Potassium channel blockers for treating diseases and disorders

Abstract

This disclosure relates to aminopyridine compounds of Formula (I), and pharmaceutically acceptable salts thereof, as well as composition and uses of same for treating diseases and disorders.

Description

[0001]Attorney Docket No.29539-0842WO1 POTASSIUM CHANNEL BLOCKERS FOR TREATING DISEASES AND DISORDERS PRIORITY CLAIM This application claims the benefit of priority to U.S. Provisional Patent Application Serial No.63 / 680,391, filed on August 7, 2024, the disclosure of which is incorporated herein by reference in its entirety. FIELD This disclosure relates to aminopyridine compounds and their use in methods of treating diseases and disorders. BACKGROUND 4-aminopyridine (4AP) is a potassium channel blocker used in the symptomatic treatment of multiple sclerosis (MS). Its mechanism of action involves binding from the intracellular side to voltage-gated K+(Kv) channels exposed due to demyelination, thereby blocking the aberrant efflux of K+ions and enhancing axonal conduction. Additionally, 4AP has demonstrated potential clinical utility for spinal cord injury (SCI), traumatic brain injury (TBI), and other diseases involving demyelination. SUMMARY The disclosure provides a compound of formula (I) R or a pharmaceutically m, and n are defined herein. In some embodiments, a composition comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In some embodiments, the disclosure provides a method of treating a neurological disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of Formula (I), or a pharmaceutically acceptable salt thereof. Attorney Docket No.29539-0842WO1 In some embodiments, the disclosure provides a kit comprising a compound disclosed herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition disclosed herein; and instructions for administering the compound, a pharmaceutically acceptable salt thereof, or the pharmaceutical composition to a subject. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs. Methods and materials are described herein for use in the present application; other, suitable methods and materials known in the art can also be used. The materials, methods, and examples are illustrative only and not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. Other features and advantages of the present application will be apparent from the following detailed description and figures, and from the claims. DESCRIPTION OF THE DRAWINGS Fig. 1 shows a scheme of demyelination: in normally myelinated axons, sodium channels concentrate at the nodes of Ranvier (also known as myelin-sheath gaps) and potassium (K+) channels at the neighboring juxtaparanodes beneath the myelin sheath. During demyelination, K+channels become exposed, migrate through the demyelinated segment and increase in expression. This exposure of K+channels results in leakage of intracellular potassium ions, which in turn impairs propagation of electrical impulses. Fig.2 shows the structures of 5Me3F4AP, 3F4AP, 3Me4AP, and 4AP, (a) CYP2E1 inhibition IC50fit curves for 4AP (star), 5Me3F4AP (diamond), 3F4AP (plus), and tranylcypromine (hexagon, positive control). (b) Representative recordings at pH of 7.4 elicited from oocytes expressing the Shaker KVion channel before (upper, black) and after (lower, colored) the blockage with 1 mM of 5Me3F4AP. Currents were recorded as the response to voltage stimulus protocol that consisted of 50 ms depolarization steps from -100 to 60 mV in increments of 10 mV. Dashed line represents the zero current value. Horizontal and vertical bars of 25 ms and 2 μA represent the time and current scale for all recordings; (c) a comparison of IC50 values to inhibition of cytochrome enzyme; (d) Relative fluorescence-time curves based on the 60-minute kinetic measurement of 4AP (star), 5Me3F4AP (diamond), 3F4AP (star), and tranylcypromine (hexagon, positive control). Fig. 3 shows the blocking potency of 4AP derivatives on Shaker KV ion channel. (a), Representative K+recordings elicited from three different oocytes expressing the Shaker KVion channel in response to a voltage stimulus at ^40 ^^^^ (upper voltage protocol) before and after addition Attorney Docket No.29539-0842WO1 of 1 mM on the external oocyte membrane vestibule of each 4AP structural analog. Dashed lines represent the zero-current level and horizontal and vertical bars indicate the time and current scale for each recording. (b), Relative current vs. the concentration curves of each 4AP derivative evaluated at +40 mV and pH=7.4. Fig. 4 shows the blocking potency of 4AP structural analogs on Shaker KV ion channel. (a), Representative K+recordings elicited from five different oocytes expressing the Shaker KVion channel in response to a voltage stimulus (upper voltage protocol) before and after addition of 1 mM of 4Me3AP, 4FAP, 4Cl3AP, 4Br3AP and 4I3AP. Dashed lines represent the zero-current level and horizontal and vertical bars indicate the time and current scale for each recording. (b), Relative current vs. the concentration curves of each 4AP structural analog showed in (a) evaluated at ^40 ^^^^ and pH=7.4. Fig. 5 shows pH and voltage dependence of the blockage of 4Me3AP evaluated in Shaker KVion channel. (a), Representative K+recordings elicited from three different oocytes expressing the Shaker KVion channel as the response to voltage stimulus protocol that consisted of 50 ms depolarization step from െ100 to ^60 ^^^^ (top left upper voltage protocol) and under different pH conditions before and after addition of 1 mM of 4Me3AP. Dashed lines represent the zero-current level and horizontal and vertical bars indicate the time and current scale for each recording. (b), Relativecurrent vs. the concentration of 4Me3AP curves assessed at ^^ ൌ ^60 ^^^^ and pH of 5.7, 7.4 and 9.1.(c), ^^^^ହ^^^^^ curves at pH of 5.7 and 7.4. Fig.6 shows pH dependence of the blockage of 4F3AP and 4I3AP evaluated in Shaker KVion channel. (a), Relative current vs. the concentration of 4F3AP at pH 6.4. (b), Relative current vs. the concentration of 4I3AP at pH 5.7. Fig. 7 shows specific blockage of certain KV ion channels expressed in the CNS by 4AP, 5Me3F4AP and 3Me4AP. From left to right, representative recordings of K+current before (black) and after (gray) addition of 1mM of 4AP (left), 5Me3F4AP (center) and 3Me4AP (right) assessed from different Xenopus laevis oocytes expressing (a), rKV1.2, (b), hKV2.1, (c), hKV2.1 / 6.4, and (d), hKV7.2 / 7.3. Currents were elicited in response to a voltage stimulus of 40 mV (left, upper protocol) and pH of 7.4. Horizontal and vertical bars for each recording indicate the time and current scale. Dashed lines represent the zero-current level. Fig. 8 shows a determination of the blockage potency of certain KVion channels expressed in the CNS by 4AP, 5Me3F4AP and 3Me4AP. Attorney Docket No.29539-0842WO1 DETAILED DESCRIPTION Compounds of Formula (I) In some embodiments, the present disclosure provides a compound of formula (I) Rn NH2or a pharmaceutically each R is independently C1-10 alkyl optionally substituted with hydroxy, C1-10alkoxy, NRARB, C1-10haloalkyl, C2-10alkenyl, C2-10alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl; each occurrence of RAand RBis independently selected from hydrogen and C1-C6alkyl; n is 0, 1, 2, or 3; and m is 0 or 1; wherein the compound is not 4-aminopyridine or 4-methyl-3-aminopyridine. In some embodiments, the present disclosure provides a compound of formula (I) RNH2or a pharmaceutically each R is independently10C1-10haloalkyl, C2-10alkenyl, C2-10 alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl; n is 0, 1, 2, or 3; and m is 0 or 1; wherein the compound is not 4-aminopyridine or 4-methyl-3-aminopyridine. In some embodiments, m is 1. In some embodiments, m is 0. In some embodiments, the C1-C10 haloalkyl is a C1-C3 haloalkyl. In some embodiments, the C1-C10 haloalkyl is a C1-C3 monofluoroalkyl. In some embodiments, the C1-C3 haloalkyl is a C1-C3 monofluoroalkyl. In some embodiments, the C1-C3 haloalkyl is a C1-C3 difluoroalkyl. In some Attorney Docket No.29539-0842WO1 embodiments, the C1-C10 haloalkyl is a trifluoroalkyl. In some embodiments, the C1-C3 haloalkyl is CHF2. In some embodiments, the C1-C3haloalkyl is CH2F. In some embodiments, the C1-C10haloalkyl is CF3. In some embodiments, when m is 1, then each R is independently selected from halogen, C1-10 alkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl. In some embodiments, n is 3. In some embodiments, n is 2. In some embodiments, n is 1. In some embodiments, n is 0. In some embodiments, m is 0 and n is 1, 2, or 3. In some embodiments, m is 1 and n is 1, 2, or 3. In some embodiments, m is 1 and n is 0, 1, 2, or 3. In some embodiments, m is 0 and n is 1, 1, 2, or 3. In some embodiments, each R is independently selected from halogen, C1-6alkyl, C1-6haloalkyl, C2-6 alkenyl, C2-6 alkynyl, 3-6 membered cycloalkyl, 4-6 membered heterocyclyl, phenyl, and 5-6 membered heteroaryl. In some embodiments, each R is independently selected from halogen, C1-3 alkyl, C1-3 haloalkyl, C2-3 alkenyl, C2-3 alkynyl, 3-6 membered cycloalkyl, and 4-6 membered heterocyclyl. In some embodiments, n is 1, 2, or 3; and each R is independently selected from halogen, hydroxy, C1-10 alkyl optionally substituted with hydroxy, C1-10 alkoxy, NRARB, C1-10 haloalkyl, C2-10 alkenyl, C2-10alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl. In some embodiments, the C1-10alkyl optionally substituted with hydroxy is C1-10alkyl. In some embodiments, the C1-10 alkyl optionally substituted with hydroxy is C1-10 alkyl substituted with hydroxy. In some embodiments, the C1-10alkyl optionally substituted with hydroxy is hydroxymethyl. In some embodiments, the C1-10 alkyl optionally substituted with hydroxy is methyl. In some embodiments, RAand RBare hydrogen. In some embodiments, RAis hydrogen and and RB is C1-6 alkyl. In some embodiments, RA and RB are C1-6 alkyl. In some embodiments, NRARBis NH2. In some embodiments, C1-10 alkoxy is methoxy. In some embodiments, n is 1; and R is selected from halogen, hydroxy, C1-10alkyl optionally substituted with hydroxy, C1-10 alkoxy, NRARB, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl. Attorney Docket No.29539-0842WO1 In some embodiments, n is 1; and R is halogen. In some embodiments, n is 1; and R is hydroxy. In some embodiments, n is 1; and R is C1-10alkyl optionally substituted with hydroxy. In some embodiments, n is 1; and R is C1-10 alkoxy. In some embodiments, n is 1; and R is NRARB. In some embodiments, n is 1; and R is C1-10haloalkyl. In some embodiments, n is 1; and R is C2-10alkenyl. In some embodiments, n is 1; and R is C2-10 alkynyl. In some embodiments, n is 1; and R is 3-10 membered cycloalkyl. In some embodiments, n is 1; and R is 3-10 membered heterocyclyl. In some embodiments, n is 1; and R is 6-10 membered aryl. In some embodiments, n is 1; and R is and 5-10 membered heteroaryl. In some embodiments, n is 2; and one R is halogen. In some embodiments, n is 2; and one R is hydroxy. In some embodiments, n is 2; and one R is C1-10alkyl optionally substituted with hydroxy. In some embodiments, n is 2; and one R is C1-10 alkoxy. In some embodiments, n is 2; and one R is NRARB. In some embodiments, n is 2; and one R is C1-10haloalkyl. In some embodiments, n is 2; and one R is C2-10 alkenyl. In some embodiments, n is 2; and one R is C2-10 alkynyl. In some embodiments, n is 2; and one R is 3-10 membered cycloalkyl. In some embodiments, n is 2; and one R is 3-10 membered heterocyclyl. In some embodiments, n is 2; and one R is 6-10 membered aryl. In some embodiments, n is 2; and one R is and 5-10 membered heteroaryl. In some embodiments, n is 2, one R is halogen, and the other R is halogen. In some embodiments, n is 2, one R is halogen, and the other R is hydroxy. In some embodiments, n is 2, one R is halogen, and the other R is C1-10alkyl optionally substituted with hydroxy. In some embodiments, n is 2, one R is halogen, and the other R is C1-10alkoxy. In some embodiments, n is 2, one R is halogen, and the other R is NRARB. In some embodiments, n is 2, one R is halogen, and the other R is C1-10haloalkyl. In some embodiments, n is 2, one R is halogen, and the other R is C2-10 alkenyl. In some embodiments, n is 2, one R is halogen, and the other R is C2-10alkynyl. In some embodiments, n is 2, one R is halogen, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is halogen, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is halogen, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is halogen, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2, one R is hydroxy, and the other R is halogen. In some embodiments, n is 2, one R is hydroxy, and the other R is hydroxy. In some embodiments, n is 2, one R is hydroxy, and the other R is C1-10alkyl optionally substituted with hydroxy. Attorney Docket No.29539-0842WO1 In some embodiments, n is 2, one R is hydroxy, and the other R is C1-10 alkoxy. In some embodiments, n is 2, one R is hydroxy, and the other R is NRARB. In some embodiments, n is 2, one R is hydroxy, and the other R is C1-10 haloalkyl. In some embodiments, n is 2, one R is hydroxy, and the other R is C2-10alkenyl. In some embodiments, n is 2, one R is hydroxy, and the other R is C2-10 alkynyl. In some embodiments, n is 2, one R is hydroxy, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is hydroxy, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is hydroxy, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is hydroxy, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2, one R is C1-10alkyl optionally substituted with hydroxy, and the other R is halogen. In some embodiments, n is 2, one R is C1-10alkyl optionally substituted with hydroxy, and the other R is hydroxy. In some embodiments, n is 2, one R is C1-10 alkyl optionally substituted with hydroxy, and the other R is C1-10 alkyl optionally substituted with hydroxy. In some embodiments, n is 2, one R is C1-10 alkyl optionally substituted with hydroxy, and the other R is C1-10alkoxy. In some embodiments, n is 2, one R is C1-10 alkyl optionally substituted with hydroxy, and the other R is NRARB. In some embodiments, n is 2, one R is C1-10 alkyl optionally substituted with hydroxy, and the other R is C1-10haloalkyl. In some embodiments, n is 2, one R is C1-10 alkyl optionally substituted with hydroxy, and the other R is C2-10alkenyl. In some embodiments, n is 2, one R is C1-10 alkyl optionally substituted with hydroxy, and the other R is C2-10alkynyl. In some embodiments, n is 2, one R is C1-10 alkyl optionally substituted with hydroxy, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is C1-10 alkyl optionally substituted with hydroxy, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is C1-10 alkyl optionally substituted with hydroxy, and the other R is 6-10 membered aryl. Attorney Docket No.29539-0842WO1 In some embodiments, n is 2, one R is C1-10 alkyl optionally substituted with hydroxy, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2, one R is C1-10 alkoxy, and the other R is halogen. In some embodiments, n is 2, one R is C1-10alkoxy, and the other R is hydroxy. In some embodiments, n is 2, one R is C1-10 alkoxy, and the other R is C1-10 alkyl optionally substituted with hydroxy. In some embodiments, n is 2, one R is C1-10 alkoxy, and the other R is C1-10 alkoxy. In some embodiments, n is 2, one R is C1-10alkoxy, and the other R is NRARB. In some embodiments, n is 2, one R is C1-10 alkoxy, and the other R is C1-10 haloalkyl. In some embodiments, n is 2, one R is C1-10alkoxy, and the other R is C2-10alkenyl. In some embodiments, n is 2, one R is C1-10 alkoxy, and the other R is C2-10 alkynyl. In some embodiments, n is 2, one R is C1-10alkoxy, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is C1-10alkoxy, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is C1-10 alkoxy, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is C1-10 alkoxy, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2, one R is NRARB, and the other R is halogen. In some embodiments, n is 2, one R is NRARB, and the other R is hydroxy. In some embodiments, n is 2, one R is NRARB, and the other R is C1-10alkyl optionally substituted with hydroxy. In some embodiments, n is 2, one R is NRARB, and the other R is C1-10alkoxy. In some embodiments, n is 2, one R is NRARB, and the other R is NRARB. In some embodiments, n is 2, one R is NRARB, and the other R is C1-10haloalkyl. In some embodiments, n is 2, one R is NRARB, and the other R is C2-10 alkenyl. In some embodiments, n is 2, one R is NRARB, and the other R is C2-10alkynyl. In some embodiments, n is 2, one R is NRARB, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is NRARB, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is NRARB, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is NRARB, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2, one R is C1-10haloalkyl, and the other R is halogen. In some embodiments, n is 2, one R is C1-10 haloalkyl, and the other R is hydroxy. Attorney Docket No.29539-0842WO1 In some embodiments, n is 2, one R is C1-10 haloalkyl, and the other R is C1-10 alkyl optionally substituted with hydroxy. In some embodiments, n is 2, one R is C1-10 haloalkyl, and the other R is C1-10 alkoxy. In some embodiments, n is 2, one R is C1-10haloalkyl, and the other R is NRARB. In some embodiments, n is 2, one R is C1-10 haloalkyl, and the other R is C1-10 haloalkyl. In some embodiments, n is 2, one R is C1-10haloalkyl, and the other R is C2-10alkenyl. In some embodiments, n is 2, one R is C1-10 haloalkyl, and the other R is C2-10 alkynyl. In some embodiments, n is 2, one R is C1-10haloalkyl, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is C1-10haloalkyl, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is C1-10haloalkyl, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is C1-10 haloalkyl, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2, one R is C2-10 alkenyl, and the other R is halogen. In some embodiments, n is 2, one R is C2-10 alkenyl, and the other R is hydroxy. In some embodiments, n is 2, one R is C2-10 alkenyl, and the other R is C1-10 alkyl optionally substituted with hydroxy. In some embodiments, n is 2, one R is C2-10alkenyl, and the other R is C1-10alkoxy. In some embodiments, n is 2, one R is C2-10 alkenyl, and the other R is NRARB. In some embodiments, n is 2, one R is C2-10alkenyl, and the other R is C1-10haloalkyl. In some embodiments, n is 2, one R is C2-10 alkenyl, and the other R is C2-10 alkenyl. In some embodiments, n is 2, one R is C2-10alkenyl, and the other R is C2-10alkynyl. In some embodiments, n is 2, one R is C2-10 alkenyl, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is C2-10 alkenyl, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is C2-10 alkenyl, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is C2-10alkenyl, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2, one R is C2-10alkynyl, and the other R is halogen. In some embodiments, n is 2, one R is C2-10 alkynyl, and the other R is hydroxy. In some embodiments, n is 2, one R is C2-10alkynyl, and the other R is C1-10alkyl optionally substituted with hydroxy. Attorney Docket No.29539-0842WO1 In some embodiments, n is 2, one R is C2-10 alkynyl, and the other R is C1-10 alkoxy. In some embodiments, n is 2, one R is C2-10alkynyl, and the other R is NRARB. In some embodiments, n is 2, one R is C2-10 alkynyl, and the other R is C1-10 haloalkyl. In some embodiments, n is 2, one R is C2-10alkynyl, and the other R is C2-10alkenyl. In some embodiments, n is 2, one R is C2-10 alkynyl, and the other R is C2-10 alkynyl. In some embodiments, n is 2, one R is C2-10alkynyl, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is C2-10alkynyl, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is C2-10alkynyl, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is C2-10 alkynyl, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is halogen. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is hydroxy. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is C1-10 alkyl optionally substituted with hydroxy. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is C1-10 alkoxy. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is NRARB. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is C1-10haloalkyl. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is C2-10alkenyl. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is C2-10alkynyl. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is 3-10 membered cycloalkyl, and the other R is 5-10 membered heteroaryl. Attorney Docket No.29539-0842WO1 In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is halogen. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is hydroxy. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is C1-10 alkyl optionally substituted with hydroxy. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is C1-10 alkoxy. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is NRARB. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is C1-10 haloalkyl. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is C2-10 alkenyl. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is C2-10 alkynyl. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is 3-10 membered heterocyclyl, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is halogen. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is hydroxy. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is C1-10alkyl optionally substituted with hydroxy. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is C1-10alkoxy. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is NRARB. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is C1-10haloalkyl. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is C2-10 alkynyl. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is 3-10 membered cycloalkyl. Attorney Docket No.29539-0842WO1 In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is . In some embodiments, n is 2, one R is 6-10 membered aryl, and the other R is . In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is halogen. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is hydroxy. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is C1-10 alkyl optionally substituted with hydroxy. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is C1-10 alkoxy. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is NRARB. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is C1-10haloalkyl. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is C2-10alkenyl. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is C2-10alkynyl. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is 3-10 membered cycloalkyl. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is 3-10 membered heterocyclyl. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is 6-10 membered aryl. In some embodiments, n is 2, one R is and 5-10 membered heteroaryl, and the other R is 5-10 membered heteroaryl. In some embodiments, n is 2 and each R is independently selected from halogen and C1-6alkyl. Attorney Docket No.29539-0842WO1 In some embodiments, n is 2 and each R is independently selected from halogen and C1-C3 monofluoroalkyl. In some embodiments, n is 1 and R is halogen. In some embodiments, n is 1 and R is C1-6alkyl. In some embodiments, R is methyl. In some embodiments, R is ethyl. In some embodiments, R is propyl. In some embodiments, n is 1 and R is C1-C3monofluoroalkyl. In some embodiments, R is - CHF. In some embodiments, R is -CF2. In some embodiments, n is 1 and R is C1-6haloalkyl. In some embodiments, n is 1 and R is C2-6 alkenyl. In some embodiments, n is 1 and R is C2-6alkynyl. In some embodiments, n is 1 and R is 3-6 membered cycloalkyl. In some embodiments, n is 1 and R is 4-6 membered heterocyclyl. In some embodiments, n is 1 and R is 6-10 membered aryl. In some embodiments, n is 1 and R is phenyl. In some embodiments, n is 1 and R is 5-10 membered heteroaryl. In some embodiments, n is 1 and R is 5-6 membered heteroaryl. In some embodiments, each R is C1-10 alkyl. In some embodiments, each R is methyl. In some embodiments, each R is ethyl. In some embodiments, each R is propyl. In some embodiments, the present disclosure provides a compound of formula (I-i) Rn NH2the present disclosure provides a compound of formula (I-i-a) the present disclosure provides a compound of formula (I-i-a-i) . Attorney Docket No.29539-0842WO1 In some embodiments, the present disclosure provides a compound of formula (I-i-a-ii) F RNH2ii). the present disclosure provides a compound of formula (I-i-a-iii) iii). In some embodiments, the present disclosure provides a compound of formula (I-i-b) NH2. embodiments, the present disclosure provides a compound of formula (I-i-c) RNH2. the present disclosure provides a compound of formula (I-i-c-i) NH2the present disclosure provides a compound of formula (I-i-c-ii) ii). Attorney Docket No.29539-0842WO1 In some embodiments, the present disclosure provides a compound of formula (I-i-c-iii) R H2N . the present disclosure provides a compound of formula (I-i-d) . the present disclosure provides a compound of formula (I-ii) Rnii). embodiments, the present disclosure provides a compound of formula (I-ii-a) RNH2ii-a). embodiments, the present disclosure provides a compound of formula (I-ii-a-i) NH2ii-a-i). embodiments, the present disclosure provides a compound of formula (I-ii-a-ii) R ii-a-ii). Attorney Docket No.29539-0842WO1 In some embodiments, the present disclosure provides a compound of formula (I-ii-b) RNH2ii-b). the compound is selected from: , , a , , , Attorney Docket No.29539-0842WO1 , , , , , , , , , , Attorney Docket No.29539-0842WO1 a pharmaceutically acceptable salt of In some embodiments, the a pharmaceutically acceptable saltthereof. Pharmaceutically acceptable salts In some embodiments, the disclosure provides a pharmaceutical composition comprising a compound of Formula of (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. In some embodiments, a salt of a compound of this disclosure is formed between an acid and a basic group of the compound, such as an amino functional group, or a base and an acidic group of the compound, such as a carboxyl functional group. According to another embodiment, the compound is a pharmaceutically acceptable acid addition salt. In some embodiments, acids commonly employed to form pharmaceutically acceptable salts of the compounds of Formula (I) include inorganic acids such as hydrogen bisulfide, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid and phosphoric acid, as well as organic acids such as para-toluenesulfonic acid, salicylic acid, tartaric acid, bitartaric acid, ascorbic acid, maleic acid, besylic acid, fumaric acid, gluconic acid, glucuronic acid, formic acid, glutamic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, lactic acid, oxalic acid, para-bromophenylsulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid and acetic acid, as well as related inorganic and organic acids. Such pharmaceutically acceptable salts thus include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexyne-l,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, sulfonate, xylene sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, maleate, tartrate, methanesu1fonate, propanesulfonate, naphthalene-1-sulfonate, Attorney Docket No.29539-0842WO1 naphthalene-2- sulfonate, mandelate and other salts. In one embodiment, pharmaceutically acceptable acid addition salts include those formed with mineral acids such as hydrochloric acid and hydrobromic acid, and especially those formed with organic acids such as maleic acid. In some embodiments, bases commonly employed to form pharmaceutically acceptable salts of the compounds of Formula (I) include hydroxides of alkali metals, including sodium, potassium, and lithium; hydroxides of alkaline earth metals such as calcium and magnesium; hydroxides of other metals, such as aluminum and zinc; ammonia, organic amines such as unsubstituted or hydroxyl- substituted mono-, di-, or tri-alkylamines, dicyclohexylamine; tributyl amine; pyridine; N-methyl, N- ethylamine; diethylamine; triethylamine; mono-, bis-, or tris-(2-OH-(C1-C6)-alkylamine), such as N,N- dimethyl-N-(2-hydroxyethyl)amine or tri-(2-hydroxyethyl)amine; N-methyl-D-glucamine; morpholine; thiomorpholine; piperidine; pyrrolidine; and amino acids such as arginine, lysine, and the like. Compositions and Methods of Use The present application also provides pharmaceutical compositions comprising an effective amount of a compound of the present disclosure (e.g., Formula (I)) disclosed herein and a pharmaceutically acceptable carrier. The carrier(s) are “acceptable” in the sense of being compatible with the other ingredients of the formulation and, in the case of a pharmaceutically acceptable carrier, not deleterious to the recipient thereof in an amount used in the medicament. In some embodiments, the composition comprises two or more (e.g., two) compounds of Formula (I), or pharmaceutically acceptable salts thereof. In some embodiments, the disclosure provides a method of treating a neurological disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the neurological disorder is a central nervous system (CNS) disorder. In some embodiments, the neurological disorder is a peripheral nervous system (PNS) disorder. In some embodiments, the neurological disorder is selected from multiple sclerosis (MS), myelin oligodendrocyte glicoprotein antibody disease (MOGAD), neuromyelitis optica, spinal cord injury, spinal cord compression, acute disseminated encephalomyelitis, optic neuromyelitis, progressive multifocal leukoencephalopathy, congenital demyelinating disease, Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy, metabolic disorders, multifocal motor neuropathy, leukodystrophy, adrenoleukodystrophy, Alexander's Disease, Metachromatic Leukodystrophy, vanishing white matter disease, Refsum Disease, Cockayne Syndrome, Van der Attorney Docket No.29539-0842WO1 Knapp Syndrome, Zellweger Syndrome, Pelizaeus-Merzbacher Disease, Krabbe Disease, Canavan Disease, traumatic brain injury, botulism intoxication, tetrodotoxin poisoning, carpal tunnel syndrome, diabetes, Epstein-Barr syndrome, amyotrophic lateral sclerosis, and other neurological diseases. In some embodiments, the neurological disorder is multiple sclerosis (MS). In some embodiments, the neurological disorder is myelin oligodendrocyte glicoprotein antibody disease (MOGAD). In some embodiments, the neurological disorder is neuromyelitis optica. In some embodiments, the neurological disorder is spinal cord injury. In some embodiments, the neurological disorder is spinal cord compression. In some embodiments, the neurological disorder is acute disseminated encephalomyelitis. In some embodiments, the neurological disorder is optic neuromyelitis. In some embodiments, the neurological disorder is progressive multifocal leukoencephalopathy. In some embodiments, the neurological disorder is congenital demyelinating disease. In some embodiments, the neurological disorder is Guillain-Barre syndrome. In some embodiments, the neurological disorder is chronic inflammatory demyelinating polyneuropathy. In some embodiments, the neurological disorder is metabolic disorders. In some embodiments, the neurological disorder is multifocal motor neuropathy. In some embodiments, the neurological disorder is leukodystrophy. In some embodiments, the neurological disorder is adrenoleukodystrophy. In some embodiments, the neurological disorder is Alexander's Disease. In some embodiments, the neurological disorder is Metachromatic Leukodystrophy. In some embodiments, the neurological disorder is vanishing white matter disease. In some embodiments, the neurological disorder is Refsum Disease. In some embodiments, the neurological disorder is Cockayne Syndrome. In some embodiments, the neurological disorder is Van der Knapp Syndrome. In some embodiments, the neurological disorder is Zellweger Syndrome. In some embodiments, the neurological disorder is Pelizaeus-Merzbacher Disease. In some embodiments, the neurological disorder is Krabbe Disease. In some embodiments, the neurological disorder is Canavan Disease. In some embodiments, the neurological disorder is traumatic brain injury. In some embodiments, the neurological disorder is botulism intoxication. In some embodiments, the neurological disorder is tetrodotoxin poisoning. Attorney Docket No.29539-0842WO1 In some embodiments, the neurological disorder is carpal tunnel syndrome. In some embodiments, the neurological disorder is diabetes. In some embodiments, the neurological disorder is Epstein-Barr syndrome. In some embodiments, the neurological disorder is amyotrophic lateral sclerosis. In some embodiments, the disclosure provides a method of treating a neurological disorder in a subject in need thereof, the method comprising: determining that the subject has a neurological disorder; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, determining that the subject has a neurological disorder comprises determining demyelination in the subject. In some embodiments, determining that the subject has a neurological disorder comprises administering to the subject an imaging effective amount of a radiotracer; and determining the presence or absence of a signal from the compound, wherein the presence of a signal indicates that the subject has a neurological disorder. In some embodiments, when a subject has a neurological disorder, the subject is identified or diagnosed as having the neurological disorder. In some embodiments, the disclosure provides a method of treating a neurological disorder in a subject in need thereof, the method comprising: detecting demyelination in the subject; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, detecting demyelination in the subject comprises administering to the subject an imaging effective amount of a radiotracer; and determining the presence or absence of a signal from the compound, wherein the presence of a signal indicates demyelination. In some embodiments, detecting demyelination in the subject comprises administering to the subject an imaging effective amount of a radiotracer; and determining the presence or absence of a signal from the radiotracer, wherein the presence of a signal indicates demyelination. In some embodiments, the disclosure provides a method of treating a neurological disorder in a subject in need thereof, the method comprising: detecting demyelination in the subject; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of treating a neurological disorder in a subject in need thereof, the method comprising: Attorney Docket No.29539-0842WO1 detecting an abnormally low axonal conduction in the subject; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. Axonal conduction refers to the velocity at which an action potential propagates along an axon. Various methods of measuring axonal conduction are known in the art. For example, see Bio. Protoc. 2017, 7(5), e2152, which is incorporated by reference herein in its entirety. In some embodiments, the disclosure provides a method of treating a neurological disorder in a subject suspected of having a neurological disorder, the method comprising administering to the subject an imaging effective amount of a radiotracer; determining the presence or absence of a signal from the radiotracer; and if a signal is detected, administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of treating a neurological disorder in a subject identified or diagnosed as having a neurological disorder, the method comprising administering to the subject an imaging effective amount of a radiotracer; determining the presence or absence of a signal from the radiotracer; and if a signal is detected, administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of treating a neurological disorder in a subject identified or diagnosed as having a neurological disorder, the method comprising: contacting the brain or spinal cord tissue of the subject with a radiotracer; detecting a signal from the radiotracer; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the brain or spinal cord tissue is brain tissue. In some embodiments, the brain tissue is CNS tissue. In some embodiments, the brain or spinal cord tissue is spinal cord tissue. In some embodiments, the brain or spinal cord tissue is brain tissue. In some embodiments, the tissue is from a biopsy sample. In some embodiments, the tissue is in the subject. In some embodiments, the disclosure provides a method of reducing the frequency, severity, and / or duration of symptoms of a neurological disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. Attorney Docket No.29539-0842WO1 In some embodiments, the disclosure provides a method of reducing the frequency, severity, and / or duration of symptoms of a neurological disorder in a subject, comprising: detecting demyelination in the subject; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of reducing the frequency, severity, and / or duration of symptoms of a neurological disorder in a subject, comprising: detecting an abnormally low axonal conduction in the subject; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of reducing the frequency, severity, and / or duration of symptoms of a neurological disorder in a subject, comprising: identifying or diagnosing the subject as having symptoms of the neurological disorder; administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, reducing the frequency, severity, and / or duration of symptoms comprising reducing the frequency of symptoms. In some embodiments, reducing the frequency, severity, and / or duration of symptoms comprising reducing the severity of symptoms. In some embodiments, reducing the frequency, severity, and / or duration of symptoms comprising reducing the duration of symptoms. In some embodiments, the symptoms of the neurological disorder are selected from the group consisting of: visual changes, numbness, tingling sensation, paralysis, vertigo, dizziness, erectile dysfunction, incontinence, tremor, slurred speech, fatigue, muscular weakness, muscular stiffness, muscle spasm, gastrointestinal dysfunction, reduced coordination, sensory loss, reduced motility, and reduced reflexes. In some embodiments, the disclosure provides a method of increasing muscular strength in a subject identified or diagnosed as having muscular weakness, the method comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of preventing or reversing muscle weakness in a subject in need thereof, the method comprising to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. Attorney Docket No.29539-0842WO1 In some embodiments, the method comprises measuring an increase in muscle mass in the subject using magnetic resonance imaging (MRI) after administering the therapeutically effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the disclosure provides a method of increasing motility in a subject, comprising administering to the subject a therapeutically effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises increasing the number of voluntary muscle contractions in the subject per minute relative to before administering the therapeutically effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises increasing the duration of a voluntary muscle contraction in the subject relative to before administering the therapeutically effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the disclosure provides a method of preventing, slowing, or reversing sarcopenia in a subject in need thereof, the method comprising administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the disclosure provides a method of treating or preventing myotonia in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises determining an improvement in the stiffness visual analogue scale (VAS). In some embodiments, the method comprises determining an improvement of at least 1 point (e.g., 1 point, 2 points, 3 points, or 4 points) in the stiffness visual analogue scale (VAS). Further information on the stiffness VAS can be found in Hammarén, Elisabet & Kjellby-Wendt, Gunilla & Lindberg, Christopher. (2005). Quantification of mobility impairment and self-assessment of stiffness in patients with myotonia congenita by the physiotherapist, which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining an increase in electrical activity in a muscle of the subject after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some Attorney Docket No.29539-0842WO1 embodiments, the method comprises determining an increase (e.g., at least 1% increase, at least 2% increase, at least 5% increase, at least 7% increase, at least 10% increase, at least 15% increase, at least 20% increase, at least 30% increase, or at least 40% increase) in electrical activity in a muscle of a subject using electromyography (EMG). In some embodiments, the disclosure provides a method of improving balance and / or coordination in a subject, comprising administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises determining an improvement in the short physical performance battery (SPPB) after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises determining an improvement of at least 1 point (e.g., 2 points, 3 points, 4 points, 5 points, 6 points, 7 points, 8 points, 9 points, 10 points, or 11 points) in the short physical performance battery (SPPB) after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, determining an improvement in the short physical performance battery (SPPB) comprises determining an improvement in the three-stage balance test. In some embodiments, determining an improvement in the short physical performance battery (SPPB) comprises determining an improvement in the gait speed test. In some embodiments, determining an improvement in the short physical performance battery (SPPB) comprises determining an improvement in the chair stand test. Further information on the SPPB can be found in, e.g., Cassidy B, Arena S. The Short Physical Performance Battery as a Predictor of Functional Decline. Home Healthcare Now. 2022 May 1;40(3):168-9 which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining an increase in hand grip strength as measured by a dynamometer after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. Further information can be found in, e.g., Journal of Bodywork and Movement Therapies, 2020, 24(1), 235- 243, which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining an at least 5% (e.g., at least 10% increase, at least 15% increase, at least 20% increase, at least 25% increase, at least 30% increase, at least 40% increase, at least 50% increase, at least 60% increase, at least 70% increase, at least 80% increase, at least 90% increase, or at least 95% increase) in hand grip strength as measured by a dynamometer after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. Attorney Docket No.29539-0842WO1 In some embodiments, the disclosure provides a method of increasing motility in a subject, the method comprising administering a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, increasing motility in the subject comprises increasing the number of voluntary muscle contractions in the subject per unit time (e.g., per minute, per 6 minutes, per 10 minutes, per 15 minutes, per 30 minutes, per 45 minutes, per hour, per 3 hours, per 12 hours, per 24 hours, per 2 days, per week, or per month) relative to before the therapeutically effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein was administered to the subject. In some embodiments, increasing motility in the subject comprises increasing the number of voluntary muscle contractions in the subject per minute. In some embodiments, increasing motility in the subject comprises increasing the duration of a voluntary muscle contraction in the subject relative to before the therapeutically effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, increasing motility in the subject comprises decreasing the length of time it takes for the subject to perform a task or an activity that requires movement and / or muscle contraction(s) relative to before administering the therapeutically effective amount of the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises determining an improvement in the activity and social participation DM1-Active Scale after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. Further information on the activity and social participation DM1-Active Scale can be found in, e.g., PLoS One 2015, 10: e0139944, which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining an improvement in the health-related quality of life InQoL questionnaire after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, determining an improvement in the health-related quality of life InQoL questionnaire comprises determining an improvement in the fatigue subdomain. In some embodiments, determining an improvement in the health-related quality of life InQoL questionnaire comprises determining an improvement in the activities subdomain. In some embodiments, determining an improvement in the health-related quality of life InQoL questionnaire comprises determining an improvement in the independence subdomain. Further information on the health- related quality of life InQoL questionnaire can be found in, e.g., Taylor VR. Measuring healthy days; Attorney Docket No.29539-0842WO1 population assessment of health-related quality of life. Atlanta: US Centers for Disease Control and Prevention; 2000, which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining an improvement in at least one clinical parameter selected from the group consisting of: myotonia indices, muscle function and strength parameter, quality of life parameter, gait parameters, and total mechanical power of gait after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. Further information on myotonia indices, muscle function and strength parameter, quality of life parameter, gait parameters, and total mechanical power of gait can be found in, e.g., Brain 2018: 141; 2855-2865, which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining an increase in the distance walked by the subject during the 6 minute walk test (6MWT) after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises determining an at least 5% (e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 100%, at least 150%, at least 200%) increase in the distance walked by the subject during the 6 minute walk test (6MWT) after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. Further information on the 6 minute walk test (6MWT) can be found in, e.g., Endocrinology 2005; 146: 1328–1337, which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining a reduction in the time taken by the subject to complete the 10 meter walk test after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises determining an at least 5% (e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%) reduction in the time taken by the subject to complete the 10 meter walk test after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. Further information on the 10 meter walk test can be found in, e.g., Journal of Neurologic Physical Therapy, 2018; 42(2):174- 220, which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining an improvement in at least one of the myotonia indices, muscle function and strength, quality of life, and total mechanical power after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described Attorney Docket No.29539-0842WO1 herein to the subject. In some embodiments, the method comprises determining an at least 5% (e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%) reduction in the time taken by the subject to complete the 10 meter walk test after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. Further information on the 10 meter walk test can be found in, e.g., Journal of Neurologic Physical Therapy, 2018; 42(2):174-220, which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining a reduction in the time taken by the subject to complete the 100 meter walk test after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises determining an at least 5% (e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%) reduction in the time taken by the subject to complete the 100 meter walk test after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. Further information on the 100 meter walk test can be found in, e.g., Alfano, Lindsay & Miller, Natalie & Berry, Katherine & Yin, Han & Rolf, Kimberly & Flanigan, Kevin & Mendell, Jerry & Lowes, Linda. (2017). The 100- meter timed test: Normative data in healthy males and comparative pilot outcome data for use in Duchenne muscular dystrophy clinical trials. Neuromuscular Disorders. 27. 10.1016 / j.nmd.2017.02.007, which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining an increase in muscle mass in the subject using magnetic resonance imaging (MRI) after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises determining an at least 1% increase (e.g., an at least 2% increase, an at least 3% increase, an at least 4% increase, an at least 5% increase, an at least 7% increase, an at least 9% increase, an at least 11% increase, an at least 13% increase, an at least 15% increase, an at least 20% increase, an at least 25% increase, an at least 30% increase, an at least 35% increase, or an at least 40% increase) in muscle mass in the subject using magnetic resonance imaging (MRI) after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the muscle mass is skeletal muscle mass. In some embodiments, the increase in muscle mass is an increase in whole body muscle mass. Further information can be found in, e.g., Eur. J. Neurol. 2022 Mar;29(3):843-854 or Radiography, 2015, 21(1), e35-e39, each of which is incorporated by reference herein in its entirety. Attorney Docket No.29539-0842WO1 In some embodiments, the method comprises determining an improvement in the Muscular Impairment Rating Scale (MIRS) after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, an improvement in the MIRS comprises an improvement in the scale of at least 1 point (e.g., 1 point, 2 points, 3 points, or 4 points). For further information on the MIRS, see, e.g., Neurology, 2001 Feb 13;56(3):336-40, which is incorporated by reference herein in its entirety. In some embodiments, the method comprises determining a decrease in the time measured for the subject to perform the timed up and go (TUG) test after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. In some embodiments, the method comprises determining an at least 2% decrease (e.g., an at least 3% decrease, an at least 4% decrease, an at least 5% decrease, an at least 7% decrease, an at least 9% decrease, an at least 11% decrease, an at least 13% decrease, an at least 15% decrease, an at least 20% decrease, an at least 25% decrease, an at least 30% decrease, an at least 35% decrease, an at least 40% decrease, an at least 50% decrease, an at least 60% decrease, or an at least 70% decrease) in the time measured for the subject to perform the timed up and go (TUG) test after administering the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein to the subject. Further information on the timed up and go (TUG) test can be found in, e.g., Osteosarcopenia, 2022, pages 181-204, which is incorporated by reference herein in its entirety. Other tests that can be used to assess the mobility of a subject comprise, but are not limited to, the Pick up Weight Test (see, e.g., Reuben DB, Siu AL. “An objective measure of physical function of elderly outpatients. The Physical Performance Test”, J Am Geriatr Soc, 1990, vol.38 (pg.1105-12), incorporated by reference herein in its entirety), the Half Turn Test (see, e.g., Berg K, Wood-Dauphinee S, Williams JI, et al. Measuring balance in the elderly: preliminary development of an instrument, Physiother Can, 1989, vol. 41 (pg. 304-11), incorporated by reference herein in its entirety), the Alternate Step Test (see, e.g., Anne Tiedemann, Hiroyuki Shimada, Catherine Sherrington, Susan Murray, Stephen Lord, Age and Ageing, Volume 37, Issue 4, July 2008, Pages 430–435, incorporated by reference herein in its entirety), and the Stairs Ascent and Descent Test (see, e.g., Anne Tiedemann, Hiroyuki Shimada, Catherine Sherrington, Susan Murray, Stephen Lord, Age and Ageing, Volume 37, Issue 4, July 2008, Pages 430–435, incorporated by reference herein in its entirety). In some embodiments, the disclosure provides a method of reducing potassium ion efflux from an axon in a subject identified or diagnosed as having demyelination, the method comprising Attorney Docket No.29539-0842WO1 administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, identifying or diagnosing a subject as having demyelination comprises administering to the subject an imaging effective amount of a radiotracer; and determining the presence or absence of a signal from the compound, wherein the presence of a signal indicates that the subject has demyelination. In some embodiments, identifying or diagnosing a subject as having demyelination comprises administering to the subject an imaging effective amount of a radiotracer; and determining the presence or absence of a signal from the radiotracer, wherein the presence of a signal indicates that the subject has demyelination. In some embodiments, the disclosure provides a method of reducing potassium ion efflux from an axon in a subject, comprising: identifying or diagnosing the subject as having demyelination; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of reducing potassium ion efflux from an axon in a subject identified or diagnosed as having demyelination, the method comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of reducing potassium ion efflux from an axon in a subject, comprising: identifying or diagnosing the subject as having a neurological disorder; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the neurological disorder is associated with demyelination. In some embodiments, the disclosure provides a method of reducing potassium ion efflux from an axon in a subject identified or diagnosed as having a neurological disorder, the method comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of increasing axonal conduction in a subject, comprising: detecting demyelination in the subject; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. Attorney Docket No.29539-0842WO1 In some embodiments, the disclosure provides a method of increasing axonal conduction in a subject, comprising: detecting an abnormally low axonal conduction in the subject; and administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of increasing axonal conduction in a subject identified or diagnosed as having demyelination, the method comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a method of increasing axonal conduction in a subject identified or diagnosed as having a neurological disorder, the method comprising administering to the subject a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the disclosure provides a kit comprising the compound described herein, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein; and instructions for administering the compound, the pharmaceutically acceptable salt thereof, or the pharmaceutical composition to a subject. Definitions As used herein, the term “about” means “approximately” (e.g., plus or minus 10% of the indicated value). The term “halo” or “halogen” refers to any radical of fluorine, chlorine, bromine or iodine. The term “alkyl” refers to a saturated hydrocarbon chain that may be a straight chain or branched chain, containing the indicated number of carbon atoms. For example, C1-C6 alkyl indicates that the group may have from 1 to 6 (inclusive) carbon atoms in it. Any atom can be optionally substituted, e.g., by one or more substituents. Examples of alkyl groups include, without limitation, methyl, ethyl, n-propyl, isopropyl, and tert-butyl. The term "alkoxy" refers to an -O-alkyl radical (e.g., -OCH3). The term “alkenyl” refers to a straight or branched hydrocarbon chain containing the indicated number of carbon atoms and having one or more carbon-carbon double bonds. Any atom can be optionally substituted, e.g., by one or more substituents. Alkenyl groups can include, e.g., vinyl, allyl, 1-butenyl, and 2-hexenyl. One of the double bond carbons can optionally be the point of attachment of the alkenyl substituent. Attorney Docket No.29539-0842WO1 The term “cycloalkyl” refers to a fully saturated monocyclic, bicyclic, tricyclic, or other polycyclic hydrocarbon group. Any atom can be optionally substituted, e.g., by one or more substituents. A ring carbon serves as the point of attachment of a cycloalkyl group to another moiety. Cycloalkyl moieties can include groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, and norbornyl (bicyclo[2.2.1]heptyl). The term “heterocyclyl” refers to a fully saturated monocyclic, bicyclic, tricyclic or other polycyclic ring system having one or more constituent heteroatom ring atoms independently selected from O, N (it is understood that one or two additional groups may be present to complete the nitrogen valence and / or form a salt), or S. The heteroatom or ring carbon can be the point of attachment of the heterocyclyl substituent to another moiety. Any atom can be optionally substituted, e.g., by one or more substituents. Heterocyclyl groups can include groups such as tetrahydrofuryl, tetrahydropyranyl, piperidyl (piperidino), piperazinyl, morpholinyl (morpholino), pyrrolinyl, and pyrrolidinyl. By way of example, a phrase such as “heterocyclic ring containing from 5-6 ring atoms”, includes (but is not limited to) tetrahydrofuryl, tetrahydropyranyl, piperidyl (piperidino), piperazinyl, morpholinyl (morpholino), pyrrolinyl, and pyrrolidinyl. The term “aryl” refers to an aromatic monocyclic, bicyclic (2 fused rings), tricyclic (3 fused rings), or polycyclic (> 3 fused rings) hydrocarbon ring system. One or more ring atoms can be optionally substituted by one or more substituents for example. Aryl moieties include groups such as phenyl and naphthyl. The term “heteroaryl” refers to an aromatic monocyclic, bicyclic (2 fused rings), tricyclic (3 fused rings), or polycyclic (> 3 fused rings) hydrocarbon groups having one or more heteroatom ring atoms independently selected from O, N (it is understood that one or two additional groups may be present to complete the nitrogen valence and / or form a salt), or S. One or more ring atoms can be optionally substituted, e.g., by one or more substituents. Examples of heteroaryl groups include, but are not limited to, 2H-pyrrolyl, 3H-indolyl, 4H-quinolizinyl, acridinyl, benzo[b]thienyl, benzothiazolyl, β-carbolinyl, carbazolyl, coumarinyl, chromenyl, cinnolinyl, dibenzo[b,d]furanyl, furazanyl, furyl, imidazolyl, imidizolyl, indazolyl, indolyl, isobenzofuranyl, isoindolyl, isoquinolyl, isothiazolyl, isoxazolyl, naphthyridinyl, oxazolyl, perimidinyl, phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolyl, quinoxalinyl, thiadiazolyl, thianthrenyl, thiazolyl, thienyl, triazolyl, and xanthenyl. The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present disclosure that contain asymmetrically substituted carbon atoms can be Attorney Docket No.29539-0842WO1 isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C=N double bonds, N=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present disclosure. Cis and trans geometric isomers of the compounds of the present disclosure are described and may be isolated or synthesized as a mixture of isomers or as separated isomeric forms. In some embodiments, the compound of Formula (I) has the (R)-configuration. In some embodiments, the compound of Formula (I) has the (S)-configuration. Compounds provided herein also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone – enol pairs, amide - imidic acid pairs, lactam – lactim pairs, enamine – imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, for example, 1H- and 3H- imidazole, 1H-, 2H- and 4H- 1,2,4-triazole, 1H- and 2H- isoindole, and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution. As used herein, the term “cell” is meant to refer to a cell that is in vitro, ex vivo or in vivo. In some embodiments, an ex vivo cell can be part of a tissue sample excised from an organism such as a mammal. In some embodiments, an in vitro cell can be a cell in a cell culture. In some embodiments, an in vivo cell is a cell living in an organism such as a mammal. As used herein, the term “subject” refers to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans. In some embodiments, the subject is a human. As used herein, the phrase “imaging effective amount” refers to the necessary amount of active compound or pharmaceutical agent that allows for imaging of a tissue in an animal, individual, or human to be detected by the detection method chosen. For example, a detectable quantity can be an administered amount sufficient to enable detection of binding of the labeled compound to a target of interest including, but not limited to myelin. As used herein, the term “radiotracer” refers to a compound described in PCT Appl. No. PCT / US2024 / 41216. It is understood that a radiotracer is typically administered to a subject and its radioactive decay detected to provide, for example, an image that indicates the location of the radiotracer in the subject’s body. Attorney Docket No.29539-0842WO1 As used herein, the phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal, or human that is being sought by a researcher, veterinarian, medical doctor or other clinician. As used herein the term “treating” or “treatment” refers to 1) inhibiting the disease; for example, inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and / or symptomatology), or 2) ameliorating the disease; for example, ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and / or symptomatology). As used herein, the term “preventing” or “prevention” of a disease, condition or disorder refers to decreasing the risk of occurrence of the disease, condition or disorder in a subject or group of subjects (e.g., a subject or group of subjects predisposed to or susceptible to the disease, condition or disorder). In some embodiments, preventing a disease, condition or disorder refers to decreasing the possibility of acquiring the disease, condition or disorder and / or its associated symptoms. In some embodiments, preventing a disease, condition or disorder refers to completely or almost completely stopping the disease, condition or disorder from occurring. NUMBERED EMBODIMENTS Numbered Embodiments Set 1 Embodiment 1. A compound of formula (I) R or a pharmaceutically each R is independently chosen from halogen, C1-10 alkyl, C1-C3 monofluoroalkyl, C1-10 haloalkyl, C2-10alkenyl, C2-10alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl; and Attorney Docket No.29539-0842WO1 n is 0, 1, 2, or 3; and m is 0 or 1; wherein the compound is not 4-aminopyridine or 4-methyl-3-aminopyridine. Embodiment 2. The compound of embodiment 1, wherein m is 1. Embodiment 3. The compound of embodiment 1, wherein n is 2. Embodiment 4. The compound of embodiment 1, wherein n is 1. Embodiment 5. The compound of any one of embodiments 1-5, wherein each R is C1-10 alkyl. Embodiment 6. The compound of any one of embodiments 1-6, wherein each R is methyl. Embodiment 7. The compound of any one of embodiments 1-6, wherein each R is ethyl. Embodiment 8. The compound of any one of embodiments 1-6, wherein each R is propyl. Embodiment 9. The compound of embodiment 1, or a pharmaceutically acceptable salt thereof, wherein In some embodiments, the compound is selected from: , , a In some embodiments, the compound is or a pharmaceutically acceptable salt thereof. Embodiment 10. The compound of embodiment 1, or a pharmaceutically acceptable saltthereof, wherein the a pharmaceutically acceptable salt thereof.Embodiment 11. A comprising a compound of any one of embodiments 1-10 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. Attorney Docket No.29539-0842WO1 Embodiment 12. A method of treating a neurological disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of embodiments 1-10 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of embodiment 11. Embodiment 13. A method of reducing potassium ion efflux from an axon in a subject identified or diagnosed as having a neurological disorder, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of embodiments 1-10 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of embodiment 11. Embodiment 14. A method of increasing axonal conduction in a subject identified or diagnosed as having a neurological disorder, the method comprising administering to the subject a therapeutically effective amount of a compound of any one of embodiments 1-10 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of embodiment 11. Embodiment 15. A kit comprising the compound of any of embodiments 1-10 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of embodiment 11; and instructions for administering the compound, or the pharmaceutical composition to a subject. Numbered Embodiments Set 2 Embodiment 1. A pharmaceutical composition comprising a compound of Formula (I): R or a pharmaceutically acceptable carrier, wherein: each R is independently selected from halogen, hydroxy, C1-10 alkyl optionally substituted with hydroxy, C1-10alkoxy, NRARB, C1-C3monofluoroalkyl, C1-10haloalkyl, C2-10alkenyl, C2-10alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl; and n is 0, 1, 2, or 3; and m is 0 or 1; wherein the compound is not 4-aminopyridine or 4-methyl-3-aminopyridine. Attorney Docket No.29539-0842WO1 Embodiment 2. The composition of embodiment 1, wherein m is 1. Embodiment 3. The composition of embodiment 1, wherein n is 2. Embodiment 4. The composition of embodiment 1, wherein n is 1. Embodiment 5. The composition of any one of embodiments 1-4, wherein at least one R is C1-10 alkyl optionally substituted with hydroxy. Embodiment 6. The composition of any one of embodiments 1-5, wherein at least one R is methyl. Embodiment 7. The composition of any one of embodiments 1-5, wherein at least one R is ethyl. Embodiment 8. The composition of any one of embodiments 1-5, wherein at least one R is propyl. Embodiment 9. The composition of any one of embodiments 1-5, wherein at least one R is hydroxymethyl. Embodiment 10. The composition of any one of embodiments 1-4, wherein at least one R is halo. Embodiment 11. The composition of any one of embodiments 1-4 and 10, wherein at least one R is fluoro. Embodiment 12. The composition of any one of embodiments 1-4 and 10, wherein at least one R is chloro. Embodiment 13. The composition of any one of embodiments 1-4, wherein at least one R is -NH2. Embodiment 14. The composition of any one of embodiments 1-4, wherein at least one R is hydroxy. Embodiment 15. The composition of any one of embodiments 1-4, wherein at least one R is C1-10haloalkyl. Attorney Docket No.29539-0842WO1 Embodiment 16. The composition of any one of embodiments 1-4 and 15, wherein at least one R is -CHF2, -CH2F, or CF3. Embodiment 17. The composition of any one of embodiments 1-4, wherein at least one R is C1-10 alkoxy. Embodiment 18. The composition of any one of embodiments 1-4 and 17, wherein at least one R is methoxy. Embodiment 19. The composition of embodiment 1, wherein the compound is selected from: , , , , , , , , Attorney Docket No.29539-0842WO1 , , , , , , , of Embodiment 20. The composition of embodiment 1, wherein the compound is , or a pharmaceutically acceptable salt thereof. Attorney Docket No.29539-0842WO1 Embodiment 21. A compound of Formula (I): Rn NH2or a pharmaceutically acceptable carrier, wherein: each R is independently selected from halogen, hydroxy, C1-10alkyl optionally substituted with hydroxy, C1-10 alkoxy, NRARB, C1-C3 monofluoroalkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl; and n is 0, 1, 2, or 3; and m is 0 or 1; wherein the compound is not 4-aminopyridine or 4-methyl-3-aminopyridine. Embodiment 22. A method of treating a neurological disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of any one of embodiments 1-20, or a compound of embodiment 21, or a pharmaceutically acceptable salt thereof. Embodiment 23. A method of reducing potassium ion efflux from an axon in a subject identified or diagnosed as having a neurological disorder, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of any one of embodiments 1-20, or a compound of embodiment 21, or a pharmaceutically acceptable salt thereof. Embodiment 24. A method of increasing axonal conduction in a subject identified or diagnosed as having a neurological disorder, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of any one of embodiments 1-20, or a compound of embodiment 21, or a pharmaceutically acceptable salt thereof. Embodiment 25. A kit comprising the pharmaceutical composition of any of embodiments 1-20, or a compound embodiment 21, or a pharmaceutically acceptable salt thereof; Attorney Docket No.29539-0842WO1 and instructions for administering the compound, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition to a subject. EXAMPLES Example 1 –Synthesis of Compound 5 A scheme showing a method that can be used to prepare compound 5 (also referred to herein as “5Me3F4AP”) is shown below: In this method, precursor 2 is synthesized by the oxidation of the amino precursor 1 with hydrogen peroxide and sulfuric acid. Compound 2 is treated with potassium fluoride to provide compound 3, which is saponified to provide free acid 4 which, after treatment with diphenylphosporyl azide, provides compound 5. Example 2 – Affinity towards K+channels. Cut-Open Voltage Clamp Electrophysiology: In this example, blocking potency of 5Me3F4AP was evaluated on the voltage-gated Shaker (homologous to mammalian Kv1.2) ion channel expressed in Xenopus laevis oocytes, as previously described. Briefly, each oocyte expressing the Shaker channel was voltage-clamped in a Cut-Open Voltage Clamp (COVC) station in order to elicit K+currents in response to the voltage stimulus protocol, which entailed steps of 50 ms from -100 to 60 mV in increments of 10 mV. External and internal recording solutions for COVC were composed (in mM) of 12 KOH, 2 Ca(OH)2, 105 NMDG-MES, 20 HEPES and 120 KOH, 2 EGTA, and 20 HEPES, respectively, with pH adjusted to 7.4 with methylsufonate. For measurements achieved at pH = 9.1 or Attorney Docket No.29539-0842WO1 6.4, HEPES was replaced by 2-(cyclohexylamino)-ethanesulfonic acid or 2-(N- Morpholino)ethanesulfonic acid, respectively. Each oocyte expressing the Shaker ion channel was voltage-clamped to record K+currents, first in the absence of 5Me3F4AP, and subsequently with the addition of 5Me3F4AP, from 0.0001 to 10 mM. Relative current (Irel) was quantified as the ratio of the current in the absence to that in the presence of the indicated concentration of 5Me3F4AP. Finally, K+currents were amplified with the Oocyte Clamp Amplifier CA-1A (Dagan Corporation, Minneapolis, MN, USA) and digitized with the USB-1604-HS-2AO Multifunction Card (Measurement Computing, Norton, MA, USA). All systems were controlled with the GpatchMC64 program (Department of Anesthesiology, UCLA, Los Angeles, CA, USA) via a PC. Electrophysiology recordings were sampled at 100 kHz and filtered at 10 kHz. Electrophysiology data analysis: In this example, data analysis was performed as previously described. Briefly, the half-maximal inhibitory concentration of 5Me3F4AP (IC50) was determined by fitting the Irel curve to the Hill equation at each value of V and pH. A Hill coefficient (h) in the range of 0.9<h<1.1 was used. Voltage and pH dependence of IC50was analyzed by fitting the IC50(V) at each pH with a one-step model of inhibition (Hermann-Gorman equation) which allowed the determination of the fractional distance through the membrane electrical field (δ) that 5Me3F4AP has to cross to reach its binding site:log ^^^^ହ^^^^^ ൌ log ^^^^^ ௭ఋி^ ହ^^^ୀ^^ ^ଶ.ଷ^ଷ ோ் Eqn. (1) where IC50(V = 0)is the value of IC50at V = 0 mV, F is the Faraday constant, R is the gas constant, T is the room temperature, and z is the apparent charge. Mean values of data ± standard deviation (s.d.) are given or plotted and the number of experiments is denoted by n. Upper and lower limits of the 95% of confidence interval (CI95) are denoted as 10^୪୭^ ூ^ఱబା^.ௗ^and10^୪୭^ ூ^ఱబି^.ௗ^, respectively. 7.4 and voltages (-100 to 60 mV) of 5Me3F4AP was evaluated by measuring the K+currents generated by Shaker voltage-gated potassium channel from D. melanogaster heterologously expressed in Xenopus laevis oocytes (Figure 2). Specifically, Figure 2B shows the calculated IC50 values using the Hill equation at different values of pH. This plot shows that the IC50 of 5Me3F4AP increases with voltage and pH indicating a drop in potency. Figure 2B compares the IC50values calculated at 40 mV using the Hill equation of the newly characterized 5Me3F4AP at different pHs with the IC50 values of the related compounds 4AP, 3F4AP and 3Me4AP. Attorney Docket No.29539-0842WO1 Table 1. IC50values of 5Me3F4AP: Hill and Hermann-Gorman parameters. Hill Hermann-Gorman parameters parameters tting of the y33. Example 3 – Metabolic stability towards CYP2E1 of 5Me3F4AP. To estimate the metabolic stability of 5Me3F4AP towards CYP2E1, an in vitro investigation was conducted utilizing a competitive inhibition assay. Compounds that are good substrates of CYP2E1 result in greater reduction in the rate of formation of a fluorescent reporter than compounds that are poor substrates. In this study, the reaction rates without competitor (blank) as well as in the presence of tranylcypromine (positive control), 4AP, 3F4AP and 5Me3F4AP were measured. As illustrated in Figure 2D, the addition of tranylcypromine, a widely recognized potent substrate of CYP2E1, resulted in the most pronounced reduction in fluorogenic emission when compared to the reaction conducted without any addition of enzyme substrates (hexagon vs. circular lines). In comparison, 4AP exhibited a minor reduction in fluorogenic emission (star vs. circular lines) indicating that it is a poor substrate of CYP2E1. 3F4AP demonstrated a substantial decrease in rate (star vs. circular lines) indicating 3F4AP is a good substrate of CYP2E1, undergoing metabolism at a much faster rate than 4AP. In comparison, 5Me3F4AP demonstrated a reaction rate between 4AP and Attorney Docket No.29539-0842WO1 3F4AP, bearing a higher resemblance to 3F4AP (Figure 2D, diamond vs. star and plus lines). To further quantify the inhibition potency of 5Me3F4AP towards CYP2E1, the CYP2E1-mediated reaction rate in the presence of varying concentrations of 5Me3F4AP and 3F4AP were measured and the dose-response fitting was performed (Figure 2A). These results were compared with previous results for 4AP, 3F4AP and the positive control tranylcypromine. This analysis showed that 5Me3F4AP has an IC50about two times higher than 3F4AP and about 23 times lower than 4AP (Figure 2C), indicating that it is more stable than 3F4AP but not as stable as 4AP. This suggests that 5Me3F4AP is a weaker competitive inhibitor of CYP2E1 than 3F4AP, but stronger than 4AP. Given the previously established role of CYP2E1 in the in vivo metabolism of this family of compounds and the direct correlation between inhibitory potency and CYP2E1 affinity for the substrate, this finding suggests that 5Me3F4AP may be metabolized slower than 3F4AP but not as slow as 4AP. CYP2E1-mediated metabolic stability assessment: The relative metabolic stability towards CYP2E1 was assessed with the competitive CYP2E1 inhibition assay utilizing the Life TechnologiesTMVivid®CYP2E1 screening kit, as described in previous studies. In this assay, fluorescence, emitted by the metabolic product of a specific CYP2E1 substrate included in the kit, was measured in the absence and presence of substrate competitors. Consequently, the highest fluorescence values were obtained from the blank experiments, which lacked any competitors. As the concentration of competitors increased, or more potent competitors were introduced, the fluorogenic emission decreased accordingly. Specifically, 40 µL of 2.5X (final concentration 25µM) solution of test compounds (4AP, 3F4AP, 5Me3F4AP, and positive control, i.e., tranylcypromine) in 1X Vivid®CYP2E1 reaction buffer was added to desired wells of a falcon black / clear 384-well plate in three replicates. Afterwards, 50 µL master pre-mix 2X (40 nM) CYP2E1 BACULOSOMES®and 2X (0.6 Units / mL) Vivid®regeneration system in 1X reaction buffer) was added to each well. The plate was incubated for 10 minutes at room temperature to allow the compounds to interact with the CYP2E1 in the absence of enzyme turnover. Next, the reaction was initiated by adding 10µL per well of 10X (100 μM) Vivid®substrate (2H-1-benzopyran-3-carbonitrile,7-(ethoxy-methoxy)-2-oxo-(9Cl)) and 10X (300 μM) Vivid® NADP+mixture. Immediately (in less than 2 minutes), the plate was transferred into the fluorescent plate reader and fluorescence was monitored over 60 minutes (reads in 1-minute intervals) at 415 nm as excitation wavelength and 460 nm as emission wavelength. The obtained reads were plotted using GraphPad Prism 9. Determination of the IC50and Kiof 5Me3F4AP to CYP2E1. A similar Vivid®CYP2E1 assay was conducted as described above. Instead of testing a single concentration of 5Me3F4AP (final concentration 15µM), a series of concentrations (4.0 mM, 1.2 mM, Attorney Docket No.29539-0842WO1 400 µM, 120 µM, 40 µM, 12 µM, 4.0 µM, 1.2 µM) were tested with three replicates for each concentration. The plate fluorescence was monitored over 60 minutes (reads in 1-minute intervals) at 415 nm as excitation wavelength and 460 nm as emission wavelength. The reads at 60 min (recalculated by the linear trend line equation) of each concentration were used and fitted with GraphPad Prism9 dose-response-inhibition (concentration is log) curve fitting to calculate the IC50 values. The corresponding Kivalues were calculated by Ki= IC50 / (1+[S] / Km)(Km= 2241, and the Vivid®EOMCC substrate concentration [S] is 10 µM). Table 2. IC50values and their respective confidence interval (C.I.) for CYP2E1 substrates. Entry Drug IC50(μM) 95% C.I. (μM) n *Prev Example 4 - Physicochemical, Biophysical and Pharmacological Evaluation of 4AP Derivatives. pKa determination. The pKa for each 4AP structural analog was determined using a titration curve. Briefly, a 0.01 M HCl solution was added dropwise to a 100 mL solution containing 15 mg of each compound. The pH recorded was plotted as a function of the added volume of HCl. Subsequently, the pKawas estimated at the halfway point to the equivalence point of the titration curve. This procedure was repeated at least 4 times for each compound. ^^^^^^^^ determination. The octanol-water partition coefficient (^^^^^^ ^^) of each 4AP structural analog was determined by means of the shake flask method. For this purpose, 3 μL at 200 mM of each compound was added to 3 mL of Phosphate Buffered Saline solution (PBS, Gibco, Thermo Fisher Scientific Inc.) at pH 7.4 and 3 mL of 1-octanol (Sigma-Aldrich, Merck KGaA, Darmstadt, Germany) and partitioned via vortexing. The mixture was placed in a separatory funnel until the phases were separated and homogenized. Subsequently, the relative concentration of each 4AP structural analog partitioned in each phase was measured by determining its absorbance by standard procedures of UV- VIS spectroscopy. A calibration curve of the absorbance vs. the concentration for each compound in Attorney Docket No.29539-0842WO1 the range of 0 to 50 μM was carried out prior to the phase separation procedure. This procedure was repeated at least 4 times for each compound. Permeability coefficient (Pe) determination. The permeability rates of each compound were determined using parallel artificial membrane permeability assay-blood–brain barrier (BBB) kit (BioAssay systems, Hayward, USA) following the manufacturer’s protocol. Initially, solutions of each test compound were prepared in DMSO at a concentration of 10 mM. These stock solutions along with the stock solutions of control compounds (high control: promazine hydrochloride, low control: diclofenac) were then diluted with PBS (pH = 7.2) to obtain the donor solutions with a final concentration of 500 μM. At the same time, 200 μM of equilibrium standards for each compound and a DMSO blank control solution were prepared. In the experimental setup, 300 μL of PBS was added to the desired well of the acceptor plate, and 5 μL of BBB lipid solution in dodecane was added to membranes of the donor plate. Next, 200 μL of the donor solutions of each test compound and each permeability control were added to the duplicate wells of the donor plate. The donor plate was carefully placed on the acceptor plate and incubator for 18 h at room temperature. After incubation, UV absorption measurements were conducted using 100 μL of the resulting solutions from the acceptor plate and the equilibrium standards. UV absorption of the controls was measured by running a UV scan in the range of 200–500 nm. UV absorption of each compound was measured using HPLC equipped with a UV detector and C18 column. Synthesis of RNA and heterogeneous expression of KVion channels in Xenopus laevis oocytes. The RNAs used in this study were synthesized in vitro by standard procedures of Molecular Biology. The vector, restriction enzyme, and promoter used for each KVcDNA plasmid clone are summarized in the in the following Table 3: Table 3: DNA plasmids Ion channel Specie Vector Restriction Promoter Attorney Docket No.29539-0842WO1 Each cDNA was amplified via a miniprep preparation kit (QIAGEN GmbH, Germany) and then linearized with the indicated (Table 3) restriction enzyme (New England Biolabs, Inc. Ipswich, MA, USA). Subsequently, each RNA was synthesized with the use of the mMESSAGE cRNA transcription kit by using the indicated promoter (AmbionTM, MEGAscript®, Austin, TX, USA). Expression of KV ion channels in Xenopus laevis oocytes. Each KV ion channel was heterologously expressed in Xenopus laevis oocytes. Methods involving Xenopus laevis frogs were performed in accordance with relevant guidelines and regulations and with the approval of the Comité Institucional del Cuidado y Uso de Animales en el Laboratorio at the University of Guadalajara, protocol CUCEI / CINV / CICUAL-03 / 2023. To this end, only mature Xenopus laevis frogs (Xenopus 1, Corp., MI., USA and Aquanimals SA de CV, Queretaro, Mexico) held in captivity were used as oocytes suppliers by extracting a volume of ~1 mL from the ovary lobes via survival surgery under anesthesia with MS-222. Subsequently, oocytes were isolated under simultaneous process of the enzymatic treatment of collagenase type II (Worthington Biochemical Corp., NJ, USA) and mechanical agitation. Then, each isolated oocyte was injected with 15-25 ng of RNA encoding for each KVby using the Nanoinyect II Auto-Nanoliter Injector system (Drummond Scientific Company, Broomall, USA) and incubated before the experiments from 1 to 5 days in a Standard Oocytes Saline (SOS) solution containing (in mM): 100 NaCl, 1 MgCl2, 10 HEPES, 2 KCl and 1.8 CaCl2 with 50 μg / mL gentamycin at pH 7.5 in an atmosphere at 17 °C. For the expression of the heteromeric KV7.2 / 7.3 or KV2.1 / 6.4 ion channels, each oocyte were co-injected with the corresponding cRNA with a stoichiometry of 1:1 or 3:1, respectively (see, e.g., Corbin-Leftwich, et al., Retigabine holds KV7 channels open and stabilizes the resting potential, J Gen Physiol (2016) 147 (3): 229–241, https: / / doi.org / 10.1085 / jgp.201511517; Möllera et al., Determining the correct stoichiometry of Kv2.1 / Kv6.4 heterotetramers, functional in multiple stoichiometrical configurations, PNAS (2020) 117(17): 9365–9376, https: / / doi / 10.1073 / pnas.1916166117; each of which is incorporated by reference herein in its entirety) Cut-Open Voltage Clamp (COVC) Electrophysiology. Shaker ion channel (or each KV channels) were heterogeneously expressed in Xenopus laevis oocytes and the K+currents were triggered as response a voltage stimulus under voltage-clamp condition with the cut-open voltage clamp (COVC) methodology (see, e.g., Brugarolas, P., Sánchez-Rodríguez, J.E., Tsai, HM. et al. Development of a PET radioligand for potassium channels to image CNS demyelination. Sci Rep 8, 607 (2018). https: / / doi.org / 10.1038 / s41598-017-18747-3; Rodríguez-Rangel, S., Bravin, A.D., Ramos-Torres, of four novel 4-aminopyridine K+ channel blockers. Sci Rep 10, 52 (2020). https: / / doi.org / 10.1038 / s41598-019-56245-w; Sun, Y., Rodríguez-Rangel, S., Zhang, L.L. et al. of novel potassium channel blocker 3- fluoro-5-methylpyridin-4-amine. Sci Rep 14, 11105 (2024). https: / / doi.org / 10.1038 / s41598-024- Attorney Docket No.29539-0842WO1 61465-w; each of which is incorporated by reference herein in its entirety). The internal and external solution for COVC procedures were composed (in mM) of: 120 KOH, 2 EGTA, 20 HEPES and 12 KOH, 2 Ca(OH)2, 105 NMDG (N-methyl-D-glucamine)-methylsufonate (MES), 20 mM HEPES, respectively. Both solutions were adjusted at pH 7.4. For measurements where the pH was varied, HEPES was interchanged by 2-(cyclohexylamino)ethanesulfonic acid (CHES, pHൌ9.1) or 2-(N- Morpholino)ethanesulfonic acid hydrate (MES-hydrate, pH= 5.7 or 6.8) buffers. The elicited K+currents were amplified and digitized with the Oocyte Clamp Amplifier CA-1A (Dagan Corporation, Minneapolis, MN, USA) and the USB-1604-HS-2AO Multifunction Card (Measurement Computing, Norton, MA, USA), respectively, and controlled with the GpatchMC64 program (Department of Anesthesiology, UCLA, Los Angeles, CA, USA) via a PC. K+currents were sampled at 100 kHz and filtered at 10 kHz. All the experiments were performed at room temperature (21–23 °C). Determination of the blocking potency of 4AP derivatives or structural analogs. Blocking potency of 4AP and 4AP structural analogs molecules were evaluated in terms of the half-maximal inhibitory concentration (^^^^ହ^) need it to inhibit the 50% of K+current yielded by the Shaker ion channel or (each KVion channels showed in Table 3) expressed in Xenopus laevis oocytes and under voltage-clamp condition. Towards that end, the relative current (^^^ ) ^^^^ the concentration of 4AP derivative orstructural analogs (^^^^) (from 0.001 to 10 mM) curve was measured in same oocyte, first in absence (^^) and then in presence of each value of [^^] (^^௫). This methodology allowed us to determine ^^^^ହ^values at different voltage and pH conditions. Electrophysiology data analysis. K+current recordings were analyzed using Analysis (Dept. of Physiology, UCLA) and OriginPro 8 (®OriginLab Corporation) software as previously described (see, e.g., Rodríguez-Rangel, S., Bravin, A.D., Ramos-Torres, K.M. et al. Structure-activity relationship studies of four novel 4-aminopyridine K+channel blockers. Sci Rep 10, 52 (2020). https: / / doi.org / 10.1038 / s41598-019-56245-w; Sun, Y., Rodríguez-Rangel, S., Zhang, L.L. et al. Chemical and biophysical characterization of novel potassium channel blocker 3-fluoro-5- methylpyridin-4-amine. Sci Rep 14, 11105 (2024). https: / / doi.org / 10.1038 / s41598-024-61465-w; each of which is incorporated by reference herein in its entirety). Briefly, ^^^^ହ^for each 4AP structural analog was determined by fitting the Irel ^ൌ ^^௫⁄ ^^ ^ vs ^^^^ curve to the Hill equation:^^ூ^^ೌ^ିூ^^^^^^^ ൌ ^^^ ^Eqn. (2) where ^^^^ೌ^and ^^^^^^are the maximal and minimal value of ^^^and ℎ is the Hill coefficient which value in the range 0.9 ^ ℎ ^ 1.1. Voltage dependence of ^^^^ହ^ (^^^^ହ^^^^^) was analyzed Attorney Docket No.29539-0842WO1 by fitting the ^^^^ହ^^^^^ curve with the one-step model of inhibition which allow to determine the fractional electrical-distance (δ) that each 4-AP analog cross through the electric field generated in the KVpore channel to reach its binding site as previously determined (see, e.g., Hermann, A. & Gorman, A. L. Effects of 4-aminopyridine on potassium currents in a molluscan neuron. J Gen Physiol 78, 63- 86 https: / / doi.org / 10.1085 / jgp.78.1.63 (1981).; Sun, Y., Rodríguez-Rangel, S., Zhang, L.L. et al. Chemical and biophysical characterization of novel potassium channel blocker 3-fluoro-5- methylpyridin-4-amine. Sci Rep 14, 11105 (2024). https: / / doi.org / 10.1038 / s41598-024-61465-w; each of which is incorporated by reference herein in its entirety):log ^^^^ ^^^^ ൌ log ^^^^ ^^௭ఋி^ହ^ ହ^^ೇసబ^ଶ.ଷ^ଷ∙ோ் Eqn. (1) gas constants, respectively, ^^ is the temperature, and ^^ is the apparent charge. Results Figure 3 shows the blocking potency of 4AP derivatives on Shaker KV ion channel. (a), Representative K+recordings elicited from three different oocytes expressing the Shaker KVion channel in response to a voltage stimulus at ^40 ^^^^ (upper voltage protocol) before and after addition of 1 mM on the external oocyte membrane vestibule of each 4AP structural analog. Dashed lines represent the zero-current level and horizontal and vertical bars indicate the time and current scale for each recording. (b), Relative current vs. the concentration curves of each 4AP derivative evaluated at +40 mV and pH=7.4. Continuous lines represent the fits with the Hill equation (Equation 2) with a Hill coefficient ranging from 0.9 to 1.1. ^^^^ହ^values are shown in Table 5. Figure 4 shows blocking potency of 4AP structural analogs on Shaker KV ion channel. (a), Representative K+recordings elicited from five different oocytes expressing the Shaker KV ion channel in response to a voltage stimulus (upper voltage protocol) before and after addition of 1 mM of 4Me3AP, 4F3AP, 4Cl3AP, 4Br3AP and 4I3AP. Dashed lines represent the zero-current level and horizontal and vertical bars indicate the time and current scale for each recording. (b), Relative current vs. the concentration curves of each 4AP structural analog showed in (a) evaluated at ^40 ^^^^ and pH=7.4. Continuous lines represent the fits with the Hill equation (Equation 2) with a Hill coefficient ranging from 0.9 to 1.1. ^^^^ହ^values are shown in Table 5. Figure 5 shows pH and voltage dependence of the blockage of 4Me3AP evaluated in Shaker ion channel. (a), Representative K+recordings elicited from three different oocytes expressing the Shaker KV ion channel as the Attorney Docket No.29539-0842WO1 response to voltage stimulus protocol that consisted of 50 ms depolarization step from െ100 to ^60 ^^^^ (top left upper voltage protocol) and under different pH conditions before and after addition of 1 mM of 4Me3AP. Dashed lines represent the zero-current level and horizontal and vertical bars indicate the time and current scale for each recording. (b), Relative current vs. the concentration of4Me3AP curves assessed at ^^ ൌ ^60 ^^^^ and pH of 5.7, 7.4 and 9.1. Continuous lines represent thefits with the Hill equation (Equation 2) with a Hill coefficient ranging from 0.9 to 1.1. ^^^^ହ^values are shown in Table 6. (c), ^^^^ହ^^^^^curves at pH of 5.7 and 7.4. The dashed lines represent the adjustment with the one-step voltage dependent model of inhibition (Equation 1). Fits parameters of voltage dependence of ^^^^ହ^are shown in Table 7. Figure 6 shows pH dependence of the blockage of 4F3AP and 4I3AP evaluated in Shaker ion channel. (a), Relative current vs. the concentration of 4F3AP at pH 6.4. (b), Relative current vs. the concentration of 4I3AP at pH 5.7. Continuous lines in (a) and (b) represents the fit with the Hill equation (Equation 2) with a Hill coefficient of 0.9 and 1.0 and ^^^^ହ^of 717 ^^^^ and 514 ^^^^, respectively. Figure 7 shows specific blockage of certain KVion channels expressed in the CNS by 4AP, 5Me3F4AP and 3Me4AP. From left to right, representative recordings of K+current before (black) and after (gray) addition of 1mM of 4AP (left), 5Me3F4AP (center) and 3Me4AP (right) assessed from different Xenopus laevis oocytes expressing (a), rKV 1.2, (b), hKV2.1, (c), hKV2.1 / 6.4, and (d), hKV7.2 / 7.3. Currents were elicited in response to a voltage stimulus of 40 mV (left, upper protocol) and pH of 7.4. Horizontal and vertical bars for each recording indicate the time and current scale. Dashed lines represent the zero-current level. Figure 8 shows a determination of the blockage potency of certain KV ion channels expressed in the CNS by 4AP, 5Me3F4AP and 3Me4AP. Relative current vs. the concentration of 4AP, 5Me3F4AP and 3Me4AP evaluated in (a), rKV 1.2, (b), hKV 2.1, (c), hKV 2.1 / 6.4, and (d), hKV 7.2 / hKV 7.3. Continues lines of the relative current curves represent the fits with the Hill equation (Eqn.2) with a Hill coefficient ranging from 0.9 to 1.1. Fits parameters are showed in Table 8. Table 4: pKa, ^^^^^^^^ and ^^^^values of 4AP structural analogs. Drug pKa ^^^^^^^^ ^^^^ (cm / s) Table 5: IC50values of 4AP structural analogs evaluated in Shaker Kv. Attorney Docket No.29539-0842WO1 Drug IC50(μM) 95% C.I. (μM) n 4AP 290.75 266.53-314.96 4 valuated in Shaker Kv. Drug pH IC50(μM) 95% C.I. (μM) n 5.7 66.33 40.83-91.83 3 p50Me3AP evaluated in Shaker Kv. Drug pH IC50(V=0mV)(μM)^^n57 2600 529 059 002 3 Table 8: IC50values of 4AP, 5Me3F4AP and 3Me4AP evaluated in KVion channels expressed in the SNC. IC50(μM) Compound 95% C.I. (μM) n Attorney Docket No.29539-0842WO1 4AP -- -- 5 Kv 2.1 / Kv 6.4 5Me3F4AP -- -- 2 OTHER EMBODIMENTS It is to be understood that while the present application has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the present application, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.29539-0842WO1 CLAIMS 1. A pharmaceutical composition comprising a compound of Formula (I): Rn NH2or a pharmaceutically acceptable carrier, wherein:each R is independently selected from halogen, hydroxy, C1-10 alkyl optionally substituted with hydroxy, C1-10alkoxy, NRARB, C1-C3monofluoroalkyl, C1-10haloalkyl, C2-10alkenyl, C2-10alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl; and n is 0, 1, 2, or 3; and m is 0 or 1; wherein the compound is not 4-aminopyridine or 4-methyl-3-aminopyridine.

2. The composition of claim 1, wherein m is 1.

3. The composition of claim 1, wherein n is 2.

4. The composition of claim 1, wherein n is 1.

5. The composition of any one of claims 1-4, wherein at least one R is C1-10 alkyl optionally substituted with hydroxy.

6. The composition of any one of claims 1-5, wherein at least one R is methyl.

7. The composition of any one of claims 1-5, wherein at least one R is ethyl.

8. The composition of any one of claims 1-5, wherein at least one R is propyl.

9. The composition of any one of claims 1-5, wherein at least one R is hydroxymethyl.

10. The composition of any one of claims 1-4, wherein at least one R is halo.Attorney Docket No.29539-0842WO1 11. The composition of any one of claims 1-4 and 10, wherein at least one R is fluoro.

12. The composition of any one of claims 1-4 and 10, wherein at least one R is chloro.

13. The composition of any one of claims 1-4, wherein at least one R is -NH2.

14. The composition of any one of claims 1-4, wherein at least one R is hydroxy.

15. The composition of any one of claims 1-4, wherein at least one R is C1-10 haloalkyl.

16. The composition of any one of claims 1-4 and 15, wherein at least one R is -CHF2, - CH2F, or CF3.

17. The composition of any one of claims 1-4, wherein at least one R is C1-10 alkoxy.

18. The composition of any one of claims 1-4 and 17, wherein at least one R is methoxy.

19. The composition of claim 1, wherein the compound is selected from: , , , , , , ,Attorney Docket No.29539-0842WO1 , , , , , , , ,a pharmaceutically acceptable salt ofAttorney Docket No.29539-0842WO1 20. The composition of claim 1, wherein the a pharmaceutically acceptable salt thereof.

21. A compound of Formula (I): Rn NH2or a pharmaceutically acceptable carrier, wherein:each R is independently selected from halogen, hydroxy, C1-10alkyl optionally substituted with hydroxy, C1-10 alkoxy, NRARB, C1-C3 monofluoroalkyl, C1-10 haloalkyl, C2-10 alkenyl, C2-10 alkynyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, and 5-10 membered heteroaryl; and n is 0, 1, 2, or 3; and m is 0 or 1; wherein the compound is not 4-aminopyridine or 4-methyl-3-aminopyridine.

22. A method of treating a neurological disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of any one of claims 1-20, or a compound of claim 21, or a pharmaceutically acceptable salt thereof.

23. A method of reducing potassium ion efflux from an axon in a subject identified or diagnosed as having a neurological disorder, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of any one of claims 1-20, or a compound of claim 21, or a pharmaceutically acceptable salt thereof.

24. A method of increasing axonal conduction in a subject identified or diagnosed as having a neurological disorder, the method comprising administering to the subject a therapeuticallyAttorney Docket No.29539-0842WO1 effective amount of a pharmaceutical composition of any one of claims 1-20, or a compound of claim 21, or a pharmaceutically acceptable salt thereof.

25. A kit comprising the pharmaceutical composition of any of claims 1-20, or a compound claim 21, or a pharmaceutically acceptable salt thereof; and instructions for administering the compound, or a pharmaceutically acceptable salt thereof, or the pharmaceutical composition to a subject.

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