Cyclopropylamines as LSD1 inhibitors

A compound of Formula IIIa:

• or a pharmaceutically acceptable salt thereof, wherein:
• ring A is phenyl;
• RZ is Cy1, CN, C(O)NRcRd, ORa, SRa, C(O)Rb, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcC(O)Rb, NRcC(O)ORa, NRcC(O)NRcRd, NRcS(O)2Rb, S(O)Rb, S(O)NRcRd, S(O)2Rb, or S(O)2NRcRd;
• each R1 is independently selected from halo or C1-6 alkyl;
• RN is H or RB;
• each RB is independently selected from Cy, halo, C1-6 alkyl, CN, ORa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2, wherein said C1-6 alkyl is optionally substituted with 1, 2, or 3 substituents independently selected from Cy, halo, CN, ORa2, SRa2, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, OC(O)Rb2, OC(O)NRc2Rd2, C(═NRe2)NRc2Rd2, NRc2C(═NRe2)NRc2Rd2, NRc2Rd2, NRc2C(O)Rb2, NRc2C(O)ORa2, NRc2C(O)NRc2Rd2 NRc2S(O)Rb2, NRc2S(O)2Rb2, NRc2S(O)2NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• wherein RB is substituted on any ring-forming atom of ring B except the ring-forming atom of ring B to which RZ is bonded;
• R3 and R4 are each independently selected from H, halo, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 cyanoalkyl, and —(C1-4 alkyl)-ORa4;
• R5 and R6 are each independently selected from H, halo, CN, C1-4 alkyl, C1-4 haloalkyl, C1-4 cyanoalkyl, and —(C1-4 alkyl)-ORa4;
• each Cy is independently selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl;
• Cy1 is phenyl, pyridinyl, pyrimidyl, cyclohexyl, or cyclobutyl, each of which is substituted with 1, 2, 3, or 4 substituents independently selected from Cy2, halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 cyanoalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(═NRe3)NRc3Rd3, NRc3C(═NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3 NRc3 S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• Cy2 is C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 cyanoalkyl, CN, NO2, ORa3, SRa3, C(O)Rb3, C(O)NRc3Rd3, C(O)ORa3, OC(O)Rb3, OC(O)NRc3Rd3, C(═NRe3)NRc3Rd3 NRc3C(═NRe3)NRc3Rd3, NRc3Rd3, NRc3C(O)Rb3, NRc3C(O)ORa3, NRc3C(O)NRc3Rd3 NRc3S(O)Rb3, NRc3S(O)2Rb3, NRc3S(O)2NRc3Rd3, S(O)Rb3, S(O)NRc3Rd3, S(O)2Rb3, and S(O)2NRc3Rd3;
• each Ra, Rb, Rc, and Rd is independently selected from H, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl-, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl- is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, C1-4 cyanoalkyl, halo, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4 NRc4C(O)Rb4, NRc4C(O)NRc4Rd4, NRc4C(O)ORa4, C(═NRe4)NRc4Rd4, NRc4C(═NRe4)NRc4Rd4 S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4;
• or any Rc and Rd 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 C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C1-6 haloalkyl, halo, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)NRc4Rd4 NRc4C(O)ORa4, C(═NRe4)NRc4Rd4, NRc4C(═NRe4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4 NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4, wherein said C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 cyanoalkyl, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)NRc4Rd4, NRc4C(O)ORa4, C(═NRe4)NRc4Rd4 NRc4C(═NRe4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4 and S(O)2NRc4Rd4;
• each Ra2, Rb2, Rc2, and Rd2 is independently selected from H, C1-6 alkyl, and Cy, wherein said C1-6 alkyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Cy, halo, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4, NRc4C(O)Rb4, NRc4C(O)NRc4Rd4, NRc4C(O)ORa4, C(═NRe4)NRc4Rd4, NRc4C(═NRe4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4;
• or any Rc2 and Rd2 is together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group;
• each Ra3, Rb3, Rc3, and Rd3 is independently selected from H, C1-6 alkyl, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl-, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkyl-, C3-10 cycloalkyl-C1-4 alkyl-, (5-10 membered heteroaryl)-C1-4 alkyl-, and (4-10 membered heterocycloalkyl)-C1-4 alkyl- is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from C1-4 alkyl, C1-4 haloalkyl, C1-4 cyanoalkyl, halo, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4 NRc4C(O)Rb4, NRc4C(O)NRc4Rd4 NRc4C(O)ORa4, C(═NRe4)NRc4Rd4, NRc4C(═NRe4)NRc4Rd4 S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4;
• or any Rc3 and Rd3 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 C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, 5-6 membered heteroaryl, C1-6 haloalkyl, halo, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4 NRc4C(O)Rb4 NRc4C(O)NRc4Rd4 NRc4C(O)ORa4, C(═NRe4)NRc4Rd4, NRc4C(═NRe4)NRc4Rd4 S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4, wherein said C1-6 alkyl, C3-7 cycloalkyl, 4-7 membered heterocycloalkyl, C6-10 aryl, and 5-6 membered heteroaryl are optionally substituted by 1, 2, or 3 substituents independently selected from halo, C1-4 alkyl, C1-4 haloalkyl, C1-4 cyanoalkyl, CN, ORa4, SRa4, C(O)Rb4, C(O)NRc4Rd4, C(O)ORa4, OC(O)Rb4, OC(O)NRc4Rd4, NRc4Rd4 NRc4C(O)Rb4, NRc4C(O)NRc4Rd4 NRc4C(O)ORa4, C(═NRe4)NRc4Rd4, NRc4C(═NRe4)NRc4Rd4, S(O)Rb4, S(O)NRc4Rd4, S(O)2Rb4, NRc4S(O)2Rb4, NRc4S(O)2NRc4Rd4, and S(O)2NRc4Rd4;
• each Ra4, Rb4, Rc4, and Rd4 is independently selected from H, C1-4 alkyl, C1-4 haloalkyl, C2-4 alkenyl, and C2-4 alkynyl, wherein said C1-4 alkyl, C2-4 alkenyl, and C2-4 alkynyl, is optionally substituted with 1, 2, or 3 substituents independently selected from OH, CN, amino, halo, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino, di(C1-4 alkyl)amino, C1-4 haloalkyl, and C1-4 haloalkoxy;
• each Re2, Re3, and Re4 is independently selected from H, C1-4 alkyl, and CN;
• n is 0, 1, 2, or 3;
• p is 0, 1, 2, or 3;
• q is 0, 1, or 2;
• and
• s is 1, 2, 3, or 4.