Phosphodiesterase inhibitors

A compound, or a pharmaceutically acceptable salt thereof, having a structure of Formula (I):

• wherein
• X, Y, and Z are each independently N or CR3;
• R is C0-6alkylene-C6-10aryl, C0-6alkylene-5-7 membered heteroaryl, C0-6alkylene-C3-10cycloalkyl, or C0-6alkylene-3-10 membered heterocycloalkyl, each optionally substituted by 1-3 R4, wherein the heteroaryl and heterocycloalkyl comprise 1-4 ring heteroatoms independently selected from N, O, and S;
• R1 is H, C1-6alkyl, or 3-10 membered heterocycloalkyl comprising 1-4 ring heteroatoms independently selected from N, O, and S, and the heterocycloalkyl is optionally substituted by 1-3 R5;
• R2 is C1-6alkyl, C0-6alkylene-C3-10cycloalkyl, or C0-6alkylene-3-10 membered heterocycloalkyl comprising 1-4 ring heteroatoms independently selected from N, O, and S, wherein the alkyl, cycloalkyl, and heterocycloalkyl are optionally substituted by 1-3 R5;
• or
• R1 and R2 together with the nitrogen atom to which they are attached form a 3-10 membered heterocycloalkyl ring comprising 0-2 additional ring heteroatoms independently selected from N, O, and S, wherein the heterocycloalkyl is optionally substituted by 1-3 R6;
• each R3 is independently H, C1-6alkyl, halogen, CF3, OH, CN, CONR7(R7), SO2NR7R7, O—C1-6alkyl, or O—C6-10aryl, and the aryl is optionally substituted with 1-3 R5;
• each R4 is independently C1-6alkyl, halogen, CF3, CN, CONHR7, SO2NR7R7, O—C1-6alkyl, or O—C6-10aryl;
• each of R5 and R6 is independently C1-6alkyl, halogen, CF3, CN, OH, or O—C1-6alkyl;
• and
• each R7 is independently H, C1-6alkyl, C0-6alkylene-C6-10aryl, C0-6alkylene-5-7 membered heteroaryl, C0-6alkylene-C3-10cycloalkyl, or C0-6alkylene-3-10 membered heterocycloalkyl, each aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is optionally substituted by 1-3 R5, and the heteroaryl and heterocycloalkyl comprise 1-4 ring heteroatoms independently selected from N, O, and S.