A compound having the following structure of Formula: Core(̵L-NHE) n or pharmaceutically acceptable salt thereof, wherein: (a) n is 2 or 3; (b) Core is a Core moiety having two or three sites thereon for attachment to two or three NHE-inhibiting small molecule moieties; (c) L is a bond or linker connecting the Core moiety to the two or three NHE-inhibitory small molecule moieties; and (d) NHE is a NHE-inhibiting small molecule moiety having the following structure of Formula: wherein: B is aryl; each R 5 is independently selected from the group consisting of hydrogen, halogen, optionally substituted C 1-4 alkyl, optionally substituted C 1-4 alkoxy, optionally substituted C 1-4 thioalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyl, oxo, cyano, nitro, -NR 7 R 8, - NR 7 C(=O)R 8, -NR 7 C(=O)OR 8, -NR 7 C(=O)NR 8 R 9, -NR 7 SO 2 R 8, -NR 7 S 2 NR 8 R 9, -C(=O)OR 7, -C(=O)R 7, -C(=O)NR 7 R 8, -S 1-2 R 7, and -SO 2 NR 7 R 8, wherein R 7, R 8, and R 9 are independently selected from the group consisting of hydrogen, C 1-4 alkyl, or a bond linking the NHE-inhibiting small molecule moiety to L, provided at least one is a bond linking the NHE-inhibiting small molecule moiety to L; R 3 and R 4 are independently selected from the group consisting of hydrogen, optionally substituted C 1-4 alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; or R 3 and R 4 form together with the nitrogen to which they are bonded an optionally substituted 4-8 membered heterocyclyl; and each R 1 is independently selected from the group consisting of hydrogen, halogen, optionally substituted C 1-6 alkyl and optionally substituted C 1-6 alkoxy. (a) n is 2 or 3; (b) Core is a Core moiety having two or three sites thereon for attachment to two or three NHE-inhibiting small molecule moieties; (c) L is a bond or linker connecting the Core moiety to the two or three NHE-inhibitory small molecule moieties; and (d) NHE is a NHE-inhibiting small molecule moiety having the following structure of Formula: wherein: B is aryl; each R 5 is independently selected from the group consisting of hydrogen, halogen, optionally substituted C 1-4 alkyl, optionally substituted C 1-4 alkoxy, optionally substituted C 1-4 thioalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyl, oxo, cyano, nitro, -NR 7 R 8, - NR 7 C(=O)R 8, -NR 7 C(=O)OR 8, -NR 7 C(=O)NR 8 R 9, -NR 7 SO 2 R 8, -NR 7 S 2 NR 8 R 9, -C(=O)OR 7, -C(=O)R 7, -C(=O)NR 7 R 8, -S 1-2 R 7, and -SO 2 NR 7 R 8, wherein R 7, R 8, and R 9 are independently selected from the group consisting of hydrogen, C 1-4 alkyl, or a bond linking the NHE-inhibiting small molecule moiety to L, provided at least one is a bond linking the NHE-inhibiting small molecule moiety to L; R 3 and R 4 are independently selected from the group consisting of hydrogen, optionally substituted C 1-4 alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; or R 3 and R 4 form together with the nitrogen to which they are bonded an optionally substituted 4-8 membered heterocyclyl; and each R 1 is independently selected from the group consisting of hydrogen, halogen, optionally substituted C 1-6 alkyl and optionally substituted C 1-6 alkoxy. B is aryl; each R 5 is independently selected from the group consisting of hydrogen, halogen, optionally substituted C 1-4 alkyl, optionally substituted C 1-4 alkoxy, optionally substituted C 1-4 thioalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, hydroxyl, oxo, cyano, nitro, -NR 7 R 8, - NR 7 C(=O)R 8, -NR 7 C(=O)OR 8, -NR 7 C(=O)NR 8 R 9, -NR 7 SO 2 R 8, -NR 7 S 2 NR 8 R 9, -C(=O)OR 7, -C(=O)R 7, -C(=O)NR 7 R 8, -S 1-2 R 7, and -SO 2 NR 7 R 8, wherein R 7, R 8, and R 9 are independently selected from the group consisting of hydrogen, C 1-4 alkyl, or a bond linking the NHE-inhibiting small molecule moiety to L, provided at least one is a bond linking the NHE-inhibiting small molecule moiety to L; R 3 and R 4 are independently selected from the group consisting of hydrogen, optionally substituted C 1-4 alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; or R 3 and R 4 form together with the nitrogen to which they are bonded an optionally substituted 4-8 membered heterocyclyl; and each R 1 is independently selected from the group consisting of hydrogen, halogen, optionally substituted C 1-6 alkyl and optionally substituted C 1-6 alkoxy.