Compounds suitable for cardiovascular disease or disorder treatment

Abstract

The present disclosure relates to compositions and methods, including prodrugs of (S)-sec-butyl 2-(3-(4-(2- (diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate that find use in the treatment of diseases and disorders, such as therapies for cardiovascular disease, including cardiac arrhythmias, including, without limitations, atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, ventricular arrhythmias, or ventricular fibrillation.

Description

[0001] Compounds suitable for cardiovascular disease or disorder treatment FIELD OF THE DISCLOSURE The present disclosure relates to, inter alia, prodrugs of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5- diiodobenzoyl)benzofuran-2-yl) acetate that find use in the treatment of diseases, such as cardiovascular disease. CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and benefit of U.S. Provisional Patent Application No.63 / 696,266, filed September 18, 2024, which is incorporated by reference herein in its entirety. BACKGROUND Cardiac arrhythmia, or an irregular heartbeat, is a medical condition characterized by an abnormal heart rate or rhythm: beating too fast, too slow, or in an irregular pattern. Atrial fibrillation (AFib) is the most common cardiac arrhythmia with an estimated prevalence of about 40 million patients globally, and about 5 million people in the U.S., and 20% of patients above age 80. Patients with untreated AFib have a significant greater risk of strokes, congestive heart failure, and peripheral embolism resulting in higher stroke recurrence and mortality rates. Only half of diagnosed atrial fibrillation patients survive another 10 years. Current therapeutics for treating cardiac arrhythmias have significant side-effects and safety issues, including long-term toxicity to the liver, lung, and thyroid, a very long half-life, and negative inotropic effects. There is a need for safe and efficacious anti-arrhythmic drugs for treating cardiovascular diseases without negatively impacting cardiac muscle function. SUMMARY Accordingly, the present disclosure provides, in part, compositions for treating or reducing the incidence of cardiac arrhythmias, including, without limitations, atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, ventricular arrhythmias, or ventricular fibrillation. Also provided are methods for treating cardiovascular diseases or disorders including cardiac arrhythmias. In embodiments, prodrugs of (S)-sec-butyl 2-(3-(4-(2- (diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate disclosed herein can favorably alter the pharmacokinetics (PK) profile of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5- diiodobenzoyl)benzofuran-2-yl) acetate, provide for increased gastrointestinal absorption by improved solubility as these prodrugs provide pH independent solubility to prolong absorption through the upper GI tract resulting in improved bioavailability and pharmacodynamic properties. In one aspect, the present disclosure provides a compound of formula (XI), or a stereoisomer thereof: wherein in formula (XI): X is a pharmaceutically acceptable anion; each of Raand Rbis independently hydrogen or C1-C6 alkyl, wherein Raand Rbare optionally joined to form a 3-6 membered carbocyclic ring; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; c. 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally wherein the heteroaryl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In embodiments, the compound is a compound of formula (XI) wherein Rais hydrogen or C1-C6alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rais hydrogen. In embodiments, the compound is a compound of formula (XI) wherein Rais independently at each occurrence alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl. In embodiments, the compound is a compound of formula (XI) wherein Rais selected from methyl, ethyl, n-propyl, isopropyl, n- butyl, and sec-butyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis hydrogen or C1-C6alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis hydrogen. In embodiments, the compound is a compound of formula (XI) wherein Rbis independently at each occurrence alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis selected from methyl, ethyl, n-propyl, isopropyl, n- butyl, and sec-butyl. In embodiments, the compound is a compound of formula (XI) wherein Raand Rbare joined to form a 3-6 membered carbocyclic ring, optionally wherein the 3-6 membered carbocyclic ring is selected from cyclohexane, cyclohexene, cyclopropane, cyclobutane; cyclopentane, cyclopropene, cyclobutene, cyclopentene and cyclopentadiene. In embodiments, the compound is a compound of formula (XI) wherein Z is -OR1. In embodiments, the compound is a compound of formula (XI) wherein R1is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI) wherein R1is selected from methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI) wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (XI) wherein -OR1is selected from -OMe, -OEt, - . rmula (XI), wherein Z is R2. In embodiments, the compound is a compound of formula (XI), wherein R2is C1-C8alkyl. In embodiments, the compound is a compound of formula (XI), wherein C1-C8 alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI), wherein C1-C8alkyl is selected from methyl and n-propyl. In embodiments, the compound is a compound of formula (XI), wherein C1-C8 alkyl is substituted with 1 to 3 substituents selected from Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (XI), wherein -R2is selected from methyl and . nts, the compound is a compound of formula (XI), wherein R2is phenyl. In embodiments, the compound is a compound of formula (XI), wherein phenyl is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (XI), wherein R2is 5 or 6 membered heteroaryl. In embodiments, the compound is a compound of formula (XI), wherein 5 or 6 membered heteroaryl is selected from pyridinyl, furyl, pyrrolidinyl, oxazole, isoxazole, pyrrazole, thiazole, isothiazole, and pyrimidine, optionally 3-pyridinyl. In embodiments, the compound is a compound of formula (XI), wherein Z is -N(R3)2. In embodiments, the compound is a compound of formula (XI), wherein Z is -NHR3. In embodiments, R3is independently at each occurrence selected from alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI), wherein each R3is methyl. In embodiments, the compound is a compound of formula (XI), wherein one or both R3are each independently substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl. In embodiments, the compound is a compound of formula (XI), wherein -N(R3)2 is -N(CH3)2. In embodiments, the compound is a compound of formula (XI) wherein Rais hydrogen or C1-C6alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rais hydrogen. In embodiments, the compound is a compound of formula (XI) wherein Rais independently at each occurrence alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl. In embodiments, the compound is a compound of formula (XI) wherein Rais selected from methyl, ethyl, n-propyl, isopropyl, n- butyl, and sec-butyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis hydrogen or C1-C6alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis hydrogen. In embodiments, the compound is a compound of formula (XI) wherein Rbis independently at each occurrence alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis selected from methyl, ethyl, n-propyl, isopropyl, n- butyl, and sec-butyl. In embodiments, the compound is a compound of formula (XI) wherein Raand Rbare joined to form a 3-6 membered carbocyclic ring, optionally wherein the 3-6 membered carbocyclic ring is selected from cyclohexane, cyclohexene, cyclopropane, cyclobutane; cyclopentane, cyclopropene, cyclobutene, cyclopentene and cyclopentadiene. In embodiments, the compound is a compound of formula (XI) wherein Z is -OR1. In embodiments, the compound is a compound of formula (XI) wherein R1is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI) wherein R1is selected from methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI) wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (XI) wherein -OR1is selected from -OMe, -OEt, - . rmula (XI), wherein Z is R2. In embodiments, the compound is a compound of formula (XI), wherein R2is C1-C8alkyl. In embodiments, the compound is a compound of formula (XI), wherein C1-C8 alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI), wherein C1-C8 alkyl is selected from methyl and n-propyl. In embodiments, the compound is a compound of formula (XI), wherein C1-C8 alkyl is substituted with 1 to 3 substituents selected from Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (XI), wherein -R2is selected from methyl and . nts, the compound is a compound of formula (XI), wherein R2is phenyl. In embodiments, the compound is a compound of formula (XI), wherein phenyl is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (XI), wherein R2is 5 or 6 membered heteroaryl. In embodiments, the compound is a compound of formula (XI), wherein 5 or 6 membered heteroaryl is selected from furyl, pyrrolidinyl, oxazole, isoxazole, pyrrazole, thiazole, isothiazole, and pyrimidine. In embodiments, the compound is a compound of formula (XI), wherein Z is -N(R3)2. In embodiments, the compound is a compound of formula (XI), wherein Z is -NHR3. In embodiments, R3is independently at each occurrence selected from alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI), wherein each R3is methyl. In embodiments, the compound is a compound of formula (XI), wherein one or both R3are each independently substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl. In embodiments, the compound is a compound of formula (XI), wherein -N(R3)2 is -N(CH3)2. In one aspect, the disclosure provides a compound of formula (XIa), or a stereoisomer thereof: wherein in formula (XIa): X is a pharmaceutically acceptable anion; each of Raand Rbis independently hydrogen or C1-C6alkyl, wherein Raand Rbare optionally joined to form a 3-6 membered carbocyclic ring; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a) and b): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In one aspect, the present disclosure provides a compound of formula (I), or a stereoisomer thereof: wherein in formula (I): X is a pharmaceutically acceptable anion; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; c. 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally wherein the heteroaryl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In embodiments, the compound is a compound of formula (I) wherein Z is -OR1. In embodiments, the compound is a compound of formula (I) wherein R1is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I) wherein R1is selected from methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I) wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (I) wherein -OR1is selected from -OMe, -OEt, - . n em o mens, e compoun s a compoun o ormula (I), wherein Z is R2. In embodiments, the compound is a compound of formula (I), wherein R2is C1-C8 alkyl. In embodiments, the compound is a compound of formula (I), wherein C1-C8 alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I), wherein C1-C8alkyl is selected from methyl and n-propyl. In embodiments, the compound is a compound of formula (I), wherein C1-C8 alkyl is substituted with 1 to 3 substituents selected from Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (I), wherein -R2is selected from methyl and . nts, the compound is a compound of formula (I), wherein R2is phenyl. I n embodiments, the compound is a compound of formula (I), wherein phenyl is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (I), wherein R2is 5 or 6 membered heteroaryl. In embodiments, the compound is a compound of formula (I), wherein 5 or 6 membered heteroaryl is selected from pyridinyl, furyl, pyrrolidinyl, oxazole, isoxazole, pyrrazole, thiazole, isothiazole, and pyrimidine, optionally 3-pyridinyl. In embodiments, the compound is a compound of formula (I), wherein 5 or 6 membered heteroaryl is selected from furyl, pyrrolidinyl, oxazole, isoxazole, pyrrazole, thiazole, isothiazole, and pyrimidine. In embodiments, the compound is a compound of formula (I), wherein Z is -N(R3)2. In embodiments, the compound is a compound of formula (I), wherein Z is -NHR3. In embodiments, R3is independently at each occurrence selected from alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I), wherein each R3is methyl. In embodiments, the compound is a compound of formula (I), wherein one or both R3are each independently substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl. In embodiments, the compound is a compound of formula (I), wherein -N(R3)2 is -N(CH3)2. In embodiments, the compound is a compound of formula (I) wherein Z is -OR1. In embodiments, the compound is a compound of formula (I) wherein R1is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I) wherein R1is selected from methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I) wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (I) wherein -OR1is selected from -OMe, -OEt, - . rmula (I), wherein Z is R2. In embodiments, the compound is a compound of formula (I), wherein R2is C1-C8alkyl. In embodiments, the compound is a compound of formula (I), wherein C1-C8 alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I), wherein C1-C8alkyl is selected from methyl and n-propyl. In embodiments, the compound is a compound of formula (I), wherein C1-C8 alkyl is substituted with 1 to 3 substituents selected from Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (I), wherein -R2is selected from methyl and . nts, the compound is a compound of formula (I), wherein R2is phenyl. In embodiments, the compound is a compound of formula (I), wherein phenyl is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (I), wherein Z is -N(R3)2. In embodiments, the compound is a compound of formula (I), wherein Z is -NHR3. In embodiments, R3is independently at each occurrence selected from alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I), wherein each R3is methyl. In embodiments, the compound is a compound of formula (I), wherein one or both R3are each independently substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl. In embodiments, the compound is a compound of formula (I), wherein -N(R3)2 is -N(CH3)2. In one aspect, the present disclosure provides a compound of formula (Ia), or a stereoisomer thereof: wherein in formula (Ia): X is a pharmaceutically acceptable anion; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a) and b): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In embodiments, the compound of formula (I) is a compound of any one of formula 1001-1015, or a pharmaceutically acceptable salt thereof: Formula Formula No. Structure No. Structure Formula No. Structure Formula No. Structure Formula Structure Formula No. No. Structure In embodiments, the compound is a compound of formula (I) or formula 1001-1015, wherein X is selected from chloride, bromide, iodide, hydroxide, sulfate (SO4-2, HSO4-2), nitrate, phosphate (e.g. PO4-3, HPO4-2, H2PO4-), acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate and p-toluenesulfonate. In embodiments, the compound is a compound of formula (I) or formula 1001-1015, wherein X is selected from chloride, bromide. iodide, acetate, HSO4-, SO4-2, p-toluenesulfonate, PO4-3, HPO4-2, H2PO4-, and tartrate. In embodiments, the compound is a compound of formula (I) or formula 1001-1015, wherein X is chloride. In embodiments, the compound of formula (I) is a compound of any one of formula 2001-2015: Formula Structure Formula Structure 2001 2009 2005 2013 Formula No. Structure Formula No. Structure O

[0002] 3004 3012

[0003] 3007 3015 ( a), ormua (), ormua (a), ormua 00 - 05, ormua 00 - 05 or ormua 300 -305) ex bts improved gastrointestinal absorption (e.g. improved permeability and / or solubility) compared to (S)-sec- butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate. In embodiments, the compound of the disclosure exhibits at least about 1 fold, at least about 2 fold, at least about 3 fold, at least about 4 fold, at least about 5 fold, at least about 6 fold, at least about 7 fold, at least about 8 fold, at least about 9 fold, at least about 10 fold, at least about 50 fold, at least about 100 fold, at least about 500 fold, or at least about 1000 fold improved gastrointestinal absorption (e.g. improved permeability and / or solubility) compared to (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate. In one aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula (XI), or a stereoisomer thereof, and a pharmaceutical acceptable carrier or excipient: formula (XI) wherein in formula (XI): X is a pharmaceutically acceptable anion; each of Raand Rbis independently hydrogen or C1-C6 alkyl, wherein Raand Rbare optionally joined to form a 3-6 membered carbocyclic ring; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; c. 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally wherein the heteroaryl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula (XIa), or a stereoisomer thereof, and a pharmaceutical acceptable carrier or excipient:

[0004] wherein in formula (XIa): X is a pharmaceutically acceptable anion; each of Raand Rbis independently hydrogen or C1-C6alkyl, wherein Raand Rbare optionally joined to form a 3-6 membered carbocyclic ring; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a) and b): a. C1-C8alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula (I), or a stereoisomer thereof, and a pharmaceutical acceptable carrier or excipient: wherein in formula (I): X is a pharmaceutically acceptable anion; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl, or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; c. 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally wherein the heteroaryl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In another aspect, the present disclosure provides a pharmaceutical composition comprising a compound of formula (Ia), or a stereoisomer thereof, and a pharmaceutical acceptable carrier or excipient: wherein in formula (Ia): X is a pharmaceutically acceptable anion; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a) and b): a. C1-C8alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In embodiments, the compound of formula (I) is a compound of any one of formula 1001-1015, formula 2001- 2015 or formula 3001-3015, or a pharmaceutically acceptable salt thereof. In embodiments, the pharmaceutical composition is formulated for oral or parenteral administration. In embodiments, the pharmaceutical composition is formulated for topical, dermal, intradermal, intramuscular, intraperitoneal, intraarticular, intravenous, subcutaneous, intraarterial, intranasal, buccal, sublingual, or transdermal administration. In embodiments, the pharmaceutical composition is formulated for topical administration. In another aspect, the present disclosure provides a method for treating cardiovascular disease or disorders in a subject in need thereof, the method comprising administering to the subject the pharmaceutical composition comprising a compound of any one of the embodiments disclosed herein. In embodiments the cardiovascular disease or disorder is selected from arrythmia or atrial fibrillation. In embodiments the method comprises treating arrhythmia or reducing the incidence of arrhythmias, restoring sinus and ventricular rhythms in a subject having persistent atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, atrial tachycardia, electrical storm, incessant ventricular tachycardia, supraventricular tachycardia (SVT), paroxysmal supraventricular tachycardia (PSVT), tachyarrhythmias, ventricular arrhythmias, ventricular premature beats (VPBs), nonsustained ventricular tachycardia (VT), sustained ventricular tachycardia (VT), or ventricular fibrillation, restoring normal cardiac rhythms in a subject, and / or reducing atrial fibrillation burden. In embodiments, the cardiovascular disease or disorder is one or more of a rare genetic atrial fibrillation syndrome (e.g. Titan, Lamin), hypertrophic cardiomyopathy (HCM), recurrent atrial fibrillation, or recurrent paroxysmal atrial fibrillation. In embodiments the cardiovascular disease or disorder is one or more of a rare genetic atrial fibrillation syndrome (e.g. Titan, Lamin), hypertrophic cardiomyopathy (HCM), recurrent paroxysmal atrial fibrillation, recurrent atrial fibrillation with Amiodarone contraindicated. In one aspect, the present disclosure relates to a method for treating a subject diagnosed with arrhythmia and / or paroxysmal or persistent atrial fibrillation (AFib), the method comprising: a) administering a first dose of any of the compound of any of the embodiments disclosed herein or the pharmaceutical composition of any of the embodiments disclosed herein to the subject while employing a wearable to monitor heart rhythm data of the subject; b) monitoring the subject for efficacy of the administered first dose to assess whether the first dose is efficacious for the subject during a comparison period of 1 or more days; c) if an administered dose of the first dose is efficacious for the subject, continuing to monitor the subject's heart rhythm data to ensure that the administered dose remains efficacious. In embodiments, the wearable is one or more of a patch, a watch, a wristband, a strap, a ring, a glass, a shirt, a finger, a bracelet, a SGPS / GPRS baby / control, a belt, a pants, a sock, a shoe, a Bluetooth key tracker, a holter, an implantable, or a device that adheres to a body when fitted. In embodiment, assessing the efficacy of the first dose is delayed for at least 7 or 14 days after administering the first dose. In embodiments, if the administered first dose is assessed as not efficacious for the subject by an end of the comparison period, dose adjusting the amount of one or more times as necessary to achieve an efficacious result using at least the comparison period and / or delay period. In embodiments, if the administered first dose or adjusted dose is no longer efficacious, step c) is repeated with the administered first dose or adjusted dose as the first dose. In embodiments, monitoring in step b) is conducted in a continuous manner. In embodiments, monitoring in step b) comprises detecting atrial fibrillation (AF). In embodiments, detecting comprises use of a photoplethysmography (PPG) algorithm. In embodiments, the efficacy at an administered dose is evaluated by comparing baseline levels of AFib against corresponding levels of AFib in the comparison period. In embodiments, the comparison period is one or more of about a day, about a week, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, or up to about 6 months. In embodiments, the subject has one or more of a rare genetic atrial fibrillation syndrome (e.g. Titan, Lamin), hypertrophic cardiomyopathy (HCM), recurrent paroxysmal atrial fibrillation, or recurrent atrial fibrillation with Amiodarone contraindicated. Any aspect or embodiment disclosed herein can be combined with any other aspect or embodiment as disclosed herein. In embodiments, the subject is selected for therapy based on a history of atrial fibrillation and / or an atrial fibrillation genetic risk score (GRS) indicating high risk of Afib recurrence over time. In embodiments, the subject is selected for therapy based on a positive result from a wearable FDA cleared device, a history of atrial fibrillation and / or an atrial fibrillation genetic risk score (GRS) indicating high risk of Afib recurrence over time. In embodiments, the wearable FDA cleared device is used to monitor the subject on therapy and dosing is adjusted over time based on the presence or absence of atrial fibrillation. In embodiments, the subject is selected for therapy based on a history of atrial fibrillation and the atrial fibrillation genetic risk score (GRS) indicating high risk of Afib recurrence over time. In embodiments, a drug therapy is administered before and / or after a cardioversion or ablation procedure intended to convert the subject to normal sinus rhythm. In embodiments, the subject is selected for therapy based on a history of atrial fibrillation and / or an atrial fibrillation genetic risk score (GRS) in combination with an algorithm comprised of at least one known clinical risk factor indicating high risk of Afib recurrence over time. In embodiments, the risk factor comprises age, ethnicity, and / or a history of cardiovascular disease, cardiac amyloidosis, illicit drug use, or diabetes. BRIEF DESCRIPTION OF THE FIGURES The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. FIGS.1A and 1B show exemplary mass spectra of compound 2007. FIGS.2A and 2B show exemplary mass spectra of compound 2002. FIGS.3A and 3B show exemplary mass spectra of compound 2011. FIGS.4A and 4B show exemplary mass spectra of compound 2006. FIGS.5A and 5B show exemplary mass spectra of compound 2003. FIGS.6A and 6B show exemplary mass spectra of compound 3009. FIGS.7A and 7B show exemplary mass spectra of compound 2001. FIGS.8A and 8B show exemplary mass spectra of compound 2005. FIGS.9A and 9B show exemplary mass spectra of compound 2004. FIGS.10A and 10B show exemplary mass spectra of compound 2012. FIGS.11A and 11B show exemplary mass spectra of compound 2013. FIGS.12A and 12B show exemplary mass spectra of compound 2014. FIGS.13A and 13B show exemplary mass spectra of compound 2015. DETAILED DESCRIPTION Disclosed herein are prodrugs of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5- diiodobenzoyl)benzofuran-2-yl) acetate that are useful, inter alia, for the treatment of disease, such as therapies for cardiovascular disease or disorders including cardiac arrhythmias, including, without limitations, atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, ventricular arrhythmias, or ventricular fibrillation. (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate is an antiarrhythmic agent with adverse side effects that include liver, lung, and thyroid toxicity as well as multiple drug interactions. (S)-sec-butyl 2-(3-(4-(2-(d e yamno)e oxy)- , - o o enzoyl)benzofuran-2-yl) acetate The term “prodrug” includes compounds which, under physiological conditions, are converted into pharmaceutical agents, i.e., a compound of the present disclosure. In embodiments, one method for making a prodrug is to include one or more selected moieties which are hydrolyzed under physiological conditions to reveal the desired molecule. As used herein, the term “alkyl” denotes branched or unbranched hydrocarbon chains, having about 1 to 10 carbons, such as, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, 2-methylpentyl, pentyl, hexyl, isohexyl, heptyl, 4,4-dimethyl pentyl, octyl, 2,2,4-trimethylpentyl, and the like. “Substituted alkyl” includes an alkyl group unsubstituted or substituted with one or more functional groups which are attached commonly to such chains, such as, hydroxy, halogen, mercapto or thio, cyano, alkylthio, carboxy, nitro, alkoxy, or unsubstituted or substituted, alkyl, amino, alkenyl, carboxamido, carbalkoxy, alkynyl, heterocyclyl, aryl, heteroaryl, and the like to form alkyl groups such as trifluoromethyl, 3-hydroxyhexyl, 2-carboxypropyl, 2-fluoroethyl, carboxymethyl, cyanobutyl, phenethyl, benzyl, and the like. The term “halogen” or “halo” as used herein alone or as part of another group refers to chloro, bromo, fluoro, or iodo. The term “alkoxy” refers to alkyl-O-, in which alkyl is as defined above. The term “alkylthio” refers to alkyl-S-, in which alkyl is as defined above. The term “alkylamino” refers to –NR’R”, in which R’ and R” each may independently represent H, alkyl, or aryl, all as defined herein. The term “alkylcarbonyl” refers to –C(=O)-alkyl, in which alkyl is as defined above. The term “carboxy” refers to the moiety –C(=O)OH. The term “carbalkoxy” refers to the moiety –C(=O)-O-alkyl, in which alkyl is as defined above. The term “carboxamido” refers to the moiety –C(=O)-NR’R”, in which R’ and R”, each may independently represent H, alkyl, or aryl, all as defined herein. The term “alkylsulfonyl” refers to the moiety –S(=O)2-alkyl, in which alkyl is as defined above. The term “arylsulfonyl” refers to the moiety –S(=O)2-aryl, in which aryl is as defined herein. For example, arylsulfonyl may be –S(=O)2-phenyl. The term “arylsulfonyloxy” refers to the moiety –OS(=O)2-alkyl, wherein alkyl is as defined above. The term “amino(monoalkylamino-, dialkylamino-)sulfinyl” refers to the moiety –S(=O)NR’R”, in which R’ and R” each may independently represent H, alkyl, or aryl, all as defined herein. The term “amino(monoalkylamino-, dialkylamino-)sulfonyl” refers to the moiety –S(=O)2NR’R”, in which R’ and R” each may independently represent H, alkyl, or aryl, all as defined herein. The term “alkylsulfonylamino” refers to the moiety –NHS(=O)2-alkyl, in which alkyl is as previously defined. The term “hydroxysulfonyloxy” refers to the moiety –OS(=O)2OH. The term “alkoxysulfonyloxy” refers to the moiety –OS(=O)2O-alkyl, in which alkyl is as defined above. The term “alkylsulfonyloxy” refers to the moiety –OS(=O)2-alkyl, in which alkyl is as previously defined. The term “hydroxysulfonyl” refers to the moiety –S(=O)2OH. The term “alkoxysulfonyl” refers to the moiety –S(=O)2O-alkyl, wherein alkyl is as previously defined. The term “alkylsulfonylalkyl” refers to the moiety –alkyl-S(=O)2-alkyl, wherein each alkyl may be as previously defined. The term “amino(monoalkylamino-, dialkylamino-)sulfonylakyl” refers to the moiety –alkyl-S(=O)2-NR’R”, wherein alkyl is as previously defined, and R’ and R” each may independently represent H, alkyl, or aryl, all as defined herein. The term “amino(monoalkylamino-, dialkylamino-)sulfinylalkyl” refer to the moieties –alkyl-S(=O)-NR’R”, wherein alkyl is as previously defined, and R’ and R” each may independently represent H, alkyl, or aryl, all as defined herein. Unless otherwise indicated, the term “cycloalkyl” as employed herein alone or as part of another group includes saturated or partially unsaturated (containing 1 or more double bonds) cyclic hydrocarbon groups containing 1 to 3 rings, including monocyclicalkyl, bicyclicalkyl and tricyclicalkyl, containing a total of 3 to 20 carbons forming the rings, preferably 3 to 10 carbons, forming the ring and which may be fused to 1 or 2 aromatic rings as described for aryl, which include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cyclododecyl, and cyclohexenyl. “Substituted cycloalkyl” includes a cycloalkyl group optionally substituted with 1 or more substituents such as halogen, alkyl, substituted alkyl, alkoxy, hydroxy, aryl, substituted aryl, aryloxy, cycloalkyl, alkylamido, alkanoylamino, oxo, acyl, arylcarbonylamino, amino, nitro, cyano, thiol and / or alkylthio and / or any of the substituents included in the definition of “substituted alkyl.” Unless otherwise indicated, the term “alkenyl” as used herein by itself or as part of another group refers to straight or branched chain of 2 to 20 carbons, preferably 2 to 12 carbons, and more preferably 2 to 8 carbons in the normal chain, which include one or more double bonds in the normal chain, such as vinyl, 2-propenyl, 3-butenyl, 2-butenyl, 4-pentenyl, 3-pentenyl, 2-hexenyl, 3-hexenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 3- octenyl, 3-nonenyl, 4-decenyl, 3-undecenyl, 4-dodecenyl, 4,8, 12-tetradecatrienyl, and the like. “Substituted alkenyl” includes an alkenyl group optionally substituted with one or more substituents, such as the substituents included above in the definition of “substituted alkyl” and “substituted cycloalkyl.” Unless otherwise indicated, the term “alkynyl” as used herein by itself or as part of another group refers to straight or branched chain of 2 to 20 carbons, preferably 2 to 12 carbons and more preferably 2 to 8 carbons in the normal chain, which include one or more triple bonds in the normal chain, such as 2-propynyl, 3-butynyl, 2-butynyl, 4-pentynyl, 3-pentynyl, 2-hexynyl, 3-hexynyl, 2-heptynyl, 3-heptynyl, 4-heptynyl, 3-octynyl, 3- nonynyl, 4-decynyl, 3-undecynyl, 4-dodecynyl and the like. “Substituted alkynyl” includes an alkynyl group optionally substituted with one or more substituents, such as the substituents included above in the definition of “substituted alkyl” and “substituted cycloalkyl.” Unless otherwise indicated, the term “aryl” or “Ar” as employed herein alone or as part of another group refers to monocyclic, bicyclic, and / or polycyclic aromatic groups containing 6 to 10 carbons in the ring portion (such as phenyl or naphthyl including 1-naphthyl and 2-naphthyl) and may optionally include one to three additional rings fused to a carbocyclic ring or a heterocyclic ring, such as aryl, cycloalkyl, heteroaryl, or cycloheteroalkyl rings or substituted forms thereof. “Substituted aryl” includes an aryl group optionally substituted with one or more functional groups, such as halo, alkyl, haloalkyl (e.g., trifluoromethyl), alkoxy, haloalkoxy (e.g., difluoromethoxy), alkenyl, alkynyl, cycloalkyl-alkyl, cycloheteroalkyl, cycloheteroalkylalkyl, aryl, heteroaryl, arylalkyl, aryloxy, aryloxyalkyl, arylalkoxy, alkoxycarbonyl, alkylcarbonyl, arylcarbonyl, arylalkenyl, aminocarbonylaryl, arylthio, arylsulfinyl, arylazo, heteroarylalkyl, heteroarylalkenyl, heteroarylheteroaryl, heteroaryloxy, hydroxy, nitro, cyano, amino, substituted amino wherein the amino includes 1 or 2 substituents (which are optionally substituted alkyl, aryl or any of the other substituents recited herein), thiol, alkylthio, arylthio, heteroarylthio, arylthioalkyl, alkoxyarylthio, alkylaminocarbonyl, arylaminocarbonyl, aminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, alkylcarbonylamino, arylcarbonylamino, arylsulfinyl, arylsulfinylalkyl, arylsulfonylamino, or arylsulfonaminocarbonyl and / or any of the alkyl substituents recited herein. The term “arylalkyl” refers to –alkyl-aryl, in which alkyl and aryl are as defined above. The term “haloalkyl” refers to an alkyl group having one or more halogen substituents. Example haloalkyl groups include -CF3, -C2F5, -CHF2, -CH2F, -CCl3, -CHCl2, -C2Cl5, and the like. An alkyl group in which all of the hydrogen atoms are replaced with halogen atoms can be referred to as “perhaloalkyl.” The term “haloalkoxy” refers to an alkoxy group having one or more halogen substituents. Example haloalkoxy groups include -OCF3, -OC2F5, -OCHF2, -OCH2F, -OCCl3, -OCHCl2, -OC2Cl5, and the like. An alkyl group in which all of the hydrogen atoms are replaced with halogen atoms can be referred to as “perhaloalkyl.” Unless otherwise indicated, the term “heteroaryl” as used herein alone or as part of another group refers to a 5- to 7-membered aromatic ring which includes 1, 2, 3 or 4 hetero atoms such as nitrogen, oxygen or sulfur and such rings fused to an aryl, cycloalkyl, heteroaryl or heterocycloalkyl ring (e.g. benzothiophene, indole, quinoline, thiazole, isooxazole, benzothiazole, benzimidizole, isoquinoline, pyridine, pyrimidine, benzopyrone, oxazole, thiazole, pyrazine), and includes possible N-oxides. “Substituted heteroaryl” includes a heteroaryl group optionally substituted with 1 to 4 substituents, such as the substituents included above in the definition of “substituted alkyl” and “substituted cycloalkyl.” Substituted heteroaryl also includes fused heteroaryl groups which include, for example, quinoline, isoquinoline, indole, isoindole, carbazole, acridine, benzopyrene, benzopyrone, benzimidazole, benzofuran, isobenzofuran, phenanthroline, purine, and the like. Moreover, the terms “heterocyclo,” “heterocycle,” “heterocyclyl,” or “heterocyclic ring,” as used herein, refer to an unsubstituted or substituted stable 5- to 7-membered monocyclic ring system which may be saturated or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from N, O or S, and wherein the nitrogen and sulfur heteroatoms may optionally be oxidized, and the nitrogen heteroatom may optionally be quaternized. The heterocyclic ring may be attached at any heteroatom or carbon atom which results in the creation of a stable structure. Examples of such heterocyclic groups include, but are not limited to, piperidinyl, piperazinyl, oxopiperazinyl, oxopiperidinyl, oxopyrrolidinyl, oxoazepinyl, azepinyl, pyrrolyl, pyrrolidinyl, benzothiophene, chromone, benzopyrene, benzopyrone, furanyl, thienyl, pyrazolyl, pyrazolidinyl, imidazolyl, imidazolinyl, imidazolidinyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, oxazolidinyl, isooxazolyl, isoxazolidinyl, morpholinyl, thiazolyl, thiazolidinyl, isothiazolyl, thiadiazolyl, tetrahydropyranyl, thiamorpholinyl, thiamorpholinylsulfoxide, thiamorpholinylsulfone, and oxadiazolyl. The term “heteroarylalkyl” refers to –alkyl-heteroaryl, in which alkyl and heteroaryl are as defined above. As used herein, the terms “optionally substituted” or “substituted” may indicate that a chemical moiety referred to, for example, alkyl, aryl, and heteroaryl, may be unsubstituted or substituted with one or more groups including, without limitation, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, arylalkyl, substituted arylalkyl, aryl, substituted aryl, heterocycle, substituted heterocycle, heteroaryl, substituted heteroaryl, hydroxyl, amino, substituted amino, alkoxy, substituted alkoxy, halogen, carboxy, nitro, carbalkoxy, substituted carbalkoxy, carboxamido, substituted carboxamido, alkylamino, substituted alkyl amino, monoalkylaminosulfinyl, substituted, monoalkylaminosulfinyl, dialkylaminosulfinyl, substituted dialkylaminosulfinyl, monoalkylaminosulfonyl, substituted monoalkylaminosulfonyl, dialkylaminosulfonyl, substituted dialkylaminosulfonyl, alkylsulfonylamino, substituted alkylsulfonylamino, hydroxysulfonyloxy, alkoxysulfonyloxy, substituted alkoxysulfonyloxy, alkylsulfonyloxy, substituted alkylsulfonyloxy, hydroxysulfonyl, alkoxysulfonyl, substituted alkoxysulfonyl, alkylsulfonylalkyl, substituted alkylsulfonylalkyl, monoalkylaminosulfonylalkyl, substituted monoalkylaminosulfonylalkyl, dialkylaminosulfonylalkyl, substituted dialkylaminosulfonylalkyl, monoalkylaminosulfinylalkyl, substituted monoalkylaminosulfinylalkyl, dialkylaminosulfinylalkyl, substituted dialkylaminosulfinylalkyl, and the like. The chemical moieties of formula (XI), formula (XIa), formula (I), formula (Ia), formula 1001-1015, formula 2001-2015, or a pharmaceutically acceptable salt thereof, above, that may be optionally substituted include alkyl, alkenyl, alkynyl, cycloalkyl, arylalkyl, aryl, heterocycle, and heteroaryl, as described herein. For example, optionally substituted alkyl may include both propyl and 2- chloro-propyl. Additionally, “optionally substituted” is also inclusive of embodiments where the named substituent or substituents have multiple substituents rather than simply a single substituent. For example, optionally substituted aryl may include both phenyl and 3-ethyl-5-methyl-6-bromo-phenyl. “Pharmaceutically acceptable” includes approved or approvable by a regulatory agency of the Federal or a state government or the corresponding agency in countries other than the United States, or that is listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, e.g., in humans. The compounds of the disclosure may be administered as salts, which are also within the scope of this disclosure. Pharmaceutically acceptable (i.e., non-toxic, physiologically compatible) salts are preferred. A "pharmaceutically acceptable salt" includes a salt of a compound of the disclosure that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. Such salts are non-toxic may be inorganic or organic acid addition salts and base addition salts. The term "pharmaceutically acceptable anion" includes the anion of such acid addition salts. If the compounds of the disclosure have, for example, at least one basic center, they can form acid addition salts. These are formed, for example, with strong inorganic acids, such as mineral acids, for example sulfuric acid, phosphoric acid or a hydrohalic acid, with strong organic carboxylic acids, such as alkane carboxylic acids of 1 to 4 carbon atoms which are unsubstituted or substituted, for example, by halogen, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic, malonic, succinic, maleic, fumaric, phthalic or terephthalic acid, such as hydroxycarboxylic acids, for example ascorbic, glycolic, lactic, malic, tartaric or citric acid, such as amino acids, (for example aspartic or glutamic acid or lysine or arginine), or benzoic acid, or with organic sulfonic acids, such as (C1-C4) alkyl or arylsulfonic acids which are unsubstituted or substituted, for example by halogen, for example methyl- or paratoluene-sulfonic acid. Corresponding acid addition salts can also be formed having plural basic centers, if desired. In embodiments, such salts include: (1) acid addition salts, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or formed with organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2- hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, and the like; or (2) salts formed when an acidic proton present in the parent compound either is replaced by a metal ion, e.g., an alkali metal ion, an alkaline earth ion, or an aluminum ion; or coordinates with an organic base such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine and the like. In embodiments, salts further include, by way of example only, sodium, potassium, calcium, magnesium, ammonium, tetraalkylammonium, and the like; and when the compound contains a basic functionality, salts of non-toxic organic or inorganic acids, such as hydrochloride, hydrobromide, tartrate, mesylate, acetate, maleate, oxalate, and the like. In embodiments, the pharmaceutically acceptable anion is selected from the deprotonated form of valproic acid, maleic acid, tartaric acid, oxalic acid, pamoic acid, phosphonic acid, benzoic acid, citric acid, salicylic acid, succinic acid, methanesulfonic acid, malic acid, and p-toluenesulfonic acid. In embodiments, the pharmaceutically acceptable salt is selected from valproic acid, maleic acid, tartaric acid, oxalic acid, and pamoic acid. The compounds of the disclosure having at least one acid group (e.g., carboxylic acid) can also form salts with suitable bases. Representative examples of such salts include metal salts, such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, thiomorpholine, piperidine, pyrrolidine, a mono, di or trihydroxy lower alkylamine, for example ethyl, tert-butyl, diethyl, diisopropyl, triethyl, tributyl or dimethyl-propylamine, or a mono, di or trihydroxy lower alkylamine, for example mono, di or triethanolamine. Corresponding internal salts may also be formed. For example, certain salts of the compounds described herein which contain a basic group include monohydrochloride, hydrogensulfate, methanesulfonate, phosphate or nitrate. Moreover, certain salts of the compounds described herein which contain an acid group include sodium, potassium and magnesium salts and pharmaceutically acceptable organic amines. All stereoisomers of the compounds of the disclosure, either in a mixture or in pure or substantially pure form, are considered to be within the scope of this disclosure. The compounds of the disclosure may have asymmetric centers at any of the carbon atoms including any one of the substituents. Consequently, compounds of the disclosure may exist in enantiomeric or diastereomeric forms or in mixtures thereof. Furthermore, where a stereocenter existing in a compound of the disclosure is represented as a racemate, it is understood that the stereocenter may encompass the racemic mixture of R and S isomers, the S isomers, and the R isomers. The processes for preparation of such compounds can utilize racemates, enantiomers, or diastereomers as starting materials. When diastereomeric or enantiomeric products are prepared, they can be separated by conventional methods including, chromatographic, chiral HPLC, fractional crystallization, or distillation. In embodiments, compounds of the present disclosure have groups including alkenyls, iminyls, and the like, which may exist as entgegen (E) or zusammen (Z) conformations, in which case all geometric forms thereof, both E and Z, cis and trans, and mixtures thereof, are within the scope of the present disclosure. Accordingly, when such geometric isomeric products are prepared, they can be separated by conventional methods for example, chromatographic, HPLC, distillation or crystallization. Accordingly, in one aspect, the present disclosure provides a compound of formula (XI), or a stereoisomer thereof: ormua ( ) wherein in formula (XI): X is a pharmaceutically acceptable anion; each of Raand Rbis independently hydrogen or C1-C6 alkyl, wherein Raand Rbare optionally joined to form a 3-6 membered carbocyclic ring; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; c. 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally wherein the heteroaryl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In embodiments, the compound is a compound of formula (XI) wherein Rais hydrogen or C1-C6 alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rais hydrogen. In embodiments, the compound is a compound of formula (XI) wherein Rais independently at each occurrence alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl. In embodiments, the compound is a compound of formula (XI) wherein Rais selected from methyl, ethyl, n-propyl, isopropyl, n- butyl, and sec-butyl. In embodiments, the compound is a compound of formula (XI) wherein Rais unbranched C1-C6alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rais a branched C1-C6alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis hydrogen or C1-C6 alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis hydrogen. In embodiments, the compound is a compound of formula (XI) wherein Rbis independently at each occurrence alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis selected from methyl, ethyl, n-propyl, isopropyl, n- butyl, and sec-butyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis unbranched C1-C6 alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis a branched C1-C6alkyl. In embodiments, the compound is a compound of formula (XI) wherein Raand Rbare joined to form a 3-6 membered carbocyclic ring, optionally wherein the 3-6 membered carbocyclic ring is selected from cyclohexane, cyclohexene, cyclopropane, cyclobutane; cyclopentane, cyclopropene, cyclobutene, cyclopentene and cyclopentadiene. In embodiments, the compound is a compound of formula (XI) wherein Z is -OR1. In embodiments, the compound is a compound of formula (XI) wherein R1is alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis unbranched C1-C6alkyl. In embodiments, the compound is a compound of formula (XI) wherein Rbis a branched C1-C6 alkyl. In embodiments, the compound is a compound of formula (XI) wherein R1is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI) wherein R1is selected from methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI) wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (XI) wherein R1is alkyl substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (XI) wherein -OR1is selected from -OMe, -OEt, - . rmula (XI), wherein Z is R2. In embodiments, the compound is a compound of formula (XI), wherein R2is C1-C8alkyl. In embodiments, the compound is a compound of formula (XI), wherein C1-C8 alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI), wherein C1-C8 alkyl is selected from methyl and n-propyl. In embodiments, the compound is a compound of formula (XI) wherein R2is unbranched C1-C6 alkyl. In embodiments, the compound is a compound of formula (XI) wherein R2is a branched C1-C6alkyl. In embodiments, the compound is a compound of formula (XI), wherein R2is C1-C8 alkyl is substituted with 1 to 3 substituents selected from Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, - OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (XI), wherein -R2is selected from methyl and . nts, the compound is a compound of formula (XI), wherein R2is phenyl. In embodiments, the compound is a compound of formula (XI), wherein R2is phenyl and is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, - OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (XI), wherein R2is 5 or 6 membered heteroaryl. In embodiments, the compound is a compound of formula (XI), wherein 5 or 6 membered heteroaryl is selected from pyridinyl, furyl, pyrrolidinyl, oxazole, isoxazole, pyrrazole, thiazole, isothiazole, and pyrimidine, optionally 3-pyridinyl. In embodiments, the compound is a compound of formula (XI), wherein Z is -N(R3)2. In embodiments, the compound is a compound of formula (XI), wherein Z is -NHR3. In embodiments, R3is independently at each occurrence selected from alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XI) wherein R3is alkyl. In embodiments, the compound is a compound of formula (XI) wherein R3is unbranched C1-C6alkyl. In embodiments, the compound is a compound of formula (XI) wherein R3is a branched C1-C6alkyl. In embodiments, the compound is a compound of formula (XI), wherein each R3is methyl. In embodiments, the compound is a compound of formula (XI), wherein one or both R3are each independently substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl. In embodiments, the compound is a compound of formula (XI), wherein -N(R3)2is -N(CH3)2. In one aspect, the present disclosure provides a compound of formula (XIa), or a stereoisomer thereof: wherein in formula (XIa): X is a pharmaceutically acceptable anion; each of Raand Rbis independently hydrogen or C1-C6alkyl, wherein Raand Rbare optionally joined to form a 3-6 membered carbocyclic ring; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a) and b): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In embodiments, the compound is a compound of formula (XIa) wherein Rais hydrogen or C1-C6 alkyl. In embodiments, the compound is a compound of formula (XIa) wherein Rais hydrogen. In embodiments, the compound is a compound of formula (XIa) wherein Rais independently at each occurrence alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl. In embodiments, the compound is a compound of formula (XIa) wherein Rais selected from methyl, ethyl, n-propyl, isopropyl, n- butyl, and sec-butyl. In embodiments, the compound is a compound of formula (XIa) wherein Rbis unbranched C1-C6 alkyl. In embodiments, the compound is a compound of formula (XIa) wherein Rbis a branched C1-C6alkyl. In embodiments, the compound is a compound of formula (XIa) wherein Rbis hydrogen or C1-C6 alkyl. In embodiments, the compound is a compound of formula (XIa) wherein Rbis hydrogen. In embodiments, the compound is a compound of formula (XIa) wherein Rbis independently at each occurrence alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, and hexyl. In embodiments, the compound is a compound of formula (XIa) wherein Rbis selected from methyl, ethyl, n-propyl, isopropyl, n- butyl, and sec-butyl. In embodiments, the compound is a compound of formula (XIa) wherein Rbis unbranched C1-C6 alkyl. In embodiments, the compound is a compound of formula (XIa) wherein Rbis a branched C1-C6 alkyl. In embodiments, the compound is a compound of formula (XIa) wherein Raand Rbare joined to form a 3-6 membered carbocyclic ring, optionally wherein the 3-6 membered carbocyclic ring is selected from cyclohexane, cyclohexene, cyclopropane, cyclobutane; cyclopentane, cyclopropene, cyclobutene, cyclopentene and cyclopentadiene. In embodiments, the compound is a compound of formula (XIa) wherein Z is -OR1. In embodiments, the compound is a compound of formula (XIa) wherein R1is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XIa) wherein R1is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XIa) wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (XIa) wherein R1is alkyl substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (XIa) wherein -OR1is selected from -OMe, -OEt, . n em o mens, e compoun s a compoun o ormula (XIa), wherein Z is R2. In embodiments, the compound is a compound of formula (XIa), wherein R2is C1-C8 alkyl. In embodiments, the compound is a compound of formula (XIa), wherein C1-C8 alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XIa), wherein C1-C8 alkyl is selected from methyl and n-propyl. In embodiments, the compound is a compound of formula (XIa) wherein R2is unbranched C1-C6alkyl. In embodiments, the compound is a compound of formula (XIa) wherein R2is a branched C1-C6alkyl. In embodiments, the compound is a compound of formula (XIa), wherein C1-C8 alkyl is substituted with 1 to 3 substituents selected from Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (XIa), wherein -R2is selected from methyl and . nts, the compound is a compound of formula (XIa), wherein R2is phenyl. I n embodiments, the compound is a compound of formula (XIa), wherein R2is phenyl and is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (XIa), wherein Z is -N(R3)2. In embodiments, the compound is a compound of formula (XIa), wherein Z is -NHR3. In embodiments, R3is independently at each occurrence selected from alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (XIa) wherein R3is alkyl. In embodiments, the compound is a compound of formula (XIa) wherein R3is unbranched C1-C6 alkyl. In embodiments, the compound is a compound of formula (XIa) wherein R3is a branched C1-C6alkyl. In embodiments, the compound is a compound of formula (XIa), wherein each R3is methyl. In embodiments, the compound is a compound of formula (XIa), wherein one or both R3are each independently substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl. In embodiments, the compound is a compound of formula (XIa), wherein -N(R3)2 is -N(CH3)2. In one aspect, the present disclosure provides a compound of formula (I), or a stereoisomer thereof: wherein in formula (I): X is a pharmaceutically acceptable anion; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally R1is phenyl, or benzyl, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; c. 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally wherein the heteroaryl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In embodiments, the compound is a compound of formula (I) wherein Z is -OR1. In embodiments, the compound is a compound of formula (I) wherein R1is alkyl. In embodiments, the compound is a compound of formula (I) wherein Rbis unbranched C1-C6 alkyl. In embodiments, the compound is a compound of formula (I) wherein Rbis a branched C1-C6 alkyl. In embodiments, the compound is a compound of formula (I) wherein R1is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I) wherein R1is selected from methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I) wherein R1is selected from methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I) wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (I) wherein R1is phenyl or benzyl. In embodiments, the compound is a compound of formula (I) wherein R1is phenyl. In embodiments, the compound is a compound of formula (I) wherein R1is benzyl. In embodiments, the compound is a compound of formula (I) wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (I) wherein -OR1is selected from -OMe, -OEt, - . , p p rmula (I), wherein Z is R2. In embodiments, the compound is a compound of formula (I), wherein R2is C1-C8 alkyl. In embodiments, the compound is a compound of formula (I), wherein R2is C1-C8alkyl, straight or branched chain, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl. In embodiments, the compound is a compound of formula (I), wherein C1-C8alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I), wherein C1-C8alkyl is selected from methyl and n-propyl. In embodiments, the compound is a compound of formula (I) wherein R2is unbranched C1-C6 alkyl. In embodiments, the compound is a compound of formula (I) wherein R2is a branched C1-C6alkyl. In embodiments, the compound is a compound of formula (I), wherein C1-C8 alkyl is substituted with 1 to 3 substituents selected from Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (I), wherein R2is selected from methyl and . 2 nts, the compound is a compound of formula (I), wherein R is phenyl. In embodiments, the compound is a compound of formula (I), wherein R2is phenyl and is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (I), wherein R2is 5 or 6 membered heteroaryl. In embodiments, the compound is a compound of formula (I), wherein 5 or 6 membered heteroaryl is selected from pyridinyl, furyl, pyrrolidinyl, oxazole, isoxazole, pyrrazole, thiazole, isothiazole, and pyrimidine, optionally 3-pyridinyl. In embodiments, the compound is a compound of formula (I), wherein Z is -N(R3)2. In embodiments, the compound is a compound of formula (I), wherein Z is -NHR3. In embodiments, R3is independently at each occurrence selected from alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (I) wherein R3is alkyl. In embodiments, the compound is a compound of formula (I) wherein R3is unbranched C1-C6alkyl. In embodiments, the compound is a compound of formula (I) wherein R3is a branched C1-C6alkyl. In embodiments, the compound is a compound of formula (I), wherein each R3is methyl. In embodiments, the compound is a compound of formula (I), wherein one or both R3are each independently substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl. In embodiments, the compound is a compound of formula (I), wherein -N(R3)2is -N(CH3)2. In one aspect, the present disclosure provides a compound of formula (Ia), or a stereoisomer thereof:

[0005] wherein in formula (Ia): X is a pharmaceutically acceptable anion; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a) and b): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In embodiments, the compound is a compound of formula (Ia) wherein Z is -OR1. In embodiments, the compound is a compound of formula (Ia) wherein R1is alkyl. In embodiments, the compound is a compound of formula (Ia) wherein Rbis unbranched C1-C6alkyl. In embodiments, the compound is a compound of formula (Ia) wherein Rbis a branched C1-C6alkyl. In embodiments, the compound is a compound of formula (Ia) wherein R1is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (Ia) wherein R1is selected from methyl, ethyl, n- propyl, isopropyl, n-butyl, sec-butyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (Ia) wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (Ia) wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl. In embodiments, the compound is a compound of formula (Ia) wherein -OR1is selected from -OMe, -OEt, - . rmula (Ia), wherein Z is R2. In embodiments, the compound is a compound of formula (Ia), wherein R2is C1-C8 alkyl. In embodiments, the compound is a compound of formula (Ia), wherein C1-C8alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (Ia), wherein C1-C8 alkyl is selected from methyl and n-propyl. In embodiments, the compound is a compound of formula (Ia) wherein R2is unbranched C1-C6alkyl. In embodiments, the compound is a compound of formula (Ia) wherein R2is a branched C1-C6 alkyl. In embodiments, the compound is a compound of formula (Ia), wherein C1-C8alkyl is substituted with 1 to 3 substituents selected from Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (Ia), wherein -R2is selected from methyl and . I n embodments, the compound is a compound of formula (Ia), wherein R2is phenyl. In embodiments, the compound is a compound of formula (Ia), wherein R2is phenyl and is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, - OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl. In embodiments, the compound is a compound of formula (Ia), wherein Z is -N(R3)2. In embodiments, the compound is a compound of formula (Ia), wherein Z is -NHR3. In embodiments, R3is independently at each occurrence selected from alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl. In embodiments, the compound is a compound of formula (Ia) wherein R3is alkyl. In embodiments, the compound is a compound of formula (Ia) wherein R3is unbranched C1-C6alkyl. In embodiments, the compound is a compound of formula (Ia) wherein R3is a branched C1-C6 alkyl. In embodiments, the compound is a compound of formula (Ia), wherein each R3is methyl. In embodiments, the compound is a compound of formula (Ia), wherein one or both R3are each independently substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl. In embodiments, the compound is a compound of formula (Ia), wherein -N(R3)2 is -N(CH3)2. In embodiments, the compound of formula (XI) or formula (I) is a compound of any one of formula 1001- 1015, or a pharmaceutically acceptable salt thereof: Formula Structure Formula Structure 1002 1010 1006 1014 In embodiments, the compound is a compound of formula (I) or formula 1001-1015, wherein X is selected from chloride, bromide, iodide, hydroxide, sulfate (SO4-2, HSO4-2), nitrate, phosphate (e.g. PO4-3, HPO4-2, H2PO4-), acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate and p-toluenesulfonate. In embodiments, the compound is a compound of formula (I) or formula 1001-1015, wherein X is selected from chloride, bromide. iodide, acetate, HSO4-, SO4-2, p-toluenesulfonate, PO4-3, HPO4-2, H2PO4-, and tartrate. In embodiments, the compound is a compound of formula (I) or formula 1001-1015, wherein X is chloride. In embodiments, the compound is a compound of formula (I) or formula 1001-1015, wherein X is iodide. In embodiments, the compound of formula (I) and / or formula (XI) is not compound 1010. In embodiments, the compound of formula (XI) or formula (I) is a compound of any one of formula 2001- 2015: Formula Formula No. Structure No. Structure 2004 2012

[0006] 2007 2015 In embodiments, the compound of formula (I) and / or formula (XI) is not compound 2010. In embodiments, the compound of formula (XI) or formula (I) is a compound of any one of formula 3001- 3015: mula Structure Formula Structure O 3002 3010 3006 3014 In embodiments, the compound of the disclosure (e.g. a compound of any one of formula (XI), formula (XIa), formula (I), formula (Ia), formula 1001-1015, formula 2001-2015, or formula 3001-3015) exhibits improved gastrointestinal absorption (e.g. improved permeability and / or solubility) compared to (S)-sec- butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate. In embodiments, the compound of the disclosure exhibits at least about 1 fold, at least about 2 fold, at least about 3 fold, at least about 4 fold, at least about 5 fold, at least about 6 fold, at least about 7 fold, at least about 8 fold, at least about 9 fold, at least about 10 fold, at least about 50 fold, at least about 100 fold, at least about 500 fold, or at least about 1000 fold improved gastrointestinal absorption (e.g. improved permeability and / or solubility) compared to (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate. Pharmaceutical compositions Aspects of the present disclosure include a pharmaceutical composition comprising a compound of formula (XI), or a stereoisomer thereof, and a pharmaceutically acceptable carrier or excipient: wherein in formula (XI): X is a pharmaceutically acceptable anion; each of Raand Rbis independently hydrogen or C1-C6alkyl, wherein Raand Rbare optionally joined to form a 3-6 membered carbocyclic ring; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; c. 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally wherein the heteroaryl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. Aspects of the present disclosure include a pharmaceutical composition comprising a compound of formula (XIa), or a stereoisomer thereof, and a pharmaceutical acceptable carrier or excipient: wherein in formula (XIa): X is a pharmaceutically acceptable anion; each of Raand Rbis independently hydrogen or C1-C6 alkyl, wherein Raand Rbare optionally joined to form a 3-6 membered carbocyclic ring; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a) and b): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. Aspects of the present disclosure include a pharmaceutical composition comprising a compound of formula (I), or a stereoisomer thereof, and a pharmaceutically acceptable carrier or excipient: wherein in formula (I): X is a pharmaceutically acceptable anion; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally R1is phenyl, or benzyl, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; c. 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally wherein the heteroaryl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. Aspects of the present disclosure include a pharmaceutical composition comprising a compound of formula (Ia), or a stereoisomer thereof, and a pharmaceutically acceptable carrier or excipient: wherein in formula (Ia): X is a pharmaceutically acceptable anion; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a) and b): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. In embodiments, the compound of formula (XI) or formula (I) is a compound of any one of formula 1001- 1015, formula 2001-2015, formula 3001-3015, or a pharmaceutically acceptable salt thereof. In embodiments, the pharmaceutical composition is formulated for oral or parenteral administration. In embodiments, the pharmaceutical composition is formulated for topical, dermal, intradermal, intramuscular, intraperitoneal, intraarticular, intravenous, subcutaneous, intraarterial, intranasal, buccal, sublingual, or transdermal administration. In embodiments, the pharmaceutical composition is formulated for topical administration. In embodiments, any of the compounds of formula (XI) or formula (I) disclosed herein (and / or additional agents) are included in various formulations. Any compound of formula (IX) or formula (I) (and / or additional agents) described herein can take the form of solutions, suspensions, emulsion, drops, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, emulsions, aerosols, sprays, suspensions, or any other form suitable for use. Other examples of suitable pharmaceutical excipients are described in Remington’s Pharmaceutical Sciences 1447-1676 (Alfonso R. Gennaro eds., 19th ed.1995), incorporated herein by reference. In embodiments, the compound of formula (XI) or formula (I) disclosed herein can possess a sufficiently basic functional group, which can react with an inorganic or organic acid, or a carboxyl group, which can react with an inorganic or organic base, to form a pharmaceutically acceptable salt. A pharmaceutically acceptable acid addition salt is formed from a pharmaceutically acceptable acid, as is well known in the art. Such salts include the pharmaceutically acceptable salts listed in, for example, Journal of Pharmaceutical Science, 66, 2-19 (1977) and The Handbook of Pharmaceutical Salts; Properties, Selection, and Use. P. H. Stahl and C. G. Wermuth (eds.), Verlag, Zurich (Switzerland) 2002, which are hereby incorporated by reference in their entirety. In embodiments, the compositions disclosed herein are in the form of a pharmaceutically acceptable salt. Further, any compound of formula (XI) or formula (I) disclosed herein can be administered to a subject as a component of a pharmaceutical composition, that comprises a pharmaceutically acceptable carrier or vehicle. Such pharmaceutical compositions can optionally comprise a suitable amount of a pharmaceutically acceptable excipient so as to provide the form for proper administration. Pharmaceutical excipients can be liquids, such as water and oils, including those of petroleum, animal, vegetable, or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. The pharmaceutical excipients can be, for example, saline, gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea and the like. In addition, auxiliary, stabilizing, thickening, lubricating, and coloring agents can be used. In embodiments, the pharmaceutically acceptable excipients are sterile when administered to a subject. Water is a useful excipient when any agent disclosed herein is administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid excipients, specifically for injectable solutions. Suitable pharmaceutical excipients also include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. Any agent disclosed herein, if desired, can also comprise minor amounts of wetting or emulsifying agents, or pH buffering agents. The present disclosure includes the disclosed compounds of formula (XI) or formula (I) in various formulations of pharmaceutical composition. Any compound of formula (XI) or formula (I) disclosed herein can take the form of solutions, suspensions, emulsion, drops, tablets, pills, pellets, capsules, capsules containing liquids, powders, sustained-release formulations, suppositories, emulsions, aerosols, sprays, suspensions, or any other form suitable for use. Other examples of suitable pharmaceutical excipients are described in Remington’s Pharmaceutical Sciences 1447-1676 (Alfonso R. Gennaro eds., 19th ed.1995), incorporated herein by reference. Where necessary, the pharmaceutical compositions comprising the compound of formula (XI) or formula (I) can also include a solubilizing agent. Also, the agents can be delivered with a suitable vehicle or delivery device as known in the art. Combination therapies outlined herein can be co-delivered in a single delivery vehicle or delivery device. Pharmaceutical compositions for administration can optionally include a local anesthetic such as, for example, lignocaine to lessen pain at the site of the injection. The pharmaceutical compositions comprising a compound of formula (XI) or formula (I) of the present disclosure may conveniently be presented in unit dosage forms and may be prepared by any of the methods well known in the art of pharmacy. Such methods generally include the step of bringing therapeutic agents into association with a carrier, which constitutes one or more accessory ingredients. Typically, the pharmaceutical compositions are prepared by uniformly and intimately bringing therapeutic agent into association with a liquid carrier, a finely divided solid carrier, or both, and then, if necessary, shaping the product into dosage forms of the desired formulation (e.g., wet or dry granulation, powder blends, etc., followed by tableting using conventional methods known in the art). In embodiments, any compound of formula (XI) or formula (I) disclosed herein is formulated in accordance with routine procedures as a pharmaceutical composition adapted for a mode of administration disclosed herein. General Synthetic Procedures The compounds of the disclosure may be prepared using the techniques described below. Some of the schemes and examples may omit details of common reactions, including oxidations, reductions, and so on, separation techniques (extraction, evaporation, precipitation, chromatography, filtration, trituration, crystallization, and the like), and analytical procedures, which are known to persons of ordinary skill in the art of organic chemistry. The details of such reactions and techniques can be found in a number of treatises, including Richard Larock, Comprehensive Organic Transformations (1999), and the multi-volume series edited by Michael B. Smith and others, Compendium of Organic Synthetic Methods (1974 et seq.). Some of the reaction schemes may omit minor products resulting from chemical transformations (e.g., an alcohol from the hydrolysis of an ester, CO2 from the decarboxylation of a diacid, etc.). In addition, in some instances, reaction intermediates may be used in subsequent steps without isolation or purification (i.e., in situ). Starting materials and reagents may be obtained from commercial sources or may be synthesized in analogy to or according to methods that are known in the art. In the preparation of starting materials, existing functional groups which do not participate in the reaction should, if necessary, be protected. Protecting groups, their introduction and their removal are described herein. In some of the reaction schemes and examples described herein, certain compounds can be prepared using protecting groups, which prevent undesirable chemical reaction at otherwise reactive sites. Protecting groups may also be used to enhance solubility or otherwise modify physical properties of a compound. For a discussion of protecting group strategies, a description of materials and methods for installing and removing protecting groups, and a compilation of useful protecting groups for common functional groups, including amines, carboxylic acids, alcohols, ketones, aldehydes, and so on, see T. W. Greene and P. G. Wuts, Protecting Groups in Organic Chemistry (1999) and P. Kocienski, Protective Groups (2000). Generally, the chemical transformations described throughout the specification may be carried out using substantially stoichiometric amounts of reactants, though certain reactions may benefit from using an excess of one or more of the reactants. Additionally, many of the reactions disclosed throughout the specification may be carried out at about room temperature (RT) and ambient pressure, but depending on reaction kinetics, yields, and so on, some reactions may be run at elevated pressures or employ higher temperatures (e.g., reflux conditions) or lower temperatures (e.g., −78° C. to 0° C.). Any reference in the disclosure to a stoichiometric range, a temperature range, a pH range, etc., whether or not expressly using the word “range,” also includes the indicated endpoints. Many of the chemical transformations may also employ one or more compatible solvents, which may influence the reaction rate and yield. Depending on the nature of the reactants, the one or more solvents may be polar protic solvents (including water), polar aprotic solvents, non-polar solvents, or some combination. Representative solvents include saturated aliphatic hydrocarbons (e.g., n-pentane, n-hexane, n-heptane, n-octane); aromatic hydrocarbons (e.g., benzene, toluene, xylenes); halogenated hydrocarbons (e.g., methylene chloride, chloroform, carbon tetrachloride); aliphatic alcohols (e.g., methanol, ethanol, propan-1-ol, propan-2-ol, butan-1-ol, 2-methyl-propan-1-ol, butan-2-ol, 2-methyl-propan-2-ol, pentan-1-ol, 3-methyl-butan-1-ol, hexan-1-ol, 2-methoxy-ethanol, 2-ethoxy-ethanol, 2-butoxy-ethanol, 2-(2-methoxy- ethoxy)-ethanol, 2-(2-ethoxy-ethoxy)-ethanol, 2-(2-butoxy-ethoxy)-ethanol); ethers (e.g., diethyl ether, di- isopropyl ether, dibutyl ether, 1,2-dimethoxyethane, 1,2-diethoxy-ethane, 1-methoxy-2-(2-methoxy-ethoxy)- ethane, 1-ethoxy-2-(2-ethoxy-ethoxy)-ethane, tetrahydrofuran, 1,4-dioxane); ketones (e.g., acetone, methyl ethyl ketone); esters (methyl acetate, ethyl acetate); nitrogen-containing solvents (e.g., formamide, N,N- dimethylformamide, acetonitrile, N-methyl-pyrrolidone, pyridine, quinoline, nitrobenzene); sulfur-containing solvents (e.g., carbon disulfide, dimethyl sulfoxide, tetrahydro-thiophene-1,1,-dioxide); and phosphorus- containing solvents (e.g., hexamethylphosphoric triamide). General scheme 1 shows exemplary methods for preparing compounds of formula (XI), formula (XIa), formula (I), formula (Ia), wherein the substituents are as defined for formula (XI) and formula (I), except where further noted. The following general procedure outlines a key transformation used in the synthesis of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate derivatives (i.e., compounds of formula (XI), formula (XIa), formula (I), formula (Ia), or formula 1001-1015, formula 2001- 2015, formula 3001-3015) by reacting a halogenated hydrocarbon group (e.g. a carbonate with a halogenated hydrocarbon group ) with (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5- diiodobenzoyl)benzofuran-2-yl) acetate via nucleophilic substitution following standard literature-reported conditions. General scheme 2 shows exemplary methods for preparing compounds of formula (XI), formula (XIa), formula (I), formula (Ia), wherein the substituents are as defined for formula (XI) and formula (I), except where further noted. The following general procedure outlines a key transformation used in the synthesis of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate derivatives (i.e., compounds of formula (XI), formula (XIa), formula (I), formula (Ia), or formula 1001-1015, formula 2001- 2015, formula 3001-3015) by reacting a halogenated hydrocarbon group (e.g. an ester with a halogenated hydrocarbon group) with (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate via nucleophilic substitution following standard literature-reported conditions. General scheme 3 shows exemplary methods for preparing compounds of formula (XI), formula (XIa), formula (I), formula (Ia), wherein the substituents are as defined for formula (XI) and formula (I), except where further noted. The following general procedure outlines a key transformation used in the synthesis of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate derivatives (i.e., compounds of formula (XI), formula (XIa), formula (I), formula (Ia), or formula 1001-1015, formula 2001- 2015, formula 3001-3015) by reacting a halogenated hydrocarbon group (e.g. an amide with a halogenated hydrocarbon group) with (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate via nucleophilic substitution following standard literature-reported conditions. While these general procedures provide exemplary foundational methodology, variations in reagents, stoichiometry, reaction time, and temperature may apply depending on the specific compound, with detailed conditions reported alongside each individual example, as would be understood by one of ordinary skill in the art. General Scheme 1 NO II OI General Scheme 3 Administration, Dosing, and Treatment Regimens In embodiments, any compound of formula (XI) or formula (I) (and / or additional agents) described herein is formulated in accordance with routine procedures as a composition adapted for a mode of administration described herein. Routes of administration include, for example: intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, oral, sublingual, intranasal, intracerebral, intravaginal, transdermal, buccal, rectally, by inhalation, or topically, particularly to the ears, nose, eyes, or skin. In embodiments, the administering is affected orally or by parenteral injection. In most instances, administration results in the release of any agent described herein into the bloodstream. Any compound of formula (XI) or formula (I) (and / or additional agents) described herein can be administered orally. Such compounds or formula (XI) or formula (I) (and / or additional agents) can also be administered by any other convenient route, for example, by intravenous infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.) and can be administered together with another biologically active agent. Administration can be systemic or local. Various delivery systems are known, e.g., encapsulation in liposomes, microparticles, microcapsules, capsules, etc., and can be used to administer. Dosage forms suitable for parenteral administration (e.g., intravenous, intramuscular, intraperitoneal, subcutaneous and intra-articular injection and infusion) include, for example, solutions, suspensions, dispersions, emulsions, and the like. They may also be manufactured in the form of sterile solid compositions (e.g., lyophilized composition), which can be dissolved or suspended in sterile injectable medium immediately before use. They may contain, for example, suspending or dispersing agents known in the art. The dosage of any compound of formula (XI) or formula (I) (and / or additional agents) described herein as well as the schedule can depend on various parameters, including, but not limited to, the disease being treated, the subject’s general health, and the administering physician’s discretion. Any compound of formula (XI) or formula (I) described herein, can be administered prior to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks before), concurrently with, or subsequent to (e.g., 5 minutes, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks after) the administration of an additional agent, to a subject in need thereof. In various embodiments the compound of formula (XI) or formula (I) and additional agent described herein are administered 1 minute apart, 10 minutes apart, 30 minutes apart, less than 1 hour apart, 1 hour apart, 1 hour to 2 hours apart, 2 hours to 3 hours apart, 3 hours to 4 hours apart, 4 hours to 5 hours apart, 5 hours to 6 hours apart, 6 hours to 7 hours apart, 7 hours to 8 hours apart, 8 hours to 9 hours apart, 9 hours to 10 hours apart, 10 hours to 11 hours apart, 11 hours to 12 hours apart, 1 day apart, 2 days apart, 3 days apart, 4 days apart, 5 days apart, 6 days apart, 1 week apart, 2 weeks apart, 3 weeks apart, or 4 weeks apart. The dosage of any compound of formula (XI) or formula (I) (and / or additional agents) described herein can depend on several factors including the severity of the condition, whether the condition is to be treated or prevented, and the age, weight, and health of the subject to be treated. Additionally, pharmacogenomic (the effect of genotype on the pharmacokinetic, pharmacodynamic or efficacy profile of a therapeutic) information about a particular subject may affect dosage used. Furthermore, the exact individual dosages can be adjusted somewhat depending on a variety of factors, including the specific combination of the agents being administered, the time of administration, the route of administration, the nature of the formulation, the rate of excretion, the particular disease being treated, the severity of the disorder, and the anatomical location of the disorder. Some variations in the dosage can be expected. In embodiments, delivery can also be in a vesicle, in particular a liposome (see Langer, 1990, Science 249:1527-1533; Treat et al., in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez-Berestein and Fidler (eds.), Liss, New York, pp.353-365 (1989). Any compound of formula (XI) or formula (I) (and / or additional agents) described herein can be administered by immediate-release, controlled-release or sustained-release means or by delivery devices that are well known to those of ordinary skill in the art. Examples include, but are not limited to, those described in U.S. Patent Nos. 3,845,770; 3,916,899; 3,536,809; 3,598,123; 4,008,719; 5,674,533; 5,059,595; 5,591,767; 5,120,548; 5,073,543; 5,639,476; 5,354,556; and 5,733,556, each of which is incorporated herein by reference in its entirety. Such dosage forms can be useful for providing controlled- or sustained-release of one or more active ingredients using, for example, hydropropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles, liposomes, microspheres, or a combination thereof to provide the desired release profile in varying proportions. Controlled- or sustained- release of an active ingredient can be stimulated by various conditions, including but not limited to, changes in pH, changes in temperature, stimulation by an appropriate wavelength of light, concentration or availability of enzymes, concentration or availability of water, or other physiological conditions or compounds. In embodiments, polymeric materials can be used (see Medical Applications of Controlled Release, Langer and Wise (eds.), CRC Pres., Boca Raton, Florida (1974); Controlled Drug Bioavailability, Drug Product Design and Performance, Smolen and Ball (eds.), Wiley, New York (1984); Ranger and Peppas, 1983, J. Macromol. Sci. Rev. Macromol. Chem.23:61; see also Levy et al., 1985, Science 228:190; During et al., 1989, Ann. Neurol.25:351; Howard et al., 1989, J. Neurosurg.71:105). In embodiments, a controlled-release system can be placed in proximity of the target area to be treated, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol.2, pp.115-138 (1984)). Other controlled-release systems discussed in the review by Langer, 1990, Science 249:1527-1533) may be used. Administration of any compound of formula (XI) or formula (I) (and / or additional agents) described herein can, independently, be one to four times daily or one to four times per month or one to six times per year or once every two, three, four or five years. Administration can be for the duration of one day or one month, two months, three months, six months, one year, two years, three years, and may even be for the life of the subject. The dosage regimen utilizing any compound of formula (XI) or formula (I) (and / or additional agents) described herein can be selected in accordance with a variety of factors including type, species, age, weight, sex and medical condition of the subject; the severity of the condition to be treated; the route of administration; the renal or hepatic function of the subject; the pharmacogenomic makeup of the individual; and the specific compound of the disclosure employed. Any compound of formula (XI) or formula (I) (and / or additional agents) described herein can be administered in a single daily dose, or the total daily dosage can be administered in divided doses of two, three or four times daily. Furthermore, any compound of formula (XI) or formula (I) (and / or additional agents) described herein can be administered continuously rather than intermittently throughout the dosage regimen. Diseases; Methods of Treatment, and Patient Selections In one aspect, the present disclosure relates to a method for treating a cardiovascular disease or disorder in a subject in need thereof, the method comprising administering to the subject a compound of formula (XI) or formula (I). In one aspect, the present disclosure relates to a method for treating a cardiovascular disease or disorder in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising a compound of formula (XI) or formula (I). In embodiments the cardiovascular disease or disorder is selected from arrythmia or atrial fibrillation. In embodiments the method comprises treating arrhythmia or reducing the incidence of arrhythmias, restoring sinus and ventricular rhythms in a subject having persistent atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, atrial tachycardia, electrical storm, incessant ventricular tachycardia, supraventricular tachycardia (SVT), paroxysmal supraventricular tachycardia (PSVT), tachyarrhythmias, ventricular arrhythmias, ventricular premature beats (VPBs), nonsustained ventricular tachycardia (VT), sustained ventricular tachycardia (VT), ventricular fibrillation, restoring normal cardiac rhythms in a subject, and / or reducing atrial fibrillation burden. In embodiments the cardiovascular disease or disorder is one or more of a rare genetic atrial fibrillation syndrome (e.g. Titan, Lamin), hypertrophic cardiomyopathy (HCM), recurrent atrial fibrillation, or recurrent paroxysmal atrial fibrillation. In embodiments the cardiovascular disease or disorder is one or more of a rare genetic atrial fibrillation syndrome (e.g. Titan, Lamin), hypertrophic cardiomyopathy (HCM), recurrent paroxysmal atrial fibrillation, or recurrent atrial fibrillation. In embodiments the cardiovascular disease or disorder is one or more of a rare genetic atrial fibrillation syndrome (e.g. Titan, Lamin), hypertrophic cardiomyopathy (HCM), recurrent paroxysmal atrial fibrillation, or recurrent atrial fibrillation with Amiodarone contraindicated. The structure of Amiodarone is shown below. (2-butylbenzofuran-3-yl)(4 -(2-(diethylamino)ethoxy)-3,5-diiodophenyl)methanone In embodiments, the arrhythmia is or comprises extra beats, supraventricular tachycardias, ventricular arrhythmias, bradyarrhythmia, premature disorders, or conduction disorders. In embodiments, the arrhythmia is or comprises premature atrial contractions, premature ventricular contractions, or premature junctional contractions. In embodiments, the arrhythmia is or comprises atrial fibrillation, atrial flutter, or paroxysmal supraventricular tachycardia. In embodiments, the arrhythmia is or comprises ventricular fibrillation or ventricular tachycardia. In embodiments, the present disclosure provides a method of treating cardiac arrhythmia or reducing the incidence of cardiac arrhythmias in a subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method of restoring sinus and ventricular rhythms in a subject having persistent atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, ventricular arrhythmias, or ventricular fibrillation, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method of restoring normal cardiac rhythms in a subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method of reducing or preventing atrial fibrillation burden in a subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for reducing or preventing atrial remodeling in a subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for reducing stroke rate in a subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for increasing time in normal sinus rhythm in a subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, normal sinus rhythm refers to regular consistent peaks at longer intervals. In embodiments, the present disclosure provides a method for reducing or preventing recurrent paroxysmal or persistent atrial fibrillation (AFib) in a subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for pharmacologic cardioversion of paroxysmal atrial fibrillation (PAF) in a subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for pretreatment before elective cardioversion or catheter ablation of atrial fibrillation (AF) in a subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for restoring and / or maintaining normal sinus rhythm (NSR) in a critically ill subject with atrial fibrillation thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for controlling ventricular rate in a critically ill subject with atrial fibrillation and rapid ventricular response thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for primary and secondary prevention of sudden cardiac death (SCD) in a subject with left ventricular (LV) dysfunction and / or the subject is not a candidate for or refuses implantable cardioverter defibrillation (ICD) implantation, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for preventing ventricular arrhythmias in a subject with implantable cardioverter defibrillation (ICD) to decrease risk of shocks, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for reducing or preventing cardiac arrest associated with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) in a subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the present disclosure provides a method for reducing or preventing electrical (VT) storm and incessant VT in a hemodynamically stable subject in need thereof, comprising administering to the subject a compound of formula (XI) or formula (I). In embodiments, the compound of formula (I) blocks sodium channels at rapid pacing frequencies, and / or exerts a noncompetitive antisympathetic action. In embodiments, with prolonged administration, the compound of formula (XI) or formula (I) lengthens the cardiac action potential. In embodiments, the compound of formula (XI) or formula (I) blocks myocardial potassium channels, which contributes to slowing of conduction and prolongation of refractoriness. In embodiments, the antisympathetic action and the block of calcium and potassium channels are responsible for the negative dromotropic effects on the sinus node and for the slowing of conduction and prolongation of refractoriness in the atrioventricular (AV) node. Its vasodilatory action can decrease cardiac workload and consequently myocardial oxygen consumption. In embodiments, the compound of formula (XI) or formula (I) prolongs the duration of the action potential of all cardiac fibers while causing minimal reduction of dV / dt (maximal upstroke velocity of the action potential). The refractory period is prolonged in all cardiac tissues. In embodiments, the compound of formula (XI) or formula (I) increases the cardiac refractory period without influencing resting membrane potential, except in automatic cells where the slope of the prepotential is reduced, generally reducing automaticity. The electrophysiologic effects are reflected in a decreased sinus rate of 15 to 20%, increased PR and QT intervals of about 10%, the development of U-waves, and changes in T-wave contour. The changes do not require discontinuation of the compound of formula (XI) or formula (I) as they are evidence of its pharmacological action. In embodiments, the subject in need of treatment is diagnosed by measuring biomarkers, genetic testing, photoplethysmography, and / or electrocardiogram. In one aspect, the present disclosure relates to a method for treating a subject diagnosed with arrythmia and / or paroxysmal or persistent atrial fibrillation (AFib), the method comprising: a) administering a first dose of the compound of any of the embodiments disclosed herein or the pharmaceutical composition of any of the embodiments disclosed herein to the subject while employing a wearable to monitor heart rhythm data of the subject; b) monitoring the subject for efficacy of the administered first dose to assess whether the first dose is efficacious for the subject during a comparison period of 1 or more days; c) if an administered dose of the first dose is efficacious for the subject, continuing to monitor the subject's heart rhythm data to ensure that the administered dose remains efficacious. In embodiments, the wearable is one or more of a patch, a watch (e.g. a smart watch), a wristband, a strap, a ring (e.g. a smart ring), a glass (e.g. a smart glass), a shirt (e.g. a smart shirt), a finger (e.g. a smart finger), a bracelet (e.g. a smart bracelet), a SGPS / GPRS baby / control, a belt (e.g. a smart belt), pants (e.g. smart pants), a sock (e.g. a smart sock), a shoe (e.g. a smart shoe), a Bluetooth key tracker, a holter, an implantable, an ECG patch, or a device that adheres to a body when fitted. In embodiments, the wearable is configured to measure the heart rhythm and transmit the heart rhythm data directly or indirectly to a second computing device. In embodiments, the wearable is a smart watch, a smart ring, a smart glass, a smart shirt, a smart finger, a smart bracelet, a SGPS / GPRS baby / control, a smart belt, smart pants, a smart sock, a smart shoe, a Bluetooth key tracker, a holter, an implantable, or an ECG patch. In embodiment, assessing the efficacy of the first dose is delayed for at least 7 or 14 days after administering the first dose. In embodiments, if the administered first dose is assessed as not efficacious for the subject by an end of the comparison period, dose adjusting the amount of one or more times as necessary to achieve an efficacious result using at least the comparison period and / or delay period. In embodiments, if the administered first dose or adjusted dose is no longer efficacious, step c) is repeated with the administered first dose or adjusted dose as the first dose. In embodiments, monitoring in step b) is conducted in a continuous manner. In embodiments, monitoring in step b) comprises detecting atrial fibrillation (AF). In embodiments, detecting comprises use of a photoplethysmography (PPG) algorithm. In embodiments, the efficacy at an administered dose is evaluated by comparing baseline levels of AFib against corresponding levels of AFib in the comparison period. In embodiments, the comparison period is one or more of about a day, about a week, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, or up to about 6 months. In embodiments, the subject has one or more of a rare genetic atrial fibrillation syndrome (e.g. Titan, Lamin), hypertrophic cardiomyopathy (HCM), recurrent paroxysmal atrial fibrillation, or recurrent atrial fibrillation with Amiodarone contraindicated. In embodiments, the subject is selected for therapy based on a history of atrial fibrillation and / or an atrial fibrillation genetic risk score (GRS) indicating high risk of Afib recurrence over time. GRS scores can be calculated using known methods, such as described in Muse et al., PLOS Medicine 1002525 (2018), which is incorporated by reference herein in its entirety. In embodiments, the subject is selected for therapy based on a positive result from a wearable FDA cleared device, a history of atrial fibrillation and / or an atrial fibrillation genetic risk score (GRS) indicating high risk of Afib recurrence over time. In embodiments, a positive result is characterized by the identification of the occurrence of atrial fibrillation episodes and / or the atrial fibrillation total burden during a time period. In embodiments, the wearable FDA cleared device is used to monitor the subject on therapy and dosing is adjusted over time based on the presence or absence of atrial fibrillation. In embodiments, the subject is selected for therapy based on a history of atrial fibrillation and the atrial fibrillation genetic risk score (GRS) indicating high risk of Afib recurrence over time. In embodiments, a drug therapy is administered before and / or after a cardioversion or ablation procedure intended to convert the subject to normal sinus rhythm. In embodiments, the subject is selected for therapy based on a history of atrial fibrillation and / or an atrial fibrillation genetic risk score (GRS) in combination with an algorithm comprised of at least one known clinical risk factor indicating high risk of Afib recurrence over time. In embodiments, the risk factor comprises age, ethnicity, or a history of cardiovascular disease, cardiac amyloidosis, illicit drug use, or diabetes. Wearables Non-limiting examples of wearables and the use of wearables for monitoring AFib are found in US 2023 / 0372284 and WO 2023 / 233510, which are incorporated by reference herein in its entirety. In one aspect, the disclosure provides a method for treating a subject diagnosed with arrythmia and / or paroxysmal or persistent atrial fibrillation (AFib). In embodiments, the method comprises a) administering a first dose of a compound of formula (XI), formula (XIa), formula (I), formula (Ia), formula 1001-1015, or formula 2001-2015, formula 3001-3015, or a pharmaceutical composition comprising the compound of formula (XI), formula (XIa), formula (I), formula (Ia), formula 1001-1015, formula 2001-2015, or formula 3001-3015 to the subject while employing a wearable to monitor heart rhythm data of the subject; b) monitoring the subject for efficacy of the administered first dose to assess whether the first dose is efficacious for the subject during a comparison period of 1 or more days; and c) if an administered dose of the first dose is efficacious for the subject, continuing to monitor the subject's heart rhythm data to ensure that the administered dose remains efficacious. In embodiments, assessing the efficacy of the first dose is delayed for at least 7 or 14 days after administering the first dose. In embodiments, the administered first dose is assessed as not efficacious for the subject by an end of the comparison period, dose adjusting the amount of one or more times as necessary to achieve an efficacious result using at least the comparison period and / or delay period. In embodiments, if the administered first dose or adjusted dose is no longer efficacious, step c) is repeated with the administered first dose or adjusted dose as the first dose. In embodiments, monitoring in step b) is conducted in a continuous manner. In embodiments, monitoring in step b) comprises detecting atrial fibrillation (AF). In embodiments, the efficacy at an administered dose is evaluated by comparing baseline levels of AFib against corresponding levels of AFib in the comparison period. In embodiments, the subject has one or more of a rare genetic atrial fibrillation syndrome (e.g. Titan, Lamin), hypertrophic cardiomyopathy (HCM), recurrent paroxysmal atrial fibrillation, and recurrent atrial fibrillation with Amiodarone contraindicated. The comparison period recited above is designed to provide a temporal limit for determining the efficacy of the pharmacotherapy which, in the absence of such a limit, could be construed to be indefinitely long extending for years or decades. Hence, for the purposes herein, a comparison period is a duration of time, after the start of efficacy monitoring as described above, over which heart rhythm data acquired from the patient (e.g., via a wearable fitted to and / or employed on the patient) is analyzed to compare with previous heart rhythm data and / or AFib data of the patient (e.g., baseline data acquired during the qualification period, and / or data acquired during previous a comparison period data). In an embodiment, the comparison period is at least as long as the qualification period described herein, or based on a different period of time such as daily, weekly, and at least about 2-weeks (e.g., 13, 14, or 15 days) or twice, three or four times as long (i.e., at least about 4 weeks, at least about 6 weeks, or at least about 8 weeks). In an example, the comparison period can be a length that at least extends beyond a time at which the drug level has substantially stabilized in the patient (e.g., at least 2-3 days, 7 days, 14 days, etc. in a patient provided the compound of the disclosure (e.g. a compound of any one of formula (XI), formula (XIa), formula (I), formula (Ia), formula 1001- 1015, formula 2001-2015, or formula 3001-3015)), or can have a shorter length (e.g., continuously, or 1 day or more) if the comparison period begins after drug levels have substantially stabilized in the patient, (e.g., beginning 2 days or beginning 3 days after initiation of administering a compound of the disclosure at a given dosage). In embodiments, the comparison period is one or more of about a day, about a week, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, or up to about 6 months. The term “wearable” refers to any device that can be worn by a user, e.g., as an accessory, as clothing and / or embedded in clothing, etc., or that can be subdermally implanted in a patient. In embodiments, a patient is “fitted with a wearable” when the wearable is being worn by, is subdermally implanted into, or is otherwise fixed to, the patient to be able to measure the heart rhythm of the patient. Instrumentation The instrumentation used in the methods described herein is designed to be fitted to the patient as part of either the qualification protocol and / or the pharmacotherapy used with the patient as described herein. Wearables that are used for diagnosis are conventional and aim to inform the clinician whether the patient either has AFib or not and / or if the patient has AFib, possibly information about the patient's AFib burden and the number of episodes of AFib. Such diagnostic analysis fails to address any pharmacotherapeutic suitability, efficacy, and / or dose, which extends beyond diagnosis. The pharmacotherapeutic methods described herein include identifying patients who qualify for drug therapy and / or monitoring the qualified patient during treatment with the pharmacotherapy to assess the drug's effectiveness (e.g., in reducing the number of episodes of long duration AFib). The monitoring may allow for dose adjusting for the patient until the patient is deemed to be responsive to therapy or is disqualified from pharmacotherapy due to a failure to respond. The pharmacotherapeutic methods described herein allow for continuous monitoring of the patient to determine an efficacious dose of the drug as well as to ensure that the patient remains responsive to that dose. Accordingly, the wearables described herein are designed and / or selected to be robust for extended use, and / or comfortable and / or easy to use by the patient. In practice, the wearable may include a cardiac monitoring component, which may be either an assisted or an unassisted component, for measuring heart rhythm in patients. Many of the wearables are engageable and removable by the patient or are sub-dermally implanted. The specific cardiac monitoring component employed in the wearable is not critical, provided it can accurately measure the heart rhythm. The wearable may be capable of reporting measured heart rhythm data, such as by generating and / or transmitting data indicating the length of time of a detected period of AFib, and / or by generating and / or transmitting data indicating the number of episodes of long duration AFib detected (e.g., over a time period of interest, such as a week, a month, etc.). Also, or alternatively, the wearable may be configured to transmit heart rhythm data to a device configured to detect AFib and / or determine the length of time of a detected period of AFib and / or a number of episodes of long duration AFib (e.g., over the time period of interest). In embodiments, the wearable is approved by one or more regulatory bodies, such as the US Food & Drug Administration (FDA). Assisted Components In embodiments, in the methods of the disclosure, detecting comprises use of photoplethysmography (PPG) (e.g. a PGG algorithm). An assisted cardiac monitoring component may use photoplethysmography (PPG) to detect a patient's heart rate and rhythm. PPG is a conventional technology found in standard oximeters, measures light reflection in tissue to detect arterial pulsations and, accordingly, heart rhythm patterns. However, to continuously and / or semi-continuously measure heart rhythm, one must account for the fact that PPG signals generated during patient movement are often distorted, weak, and have a significant amount of noise relative to detected data. To account for such deficiencies, an algorithm may be used to reduce enough the distortion and / or noise to provide a reliable signal. In embodiments, both a PPG sensor and accelerometer are employed with an algorithm that allows for appropriate (e.g., sufficient signal-to-noise ratio). When so assisted, PPG may allow for reliable detection of both heart rates and heart rhythm. See, for example, Wojcikowski, et al., Photoplethysmographic time-domain heart rate measurement algorithm for resource-constrained wearable devices and its implementation, SENSORS 20, no.6 (2020): 1783 which is incorporated herein by reference in its entirety. In embodiments, the cardiac monitor component uses piezoelectric material and / or rhythm electroactive polymers to detect blood flow, thereby indirectly measuring heart rhythm. In embodiments, a combination of PPG and / or piezoelectric measurements and electrocardiogram data from single-electrode wearables (i.e., iEKG, e.g., as opposed to EKG, which refers to a conventional multiple- electrode electrocardiogram) can be combined to increase the specificity of the measurement. The iEKG (i.e., iECG) and the PPG or the piezoelectric data can originate either from two separate devices communicating by transceivers, for example, an armband and a smartwatch, or they can originate from a single device, for example, a wristband on a smartwatch (e.g., the Kardia™ Band on an iWatch). Once an arrhythmia is detected in the PPG data, the corresponding (e.g., in time) iECG data may be analyzed by an algorithm. Unassisted Components In embodiments, the wearable may include an unassisted cardiac monitor component, such as a portable electrocardiogram. The portable electrocardiogram component may be wearable, engageable at-will by the patient, and / or capable of transmitting data, e.g., via a built-in antenna or Bluetooth data transmitting device. The wearable comprising the unassisted cardiac monitor component can measure heart rates and heart rhythms. The wearable may be configured to detect and log AFib burden and / or long episodes of AFib (LEAF) over an observation period (e.g., of about 2 weeks or longer). The unassisted cardiac monitor component employs direct measurement, which means that the device is reading electrical signals generated by the heart. The direct measurement may be less affected by noise and distortion than indirect measurements, such as PPG measurements, which may enable transmitting measurement data to a clinician without the use of an algorithm, and / or with reduced use of any algorithm or data processing. In embodiments, the wearable may further include a specialized accessory, such as a cardiac monitor device, that can detect the electrical activities of a heart including heart rhythm through an electrode. The specialized accessory may be capable of initiating transmission and / or may comprise and / or be connected to a transmission device. In embodiments, the cardiac monitor device can be a component that is an integral part of a single wearable device, such as a smartwatch. By providing a single device that is wearable by a user and is capable of monitoring the electric field of the heart of the user, the electrical activities of the heart can be monitored continuously over a prolonged period, such as days or even months. In embodiments, the cardiac monitor device may include an analog-to-digital converter capable of digitalizing measured electric field data (e.g., measured potential difference data) to transmit and / or store in memory the measured data as digitized data. The cardiac monitor device can include an output that can transmit signals carrying information about the difference of potential between the limb and the body to an external circuit. The output can take various forms. In one case, the output can be a transceiver that communicates to another transceiver / receiver in another unit, for example, a watch or a tablet. In embodiments, a central analysis center (e.g., a remote lab, such as a CORE lab and / or a remote data analysis center and / or a server) may interpret and / or summarize the AFib data and / or the long episodes of Afib (LEAF) data. The central analysis center may also transmit a dose adjustment recommendation to the treating clinician, without a need for the patient to visit his or her physician (e.g., as part of a patient monitoring program). Also, or alternatively, an artificial intelligence algorithm may be used to determine the dose adjustment and may transmit the dose adjustment recommendation to the physician. In embodiments, the wearable may be a small consumer electronic device, for example, a watch, an armband, a ring, a strap, and / or a wristband. The wearable may include a housing that carries the cardiac monitor component and any associated circuitry, CPU, and the like. The wearable can also be worn at other locations on the user, including, but not limited to, the wrist, leg, neck, and / or body. The wearable may comprise a specialized accessory capable of communicating with another electronic device such as a tablet, a laptop computer, a desktop computer, and / or other similar devices, which, in turn, can communicate to a cloud network to transmit information from the device to the clinician. Also, or alternatively, the specialized accessory may be capable of transmitting information directly and / or via a network to the clinician. The heart rhythm and iECG wearables may be Bluetooth, Z-Wave, Zigbee, and / or Advanced and Adaptive Network Technology (ANT)-enabled. For example, the iECG and / or the heart rhythm monitoring and / or recording device (e.g., PPG or a piezoelectric heart rhythm monitoring and / or recording device) may be paired with an application that may be configured to automatically detect AFib based on data from the iECG and / or the heart rhythm monitoring and / or recording device. The iECG device and / or the rhythm monitoring and / or recording device may be configured to transmit data to the application. The data can be transmitted using one or more data transmissions methods such as Bluetooth, Z-Wave, Zigbee, or ANT protocols. The application may be configured to analyze the data using a proprietary software. Based on the data from the iECG and / or the heart rhythm monitoring and / or recording device, the application may be able to interpret and / or detect AFib with a sensitivity of >90% and a specificity of >80%. Combination Therapies and Conjugation In embodiments, the disclosure provides for compounds of formula (XI) or formula (I) and methods that further comprise administering an additional agent to a subject. In embodiments, the disclosure pertains to co- administration and / or co-formulation. Any of the compositions described herein may be co-formulated and / or co-administered. In embodiments, the compounds of formula (XI) or formula (I) (and / or additional agents) described herein, include derivatives that are modified, i.e., by the covalent attachment of any type of molecule to the composition such that covalent attachment does not prevent the activity of the composition. For example, but not by way of limitation, derivatives include composition that have been modified by, inter alia, glycosylation, lipidation, acetylation, pegylation, phosphorylation, amidation, derivatization by known protecting / blocking groups, proteolytic cleavage, linkage to a cellular ligand or other protein, etc. Any of numerous chemical modifications can be carried out by known techniques, including, but not limited to specific chemical cleavage, acetylation, formylation, metabolic synthesis of turicamycin, etc. Additionally, the derivative can contain one or more non-classical amino acids. Subjects and / or Animals In embodiments, the subject and / or animal is a mammal, e.g., a human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, rabbit, sheep, or non-human primate, such as a monkey, chimpanzee, or baboon. In embodiments, the subject and / or animal is a non-mammal, such, for example, a zebrafish. In embodiments, the subject and / or animal may comprise fluorescently-tagged cells (with e.g. GFP). In embodiments, the subject and / or animal is a transgenic animal comprising a fluorescent cell. In embodiments, the subject and / or animal is a human. In embodiments, the human is a pediatric human. In embodiments, the human is an adult human. In embodiments, the human is a geriatric human. In embodiments, the human may be referred to as a patient. In certain embodiments, the human has an age in a range of from about 0 months to about 6 months old, from about 6 to about 12 months old, from about 6 to about 18 months old, from about 18 to about 36 months old, from about 1 to about 5 years old, from about 5 to about 10 years old, from about 10 to about 15 years old, from about 15 to about 20 years old, from about 20 to about 25 years old, from about 25 to about 30 years old, from about 30 to about 35 years old, from about 35 to about 40 years old, from about 40 to about 45 years old, from about 45 to about 50 years old, from about 50 to about 55 years old, from about 55 to about 60 years old, from about 60 to about 65 years old, from about 65 to about 70 years old, from about 70 to about 75 years old, from about 75 to about 80 years old, from about 80 to about 85 years old, from about 85 to about 90 years old, from about 90 to about 95 years old or from about 95 to about 100 years old. In embodiments, the subject is a non-human animal, and therefore disclosure pertains to veterinary use. In a specific embodiment, the non-human animal is a household pet. In another specific embodiment, the non- human animal is a livestock animal. In embodiments, the livestock animal Is selected from pigs, hogs, calves, cows, steers, horses, lambs, sheep, turkeys, ducks, and chicken. Kits The disclosure provides kits that can simplify the administration of any agent described herein. An illustrative kit of the disclosure comprises any composition described herein in unit dosage form. In embodiments, the unit dosage form is a container, such as a pre-filled syringe, which can be sterile, containing any agent described herein and a pharmaceutically acceptable carrier, diluent, excipient, or vehicle. The kit can further comprise a label or printed instructions instructing the use of any agent described herein. The kit may also include a lid speculum, topical anesthetic, and a cleaning agent for the administration location. The kit can also further comprise one or more additional agent described herein. In embodiments, the kit comprises a container containing an effective amount of a composition of the disclosure and an effective amount of another composition, such those described herein. Any aspect or embodiment described herein can be combined with any other aspect or embodiment as disclosed herein. The disclosure will be further described in the following examples, which do not limit the scope of the disclosure described in the claims. EXAMPLES The examples herein are provided to illustrate advantages and benefits of the present disclosure and to further assist a person of ordinary skill in the art with preparing or using the (S)-sec-butyl 2-(3-(4-(2- (diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate prodrugs of the present disclosure. The examples herein are also presented in order to more fully illustrate the preferred aspects of the present disclosure. The examples should in no way be construed as limiting the scope of the present disclosure, as defined by the appended claims. The examples can include or incorporate any of the variations, aspects or embodiments of the present disclosure described above. The variations, aspects or embodiments described above may also further each include or incorporate the variations of any or all other variations, aspects or embodiments of the present disclosure.

[0007] Example 1: Synthesis of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate prodrugs General Scheme 1 NO II OI General Scheme 3

[0008] General scheme for converting compounds of the disclosure from iodide salts to chloride salts: OClO I R O N I Amberlite-IRA-900 RESIN (15 g) was packed in glass column and was eluted with Acetonitrile to remove colour impurities. A solution of iodide salt 1 (0.15 g, 1 eq.) in acetonitrile (30 ml) was passed through a column. The flow rate was maintained dropwise to collect fractions. The desired fractions were then concentrated and dried to afford the chloride. A) Synthesis of compound 2007 (chloride of compound 1007):

[0009] To a solution of ethanol 1 (1.0 g, 31.25 mmol) in DCM (20 mL) was added pyridine (10 mL, 78.15 mmol) at 0 °C. It was followed by the dropwise addition of chloromethyl chloroformate (3.4 mL, 37.5 mmol). The reaction was stirred overnight at room temperature. After completion, reaction mixture was washed with sodium bicarbonate, 2N HCl, water and compound were extracted with DCM to afford chloromethyl ethyl carbonate 3 (680 mg). ESI-MS (C4H7ClO3), no ionisation observed. Step 2: Synthesis of ethyl (iodomethyl) carbonate (4): To a solution of chloromethyl ethyl carbonate 3 (2.6 g, 24.0 mmol, 1 eq) in acetone (30 mL) was added sodium iodide (10.7 g, 72.0 mmol, 3 eq). The reaction was stirred overnight at room temperature. After completion, reaction mixture was filtered off, filtrate was concentrated. Crude was purified using 100-200 mesh silica gel and 5% ethyl acetate in hexanes as eluent to afford ethyl (iodomethyl) carbonate 4 (1.5 g, 83.3%). ESI-MS (C4H7IO3),no ionisation observed. Step 3: (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N- (((ethoxycarbonyl)oxy)methyl)-N,N-diethylethan-1-aminium iodide (3007): To a stirred solution of (S)- sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate (0.15 g, 0.21 mmol, 1 eq.) in sealed tube in acetonitrile (1 ml) was added ethyl (iodomethyl) carbonate 4 (0.075 g, 0.32 mmol, 1.5 eq). The reaction mixture was stirred at room temperature for 3 h. After completion of reaction, added diethyl ether to the reaction mixture, obtained precipitates were filtered off and dried. Washed with n-pentane: diethyl ether and dried under vacuum to obtain (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N-(((ethoxycarbonyl)oxy) methyl)-N, N-diethylethan-1-aminium iodide 3007 (110 mg, 55%). ESI-MS (C31H38I2NO8+),805.7 observed.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44-7.40 (m, 2H), 7.35-7.30 (m, 1H), 5.52 (s, 2H), 4.80-4.74 (m, 1H), 4.40-4.37 (m, 2H), 4.30-4.23 (m, 2H), 4.01-3.97 (m, 4H), 3.72-3.62 (m, 4H), 1.53-1.43 (m, 2H), 1.39-1.34 (m, 6H), 1.29-1.25 (m, 2H), 1.15- 1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (t, 3H). HPLC- 95.56%. Step 4: (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N- (((ethoxycarbonyl)oxy) methyl)-N, N-diethylethan-1-aminium chloride (2007): Amberlite-IRA-900 RESIN (11 g) was packed in glass column and was eluted with Acetonitrile to remove colour impurities. A solution of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N-(((ethoxycarbonyl)oxy) methyl)-N, N-diethylethan-1-aminium iodide 3007 (0.11 g, 0.11 mmol, 1 eq.) in acetonitrile (30 ml) was passed through a column bed of amberlite-IRA-900 RESIN (15 g). The flow rate was maintained dropwise to collect fractions. The desired fractions were concentrated and dried to afford (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N- (((ethoxycarbonyl)oxy) methyl)-N,N-diethylethan-1-aminium chloride (2007) (0.062 g, 62%) as an off-white solid. ESI-MS (C31H38I2NO8+), 805.7 observed.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44-7.40 (m, 2H), 7.35-7.30 (m, 1H), 5.52 (s, 2H), 4.80-4.73 (m, 1H), 4.40-4.37 (m, 2H), 4.30-4.23 (q, 2H), 4.01-3.98 (m, 4H), 3.68-3.61 (m, 4H), 1.53-1.43 (m, 2H), 1.39-1.34 (m, 6H), 1.29-1.25 (m, 2H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (t, 3H). HPLC- 93.41%. Mass spectra of compound 2007 are shown in FIGS.1A and 1B. B) Synthesis of 2002 (chloride of compound 1002): Step 1: Synthesis of chloromethyl isopropyl carbonate (3): To a solution of propan-2-ol 1 (1.5 mL, 20.0 mmol) in dry DCM (20 mL) was added chloromethyl chloroformate, 2 (2.3 mL, 26.0 mmol) dropwise at 0 ℃ and inert atmosphere. Then, pyridine (4.0 mL, 40.0 mmol) was added to the reaction mixture and reaction mixture was stirred at room temperature for 16 h. After completion of the reaction, reaction mixture was quenched by 2N HCl and diluted with water (200 mL), extracted with DCM (2 X 150 mL), combined organic layer was washed with water (150 mL), sodium bicarbonate solution (100 mL) dried over sodium sulfate and concentrated to afford chloromethyl isopropyl carbonate 590 mg (3). ESI-MS (C5H9ClO3) No ionisation observed.1H NMR (300 MHz, DMSO-d6); 5.87 (s, 2H), 4.89-4.81 (m, 1H), 1.27-1.19 (m, 6H). Step 2: Synthesis of iodomethyl isopropyl carbonate (4): To a solution of chloromethyl isopropyl carbonate 3 (2.6 g, 24.0 mmol, 1 eq) in acetone (30 mL) was added sodium iodide (10.7 g, 72.0 mmol, 3 eq). The reaction was stirred overnight at room temperature. After completion, reaction mixture was filtered off, filtrate was concentrated. Crude was purified using 100-200 mesh silica gel and 5% Ethyl acetate in hexanes as eluent to afford iodomethyl isopropyl carbonate 4 (1.5 g, 83.3%). ESI-MS (C5H9IO3)No ionisation observed.1H NMR (300 MHz, DMSO-d6); 5.87 (s, 2H), 4.89-4.81 (m, 1H), 1.27-1.19 (m, 6H). Step 3: (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N- diethyl-N-(((isopropoxycarbonyl)oxy)methyl)ethan-1-aminium iodide (5; Compound 3002): To a stirred solution of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate (0.15 g, 0.21 mmol, 1 eq.) in sealed tube in acetonitrile (1 ml) was added iodomethyl isopropyl carbonate 4 (0.065 g, 0.32 mmol, 1.5 eq). The reaction mixture was stirred at room temperature for 3 h. After completion of reaction, added diethyl ether to the reaction mixture, obtained precipitates were filtered off and dried. Washed with n-pentane: diethyl ether and dried under vacuum to afford (S)-2-(4-(2-(2-(sec-butoxy)-2- oxoethyl)-benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethyl-N- (((isopropoxycarbonyl)oxy)methyl)ethan-1-aminium iodide 5 (Compound 3002) (160 mg, 79%). ESI-MS (C32H40I2NO8+),819.7 observed.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44-7.40 (m, 2H), 7.35-7.30 (m, 1H), 5.52 (s, 2H), 4.92-4.84 (m, 1H), 4.80-4.74 (m, 1H), 4.40-4.37 (m, 2H), 4.03- 3.98 (m, 4H), 3.68-3.63 (m, 4H), 1.50-1.43 (m, 2H), 1.38-1.34 (m, 6H), 1.29-1.27 (m, 6H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (t, 3H). HPLC 93.28%. Step 4: (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N- diethyl-N-(((isopropoxycarbonyl)oxy)methyl)ethan-1-aminium chloride (2002): A solution of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N- diethyl-N-(((isopropoxycarbonyl)oxy)methyl)ethan-1-aminium iodide 5 (Compound 3002) (0.16 g, 0.17 mmol, 1 eq.) in acetonitrile (45 ml) was passed through a column bed of amberlite-IRA-900 RESIN (15 g). The desired fractions were concentrated and dried to afford (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethyl-N-(((isopropoxycarbonyl)oxy)methyl)ethan-1- aminium chloride (2002) (0.11 g, 76%) as a yellow solid. ESI-MS (C32H40I2NO8+), 819.7 observed.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44-7.40 (m, 2H), 7.35-7.30 (m, 1H), 5.53 (s, 2H), 4.92-4.82 (m, 1H), 4.80-4.72 (m, 1H), 4.40-4.37 (m, 2H), 4.01-3.98 (m, 4H), 3.68-3.61 (m, 4H), 1.55-1.48 (m, 2H), 1.46-1.38 (m, 6H), 1.34-1.29 (m, 6H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (t, 3H). HPLC- 90.75%. Mass spectra of compound 2002 are shown in FIGS.2A and 2B. C) Synthesis of compound 2011 (chloride of compound 1011): Step 1: Synthesis of chloromethyl (2-methoxyethyl) carbonate (3): To a solution of 2-methoxyethan-1-ol 1 (5 g, 66.0 mmol, 1 eq) in dry DCM (50 mL) was added chloromethyl chloroformate (9.1 mL, 99.0 mmol, 1.5 eq) drop-wise at 0 ℃ and inert atmosphere. Then, pyridine (17.4 mL, 198.0 mmol, 3.0 eq) was added to the reaction mixture and stirred at room temperature for 16 h. After completion of the reaction, reaction mixture was quenched by 2N HCl and diluted with water (200 mL), extracted with DCM (2 X 150 mL), combined organic layer was washed with water (150 mL), sodium bicarbonate solution (100 mL) dried over sodium sulfate and concentrated to afford chloromethyl (2- methoxyethyl) carbonate 3 (3.5 g). ESI-MS (C5H9ClO4), No ionisation observed.1H NMR (300 MHz, DMSO- d6); 5.90 (s, 2H), 4.32-4.29 (d, J= 9 Hz, 2H), 3.56-3.54 (d, J=6 Hz, 2H), 3.26 (s, 3 H). Step-2: Synthesis of iodomethyl (2-methoxyethyl) carbonate (4): To a solution of chloromethyl (2-methoxyethyl) carbonate 3 (1.5 g, 9.80 mmol, 1 eq) in acetone (30 mL) was added sodium iodide (4.41 g, 29.41 mmol, 3 eq). The reaction was stirred overnight at room temperature. After completion, reaction mixture was filtered off, filtrate was concentrated. Crude was purified using 100- 200 mesh silica gel and 5% ethyl acetate in hexanes as eluent to afford iodomethyl (2-methoxyethyl) carbonate 4 (1.3 g, 59.09%). ESI-MS (C5H9ClO4), No ionisation was observed. Step-3: Synthesis of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N,N-diethyl-N-((((2-methoxyethoxy)carbonyl)oxy)methyl)ethan-1-aminium iodide (5; Compound 3011): To a stirred solution of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate (0.2 g, 0.28 mmol, 1 eq.) in seal tube in acetonitrile (2 ml) was added iodomethyl (2-methoxyethyl) carbonate 4 (0.090 g, 0.34 mmol, 1.2 eq). The reaction mixture was stirred at room temperature for 3 h. After completion of reaction, added diethyl ether to the reaction mixture, obtained precipitates were filtered off and dried. Washed with n-pentane: diethyl ether and dried under vacuum to afford (S)-2-(4-(2-(2-(sec-butoxy)-2- oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethyl-N-((((2-methoxyethoxy)carbonyl)oxy) methyl)ethan-1-aminium iodide 5 (Compound 3011) (150 mg, 54.7%). ESI-MS (C32H40I2NO9+), 835.6 observed.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.45-7.40 (m, 2H), 7.35-7.30 (m, 1H), 5.54 (s, 2H), 4.80-4.74 (m, 1H), 4.39-4.33 (m, 4H), 4.01-3.97 (m, 4H), 3.69-3.57 (m, 6H), 3.26 (s, 3H), 1.50-1.43 (m, 2H), 1.39-1.34 (m, 6H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (t, 3H). HPLC- 95.48%. Step-4: (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N- diethyl-N-((((2-methoxyethoxy)carbonyl)oxy)methyl)ethan-1-aminium chloride (2011): A solution of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethyl- N-((((2-methoxyethoxy)carbonyl)oxy)methyl)ethan-1-aminium iodide 5 (Compound 3011) (0.15 g, 0.15 mmol, 1 eq.) in acetonitrile (30 ml) was passed through a column bed of amberlite-IRA-900 RESIN (15 g). The desired fractions were concentrated and dried to afford (S)-2-(4-(2-(2-(sec-butoxy)-2- oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethyl-N-((((2- methoxyethoxy)carbonyl)oxy)methyl)ethan-1-aminium chloride (2011) (0.11 g, 81.4%) as a yellow solid. ESI- MS (C32H40I2NO9+),835.6 observed.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.45- 7.40 (m, 2H), 7.35-7.30 (m, 1H), 5.54 (s, 2H), 4.80-4.74 (m, 1H), 4.39-4.33 (m, 4H), 4.01 (brs, 4H), 3.69- 3.62 (m, 4H), 3.60-3.57 (m, 2H), 3.26 (s, 3H), 1.53-1.43 (m, 2H), 1.39-1.34 (m, 6H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (t, 3H). HPLC- 93.99%. Mass spectra of compound 2011 are shown in FIGS.3A and 3B. D) Synthesis of compound 2006 (chloride of compound 1006): Step 1: Synthesis of chloromethyl methyl carbonate (3): To a solution of methanol (1.0 g, 31.25 mmol) in DCM (20 mL) was added pyridine (10 mL, 78.15 mmol) at 0 °C. It was followed by the dropwise addition of chloromethyl chloroformate (3.4 mL, 37.5 mmol). The reaction was stirred overnight at room temperature. After completion, reaction mixture was washed with sodium bicarbonate, 2N HCl, water and compound was extracted with DCM to afford chloromethyl methyl carbonate 3 (680 mg). ESI-MS (C3H5ClO3), no ionisation observed. Step 2: Synthesis of iodomethyl methyl carbonate (4): To a solution of 3 (0.5 g, 4.03 mmol, 1 eq) in acetone (5 mL) was added sodium iodide (1.8 g, 12.09 mmol, 3 eq). The reaction was stirred overnight at room temperature. After completion, reaction mixture was filtered off, filtrate was concentrated. Crude was purified using 100-200 mesh silica gel and 5% ethyl acetate in hexanes as eluent to afford iodomethyl methyl carbonate 4 (306 mg, 35.17%). ESI-MS (C3H5IO3), no ionisation observed. Step-3: Synthesis of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N,N-diethyl-N-(((methoxycarbonyl)oxy)methyl)ethan-1-aminium iodide (5; Compound 3006): To a stirred solution of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2- yl)acetate (0.13 g, 0.18 mmol, 1 eq.) in a sealed tube in acetonitrile (2 ml) was added iodomethyl methyl carbonate 4 (0.060 g, 0.28 mmol, 1.5 eq). The reaction mixture was stirred at room temperature for 3 h. After completion of reaction, added diethyl ether to the reaction mixture, obtained precipitates were filtered off and dried. Washed with n-pentane: diethyl ether and dried under vacuum to afford (S)-2-(4-(2-(2-(sec-butoxy)-2- oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethyl-N-(((methoxycarbonyl)oxy)methyl)ethan- 1-aminium iodide 5 (Compound 3006) (110 mg, 75%). ESI-MS (C30H36I2NO8+), 791.6 observed1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44-7.40 (m, 2H), 7.35-7.30 (m, 1H), 5.52 (s, 2H), 4.80-4.73 (m, 1H), 4.40-4.37 (m, 2H), 4.01-3.97 (m, 4H), 3.85 (s, 3H), 3.69-3.61 (m, 4H), 1.53-1.43 (m, 2H), 1.39-1.34 (m, 6H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (t, 3H). HPLC- 92.61%. Step-4: Synthesis of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N,N-diethyl-N-(((methoxycarbonyl)oxy)methyl)ethan-1-aminium chloride (2006): A solution of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethyl- N-(((methoxycarbonyl)oxy)methyl)ethan-1-aminium iodide 5 (Compound 3006) (0.11 g, 0.11 mmol, 1 eq.) in acetonitrile (10 ml) was passed through a column bed of amberlite-IRA-900 RESIN (15 g). The desired fractions were concentrated and dried to afford (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3- carbonyl)-2,6-diiodophenoxy)-N, N-diethyl-N-(((methoxycarbonyl)oxy)methyl)ethan-1-aminium chloride (2006) (0.06 g, 66.7%) as a yellow solid. ESI-MS (C30H36I2NO8+), observed 791.6.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.45-7.40 (m, 2H), 7.36-7.30 (m, 1H), 5.52 (s, 2H), 4.80-4.74 (m, 1H), 4.40-4.36 (m, 2H), 4.01-3.98 (m, 4H), 3.85 (s, 3H), 3.69-3.62 (m, 4H), 1.50-1.43 (m, 2H), 1.39- 1.34 (m, 6H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (t, 3H). HPLC-91.32%. Mass spectra of compound 2006 are shown in FIGS.4A and 4B. E) Synthesis of compound 2003 (chloride of compound 1003): ep y ess o uy c oo e y ca o ae To a solution of n-butanol 1 (4.3 mL, 58.14 mmol, 2.5 eq) in DCM (30 mL) was added pyridine (5.1 mL, 58.13 mmol, 2.5 eq) at 0 °C. It was followed by the dropwise addition of chloromethyl chloroformate (3.0 g, 23.25 mmol, 1.0 eq). The reaction was stirred overnight at room temperature. After completion, reaction mixture was washed with sodium bicarbonate, 2N HCl, water and compound was extracted with DCM to afford butyl (chloromethyl) carbonate 3 (3.01 g, 77.7%). ESI-MS (C6H11ClO3), no ionisation observed. Step 2: Synthesis of butyl (iodomethyl) carbonate (4): To a solution of butyl (chloromethyl) carbonate 3 (3.0 g, 18.00 mmol, 1.0 eq) in acetone (30 mL) was added sodium iodide (8.0 g, 54.02 mmol, 3 eq). The reaction was stirred overnight at room temperature. After completion, reaction mixture was filtered off, filtrate was concentrated. Crude was purified using 100-200 mesh silica gel and 4% ethyl acetate in hexanes as eluent to afford butyl (iodomethyl) carbonate 4 (2.35 g, 50.42%). ESI-MS (C6H11IO3), no ionisation observed. Step 3: Synthesis of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N-(((butoxycarbonyl)oxy)methyl)-N,N-diethylethan-1-aminium iodide (5; Compound 3003): To a stirred solution of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate (0.13 g, 0.18 mmol, 1 eq.) in in acetonitrile (2 ml) a sealed tube was added butyl (iodomethyl) carbonate 4 (0.072 g, 0.28 mmol, 1.5 eq). The reaction mixture was stirred at room temperature for 3 h. After completion of reaction, added diethyl ether to the reaction mixture, obtained precipitates were filtered off and dried. Washed with n-pentane: diethyl ether and dried under vacuum to afford (S)-2-(4-(2-(2-(sec-butoxy)-2- oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N-(((butoxycarbonyl)oxy)methyl)-N,N-diethylethan-1- aminium iodide 5 (Compound 3003) (100 mg, 56%). ESI-MS (C33H42I2NO8+), observed 833.7,1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44-7.40 (m, 2H), 7.35-7.30 (m, 1H), 5.52 (s, 2H), 4.80- 4.74 (m, 1H), 4.40-4.37 (m, 2H), 4.24-4.20 (t, 2H), 4.01-3.97 (m, 4H), 3.68-3.61 (m, 4H), 1.68-1.58 (m, 2H), 1.50-1.43 (m, 6H), 1.38-1.34 (m, 8H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.91-0.86 (m, 3H), 0.81-0.76 (m, 3H). Step 4: Synthesis of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N-(((butoxycarbonyl)oxy)methyl)-N,N-diethylethan-1-aminium chloride (2003): A solution of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N- (((butoxycarbonyl)oxy) methyl)-N,N-diethylethan-1-aminium iodide 5 (Compound 3003) (0.11 g, 0.10 mmol, 1 eq.) in acetonitrile (10 ml) was passed through a column bed of amberlite-IRA-900 RESIN (15 g). The desired fractions were concentrated and dried to afford (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran- 3-carbonyl)-2,6-diiodophenoxy)-N-(((butoxycarbonyl)oxy)methyl)-N,N-diethylethan-1-aminium chloride (2003) (0.055 g, 61.0%) as a off-white solid. ESI-MS (C33H42I2NO8+), observed 833.8.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44-7.40 (m, 2H), 7.35-7.30 (m, 1H), 5.52 (s, 2H), 4.80-4.73 (m, 1H), 4.40-4.37 (m, 2H), 4.24-4.20 (t, 2H), 4.01-3.98 (m, 4H), 3.68-3.61 (m, 4H), 1.68-1.58 (m, 2H), 1.50-1.43 (m, 6H), 1.38-1.34 (m, 8H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.91-0.86 (m, 3H), 0.81-0.76 (m, 3H). HPLC- 96.22%. Mass spectra of compound 2003 are shown in FIGS.5A and 5B. F) Synthesis of compound 2012 (chloride of compound 1012), compound 2013 (chloride of compound 1013), and compound 2015 (chloride of compound 1015) Synthesis of compound 2012 (chloride of compound 1012), compound 2013 (chloride of compound 1013), and compound 2015 (chloride of compound 1015) were conducted by making appropriate changes in starting material and using the same reaction conditions as used to prepare the compounds in the General Scheme and in Examples A-E. Synthesis of compound 2012 (chloride of compound 1012): 2-(4-(2-(2-((S)-sec-butoxy)-2- oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N-((((S)-sec-butoxycarbonyl)oxy)methyl)-N,N- diethylethan-1-aminium chloride (2012). ESI-MS (C33H42I2NO8+Cl-), observed 834.1.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.72 (d, 1H), 7.45-7.41 (m, 2H), 7.35-7.30 (m, 1H), 5.54 (s, 2H), 4.78-4.72 (m, 2H), 4.39 (s, 2H), 4.01-3.90 (brs, 4H), 3.65 (d, 4H), 1.63-1.61 (m, 2H), 1.50-1.46 (m, 2H), 1.36(t, 6H), 1.26 (d, 3H), 1.14 (d, 3H), 0.89 (t, 3H), 0.78 (t, 3H). HPLC- 95.16%. Mass spectra of compound 2012 are shown in FIGS.10A and 10B. G). Synthesis of compound 2013 (chloride of compound 1013): S)-2-(4-(2-(2-(sec-butoxy)-2- oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethyl-N-(((propoxycarbonyl)oxy)methyl)ethan-1- aminium chloride (2013). ESI-MS (C32H40I2NO8+Cl-), observed 819.6.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.72 (d, 1H), 7.43-7.40 (m, 2H), 7.35-7.32 (m, 1H), 5.53 (s, 2H), 4.80-4.76 (m, 1H), 4.39 (s, 2H), 4.18 (t, 2H), 4.01 (s, 4H), 3.65 (d, 4H), 1.68-1.63 (m, 2H), 1.51-1.46 (m, 2H), 1.36 (t, 6H), 1.14 (d, 3H), 0.91 (t, 3H), 0.78 (t, 3H). HPLC- 94.96%. Mass spectra of compound 2013 are shown in FIGS.11A and 11B. H). Synthesis of compound 2015 (chloride of compound 1015): 2-(4-(2-(2-((S)-sec-butoxy)-2- oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N-((((R)-sec-butoxycarbonyl)oxy)methyl)-N,N- diethylethan-1-aminium chloride (2015). ESI-MS (C33H42I2NO8+Cl), observed 834.1.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.72 (d, 1H), 7.45-7.43 (m, 2H), 7.35-7.32 (m, 1H), 5.54 (s, 2H), 4.78-4.72 (m, 2H), 4.39 (s, 2H), 4.01 (s, 4H), 3.64 (d, 4H), 1.65-1.61 (m, 2H), 1.59-1.46 (m, 2H), 1.39-1.34 (m, 6H), 1.26 (d, 3H), 1.14 (d, 3H), 0.89 (t, 3H), 0.79 (t, 3H). HPLC- 95.70%. Mass spectra of compound 2015 are shown in FIGS.13A and 13B. I) Synthesis of compound 3009 (iodide of compound 1009): St To a solution of phenylacetic acid (1.0 g, 7.35 mmol) in DCM: H2O (1:1, 40 mL) was added sodium bicarbonate (3.0 g, 27.9 mmol) followed by dropwise addition of tetra-butyl-ammonium-hydrogen-sulfate (TBAHS) (0.3 g, 0.73 mmol) at 0 °C. Then, chloromethyl chlorosulfate (0.84 mL, 8.4 mmol) was added. The reaction mixture was stirred at room temperature for overnight. After completion, reaction mixture was washed with 10% sodium bicarbonate solution, dried over anhyd. Na2SO4 and concentrated under vacuum and at temp below 30 °C. The compound was purified with 6% ethyl acetate in hexane to afford chloromethyl 2-phenylacetate 2 (650 mg). ESI-MS (C9H9ClO2) 184.03, no ionisation observed. Step 2: Synthesis of iodomethyl 2-phenylacetate (3): To a stirred solution of chloromethyl 2-phenylacetate 2 (0.7 g, 3.8 mmol) in dry acetone (20 mL) was added sodium iodide (2.2 g, 15.0 mmol) and the reaction mixture was stirred for 4 hrs. After completion, solid precipitate was filtered off and washed with acetone. Filtrate was dried to afford iodomethyl 2-phenylacetate 3 (0.8 g). ESI-MS (C9H9IO2), 275.96, no ionisation observed. Step 3: Synthesis of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N,N-diethyl-N-((2-phenylacetoxy)methyl)ethan-1-aminium iodide (3009): To a stirred solution of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2- yl)acetate (0.25 g, 0.35 mmol, 1 eq.) in a sealed tube in DCM (2 ml) was added iodomethyl 2-phenylacetate 3 (0.053 g, 0.53 mmol, 1.5 eq) at 0 ºC. Temperature was raised from 0 ºC to 25 ºC over 1 hr. Submitted aliquot for HPLC and mass analysis. After completion of reaction, removed DCM under reduced pressure and washed the residue with diethyl ether and ethyl acetate. Dried under vacuum to afford (S)-2-(4-(2-(2- (sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethyl-N-((2-phenylacetoxy) methyl)ethan-1-aminium iodide (2009) (50 mg, 15%) as a yellow solid. ESI-MS (C36H40I2NO7+), observed 851.5.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 1H), 7.74-7.71 (d, 1H), 7.45-7.40 (m, 2H), 7.35-7.30 (m, 6H), 5.49 (s, 2H), 4.80-4.74 (q, 1H), 4.36-4.33 (brs, 2H), 4.01-3.93 (m, 6H), 3.62-3.56 (m, 4H), 1.53- 1.43 (m, 2H), 1.34-1.29 (m, 7H), 1.19-1.12 (m, 4H), 0.80-0.75 (t, 3H). HPLC 91.04%. Mass spectra of compound 2009 are shown in FIGS.6A and 6B. J) Synthesis of compound 2001 (chloride of compound 1001): Step 1: Synthesis of iodomethyl acetate (2): To a stirred solution of chloromethyl acetate 1 (2.0 g, 18.51 mmol, 1.0 eq) in dry acetone (50 mL) was added sodium iodide (7.0 g, 46.2 mmol, 2.5 eq) and the reaction mixture was stirred for 4 hrs. After completion, solid precipitate was filtered off and washed with acetone. Concentrated the filtrate and added DCM to the residue again, thus precipitated solid was filtered off. Filtrate was concentrated to afford iodomethyl acetate (1.2 g, 32%). ESI-MS (C3H5IO2), no ionisation observed. Step 2: Synthesis of (S)-N-(acetoxymethyl)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3- carbonyl)-2,6-diiodophenoxy)-N,N-diethylethan-1-aminium iodide (3; Compound 3001): To a stirred solution of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2- yl)acetate (0.17 g, 0.24 mmol, 1 eq.) in a sealed tube in ACN (2 ml) was added iodomethyl acetate 2 (0.073 g, 0.36 mmol, 1.5 eq) at 0 ºC. Stirred for 10 min at 25 ºC. After completion of reaction, added diethyl ether and filtered off the precipitated solid. Dried under vacuum to afford (S)-N-(acetoxymethyl)-2-(4-(2-(2-(sec- butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethylethan-1-aminium iodide 3 (170 mg, 53%). ESI-MS (C30H36I2NO7+), observed 775.7.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44-7.40 (m, 2H), 7.35-7.31 (m, 1H), 5.45 (s, 2H), 4.80-4.74 (m, 1H), 4.39-4.35 (m, 2H), 4.01- 3.97 (m, 4H), 3.66-3.60 (m, 4H), 3.41-3.32 (m, 1H), 2.26 (s, 3H), 2.07 (s, 1H), 1.53-1.43 (m, 2H), 1.38-1.33 (m, 6H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (m, 3H). HPLC- 89.16% Step 3: Synthesis of (S)-N-(acetoxymethyl)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3- carbonyl)-2,6-diiodophenoxy)-N,N-diethylethan-1-aminium chloride (2001): A solution of (S)-N-(acetoxymethyl)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N,N-diethylethan-1-aminium iodide 3 (Compound 3001) (0.17 g, 0.018 mmol, 1 eq.) in acetonitrile (10 ml) was passed through a column bed of amberlite-IRA-900 RESIN (15 g). The desired fractions were concentrated and dried to afford (S)-N-(acetoxymethyl)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N, N-diethylethan-1-aminium chloride (2001) (0.070 g, 70.0%) as a off-white solid. ESI-MS (C30H36I2NO7+), observed 775.7.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44-7.40 (m, 2H), 7.35-7.31 (m, 1H), 5.45 (s, 2H), 4.80-4.74 (m, 1H), 4.39-4.35 (m, 2H), 4.01-3.97 (m, 4H), 3.66-3.60 (m, 4H), 3.41-3.32 (m, 1H), 2.26 (s, 3H), 2.07 (s, 1H), 1.53-1.43 (m, 2H), 1.38-1.33 (m, 6H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (m, 3H). HPLC- 96.12%. Mass spectra of compound 2001 are shown in FIGS.7A and 7B. K) Synthesis of compound 2005 (chloride of compound 1005): Step 1: Synthesis of chloromethyl dimethylcarbamate (3): To a stirred solution of dimethylamine hydrochloride 2 (4.7 g, 58.13 mmol, 1.5 eq) in dry ACN (50 mL) was added DIPEA (21 mL, 116.27 mmol, 3.0 eq) and stirred at 0 ºC for 10 min, and added chloromethyl chloroformate 1 (5.0 g, 38.75 mmol, 1.0 eq). The reaction mixture was stirred for 2 hrs at 25 ºC. After completion, diluted the reaction mixture with NaHCO3 solution and ethyl acetate. Separated organic layer was dried over Na2SO4and concentrated under reduced pressure to afford chloromethyl dimethylcarbamate (1.0 g, 13%). ESI-MS (C4H8ClNO2), no ionisation observed. Step 2: Synthesis of iodomethyl dimethylcarbamate (4): To a stirred solution of chloromethyl dimethylcarbamate 3 (700 mg, 51.0 mmol, 1.0 eq) in dry acetone (50 mL) was added sodium iodide (2.0 g, 12.75 mmol, 2.5 eq), and the reaction mixture was stirred for 4 hrs. After completion, solid precipitate was filtered off and washed with acetone. Concentrated the filtrate and added DCM to the residue again, thus precipitated solid was filtered off. Filtrate was concentrated under reduced pressure. Crude was purified using 100-200 mesh silica gel and 10% EtOAc in hexanes to afford iodomethyl dimethylcarbamate 4 (250 mg, 21.3%). ESI-MS (C4H8INO2), no ionisation observed. Step 3: Synthesis of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N-(((dimethylcarbamoyl)oxy)methyl)-N,N-diethylethan-1-aminium iodide (5; Compound 3005): To a stirred solution of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2- yl)acetate (API) (0.2 g, 0.28 mmol, 1 eq.) in a sealed tube in DCM (1 ml) was added compound 4 (0.070 g, 0.31 mmol, 1.1 eq) at 0 ºC. Stirred for 10 min at 25 ºC. After completion of reaction, concentrated the reaction mixture under vacuum. Added diethyl ether to the residue and filtered off the precipitates and dried to afford (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)-benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N- (((dimethylcarbamoyl)oxy)methyl)-N,N-diethylethan-1-aminium iodide 5 (Compound 3005) (70 mg, 27%). ESI-MS (C31H39I2N2O7+) observed 804.6.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.43-7.40 (m, 2H), 7.35-7.30 (m, 1H), 5.44 (s, 2H), 4.80-4.71 (m, 1H), 4.40-4.36 (m, 2H), 4.01 (s, 2H), 3.96-3.93 (m, 2 H), 3.64-3.56 (m, 4H), 3.32 (s, 3H), 2.99 (s, 3H), 1.50-1.43 (m, 2H), 1.38-1.34 (m, 6H), 1.15- 1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (m, 3H). HPLC- 74.33% Step 4: Synthesis of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N-(((dimethylcarbamoyl)oxy) methyl)-N,N-diethylethan-1-aminium chloride (2005): A solution of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N- (((dimethylcarbamoyl)oxy) methyl)-N,N-diethylethan-1-aminium iodide 5 (Compound 3005) (0.07 g, 0.074 mmol, 1 eq.) in acetonitrile (10 ml) was passed through a column bed of amberlite-IRA-900 RESIN (15 g). The desired fractions were concentrated and dried to afford (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N-(((dimethylcarbamoyl)oxy) methyl)-N,N-diethylethan-1- aminium chloride (2005) (0.035 g, 52.0%) as a yellow solid. ESI-MS (C31H39I2N2O7+) observed 804.6.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.45-7.40 (m, 2H), 7.35-7.31 (m, 1H), 5.44 (s, 2H), 4.80-4.73 (m, 1H), 4.40-4.36 (m, 2H), 4.01 (s, 2H), 3.96-3.93 (m, 2H), 3.63-3.57 (m, 4H), 3.17 (s, 3H), 3.15 (s, 3H), 1.50-1.43 (m, 2H), 1.39-1.34 (m, 6H), 1.15-1.13 (d, J= 6 Hz, 3H), 0.81-0.76 (m, 3H). HPLC- 90.10%. Mass spectra of compound 2005 are shown in FIGS.8A and 8B.

[0010] L) Synthesis of compound 2014 (chloride of compound 1014): To a solution of hexanoic acid 1 (3 gm, 25 mmol, 1 eq) in DCM (60 mL): (water 60 mL) was added NaHCO3 (7.8 gm, 75 mmol, 3 eq) at 0 °C. Then added TBASH (0.850 gm, 2.5 mmol, 0.1 eq), TBASH, at 0 °C It was followed by the drop wise addition of CMSCl (3 ml, 30 mmol, 1.2 eq). The reaction was stirred 3 hrs at room temperature. After completion, reaction mixture was washed with sodium bicarbonate, 1N HCl, water and compound was extracted with DCM to afford chloromethyl hexanoate (2) (3 g, 71.41 %). ESI-MS (C7H13ClO2), no ionisation observed.1H NMR (300 MHz, DMSO-δ6); 5.69 (s, 2H), 2.39-2.34 (t, 2H), 1.67-1.60, (m, 2H), 1.35-1.31 (t, 4H), 0.91-0.87 (t, 3H), Step-2: Synthesis of iodomethyl hexanoate (3): To a solution of chloromethyl hexanoate (2) (3 g, 11.7 mmol, 1 eq) in acetone (40 mL) was added sodium iodide (7 g, 46.8 mmol, 4 eq). The reaction was stirred 4-5 h at room temperature. After completion, reaction mixture was filtered off, filtrate was concentrated. Crude was purified using 60-120 mesh silica gel and 2% ethyl acetate in hexanes as eluent to afford iodomethyl hexanoate 3 (2.0 g, 41.6%). ESI-MS (C7H13IO2), Step-3: Synthesis of (5): (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N,N-diethyl-N-((hexanoyloxy)methyl)ethan-1-aminium iodide (5; Compound 3014) To a stirred solution of (S)-sec-butyl 2-(3-(4-(2-(diethylamino) ethoxy)-3,5-diiodobenzoyl) benzofuran-2- yl)acetate (API) (0.250 g, 0.3 mmol, 1 eq.) in DCM (2 ml) a sealed tube was added iodomethyl hexanoate 3 (0.115 g, 0.45 mmol, 1.5 eq). The reaction mixture was stirred at room temperature for 1.5 h. After completion of reaction, added diethyl ether to the reaction mixture, obtained precipitates were filtered off and dried. Washed with diethyl ether and dried under vacuum to (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3- carbonyl)-2,6-diiodophenoxy)-N,N-diethyl-N-((hexanoyloxy)methyl)ethan-1-aminium iodide 5 (Compound 3005) (100 mg, 35%). ESI-MS (C34H44I2NO7+), observed 832.14, Step-4: Synthesis of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6- diiodophenoxy)-N,N-diethyl-N-((hexanoyloxy)methyl)ethan-1-aminium chloride (2014): A solution of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethyl- N-((hexanoyloxy)methyl)ethan-1-aminium iodide 5 (Compound 3005) (0.100 g, 102 mmol, 1 eq.) in acetonitrile (5 ml) was passed through a column bed of amberlite-IRA-900 RESIN (15 g). The desired fractions were concentrated and dried to afford (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3- carbonyl)-2,6-diiodophenoxy)-N,N-diethyl-N-((hexanoyloxy)methyl)ethan-1-aminium chloride (2014) (0.075 g, 83.0%) as an off-white solid. ESI-MS (C34H44I2NO8+), observed 832.13,1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74 (d, J= 8.4 Hz, 1H), 7.43-7.40 (m, 2H), 7.45-7.40 (m, 2H), 7.34 (d, J= 7.8 Hz, 1H), 5.48 (s, 2H), 4.76-4.71 (m, 1H), 4.38-4.37 (m, 2H), 4.01-3.99 (m, 4H), 3.64-3.62 (m, 4H), 2.57-2.50 (m, 2H), 1.58- 1.56 (m, 3H), 1.50-1.48 (m, 2H), 1.48-1.37(m, 6H), 1.35-1.29 (m, 4H), 1.15 (d, J= 6.3 Hz, 3H), 0.85- 0.81(m, 6H) HPLC- 93.96%. Mass spectra of compound 2004 are shown in FIGS.12A and 12B. M) Synthesis of compound 2008 (chloride of compound 1008): Synthesis of (S)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N- ((butyryloxy)methyl)-N,N-diethylethan-1-aminium chloride (2008) was conducted by making appropriate change in starting material and using the same reaction condition as shown in examples I to L.

[0011] N) Synthesis of compound 2004 (chloride of compound 1004): To a stirred solution of benzyl alcohol (3 g, 27.78 mmol, 1 eq) in dry DCM (50 mL) was added pyridine (5.6 mL, 69.44 mmol, 2.5 eq) and stirred at 0 ºC for 10 min, and added chloromethyl chloroformate (6.28 g, 69.44 mmol, 2.5 eq). The reaction mixture was stirred for 16 hrs at 25 ºC. After completion, diluted the reaction mixture with NaHCO3 solution and DCM. Separated organic layer was dried over Na2SO4 and concentrated under reduced pressure. Crude was purified using 100-200 mesh silica gel and 10% EtOAc in hexanes as eluent to afford benzyl (chloromethyl) carbonate 3 (565 mg, 10%). ESI-MS (C9H9ClO3), no ionisation observed. Step 2: Synthesis of benzyl (iodomethyl) carbonate (4): To a stirred solution of benzyl (chloromethyl) carbonate 3 (1.8 g, 9.00 mmol, 1.0 eq) in dry acetone (50 mL) was added sodium iodide (4.0 g, 27.00 mmol, 3 eq), and the reaction mixture was stirred for 16 hrs. After completion, solid precipitate was filtered off and washed with acetone. Precipitated solid was filtered off. Filtrate was concentrated under reduced pressure. Crude was purified using 100-200 mesh silica gel and10% EtOAc in hexanes to afford benzyl (iodomethyl) carbonate 4 (1.5 g, 57.7%). ESI-MS (C9H9IO3), no ionisation observed. Step 3: Synthesis of (S)-N-((((benzyloxy)carbonyl) oxy) methyl)-2-(4-(2-(2-(sec-butoxy)-2- oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethylethan-1-aminium iodide (5; Compound 3004): To a stirred solution of (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5-diiodobenzoyl) benzofuran-2-yl) acetate (0.13 g, 0.18 mmol, 1 eq.) in a sealed tube in ACN (2 ml) was added benzyl (iodomethyl) carbonate 4 (0.080 g, 0.27 mmol, 1.5 eq) at 0 ºC. Stirred for 1 h at 25 ºC. After completion of reaction, added diethyl ether to the residue and filtered off the precipitates and dried to afford (S)-N-((((benzyloxy)carbonyl) oxy)methyl)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N- diethylethan-1-aminium iodide 5 (100 mg, 55%). ESI-MS (C36H40I2NO8+), observed 867.7,1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44- 7.30 (m, 8H), 5.55 (s, 2H), 5.28 (s, 2H), 4.80-4.73 (m, 1H), 4.40-4.36 (m, 2H), 4.01-3.98 (m, 4H), 3.68-3.62 (m, 4H), 3.41-3.31 (m, 2H), 1.50-1.43 (m, 2H), 1.38-1.33 (m, 6H), 1.30-1.06 (m, 5H), 0.81-0.76 (m, 3H). HPLC- 96.91% Step-4: Synthesis of (S)-N-((((benzyloxy)carbonyl) oxy) methyl)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethylethan-1-aminium chloride (2004): A solution of (S)-N-((((benzyloxy)carbonyl)oxy)methyl)-2-(4-(2-(2-(sec-butoxy)-2-oxoethyl)benzofuran-3- carbonyl)-2,6-diiodophenoxy)-N,N-diethylethan-1-aminium iodide 5 (Compound 3004) (0.1 g, 0.010 mmol, 1 eq.) in acetonitrile (20 ml) was passed through a column bed of amberlite-IRA-900 RESIN (15 g). The desired fractions were concentrated and dried to afford (S)-N-((((benzyloxy)carbonyl) oxy) methyl)-2-(4-(2- (2-(sec-butoxy)-2-oxoethyl) benzofuran-3-carbonyl)-2,6-diiodophenoxy)-N,N-diethylethan-1-aminium chloride (2004) (0.060 g, 66.0%) as a off-white solid. ESI-MS (C36H40I2NO8+), observed 867.8.1H NMR (300 MHz, DMSO-δ6); 8.16 (s, 2H), 7.74-7.71 (d, 1H), 7.44- 7.30 (m, 8H), 5.55 (s, 2H), 5.28 (s, 2H), 4.82-4.71 (m, 1H), 4.39-4.36 (m, 2H), 4.01 (brs, 4H), 3.66-3.64 (m, 4H), 3.41-3.31 (m, 2H), 1.52-1.43 (m, 2H), 1.36- 1.33 (m, 6H), 1.14-1.12 (d, J= 6 Hz, 3H), 0.81-0.75 (m, 3H). HPLC- 92.48%. Mass spectra of compound 2004 are shown in FIGS.9A and 9B.

[0012] Example 2: Ex-vivo results of plasma conversion: (S)-sec-butyl 2-(3-(4-(2-(diethylamino)ethoxy)-3,5- diiodobenzoyl)benzofuran-2-yl) acetate (Compound 1000) and prodrugs thereof of the disclosure Conversion of compounds 1002, 1003, 1005, 1007, and 1009 into (S)-sec-butyl 2-(3-(4-(2- (diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate (Compound 1000) was examined in rat plasma, and all were found to convert into Compound 1000 beginning at 0 minutes, with the majority of the compound converted to Compound 1000 after 15 minutes in most cases (Table 1). Table 1. Rat plasma conversion of compounds 1002, 1005, 1007 and 1009 Compound in 1002 1003 1005 1007 1009 HPLC 0 5 3 2 Conversion of compounds 1012 and 1015 to Compound 1000 was evaluated in rat, dog, and human plasma using the following protocol: Control sample was prepared by adding 100 µl of 100% acetonitrile to 47.5 µl of blank plasma, then 2.5 µl 10 mg / ml stock solution was added. Solution was vortexed for about 5 min and centrifuged for 10 min. Supernatant was analyzed by HPLC. Reaction Mixture was prepared by incubating 25 µl of stock solution (10 mg / ml) in 475 µl plasma at 37°C. 50 µl sample from the reaction mixture was taken out and immediately the reaction was stopped with 100 µl of 100% acetonitrile (0-minute sample).50 µl of reaction mixture was taken out at different time points (0, 5, 15, 30 min 1, 2, 4, 6 and 24hr) and the reaction was stopped with 100 µl of 100% acetonitrile. Solution was vortexed for about 5 min and centrifuged for 10 mins at 10,000 rpm (4°C). Supernatants were analyzed by HPLC. Complete conversion of the prodrugs to Compound 1000 was found to occur within 15-30 minutes in rat plasma, 2-4 hours in dog plasma, and within 30 minutes of incubation in human plasma (Table 2). Table 2: Rat, dog and human plasma conversion of compounds 1012 and 1015 1012 1015 Drug in HPLC Rat Dog Human Rat Dog Human 0 0 5 11 0 0 0 0 - o esu s The pharmacokinetic parameters of compounds 1000, 1003, 1007, 1002, 1009, 1005, 1011, 1012, 1013, 1014, and 1015 were measured in rats. Six rats per compound were evaluated, and compounds were administered via a single oral dose. The results with various single oral dosage are shown in Tables 3-5, and disclose averages over all six rats. Pharmacokinetic parameters of Compound 1003 and Compound 1009 were compared with Compound 1000 at 100 mg / kg (Table 3). Compound 1003 and Compound 1009 were observed to have a higher volume of distribution (Vd) when compared to Compound 1000 at 100 mg / kg, demonstrating that prodrugs of the disclosure have increased solubility and permeability, and therefore improved absorption, compared to Compound 1000. Compound 1003 and Compound 1009 were also observed to have a shorter half-life (T1 / 2) than Compound 1000, suggesting that this enhanced absorption is quickly followed by conversion into the active therapeutic agent Compound 1000. Compound 1003 and Compound 1009 have a lower area under the curve (AUC), likely due to its rapid conversion to Compound 1000. While not wishing to be bound by theory, these results demonstrate that upon oral administration, liver enzymes rapidly convert the prodrug into the active drug so that less of the prodrug will enter the bloodstream, reducing the prodrug's systemic AUC while boosting the active drug's exposure. Table 3. Pharmacokinetic parameters of Compounds 1000, 1003 and 1009 (100 mg / kg) Compound 1000 Compound 1003 Compound 1009 Parameters Average SD CV% Average SD CV% Average SD CV% 04 25 2 9 9 8 7 Vd = Tables 4 and 5 disclose the pharmacokinetic parameters of Compounds 1002, 1007, 1009, 1011, 1012, 1013, 1014, and 1015 at 25 mg / kg. Table 4. Pharmacokinetic parameters of Compounds 1002, 1007, 1009, and 1011 (25 mg / kg) Compound 1002 Compound 1007 Compound 1009 Compound 1011 Parameters Average CV% Average CV% Average CV% Average CV% Table 5. Pharmacokinetic parameters of Compounds 1012, 1013, 1014, and 1015 (25 mg / kg) Compound 1012 Compound 1013 Compound 1014 Compound 1015 C (ngm / maxL) 120.47 53.61 70.55 48.35 52.59 33.51 68.93 51.67 T (h) 333 4721 192 6855 263 13680 433 5608 ; Vd = Table 6 discloses the concentration of compounds in the disclosure in individual rat plasma (ng / mL). Table 6. Individual rat plasma concentration data (ng / mL) of Compounds 1002, 1007, 1009, 1011, 1012, 1013, 1014, and 1015 at 25 mg / kg T.Point Comp Comp Comp Comp Comp Comp Comp Comp Comp (h) 1000 1002 1007 1009 1011 1012 1013 1014 1015 , , , , , , , stream were observed to be higher than that of Compound 1000 at almost all time points and over the total duration of exposure (Table 6). Without being bound by theory, these results demonstrate that the prodrugs of the disclosure exhibit improved properties of the active drug (Compound 1000), such as improved water or fat solubility to allow for easier absorption through the gastrointestinal tract than the active drug, which can result in a high concentration of the prodrugs in the blood stream. Further, the prodrugs of the disclosure are shown to be converted into the active drug slowly over time, which results in a prolonged release of the active drug over time so the prodrugs can accumulate to higher peak concentrations in the plasma before gradually being metabolized. The prodrugs of the disclosure also have a slower elimination rate compared to the active drug, leading to a higher concentration and a longer half-life. With oral administration, the prodrug is absorbed from the gut and travels to the liver, where it can undergo first-pass metabolism. The prodrugs of the disclosure are also capable of being rapidly metabolized in the liver, leading to a higher concentration of the prodrug in the systemic circulation before conversion. INCORPORATION BY REFERENCE All patents and publications referenced herein are hereby incorporated by reference in their entireties. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior disclosure. As used herein, all headings are simply for organization and are not intended to limit the disclosure in any manner. The content of any individual section may be equally applicable to all sections. EQUIVALENTS While the disclosure has been disclosed in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the disclosure following, in general, the principles of the disclosure and including such departures from the present disclosure as come within known or customary practice within the art to which the disclosure pertains and as may be applied to the essential features hereinbefore set forth and as follows in the scope of the appended claims. Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific embodiments disclosed specifically herein. Such equivalents are intended to be encompassed in the scope of the following claims.

Claims

CLAIMS What is claimed is:

1. A compound of formula (XI), or a stereoisomer thereof,: wherein in formula (XI): X is a pharmaceutically acceptable anion; each of Raand Rbis independently hydrogen or C1-C6 alkyl, wherein Raand Rbare optionally joined to form a 3-6 membered carbocyclic ring; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; c. 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally wherein the heteroaryl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy,iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy.

2. The compound of claim 1, wherein the compound of formula (XI) is a compound of formula (XIa), or a stereoisomer thereof:wherein in formula (XI): X is a pharmaceutically acceptable anion; each of Raand Rbis independently hydrogen or C1-C6alkyl, wherein Raand Rbare optionally joined to form a 3-6 membered carbocyclic ring; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl;b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy.

3. The compound of claim 1 or claim 2, wherein Rais hydrogen or C1-C6alkyl.

4. The compound of any one of claims 1-3, wherein Rbis hydrogen or C1-C6 alkyl.

5. The compound of any one of claims 1-4, wherein Raand Rbare joined to form a 3-6 membered carbocyclic ring.

6. The compound of any one of claims 1-4, wherein Rais hydrogen or Rbis hydrogen.

7. The compound of claim 1 or claim 6, wherein the compound of formula (XI) or (XIa) is a compound of formula (I): or a stereoisomer thereof, whereX is a pharmaceutically acceptable anion; Z is selected from i), ii), and iii):i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy; c. 5 or 6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, optionally wherein the heteroaryl is substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy 8. The compound of claim 7, wherein the compound of formula (I) is a compound of formula (Ia), or a stereoisomer thereof:formula (Ia) wherein in formula (Ia): X is a pharmaceutically acceptable anion; Z is selected from i), ii), and iii): i) -OR1, wherein R1is selected from alkyl, aryl, arylalkyl, alkenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O, S and N, wherein the alkyl, aryl, arylalkyl, alkenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, aryl, arylalkyl, alkenyl, halogen, alkoxy, haloalkyl, and haloalkoxy, ii) R2, wherein R2is selected from a), b), and c): a. C1-C8 alkyl, wherein the alkyl is optionally interrupted by 1 to 2 heteroatoms, and / or optionally substituted with 1 to 3 substituents selected from halogen, alkoxy, haloalkyl, haloalkoxy, and aryl; b. benzyl or phenyl, optionally wherein the benzyl or phenyl is substituted with 1 to 3 substituents selected from C1-C6alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy. iii) -NHR3or -N(R3)2, wherein R3is independently at each occurrence selected from alkyl, phenyl, and 5-6 membered heteroaryl containing 1-3 heteroatoms selected from O and N, wherein the alkyl, phenyl, and heteroaryl are optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy, wherein in -N(R3)2 both R3can optionally be joined to form a 4-6 membered ring, wherein the ring optionally contains 1-2 heteroatoms, and is optionally substituted with 1 to 3 substituents selected from C1-C6 alkyl, halogen, alkoxy, haloalkyl, and haloalkoxy.

9. The compound of any one of claims 1-8, wherein Z is -OR1.

10. The compound of any one of claims 1-9, wherein R1is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl.

11. The compound of any one of claims 1-10, wherein R1is selected from methyl, ethyl, n-propyl, isopropyl, sec-butyl, n-butyl, hexyl, and octyl.

12. The compound of any one of claims 1-11, wherein R1is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, - CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally -OMe or phenyl.

13. The compound of any one of claims 1-12, wherein -OR1is selected from -OMe, -OEt, -O-iPr, -O- .

14. The compound of any one of claims 1-8, wherein Z is R2.

15. The compound of any one of claims 1-8 or 14, wherein R2is C1-C8 alkyl.

16. The compound of any one of claims 1-8, 14, or 15, wherein C1-C8 alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl.

17. The compound of any one of claims 1-8 or 14-16, wherein C1-C8 alkyl is selected from methyl and n-propyl.

18. The compound of any one of claims 1-8 or 14-17, wherein C1-C8 alkyl is substituted with 1 to 3 substituents selected from Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl.

19. The compound of any one of claims 1-8 or 14-18, wherein -R2is selected from methyl and .

20. The compound of any one of claims 1-8 or 14, wherein R2is phenyl.

21. The compound of any one of claims 1-8 or 20, wherein phenyl is substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi- Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl, optionally phenyl.

22. The compound of any one of claims 1, 3-7 or 14, wherein R2is 5 or 6 membered heteroaryl.

23. The compound of any one of claims 1, 3-7, 14, or 22, wherein 5 or 6 membered heteroaryl is selected from pyridinyl, furyl, pyrrolidinyl, oxazole, isoxazole, pyrrazole, thiazole, isothiazole, and pyrimidine, optionally 3-pyridinyl.

24. The compound of any one of claims 1-8, wherein Z is -N(R3)2.

25. The compound of any one of claims 1-8, wherein Z is -NHR3.

26. The compound of any one of claims 1-8 or 24, or 25, wherein R3is independently at each occurrence selected from alkyl, optionally wherein the alkyl is selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, and octyl.

27. The compound of any one of claims 1-8 or 24-26, wherein each R3is methyl.

28. The compound of any one of claims 1-8 or 24-27, wherein one or both R3are each independently substituted with 1 to 3 substituents selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, Cl, Br, I, -OMe, -OEt, -Oi-Pr, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, and phenyl.

29. The compound of any one of claims 24, 26, or 27, wherein -N(R3)2 is -N(CH3)2.

30. The compound of any one of claims 1-29, wherein the compound of formula (XI) has a formula of any one of formula 1001-1015: Formula Structure Formula Structure1001 10091005 101331. The compound of any one of claims 1-30, wherein X is selected from chloride, bromide, iodide, hydroxide, sulfate (SO4-2, HSO4-2), nitrate, phosphate (e.g. PO4-3, HPO4-2, H2PO4-), acetate, trifluoroacetate, fumarate, citrate, tartrate, oxalate, succinate, mandelate, methanesulfonate and p-toluenesulfonate.

32. The compound of any one of claims 1-31, wherein X is selected from chloride, bromide. iodide, acetate, HSO4-, SO4-2, p-toluenesulfonate, PO4-3, HPO4-2, H2PO4-, and tartrate.

33. The compound of any one of claims 1-32, wherein X is chloride.

34. The compound of claim 33, wherein the compound of formula (XI) has a formula of any one of formula 2001-2015 or formula 3001-3015: Formula Structure Formula Structure N N2003 20112006 2014Formula No. Structure Formula No. Structure OFormula No. Structure Formula No. StructureFormula N Structure Formula o. No. Structure35. The compound of any one of claims 1-34, wherein the compound of formula (XI) exhibits improved gastrointestinal absorption (e.g. improved permeability and / or solubility) compared to (S)-sec-butyl 2-(3-(4- (2-(diethylamino)ethoxy)-3,5-diiodobenzoyl)benzofuran-2-yl) acetate.

36. The compound of claim 35, wherein the compound of formula (XI) exhibits at least about 1 fold, at least about 2 fold, at least about 3 fold, at least about 4 fold, at least about 5 fold, at least about 6 fold, at least about 7 fold, at least about 8 fold, at least about 9 fold, at least about 10 fold, at least about 50 fold, at least about 100 fold, at least about 500 fold, or at least about 1000 fold improved gastrointestinal absorption (e.g. improved permeability and / or solubility) compared to (S)-sec-butyl 2-(3-(4-(2-(diethylamino) ethoxy)-3,5-diiodobenzoyl) benzofuran-2-yl) acetate.

37. A pharmaceutical composition comprising a compound of any one of claims 1-36, and a pharmaceutically acceptable excipient.

38. A method of treating a disease or disorder, the method comprising administering to a subject in need thereof a compound of any one of claims 1-36 or a pharmaceutical composition of claim 37 to the subject.

39. The method of claim 38, wherein the disease or disorder is a cardiovascular disease or disorder.

40. The method of claim 39, wherein the cardiovascular disease or disorder is arrythmia or atrial fibrillation.

41. The method of any one of claims 38-40, wherein the method comprises treating arrhythmia or reducing the incidence of arrhythmias, restoring sinus and ventricular rhythms in a subject having persistent atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, atrial tachycardia, electrical storm, incessant ventricular tachycardia, supraventricular tachycardia (SVT), paroxysmal supraventricular tachycardia (PSVT), tachyarrhythmias, ventricular arrhythmias, ventricular premature beats (VPBs), nonsustained ventricular tachycardia (VT), sustained ventricular tachycardia (VT), or ventricular fibrillation, restoring normal cardiac rhythms in a subject, and / or reducing atrial fibrillation burden.

42. The method of any one of claims 38-41, wherein the subject has one or more of a rare genetic atrial fibrillation syndrome (e.g. Titan, Lamin), hypertrophic cardiomyopathy (HCM), recurrent paroxysmal atrial fibrillation, and recurrent atrial fibrillation with Amiodarone contraindicated.

43. A method for treating a subject diagnosed with arrythmia and / or paroxysmal or persistent atrial fibrillation (AFib), the method comprising: a) administering a first dose of a compound of any one of claims 1-36 or a pharmaceutical composition of claim 37 to the subject while employing a wearable to monitor heart rhythm data of the subject; b) monitoring the subject for efficacy of the administered first dose to assess whether the first dose is efficacious for the subject during a comparison period of 1 or more days; c) if an administered dose of the first dose is efficacious for the subject, continuing to monitor the subject's heart rhythm data to ensure that the administered dose remains efficacious.

44. The method of claim 43, wherein assessing the efficacy of the first dose is delayed for at least 7 or 14 days after administering the first dose.

45. The method of claim 43 or 44, wherein if the administered first dose is assessed as not efficacious for the subject by an end of the comparison period, dose adjusting the amount of one or more times as necessary to achieve an efficacious result using at least the comparison period and / or delay period.

46. The method of any one of claims 43-45, wherein if the administered first dose or adjusted dose is no longer efficacious, step c) is repeated with the administered first dose or adjusted dose as the first dose.

47. The method of any one of claims 43-46, wherein monitoring in step b) is conducted in a continuous manner.

48. The method of any one of claims 43-47, wherein monitoring in step b) comprises detecting atrial fibrillation (AF).

49. The method of claim 48, wherein detecting comprises use of a photoplethysmography (PPG) algorithm.

50. The method of any one of claims 43-49, wherein the efficacy at an administered dose is evaluated by comparing baseline levels of AFib against corresponding levels of AFib in the comparison period.

51. The method of any one of claims 43-50, wherein the comparison period is one or more of about a day, about a week, about 1 month, about 2 months, about 3 months, about 4 months, about 5 months, or up to about 6 months.

52. The method of any one of claims 43-51, wherein the subject has one or more of a rare genetic atrial fibrillation syndrome (e.g. Titan, Lamin), hypertrophic cardiomyopathy (HCM), recurrent paroxysmal atrial fibrillation, and recurrent atrial fibrillation with Amiodarone contraindicated.

53. The method of any one of claims 43-52, wherein the wearable is one or more of a patch, a watch, a wristband, a strap, a ring, a glass, a shirt, a finger, a bracelet, a SGPS / GPRS baby / control, a belt, a pants, a sock, a shoe, a Bluetooth key tracker, a holter, an implantable, or a device that adheres to a body when fitted.

54. The method of any one of claims 38-53, wherein the subject is selected for therapy based on a history of atrial fibrillation and / or an atrial fibrillation genetic risk score (GRS) indicating high risk of Afib recurrence over time.

55. The method of any one of claims 38-53, wherein the subject is selected for therapy based on a positive result from a wearable FDA cleared device, a history of atrial fibrillation and / or an atrial fibrillation genetic risk score (GRS) indicating high risk of Afib recurrence over time.

56. The method of claim 55, wherein the wearable FDA cleared device is used to monitor the subject on therapy and dosing is adjusted over time based on the presence or absence of atrial fibrillation.

57. The method of claim 55 or 56, wherein the subject is selected for therapy based on a history of atrial fibrillation and the atrial fibrillation genetic risk score (GRS) indicating high risk of Afib recurrence over time.

58. The method of any one of claims 38-57, wherein a drug therapy is administered before and / or after a cardioversion or ablation procedure intended to convert the subject to normal sinus rhythm.

59. The method of any one of claims 38-58, wherein the subject is selected for therapy based on a history of atrial fibrillation and / or an atrial fibrillation genetic risk score (GRS) in combination with an algorithm comprised of at least one known clinical risk factor indicating high risk of Afib recurrence over time.

60. The method of claim 59, wherein the risk factor comprises age, ethnicity, or a history of cardiovascular disease, cardiac amyloidosis, illicit drug use, or diabetes.

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