Substituted indolyl compounds, compositions thereof, and therapeutic uses thereof

Abstract

The application is directed to compounds of Formula (I): (I), and their salts and solvates, wherein A1, A2, A3, and R1, R2, R3a, R3b, R4, and R5 are defined as set forth in the specification, and their use in the treatment and / or prevention of diseases and conditions associated with the alteration of the activity of β-galactosidase, specially galactosidase β-1 or GLB1, including GM1 gangliosidosis and Morquio syndrome, Type B.

Description

[0001] SUBSTITUTED INDOLYL COMPOUNDS, COMPOSITIONS THEREOF, AND THERAPEUTIC USES THEREOF CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to European Patent Application No. EP23383116.3 filed on November 2, 2023, the entirety of which is incorporated by reference herein. FIELD OF THE DISCLOSURE The present disclosure provides compounds and their use in the treatment and / or prevention of diseases and conditions associated with the alteration of the activity of beta-galactosidase, specially galactosidase beta-1 or GLB1, including GM1 gangliosidosis and Morquio syndrome, Type B. BACKGROUND OF THE DISCLOSURE GM1 gangliosidosis and Morquio B, both arising from beta-galactosidase (GLB1) deficiency, are extremely rare lysosomal storage diseases with an incidence of about 1:100,000– 1:200,000 live births worldwide (Caciotti A. et al., Biochim Biophys Acta 1812(7):782-890 (July 2011)). These conditions are caused by mutations in the GLB1 gene, which lead to a deficiency of the enzyme β-galactosidase. The enzyme β-galactosidase is responsible for removing β-galactose from various substrates (i.e., gangliosides and oligosaccharides carrying terminal β-linked galactose, such as ganglioside GM1 and glycosaminoglycans such as keratan sulfate), and deficiencies in its activity result in toxic accumulation of these substrates in patients with conditions associated with GLB1 activity, such as GM1 gangliosidosis and mucopolysaccharidosis type IVB (MPS IVB) (Morquio syndrome type B, Morquio B, Morquio syndrome). GM1 gangliosidosis is a neurodegenerative disorder, whereas Morquio B is characterized by bone involvement and an absence of neurological manifestations. Suzuki et al. (Cell. Mol. Life Sci. 65:351-353 (2008)) reported that the mutations of the GLB1 gene can result in mutant β-galactosidase enzyme protein with deficient catalytic activity or enzyme protein with normal or near-normal catalytical function but unstable at neutral pH. These mutant enzyme proteins were unstable in the endoplasmic reticulum ER / Golgi apparatus, and rapidly degraded because of inappropriate molecular folding and this is the reason behind their impaired activity. The authors reported that the use of a competitive inhibitor binding to the misfolded mutant protein as a molecular chaperone (i.e. a small molecule that interacts with a misfolded protein to achieve a recovery on its activity) resulted in stabilization of the mutant enzyme and enhancement of its biological activity. Therefore, small molecules capable of binding to mutated β-galactosidase enzyme, either allosterically or competitively, thereby stabilizing the enzyme against degradation (chaperones) constitute an important therapeutic target in conditions associated with the alteration of the activity of beta-galactosidase, specially galactosidase beta-1 or GLB1. Currently, there is no cure for both Morquio B and GM1 gangliosidosis, and treatment options primarily focus on managing symptoms and providing supportive care. There is a need for the development of compounds that exhibit improved properties in the treatment or prevention of conditions associated with the altered activity of beta-galactosidase, and specifically galactosidase beta-1 or GLB1, including GM1 gangliosidosis and Morquio syndrome, type B. BRIEF SUMMARY OF THE DISCLOSURE In one aspect, the present disclosure provides compounds represented by Formulae (I), (II), (III), and (IV), below, and pharmaceutically acceptable salts and solvates thereof, collectively referred to herein as "Compounds of the Disclosure" (each is individually referred to hereinafter as a "Compound of the Disclosure"). In another aspect, the present disclosure provides a pharmaceutical composition comprising a Compound of the Disclosure and at least one pharmaceutically acceptable excipient. In another aspect, the present disclosure provides a method of treating or preventing a disease or condition associated with the alteration of the activity of GLB1 in a patient in need thereof. The method comprises administering to the patient in need thereof an effective amount of a Compound of the Disclosure. In another aspect, the present disclosure provides a method of treating or preventing Morquio B or GM1 gangliosidosis in a patient in need thereof, comprising administering to said patient an effective amount of a Compound of the Disclosure. In another aspect, the methods described herein further comprise administering to the patient at least one other therapeutic agent. In another aspect, the present method of treating GM1 gangliosidosis or Morquio B in a patient further comprises administering to the patient an effective amount of an enzyme for enzyme replacement therapy. In one embodiment, the enzyme is β-galactosidase or an analog thereof. In another aspect, the method further comprises administering to the patient a small molecule chaperone. In one embodiment, the small molecule chaperone binds competitively to an enzyme. In another embodiment, the small molecule chaperone is selected from the group consisting of iminoalditols, iminosugars, aminosugars, thiophenylglycosides, glycosidase, sulfatase, glycosyl transferase, phosphatase, and peptidase inhibitors. In another aspect, the present disclosure provides a method of increasing β-galactosidase activity in a patient in need thereof, comprising administering to the patient an effective amount of a Compound of the Disclosure, or a pharmaceutically acceptable salt or solvate thereof. In another aspect, the present disclosure provides Compounds of the Disclosure for use in the prevention or treatment of a condition associated with the alteration of the activity of GLB1. In another aspect, the present disclosure provides use of a Compound of the Disclosure in the preparation of a medicament for the prevention or treatment of a condition associated with the alteration of the activity of GLB1. In another aspect, the present disclosure provides a Compound of the Disclosure, as described herein, for use as a medicament. Other aspects and advantages of the disclosure will be readily apparent from the following detailed description of the disclosure. The embodiments and advantages of the disclosure will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing summary and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosure as claimed. DETAILED DESCRIPTION OF THE DISCLOSURE The inventors have found that certain Compounds of the Disclosure are capable of reducing exogenous GM1 ganglioside accumulation in in vitro cell models. Therefore, Compounds of the Disclosure are expected to be useful in the treatment or prevention of diseases or conditions associated with the alteration of the activity of GLB1, including Morquio B and GM1 gangliosidosis. Compounds of the Disclosure useful in this aspect of the disclosure are compounds of Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein: A1, A2, and A3 are each independently N or CH, with the proviso that one of A1, A2, and A3 is N and two of A1, A2, and A3 are CH; R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, -ORa, -C1-4 alkyl, -C3-6 cycloalkyl, and –(5- to 10-membered)-C3-7 heterocyclyl, wherein said -C1-4 alkyl, -C3-6 cycloalkyl, and –(5- to 10-membered)-C3-7 heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; Ra is –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; R3a is –NR6R7, wherein R6 is hydrogen or –C1-4 alkyl, and R7 is selected from the group consisting of hydrogen, -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl, wherein said -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; R3b is selected from the group consisting of hydrogen, halogen, and C1-4 alkyl; R4 is –NR8R9, wherein R8 is hydrogen or –C1-4 alkyl, and R9 is selected from the group consisting of –C6-10 aryl and -(5- to 10-membered)-C1-9 heteroaryl, wherein said –C6-10 aryl and -(5- to 10-membered)-C1-9 heteroaryl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; and Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms, wherein R3a, R3b, R4 and R5 each take the place of a hydrogen atom that would otherwise be present in any position on the rings of Formula (I) to which R3a, R3b, R4 and R5 are attached. In another embodiment, Compounds of the Disclosure are compounds of Formula (I), wherein A1 is N and A2 and A3 are both CH, having the structure of Formula (II): and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3a, R3b, R4, and R5 are as defined for Formula (I). In another embodiment, R3a is attached to the 5- or 6-position of the 2-pyridyl ring. In another embodiment, Compounds of the Disclosure are compounds of Formula (I), wherein A2 is N and A1 and A3 are both CH, having the structure of Formula (III): and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3a, R3b, R4, andR5 are as defined above for Formula (I).In another embodiment, Compounds of the Disclosure are compounds of Formula (I), wherein A3 is N and A1 and A2 are both CH, having the structure of Formula (IV): and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3a, R3b, R4, and R5 are as defined above for Formula (I). In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R4 is attached to the 4-position of the indolyl ring. In some embodiments, R5is hydrogen. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R4 is attached to the 5-position of the indolyl ring. In some embodiments, R5 is hydrogen. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, -ORa, -C1-4 alkyl, and -C3-6 cycloalkyl, wherein said -C1-4 alkyl, and -C3-6 cycloalkyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4) alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-, wherein Ra is –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, -C1-4 alkoxy, and -C1-4alkyl, wherein said -C1-4alkyl is unsubstituted or substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy. In some embodiments, R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, and unsubstituted -C1-2 alkyl. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R5 is hydrogen and R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, and unsubstituted –C1-2 alkyl. In some embodiments, R1 and R5 are each hydrogen and R2 is unsubstituted –C1-2 alkyl. In some embodiments, R2 and R5 are each hydrogen and R1 is unsubstituted –C1-2 alkyl. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, and R5 are each hydrogen. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R6 is hydrogen and R3a is –NHR7, wherein R7 is selected from the group consisting of hydrogen, -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl, wherein said -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1- 4)alkyl-, and halo(C1-4)alkoxy-. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R3ais –NHR7, wherein R7is -C1-4alkyl, such as e.g. methyl or ethyl. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R6 and R7 are each hydrogen and R3a is –NH2. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R6 is –C1-4 alkyl and R3a is –N(C1-4 alkyl)R7, wherein R7 is selected from the group consisting of -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl, wherein said -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. In some embodiments, R6is –C1-2alkyl. In some embodiments, R6 is methyl. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R7 is -C1-4 alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-. In some embodiments, R7 is unsubstituted -C1-4 alkyl. In some embodiments, R7is unsubstituted methyl or unsubstituted ethyl. In some embodiments, R7 is –C1-4 alkyl substituted with 1 or 2 substituents substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-. In some embodiments, R7 is –C1-2 alkyl substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-2 alkoxy, monohalo(C1-2)alkyl-, dihalo(C1-2)alkyl-, trihalo(C1-2)alkyl-, monohalo(C1-2)alkoxy-, dihalo(C1-2)alkoxy-, and trihalo(C1-2)alkoxy-. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R7 is -C3-10 cycloalkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1- 4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-. In some embodiments, R7 is unsubstituted -C3-10 cycloalkyl. In some embodiments, R7 is unsubstituted -C3-6 cycloalkyl. In some embodiments, R7 is -C3-10 cycloalkyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-. In some embodiments, R7is -C3-6cycloalkyl substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-2 alkoxy, monohalo(C1-2)alkyl-, dihalo(C1-2)alkyl-, trihalo(C1-2)alkyl-, monohalo(C1-2)alkoxy-, dihalo(C1-2)alkoxy-, and trihalo(C1-2)alkoxy-. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R7 is –C1-4 alkyl-C3-10 cycloalkyl, wherein said –C1-4 alkyl-C3-10 cycloalkyl group is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-. In some embodiments, R7 is unsubstituted –C1-4alkyl-C3-10cycloalkyl. In some embodiments, R7is unsubstituted –C1-2alkyl- C3-6 cycloalkyl. In some embodiments, R7 is –C1-4 alkyl-C3-10 cycloalkyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-. In some embodiments, R7 is –C1-2 alkyl-C3-6 cycloalkyl substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-2 alkoxy, monohalo(C1-2)alkyl-, dihalo(C1-2)alkyl-, trihalo(C1- 2)alkyl-, monohalo(C1-2)alkoxy-, dihalo(C1-2)alkoxy-, and trihalo(C1-2)alkoxy-. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R3a is –NHR7 or –N(C1-4 alkyl)R7, wherein R7 is selected from the group consisting of hydrogen, -C1-4 alkyl, -C3-6 cycloalkyl, and –C1-4 alkyl-C3-6 cycloalkyl, wherein said -C1-4 alkyl, -C3-6 cycloalkyl, and –C1-4 alkyl-C3-6 cycloalkyl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, methoxy, monohalo(C1-2) alkyl-, dihalo(C1-2)alkyl-, trihalo(C1-2)alkyl-, monohalomethoxy-, dihalomethoxy-, and trihalomethoxy-. In some embodiments, R7 is hydrogen, methyl or ethyl. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R6 and R7 are each –C1-4 alkyl and R3a is –N(C1-4 alkyl)2. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R3a is –N(C1-2 alkyl)2. In some embodiments, R3a is –N(CH3)2. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R3a is –NH2, -NH(CH3), or –N(CH3)2. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R3b is hydrogen. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R3b is halogen. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R3b is -C1-4 alkyl. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R8 is hydrogen and R4 is –NHR9, wherein R9 is selected from the group consisting of –C6-10 aryl and -(5- to 10-membered)-C1-9 heteroaryl, wherein said –C6-10 aryl and -(5- to 10-membered)-C1-9 heteroaryl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; and Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R8 is –C1-4 alkyl and R4 is –N(C1-4 alkyl)R9, wherein R9 is selected from the group consisting of –C6-10 aryl and -(5- to 10-membered)-C1-9 heteroaryl, wherein said –C6-10 aryl and -(5- to 10-membered)- C1-9 heteroaryl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; and Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms. In some embodiments, R8 is –C1-2 alkyl. In some embodiments, R8 is methyl. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R9 is –C6-10 aryl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4alkyl optionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms. In some embodiments, R9 is unsubstituted –C6-10 aryl. In some embodiments, R9 is unsubstituted phenyl. In some embodiments, R9 is unsubstituted naphthyl. In some embodiments, R9 is –C6-10 aryl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms. In some embodiments, R9 is phenyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-2 alkyl optionally substituted by 1, 2 or 3 halogen atoms. In some embodiments, Rb and Rc are both hydrogen. In some embodiments, R9 is phenyl substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, -CN, -OH, -O(C1-2)alkyl, unsubstituted –C1-4 alkyl, and –C1-4 alkyl substituted with 1, 2, or 3 halogen atoms. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R9 is , wherein m is 1 or 2 and R10 is selected from the group consisting of halogen, -CN, -OH, -C1-4 alkyl, and -C1-4 alkoxy. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R9 is , wherein R10 is selected from the group consisting of halogen, -CN, -O(C1-2)alkyl, and –C1-4 alkyl. In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R9 is In some embodiments, Compounds of the Disclosure are compounds of any one of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R9 is -(5- to 10-membered)-C1-9 heteroaryl, wherein said -(5- to 10-membered)-C1-9 heteroaryl group is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; and Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms. In some embodiments, R9 is unsubstituted -(5- to 10- membered)-C1-9 heteroaryl. In some embodiments, R9 is unsubstituted 5- or 6-membered heteroaryl having 1, 2 or 3 heteroatoms. In some embodiments, R9 is -(5- to 10-membered)-C1-9 heteroaryl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms. In some embodiments, R9 is 5- or 6-membered heteroaryl having 1, 2 or 3 heteroatoms, wherein said 5- or 6-membered heteroaryl is substituted with with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; and Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms. In some embodiments, Rb and Rc are both hydrogen. In some embodiments, Compounds of the Disclosure are compounds of Formula (I), and the pharmaceutically acceptable salts and solvates thereof, wherein In some embodiments, Compounds of the Disclosure are compounds of any of Formulae (I)-(IV), and the pharmaceutically acceptable salts and solvates thereof, wherein R4 is R4a: wherein m and R10 are as defined above. In some embodiments, R4a and R4b are attached to the 4- or 5-position of the indolyl ring. In some embodiments, Compounds of the Disclosure are compounds of any of Formulae (I) or (II), and the pharmaceutically acceptable salts and solvates thereof, wherein R3a is as defined above and is attached to the 5-position of the 2-pyridyl ring, R3b is hydrogen, R4 is as defined above and is attached to the 4-position of the indolyl ring, R5 is hydrogen, and R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, and –C1-2 alkyl. In some embodiments, R1 is hydrogen and R2 is methyl or ethyl. In some embodiments, R1 is methyl or ethyl and R2 is hydrogen. In some embodiments, both R1 and R2 are hydrogen. In some embodiments, R3a is –NH2 or –N(Me)2. In some embodiments, Compounds of the Disclosure are compounds of any of Formulae (I) or (II), and the pharmaceutically acceptable salts and solvates thereof, wherein R3a is as defined above and is attached to the 6-position of the 2-pyridyl ring, R3b is hydrogen, R4 is as defined above and is attached to the 4-position of the indolyl ring, R5 is hydrogen, and R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, and –C1-2 alkyl. In some embodiments, R1 is hydrogen and R2 is methyl or ethyl. In some embodiments, R1 is methyl or ethyl and R2 is hydrogen. In some embodiments, both R1 and R2 are hydrogen. In some embodiments, R3a is –NH2 or –N(Me)2. In some embodiments, Compounds of the Disclosure are compounds of any of Formulae (I) or (II), and the pharmaceutically acceptable salts and solvates thereof, wherein R3a is as defined above and is attached to the 5-position of the 2-pyridyl ring, R3b is hydrogen, R4 is as defined above and is attached to the 5-position of the indolyl ring, R5 is hydrogen, and R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, and –C1-2 alkyl. In some embodiments, R1 is hydrogen and R2 is methyl or ethyl. In some embodiments, R1 is methyl or ethyl and R2 is hydrogen. In some embodiments, both R1 and R2 are hydrogen. In some embodiments, R3a is –NH2 or –N(Me)2. In some embodiments, Compounds of the Disclosure are compounds of any of Formulae (I) or (II), and the pharmaceutically acceptable salts and solvates thereof, wherein R3a is as defined above and is attached to the 6-position of the 2-pyridyl ring, R3b is hydrogen, R4 is as defined above and is attached to the 5-position of the indolyl ring, R5 is hydrogen, and R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, and –C1-2 alkyl. In some embodiments, R1 is hydrogen and R2 is methyl or ethyl. In some embodiments, R1 is methyl or ethyl and R2 is hydrogen. In some embodiments, both R1 and R2 are hydrogen. In some embodiments, R3a is –NH2 or –N(Me)2. In some embodiments, Compounds of the Disclosure are provided as a pharmaceutically acceptable salt. In some embodiments, the pharmaceutically acceptable salt of a Compound of the Disclosure is a hydrochloride salt (a HCl-salt). In another embodiment, Compounds of the Disclosure are compounds selected from any one or more of the compounds of Table 1, or a pharmaceutically acceptable salt or solvate thereof. Table 1 Example No. Structure Name 1-(5-(dimethylamino)pyridin-2-yl)-N-(4- 1 methoxyphenyl)-1H-indol-5-amine 1-(5-aminopyridin-2-yl)-N-(p-tolyl)-1H- indol-5-amine 2 Example No. Structure Name 1-(5-aminopyridin-2-yl)-N-(3- methoxyphenyl)-1H-indol-5-amine 3 1-(5-aminopyridin-2-yl)-N-(m-tolyl)-1H- indol-5-amine 4 1-(5-aminopyridin-2-yl)-N-(3- methoxyphenyl)-N-methyl-1H-indol-5- 5 amine 1-(6-aminopyridin-2-yl)-N-(4- 6 chlorophenyl)-1H-indol-5-amine 1-(6-aminopyridin-2-yl)-N-(3- 7 methoxyphenyl)-1H-indol-5-amine 1-(5-aminopyridin-2-yl)-N-(4- 8 methoxyphenyl)-1H-indol-4-amine Example No. Structure Name 1-(5-aminopyridin-2-yl)-N-(4- 9 chlorophenyl)-1H-indol-4-amine 1-(6-aminopyridin-2-yl)-N-(p-tolyl)-1H- 10 indol-4-amine 1-(6-aminopyridin-2-yl)-N-(4- 11 chlorophenyl)-1H-indol-4-amine 1-(5-aminopyridin-2-yl)-N-(4- methoxyphenyl)-3-methyl-1H-indol-5- 12 amine 1-(5-aminopyridin-2-yl)-N-(4- methoxyphenyl)-2-methyl-1H-indol-5- 13 amine 14 1-(6-aminopyridin-2-yl)-N-(4- methoxyphenyl)-1H-indol-5-amine Example No. Structure Name 1-(6-aminopyridin-2-yl)-N-(4- 15 methoxyphenyl)-1H-indol-4-amine 1-(5-aminopyridin-2-yl)-N-(4- 16 methoxyphenyl)-1H-indol-5-amine 1-(5-aminopyridin-2-yl)-N-(4- chlorophenyl)-1H-indol-5-amine 17 1-(5-aminopyridin-2-yl)-N-(3- chlorophenyl)-1H-indol-5-amine 18 4-((1-(5-aminopyridin-2-yl)-1H-indol-5- yl)amino)benzonitrile 19

[0002] Example No. Structure Name 1-(5-aminopyridin-2-yl)-N-(p-tolyl)-1H- indol-4-amine 20 1-(5-aminopyridin-2-yl)-N-(3- methoxyphenyl)-1H-indol-4-amine 21 1-(5-aminopyridin-2-yl)-N-(m-tolyl)-1H- indol-4-amine 22 1-(5-aminopyridin-2-yl)-N-(3- chlorophenyl)-1H-indol-4-amine 23 Optional substituents attached to aryl, e.g., phenyl, and heteroaryl, e.g., pyridyl, rings each take the place of a hydrogen atom that would otherwise be present in any position on the aryl or heteroaryl rings. As used herein, the terms “halogen” or “halo” by itself or as part of another group refer to fluorine (-F), chlorine (-Cl), bromine (-Br), or iodine (-I). As used herein, the term “hydroxyl” or “hydroxyl” by itself or as part of another group refers to the group –OH. The term “cyano” as used herein by itself or as part of another group refers to the group -CN. As used herein, the term “alkyl” by itself or as part of another group refers to a linear or branched hydrocarbon chain radical consisting of carbon and hydrogen atoms, containing no unsaturation, which is attached to the rest of the molecule by a single bond and, unless otherwise specified, an alkyl radical typically has from 1 to 4 carbon atoms, i.e., -C1-4 alkyl. Exemplary -C1-4 alkyl groups can be methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, i-butyl and sec-butyl. In another embodiment, the alkyl is -C1-2alkyl (methyl or ethyl). The term “alkoxy” as used herein by itself or as part of another group refers to an alkyl group attached to a terminal oxygen atom. In one embodiment, the alkyl is a -C1-C6 alkyl. In another embodiment, the alkyl is a -C1-C4 alkyl group. In another embodiment, the alkyl is a -C1-C2 alkyl group. Non-limiting exemplary alkoxy groups include methoxy, ethoxy, and tert- butoxy. As used herein, the term “C1-4 alkoxy” as used herein by itself or as part of another group refers to oxygen substituted by one of the -C1-4 alkyl groups mentioned above (e.g., methoxy, ethoxy, propoxy, iso-propoxy, butoxy, tert-butoxy, iso-butoxy, and sec-butoxy), for example by one of the -C1-2 alkyl groups. The term “haloalkyl” as used herein by itself or as part of another group refers to an alkyl group substituted by one or more fluorine, chlorine, bromine, and / or iodine atoms. In one embodiment, the alkyl is substituted by one, two, or three fluorine and / or chlorine atoms. In another embodiment, the alkyl is substituted by one, two, or three fluorine atoms. In another embodiment, the alkyl is a -C1-C6 alkyl. In another embodiment, the alkyl is a -C1-C4 alkyl. In another embodiment, the alkyl group is a C1 or C2 alkyl. In some embodiments, the haloalkyl is monohalo(C1-4)alkyl- (i.e., -C1-4 alkyl group substituted by one halogen atom), dihalo(C1-4)alkyl- (i.e., -C1-4 alkyl group substituted by two halogen atoms), or trihalo(C1-4)alkyl (i.e., -C1-4 alkyl group substituted by three halogen atoms). In some embodiments, the haloalkyl is monohalo(C1- 2)alkyl-, dihalo(C1-2)alkyl-, or trihalo(C1-2)alkyl. Non-limiting exemplary haloalkyl groups include fluoromethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, 1,1-difluoroethyl, 2,2- difluoroethyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, and trichloromethyl groups. The term “haloalkoxy” as used herein by itself or as part of another group refers to an haloalkyl group attached to a terminal oxygen atom. In one embodiment, the haloalkyl is a C1-C4 haloalkyl group. In some embodiments, the haloalkoxy is monohalo(C1-4)alkoxy- (i.e., -C1-4 alkoxy group substituted by one halogen atom), dihalo(C1-4)alkoxy- (i.e., -C1-4 alkoxy group substituted by two halogen atoms), or trihalo(C1-4)alkoxy (i.e., -C1-4 alkoxy group substituted by three halogen atoms). In some embodiments, the haloalkoxy is monohalo(C1-2)alkoxy-, dihalo(C1- 2)alkoxy-, or trihalo(C1-2)alkoxy. A non-limiting exemplary haloalkoxy group is -OCF3. As used herein, the term “cycloalkyl” as used herein by itself or as part of another group embraces saturated carbocyclic radicals and, unless otherwise specified, a cycloalkyl radical typically has from 3 to 6 carbon atoms. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. It is, for example, cyclopropyl, cyclopentyl and cyclohexyl. In another embodiment, the cycloalkyl group is -C3-10 cycloalkyl. As used herein, the term “alkylcycloalkyl” when employed in the definition of a substituent refers to a cycloalkyl group as defined above which is linked through an alkylene radical, such as C1-4 alkylene, with the core structure which it substitutes. As an example, a cyclopentylethyl substituent is a substituent consisting of a cyclopentyl group linked through an ethylene group to the core structure which it substitutes. In another embodiment, the alkylcycloalkyl group is –C1-4 alkyl-C3-10 cycloalkyl. In another embodiment, the alkylcycloalkyl group is –C1-2 alkyl-C3-6 cycloalkyl. As used herein, the terms “heterocyclyl” or “heterocyclic group” as used herein by itself or as part of another group embrace typically a monocyclic or polycyclic, non-aromatic, saturated or unsaturated C2-10 carbocyclic ring, such as a 5- to 10-membered radical, in which one or more, for example 1, 2, 3 or 4 of the carbon atoms, for example, 1 or 2 of the carbon atoms are replaced by a heteroatom selected from N, O and S. In one embodiment, the heterocyclyl is a C3-7 heterocyclyl, i.e., a heterocycle having 3-7 carbon atoms and at least one heteroatom. In another embodiment, a heterocyclyl is a (5- to 10-membered)-C2-9 heterocyclyl, i.e., a heterocycle having 5- to 10- members, of which 2-9 members are carbon. In another embodiment, the heteroatom is N. In another embodiment, when a hydrogen atom is attached to the heteroatom N, the hydrogen atom can be replaced with a C1-4 alkyl group, such as e.g., CH3. In another embodiment, the heteroatom is O. In some embodiments, the heterocyclyl is a -(5- to 6-membered)-C2-5 heterocyclyl. In another embodiment, the heterocyclyl radicals are saturated. A heterocyclic radical can be a single ring or two or more fused rings wherein at least one ring contains a heteroatom. When a heterocyclyl radical carries one or more substituents, the substituents can be the same or different. A said optionally substituted heterocyclyl is typically unsubstituted or substituted with 1, 2 or 3 substituents which can be the same or different. Examples of heterocyclic radicals include piperidyl, pyrrolidyl, pyrrolinyl, piperazinyl, morpholinyl, thiomorpholinyl, pyrazolinyl, pyrazolidinyl, quinuclidinyl, tetrazolyl, cromanyl, isocromanyl, imidazolidinyl, oxiranyl, azaridinyl, 4,5-dihydro-oxazolyl and 3-aza-tetrahydrofuranyl. The substituents are, for example, selected from halogen atoms, for example, fluorine or chlorine atoms, hydroxy groups, alkoxycarbonyl groups in which the alkyl moiety has from 1 to 4 carbon atoms, hydroxycarbonyl groups, carbamoyl groups, nitro groups, cyano groups, C1-4 alkyl groups optionally substituted by one or more halogen atoms, C1-4 alkoxy groups, optionally substituted by one or more halogen atoms and C1-4hydroxyalkyl groups. In another embodiment, the heterocyclyl is –(5- to 10-membered)-C3-7 heterocyclyl optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-. As used herein, the term “aryl” as used herein by itself or as part of another group refers to an aromatic ring system having six to fourteen carbon atoms, i.e., C6-C14 aryl. Non-limiting exemplary aryl group is typically a C6-10 monocyclic or polycyclic aryl radical such as phenyl and naphthyl. In another embodiment, the aryl is phenyl. A said optionally substituted aryl radical is typically unsubstituted or substituted with 1, 2 or 3 substituents which can be the same or different. The substituents are, for example, selected from halogen atoms, for example, fluorine or chlorine atoms, hydroxy groups, alkoxycarbonyl groups in which the alkyl moiety has from 1 to 4 carbon atoms, hydroxycarbonyl groups, carbamoyl groups, nitro groups, cyano groups, C1-4 alkyl groups optionally substituted by one or more halogen atoms, C1-4 alkoxy groups, optionally substituted by one or more halogen atoms and C1-4 hydroxyalkyl groups. When an aryl radical carries 2 or more substituents, the substituents can be the same or different. Unless otherwise specified, the substituents on an aryl group are typically themselves unsubstituted. As used herein, the term “heteroaryl” as used herein by itself or as part of another group refers to monocyclic and bicyclic aromatic ring systems having 5 to 14 ring members, i.e., a 5- to 14-membered heteroaryl, comprising one, two, three, or four heteroatoms. In some embodiments, the heteroaryl is a 5- to 10-membered ring system, comprising at least one heteroaromatic ring and containing at least one heteroatom selected from O, S and N, typically 1, 2, 3, or 4 heteroatoms. In some embodiments, the heteroaryl is a 5- or 6-membered heteroaryl having 1, 2, or 3 heteroatoms selected from O, S, and N. A heteroaryl group can comprise a single ring or two or more fused rings wherein at least one ring contains a heteroatom. A said optionally substituted heteroaryl group is typically unsubstituted or substituted with 1, 2 or 3 substituents which can be the same or different. The substituents are, for example, selected from halogen atoms, for example, fluorine, chlorine or bromine atoms, alkoxycarbonyl groups in which the alkyl moiety has from 1 to 4 carbon atoms, carbamoyl groups, nitro groups, hydroxy groups, C1-4 alkyl groups, optionally substituted by one or more halogen atoms and C1-4 alkoxy groups, optionally substituted by one or more halogen atoms. When a heteroaryl radical carries 2 or more substituents, the substituents can be the same or different. Unless otherwise specified, the substituents on a heteroaryl radical are typically themselves unsubstituted. Examples of heteroaryl groups include pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, furyl, tetrazolyl, benzofuranyl, oxadiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, imidazolyl, benzimidazolyl, thiazolyl, thiadiazolyl, thienyl, pyrrolyl, pyridinyl, benzothiazolyl, indolyl, indazolyl, purinyl, quinolyl, isoquinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, quinolizinyl, cinnolinyl, triazolyl, indolizinyl, indolinyl, isoindolinyl, isoindolyl, imidazolidinyl, pteridinyl, thianthrenyl, pyrazolyl, 2H-pyrazolo[3,4-d]pyrimidinyl, 1H-pyrazolo[3,4- d]pyrimidinyl, thieno[2,3-d]pyrimidinyl, and the various pyrrolopyridyl radicals. In another embodiment, the heteroaryl is a (5- to 10-membered)-C1-9 heteroaryl. In another embodiment, the heteroaryl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms. In another embodiment, the heteroaryl is optionally substituted with 1, 2, or 3 groups independently selected from the group consisting of halogen, hydroxy, -CN, -ORc, -N(Rc)2, and -C1-4alkyl optionally substituted with 1, 2, or 3 halogen atoms. The mention of optionally substituted heteroaryl radicals or rests within the present disclosure is intended to cover the N-oxides obtainable from these radicals when they comprise N- atoms. The term “triflate” refers to a trifluoromethanesulfonate group, which is a functional group represented with the formula −OS(=O)2CF3. Xantphos is an organophosphorus compound derived from the heterocycle xanthene. XPhos is a phosphine ligand derived from biphenyl. It is especially efficient and general when employed as a (2-aminobiphenyl)-cyclometalated palladium mesylate precatalyst complex (Buchwald's third generation precatalyst system), XPhos-G3-Pd, which is commercially available and stable to bench storage. The term “pharmaceutically acceptable” refers to compositions and molecular entities that are physiologically tolerable and do not typically produce an allergic reaction or a similar unfavorable reaction, such as gastric disorders, dizziness and suchlike, when administered to a human or animal. For example, the term "pharmaceutically acceptable" means it is approved by a regulatory agency of a state or federal government or is included in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly in humans. The term “treatment” or “treating” refers to administering a therapy in an amount, manner or mode effective to improve a condition, symptom, or parameter associated with a condition or to prevent progression of a condition, to either a statistically significant degree or to a degree detectable to one skilled in the art. An effective amount, manner, or mode can vary depending on the subject and can be tailored to the patient. By an “effective” amount or a “therapeutically effective amount” of a drug or pharmacologically active agent is meant a nontoxic but sufficient amount of the drug or agent to provide the desired effect. The amount that is “effective” will vary from subject to subject, depending on the age and general condition of the individual, the particular active agent or agents, and the like. Thus, it is not always possible to specify an exact “effective amount.” However, an appropriate “effective” amount in any individual case may be determined by one of ordinary skill in the art using routine experimentation. The term “prevention” or “to prevent” refers to the reduction in the risk of acquiring or developing a given disease or disorder, or the reduction or inhibition of the recurrence or a disease or disorder. The term “about”, as used herein in connection with a measured quantity, refers to the normal variations in that measured quantity, as expected by the skilled artisan making the measurement and exercising a level of care commensurate with the objective of measurement and precision of the measuring equipment. Typically, the term “about” includes the recited number ± 10%. Thus, “about 10” means 9 to 11. As used herein, the term “optionally substituted” refers to a group that can be unsubstituted or substituted. The term “patient” as used herein refers to a human. In some embodiments, the patient is an adult. In some embodiments, the patient is a geriatric patient. In some embodiments, the patient is a child. In some embodiments, the patient is an infant. In some embodiments, the patient is a toddler. In some embodiments, the patient is a preadolescent. In some embodiments, the patient is an adolescent. As used herein, the term “child” is a human being between the stages of birth and puberty. The term "puberty" is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. On average, girls begin puberty around ages 10–11 and end puberty around 15–17; boys begin around ages 11–12 and end around 16–17. As used herein, the term “infant” is the synonym for “baby,” the very young offspring of a human. The term “infant” is typically applied to young children under one year of age. As used herein, the term “toddler” refers to a child of 12 to 36 months old. As used herein, the term “preadolescent” refers to a person of 10–13 years old. As used herein, the term “adolescent” refers to a person between ages 10 and 19. The term “solvate” means any form of the active compound of the disclosure which has another molecule (for example a polar solvent such as water or ethanol, a cyclodextrin or a dendrimer) attached to it through noncovalent bonds. Methods of solvation are known within the art. The disclosure also provides salts of the Compounds of the Disclosure. Non-limiting examples are sulphates; hydrohalide salts; phosphates; lower alkane sulphonates; arylsulphonates; salts of C1-20 aliphatic mono-, di- or tribasic acids which can contain one or more double bonds, an aryl nucleus or other functional groups such as hydroxy, amino, or keto; salts of aromatic acids in which the aromatic nuclei may or may not be substituted with groups such as hydroxyl, lower alkoxyl, amino, mono- or di- lower alkylamino sulphonamido. Also included within the scope of the disclosure are quaternary salts of the tertiary nitrogen atom with lower alkyl halides or sulphates, and oxygenated derivatives of the tertiary nitrogen atom, such as the N-oxides. In preparing dosage formulations, those skilled in the art will select the pharmaceutically acceptable salts. Solvates and salts can be prepared by methods known in the state of the art. Note that the non-pharmaceutically acceptable solvates also fall within the scope of the disclosure because they can be useful in preparing pharmaceutically acceptable salts and solvates. The Compounds of the Disclosure also seek to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of a hydrogen by a deuterium or tritium, or the replacement of a carbon by a carbon enriched in11C,13C or14C or the replacement of a nitrogen by a15N enriched nitrogen are within the scope of this disclosure. Some of the compounds disclosed herein can contain one or more asymmetric centers and can thus give rise to enantiomers, diastereomers, and other stereoisomeric forms, such as epimers. The present disclosure is meant to encompass the uses of all such possible forms, as well as their racemic and resolved forms and mixtures thereof. The individual enantiomers can be separated according to methods known to those of ordinary skill in the art in view of the present disclosure. When the compounds described herein contain olefinic double bonds or other centers of geometric asymmetry, and unless specified otherwise, it is intended that they include both E and Z geometric isomers. All tautomers are intended to be encompassed by the present disclosure as well. As used herein, the term “stereoisomers” is a general term for all isomers of individual molecules that differ only in the orientation of their atoms in space. It includes enantiomers and isomers of compounds with more than one chiral center that are not mirror images of one another (diastereomers). The term “chiral center” refers to a carbon atom to which four different groups are attached. The term “epimer” refers to diastereomers that have opposite configuration at only one of two or more tetrahedral stereogenic centers present in the respective molecular entities. The term “stereogenic center” is an atom, bearing groups such that an interchanging of any two groups leads to a stereoisomer. The terms “enantiomer” and “enantiomeric” refer to a molecule that cannot be superimposed on its mirror image and hence is optically active wherein the enantiomer rotates the plane of polarized light in one direction and its mirror image compound rotates the plane of polarized light in the opposite direction. The term “racemic” refers to a mixture of equal parts of enantiomers and which mixture is optically inactive. The term “resolution” refers to the separation or concentration or depletion of one of the two enantiomeric forms of a molecule. The terms “a” and “an” refer to one or more. As used herein, the term “enzyme replacement therapy,” or “ERT” refers to administering an exogenously-produced natural or recombinant enzyme or analog thereof to a patient in need thereof. In the case of a lysosomal storage disease, for example, the patient accumulates harmful levels of a substrate (i.e., material stored) in lysosomes due to a deficiency or defect in an enzyme responsible for metabolizing the substrate, or due to a deficiency in an enzymatic activator required for proper enzymatic function. Enzyme replacement therapy is provided to the patient to reduce the levels of (i.e., debulk) accumulated substrate in affected tissues. Enzyme replacement therapies for treating lysosomal storage diseases are known in the art. In accordance with a combination therapy of the disclosure, a lysosomal enzyme, e.g., β-galactosidase, can be used for enzyme replacement therapy to reduce the levels of corresponding substrate, e.g., GM1-ganglioside, glycoprotein, keratan sulfate, in a patient having GM1 gangliosidosis or Morquio B. As used herein, an “effective amount” of an enzyme, when administered to a subject in a combination therapy of the disclosure, is an amount sufficient to improve the clinical course of a lysosomal storage disease, where clinical improvement is measured by any of the variety of defined parameters well known to the skilled artisan. As used herein the term “small molecule chaperone” refers to a compound, other than a Compound of the Disclosure, that is capable of binding allosterically or competitively to a mutated enzyme, e.g., β-galactosidase, thereby stabilizing the enzyme against degradation. In some embodiments, the small molecule chaperone facilitates proper folding and transport of an enzyme to its site of action. Small molecule chaperones for the treatment of lysosomal storage diseases are known in the art. See, e.g., US 2016 / 0207933 A1 and WO 2011 / 049737 A1. Some reactions for preparing Compounds of the Disclosure involve employing amino protecting groups. As used herein, an “amine protecting group” or “amino protecting group” refers to a group that blocks (i.e., protects) the amine functionality while reactions are carried out on other functional groups or parts of the molecule. Those skilled in the art will be familiar with the selection, attachment, and cleavage of amine protecting groups and will appreciate that many different protective groups are known in the art, the suitability of one protective group or another being dependent on the particular synthetic scheme planned. Treatises on the subject are available for consultation, such as Wuts, P. G. M. & Greene, T. W., Greene's Protective Groups in Organic Synthesis, 4rd Ed. (J. Wiley & Sons, 2007), herein incorporated by reference in its entirety. Suitable amine protecting groups include methyl carbamate, tert-butyloxycarbonyl (tert-butyl carbamate; BOC), 9-fluorenylmethyl carbamate, benzyl carbamate, 2-(trimethylsilyl)ethyl carbamate, trifluoroacetamide, benzylamine, allylamine, tritylamine, trichloroacetyl, trifluoroacetyl, p- toluenesulfonyl, and allyl carbamate. In another embodiment, the protected amino group can be a phthalimide-protected amino group (NPhth). As used herein, an “effective amount” of another therapeutic agent, when administered to a subject in a combination therapy of the disclosure, is an amount sufficient to improve the clinical course of a disease or condition associated with the alteration of the activity of GLB1, where clinical improvement is measured by any of the variety of defined parameters well known to the skilled artisan. Synthesis of Compounds of the Disclosure Compounds of the Disclosure can be prepared using methods known to those skilled in the art in view of this disclosure, or by illustrative methods shown in the schemes below. For example, methods described in Schemes 1-5 below can be used for preparing Compounds of the Disclosure having Formula (I). Additional methods of synthesis are described and illustrated in the working examples set forth below. Scheme 1 Reaction A In one method, a compound of Formula (V), wherein L1 represents a suitable leaving group, such as a halogen, a triflate, a tosylate or a mesylate group, and each of R1, R2 and R5 are as defined above for Formula (I), is reacted with a compound of Formula (VI), wherein M can be NO2, NR6R7 or NH-PG, where PG is an amino protecting group, L2 is a leaving group, and each of A1, A2 and A3 are as defined above for Formula (I), to yield compounds of Formula (VII), as illustrated in reaction A of the scheme above (Scheme 1). Reaction A can be performed under standard conditions in the presence of a suitable base (such as pyridine, triethylamine, dimethylaminopyridine, diisopropylamine, potassium hydroxide, or mixtures thereof), and an appropriate solvent (such as pyridine, dichloromethane, chloroform, tetrahydrofuran, toluene, dimethylformamide, dimethylsulphoxide, water or mixtures thereof) and, for example, at around room temperature or above, or under microwave irradiation reaction conditions. The reaction can also be carried out in the presence of an appropriate metal catalyst (or a salt or complex thereof), such as Cu, Cu(OAc)2, CuI (or CuI / diamine complex), copper tris(triphenyl-phosphine)bromide, Pd(OAc)2, tris(dibenzylideneacetone) dipalladium(0) (Pd2(dba)3), or NiCl2, and also optionally in the presence of an additive, such as for example Ph3P, 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl, xantphos, (1R,2R)-N1,N2-dimethylcyclohexane- 1,2-diamine, NaI or an appropriate crown ether, such as 18-crown-6-benzene, in the presence of an appropriate base, such as sodium hydride, triethylamine, pyridine, N,N’- dimethylethylenediamine, imidazole, sodium carbonate, potassium carbonate, tripotassium phosphate, potassium phosphate, cesium carbonate, sodium tert-butoxide or potassium tert- butoxide (or a mixture thereof, optionally in the presence of 4Å molecular sieves), in a suitable solvent (e.g. dichloromethane, dioxane, toluene, ethanol, isopropanol, dimethylformamide, ethylene glycol, ethylene glycol dimethyl ether, water, dimethylsulfoxide, acetonitrile, dimethylacetamide, N-methylpyrrolidinone, or tetrahydrofuran) or a mixture thereof. This reaction can be carried out under microwave irradiation reaction conditions. The reaction mixture can be stirred at room temperature or heated until the starting materials have been consumed. Compounds of Formula (V) and (VI) are commercially available or can be obtained by procedures described in the literature as is known by the person skilled in the art. The reaction can be carried out with protecting groups present and those protecting groups can be removed after the reaction. Suitable protecting groups are known to the person skilled in the art (see T. W. Greene, “Protective Groups in Organic Synthesis”, 3rd Edition, New York, 1999). Scheme 2 Reaction B In another method according to the disclosure, a compound of Formula (VII), wherein L1 is a leaving group, such as a halogen, a triflate, a tosylate or a mesylate group, M can be NO2, NR6R7 or NH-PG, where PG is a protecting group, and each of A1, A2, A3, R1, R2, R5, R6 and R7 are defined above for Formula (I) is reacted with an amine compound of Formula (VIII) where each of R8 and R9 are as defined above to yield a compound of Formula (IX) as illustrated in reaction B of the scheme above (Scheme 2). Reaction B can be performed under standard conditions in the presence of a suitable palladium catalyst, such as Pd(dba)2, palladium acetate, XantPhos Pd G3, tBuXPhos Pd G3, or Pd2(dba)3, the appropriate base (cesium carbonate or triethylamine, among others) and a suitable ligand, such as 1,2,3,4,5-pentaphenyl-1′-(di-tert-butylphosphino)ferrocene, Xantphos, or XPhos in the appropriate solvent (e.g., butanol, toluene, dioxane or mixtures thereof) and, for example, at around room temperature or reflux temperature. Alternatively, the transformation can be carried out in the presence of a suitable base (e.g., N,N-diisopropylethylamine or triethylamine) and an appropriate solvent, such as dimethyl sulphoxide, tetrahydrofuran, dichloromethane, acetonitrile, dimethylformamide, methanol, ethanol, or mixtures thereof. Compounds of Formula (VIII) are commercially available or can be obtained by procedures described in the literature as is known by the person skilled in the art. The reaction can be carried out with protecting groups present and those protecting groups can be removed after reaction. Suitable protecting groups are known to the person skilled in the art (see T. W. Greene, “Protective Groups in Organic Synthesis,” 3rdEdition, New York, 1999). Scheme 3 Reaction C The nitro group of the compound of Formula (IX), where M is NO2 from Scheme 2 can be subsequently reduced to a primary amine group. Accordingly, as illustrated in reaction C of the scheme above (Scheme 3), the compound of Formula (X) is reduced to yield a compound of Formula (XI), i.e., a compound of Formula (I), where R3a is –NH2. Reaction C is carried out with a suitable reducing agent, such as Fe, SnCl2, and hydrogen in the presence of a hydrogenation catalyst, such as Raney-nickel, palladium or PtO2. The reaction can be carried out in the presence of an acid, such as acetic acid, hydrochloric acid, or sulfuric acid, and in a suitable solvent such as ethyl acetate, water, methanol, ethanol and / or tetrahydrofuran. Other reducing agents or acids can be employed, as are known by the person skilled in the art. The reaction mixture is stirred at room temperature or heated until the starting materials have been consumed. The reaction can be carried out with protecting groups present and those protecting groups can be removed after the reaction. Suitable protecting groups are known to the person skilled in the art (see T. W. Greene, “Protective Groups in Organic Synthesis”, 3rd Edition, New York, 1999). Scheme 4 Reaction D In another method according to the disclosure, a compound of Formula (XII), wherein PG is a protecting group, and each of A1, A2, A3, R1, R2, R5, R8 and R9 are defined above for Formula (I), is reacted to yield a compound of Formula (XI), i.e., a compound of Formula (I) where R3a is –NH2, as illustrated in reaction D of the scheme above (Scheme 4). The protecting group PG of the amine moiety of the compound of Formula (XII) (for instance tert-octylamine, tert-butyl carbamate, or diphenylmethanimine) is treated to form the corresponding primary amino group. The compound of Formula (XI) can be delivered as its free base or transformed into its salt form (for example HCl salt) by standard salt formation procedures. Reaction D can be carried out under standard deprotection conditions, for example in the presence of HCl, trifluoroacetic acid, or boron tribromide. Such reactions may be performed in the presence of an appropriate solvent, such as tetrahydrofuran, dioxane, dichloromethane, or mixtures thereof. The reaction mixture is stirred at a low temperature, room temperature, or heated until the starting materials have been consumed. The reaction can be carried out with protecting groups present and those protecting groups can be removed after the reaction. Suitable protecting groups are known to the person skilled in the art (see T. W. Greene, “Protective Groups in Organic Synthesis”, 3rd Edition, New York, 1999). Scheme 5 Reaction E In another method according to the disclosure, the intermediate of Formula (X) can be prepared from a compound of Formula (XIII), wherein each of A1, A2, A3, R1, R2, R5 and R9 are defined above by reacting with an appropriate aldehyde of Formula (XIV) where R8' is as defined above in Scheme 5 via reductive amination to yield a compound of Formula (X) as illustrated in reaction E of the scheme above (Scheme 5). Reaction E is carried out under standard reductive amination, for example in the presence of a reducing agent (e.g., sodium triacetoxyborohydride, sodium cyanoborohydride or sodium borohydride), alternatively in the presence of a suitable acid such as acetic acid and an appropriate solvent (e.g., acetonitrile, dichloromethane, methanol, ethanol, ethyl acetate, chloroform, dimethylformamide, toluene or mixtures thereof). The reaction mixture is stirred at room temperature or heated until the starting materials have been consumed. Compounds of Formula (XIV) is commercially available or can be obtained by procedures described in the literature as is known by the person skilled in the art. The reaction can be carried out with protecting groups present and those protecting groups can be removed after the reaction. Suitable protecting groups are known to the person skilled in the art (see T. W. Greene, “Protective Groups in Organic Synthesis,” 3rdEdition, New York, 1999). Compounds of Formula (I) where R3b is other than hydrogen, i.e., halogen or –C1-4 alkyl, can be prepared using the methods described above and the working examples below using appropriate starting compounds. The compound of Formula (I) can be delivered as its free base or transformed into its salt form (for example HCl salt) by standard salt formation procedures. The starting materials and reactants can be purchased or synthesized as shown in the working examples below. Use of the Compounds of the Disclosure The utility of Compounds of the Disclosure, including pharmaceutically acceptable salts or solvates, in the present methods can be demonstrated in appropriate in vitro or in vivo assays. Suitable in vivo assays include, for example, those described in the following publications: 1) Takai, T., et al., “A bicyclic 1-deoxygalactonojirimycin derivative as a novel pharmacological chaperone for GM1 gangliosidosis,” Mol. Ther. 21:526–532 (2013); 2) Suzuki, Y., et al., “Chemical chaperone therapy: clinical effect in murine G(M1)-gangliosidosis,“ Ann. Neurol. 62(6):671-675 (2007); and 3) Yoshiyuki, S., et al., “Therapeutic chaperone effect of N-Octyl 4- Epi-β-valienamine on murine GM1-gangliosidosis,” Molecular Genetics and Metabolism 106(1):92-98 (2012). Compounds of the Disclosure have the ability to bind allosterically to mutated ß- galactosidase enzyme and, thereby, stabilizing the enzyme against denaturation. Therefore, Compounds of the Disclosure can be used / administered to treat and / or prevent conditions associated with the alteration of the activity of ß-galactosidase, specifically galactosidase ß-1 or GLB1, including GM1 gangliosidoses and Morquio syndrome, type B, in a patient suffering from said condition. Accordingly, the present disclosure is directed to a method of treating or preventing a condition associated with the alteration of the activity of GLB1 in a patient, comprising administering to the patient in need thereof an effective amount of a compound of any one of Formulae (I), (II), (III), or (IV), or a pharmaceutically acceptable salt or solvate thereof. The present disclosure is also directed to a method of treating GM1 gangliosidosis or Morquio B in a patient, comprising administering to the patient in need thereof an effective amount of a compound of any one of Formulae (I), (II), (III), or (IV), or a pharmaceutically acceptable salt or solvate thereof. In one embodiment, the method of treating GM1 gangliosidosis or Morquio B in a patient further comprises administering to the patient an effective amount of an enzyme for enzyme replacement therapy. In another embodiment, the enzyme is β-galactosidase or an analog thereof. In another embodiment, the method further comprises administering to the patient a small molecule chaperone. In one embodiment, the small molecule chaperone binds competitively to an enzyme. In another embodiment, the small molecule chaperone is selected from the group consisting of iminoalditols, iminosugars, aminosugars, thiophenylglycosides, glycosidase, sulfatase, glycosyl transferase, phosphatase, and peptidase inhibitors. In another embodiment, suitable small molecule chaperones are selected from the group consisting of 1- deoxygalactonojirimycin (DGJ), N-nonyldeoxynojirimycin (NN-DNJ), N- butyldeoxygalactonojirimycin (NB-DGJ), galactose, fluorous iminoalditol, and epi-isofagomine. The present disclosure is also directed to a method of increasing β-galactosidase activity in a patient in need thereof, comprising administering to the patient an effective amount of a compound of any one of Formulae (I), (II), (III), or (IV), or a pharmaceutically acceptable salt or solvate thereof. The present disclosure is also directed to the use of a compound represented by any of Formulae (I), (II), (III), or (IV), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for treating and / or preventing a condition associated with the alteration of the activity of ß-galactosidase, specifically galactosidase ß-1 or GLB1, including GM1 gangliosidoses and Morquio syndrome, type B, in a patient suffering from said condition. The present disclosure is also directed to a compound of any one of Formulae (I), (II), (III), or (IV), or a pharmaceutically acceptable salt or solvate thereof, for use in treating GM1 gangliosidosis or Morquio B in a patient. In one embodiment, the compound of any one of Formulae (I), (II), (III), or (IV), or a pharmaceutically acceptable salt or solvate thereof, is administered to the patient in combination with an effective amount of an enzyme for enzyme replacement therapy. In another embodiment, the enzyme is β-galactosidase or an analog thereof. In another embodiment, the compound of any one of Formulae (I), (II), (III), or (IV), or a pharmaceutically acceptable salt or solvate thereof, is administered to the patient in combination with a small molecule chaperone. In one embodiment, the small molecule chaperone binds competitively to an enzyme. In another embodiment, the small molecule chaperone is selected from the group consisting of iminoalditols, iminosugars, aminosugars, thiophenylglycosides, glycosidase, sulfatase, glycosyl transferase, phosphatase, and peptidase inhibitors. In another embodiment, suitable small molecule chaperones are selected from the group consisting of 1- deoxygalactonojirimycin (DGJ), N-nonyldeoxynojirimycin (NN-DNJ), N- butyldeoxygalactonojirimycin (NB-DGJ), galactose, fluorous iminoalditol, and epi-isofagomine. As shown in Table 2 below, Compounds of the Disclosure produce a reduction in GM1 ganglioside accumulation in p.R60H / p.R60H-β-Gal canine fibroblasts at concentrations of 1.56 µM and 0.05 µM. Accordingly, Compounds of the Disclosure show efficacy in the treatment and / or prevention of conditions associated with the alteration of the activity of ß-galactosidase, specifically galactosidase ß-1 or GLB1, because they reduce the accumulation of GM1 gangloside. Pharmaceutical compositions The present disclosure is also directed to pharmaceutical compositions, comprising an effective amount of a Compound of the Disclosure and at least one pharmaceutically acceptable excipient. In another aspect, the composition comprises an effective amount of a Compound of the Disclosure, or a pharmaceutically acceptable salt or solvate thereof, as described herein, and at least one pharmaceutically acceptable excipient. In another aspect, the composition comprises an effective amount of a compound of Formula (I), (II), (III), or (IV), or a pharmaceutically acceptable salt or solvate thereof, as described herein, and at least one pharmaceutically acceptable excipient. Due to their activity, Compounds of the Disclosure can be used in human medicine. As described above, Compounds of the Disclosure are useful for treating or preventing conditions associated with alteration of GLB1 activity. Compounds of the Disclosure can be administered to any patient suffering any of said conditions. The term “patient” as used herein refers to any human that can experience the beneficial effects of a Compound of the Disclosure. When administered to a patient, a Compound of the Disclosure can be administered as a component of a composition that comprises a pharmaceutically acceptable excipient or carrier. Compounds of the Disclosure can be administered in combination with at least one other therapeutic agent. Administration of Compounds of the Disclosure with at least one other therapeutic agent can be sequential or concurrent. In another aspect, the Compound of the Invention and at least one other therapeutic agent are administered in separate dosage forms. In another aspect, the Compound of the Invention and at least one other therapeutic agent are administered concurrently in the same dosage form. The term “excipient” refers to a vehicle, diluent, or adjuvant that is administered with the active ingredient. Such pharmaceutical excipients can be sterile 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 similar. Water or saline aqueous solutions and aqueous dextrose and glycerol solutions, for example, for injectable solutions, can be used as vehicles. Suitable pharmaceutical vehicles are described in “Remington’s Pharmaceutical Sciences” by E.W. Martin, 21stEdition, 2005; or “Handbook of Pharmaceutical Excipients,” Rowe C.R.; Paul J.S.; Marian E.Q., sixth Edition, incorporated herein by reference. Examples of pharmaceutical compositions include any solid composition (tablets, pills, capsules, granules, etc.) or liquid compositions (solutions, suspensions, or emulsions) for oral, topical, or parenteral administration. In another embodiment, the pharmaceutical compositions are in an oral delivery form. Pharmaceutical forms suitable for oral administration can be tablets and capsules, and can contain conventional excipients known in the art, such as binders, for example syrup, gum Arabic, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone; fillers, for example lactose, sugar, cornstarch, calcium phosphate, sorbitol, or glycine; lubricants for the preparation of tablets, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycolate, or microcrystalline cellulose; or pharmaceutically acceptable wetting agents, such as sodium lauryl sulphate. Solid oral compositions can be prepared by conventional methods of blending, filling, or preparation of tablets. Repeated blending operations can be used to distribute the active ingredient in all the compositions that use large amounts of fillers. Such operations are conventional in the art. The tablets can be prepared, for example, by dry or wet granulation and optionally can be coated by well-known methods in normal pharmaceutical practice, in particular enteric coating. Pharmaceutical compositions can also be adapted for parenteral administration, such as sterile solutions, suspensions, or lyophilized products in the appropriate unit dosage form. Suitable excipients, such as fillers, buffering agents, or surfactants can be used. The mentioned formulations can be prepared using standard methods, such as those described or referred to in the Spanish and U.S. Pharmacopoeias and similar reference texts. In general, the effective amount of a Compound of the Disclosure to be administered depends on the relative efficacy of the compound chosen, the severity of the condition or disorder being treated, and the patient’s weight. The active compound can be administered one or more times a day, for example 1, 2, 3, or 4 times daily, with typical total daily doses in the range from about 0.01 mg / kg of body weight / day to about 1000 mg / kg of body weight / day. In another embodiment, the effective dosage amount of a Compound of the Disclosure is about 500 mg / kg of body weight / day or less. In another embodiment, the effective dosage amount of a Compound of the Disclosure is about 100 mg / kg of body weight / day or less. In another embodiment, the effective dosage amount ranges from about 0.01 mg / kg of body weight / day to about 100 mg / kg of body weight / day of a Compound of the Disclosure; in another embodiment, from about 0.02 mg / kg of body weight / day to about 50 mg / kg of body weight / day of a Compound of the Disclosure; and in another embodiment, from about 0.025 mg / kg of body weight / day to about 20 mg / kg of body weight / day of a Compound of the Disclosure. A composition of the disclosure can be prepared by a method comprising admixing a Compound of the Disclosure with a pharmaceutically acceptable excipient or carrier. Admixing can be accomplished using methods known for admixing a compound and a pharmaceutically acceptable excipient or carrier. In another embodiment, the Compound of the Disclosure is present in the composition in an effective amount. The following examples are illustrative, but not limiting, of the compounds, compositions and methods of the present disclosure. Suitable modifications and adaptations of the variety of conditions and parameters normally encountered in clinical therapy, and which are obvious to those skilled in the art in view of this disclosure are within the spirit and scope of the disclosure. EXAMPLES General experimental conditions for Examples 1-23 Hereinafter, the term “h” means hours, “eq” means equivalents, “RT” means room temperature, “LC-MS” means Liquid chromatography–mass spectrometry, UPLC means Ultra Performance Liquid Chromatography, “Rt” means retention time, “DMSO-d6” means deuterated dimethyl sulfoxide, “NH4OAc” means ammonium acetate, “DCM” means dichloromethane, “ACN” means acetonitrile, “EtOAc” means ethyl acetate, “DMSO” means dimethyl sulfoxide, “EtOH” means ethanol, “MeOH” means methanol, “Pd2(dba)3” means tris(dibenzylideneacetone)dipalladium (0), ”Boc” means tert-Butyloxycarbonyl, “XantPhos” means 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, “XantPhos Pd G3” means [(4,5- bis(diphenylphosphino)-9,9-dimethylxanthene)-2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate and “tBuXPhos Pd G3” means [(2-di-tert-butylphosphino-2′,4′,6′-triisopropyl- 1,1′-biphenyl)-2-(2′-amino-1,1′-biphenyl)] palladium(II) methanesulfonate. 1H NMR spectra were recorded on a Variant (400 MHz). LC-MS analysis of the compounds was conducted as per one of the following methods: METHOD-A: BEH C18 (50 mm x 2.1 mm, 1.7 µm); wavelength: PDA MaxPlot 210.0 - 400 nm; flow: 0.50 mL / min; column temperature: 35 °C; run time: 9 min; mobile phase A: 50 mM ammonium formate solution adjusted at pH 4 with formic acid, B: water, C: ACN; gradient: A:B:C 0.5 min in 5:85:10 + from 5:85:10 to 5:10:85 in 4.5 min + 4 min in 5:10:85; chromatographic system: Acquity H Class UPLC; mass spectrometer: Acquity QDa. METHOD-B: Luna C18 (50 mm x 2.0 mm, 5 µm); wavelength: PDA MaxPlot 210.0 - 400 nm; flow: 0.50 mL / min; column temperature: 40 °C; run time: 5 min; mobile phase A: 10 mM ammonium formate buffer pH 4 with HCOOH, B: water, C: ACN; gradient: A:B:C 0.3 min in 5:85:10 + from 5:85:10 to 5:10:85 in 1.7 min + 3.0 min in 5:10:85; chromatographic system: Waters Alliance HT 2795 and PDA 2996; mass spectrometer: Micromass ZQ2000 single quadrupole (ESI). METHOD-C: SunFire C18 (100 mm x 2.1 mm, 3.5 µm); wavelength: PDA MaxPlot 210.0 - 400 nm; flow: 0.50 mL / min; column temperature: 40 °C; run time: 20 min; mobile phase A: 10 mM ammonium formate buffer pH 4 with HCOOH, B: water, C: ACN; gradient: A:B:C 3 min in 5:85:10 + 5:85:10 to 5:10:85 in 9 min + 8 min in 5:10:85; chromatographic system: Waters Alliance HT 2795 and PDA 2996; mass spectrometer: Micromass ZQ2000 single quadrupole (ESI). General Procedure A Method 1 1,2-Dimethylethylenediamine (0.2 eq) was added to a stirred solution of the appropriate bromoindole derivative (ex: 5-bromoindole) (1 eq), the appropriate substituted bromopyridine (ex: 2-bromo-5-nitropyridine) (1.3 eq), K3PO4 (2.6 eq) and CuI (0.1 eq) in toluene (3 mL / mmol). The solution was purged with argon and stirred at 110 °C for 16 h. After the reaction mixture was cooled to RT, water and EtOAc were added. The aqueous layer was extracted with EtOAc (x3). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, filtered and volatiles were removed under reduced pressure. The resulting crude product was purified by column chromatography on silica gel using hexane / EtOAc to obtain the desired bromoindole intermediate (ex: 5-bromo-1-(5-nitropyridin-2-yl)-1H-indole). Method 2 The appropriate bromoindole derivative (ex: 4-bromo-1H-indole) (1 eq), the appropriate bromo nitropyridine (ex: 2-bromo-5-nitropyridine) (1.5 eq) and KOH (2.5 eq) were mixed in DMSO (1.3 mL / mmol) and the solution was purged with argon and stirred at 140 °C for 16 h. After the reaction mixture was cooled to RT, NH4Cl and EtOAc were added. The aqueous layer was extracted with EtOAc (x3). The combined organic layers were washed with water (x2) and brine, dried over anhydrous sodium sulfate, filtered and volatiles were removed under reduced pressure. The resulting crude was purified by column chromatography on silica gel using hexane / DCM to obtain the desired indole intermediate (ex: 4-bromo-1-(5-nitropyridin-2-yl)-1H-indole). Intermediate 1 5-Bromo-1-(5-nitropyridin-2-yl)-1H-indole Synthesized following the General Procedure A, method 1, using 5-bromoindole and 2- bromo-5-nitropyridine. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-50%), and isolated as a yellow solid. Yield: 68 mg (42%). 1H NMR (400 MHz, DMSO-d6): δ 9.38 (dd, J = 2.8, 0.6 Hz, 1H), 8.72 (dd, J = 9.2, 2.8 Hz, 1H), 8.64 – 8.59 (m, 1H), 8.29 (d, J = 3.7 Hz, 1H), 8.06 (dd, J = 9.3, 0.6 Hz, 1H), 7.91 – 7.88 (m, 1H), 7.49 (dd, J = 8.9, 2.1 Hz, 1H), 6.89 (dd, J = 3.6, 0.8 Hz, 1H). Intermediate 2 Tert-butyl (6-(5-bromo-1H-indol-1-yl)pyridin-3-yl)carbamate Synthesized following the General Procedure A, method 1, using 5-bromoindole and tert- butyl (6-bromopyridin-3-yl)carbamate. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as an off-white solid. Yield: 500 mg (50%). LC-MS [M+H]+: 388.0 / 390.0, Rt = 3.98 min (Method-B). Intermediate 3 5-Bromo-1-(6-nitropyridin-2-yl)-1H-indole Synthesized following the General Procedure A, method 1, using 5-bromoindole and 2- bromo-6-nitropyridine. The reaction mixture was stirred at 110 °C for 72 h. The crude product was purified by column chromatography on silica gel using hexane / DCM (0%-100%), and isolated as a yellow solid. Yield: 666 mg (82%). 1H NMR (400 MHz, DMSO-d6): δ 8.77 (d, J = 8.9 Hz, 1H), 8.38 (t, J = 8.0 Hz, 1H), 8.32 – 8.27 (m, 2H), 8.16 (d, J = 7.6 Hz, 1H), 7.89 (d, J = 2.0 Hz, 1H), 7.51 (dd, J = 8.9, 2.1 Hz, 1H), 6.86 (d, J = 3.6 Hz, 1H). Intermediate 4 4-Bromo-1-(5-nitropyridin-2-yl)-1H-indole Synthesized following the General Procedure A, method 2, using 4-bromo-1H-indole and 2-bromo-5-nitropyridine. The crude product was purified by column chromatography on silica gel using hexane / DCM (0%-60%), and isolated as a yellow solid. Yield: 446 mg (55%). 1H NMR (400 MHz, DMSO-d6): δ 9.40 (dd, J = 2.8, 0.6 Hz, 1H), 8.74 (dd, J = 9.2, 2.8 Hz, 1H), 8.66 (d, J = 8.5 Hz, 1H), 8.35 (d, J = 3.7 Hz, 1H), 8.09 (dd, J = 9.3, 0.7 Hz, 1H), 7.50 (dd, J = 7.7, 0.8 Hz, 1H), 7.34 – 7.27 (m, 1H), 6.86 (dd, J = 3.7, 0.8 Hz, 1H). Intermediate 5 Tert-butyl (6-(4-bromo-1H-indol-1-yl)pyridin-3-yl)carbamate Synthesized following the General Procedure A, method 1, using 4-bromo-1H-indole and tert-Butyl (6-bromopyridin-3-yl)carbamate. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-30%), and isolated as an off-white solid. Yield: 101 mg (51%). LC-MS [M+H]+: 387.8 / 389.9, Rt = 3.98 min (Method-B). Intermediate 6 4-Bromo-1-(6-nitropyridin-2-yl)-1H-indole Synthesized following the General Procedure A, method 1, using 4-bromo-1H-indole and 2-bromo-6-nitropyridine. The reaction mixture was stirred at 110 °C for 96 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-50%), and isolated as a yellow solid. Yield: 330 mg (68%). 1H NMR (400 MHz, DMSO-d6): δ 8.84 (d, J = 8.4 Hz, 1H), 8.44 – 8.32 (m, 3H), 8.20 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 7.7 Hz, 1H), 7.33 (t, J = 8.1 Hz, 1H), 6.84 (d, J = 3.6 Hz, 1H). Intermediate 7 6-(5-Bromo-1H-indol-1-yl)-N,N-dimethylpyridin-3-amine Synthesized following the General Procedure A, method 1, using 5-bromoindole and 6- bromo-N,N-dimethylpyridin-3-amine. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as an orange oil. Yield: 280 mg (58%). LC-MS [M+H]+: 316.0 / 318.0, Rt = 3.89 min (Method-B). Intermediate 8 5-Bromo-3-methyl-1-(5-nitropyridin-2-yl)-1H-indole Synthesized following the General Procedure A, method 1, using 5-bromo-3-methyl-1H- indole and 2-bromo-5-nitropyridine. The reaction mixture was stirred at 110 °C for 72 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%- 20%), and isolated as a yellow solid. Yield: 94 mg (15%). LC-MS [M+H]+: Rt = 4.07 min (Method-B). Intermediate 9 5-Bromo-2-methyl-1-(5-nitropyridin-2-yl)-1H-indole Synthesized following the General Procedure A, method 1, using 5-bromo-2-methylindole and 2-bromo-5-nitropyridine. The reaction mixture was stirred at 110 °C for 72 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as an orange solid. Yield: 190 mg (42%). LC-MS [M+H]+: Rt = 3.83 min (Method-B). General Procedure B Method 1 In a sealed tube, to a degassed solution of the appropriate indole derivative (ex: Intermediate 1: 5-bromo-1-(5-nitropyridin-2-yl)-1H-indole) (1 eq), the appropriate amine (ex: p- toluidine) (1.35 eq) and Cs2CO3 (2.09 eq) in dioxane (5 mL / mmol) were added Pd2(dba)3 (0.11 eq) and XantPhos (0.23 eq). The solution was degassed again and stirred at 140 °C for 3 h. After the reaction mixture was cooled to RT, water and EtOAc were added. The aqueous layer was extracted with EtOAc (x3). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, filtered and volatiles were removed under reduced pressure. The resulting crude product was purified by column chromatography on silica gel using hexane / EtOAc to obtain the desired indole intermediate (ex: Intermediate 10: 1-(5-nitropyridin-2- yl)-N-(p-tolyl)-1H-indol-5-amine). Method 2 To a solution of the appropriate indole derivative (ex: Intermediate 3: 5-bromo-1-(6- nitropyridin-2-yl)-1H-indole) (1 eq), the appropriate amine (ex: 4-chloroaniline) (1.3 eq) and Cs2CO3 (2.6 eq) in dioxane (3 mL / mmol) was added XantPhos Pd G3 (0.1 eq). The solution was degassed again and stirred at 100 °C for 16 h. After the reaction mixture was cooled to RT, water and EtOAc were added. The aqueous layer was extracted with EtOAc (x3). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, filtered and volatiles were removed under reduced pressure. The resulting crude product was purified by column chromatography on silica gel using hexane / DCM to obtain the desired indole intermediate (ex: Intermediate 16: N-(4-chlorophenyl)- 1-(6-nitropyridin-2-yl)-1H-indol-5-amine). Intermediate 10 1-(5-Nitropyridin-2-yl)-N-(p-tolyl)-1H-indol-5-amine Synthesized following the General Procedure B, method 1, using 5-bromo-1-(5- nitropyridin-2-yl)-1H-indole (Intermediate 1) and p-toluidine. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as a red solid. Yield: 40 mg (46%).1H NMR (400 MHz, DMSO-d6): δ 9.34 (d, J = 2.6 Hz, 1H), 8.65 (dd, J = 9.3, 2.8 Hz, 1H), 8.53 (d, J = 9.0 Hz, 1H), 8.14 (d, J = 3.7 Hz, 1H), 7.97 (s, 2H), 7.29 (d, J = 2.2 Hz, 1H), 7.08 – 6.96 (m, 4H), 6.79 (dd, J = 3.6, 0.7 Hz, 1H), 6.46 (d, J = 8.3 Hz, 1H), 2.23 (s, 3H). Intermediate 11 N-(3-methoxyphenyl)-1-(5-nitropyridin-2-yl)-1H-indol-5-amine Synthesized following the General Procedure B, method 1, using 5-bromo-1-(5- nitropyridin-2-yl)-1H-indole (Intermediate 1) and m-anisidine. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-10%), and isolated as a red solid. Yield: 30 mg (41%). 1H NMR (400 MHz, DMSO-d6): δ 9.35 (dd, J = 2.8, 0.6 Hz, 1H), 8.66 (dd, J = 9.3, 2.8 Hz, 1H), 8.56 (d, J = 8.9 Hz, 1H), 8.17 (d, J = 3.7 Hz, 1H), 8.13 (s, 1H), 7.99 (dd, J = 9.4, 0.6 Hz, 1H), 7.38 (d, J = 2.2 Hz, 1H), 7.15 – 7.07 (m, 2H), 6.82 (dd, J = 3.7, 0.7 Hz, 1H), 6.69 – 6.62 (m, 1H), 6.60 (t, J = 2.2 Hz, 1H), 6.36 (ddd, J = 8.2, 2.5, 0.8 Hz, 1H), 3.71 (s, 3H). Intermediate 12 1-(5-Nitropyridin-2-yl)-N-(m-tolyl)-1H-indol-5-amine Synthesized following the General Procedure B, method 1, using 5-bromo-1-(5- nitropyridin-2-yl)-1H-indole (Intermediate 1) and m-toluidine. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as a red solid. Yield: 30 mg (28%). 1H NMR (400 MHz, DMSO-d6): δ 9.33 (dd, J = 2.8, 0.6 Hz, 1H), 8.63 (dd, J = 9.3, 2.8 Hz, 1H), 8.53 (dt, J = 9.0, 0.7 Hz, 1H), 8.14 (d, J = 3.7 Hz, 1H), 8.04 – 7.92 (m, 2H), 7.33 (d, J = 2.1 Hz, 1H), 7.10 – 7.04 (m, 2H), 6.88 – 6.82 (m, 2H), 6.79 (dd, J = 3.7, 0.7 Hz, 1H), 6.60 – 6.56 (m, 1H), 2.22 (s, 3H). Intermediate 13 Tert-butyl (6-(5-((4-chlorophenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate Synthesized following the General Procedure B, method 2, using tert-butyl (6-(5-bromo- 1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 2) and 4-chloroaniline. tBuXPhos Pd G3 (0.1 eq) was also added, and the solution was degassed and stirred at 100 ºC for additional 24 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%- 40%), and isolated as a colorless oil. Yield: 65 mg (25%). LC-MS [M+H]+: 435.1 / 437.0, Rt = 4.00 min (Method-B). Intermediate 14 Tert-butyl (6-(5-((3-chlorophenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate Synthesized following the General Procedure B, method 2, using tert-butyl (6-(5-bromo- 1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 2) and 3-chloroaniline. tBuXPhos Pd G3 (0.1 eq) was also added, and the solution was degassed and stirred at 100 ºC for additional 32h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%- 40%), and isolated as an off-white solid. Yield: 40 mg (16%). LC-MS [M+H]+: 435.1 / 437.0, Rt = 4.01 min (Method-B). Intermediate 15 Tert-butyl (6-(5-((4-cyanophenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate Synthesized following the General Procedure B, method 2, using tert-butyl (6-(5-bromo- 1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 2) and 4-aminobenzonitrile. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-100%), and isolated as a colorless oil. Yield: 40 mg (15%). LC-MS [M+H]+: 426.1, Rt = 3.68 min (Method-B). Intermediate 16 N-(4-chlorophenyl)-1-(6-nitropyridin-2-yl)-1H-indol-5-amine Synthesized following the General Procedure B, method 2, using 5-bromo-1-(6- nitropyridin-2-yl)-1H-indole (Intermediate 3) and 4-chloroaniline. The crude product was purified by column chromatography on silica gel using hexane / DCM (0%-100%), and isolated as a yellow solid. Yield: 48 mg (21%).1H NMR (400 MHz, DMSO-d6): δ 8.77 – 8.71 (m, 1H), 8.32 (dd, J = 8.3, 7.6 Hz, 1H), 8.28 – 8.19 (m, 2H), 8.17 (d, J = 3.6 Hz, 1H), 8.09 (dd, J = 7.6, 0.6 Hz, 1H), 7.36 (d, J = 2.4 Hz, 1H), 7.24 – 7.18 (m, 2H), 7.10 (dd, J = 8.9, 2.3 Hz, 1H), 7.05 – 7.00 (m, 2H), 6.77 (dd, J = 3.6, 0.8 Hz, 1H). Intermediate 17 N-(3-methoxyphenyl)-1-(6-nitropyridin-2-yl)-1H-indol-5-amine Synthesized following the General Procedure B, method 2, using 5-bromo-1-(6- nitropyridin-2-yl)-1H-indole (Intermediate 3) and m-anisidine. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-100%), and isolated as a pale- yellow solid. Yield: 129 mg (57%). 1H NMR (400 MHz, DMSO-d6): δ 8.75 – 8.69 (m, 1H), 8.35 – 8.21 (m, 2H), 8.16 (d, J = 3.6 Hz, 1H), 8.10 – 8.06 (m, 2H), 7.37 (d, J = 2.1 Hz, 1H), 7.13 – 7.04 (m, 2H), 6.77 (dd, J = 3.6, 0.8 Hz, 1H), 6.63 (ddd, J = 8.1, 2.1, 0.9 Hz, 1H), 6.57 (t, J = 2.2 Hz, 1H), 6.33 (ddd, J = 8.2, 2.4, 0.8 Hz, 1H), 3.69 (s, 3H). Intermediate 18 N-(4-methoxyphenyl)-1-(5-nitropyridin-2-yl)-1H-indol-4-amine Synthesized following the General Procedure B, method 2, using 4-bromo-1-(5- nitropyridin-2-yl)-1H-indole (Intermediate 4) and p-Anisidine. tBuXPhos Pd G3 (0.1 eq) was used instead of XantPhos Pd G3. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as a red solid. Yield: 40 mg (16%). LC-MS [M+H]+: 360.9, Rt = 3.71 min (Method-B). 1H NMR (400 MHz, DMSO-d6): δ 9.37 (d, J = 2.8 Hz, 1H), 8.69 (dd, J = 9.2, 2.8 Hz, 1H), 8.06 (d, J = 3.7 Hz, 1H), 8.01 (t, J = 7.9 Hz, 2H), 7.91 (s, 1H), 7.17 – 7.06 (m, 4H), 6.94 – 6.88 (m, 2H), 6.80 (d, J = 7.8 Hz, 1H), 3.74 (s, 3H). Intermediate 19 N-(4-chlorophenyl)-1-(5-nitropyridin-2-yl)-1H-indol-4-amine Synthesized following the General Procedure B, method 2, using 4-bromo-1-(5- nitropyridin-2-yl)-1H-indole (Intermediate 4) and 4-chloroaniline. tBuXPhos Pd G3 (0.1 eq) was used instead of XantPhos Pd G3. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as a red solid. Yield: 90 mg (36%). 1H NMR (400 MHz, DMSO-d6): δ 9.39 (d, J = 2.8 Hz, 1H), 8.77 – 8.64 (m, 1H), 8.33 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 3.7 Hz, 1H), 8.02 (d, J = 9.2 Hz, 1H), 7.31 – 7.20 (m, 3H), 7.16 – 7.08 (m, 2H), 7.05 (d, J = 7.8 Hz, 1H), 6.97 (d, J = 3.7 Hz, 1H). Intermediate 20 Tert-butyl (6-(4-(p-tolylamino)-1H-indol-1-yl)pyridin-3-yl)carbamate Synthesized following the General Procedure B, method 2, using tert-butyl (6-(4-bromo- 1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 5) and p-toluidine. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as a yellow solid. Yield: 26 mg (35%). LC-MS [M+H]+: 415.3, Rt = 3.97 min (Method-B). Intermediate 21 Tert-butyl (6-(4-((3-methoxyphenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate Synthesized following the General Procedure B, method 2, using tert-butyl (6-(4-bromo- 1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 5) and m-Anisidine. tBuXPhos Pd G3 (0.1 eq) was used instead of XantPhos Pd G3. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as an orange oil. Yield: 120 mg (60%). LC-MS [M+H]+: 431.2, Rt = 3.82 min (Method-B). Intermediate 22 Tert-butyl (6-(4-(m-tolylamino)-1H-indol-1-yl)pyridin-3-yl)carbamate Synthesized following the General Procedure B, method 2, using tert-butyl (6-(4-bromo- 1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 5) and m-toluidine. tBuXPhos Pd G3 (0.1 eq) was used instead of XantPhos Pd G3. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as an orange oil. Yield: 120 mg (62%). LC-MS [M+H]+: 415.2, Rt = 3.99 min (Method-B). Intermediate 23 Tert-butyl (6-(4-((3-chlorophenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate Synthesized following the General Procedure B, method 2, using tert-butyl (6-(4-bromo- 1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 5) and 3-chloroaniline. tBuXPhos Pd G3 (0.1 eq) was used instead of XantPhos Pd G3. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-10%), and isolated as a yellow oil. Yield: 110 mg (38%). LC-MS [M+H]+: 435.2 / 437.0, Rt = 4.06 min (Method-B). Intermediate 24 1-(6-Nitropyridin-2-yl)-N-(p-tolyl)-1H-indol-4-amine Synthesized following the General Procedure B, method 2, using 4-bromo-1-(6- nitropyridin-2-yl)-1H-indole (Intermediate 6) and p-toluidine. tBuXPhos Pd G3 (0.1 eq) was used instead of XantPhos Pd G3. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-50%), and isolated as an orange solid. Yield: 92 mg (26%). LC-MS [M+H]+: 345.1, Rt = 3.83 min (Method-B). Intermediate 25 N-(4-chlorophenyl)-1-(6-nitropyridin-2-yl)-1H-indol-4-amine Synthesized following the General Procedure B, method 2, using 4-bromo-1-(6- nitropyridin-2-yl)-1H-indole (Intermediate 6) and 4-chloroaniline. tBuXPhos Pd G3 (0.3 eq) was used instead of XantPhos Pd G3. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-50%), and isolated as a brown solid. Yield: 120 mg (42%). 1H NMR (400 MHz, DMSO-d6): δ 8.42 – 8.26 (m, 4H), 8.16 (s, 1H), 8.15 – 8.11 (m, 1H), 7.31 – 7.22 (m, 3H), 7.15 – 7.08 (m, 2H), 7.05 (d, J = 7.7 Hz, 1H), 6.96 – 6.92 (m, 1H). Example 1 1-(5-(Dimethylamino)pyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-5-amine Synthesized following the General Procedure B, method 2, using 6-(5-bromo-1H-indol-1- yl)-N,N-dimethylpyridin-3-amine (Intermediate 7) and p-Anisidine. tBuXPhos Pd G3 (0.2 eq) was used instead of XantPhos Pd G3. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-10%), followed by reverse phase flash column chromatography (C18, NH4OAc (aq) 10 mM (pH 7) / ACN 0%-100%), and isolated as an off-white solid. Yield: 38 mg (12%). LC-MS [M+H]+: 359.5, Rt = 11.90 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 8.04 (d, J = 3.1 Hz, 1H), 8.03 – 7.96 (m, 1H), 7.75 (d, J = 3.3 Hz, 1H), 7.57 (s, 1H), 7.51 (dd, J = 9.0, 0.6 Hz, 1H), 7.34 (dd, J = 9.0, 3.2 Hz, 1H), 7.19 (d, J = 2.2 Hz, 1H), 7.02 – 6.96 (m, 2H), 6.90 (dd, J = 8.9, 2.2 Hz, 1H), 6.86 – 6.80 (m, 2H), 6.51 (dd, J = 3.4, 0.8 Hz, 1H), 3.70 (s, 3H), 2.97 (s, 6H). Intermediate 26 N-(4-methoxyphenyl)-3-methyl-1-(5-nitropyridin-2-yl)-1H-indol-5-amine Synthesized following the General Procedure B, method 2, using 5-bromo-3-methyl-1-(5- nitropyridin-2-yl)-1H-indole (Intermediate 8) and p-Anisidine. The crude was purified by column chromatography on silica gel using hexane / EtOAc (0%-40%), and isolated as an orange solid. Yield: 51 mg (48%). LC-MS [M+H]+: 374.8, Rt = 3.83 min (Method-B). Intermediate 27 N-(4-methoxyphenyl)-2-methyl-1-(5-nitropyridin-2-yl)-1H-indol-5-amine Synthesized following the General Procedure B, method 2, using 5-bromo-2-methyl-1-(5- nitropyridin-2-yl)-1H-indole (Intermediate 9) and p-Anisidine. The crude was purified by column chromatography on silica gel using hexane / EtOAc (0%-40%), and isolated as an orange solid. Yield: 94 mg (44%). LC-MS [M+H]+: 374.8, Rt = 3.71 min (Method-B). Intermediate 28 N-(4-methoxyphenyl)-1-(6-nitropyridin-2-yl)-1H-indol-5-amine Synthesized following the General Procedure B, method 1, using 5-bromo-1-(6- nitropyridin-2-yl)-1H-indole (Intermediate 3) and p-anisidine. The crude was used in the next step without further purification. Yield: 117 mg (quantitative). Intermediate 29 N-(4-methoxyphenyl)-1-(6-nitropyridin-2-yl)-1H-indol-4-amine Synthesized following the General Procedure B, method 1, using 4-bromo-1-(6- nitropyridin-2-yl)-1H-indole (Intermediate 6) and p-anisidine. The crude was used in the next step without further purification. Yield: 170 mg (quantitative). Intermediate 30 N-(4-methoxyphenyl)-1-(5-nitropyridin-2-yl)-1H-indol-5-amine Synthesized following the General Procedure B, method 1, using 5-bromo-1-(5- nitropyridin-2-yl)-1H-indole (Intermediate 1) and p-anisidine. The crude was used in the next step without further purification. Yield: 170 mg (quantitative). Intermediate 31 N-(3-methoxyphenyl)-N-methyl-1-(5-nitropyridin-2-yl)-1H-indol-5-amine N-(3-methoxyphenyl)-1-(5-nitropyridin-2-yl)-1H-indol-5-amine (Intermediate 11, 80 mg, 0.22 mmol, 1 eq) and CH2O 37% in H2O (35 µL, 0.44 mmol, 2 eq) were mixed in 1.5 mL of ACN. The solution was stirred at RT for 30 min and then NaBH3CN (18 mg, 0.29 mmol, 1.3 eq) was added. The reaction mixture was stirred at RT for 16 h and the solvent was removed under vacuum. The dry residue was taken up into EtOAc and washed with water. After extraction with EtOAc (x3), the combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, filtered and volatiles were removed under reduced pressure. Purification of the crude product by column chromatography on silica gel using hexane / EtOAc (0%-30%) afforded the desired indole as an orange solid. Yield: 40 mg (48%). LC-MS [M+H]+: 375.0, Rt = 3.99 min (Method-B). General Procedure C Method 1 To a solution of the appropriate nitro-substituted intermediate (ex: Intermediate 11: N-(3- methoxyphenyl)-1-(5-nitropyridin-2-yl)-1H-indol-5-amine) in EtOH (25 mL / mmol) was added Pd / C 10% (wet) (0.1 eq). The solution was stirred under H2 atmosphere at RT for 16 h. The reaction mixture was filtered through a plug of celite which was washed with MeOH. The filtrate was concentrated under vacuum. The resulting crude was purified by column chromatography on silica gel using hexane / EtOAc to obtain the desired indole compound (ex: Example 3: 1-(5- aminopyridin-2-yl)-N-(3-methoxyphenyl)-1H-indol-5-amine). Method 2 A mixture of the appropriate nitro-substituted intermediate (ex: Intermediate 31: N-(4- methoxyphenyl)-1-(6-nitropyridin-2-yl)-1H-indol-5-amine) and SnCl2 ^ H2O (4 eq) in EtOAc (12 mL / mmol) was refluxed overnight. On cooling, the reaction mixture was filtered through a short silica gel pad. The obtained solution was washed with saturated aqueous sodium bicarbonate and extracted with EtOAc (x3). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and volatiles were removed under reduced pressure. The resulting crude was purified by column chromatography on silica gel using DCM / MeOH to obtain the desired indole compound (ex: Example 14: 1-(6-aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-5-amine). Example 2 1-(5-Aminopyridin-2-yl)-N-(p-tolyl)-1H-indol-5-amine Synthesized following the General Procedure C, method 1, using 1-(5-nitropyridin-2-yl)- N-(p-tolyl)-1H-indol-5-amine (Intermediate 10). The crude product was purified by preparative HPLC (water with 0.2% HCOOH / ACN, 45%-65 %), and isolated as a grey solid. Yield: 5.8 mg (16%). LC-MS [M+H]+: 315.2, Rt = 4.21 min (Method-A). 1H NMR (400 MHz, DMSO-d6): δ 7.96 – 7.86 (m, 2H), 7.76 – 7.62 (m, 2H), 7.36 (d, J = 8.7 Hz, 1H), 7.26 (d, J = 2.1 Hz, 1H), 7.19 – 7.11 (m, 1H), 7.03 – 6.87 (m, 5H), 6.55 – 6.46 (m, 1H), 5.34 (s, 2H), 2.20 (s, 3H). Example 3 1-(5-Aminopyridin-2-yl)-N-(3-methoxyphenyl)-1H-indol-5-amine Synthesized following the General Procedure C, method 1, using N-(3-methoxyphenyl)-1- (5-nitropyridin-2-yl)-1H-indol-5-amine (Intermediate 11). The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-50%), and isolated as a brown solid. Yield: 9 mg (34%). LC-MS [M+H]+: 331.4, Rt = 10.18 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 7.94 (d, J = 8.8 Hz, 1H), 7.92 – 7.87 (m, 2H), 7.71 (d, J = 3.3 Hz, 1H), 7.37 (d, J = 8.6 Hz, 1H), 7.32 (d, J = 2.1 Hz, 1H), 7.15 (dd, J = 8.7, 2.9 Hz, 1H), 7.06 (t, J = 8.1 Hz, 1H), 6.99 (dd, J = 8.9, 2.2 Hz, 1H), 6.60 – 6.48 (m, 3H), 6.28 (dd, J = 8.0, 2.4 Hz, 1H), 5.35 (s, 2H), 3.68 (s, 3H). Example 4 1-(5-Aminopyridin-2-yl)-N-(m-tolyl)-1H-indol-5-amine Synthesized following the General Procedure C, method 1, using 1-(5-nitropyridin-2-yl)- N-(m-tolyl)-1H-indol-5-amine (Intermediate 12). The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), followed by preparative HPLC (10 mM NH4HCO3 (pH 7 with HCOOH) / ACN, 50-70 %), and isolated as a grey solid. Yield: 8 mg (29%). LC-MS [M+H]+: 315.2, Rt = 4.19 min (Method-A). 1H NMR (400 MHz, DMSO-d6) δ 7.96 – 7.83 (m, 2H), 7.77 (s, 1H), 7.69 (d, J = 3.3 Hz, 1H), 7.35 (d, J = 8.6 Hz, 1H), 7.28 (d, J = 2.2 Hz, 1H), 7.13 (dd, J = 8.7, 2.9 Hz, 1H), 7.06 – 6.91 (m, 2H), 6.81 – 6.72 (m, 2H), 6.54 – 6.46 (m, 2H), 5.33 (s, 2H), 2.19 (s, 3H). Example 5 1-(5-Aminopyridin-2-yl)-N-(3-methoxyphenyl)-N-methyl-1H-indol-5-amine Synthesized following the General Procedure C, method 1, using N-(3-methoxyphenyl)-N- methyl-1-(5-nitropyridin-2-yl)-1H-indol-5-amine (Intermediate 31). The reaction was stirred under H2 atmosphere at RT for 2h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-100%), and isolated as a brown solid. Yield: 4 mg (11%). LC-MS [M+H]+: 345.5, Rt = 11.34 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 8.02 – 7.96 (m, 1H), 7.92 – 7.89 (m, 1H), 7.77 (d, J = 3.3 Hz, 1H), 7.41 – 7.37 (m, 2H), 7.16 (dd, J = 8.6, 2.9 Hz, 1H), 7.06 – 6.97 (m, 2H), 6.62 – 6.59 (m, 1H), 6.29 (dd, J = 8.2, 2.4 Hz, 2H), 6.24 (t, J = 2.3 Hz, 1H), 5.39 (s, 2H), 3.64 (s, 3H), 3.26 (s, 3H). Example 6 1-(6-Aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-5-amine Synthesized following the General Procedure C, method 1, using N-(4-chlorophenyl)-1-(6- nitropyridin-2-yl)-1H-indol-5-amine (Intermediate 16). PtO2 (0.1 eq) was used instead of Pd / C 10% (wet) and the reaction was stirred under H2 atmosphere at RT for 3h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-50%), followed by preparative HPLC (10 mM NH4HCO3 (pH 7 with HCOOH) / ACN, 60%-80%), and isolated as a white solid. Yield: 17 mg (39%). LC-MS [M+H]+: 335.2 / 337.1, Rt = 4.65 min (Method-A). 1H NMR (400 MHz, DMSO-d6): δ 8.41 (d, J = 8.9 Hz, 1H), 8.09 (s, 1H), 7.86 (d, J = 3.5 Hz, 1H), 7.51 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 2.2 Hz, 1H), 7.22 – 7.15 (m, 2H), 7.01 – 6.95 (m, 3H), 6.75 (d, J = 7.7 Hz, 1H), 6.60 – 6.55 (m, 1H), 6.30 (d, J = 8.0 Hz, 1H), 6.21 (s, 2H). Example 7 1-(6-Aminopyridin-2-yl)-N-(3-methoxyphenyl)-1H-indol-5-amine Synthesized following the General Procedure C, method 1, using N-(3-methoxyphenyl)-1- (6-nitropyridin-2-yl)-1H-indol-5-amine (Intermediate 17). The reaction was stirred under H2 atmosphere at RT for 3h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-50%), followed by reverse phase flash column chromatography (C18, HCOONH4 (aq) 10 mM (pH 4) / ACN 0%-100%), and isolated as an off-white solid. Yield: 52 mg (44%). LC-MS [M+H]+: 331.1, Rt = 11.00 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 8.39 (d, J = 8.8 Hz, 1H), 7.94 (s, 1H), 7.85 (d, J = 3.4 Hz, 1H), 7.50 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 2.2 Hz, 1H), 7.07 (t, J = 8.1 Hz, 1H), 7.00 (dd, J = 8.9, 2.2 Hz, 1H), 6.75 (d, J = 7.3 Hz, 1H), 6.62 – 6.56 (m, 2H), 6.54 (t, J = 2.2 Hz, 1H), 6.33 – 6.27 (m, 2H), 6.21 (s, 2H), 3.69 (s, 3H). Example 8 1-(5-Aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-4-amine Synthesized following the General Procedure C, method 1, using N-(4-methoxyphenyl)-1- (5-nitropyridin-2-yl)-1H-indol-4-amine (Intermediate 18). The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-100%), and isolated as a brown solid. Yield: 7 mg (19%). LC-MS [M+H]+: 331.1, Rt = 10.32 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 7.90 (dt, J = 2.9, 0.7 Hz, 1H), 7.75 (s, 1H), 7.58 (d, J = 3.5 Hz, 1H), 7.37 – 7.30 (m, 2H), 7.18 – 7.10 (m, 3H), 6.97 (t, J = 8.0 Hz, 1H), 6.91 – 6.85 (m, 2H), 6.79 (dt, J = 3.4, 0.8 Hz, 1H), 6.67 (d, J = 7.7 Hz, 1H), 5.38 (s, 2H), 3.73 (s, 3H). Example 9 1-(5-Aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-4-amine Synthesized following the General Procedure C, method 1, using N-(4-chlorophenyl)-1-(5- nitropyridin-2-yl)-1H-indol-4-amine (Intermediate 19). PtO2 (0.1 eq) was used instead of Pd / C 10% (wet). The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-100%), and isolated as a brown solid. Yield: 25 mg (30%). LC-MS [M+H]+: 335.1 / 337.0, Rt = 11.35 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 8.21 (s, 1H), 7.91 (dd, J = 2.9, 0.7 Hz, 1H), 7.64 (d, J = 3.4 Hz, 1H), 7.53 (dt, J = 8.3, 0.8 Hz, 1H), 7.36 (dd, J = 8.6, 0.7 Hz, 1H), 7.28 – 7.21 (m, 2H), 7.16 (dd, J = 8.6, 2.9 Hz, 1H), 7.13 – 7.04 (m, 3H), 6.90 (d, J = 7.6 Hz, 1H), 6.68 (dt, J = 3.5, 0.7 Hz, 1H), 5.41 (s, 2H). Example 10 1-(6-Aminopyridin-2-yl)-N-(p-tolyl)-1H-indol-4-amine Synthesized following the General Procedure C, method 1, using 1-(6-nitropyridin-2-yl)- N-(p-tolyl)-1H-indol-4-amine (Intermediate 24). The reaction was stirred under H2 atmosphere at RT for 3 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-40%), followed by reverse phase flash column chromatography (C18, NH4OAc (aq) 10 mM (pH 7) / ACN 60%-75%), and isolated as an off-white solid. Yield: 24 mg (29%). LC-MS [M+H]+: 315.4, Rt = 11.76 min (Method-C).1H NMR (400 MHz, DMSO-d6): δ 7.90 (s, 1H), 7.83 (dt, J = 8.3, 0.8 Hz, 1H), 7.74 (d, J = 3.6 Hz, 1H), 7.52 (t, J = 7.9 Hz, 1H), 7.06 (s, 4H), 7.03 (d, J = 8.0 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 6.80 (dd, J = 3.5, 0.8 Hz, 1H), 6.74 (d, J = 7.8 Hz, 1H), 6.33 (d, J = 8.1 Hz, 1H), 6.21 (s, 2H), 2.24 (s, 3H). Example 11 1-(6-Aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-4-amine Synthesized following the General Procedure C, method 1, using N-(4-chlorophenyl)-1-(6- nitropyridin-2-yl)-1H-indol-4-amine (Intermediate 25). PtO2 (0.2 eq) was used instead of Pd / C 10% (wet) and the reaction was stirred under H2 atmosphere at RT for 2 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-50%), followed by reverse phase flash column chromatography (C18, NH4OAc (aq) 10 mM (pH 7) / ACN 60%- 80%), and isolated as a grey solid. Yield: 17 mg (15%). LC-MS [M+H]+: 335.1, Rt = 12.01 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 8.21 (s, 1H), 7.95 (dt, J = 8.4, 0.8 Hz, 1H), 7.78 (d, J = 3.5 Hz, 1H), 7.56 – 7.50 (m, 1H), 7.27 – 7.21 (m, 2H), 7.13 – 7.06 (m, 3H), 6.93 (d, J = 7.7 Hz, 1H), 6.79 – 6.69 (m, 2H), 6.34 (dd, J = 8.1, 0.6 Hz, 1H), 6.23 (s, 2H). Example 12 1-(5-Aminopyridin-2-yl)-N-(4-methoxyphenyl)-3-methyl-1H-indol-5-amine Synthesized following the General Procedure C, method 1, using N-(4-methoxyphenyl)-3- methyl-1-(5-nitropyridin-2-yl)-1H-indol-5-amine (Intermediate 26). The reaction was stirred under H2 atmosphere at RT for 3 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-70%), and isolated as a pale-brown solid. Yield: 30 mg (64%). LC-MS [M+H]+: 345.4, Rt = 10.57 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 7.92 (d, J = 8.5 Hz, 1H), 7.86 (dd, J = 2.9, 0.7 Hz, 1H), 7.56 (s, 1H), 7.50 (d, J = 1.2 Hz, 1H), 7.30 (d, J = 8.4 Hz, 1H), 7.14 – 7.09 (m, 2H), 7.01 – 6.96 (m, 2H), 6.90 (dd, J = 8.9, 2.2 Hz, 1H), 6.86 – 6.79 (m, 2H), 5.25 (s, 2H), 3.69 (s, 3H), 2.22 (d, J = 1.2 Hz, 3H). Example 13 1-(5-Aminopyridin-2-yl)-N-(4-methoxyphenyl)-2-methyl-1H-indol-5-amine Synthesized following the General Procedure C, method 1, using N-(4-methoxyphenyl)-2- methyl-1-(5-nitropyridin-2-yl)-1H-indol-5-amine (Intermediate 27). The reaction was stirred under H2 atmosphere at RT for 3 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-60%), and isolated as an off-white solid. Yield: 54 mg (62%). LC-MS [M+H]+: 345.5, Rt = 10.24 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 7.96 – 7.90 (m, 1H), 7.43 (s, 1H), 7.18 – 7.10 (m, 2H), 7.07 (d, J = 2.1 Hz, 1H), 6.98 (dd, J = 8.7, 0.7 Hz, 1H), 6.96 – 6.89 (m, 2H), 6.84 – 6.77 (m, 2H), 6.74 (dd, J = 8.7, 2.1 Hz, 1H), 6.19 (d, J = 0.8 Hz, 1H), 5.54 (s, 2H), 3.69 – 3.66 (m, 3H), 2.28 – 2.24 (m, 3H). Example 14 1-(6-Aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-5-amine Synthesized following the General Procedure C, method 2, using N-(4-methoxyphenyl)-1- (6-nitropyridin-2-yl)-1H-indol-5-amine (Intermediate 28). The crude product was purified by column chromatography on silica gel using DCM / MeOH (0%-20%), and isolated as a pale-brown solid. Yield: 8.2 mg (8%). 1H NMR (400 MHz, MeOD): δ 8.08 – 8.03 (m, 1H), 7.65 (d, J = 3.4 Hz, 1H), 7.55 (t, J = 7.9 Hz, 1H), 7.22 – 7.19 (m, 1H), 7.04 – 6.98 (m, 2H), 6.95 (dd, J = 8.9, 2.3 Hz, 1H), 6.84 – 6.80 (m, 2H), 6.75 (dd, J = 7.7, 0.6 Hz, 1H), 6.49 (dd, J = 3.5, 0.8 Hz, 1H), 6.40 (dd, J = 8.1, 0.6 Hz, 1H), 3.76 (s, 3H). Example 15 1-(6-Aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-4-amine Synthesized following the General Procedure C, method 2, using N-(4-methoxyphenyl)-1- (6-nitropyridin-2-yl)-1H-indol-4-amine (Intermediate 29). The crude product was purified by column chromatography on silica gel using DCM / MeOH (0%-20%), and isolated as a yellow solid. Yield: 23 mg (15%). 1H NMR (400 MHz, MeOD): δ 7.61 – 7.53 (m, 3H), 7.14 – 7.09 (m, 2H), 7.04 (t, J = 8.0 Hz, 1H), 6.89 – 6.83 (m, 2H), 6.80 – 6.70 (m, 3H), 6.44 (dd, J = 8.1, 0.6 Hz, 1H), 3.78 (s, 3H). Example 16 1-(5-Aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-5-amine Synthesized following the General Procedure C, method 2, using N-(4-methoxyphenyl)-1- (5-nitropyridin-2-yl)-1H-indol-5-amine (Intermediate 30). The crude product was purified by column chromatography on silica gel using DCM / MeOH (0%-20%), and isolated as a pale-brown solid. Yield: 21 mg (18%). 1H NMR (400 MHz, MeOD): δ 7.95 (dd, J = 2.8, 0.8 Hz, 1H), 7.70 – 7.65 (m, 1H), 7.50 (d, J = 3.3 Hz, 1H), 7.32 (dd, J = 8.6, 0.8 Hz, 1H), 7.27 (dd, J = 8.6, 2.8 Hz, 1H), 7.22 (d, J = 2.2 Hz, 1H), 7.02 – 6.97 (m, 2H), 6.93 (dd, J = 8.8, 2.2 Hz, 1H), 6.84 – 6.77 (m, 2H), 6.48 (dd, J = 3.3, 0.8 Hz, 1H), 3.75 (s, 3H). General Procedure D A solution of the appropriate carbamate (ex: Intermediate 13: Tert-butyl(6-(5-((4- chlorophenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate) in HCl 4M in dioxane (6 mL / mmol) was stirred at RT for 5 h. The crude volatiles were removed under reduced pressure. Then, saturated aqueous sodium bicarbonate and EtOAc were added, and the mixture was stirred at RT for 1 h. The aqueous layer was extracted with EtOAc (x3). The combined organic layers were washed with saturated aqueous sodium bicarbonate, water and brine. The resulting organic layer was dried over anhydrous sodium sulfate, filtered and volatiles were removed under reduced pressure. The resulting crude product was purified by column chromatography on silica gel using hexane / EtOAc to obtain the desired indole product (ex: Example 17: 1-(5-aminopyridin-2-yl)-N- (4-chlorophenyl)-1H-indol-5-amine). Example 17 1-(5-Aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-5-amine Synthesized following the General Procedure D, using tert-butyl(6-(5-((4- chlorophenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 13). The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-100%), and isolated as a brown solid. Yield: 24 mg (48%). LC-MS [M+H]+: 335.1 / 337.0, Rt = 11.19 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 8.05 (s, 1H), 7.99 – 7.93 (m, 1H), 7.89 (dd, J = 2.9, 0.7 Hz, 1H), 7.72 (d, J = 3.3 Hz, 1H), 7.39 – 7.35 (m, 1H), 7.32 (d, J = 2.1 Hz, 1H), 7.21 – 7.11 (m, 3H), 7.00 – 6.92 (m, 3H), 6.55 (dd, J = 3.3, 0.8 Hz, 1H), 5.36 (s, 2H). Example 18 1-(5-Aminopyridin-2-yl)-N-(3-chlorophenyl)-1H-indol-5-amine Synthesized following the General Procedure D, using tert-butyl (6-(5-((3- chlorophenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 14). The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-100%), and isolated as a brown solid. Yield: 13 mg (42%). LC-MS [M+H]+: 335.1 / 337.0, Rt = 11.19 min (Method-C).1H NMR (400 MHz, DMSO-d6): δ 8.16 (s, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.90 (dd, J = 2.9, 0.6 Hz, 1H), 7.74 (d, J = 3.3 Hz, 1H), 7.40 – 7.33 (m, 2H), 7.18 – 7.12 (m, 2H), 7.00 (dd, J = 8.8, 2.2 Hz, 1H), 6.90 – 6.85 (m, 2H), 6.70 – 6.65 (m, 1H), 6.58 (dd, J = 3.3, 0.8 Hz, 1H), 5.37 (s, 2H). Example 19 4-((1-(5-Aminopyridin-2-yl)-1H-indol-5-yl)amino)benzonitrile Synthesized following the General Procedure D, using tert-butyl (6-(5-((4- cyanophenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 15). The crude product was purified by preparative HPLC (10 mM NH4HCO3 (pH 7 with HCOOH) / ACN, 40%-55%), and isolated as a white solid. Yield: 7 mg (23%). LC-MS [M+H]+: 326.2, Rt = 3.67 min (Method-A). 1H NMR (400 MHz, DMSO-d6): δ 8.75 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.90 (d, J = 2.8 Hz, 1H), 7.77 (d, J = 3.3 Hz, 1H), 7.55 – 7.49 (m, 2H), 7.44 – 7.36 (m, 2H), 7.16 (dd, J = 8.6, 2.9 Hz, 1H), 7.04 (dd, J = 8.8, 2.2 Hz, 1H), 6.99 – 6.92 (m, 2H), 6.63 – 6.58 (m, 1H), 5.39 (s, 2H). Example 20 1-(5-Aminopyridin-2-yl)-N-(p-tolyl)-1H-indol-4-amine Synthesized following the General Procedure D, using tert-butyl (6-(4-(p-tolylamino)-1H- indol-1-yl)pyridin-3-yl)carbamate (Intermediate 20). The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-100%), and isolated as a brown solid. Yield: 13 mg (45%). LC-MS [M+H]+: 315.1, Rt = 11.13 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 7.91 – 7.87 (m, 2H), 7.60 (d, J = 3.4 Hz, 1H), 7.41 (dt, J = 8.2, 0.8 Hz, 1H), 7.35 (d, J = 8.6 Hz, 1H), 7.15 (dd, J = 8.6, 2.9 Hz, 1H), 7.06 (s, 4H), 7.01 (t, J = 8.0 Hz, 1H), 6.82 (d, J = 7.2 Hz, 1H), 6.76 (dd, J = 3.5, 0.8 Hz, 1H), 5.39 (s, 2H), 2.24 (s, 3H). Example 21 1-(5-Aminopyridin-2-yl)-N-(3-methoxyphenyl)-1H-indol-4-amine Synthesized following the General Procedure D, using tert-butyl (6-(4-((3- methoxyphenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 21). The reaction mixture was stirred at RT for 16 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-20%), and isolated as a brown solid. Yield: 46 mg (50%). LC-MS [M+H]+: 331.4, Rt = 10.35 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 8.06 (s, 1H), 7.90 (dd, J = 2.9, 0.7 Hz, 1H), 7.63 (d, J = 3.4 Hz, 1H), 7.49 (dt, J = 8.3, 0.8 Hz, 1H), 7.36 (d, J = 8.6 Hz, 1H), 7.19 – 7.02 (m, 3H), 6.93 (d, J = 7.3 Hz, 1H), 6.76 – 6.66 (m, 3H), 6.39 (ddd, J = 8.2, 2.5, 0.9 Hz, 1H), 5.40 (s, 2H), 3.70 (s, 3H). Example 22 1-(5-Aminopyridin-2-yl)-N-(m-tolyl)-1H-indol-4-amine Synthesized following the General Procedure D, using tert-butyl (6-(4-(m-tolylamino)-1H- indol-1-yl)pyridin-3-yl)carbamate (Intermediate 22). The reaction mixture was stirred at RT for 16 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-100%), and isolated as a brown solid. Yield: 50 mg (55%). LC-MS [M+H]+: 315.4, Rt = 10.98 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 7.96 (s, 1H), 7.91 (dt, J = 2.9, 0.6 Hz, 1H), 7.61 (d, J = 3.4 Hz, 1H), 7.46 (dt, J = 8.3, 0.8 Hz, 1H), 7.36 (dd, J = 8.6, 0.7 Hz, 1H), 7.16 (ddd, J = 8.6, 2.9, 0.6 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H), 7.04 (t, J = 8.0 Hz, 1H), 6.98 – 6.87 (m, 3H), 6.74 (dt, J = 3.4, 0.7 Hz, 1H), 6.67 – 6.61 (m, 1H), 5.40 (s, 2H), 2.25 (s, 3H). Example 23 1-(5-Aminopyridin-2-yl)-N-(3-chlorophenyl)-1H-indol-4-amine Synthesized following the General Procedure D, using tert-butyl (6-(4-((3- chlorophenyl)amino)-1H-indol-1-yl)pyridin-3-yl)carbamate (Intermediate 23). The reaction mixture was stirred at RT for 16 h. The crude product was purified by column chromatography on silica gel using hexane / EtOAc (0%-50%), followed by reverse phase flash column chromatography (C18, NH4OAc (aq) 10 mM (pH 7) / ACN 0%-100%), and isolated as a brown solid. Yield: 14 mg (17%). LC-MS [M+H]+: 335.0 / 336.8, Rt = 11.27 min (Method-C). 1H NMR (400 MHz, DMSO-d6): δ 8.32 (s, 1H), 7.91 (dd, J = 2.9, 0.7 Hz, 1H), 7.66 (d, J = 3.4 Hz, 1H), 7.58 (dt, J = 8.3, 0.9 Hz, 1H), 7.37 (d, J = 8.6 Hz, 1H), 7.24 – 7.08 (m, 3H), 7.06 – 7.00 (m, 2H), 6.94 (d, J = 6.9 Hz, 1H), 6.78 (ddd, J = 7.9, 2.0, 0.9 Hz, 1H), 6.65 (dd, J = 3.4, 0.8 Hz, 1H), 5.41 (s, 2H). Biological Assays The capacity of certain Compounds of the Disclosure to produce a reduction in GM1 ganglioside accumulation in p.R60H / p.R60H-β-Gal canine fibroblasts was assessed as follows. Cell culture, transfection, and use of compounds WT β-Gal (ref. SV-2025-V04, STEMNOVATE) and p.R60H / p.R60H-β-Gal canine fibroblasts (ref. GM11473, Coriell) were cultured in DMEM (ref. 11574486, Gibco) with 10% FCS (ref. 10500, Gibco) and 1% Penicillin / streptomycin (P / S) (10,000 µg / mL) (ref. 15140122, Gibco) in 96 well plates (ref.89626, IBIDI) at 37 ºC and 5% CO2.48 h after seeding, 0.1 mg / mL of exogenous GM1 bovine ganglioside (ref. G7641, Sigma Aldrich) was added. Two days after that, tested compounds (or DMSO as control) were added at the indicated concentration for four subsequent days. Cultures were fixed with 4% paraformaldehyde (ref.15710, Electron Microscopy Sciences) in PBS for 15 min at RT. Immunocytochemistry and microscopy imaging Canine fibroblasts were permeabilized for 15 min at RT with PBS containing 0.3% Triton X-100 (ref. T8787, Sigma-Aldrich). Cytoplasm was labeled using HCS CellMask (ThermoFisher Scientific) (S2 Table) for 15 min at RT. Subsequently, fibroblasts were blocked with PBS containing 0.5% Bovine Serum Albumin (BSA, ref. A9647, Sigma-Aldrich) and 10% normal donkey serum (ref. S30, EMD Millipore) for 1 h at RT. Antibodies were diluted in PBS+0.5% BSA; incubation with primary antibody against Ganglioside GM1 (Abcam) was performed overnight at 4 ºC. Alexa Fluor® 488 Donkey anti-Rabbit IgG (Invitrogen) was used as a secondary antibody for 1 h at RT. Nuclei were counterstained using DAPI (ThermoFisher Scientific) in PBS for 10 min at RT. Cells were imaged using a LIPSI Nikon microscope, using a 40x objective (NA=1.15). Twenty-five images in each channel were acquired per well, with a 10% overlap (5x5 square) and a frame size of 2048x2048 pixels. Images were analyzed with NIS software analysis tool. Cell Mask staining was used to delimitate the cell area and DAPI to delimitate the nuclei area. Green dots (GM1 ganglioside) area was determined inside the cytoplasm, excluding the nuclei area. A ratio between the area of GM1 ganglioside and the total cell area was calculated to consider the differences in cell size. In addition, only cells with nuclei were included in the analysis. The capacity of certain Compounds of the Disclosure to produce a reduction in GM1 ganglioside accumulation in p.R60H / p.R60H-β-Gal canine fibroblasts at concentrations of 1.56 µM and 0.05 µM is denoted as follows: ^ Reduction in comparison with non-treated of >90% is shown as A; ^ Reduction in comparison with non-treated between 70% and 90% is shown as B; ^ Reduction in comparison with non-treated of <70% is shown as C; Table 2 below provides the % of GM1 ganglioside reduction range at 1.56 µM and 0.05 µM for Examples 1-23. Table 2 Example %GM1 ganglioside number reduction range at 1.56 %GM1 ganglioside µM reduction range at 0.05 µM 1 B B 2 B B 3 B C 4 B A 5 B C 6 B C 7 B C 8 B C 9 B B 10 B C 11 C C 12 B C 13 B C 14 A B 15 A C 16 A B 17 B B 18 B C Example %GM1 ganglioside number reduction range at 1.56 %GM1 ganglioside µM reduction range at 0.05 µM 19 B C 20 A C 21 B C 22 B C 23 B C The disclosure also relates to the following particular embodiments designated as [1] for the first embodiment, [2] for the second embodiment, and so on: [1] A compound of Formula (I): or a pharmaceutically acceptable salt or solvate thereof, wherein: A1, A2, and A3 are each independently N or CH, with the proviso that one of A1, A2, and A3 is N and two of A1, A2, and A3 are CH; R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, -ORa, -C1-4 alkyl, -C3-6 cycloalkyl, and –(5- to 10-membered)-C3-7 heterocyclyl, wherein said -C1-4 alkyl, -C3-6 cycloalkyl, and –(5- to 10-membered)-C3-7 heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; Ra is –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; R3a is –NR6R7, wherein R6 is hydrogen or –C1-4 alkyl, and R7 is selected from the group consisting of hydrogen, -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl, wherein said -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1- 4)alkoxy-; R3b is selected from the group consisting of hydrogen, halogen, and C1-4 alkyl; R4 is –NR8R9, wherein R8 is hydrogen or –C1-4 alkyl, and R9 is selected from the group consisting of –C6-10 aryl and -(5- to 10-membered)-C1-9 heteroaryl, wherein said –C6-10 aryl and -(5- to 10-membered)-C1-9 heteroaryl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; and Rb and Rc are each independently selected from the group consisting of hydrogen and -C1- 4 alkyl optionally substituted by 1, 2 or 3 halogen atoms; R3a, R3b, R4 and R5 each take the place of a hydrogen atom that would otherwise be present in any position on the rings of Formula (I) to which R3a, R3b, R4 and R5 are attached. [2] The compound of [1], wherein the compound has the structure of Formula (II): or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3a, R3b, R4, and R5 are as defined in [1]. [3] The compound of [1], wherein the compound has the structure of Formula (III): or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3a, R3b, R4, and R5 are as defined in [1]. [4] The compound of [1], wherein the compound has the structure of Formula (IV): or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3a, R3b, R4, and R5 are as defined in [1]. [5] The compound of any one of [1]-[4], and the pharmaceutically acceptable salts and solvates thereof, wherein R4 is attached to the 4-position of the indolyl ring. [6] The compound of any one of [1]-[4], and the pharmaceutically acceptable salts and solvates thereof, wherein R4 is attached to the 5-position of the indolyl ring. [7] The compound of any one of [1]-[6], or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, -C1-4 alkoxy, and -C1-4 alkyl, wherein said -C1-4 alkyl is unsubstituted or substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-. [8] The compound of any one of [1]-[7], or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, and -C1-2alkyl. [9] The compound of any one of [1]-[8], or a pharmaceutically acceptable salt or solvate thereof, wherein R6 is hydrogen and R3a is –NHR7, wherein R7 is as defined in [1].

[0010] The compound of any one of [1]-[9], or a pharmaceutically acceptable salt or solvate thereof, wherein R6 and R7 and both hydrogen and R3a is –NH2.

[0011] The compound of any one of [1]-[8], or a pharmaceutically acceptable salt or solvate thereof, wherein R6 is –C1-4 alkyl and R3a is –N(C1-4 alkyl)R7, wherein R7 is as defined in [1].

[0012] The compound of any one of [1]-[9] or

[0011] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is selected from the group consisting of -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl, wherein said -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1- 4)alkoxy-.

[0013] The compound of any one of [1]-[9],

[0011] , or

[0012] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is -C1-4 alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1- 4)alkoxy-, and trihalo(C1-4)alkoxy-.

[0014] The compound of any one of [1]-[9],

[0011] , or

[0012] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is -C3-10 cycloalkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-.

[0015] The compound of any one of [1]-[9],

[0011] , or

[0012] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is –C1-4 alkyl-C3-10 cycloalkyl, wherein said –C1-4 alkyl-C3-10 cycloalkyl is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-.

[0016] The compound of any one of [1]-

[0015] , or a pharmaceutically acceptable salt or solvate thereof, wherein R8 is hydrogen and R4 is –NHR9, wherein R9 is as defined in [1].

[0017] The compound of any one of [1]-

[0015] , or a pharmaceutically acceptable salt or solvate thereof, wherein R8 is –C1-4 alkyl and R4 is –N(C1-4 alkyl)R9, wherein R9 is as defined in [1].

[0018] The compound of any one of [1]-

[0017] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is –C6-10 aryl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms.

[0019] The compound of any one of [1]-

[0018] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is unsubstituted phenyl or phenyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-2 alkyl optionally substituted by 1, 2 or 3 halogen atoms.

[0020] The compound of any one of [1]-

[0019] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is phenyl substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, -CN, -OH, -O(C1-2)alkyl, unsubstituted –C1-4 alkyl, and –C1-4 alkyl substituted with 1, 2, or 3 halogen atoms.

[0021] The compound of any one of [1]-

[0017] , or a pharmaceutically acceptable salt or solvate thereof, wherein wherein R9 is -(5- to 10-membered)-C1-9 heteroaryl, wherein said -(5- to 10-membered)-C1-9 heteroaryl group is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; and Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4alkyl optionally substituted by 1, 2 or 3 halogen atoms.

[0022] The compound of any one of [1]-

[0021] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3b is hydrogen.

[0023] The compound of [1] selected from the group consisting of 1-(5-(dimethylamino)pyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(p-tolyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(3-methoxyphenyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(m-tolyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(3-methoxyphenyl)-N-methyl-1H-indol-5-amine; 1-(6-aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-5-amine; 1-(6-aminopyridin-2-yl)-N-(3-methoxyphenyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-4-amine; 1-(5-aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-4-amine; 1-(6-aminopyridin-2-yl)-N-(p-tolyl)-1H-indol-4-amine; 1-(6-aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-4-amine; 1-(5-aminopyridin-2-yl)-N-(4-methoxyphenyl)-3-methyl-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(4-methoxyphenyl)-2-methyl-1H-indol-5-amine; 1-(6-aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-5-amine; 1-(6-aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-4-amine; 1-(5-aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(3-chlorophenyl)-1H-indol-5-amine; 4-((1-(5-aminopyridin-2-yl)-1H-indol-5-yl)amino)benzonitrile; 1-(5-aminopyridin-2-yl)-N-(p-tolyl)-1H-indol-4-amine; 1-(5-aminopyridin-2-yl)-N-(3-methoxyphenyl)-1H-indol-4-amine; 1-(5-aminopyridin-2-yl)-N-(m-tolyl)-1H-indol-4-amine; and 1-(5-aminopyridin-2-yl)-N-(3-chlorophenyl)-1H-indol-4-amine, or a pharmaceutically acceptable salt or solvate thereof.

[0024] A pharmaceutical composition, comprising a compound of any one of [1]-

[0023] , or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

[0025] A method of treating or preventing a condition associated with the alteration of the activity of GLB1 in a patient, comprising administering to the patient in need thereof an effective amount of a compound as defined in any one of [1]-

[0023] , or a pharmaceutically acceptable salt or solvate thereof.

[0026] A method of treating or preventing GM1 gangliosidosis or Morquio syndrome, type B in a patient, comprising administering to the patient in need thereof an effective amount of a compound as defined in any one of [1]-

[0023] , or a pharmaceutically acceptable salt or solvate thereof.

[0027] The method of

[0026] , further comprising administering to the patient an effective amount of an enzyme for enzyme replacement therapy.

[0028] The method of

[0027] , wherein the enzyme is β-galactosidase or an analog thereof.

[0029] The method of any one of

[0026] -

[0028] , further comprising administering to the patient a small molecule chaperone.

[0030] The method of

[0029] , wherein the small molecule chaperone binds competitively to an enzyme.

[0031] The method of

[0029] or

[0030] , wherein the small molecule chaperone is selected from the group consisting of iminoalditols, iminosugars, aminosugars, thiophenylglycosides, glycosidase, sulfatase, glycosyl transferase, phosphatase, and peptidase inhibitors.

[0032] The method of any one of

[0026] -

[0031] , wherein the small molecule chaperone is selected from the group consisting of 1-deoxygalactonojirimycin (DGJ), N- nonyldeoxynojirimycin (NN-DNJ), N-butyldeoxygalactonojirimycin (NB-DGJ), galactose, fluorous iminoalditol, and epi-isofagomine.

[0033] A method of increasing β-galactosidase activity in a patient in need thereof, comprising administering to the patient an effective amount of a compound as defined in any one of [1]-

[0023] , or a pharmaceutically acceptable salt or solvate thereof.

[0034] A compound of any one of [1]-

[0023] , or a pharmaceutically acceptable salt or solvate thereof, for use as a medicament.

[0035] A compound of any one of [1]-

[0023] , or a pharmaceutically acceptable salt of solvate thereof, for use in the prevention or treatment of a condition associated with the alteration of the activity of GLB1.

[0036] A compound for use according to

[0035] , wherein the condition associated with the alteration of the activity of GLB1 is selected from the group consisting of GM1 gangliosidoses and Morquio syndrome, type B.

[0037] Use of compound of anyone of [1]-

[0023] , or a pharmaceutically acceptable salt of solvate thereof, for the manufacture of a medicament for the prevention or treatment of a condition associated with the alteration of the activity of GLB1.

[0038] Use of a compound according to

[0037] , wherein the condition associated with the alteration of the activity of GLB1 is selected from the group consisting of GM1 gangliosidoses and Morquio syndrome, type B.

[0039] A pharmaceutical composition comprising a compound as defined in any one of [1]-

[0023] , or a pharmaceutically acceptable salt of solvate thereof, for use in prevention or treatment of a condition associated with the alteration of the activity of GLB1.

[0040] The pharmaceutical composition for use according to

[0039] , wherein the condition associated with the alteration of the activity of GLB1 is selected from the group consisting of GM1 gangliosidoses and Morquio syndrome, type B.

[0041] The compound of any one of [1]-[6] or [9]-

[0022] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, -ORa, -C1-4 alkyl, and -C3-6 cycloalkyl, wherein said -C1-4 alkyl, and -C3-6 cycloalkyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4) alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1- 4)alkoxy-, wherein Ra is –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms.

[0042] The compound of any one of [1]-

[0022] or

[0041] , or a pharmaceutically acceptable salt or solvate thereof, wherein R5 is hydrogen and R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, and unsubstituted –C1-2 alkyl.

[0043] The compound of any one of [1]-

[0022] ,

[0041] , or

[0042] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1 and R5 are each hydrogen and R2 is unsubstituted – C1-2 alkyl.

[0044] The compound of any one of [1]-

[0022] or

[0041] -

[0043] , or a pharmaceutically acceptable salt or solvate thereof, wherein R2 and R5 are each hydrogen and R1 is unsubstituted –C1-2 alkyl.

[0045] The compound of any one of [1]-

[0022] or

[0041] -

[0044] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, and R5 are each hydrogen.

[0046] The compound of any one of [1]-[9],

[0012] ,

[0013] ,

[0016] -

[0022] , or

[0041] -

[0045] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is –NHR7, wherein R7 is -C1-4 alkyl.

[0047] The compound of any one of [1]-[8],

[0011] -

[0013] ,

[0016] -

[0022] , or

[0041] -

[0045] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3ais –N(C1-2alkyl)R7, wherein R7is -C1-4 alkyl.

[0048] The compound of

[0046] or

[0047] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is methyl or ethyl.

[0049] The compound of [1]-[8],

[0011] -

[0022] , or

[0041] -

[0045] , or a pharmaceutically acceptable salt or solvate thereof, wherein R6 is methyl.

[0050] The compound of any one of [1]-[9],

[0011] -

[0013] ,

[0016] -

[0022] , or

[0041] -

[0045] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is –C1-4 alkyl substituted with 1 or 2 substituents substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-.

[0051] The compound of

[0050] , or a pharmaceutically acceptable salt or solvate thereof, wherein wherein R7 is –C1-2 alkyl substituted with 1 or 2 substituents substituents each independently selected from the group consisting of halogen, hydroxy, -C1-2 alkoxy, monohalo(C1- 2)alkyl-, dihalo(C1-2)alkyl-, trihalo(C1-2)alkyl-, monohalo(C1-2)alkoxy-, dihalo(C1-2)alkoxy-, and trihalo(C1-2)alkoxy-.

[0052] The compound of any one of [1]-[9],

[0011] ,

[0012] ,

[0014] ,

[0016] -

[0022] , or

[0041] -

[0045] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is unsubstituted -C3-10 cycloalkyl.

[0053] The compound of

[0052] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is unsubstituted -C3-6 cycloalkyl.

[0054] The compound of any one of [1]-[9],

[0011] ,

[0012] ,

[0014] ,

[0016] -

[0022] , or

[0041] -

[0045] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is -C3-10 cycloalkyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-.

[0055] The compound of

[0054] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is -C3-6 cycloalkyl substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-2 alkoxy, monohalo(C1-2)alkyl-, dihalo(C1-2)alkyl-, trihalo(C1-2)alkyl-, monohalo(C1-2)alkoxy-, dihalo(C1-2)alkoxy-, and trihalo(C1-2)alkoxy-.

[0056] The compound of any one of [1]-[9],

[0011] ,

[0012] ,

[0015] -

[0022] , or

[0041] -

[0045] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is unsubstituted –C1-2 alkyl-C3-6 cycloalkyl.

[0057] The compound of any one of [1]-[9],

[0011] ,

[0012] ,

[0015] -

[0022] , or

[0041] -

[0045] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7is –C1-4alkyl-C3-10cycloalkyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-.

[0058] The compound of

[0057] , or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is –C1-2 alkyl-C3-6 cycloalkyl substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-2 alkoxy, monohalo(C1-2)alkyl-, dihalo(C1-2)alkyl-, trihalo(C1-2)alkyl-, monohalo(C1-2)alkoxy-, dihalo(C1-2)alkoxy-, and trihalo(C1- 2)alkoxy-.

[0059] The compound of any one of [1]-[8],

[0011] -

[0013] ,

[0016] -

[0022] , or

[0041] -

[0045] , or a pharmaceutically acceptable salt or solvate thereof, wherein R6and R7are each –C1-4alkyl and R3ais –N(C1-4 alkyl)2.

[0060] The compound of

[0059] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is –N(C1-2 alkyl)2.

[0061] The compound of

[0059] or

[0060] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is –N(CH3)2.

[0062] The compound of any one of [1]-

[0013] ,

[0016] -

[0022] , or

[0041] -

[0046] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is –NH2, -NH(CH3), or –N(CH3)2.

[0063] The compound of any one of [1]-

[0015] ,

[0017] -

[0022] , or

[0041] -

[0062] , or a pharmaceutically acceptable salt or solvate thereof, wherein R8 is methyl or ethyl.

[0064] The compound of

[0063] , or a pharmaceutically acceptable salt or solvate thereof, wherein R8 is methyl.

[0065] The compound of any one of [1]-

[0018] ,

[0022] , or

[0041] -

[0064] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is –C6-10 aryl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms.

[0066] The compound of [1]-

[0019] ,

[0022] , or

[0041] -

[0065] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is phenyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-2 alkyl optionally substituted by 1, 2 or 3 halogen atoms.

[0067] The compound of any one of [1]-

[0019] ,

[0022] , or

[0041] -

[0066] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is , wherein m is 1 or 2 and R10 is selected from the group consisting of halogen, -CN, -OH, -C1-4 alkyl, and -C1-4 alkoxy.

[0068] The compound of [1]-

[0019] ,

[0022] , or

[0041] -

[0067] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is , wherein R10 is selected from the group consisting of halogen, -CN, -O(C1-2)alkyl, and –C1-4 alkyl.

[0069] The compound of [1]-

[0019] ,

[0022] , or

[0041] -

[0068] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is

[0070] The compound of [1]-

[0017] ,

[0021] ,

[0022] , or

[0041] -

[0064] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is unsubstituted -(5- to 10-membered)-C1-9 heteroaryl.

[0071] The compound of

[0070] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is unsubstituted 5- or 6-membered heteroaryl having 1, 2 or 3 heteroatoms.

[0072] The compound of [1]-

[0017] ,

[0021] ,

[0022] , or

[0041] -

[0064] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is -(5- to 10-membered)-C1-9 heteroaryl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms.

[0073] The compound of

[0072] , or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is 5- or 6-membered heteroaryl having 1, 2 or 3 heteroatoms, wherein said 5- or 6- membered heteroaryl is substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2,-NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; and Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms.

[0074] The compound of any one of [1]-

[0019] ,

[0021] ,

[0022] ,

[0041] -

[0046] ,

[0072] , or

[0073] , or a pharmaceutically acceptable salt or solvate thereof, wherein Rb and Rc are both hydrogen.

[0075] The compound of any one of [1], [5]-[8],

[0016] -

[0022] ,

[0041] -

[0045] , or

[0063] -

[0074] , or a pharmaceutically acceptable salt or solvate thereof, wherein

[0076] The compound of any one of [1]-

[0020] ,

[0022] ,

[0041] -

[0068] , or

[0075] , or a pharmaceutically acceptable salt or solvate thereof, wherein R4 is R4a: or R4b: , wherein m is 1 or 2 and R10 is selected from the group consisting of halogen, -CN, -OH, -C1-4 alkyl, and -C1-4 alkoxy.

[0077] The compound of

[0076] , or a pharmaceutically acceptable salt or solvate thereof, wherein R4a and R4b are attached to the 4- or 5-position of the indolyl ring.

[0078] The compound of any one [1], [2], [5], [7]-

[0022] ,

[0041] , or

[0045] -

[0076] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is attached to the 5-position of the 2-pyridyl ring, R3b is hydrogen, R4 is attached to the 4-position of the indolyl ring, R5 is hydrogen, and R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, and –C1-2 alkyl.

[0079] The compound of

[0078] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is hydrogen and R2 is methyl or ethyl.

[0080] The compound of

[0078] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is methyl or ethyl and R2 is hydrogen.

[0081] The compound of

[0078] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1 and R2 are hydrogen.

[0082] The compound of any one of

[0078] -

[0081] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is –NH2 or –N(Me)2.

[0083] The compound of any one of [1], [2], [5], [7]-

[0022] , or

[0041] -

[0076] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is attached to the 6-position of the 2-pyridyl ring, R3b is hydrogen, R4 is attached to the 4-position of the indolyl ring, R5 is hydrogen, and R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, and –C1-2 alkyl.

[0084] The compound of

[0083] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1is hydrogen and R2is methyl or ethyl.

[0085] The compound of

[0083] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is methyl or ethyl and R2 is hydrogen.

[0086] The compound of

[0083] , or a pharmaceutically acceptable salt or solvate thereof, wherein both R1 and R2 are hydrogen.

[0087] The compound of any one of

[0083] -

[0086] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is –NH2 or –N(Me)2.

[0088] The compound of any one of [1], [2], [6]-

[0022] , or

[0041] -

[0076] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is attached to the 5-position of the 2-pyridyl ring, R3b is hydrogen, R4 is attached to the 5-position of the indolyl ring, R5 is hydrogen, and R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, and –C1-2 alkyl.

[0089] The compound of

[0088] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is hydrogen and R2 is methyl or ethyl.

[0090] The compound of

[0088] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is methyl or ethyl and R2 is hydrogen.

[0091] The compound of

[0088] , or a pharmaceutically acceptable salt or solvate thereof, wherein both R1 and R2 are hydrogen.

[0092] The compound of any one of

[0088] -

[0091] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is –NH2 or –N(Me)2.

[0093] The compound of any one of [1], [2], [7]-

[0022] , or

[0041] -

[0076] , or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is attached to the 6-position of the 2-pyridyl ring, R3b is hydrogen, R4 is attached to the 5-position of the indolyl ring, R5 is hydrogen, and R1 and R2 are each independently selected from the group consisting of hydrogen, halogen, and –C1-2 alkyl.

[0094] The compound of

[0093] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is hydrogen and R2 is methyl or ethyl.

[0095] The compound of

[0093] , or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is methyl or ethyl and R2 is hydrogen.

[0096] The compound of

[0093] , or a pharmaceutically acceptable salt or solvate thereof, wherein both R1 and R2 are hydrogen.

[0097] The compound of any one of

[0093] -96], or a pharmaceutically acceptable salt or solvate thereof, wherein R3a is –NH2 or –N(Me)2.

[0098] The pharmaceutical composition of

[0024] , wherein the compound is as defined in any one of

[0041] -

[0097] , or a pharmaceutically acceptable salt or solvate thereof.

[0099] The method of

[0025] , wherein the compound is as defined in any one of

[0041] -

[0097] , or a pharmaceutically acceptable salt or solvate thereof.

[0100] The method of any one of

[0026] -

[0032] , wherein the compound is as defined in any one of

[0041] -

[0097] , or a pharmaceutically acceptable salt or solvate thereof.

[0101] The method of

[0033] , wherein the compound is as defined in any one of

[0041] -

[0097] , or a pharmaceutically acceptable salt or solvate thereof.

[0102] The compound for use of

[0034] , wherein the compound is as defined in any one of

[0041] -

[0097] , or a pharmaceutically acceptable salt or solvate thereof.

[0103] The compound for use of

[0035] or

[0036] , wherein the compound is as defined in any one of

[0041] -

[0097] , or a pharmaceutically acceptable salt of solvate thereof.

[0104] Use of compound of

[0037] or

[0038] , wherein the compound is as defined in any one of

[0041] -

[0097] , or a pharmaceutically acceptable salt of solvate thereof.

[0105] The pharmaceutical composition of

[0039] or

[0040] , wherein the compound is as defined in any one of

[0041] -

[0097] , or a pharmaceutically acceptable salt of solvate thereof.

[0106] A compound of any one of [1]-

[0023] or

[0041] -

[0097] for use in a method of increasing β-galactosidase activity in a patient in need thereof.

[0107] Use of compound of anyone of [1]-

[0023] or

[0041] -

[0097] for the manufacture of a medicament for increasing β-galactosidase activity in a patient in need thereof. All publications cited in this specification are incorporated herein by reference. While the disclosure has been described with reference to particular embodiments, it will be appreciated that modifications can be made without departing from the spirit of the disclosure. Such modifications are intended to fall within the scope of the appended claims.

Claims

WHAT IS CLAIMED IS:

1. A compound of Formula (I):or a pharmaceutically acceptable salt or solvate thereof, wherein: A1, A2, and A3 are each independently N or CH, with the proviso that one of A1, A2, and A3 is N and two of A1, A2, and A3 are CH; R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, -ORa, -C1-4 alkyl, -C3-6 cycloalkyl, and –(5- to 10-membered)-C3-7 heterocyclyl, wherein said -C1-4 alkyl, -C3-6 cycloalkyl, and –(5- to 10-membered)-C3-7 heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; Ra is –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; R3a is –NR6R7, wherein R6 is hydrogen or –C1-4 alkyl, and R7 is selected from the group consisting of hydrogen, -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl, wherein said -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl- C3-10 cycloalkyl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-; R3b is selected from the group consisting of hydrogen, halogen, and C1-4 alkyl; R4 is –NR8R9, wherein R8 is hydrogen or –C1-4 alkyl, and R9 is selected from the group consisting of –C6-10 aryl and -(5- to 10-membered)- C1-9 heteroaryl, wherein said –C6-10 aryl and -(5- to 10-membered)-C1-9 heteroaryl groups are optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2,-NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; and Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms; R3a, R3b, R4and R5each take the place of a hydrogen atom that would otherwise be present in any position on the rings of Formula (I) to which R3a, R3b, R4 and R5 are attached.

2. The compound of claim 1, wherein the compound has the structure of Formula (II):or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3a, R3b, R4, and R5 are as defined in claim 1.

3. The compound of claim 1, wherein the compound has the structure of Formula (III):or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3a, R3b, R4, and R5 are as defined in claim 1.

4. The compound of claim 1, wherein the compound has the structure of Formula (IV):or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3a, R3b, R4, and R5 are as defined in claim 1.

5. The compound of any one of claims 1-4, and the pharmaceutically acceptable salts and solvates thereof, wherein R4is attached to the 4-position of the indolyl ring.

6. The compound of any one of claims 1-4, and the pharmaceutically acceptable salts and solvates thereof, wherein R4 is attached to the 5-position of the indolyl ring.

7. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, -C1-4 alkoxy, and -C1-4 alkyl, wherein said -C1-4 alkyl is unsubstituted or substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-.

8. The compound of any one of claims 1-7, or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, and R5 are each independently selected from the group consisting of hydrogen, halogen, and -C1-2 alkyl.

9. The compound of any one of claims 1-8, or a pharmaceutically acceptable salt or solvate thereof, wherein R6 is hydrogen and R3a is –NHR7, wherein R7 is as defined in claim 1.

10. The compound of any one of claims 1-9, or a pharmaceutically acceptable salt or solvate thereof, wherein R6 and R7 and both hydrogen and R3a is –NH2.

11. The compound of any one of claims 1-8, or a pharmaceutically acceptable salt or solvate thereof, wherein R6 is –C1-4 alkyl and R3a is –N(C1-4 alkyl)R7, wherein R7 is as defined in claim 1.

12. The compound of any one of claims 1-9 or 11, or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is selected from the group consisting of -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl, wherein said -C1-4 alkyl, -C3-10 cycloalkyl, and –C1-4 alkyl-C3-10 cycloalkyl groups are optionally substituted with 1, 2, or 3 substituentseach independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, halo(C1-4)alkyl-, and halo(C1-4)alkoxy-.

13. The compound of any one of claims 1-9, 11, or 12, or a pharmaceutically acceptable salt or solvate thereof, wherein R7is -C1-4alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-.

14. The compound of any one of claims 1-9, 11, or 12, or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is -C3-10 cycloalkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1-4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1- 4)alkoxy-, dihalo(C1-4)alkoxy-, and trihalo(C1-4)alkoxy-.

15. The compound of any one of claims 1-9, 11, or 12, or a pharmaceutically acceptable salt or solvate thereof, wherein R7 is –C1-4 alkyl-C3-10 cycloalkyl, wherein said –C1-4 alkyl-C3-10 cycloalkyl group is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, hydroxy, -C1-4 alkoxy, monohalo(C1- 4)alkyl-, dihalo(C1-4)alkyl-, trihalo(C1-4)alkyl-, monohalo(C1-4)alkoxy-, dihalo(C1- 4)alkoxy-, and trihalo(C1-4)alkoxy-.

16. The compound of any one of claims 1-15, or a pharmaceutically acceptable salt or solvate thereof, wherein R8 is hydrogen and R4 is –NHR9, wherein R9 is as defined in claim 1.

17. The compound of any one of claims 1-15, or a pharmaceutically acceptable salt or solvate thereof, wherein R8 is –C1-4 alkyl and R4 is –N(C1-4 alkyl)R9, wherein R9 is as defined in claim 1.

18. The compound of any one of claims 1-17, or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is –C6-10 aryl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyloptionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms.

19. The compound of any one of claims 1-18, or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is unsubstituted phenyl or phenyl substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, wherein Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-2 alkyl optionally substituted by 1, 2 or 3 halogen atoms.

20. The compound of any one of claims 1-19, or a pharmaceutically acceptable salt or solvate thereof, wherein R9 is phenyl substituted with 1 or 2 substituents each independently selected from the group consisting of halogen, -CN, -OH, -O(C1-2)alkyl, unsubstituted –C1-4 alkyl, and –C1-4 alkyl substituted with 1, 2, or 3 halogen atoms.

21. The compound of any one of claims 1-17, or a pharmaceutically acceptable salt or solvate thereof, wherein wherein R9 is -(5- to 10-membered)-C1-9 heteroaryl, wherein said -(5- to 10-membered)-C1-9 heteroaryl group is optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, -C(=O)N(Rb)2, -NHC(=O)Rb, -S(=O)2N(Rb)2, -NHS(=O)2Rb, -CN, -ORc, -N(Rc)2, and –C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms; and Rb and Rc are each independently selected from the group consisting of hydrogen and -C1-4 alkyl optionally substituted by 1, 2 or 3 halogen atoms.

22. The compound of any one of claims 1-21, or a pharmaceutically acceptable salt or solvate thereof, wherein R3b is hydrogen.

23. The compound of claim 1 selected from the group consisting of 1-(5-(dimethylamino)pyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(p-tolyl)-1H-indol-5-amine;1-(5-aminopyridin-2-yl)-N-(3-methoxyphenyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(m-tolyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(3-methoxyphenyl)-N-methyl-1H-indol-5-amine; 1-(6-aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-5-amine; 1-(6-aminopyridin-2-yl)-N-(3-methoxyphenyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-4-amine; 1-(5-aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-4-amine; 1-(6-aminopyridin-2-yl)-N-(p-tolyl)-1H-indol-4-amine; 1-(6-aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-4-amine; 1-(5-aminopyridin-2-yl)-N-(4-methoxyphenyl)-3-methyl-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(4-methoxyphenyl)-2-methyl-1H-indol-5-amine; 1-(6-aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-5-amine; 1-(6-aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-4-amine; 1-(5-aminopyridin-2-yl)-N-(4-methoxyphenyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(4-chlorophenyl)-1H-indol-5-amine; 1-(5-aminopyridin-2-yl)-N-(3-chlorophenyl)-1H-indol-5-amine; 4-((1-(5-aminopyridin-2-yl)-1H-indol-5-yl)amino)benzonitrile; 1-(5-aminopyridin-2-yl)-N-(p-tolyl)-1H-indol-4-amine; 1-(5-aminopyridin-2-yl)-N-(3-methoxyphenyl)-1H-indol-4-amine; 1-(5-aminopyridin-2-yl)-N-(m-tolyl)-1H-indol-4-amine; and 1-(5-aminopyridin-2-yl)-N-(3-chlorophenyl)-1H-indol-4-amine, or a pharmaceutically acceptable salt or solvate thereof.

24. A pharmaceutical composition, comprising a compound of any one of claims 1-23, or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

25. A method of treating or preventing a condition associated with the alteration of the activity of GLB1 in a patient, comprising administering to the patient in need thereof an effective amount of a compound as defined in any one of claims 1-23, or a pharmaceutically acceptable salt or solvate thereof.

26. A method of treating or preventing GM1 gangliosidosis or Morquio syndrome, type B in a patient, comprising administering to the patient in need thereof an effective amount of a compound as defined in any one of claims 1-23, or a pharmaceutically acceptable salt or solvate thereof.

27. The method of claim 26, further comprising administering to the patient an effective amount of an enzyme for enzyme replacement therapy.

28. The method of claim 27, wherein the enzyme is β-galactosidase or an analog thereof.

29. The method of any one of claims 26-28, further comprising administering to the patient a small molecule chaperone.

30. The method of claim 29, wherein the small molecule chaperone binds competitively to an enzyme.

31. The method of claim 29 or 30, wherein the small molecule chaperone is selected from the group consisting of iminoalditols, iminosugars, aminosugars, thiophenylglycosides, glycosidase, sulfatase, glycosyl transferase, phosphatase, and peptidase inhibitors.

32. The method of any one of claims 26-31, wherein the small molecule chaperone is selected from the group consisting of 1-deoxygalactonojirimycin (DGJ), N-nonyldeoxynojirimycin (NN-DNJ), N-butyldeoxygalactonojirimycin (NB-DGJ), galactose, fluorous iminoalditol, and epi-isofagomine.

33. A method of increasing β-galactosidase activity in a patient in need thereof, comprising administering to the patient an effective amount of a compound as defined in any one of claims 1-23, or a pharmaceutically acceptable salt or solvate thereof.

34. A compound of any one of claims 1-23, or a pharmaceutically acceptable salt or solvate thereof, for use as a medicament.

35. A compound of any one of claims 1-23, or a pharmaceutically acceptable salt of solvate thereof, for use in the prevention or treatment of a condition associated with the alteration of the activity of GLB1.

36. A compound for use according to claim 35, wherein the condition associated with the alteration of the activity of GLB1 is selected from the group consisting of GM1 gangliosidoses and Morquio syndrome, type B.

37. Use of compound of anyone of claims 1-23, or a pharmaceutically acceptable salt or solvate thereof, for the manufacture of a medicament for the prevention or treatment of a condition associated with the alteration of the activity of GLB1.

38. Use of a compound according to claim 37, wherein the condition associated with the alteration of the activity of GLB1 is selected from the group consisting of GM1 gangliosidoses and Morquio syndrome, type B.

39. A pharmaceutical composition comprising a compound as defined in any one of claims 1- 23, or a pharmaceutically acceptable salt or solvate thereof, for use in prevention or treatment of a condition associated with the alteration of the activity of GLB1.

40. The pharmaceutical composition for use according to claim 39, wherein the condition associated with the alteration of the activity of GLB1 is selected from the group consisting of GM1 gangliosidoses and Morquio syndrome, type B.

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