Cyclopropylamines as lsd1 inhibitors

Abstract

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 II: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 X is —CH 2 —; 
 Y is —CH 2 — or —CH 2 —CH 2 —; 
 wherein each R 2  is substituted on any ring-forming carbon atom of the ring in Formula II containing X and Y except the ring-forming carbon atom to which R Z  is bonded; 
 ring A is phenyl; 
 ring C is (1) phenyl, (2) monocyclic 5-6 membered heteroaryl having carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S, or (3) a fused bicyclic moiety having Formula (A): 
 
       
         
           
           
               
               
           
         
         wherein:
 ring C1 is phenyl or 5-6 membered heteroaryl having carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S; 
 ring C2 is (1) phenyl, (2) C 5-6  cycloalkyl, (3) 5-6 membered heteroaryl having carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S, or (4) 5-6 membered heterocycloalkyl having carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S; 
 
         wherein said fused bicyclic moiety of Formula A is bonded to ring B via ring Cl, and wherein Ring C substituents R 3  and R 4  are substituted on either or both of C1 and C2; 
         wherein ring C is substituted on any ring-forming atom of ring 
       
       
         
           
           
               
               
           
         
       
       except the ring-forming atom of ring 
       
         
           
           
               
               
           
         
       
       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 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 , NRclR 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, 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 , and 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 H; 
 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  cyanoalkyl, 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 b , 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 e )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 e )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 b , 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 b , 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 e )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, or 3; and 
 q is 0 or 1. 
 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The compound of  claim 1  having Formula IIIa: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 wherein each R 2  is substituted on any ring-forming carbon atom of the azetidine ring depicted in Formula IIIa except the ring-forming carbon atom to which R Z  is bonded. 
 
     
     
         5 . The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, having Formula IVa: 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound of  claim 1  having Formula Va: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein q is 0. 
     
     
         8 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein q is 1. 
     
     
         9 . (canceled) 
     
     
         10 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein n is 0. 
     
     
         11 . (canceled) 
     
     
         12 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring C is phenyl. 
     
     
         13 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring C is monocyclic 5-6 membered heteroaryl having carbon and 1, 2, 3 or 4 heteroatoms selected from N, O, and S. 
     
     
         14 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring C is phenyl, pyridyl, piperazinyl, pyrazinyl, pyrimidinyl, or pyrazolyl. 
     
     
         15 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein ring C is phenyl, pyridyl, piperazinyl, pyrazinyl, or pyrazolyl. 
     
     
         16 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is C 1-6  alkyl, C 1-6  haloalkyl, C 3-10  cycloalkyl, 4-10 membered heterocycloalkyl, CN, NR c3 R d3 , C(O)OR a3 , or C(O)NR c3 R d3 , wherein said C 1-6  alkyl, 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 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 . 
     
     
         17 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4  is C 1-6  alkyl, C 1-6  haloalkyl, 4-10 membered heterocycloalkyl, CN, or C(O)NR c3 R d3 , wherein said C 1-6  alkyl 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 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 . 
     
     
         18 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein each R 3  is independently selected from halo, C 1-6  alkyl, C 1-6  haloalkyl, CN, OR a2 , and C(O)NR c2 R d2 , wherein said C 1-6  alkyl is 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 each R 3  is independently selected from halo, C 1-6  alkyl, C 1-6  haloalkyl, CN, OR a2 , and C(O)NR c2 R d2 . 
     
     
         20 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein p is 0. 
     
     
         21 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein p is 1. 
     
     
         22 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein p is 2. 
     
     
         23 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 0. 
     
     
         24 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 1. 
     
     
         25 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z  is 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, CN, or OR a4 . 
     
     
         26 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z  is C 1-4  alkyl. 
     
     
         27 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z  is C 1-4  alkyl substituted by CN or methoxy. 
     
     
         28 . 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. 
     
     
         29 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z  is methyl, cyanomethyl, methoxymethyl, or 4-fluorophenylmethyl. 
     
     
         30 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z  is C 1-4  alkyl substituted by CN. 
     
     
         31 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z  is cyanomethyl. 
     
     
         32 . The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein R Z  is H. 
     
     
         33 . 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 II. 
     
     
         34 . The compound of  claim 1 , wherein the compound is selected from:
 3-Fluoro-4-[3-({[trans-2-phenylcyclopropyl]amino}methyl)azetidin-1-yl]benzonitrile;   3,5-Difluoro-4-[3-({[trans-2-phenylcyclopropyl]amino}methyl)azetidin-1-yl]benzonitrile;   2,5-Difluoro-N-isopropyl-4-(3-{[(trans-2-phenylcyclopropyl)amino]methyl}azetidin-1-yl)benzamide;   2-Methyl-6-[3-({[trans-2-phenylcyclopropyl]amino}methyl)azetidin-1-yl]nicotinonitrile;   N-Ethyl-5-(3-{[(trans-2-phenylcyclopropyl)amino]methyl}azetidin-1-yl)pyrazine-2-carboxamide;   3,5-Difluoro-N-isopropyl-4-(3-{[(trans-2-phenylcyclopropyl)amino]methyl}azetidin-1-yl)benzamide;   2,6-Difluoro-N-isopropyl-4-(3-{[(trans-2-phenylcyclopropyl)amino]methyl}azetidin-1-yl)benzamide;   2,3-Difluoro-N-isopropyl-4-(3-{[(trans-2-phenylcyclopropyl)amino]methyl}azetidin-1-yl)benzamide;   2-Chloro-5-fluoro-N-isopropyl-4-(3-{[(trans-2-phenylcyclopropyl)amino]methyl}-azetidin-1-yl)benzamide;   3-Fluoro-N-isopropyl-4-(3-{[(trans-2-phenylcyclopropyl)amino]methyl}azetidin-1-yl)benzamide;   2-Fluoro-N-isopropyl-4-(3-{[(trans-2-phenylcyclopropyl)amino]methyl}azetidin-1-yl)benzamide;   2-Fluoro-N-isopropyl-5-methyl-4-(3-{[(trans-2-phenylcyclopropyl)amino]methyl})-azetidin-1-yl)benzamide;   N-Isopropyl-2-methoxy-4-(3-{[(trans-2-phenylcyclopropyl)amino]methyl}azetidin-1-yl)benzamide;   3-Chloro-N-isopropyl-4-(3-{[(trans-2-phenylcyclopropyl)amino]methyl}azetidin-1-yl)benzamide;   5-(3-{[(trans-2-Phenylcyclopropyl)amino]methyl}azetidin-1-yl)-N-[1-(trifluoromethyl)cyclopropyl]pyridine-2-carboxamide;   N-({1-[6-(4-Methylpiperazin-1-yl)pyrimidin-4-yl]azetidin-3-yl}methyl)-trans-2-phenylcyclopropanamine; and   trans-N-{[1-(1-Methyl-1H-pyrazol-4-yl)azetidin-3-yl]methyl}-2-phenylcyclopropanamine;   or a pharmaceutically acceptable salt of any of the aforementioned.   
     
     
         35 . (canceled) 
     
     
         36 . A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. 
     
     
         37 . A method of inhibiting LSD1 comprising contacting a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, with said LSD1. 
     
     
         38 . A method of treating a disease comprising administering to a patient a therapeutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein said disease is cancer. 
     
     
         39 . The method of  claim 38  wherein said cancer is a hematological cancer. 
     
     
         40 . The method of  claim 39  wherein said hematological cancer is selected from acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), acute promyelocytic leukemia (APL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, Non-Hodgkin lymphoma, Hodgkin lymphoma, primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocytosis (ET)), myelodysplasia syndrome (MDS), or multiple myeloma. 
     
     
         41 . The method of  claim 38  wherein said cancer is a sarcoma, lung cancer, gastrointestinal cancer, genitourinary tract cancer, liver cancer, bone cancer, nervous system cancer, gynecological cancer, or skin cancer. 
     
     
         42 . A method of treating a disease comprising administering to a patient a therapeutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein said disease is a viral disease or a beta-globinopathy. 
     
     
         43 . The method of  claim 40 , wherein said hematological cancer is myelodysplasia syndrome. 
     
     
         44 . The method of  claim 40 , wherein said hematological cancer is acute myelogenous leukemia. 
     
     
         45 . The method of  claim 40 , wherein said hematological cancer is primary myelofibrosis. 
     
     
         46 . The method of  claim 41 , wherein said lung cancer is undifferentiated small cell lung cancer. 
     
     
         47 . The method of  claim 38 , wherein said cancer is Ewing's sarcoma.