)azetidin-3-yl]acetonitrile;
N,N-dimethyl-2-[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(tetrahydro-2H-pyran-4-yl)azetidin-3-yl]acetamide;
N-methyl-2-[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(tetrahydro-2H-pyran-4-yl)azetidin-3-yl]acetamide;
2-[1-(cyclopropylmethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]-N,N-dimethylacetamide;
2-[1-(cyclopropylmethyl)-3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)azetidin-3-yl]-N-methylacetamide;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(pyrimidin-2-ylmethyl)azetidin-3-yl]acetic acid;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(pyrimidin-5-ylmethyl)azetidin-3-yl]acetic acid;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(1,3-thiazol-4-ylmethyl)azetidin-3-yl]acetic acid;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(1,3-thiazol-5-ylmethyl)azetidin-3-yl]acetic acid;
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(1,3-thiazol-2-ylmethyl)azetidin-3-yl]acetic acid; and
[3-(4-{[(1R,2S)-2-phenylcyclopropyl]amino}piperidin-1-yl)-1-(3,3,3-trifluoropropyl)azetidin-3-yl]acetic acid,
or a pharmaceutically acceptable salt of any of the aforementioned.
33. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.