Compounds usable as modulators of PERK activity

Abstract

Newly designed compounds represented by Formulae I-IVa*** and / or V-VI*.4a and / or VI** as described in the instant specification and uses thereof as modulators (e.g., activators) of pancreatic endoplasmic reticulum kinase (PERK) and in treating medical conditions associated with PERK activity, including viral infections, are provided.

Description

[0001] COMPOUNDS USABLE AS MODULATORS OF PERK ACTIVITY

[0002] RELATED APPLICATION / S

[0003] This application claims the benefit of priority of U. S. Provisional Application No. 63 / 719,147 filed on November 12, 2024, the contents of which are incorporated herein by reference in their entirety.

[0004] FIELD AND BACKGROUND OF THE INVENTION

[0005] The present invention, in some embodiments thereof, relates to therapy and, more particularly, but not exclusively, to newly designed compounds which are usable as modulators of PERK activity and in treating medical conditions associated with PERK activity, such as, but not limited to, medical conditions associated with aggregation-prone protein and / or viral infections.

[0006] Proteins fold into their native conformation and undergo a series of post-translational modifications in the endoplasmic reticulum (ER) as part of the normal process of cellular homeostasis. Disruption of cellular protein folding results in ER stress. Cells respond to ER stress by activation of the unfolded protein response (UPR) pathways to survive the stress.

[0007] PERK, one of the three identified UPR transducers, is a kinase that phosphorylates a single known substrate eIF2a, leading to lower levels of translation initiation, which in turn globally reduces the load of newly synthesized proteins in the ER. Reduction in the overall protein-folding load is an effective response to reduce ER stress. In addition, PERK-mediated eIF2a phosphorylation also induces transcriptional activation to improve protein-folding capacity, thereby further promoting cell survival in stressed cells. Among the group of three prominent UPR transducers that includes also XBP1 and ATF6, PERK may have a broader range of cellular effects than other transducers, perhaps because of its unique role in regulating the general translation rate through the phosphorylation of eIF2a. Indeed, eIF2a phosphorylation appears to account for the entire range of the protective effects of PERK under ER stress. See, for example, Wang et al. [Chem Biol Drug Des (2010), 76, 480-495], and references cited therein.

[0008] Small molecules modulators of PERK, such as GSK2606414, GSK2656157 and A4, have been designed primarily as cancer- treating drugs, but also as candidates for treating neurodegenerative diseases [see for example, Wang et al. (2010) supra;, Axten et al. J Med Chem (2012) 55, 7193-7207; Axten et al. ACS Med Chem Let (2013) 4, 964-968; Moreno et al. Sci Transl Med (2013) 5(206), 206ra138; Radford et al. Acta Neuropathol (2015) 130, 633-642; and PCT International Patent Application Publication Nos. WO 2011 / 119663 and WO 2011 / 146748].

[0009] Bruch et al. [EM BO molecular medicine (2017) 9, 371-384] teaches PERK activation mitigates tau pathology in vitro and in vivo by reducing tau phosphorylation, improving cell viability, and enhancing memory and locomotor function, suggesting a potential therapeutic strategy for progressive supranuclear palsy (PSP) and other tauopathies.

[0010] Hydrazone derivatives such as A4 and MK-28 (see, Background Art FIG. 1) have been found to modulate protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) and to rescue Huntington's disease model mice from UPR-induced apoptosis [see, for example, Ganz et al. (2020) Scientific Reports, 10, 6875; and U. S. Patent No. 11,104,651]. While A4 was reported to be a PERK inhibitor [Wang et al. (2010) supra], MK-28 was found to be a PERK activator [Ganz et al. (2020) supra]. Hydrazone and hydrazine -based compounds, such as GLB-7 (see, Background Art FIG. 1), were found to activate PERK and to reduce toxicity in Huntington’s disease models [WO 2023 / 187783] and that activation of PERK (using, e.g., GLB-7) can result in antiviral activity against a variety of viruses [WO 2023 / 187791],

[0011] Shacham et al. [Neurotherapeutics (2024) 21(2), e00335] teach the efficacy of MK-28 in reducing ER stress, and extending lifespan in Huntington's disease model mice through long-term treatment without observable toxicity. It also shows that treatment with CCT020312 (see, Background Art FIG. 1) as a PERK activator which is commonly used for research purposes, results in improvements in weight, blood glucose levels, and some motor function parameters. While MK-28 showed much higher efficacy in vitro [Ganz et al. (2020) supra], CCT020312 displayed similar effect in vivo, yet showed more limited and transient effects, especially in grip strength and motor performance, indicating MK-28 is more effective in these preclinical studies [Shacham et al. (2024) supra].

[0012] SUMMARY OF THE INVENTION

[0013] According to an aspect of some embodiments of the present invention there is provided a compound represented by Formula I:

[0014]

[0015] Formula I or a pharmaceutically acceptable salt thereof,

[0016] wherein:

[0017] B is a bridging moiety which is or comprises an amide, a sulfonamide, a urea, or an N-heterocyclic group;

[0018] X is N or CR12;

[0019] Y is N or CR13;

[0020] R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R10-R14 or two or more of R10, R11 and R14; and

[0021] R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R1-R5.

[0022] According to some embodiments of any of the embodiments described herein, R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

[0023] According to some embodiments of any of the embodiments described herein, R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N- thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

[0024] According to some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is N.

[0025] According to some embodiments of any of the embodiments described herein, at least two of R1-R5, preferably at least two of R2, R3 and R4 are each hydroxy.

[0026] According to some embodiments of any of the embodiments described herein, at least one or both of R3 and R4 is hydroxy.

[0027] According to some embodiments of any of the embodiments described herein, Ri and R5 are each hydrogen.

[0028] According to some embodiments of any of the embodiments described herein, at least one, or each, of R10and R14is independently selected from an aryl, a heteroaryl, a cycloalkyl, and a heteroalicyclic.

[0029] According to some embodiments of any of the embodiments described herein, R10and R14are each independently an aryl.

[0030] According to some embodiments of any of the embodiments described herein, at least one of R10and R14is selected from a heteroalicyclic and a heteroaryl.

[0031] According to some embodiments of any of the embodiments described herein, one of R10and R14is an aryl and the other one is selected from a heteroalicyclic and a heteroaryl.

[0032] According to some embodiments of any of the embodiments described herein, R14 is hydrogen. According to some embodiments of any of the embodiments described herein, the bridging moiety is or comprises an N-heterocyclic group.

[0033] According to some embodiments of any of the embodiments described herein, the N-heterocyclic group is selected from a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazoles, a thiadiazole, a thiazole, and an isoxazole.

[0034] According to some embodiments of any of the embodiments described herein, the N-heterocyclic group is a 1,2,3-triazole.

[0035] According to some embodiments of any of the embodiments described herein, the bridging moiety is or comprises a urea.

[0036] According to some embodiments of any of the embodiments described herein, the bridging moiety is or comprises an amide or a sulfonamide.

[0037] According to some embodiments of any of the embodiments described herein, the bridging moiety comprises an amide. According to some embodiments of any of the embodiments described herein, the bridging moiety B is a urea moiety, the compound being represented by Formula II:

[0038]

[0039] Formula II

[0040] or a pharmaceutically acceptable salt thereof,

[0041] wherein R15 and Ri6 are as described herein in any of the respective embodiments, and, for example, are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl.

[0042] According to some embodiments of any of the embodiments described herein, at least one, or each, of R15 and Ri6 is hydrogen.

[0043] According to some embodiments of any of the embodiments described herein, the bridging moiety B is a 1,2,3-triazole, the compound being represented by Formula III or by Formula Illa:

[0044]

[0045] Formula III

[0046]

[0047] or a pharmaceutically acceptable salt thereof,

[0048] wherein R17 is as described herein in any of the respective embodiments, and, for example, is selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl.

[0049] According to some embodiments of any of the embodiments described herein, R17 is hydrogen. According to some embodiments of any of the embodiments described herein, the bridging moiety B comprises an amide, the compound being represented by Formula IV or by Formula IVa:

[0050] Formula IV

[0051]

[0052] or a pharmaceutically acceptable salt thereof, wherein R18-R20 are as described herein in any of the respective embodiments, and, for example, are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl.

[0053] According to some embodiments of any of the embodiments described herein, R20is hydrogen. According to some embodiments of any of the embodiments described herein, at least one, or each, of Ris and R19 is hydrogen.

[0054] The compounds according to some embodiments of the present invention can, additional or alternatively, encompass compounds represented by Formula V:

[0055]

[0056] Formula V

[0057] or a pharmaceutically acceptable salt thereof,

[0058] wherein:

[0059] B is a bridging moiety which is or comprises an amide, a sulfonamide, a urea, or an N-heterocyclic group;

[0060] Al and A2 are each independently selected from an aryl or a heteroaryl, each independently being substituted or unsubstituted;

[0061] wherein each of Al and A2, when substituted, independently features at least one substituent selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered, or 4-6-membered cyclic or heterocyclic ring formed of at least two of the substituents.

[0062] According to some embodiments of any of the embodiments described herein, the compound is represented by Formula VI:

[0063] A2

[0064]

[0065] Formula VI wherein:

[0066] B and A2 are as described herein in any of the respective embodiments;

[0067] X is N or CR12;

[0068] Y is N or CR13; and

[0069] R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered, or 4-6-membered cyclic or heteroalicyclic ring formed of two or more of R10-R14 or two or more of R10, R11 and R14.

[0070] According to some embodiments of any of the embodiments described herein, R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

[0071] According to some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N.

[0072] According to some embodiments of any of the embodiments described herein, at least one, or each, of R10and R14is independently selected from an aryl, a heteroaryl, a cycloalkyl, and a heteroalicyclic.

[0073] According to some embodiments of any of the embodiments described herein, R10and R14are each independently an aryl.

[0074] According to some embodiments of any of the embodiments described herein, at least one of R10and R14is a heteroalicyclic or a heteroaryl.

[0075] According to some embodiments of any of the embodiments described herein, one of R10and R14is an aryl and the other one is a heteroalicyclic or a heteroaryl.

[0076] According to some embodiments of any of the embodiments described herein, R14 is hydrogen. According to some embodiments of any of the embodiments described herein, A2 is an aryl. According to some embodiments of any of the embodiments described herein, such compounds are represented by Formula I as described herein in any of the respective embodiments and any combination thereof.

[0077] According to some embodiments of any of the embodiments described herein, at least two of R2, R3 and R4 are each hydroxy.

[0078] According to some embodiments of any of the embodiments described herein, R3 and R4 are each hydroxy.

[0079] According to some embodiments of any of the embodiments described herein, Ri and R5 are each hydrogen.

[0080] According to some embodiments of any of the embodiments described herein, two of R1-R5 together form the cyclic or heterocyclic ring, which can be substituted or unsubstituted.

[0081] According to some embodiments of any of the embodiments described herein, two of R1-R5 together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted.

[0082] According to some embodiments of any of the embodiments described herein, R3 and R4 together form the cyclic or heterocyclic ring.

[0083] According to some embodiments of any of the embodiments described herein, the cyclic or heterocyclic ring is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic.

[0084] According to some embodiments of any of the embodiments described herein, the heteroaryl or heteroalicyclic ring is an N-containing heteroaryl or heteroalicyclic.

[0085] According to some embodiments of any of the embodiments described herein, the heteroaryl or heteroalicyclic ring is selected from pyrrole, imidazole, pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine, pyridinone, pyridazine, pyrimidine, pyrazine, morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine, thiazolidine, and pyrazolidine, preferably selected from imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, and pyrazolidinone, each being substituted or unsubstituted.

[0086] According to some embodiments of any of the embodiments described herein, A2 is a substituted or unsubstituted heteroaryl.

[0087] According to some embodiments of any of the embodiments described herein, the heteroaryl is a nitrogen-containing heteroaryl.

[0088] According to some embodiments of any of the embodiments described herein, the heteroaryl is selected from thiazole, benzothiazole, thiadiazole, benzothiadiazole, pyridine, quinoline, isoquinoline, quinazoline, quinoxaline, pyrrole, indole, indazole, oxazole, benzoxazole, indole, pyrimidine, purine, pyrazine, pyridazine, phthalazine, imidazole, benzimidazole, triazole, benzotriazole, and tetrazole, each being substituted or unsubstituted.

[0089] According to some embodiments of any of the embodiments described herein, the heteroaryl is a substituted heteroaryl featuring at least one substituent selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, preferably selected from hydroxy and amino.

[0090] According to some embodiments of any of the embodiments described herein, the bridging moiety is or comprises an N-heterocyclic group.

[0091] According to some embodiments of any of the embodiments described herein, the N-heterocyclic group is selected from a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazoles, a thiadiazole, a thiazole, and an isoxazole.

[0092] According to some embodiments of any of the embodiments described herein, the N-heterocyclic group is a 1,2,3-triazole.

[0093] According to some embodiments of any of the embodiments described herein, the bridging moiety is or comprises a urea.

[0094] According to some embodiments of any of the embodiments described herein, the bridging moiety is or comprises an amide or a sulfonamide.

[0095] According to some embodiments of any of the embodiments described herein, the bridging moiety comprises an amide.

[0096] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises urea, and the compound is being represented by Formula V.2:

[0097]

[0098] Formula V.2 or a pharmaceutically acceptable salt thereof,

[0099] wherein R15 and Ri6 are as described herein.

[0100] According to some embodiments of any of the embodiments described herein, the compound is represented by Formula VI.2:

[0101] R15R16

[0102]

[0103] R11

[0104] Formula VI.2

[0105] or a pharmaceutically acceptable salt thereof,

[0106] wherein R10, R11and R14are as defined and described herein in any of the respective embodiments and any combination thereof.

[0107] According to some embodiments of any of the embodiments described herein, the bridging moiety is or comprises a 1,2,3-triazole, and the compound is being represented by Formula V.3 or V.3a:

[0108]

[0109] or a pharmaceutically acceptable salt thereof, wherein R17 is as is defined and described herein in any of the respective embodiments and any combination thereof.

[0110] According to some embodiments of any of the embodiments described herein, the compound is represented by Formula VI.3 or VI.3a:

[0111]

[0112] or a pharmaceutically acceptable salt thereof,

[0113] wherein R10, R11 and R14 are as defined and described herein in any of the respective embodiments and any combination thereof.

[0114] According to some embodiments of any of the embodiments described herein, the bridging moiety is or comprises an amide, and the compound is being represented by Formula V.4 or V.4a:

[0115]

[0116] Formula V.4

[0117]

[0118] or a pharmaceutically acceptable salt thereof,

[0119] wherein:

[0120] R18-R20 are as described and defined herein in any of the respective embodiments.

[0121] According to some embodiments of any of the embodiments described herein, the compound is represented by Formula VI.4 or VI.4a:

[0122] Formula VI.4

[0123]

[0124] or a pharmaceutically acceptable salt thereof,

[0125] wherein R10, R11and R14are as defined and described herein in any of the respective embodiments and any combination thereof. Herein throughout, whenever variables of a Formula are not specifically indicated, it is to be understood that these variables are as defined and described in any of the respective embodiments and any combination thereof.

[0126] According to some embodiments of the present invention, there is provided a compound represented by Formula VI**:

[0127]

[0128] Rii

[0129] Formula VI**

[0130] or a pharmaceutically acceptable salt thereof,

[0131] wherein:

[0132] B is a bridging moiety which is or comprises an amide, a sulfonamide, a urea, or an N-heterocyclic group;

[0133] X is N or CR12;

[0134] Y is N or CR13;

[0135] R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, or, alternatively, two or more of R10-R14 form together a 3-8-membered, or 4-6-membered cyclic or heteroalicyclic ring; and A2 is either a substituted or unsubstituted heteroaryl or an aryl, having a 3-8-membered, or 4-6-membered cyclic or heteroalicyclic ring fused thereto.

[0136] According to some embodiments of any of the embodiments described herein, R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N- thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

[0137] According to some embodiments of any of the embodiments described herein, R1-R14 are as defined and described herein in any of the respective embodiments.

[0138] According to an aspect of some embodiments of the present invention there is provided a pharmaceutical composition comprising a compound as described herein in any of the respective embodiments and any combination thereof, and a pharmaceutically acceptable carrier. According to some embodiments of any of the embodiments described herein, the composition can be formulated or configured for application via any of routes of administration as described herein, including, for example, systemic administration and topical administration.

[0139] According to an aspect of some embodiments of the present invention there is provided a compound as described herein in any of the respective embodiments and any combination thereof, or a pharmaceutical composition comprising same, for use in treating a medical condition in which activating PERK is beneficial; and / or a medical condition associated with an aggregation-prone protein; and / or a medical condition in which upregulating an unfolded protein response is beneficial.

[0140] According to some embodiments of any of the embodiments described herein, the medical condition is a viral infection.

[0141] According to some embodiments of any of the embodiments described herein, the medical condition is selected from Huntington’s disease, amyloidosis, cataract, type II diabetes, cancer, and memory deficiency.

[0142] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0143] BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

[0144] Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

[0145] In the drawings: FIG. 1 (Background art) presents chemical structures of exemplary previously described PERK modulators A4, CCT020312, MK-28, and GLB-7, as indicated.

[0146] FIGs. 2A-B present comparative plots showing the apoptosis rate of murine striatal cells expressing full-length polyQ-expanded mHtt (ST Hdh(^nmn') as a function of concentration of exemplary compounds according to some embodiments of the present invention (presented in Tables 1 and 2, respectively), following UPR-induced apoptosis (triggered by incubation with 10 pg / ml tunicamycin for 48 hours), measured by FACS analysis of cell cycle progression with propidium iodide (PI). Average of 3 independent experiments +SD. Apoptosis in the presence of the ER stressor tunicamycin and in the absence of other compounds was normalized to 100 to allow comparison between experiments.

[0147] FIG. 3 is a bar graph showing the effect of exemplary compounds GLB-12, GLB-14, GLB- 15 and GLB-16, according to some embodiments of the present invention, compared to MK-28 and GLB-7, on ER stress levels in CHO KI cells stably expressing XBPl-mTurquoise. Cells were incubated for 48 hours with (denoted “TG”) or without (denoted “Untreated”) the ER stressor thapsigargin (TG; 2.g / ml), and in the presence of the indicated compounds (1 or 2 pM, as indicated) or in their absence (the control is denoted as “-“). mTurquoise fluorescence was determined using a fluorimeter and was normalized to cells treated only with TG (=100).

[0148] FIG. 4 is a bar graph showing the effect of exemplary compounds GLB-7, GLB-12, or GLB- 15 (0.01 pM, 0.1 pM or 1 pM, as indicated), on the levels of eIF2a-phosphorylation (eIF2a-P) relatively to total eIF2a (eIF2a) in lysed HEK293 cells. Data was obtained from quantification of immunoblotting with anti-eIF2a-P or anti-total eIF2a antibodies. The graph shows this ratio relative to that in untreated cells (=100), average of three independent experiments +SD.

[0149] DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

[0150] The present invention, in some embodiments thereof, relates to therapy and, more particularly, but not exclusively, to newly designed compounds which are usable as modulators of PERK activity and in treating medical conditions associated with PERK activity, such as, but not limited to, medical conditions associated with aggregation-prone protein and / or viral infections.

[0151] Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0152] Following the design and successful practice of hydrazine and hydrazone compounds as modulators of PERK, as described, for example, in WO 2023 / 187783, and in a search for additional PERK modulators featuring enhanced druggability, the present inventors have studied the effect of chemically modifying compounds such as taught in WO 2023 / 187783 on their activity as PERK modulators.

[0153] The present inventors have designed and successfully synthesized a set of compounds that are devoid of hydrazone-containing and hydrazine-containing bridging moieties (see, Tables 1 and 2 in the Examples section that follows), and have demonstrated the activity of the newly designed compounds as PERK modulators while testing their effect on ER stress-induced apoptosis and on eIF2a-phosphorylation (see, e.g., FIGs. 2, 3 and 4).

[0154] The newly designed compounds are collectively represented herein by Formula I, or by Formulae II-IVa*** and / or V-VI*.4a and VI**.

[0155] Embodiments of the present invention relate to newly designed compounds that are usable as modulators of PERK activity and to uses thereof in treating medical conditions associated with PERK activity, such as, but not limited to, conditions associated with aggregation-prone protein and / or viral infections.

[0156] Embodiments of the present invention relate to compounds represented by Formulae I-IVa*** or V-VI*.4a, and to uses thereof as pancreatic endoplasmic reticulum kinase (PERK) modulators (e.g., activators). Exemplary such compounds are shown in Tables 1-4 in the Examples section that follows.

[0157] Modulation of PERK can affect the cellular integrated stress response (ISR). Activation of PERK can upregulate an unfolded protein response, which is beneficial in treating diseases associated with aggregation-prone proteins, such as, but not limited to, Huntington’s disease and other diseases, as described in further detail hereinunder. Activation of PERK can further boost the cellular integrated stress response (ISR) and reduce viral protein synthesis, rendering these compounds also usable in treating viral infections.

[0158] The improved druggability of the newly designed compounds allows employing these compounds also in case a higher amount or concentration is required for providing the desired therapeutic effect.

[0159] Compounds:

[0160] According to an aspect of some embodiments of the present invention there are provided newly designed compounds, which can be collectively represented by Formula V:

[0161]

[0162] Formula V or a pharmaceutically acceptable salt thereof,

[0163] wherein:

[0164] B is a bridging moiety which is or comprises an amide, a sulfonamide, a urea, or an N-heterocyclic group;

[0165] Al and A2 are each independently selected from an aryl or a heteroaryl, each can substituted or unsubstituted, and each is preferably substituted, for example, but one or more substituents as described herein in any of the respective embodiments.

[0166] When substituted, a substituted Al and / or a substituted A2 can each independently feature one or more substituents. Any of the substituents described herein is / are contemplated. Non-limiting examples include one or more of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, as these moieties are defined and described herein, and a cyclic or heterocyclic ring, as defined herein, formed of two or more of the substituents.

[0167] The phrase “cyclic or heterocyclic ring formed of two or more of the substituents”, as used herein throughout, encompasses all-carbon rings, which can be aromatic, e.g., an aryl as defined herein, or non-aromatic, e.g., alicyclic (cycloalkyl) as defined herein, and heteroatom-containing rings, which can be aromatic, e.g., a heteroaryl as defined herein, or non-aromatic, e.g., a heteroalicyclic as defined herein. The formed cycloalkyl, aryl, heteroaryl or heteroalicyclic can be unsubstituted or can feature one or more substituents as defined herein and described in any of the respective embodiments. The formed cyclic or heterocyclic ring can be, for example, a 3-, 4-, 5-, 6-, 7- or 8-membered ring, and can optionally be 9-, 10- and up to 12-membered ring. The ring can be monocyclic or bicyclic. In some embodiments, the cyclic or heterocyclic ring is a 4-, 5-, or 6-membered, or 5-membered or 6-membered cyclic or heteroalicyclic ring.

[0168] Non-limiting examples of cyclic or heterocyclic rings formed of two or more substituents of Al and / or A2 include phenyl, naphthyl, biphenyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, pyrrole, imidazole (e.g., imidazolone), pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine (e.g., pyridinone), pyridazine (e.g., pyridazinone), pyrimidine (e.g., pyrimidinone), pyrazine (e.g., pyrazinone), morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine (e.g., imidazolidinone), thiazolidine (e.g., thiazolidinone), and pyrazolidine (e.g., pyrazolidinone); bicyclic or fused heteroaromatic and heteroalicyclic rings such as indole (e.g., indolinone), indazole, benzimidazole (e.g., benzimidazolone), benzothiazole, benzothiadiazole, benzoxazole, benzotriazole, quinoline (e.g., quinolinone), isoquinoline, quinazoline (e.g., quinazolinone), quinoxaline (e.g., quinoxalinone), purine, and phthalazine.

[0169] According to some embodiments of any of the embodiments described herein, the cyclic or heterocyclic ring is aromatic, and can be an aryl or a heteroaryl.

[0170] In some embodiments of any of the embodiments described herein, one or each of Al and A2 is / are independently a heteroaryl or an aryl, optionally having a 3-8-membered, or 4-6-membered cyclic or heteroalicyclic ring fused thereto.

[0171] In some embodiments of any of the embodiments described herein, A2 is a heteroaryl or an aryl. In some embodiments of any of the embodiments described herein, A2 is a heteroaryl or an aryl having a 3-8-membered, or 4-6-membered cyclic or heteroalicyclic ring fused thereto.

[0172] In some of these embodiments, when Al and / or A2 is substituted by cyclic or heterocyclic ring fused thereto, as described herein, the substituted Al and / or A2 and the fused ring form together a bicyclic moiety, e.g., a bicyclic aryl or a bicyclic heteroaryl.

[0173] Non-limiting examples of 3-8-membered cyclic or heteroalicyclic rings include carbocyclic (allcarbon) rings such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl; aromatic or heteroaromatic rings such as phenyl, pyrrole, imidazole (e.g., imidazolone), pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine (e.g., pyridinone), pyridazine (e.g., pyridazinone), pyrimidine (e.g., pyrimidinone), and pyrazine (e.g., pyrazinone); and saturated or partially saturated heterocycles such as morpholine, piperidine, piperazine, pyrrolidine, azetidine, azepane, oxetane, oxepane, thiepane, azocane, dioxolane, imidazolidine (e.g., imidazolidinone), thiazolidine (e.g., thiazolidinone), and pyrazolidine (e.g., pyrazolidinone).

[0174] In some embodiments of any of the embodiments described herein, one or each of Al and A2 is / are independently a heteroaryl or an aryl, optionally having a five- or six-membered heteroaryl or heteroalicyclic ring fused thereto.

[0175] Non-limiting examples of five- or six-membered heteroaryl or heteroalicyclic rings include pyrrole, imidazole (e.g., imidazolone), pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine (e.g., pyridinone, pyridazine (e.g., pyridazinone), pyrimidine (e.g., pyrimidinone), pyrazine (e.g., pyrazinone), morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidin (e.g., imidazolidinone), thiazolidine (e.g., thiazolidinone), and pyrazolidine (e.g., pyrazolidinone). Preferably, the five- or six-membered heteroaryl or heteroalicyclic rings is imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, or pyrazolidinone.

[0176] Any other cyclic or heterocyclic ring is also contemplated. In some embodiments of any of the embodiments described herein, one or each of Al and A2 is / are independently a substituted heteroaryl or a substituted aryl as defined herein, each independently featuring one or more substituents selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, as these are described and defined herein.

[0177] In some embodiments of any of the embodiments described herein, one or each of Al and A2 is / are independently a heteroaryl, optionally a substituted heteroaryl featuring at least one substituent selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

[0178] In some embodiments of any of the embodiments described herein, A2 is a substituted heteroaryl featuring at least one substituent selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

[0179] In some embodiments of any of the embodiments described herein, the substituted Al and / or the substituted A2 forms a bicyclic moiety. Non-limiting examples of bicyclic moieties include naphthyl, benzimidazole, benzoxazole, benzothiazole, benzothiadiazole, benzotriazole, benzoxazine, quinoline, isoquinoline, quinazoline, quinoxaline, purine, phthalazine, and their pyrido-fused analogs, whereby each can be substituted or unsubstituted.

[0180] In some embodiments of any of the embodiments described herein, A2 is a bicyclic moiety (e.g., naphthyl, benzimidazole, benzoxazole, benzothiazole, benzothiadiazole, benzotriazole, benzoxazine, quinoline, isoquinoline, quinazoline, quinoxaline, purine, phthalazine). In some embodiments of any of the embodiments described herein, A2 is substituted as described herein. In some embodiments of any of the embodiments described herein, A2 is a bicyclic moiety that is substituted as described herein. In some embodiments, when A2 is a substituted bicyclic moiety, it is substituted by one or more of hydroxy, thiol, alkoxy, thioalkoxy, and amino, for example, by one or both of hydroxy and amino. In some embodiments of any of the embodiments described herein, A2 is a heteroaryl (a substituted or unsubstituted heteroaryl). In some embodiments, A2 is a nitrogen-containing heteroaryl (e.g., thiazole, benzothiazole, thiadiazole, benzothiadiazole, pyridine, quinoline (e.g., quinolinone), isoquinoline, quinazoline (e.g., quinazolinone), quinoxaline (e.g., quinoxalinone), pyrrole, indole, indazole, oxazole, benzoxazole, indole (e.g., indolinone), pyrimidine, purine, pyrazine, pyridazine, phthalazine, imidazole, benzimidazole (e.g., benzimidazolone), triazole, benzotriazole, tetrazole, each being substituted as defined herein (e.g. by at least one hydroxy, thiol or amino) or unsubstituted). In some embodiments of any of the embodiments described herein, A2 is a heteroaryl that is substituted as defined herein (e.g., by one or more of hydroxy, thiol, alkoxy, thioalkoxy, and amino, for example, by one or both of hydroxy and / or amino). In some embodiments of any of the embodiments described herein, A2 is a nitrogen-containing heteroaryl that is substituted (e.g., one or more of hydroxy, thiol, alkoxy, thioalkoxy, and amino, for example, by one or both of hydroxy and / or amino). In some embodiments of any of the embodiments described herein, A2 is a heteroaryl that is substituted by one or more of hydroxy, thiol, alkoxy, thioalkoxy, and amino, for example, by one or both of hydroxy and / or amino. In some embodiments of any of the embodiments described herein, A2 is a nitrogen-containing heteroaryl that is substituted by one or more of hydroxy, thiol, alkoxy, thioalkoxy, and amino, for example, by one or both of hydroxy and / or amino.

[0181] In some embodiments of any of the embodiments described herein, A2 is an aryl. In some embodiments of any of the embodiments described herein, A2 is an aryl that is substituted as described herein (e.g., one or more of hydroxy, thiol, alkoxy, thioalkoxy, and amino, for example, by one or both of hydroxy and / or amino). In some embodiments of any of the embodiments described herein, A2 is a phenyl that is substituted by one or more substituents, each independently is as described herein. In some embodiments of any of the embodiments described herein, A2 is a phenyl that is substituted by one or more hydroxy, thiol, alkoxy, thioalkoxy, and / or amino, for example, by one or both of hydroxy and / or amino.

[0182] In some embodiments of any of the embodiments described herein, Al is a heteroaryl. In some embodiments of any of the embodiments described herein, Al is a heteroaryl substituted by one or more of any of the substituents as described herein. In some embodiments of any of the embodiments described herein, Al is a heteroaryl substituted by one or more substituents selected from an aryl, a heteroaryl, a cycloalkyl, and / or a heteroalicyclic. In some embodiments of any of the embodiments described herein, Al is a heteroaryl substituted by two or more substituents as defined herein. In some embodiments of any of the embodiments described herein, Al is a heteroaryl substituted by two or more substituents selected from an aryl, a heteroaryl and / or a heteroalicyclic. In some such embodiments, the aryl, heteroaryl and / or heteroalicyclic is / are substituted as described herein, optionally with at least one substituent selected from hydroxy, thiol, alkoxy (e.g., methoxy), thioalkoxy, and amino. In some embodiments of any of the embodiments described herein, Al is a heteroaryl substituted by two phenyls, each is independently optionally substituted by a substituent as described herein. In some embodiments of any of the embodiments described herein, Al is a heteroaryl substituted by two unsubstituted phenyls. In some embodiments of any of the embodiments described herein, Al is a heteroaryl substituted by a phenyl and a heteroalicyclic or a heteroaryl, which is / are optionally independently substituted by a substituent as described herein. In some embodiments of any of the embodiments described herein, Al is a heteroaryl substituted by at least one heteroalicyclic or heteroaryl, which is / are optionally independently substituted by a substituent as described herein.

[0183] According to some embodiments of any of the embodiments described herein, Al is a nitrogencontaining heteroaryl, which can be unsubstituted or substituted, as described herein in any of the respective embodiments.

[0184] Examples of nitrogen-containing heteroaryls that can be included as moiety Al include, without limitation, thiazole, benzothiazole, thiadiazole, benzothiadiazole, pyridine, quinoline (e.g., quinolinone), isoquinoline, quinazoline (e.g., quinazolinone), quinoxaline (e.g., quinoxalinone), pyrrole, indole, indazole, oxazole, benzoxazole, indole (e.g., indolinone), pyrimidine, purine, pyrazine, pyridazine, phthalazine, imidazole, benzimidazole (e.g., benzimidazolone), triazole, benzotriazole, tetrazole. The heteroaryl can be connected to the bridging moiety B via any of the N or C atoms of the heteroaryl.

[0185] In some embodiments of any of the embodiments described herein, Al is a pyridine, pyrimidine or pyrazine. In some embodiments of any of the embodiments described herein, Al is a pyridine, pyrimidine or pyrazine that is substituted by one or more of any of the substituents as described herein. In some embodiments of any of the embodiments described herein, Al is a pyrimidine or pyrazine that is substituted by one or more substituents selected from an aryl, a heteroaryl, a cycloalkyl, and / or a heteroalicyclic. In some embodiments of any of the embodiments described herein, Al is a pyrimidine or pyrazine that is substituted by two or more substituents as defined herein. In some embodiments of any of the embodiments described herein, Al is a pyrimidine or pyrazine that is substituted by two or more substituents selected from an aryl, a heteroaryl and / or a heteroalicyclic. In some such embodiments, the aryl, heteroaryl and / or heteroalicyclic is / are substituted as described herein, optionally with at least one substituent selected from hydroxy, thiol, alkoxy (e.g., methoxy), thioalkoxy, and amino. In some embodiments of any of the embodiments described herein, Al is a pyrimidine or pyrazine that is substituted by two phenyls, each is independently optionally substituted by a substituent as described herein. In some embodiments of any of the embodiments described herein, Al is a pyrimidine or pyrazine that is substituted by two unsubstituted phenyls. In some embodiments of any of the embodiments described herein, Al is a pyrimidine or pyrazine that is substituted by a phenyl and a heteroalicyclic or a heteroaryl, which is / are optionally independently substituted by a substituent as described herein. In some embodiments of any of the embodiments described herein, Al is a pyrimidine or pyrazine that is substituted by at least one heteroalicyclic or heteroaryl, which is / are optionally independently substituted by a substituent as described herein.

[0186] In some embodiments of any of the embodiments described herein, Al is a heteroaryl and A2 is a bicyclic moiety as described herein. In some embodiments of any of the embodiments described herein, Al is a heteroaryl and A2 is a bicyclic moiety as described herein that is substituted as described herein. In some embodiments of any of the embodiments described herein, Al is a heteroaryl that is substituted as described herein and A2 is a bicyclic moiety as described herein that is substituted as described herein.

[0187] According to some embodiments of any of the embodiments described herein, Al is a phenyl, pyridine or pyrimidine. According to some embodiments of any of the embodiments described herein, Al is a phenyl, pyridine or pyrimidine, and A2 is a bicyclic moiety as described herein. According to some embodiments of any of the embodiments described herein, Al is a phenyl, pyridine or pyrimidine, and A2 is an aryl (e.g., phenyl) as described herein.

[0188] Further embodiments defining moieties Al and A2 are as described hereinafter in further detail for Formulae I-IVa*** and / or VI- VI*.4a.

[0189] Herein throughout, the phrase "bridging moiety" describes a bi-radical moiety that is covalently linked to each of the adjacent moieties, that is, Al and A2, as described herein. The bridging moiety represents the moiety that covalently connects moieties Al and A2.

[0190] According to some embodiments of any of the embodiments described herein, the bridging moiety B features a length the bridging moiety B features a length defined by the number of atoms between Al and A2, which is at least three atoms, for example, from 3 to 8, from 3 to 6, from 3 to 5, or from 3 to 4 atoms, and is preferably three atoms in length.

[0191] According to the present embodiments, the bridging moiety B is devoid of hydrazine or hydrazone, as these are defined herein.

[0192] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an N-containing moiety, or one or more N-containing moieties. In some of these embodiments, the bridging moiety is or comprises an N-containing moiety other than hydrazine or hydrazone.

[0193] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an N-heterocyclic group, which can be, for example, an N-containing heteroalicyclic or an N-containing heteroaryl, as these are described herein. Representative examples of nitrogen-containing (N-containing) heteroaryls include, but are not limited to thiadiazole, pyridine, pyrrole, oxazole, indole, purine and the like. Other moieties are also contemplated.

[0194] Representative examples of nitrogen-containing (N-containing) heteroalicyclic include, but are not limited to, morpholine, thiomorpholine, piperidine, piperazine, hexahydroazepine and tetrahydropyrane. Other moieties are also contemplated.

[0195] According to some embodiments of any of the embodiments described herein, the N-heterocyclic group is a triazole (e.g., a 1,2,3-triazole; a 1,2,4-triazole), a tetrazole (e.g., a IH-tetrazole; a 2H-tetrazole), an imidazole, a pyridine, a pyrazole, an oxadiazoles, a thiadiazole (e.g., a 1,2,3-thiadiazole; a 1,2,4- thiadiazole; a 1,2,5- thiadiazole; a 1,3,4- thiadiazole), a thiazole (e.g., a 1,3-thiazole, a 1,2-thiazole), or an isoxazole.

[0196] The phrase “N-containing moiety” as used herein describes a chemical group that comprises at least one nitrogen atom.

[0197] Non-limiting examples of N-containing moieties include amine, amide, sulfonamide, urea, carbamate, thiourea, guanidine, amidine, imine, and N-heterocyclic groups. In some embodiments, the N-containing moiety is an amide, a sulfonamide, a urea, or an N-heterocyclic group.

[0198] As used herein, the phrase “N-heterocyclic group” encompasses N-containing heteroalicyclics or N-containing heteroaryls. Non-limiting examples include pyridine, pyrazole, imidazole, triazole, tetrazole, oxadiazole, thiadiazole, thiazole, piperidine, piperazine, morpholine, and pyrrolidine.

[0199] The N-containing moiety can form the bridging moiety per se, or form a part of a bridging moiety that further comprises additional atoms or chemical groups.

[0200] For example, the bridging moiety can comprise a hydrocarbon, as defined herein, preferably of 1 to 4 atoms in length, and the N-containing moiety can be part of a hydrocarbon moiety, such that is forms a part of a substituent (end group) of the or can form a part of a chemical group (linking group) that interrupts a hydrocarbon chain.

[0201] According to some embodiments of any of the embodiments described herein, the N-heterocyclic group is or comprises a 1,2,3-triazole which is substituted or unsubstituted. In some embodiments of any of these embodiments, the 1,2,3-triazole is unsubstituted.

[0202] Additional N-heterocyclic group-containing bridging groups B are also contemplated.

[0203] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises a urea, as defined herein. The bridging moiety can be, for example, a urea moiety, or a urea moiety that features one or more alkyl groups, for example, -L1-NR’-C(=O)-NR”-L2-, wherein R’ and R” are as described herein, and LI and L2 are each independently absent or is an alkylene linking moiety. Additional urea-containing bridging groups B are also contemplated.

[0204] bridging moiety B is or comprises a thiourea, as defined herein, for example, -L1-NR’-C(=S)-NR”-L2-, wherein R’ and R” are as described herein, and LI and L2 are each independently absent or is an alkylene linking moiety.

[0205] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an amide, as defined herein. The bridging moiety can be, for example, an amide moiety, or an amide moiety that features one or more alkyl groups, for example, -L1-NR’-C(=O)-L2-, or -Ll-C(=0)-NR’-L2-, wherein R’ is as described herein, and LI and L2 are each independently absent or is an alkylene linking moiety.

[0206] Additional amide-containing bridging groups B are also contemplated.

[0207] According to some embodiments of any of the embodiments described herein, the bridging moiety B is devoid of hydrazine or hydrazone, and one or each of Al and A2 is / are independently a heteroaryl or an aryl, optionally having a five- or six-membered heteroaryl or heteroalicyclic ring fused thereto, as described herein in any of the respective embodiments.

[0208] According to some embodiments of any of the embodiments described herein, the bridging moiety B is devoid of hydrazine or hydrazone, Al is a substituted heteroaryl or a substituted aryl, and A2 is an aryl or a heteroaryl, each can optionally be substituted.

[0209] According to some embodiments of any of the embodiments described herein, the bridging moiety B is devoid of hydrazine or hydrazone, Al is a substituted heteroaryl or a substituted aryl, and A2 is an aryl or a heteroaryl having a 3-8-membered, or 4-6-membered cyclic or heteroalicyclic ring fused thereto, as described herein in any of the respective embodiments.

[0210] According to some embodiments of any of the embodiments described herein, the bridging moiety B is devoid of hydrazine or hydrazone, Al is a substituted heteroaryl or a substituted aryl, and A2 is an aryl.

[0211] According to some embodiments of any of the embodiments described herein, the bridging moiety B is devoid of hydrazine or hydrazone, Al is a substituted heteroaryl or a substituted aryl, and A2 is an aryl that is substituted as described herein in any of the respective embodiments.

[0212] According to some embodiments of any of the embodiments described herein, the bridging moiety B is devoid of hydrazine or hydrazone, Al is a substituted heteroaryl or a substituted aryl, and A2 is a phenyl that is substituted as described herein (in any of the respective embodiments.

[0213] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an N-containing moiety, as described herein in any of the respective embodiments, Al is a substituted heteroaryl or a substituted aryl, and A2 is a heteroaryl or an aryl, which can be unsubstituted or substituted, as described herein in any of the respective embodiments.

[0214] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an N-containing moiety, as described herein in any of the respective embodiments, Al is a substituted heteroaryl or a substituted aryl, and A2 is a heteroaryl or an aryl having a 3-8-membered, or 4-6-membered cyclic or heteroalicyclic ring fused thereto, as described herein in any of the respective embodiments.

[0215] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an N-containing moiety, as described herein in any of the respective embodiments, Al is a substituted heteroaryl or a substituted aryl, and A2 is an aryl (e.g., phenyl).

[0216] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an N-containing moiety, Al is a substituted heteroaryl or a substituted aryl, and A2 is an aryl (e.g., phenyl) that is substituted by one or more substituents as described herein in any of the respective embodiments.

[0217] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an N-containing moiety, as described herein in any of the respective embodiments, and one or each of Al and A2 is independently a heteroaryl or an aryl, optionally having a five- or six-membered heteroaryl or heteroalicyclic ring fused thereto, as described herein in any of the respective embodiments.

[0218] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an N-containing moiety, as described herein in any of the respective embodiments, Al and A2 is each independently a heteroaryl or an aryl as defined herein, each can be unsubstituted or substituted as described herein in any of the respective embodiments.

[0219] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises urea or thiourea, as defined and described herein in any of the respective embodiments.

[0220] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises a urea moiety, as defined and described herein in any of the respective embodiments.

[0221] According to some embodiments of any of the embodiments described herein, the bridging moiety B is a urea moiety, as defined and described herein in any of the respective embodiments.

[0222] Exemplary compounds of Formula V in which the bridging moiety B is a urea moiety are collectively represented by Formula V.2: R15R16

[0223]

[0224] wherein Al and A2 are each as described herein in any of the respective embodiments for Formula V, or hereinunder in any of the respective embodiments (e.g., for Formula I-I** or VI- VI***); and wherein R15and R16are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino. According to some embodiments of any of the embodiments described herein, R15and R16are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl.

[0225] According to some embodiments of any of the embodiments described herein, at least one, or each, of R15and R16, is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heteroalicyclic. According to some embodiments of any of the embodiments described herein, at least one, or each, of R15and R16, selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl. According to some embodiments of any of the embodiments described herein, at least one, or each, of R15and R16, is hydrogen or an alkyl. In some such embodiments, the alkyl is an alkyl of up to 8, or up to 5, or up to 3, carbon atoms in length. According to some embodiments of any of the embodiments described herein, at least one, or each, of R15and R16is hydrogen. According to some embodiments of any of the embodiments described herein, each of R15and R16is hydrogen.

[0226] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an N-containing heterocyclic moiety (also referred to herein as N-heterocyclic group), as described herein in any of the respective embodiments.

[0227] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises a 1,2,3-triazole (as an exemplary N-heterocyclic group).

[0228] According to some embodiments of any of the embodiments described herein, the bridging moiety B is a 1,2,3-triazole. Exemplary compounds of Formula V in which the bridging moiety B is a 1,2, 3 -triazole (as an exemplary N-heterocyclic group) are collectively represented by Formula V.3 or V.3a:

[0229]

[0230] wherein Al and A2 are each as described herein in any of the respective embodiments for Formula V; and R17is R17is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, or amino.

[0231] According to some embodiments of any of the embodiments described herein, R17is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl. According to some embodiments of any of the embodiments described herein, R17is hydrogen or an alkyl. In some such embodiments, the alkyl is an alkyl of up to 8, or up to 5, or up to 3, carbon atoms in length. According to some embodiments of any of the embodiments described herein, R17is hydrogen.

[0232] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an amide or a thioamide, as defined and described herein in any of the respective embodiments.

[0233] According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an amide, as defined and described herein in any of the respective embodiments. According to some embodiments of any of the embodiments described herein, the bridging moiety B comprises an amide, for example, an alkylamide or an amidoalkyl. In some of these embodiments, the alkyl is a lower alkyl, or 1 to 6, or 1 to 4, or 1-2 carbon atoms in length. In some of these embodiments, the alkyl is methylene, and the bridging moiety B is amidomethylene (for example, -CONH-CR’R”-) or methyleneamido (for example, -CR’R”-CONH-), wherein R’ and R”’ are as defined herein, or as defined for.

[0234] Exemplary compounds of Formula V in which the bridging moiety B comprises an amide are collectively represented by Formula V.4 or V.4a:

[0235] Formula V.4

[0236]

[0237] Formula V.4a

[0238] wherein Al and A2 are each as described herein in any of the respective embodiments for Formula V; and R18-R20are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

[0239] According to some embodiments of any of the embodiments described herein, R18and R19are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, and R20is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl. According to some embodiments of any of the embodiments described herein, R20is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl. According to some embodiments of any of the embodiments described herein, R20is hydrogen or alkyl. In some such embodiments, the alkyl is an alkyl of up to 8, or up to 5, or up to 3, carbon atoms in length. According to some embodiments of any of the embodiments described herein, R20is hydrogen.

[0240] According to some embodiments of any of the embodiments described herein, Ris and R19 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl. According to some embodiments of any of the embodiments described herein, Ris and R19 are each independently selected from hydrogen and alkyl. According to some embodiments of any of the embodiments described herein, at least one, or each, of Ris and R19 is hydrogen. According to some embodiments of any of the embodiments described herein, each of Ris and R19 is hydrogen.

[0241] According to some embodiments of any of the embodiments described herein, R18-R20are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl. According to some embodiments of any of the embodiments described herein, R18-R20are each independently selected from hydrogen and alkyl. According to some embodiments of any of the embodiments described herein, at least one, or two, or each, of R18-R20is hydrogen. According to some embodiments of any of the embodiments described herein, each of R18-R20is hydrogen.

[0242] According to some embodiments of any of the embodiments described herein, Al is an aryl, for example, phenyl, which can be unsubstituted or substituted, as described herein in any of the respective embodiments.

[0243] According to some embodiments of any of the embodiments described herein, Al is pyridine or pyrimidine, which can be connected to the bridging moiety B via any of the N or C atoms of the pyridine or pyrimidine, and which can be unsubstituted or substituted, as described herein in any of the respective embodiments.

[0244] According to some embodiments of any of the embodiments described herein, Al is pyridine, which can be unsubstituted or substituted, as described herein in any of the respective embodiments, and in some of these embodiments, the pyridine moiety in 2-pyridine, such that the pyridine is connected to the bridging moiety B via the carbon atom adjacent to the nitrogen.

[0245] According to some embodiments of any of the embodiments described herein, Al is pyrimidine, which can be unsubstituted or substituted, as described herein in any of the respective embodiments, in some of these embodiments, the pyrimidine moiety is 2-pyrimidine, such that the pyrimidine is connected to the bridging moiety B via the carbon atom that is between the two nitrogen atoms. According to some embodiments of any of the embodiments described herein, Al is a heteroaryl, for example, an N-containing heteroaryl as described herein, which can be unsubstituted or substituted, as described herein in any of the respective embodiments.

[0246] According to some embodiments of any of the embodiments described herein, Al is a phenyl, pyridine or pyrimidine, and can be substituted or unsubstituted, such that the compound is represented by Formula VI:

[0247]

[0248] R11

[0249] Formula VI

[0250] wherein:

[0251] A2 and B are as defined herein in any of the respective embodiments (e.g., for Formula V); X is N or CR12;

[0252] Y is N or CR13; and

[0253] R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R10-R14 or two or more of R10, R11 and R14.

[0254] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N. In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N.

[0255] In some embodiments of any of the embodiments described herein, at least one of X and Y is N, and R10, R11, and R14, and R12 and / or R13, if present, are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O- thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R10-R14 or two or more of R10, R11 and R14.

[0256] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, and R10, R11, and R14, and R12 and / or R13, if present, are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R10-R14 or two or more of R10, R11 and R14.

[0257] In some embodiments of any of the embodiments described herein, X and Y are each N, and R10, R11, and R14, and R12 and / or R13, if present, are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R10-R14 or two or more of R10, R11 and R14.

[0258] In some embodiments of any of the embodiments described herein, R14 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl. In some embodiments of any of the embodiments described herein, R14 is hydrogen or an alkyl. In some such embodiments, the alkyl is of up to 8, or up to 5, or up to 3, carbon atoms in length. According to some embodiments of any of the embodiments described herein, R14 is hydrogen.

[0259] According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is other than hydrogen, and each can independently be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, or a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of R10 and R11.

[0260] According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is other than hydrogen, and each can independently be alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, or amino.

[0261] According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is independently a cyclic group, e.g., an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, as these are defined herein, whereby each can be substituted or unsubstituted.

[0262] According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is independently an aryl, which can be substituted (as defined herein) or unsubstituted. According to some embodiments of any of the embodiments described herein, R10 and R11 are each independently an aryl (e.g., phenyl), which can be substituted (as defined herein) or unsubstituted. When the aryl is substituted, it may feature one or more (e.g., two, three, four or five) substituents, each independently can be selected from hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, as these are defined herein. In some such embodiments, when the aryl is substituted, it may feature one or more (e.g., two, three, four or five) substituents, each being independently hydroxy and alkoxy. In some such embodiments, when the aryl is substituted, it may feature at least one (e.g., two, three, four, five) substituents, each independently is an alkoxy (e.g., methoxy).

[0263] According to some embodiments of any of the embodiments described herein, R10 is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11 is a substituted aryl, as described herein (e.g., an aryl which is substituted by an alkoxy (e.g., methoxy)). According to some embodiments of any of the embodiments described herein, R10 is a phenyl as described herein and R11 is a phenyl which is substituted by an alkoxy (e.g., methoxy). According to some embodiments of any of the embodiments described herein, R10 is a phenyl which is unsubstituted and R11 is a phenyl which is substituted by an alkoxy (e.g., methoxy). According to some embodiments of any of the embodiments described herein, R10 is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11 is a phenyl meta-substituted by an alkoxy (e.g., methoxy). According to some embodiments of any of the embodiments described herein, R10 is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11 is a phenyl para-substituted by an alkoxy (e.g., methoxy).

[0264] According to some embodiments of any of the embodiments described herein, R10 and R11 are each independently a phenyl which can be substituted (as defined herein) or unsubstituted. According to some embodiments of any of the embodiments described herein, R10 and R11 are each independently a phenyl which is unsubstituted.

[0265] According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is independently a heteroalicyclic or a heteroaryl, as these are defined herein. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a heteroalicyclic or a heteroaryl, as these are defined herein.

[0266] According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is independently a nitrogen-containing heteroalicyclic or a nitrogen-containing heteroaryl.

[0267] Representative examples of nitrogen-containing (N-containing) heteroalicyclic R10 and / or R11 include, but are not limited to, morpholine, thiomorpholine, piperidine, piperazine, hexahydroazepine, pyrrolidine, azepine, azocane and tetrahydropyrane. Other moieties are also contemplated.

[0268] Representative examples of nitrogen-containing (N-containing) heteroaryls R10 and / or R11 include, but are not limited to, thiazole, thiadiazole, pyridine, pyrrole, oxazole, indole (e.g., indolinone), pyrimidine, pyrazine, pyridazine, imidazole, triazole, tetrazole, indazole, benzimidazole (e.g., benzimidazolone), benzotriazole, quinoline (e.g., quinolinone), quinoxaline (e.g., quinoxalinone), isoquinoline, quinazoline (e.g., quinazolinone), and purine and the like. Other moieties are also contemplated.

[0269] For N-containing heteroaryls and N-containing heteroalicyclic substituents, the substituent can be covalently attached to the respective carbon atom via the nitrogen or via one of the ring carbon atoms.

[0270] According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is independently an oxygen-containing heteroalicyclic or an oxygen-containing heteroaryl.

[0271] Representative examples of oxygen-containing (O-containing) heteroalicyclics include, but are not limited to, tetrahydrofuran, tetrahydropyran, 1,4-dioxane, 1,3-dioxolane, and oxepane. Other moieties are also contemplated. In some of these embodiments, each heteroalicyclic can independently be an N-containing heteroaryl or an O-containing heteroaryl.

[0272] Representative examples of oxygen-containing (O-containing) heteroaryls include, but are not limited to, furan, benzofuran, isobenzofuran, oxazole, isoxazole, benzoxazole, and benzodioxole. Other moieties are also contemplated.

[0273] In some embodiments, when one, or each, of R10 and R11 is / are an oxygen-containing heteroalicyclic or an oxygen-containing heteroaryl, the substituent is linked to the respective carbon in Formula I, via a ring carbon atom.

[0274] According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is independently a pyridine (e.g., 2-pyridine, 3-pyridine, 4-pyridine), a piperidine (e.g., N-piperidine, 4-piperidine), a morpholine (e.g., N-morpholine (connected via the ring nitrogen), 2-morpholine (connected via a ring carbon)), or a pyrrole (e.g., N-pyrrole, 2-pyrrole, 3-pyrrole). According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is a pyridine. According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is a piperidine. According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is a morpholine. According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is an N-morpholine. According to some embodiments of any of the embodiments described herein, at least one, or each, of R10 and R11 is a pyrrole.

[0275] According to some embodiments of any of the embodiments described herein, when R10 and R11 is / are a heteroalicyclic or a heteroaryl, or an aryl, each of which can be independently substituted or unsubstituted. When the aryl, heteroalicyclic or heteroaryl is / are substituted, it / they may feature one or more (e.g., two, three, four or five) substituents, each independently can be selected from hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, as these are defined herein. In some such embodiments, when the heteroalicyclic or heteroaryl is / are substituted, it / they may feature one or more (e.g., two, three, four or five) substituents, each being independently hydroxy and alkoxy (e.g., methoxy).

[0276] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl (e.g., phenyl), as described herein in any of the respective embodiments and any combination thereof and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein in any of the respective embodiments and any combination thereof. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl which is unsubstituted, and the other one is an aryl which is substituted as described herein. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a phenyl which is unsubstituted, and the other one is a phenyl which is substituted as described herein.

[0277] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a heteroalicyclic which is unsubstituted, and the other one is a heteroalicyclic which is substituted as described herein. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a heteroalicyclic which is unsubstituted, and the other one is a heteroaryl which is substituted as described herein. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a heteroaryl which is unsubstituted, and the other one is a heteroalicyclic which is substituted as described herein. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a heteroaryl which is unsubstituted, and the other one is a heteroaryl which is substituted as described herein.

[0278] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a phenyl which is substituted or unsubstituted, and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a phenyl which is unsubstituted, and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein.

[0279] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a phenyl which is substituted or unsubstituted, and the other one is an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a phenyl which is unsubstituted, and the other one is an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl.

[0280] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a phenyl which is substituted or unsubstituted, and the other one is an N-containing heteroalicyclic or an N-containing heteroaryl. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a phenyl which is unsubstituted, and the other one is an N-containing heteroalicyclic or an N-containing heteroaryl.

[0281] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a phenyl which can be substituted or unsubstituted, and the other one is independently a pyridine, a piperidine, a morpholine, or a pyrrole. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is a phenyl which is unsubstituted, and the other one is independently a pyridine, a piperidine, a morpholine, or a pyrrole.

[0282] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl, which can be substituted or unsubstituted, and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein.

[0283] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl, which can be substituted or unsubstituted, and the other one is an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl.

[0284] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl, which can be substituted or unsubstituted, and the other one is independently a pyridine, a piperidine, a morpholine, or a pyrrole.

[0285] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl which is substituted by a substituent selected from hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein.

[0286] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl which is substituted by a substituent selected from hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, and the other one is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl.

[0287] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl which is substituted by a substituent selected from hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, and the other one is independently a pyridine, a piperidine, a morpholine, or a pyrrole. According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl which is substituted by hydroxy or alkoxy, and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein.

[0288] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl which is substituted by hydroxy or alkoxy, and the other one is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl.

[0289] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl which is substituted by hydroxy or alkoxy, and the other one is a pyridine, a piperidine, a morpholine, or a pyrrole.

[0290] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl which is substituted by an alkoxy (e.g., methoxy), and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein.

[0291] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl which is substituted by an alkoxy (e.g., methoxy), and the other one is an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl.

[0292] According to some embodiments of any of the embodiments described herein, one of R10 and R11 is an aryl which is substituted by an alkoxy (e.g., methoxy), and the other one is a pyridine, a piperidine, a morpholine, or a pyrrole.

[0293] According to some embodiments of any of the embodiments described herein, at least two of R1-R5 are each independently hydroxy, R10 and R11 are each independently an aryl, and R14 is optionally hydrogen.

[0294] According to some embodiments of any of the embodiments described herein, at least two of R2, R3 and R4 are each hydroxy, R10 and R11 are each independently an aryl, and R14 is optionally hydrogen.

[0295] According to some embodiments of any of the embodiments described herein, R10 and R11 are each independently a phenyl which is substituted as described herein or is unsubstituted, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, R10 and R11 are each independently a phenyl which is unsubstituted, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, and R14 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl. According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, and R14 is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0296] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, and R14 is hydrogen.

[0297] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, and R14 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0298] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, and R14 is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0299] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, and R14 is hydrogen.

[0300] According to some embodiments of any of the embodiments described herein, X and Y are each N, and R14 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0301] According to some embodiments of any of the embodiments described herein, X and Y are each N, and R14 is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0302] According to some embodiments of any of the embodiments described herein, X and Y are each N, and R14 is hydrogen.

[0303] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, and R10 and R11 are each independently a phenyl which is substituted or unsubstituted. According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, and R10 and R11 are each independently a phenyl which is unsubstituted.

[0304] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, and at least one, or each, of R10 and R11 is independently a heteroalicyclic or a heteroaryl, as these are defined herein.

[0305] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, and at least one, or each, of R10 and R11 is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl.

[0306] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, and at least one, or each, of R10 and R11 is independently a pyridine, a piperidine, a morpholine, or a pyrrole.

[0307] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, and one of R10 and R11 is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein.

[0308] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, and R10 and R11 are each independently a phenyl which is substituted or unsubstituted. In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, and R10 and R11 are each independently a phenyl which is unsubstituted.

[0309] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, and at least one, or each, of R10 and R11 is independently a heteroalicyclic or a heteroaryl, as these are defined herein.

[0310] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, and at least one, or each, of R10 and R11 is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl.

[0311] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, and at least one, or each, of R10 and R11 is independently a pyridine, a piperidine, a morpholine, or a pyrrole.

[0312] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, and one of R10 and R11 is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein.

[0313] According to some embodiments of any of the embodiments described herein, X and Y are each N, and R10 and R11 are each independently a phenyl which is substituted or unsubstituted. According to some embodiments of any of the embodiments described herein, X and Y are each N, and R10 and R11 are each independently a phenyl which is unsubstituted.

[0314] According to some embodiments of any of the embodiments described herein, X and Y are each N, and at least one, or each, of R10 and R11 is independently a heteroalicyclic or a heteroaryl, as these are defined herein.

[0315] According to some embodiments of any of the embodiments described herein, X and Y are each N, and at least one, or each, of R10 and R11 is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or O-containing heteroaryl.

[0316] According to some embodiments of any of the embodiments described herein, X and Y are each N, and at least one, or each, of R10 and R11 is independently a pyridine, a piperidine, a morpholine, or a pyrrole. According to some embodiments of any of the embodiments described herein, X and Y are each N, and one of R10and R11is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein.

[0317] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, R10and R11are each independently a phenyl which is substituted or unsubstituted, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0318] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, R10and R11are each independently a phenyl which is substituted or unsubstituted, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0319] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, R10and R11are each independently a phenyl which is substituted or unsubstituted, and R is hydrogen.

[0320] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, at least one, or each, of R10and R11is independently a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0321] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, at least one, or each, of R10and R11is independently a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0322] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, at least one, or each, of R10and R11is independently a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen.

[0323] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, at least one, or each, of R10and R11is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0324] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, at least one, or each, of R10and R11is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0325] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, at least one, or each, of R10and R11is independently an N-containing heteroalicyclic, an N- containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl, and R14is hydrogen.

[0326] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, at least one, or each, of R10and R14is independently a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0327] According to some embodiments of any of the embodiments described herein, at least one of X and Y is independently N, at least one, or each, of R10and R14is independently a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0328] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, at least one, or each, of R10and R14is independently a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is hydrogen.

[0329] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, one of R10and R14is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0330] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, one of R10and R14is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0331] According to some embodiments of any of the embodiments described herein, at least one of X and Y is N, one of R10and R14is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen.

[0332] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, R10and R14are each independently a phenyl which is substituted or unsubstituted, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0333] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, R10and R14are each independently a phenyl which is substituted or unsubstituted, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length). In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl which is substituted or unsubstituted, and R14is hydrogen.

[0334] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0335] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0336] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen.

[0337] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0338] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0339] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl, and R14is hydrogen.

[0340] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0341] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length). In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is hydrogen.

[0342] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0343] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0344] In some embodiments of any of the embodiments described herein, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen.

[0345] According to some embodiments of any of the embodiments described herein, X and Y are each N, R10and R11are each independently a phenyl which is substituted or unsubstituted, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0346] According to some embodiments of any of the embodiments described herein, X and Y are each N, R10and R11are each independently a phenyl which is substituted or unsubstituted, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0347] According to some embodiments of any of the embodiments described herein, X and Y are each N, R10and R11are each independently a phenyl which is substituted or unsubstituted, and R14is hydrogen.

[0348] According to some embodiments of any of the embodiments described herein, X and Y are each N, at least one, or each of R10and R11is independently a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0349] According to some embodiments of any of the embodiments described herein, X and Y are each N, at least one, or each, of R10and R11is independently a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length). According to some embodiments of any of the embodiments described herein, X and Y are each N, at least one, or each, of R10and R11is independently a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen.

[0350] According to some embodiments of any of the embodiments described herein, X and Y are each N, at least one, or each, of R10and R11is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0351] According to some embodiments of any of the embodiments described herein, X and Y are each N, at least one, or each, of R10and R11is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl, and R is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0352] According to some embodiments of any of the embodiments described herein, X and Y are each N, at least one, or each, of R10and R11is independently an N-containing heteroalicyclic, an N-containing heteroaryl, an O-containing heteroalicyclic, or an O-containing heteroaryl, and R14is hydrogen.

[0353] According to some embodiments of any of the embodiments described herein, X and Y are each N, at least one, or each, of R10and R11is independently a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0354] According to some embodiments of any of the embodiments described herein, X and Y are each N, at least one, or each, of R10and R11is independently a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0355] According to some embodiments of any of the embodiments described herein, X and Y are each N, at least one, or each, of R10and R11is independently a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is hydrogen.

[0356] According to some embodiments of any of the embodiments described herein, X and Y are each N, one of R10and R11is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, or aryl.

[0357] According to some embodiments of any of the embodiments described herein, X and Y are each N, one of R10and R11is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein, and R14 is hydrogen or an alkyl (which is optionally substituted or unsubstituted and / or is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0358] According to some embodiments of any of the embodiments described herein, X and Y are each N, one of R10and R11is an aryl (e.g., phenyl; the aryl can be substituted as described hereinabove or unsubstituted) and the other one is a heteroalicyclic or a heteroaryl, as these are defined herein, and R14is hydrogen.

[0359] In some embodiments of any of the embodiments described herein, when X is CR12 and / or Y is CR13, R12 and / or R13 is each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, or a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R10-R14. In some embodiments of any of the embodiments described herein, when X is CR12 and / or Y is CR13, R12 and / or R13 is each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, or amino. In some embodiments of any of the embodiments described herein, when X is CR12 and / or Y is CR13, R12 and / or R13 is each independently an alkyl (e.g., an alkyl is of up to 8, or up to 5, or up to 3, carbon atoms in length), a cycloalkyl, or an aryl, a heteroaryl, a heteroalicyclic, or halo, as these are defined herein in any of the respective embodiments. In some embodiments of any of the embodiments described herein, when X is CR12 and / or Y is CR13, R12 and / or R13 is independently hydrogen

[0360] In some embodiments of any of the embodiments described herein, when X is CR12 and / or Y is CR13, R12 and / or R13 is each independently hydrogen or an alkyl (e.g., an alkyl is of up to 8, or up to 5, or up to 3, carbon atoms in length).

[0361] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0362] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of R10and R11is independently an aryl, which can be substituted (e.g., by an alkoxy) or unsubstituted, and R14is optionally hydrogen.

[0363] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, R10and R14are each independently a phenyl which is substituted or unsubstituted, and R14is optionally hydrogen.

[0364] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, one of R10and R14is an aryl and the other one is a heteroalicyclic or a heteroaryl, and R14is optionally hydrogen.

[0365] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, one of R10and R14is an aryl, which can be substituted or unsubstituted, and the other one is independently a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is optionally hydrogen.

[0366] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14is optionally hydrogen.

[0367] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R10and R14is independently an aryl, which can be substituted (e.g., by an alkoxy) or unsubstituted, and R14is optionally hydrogen.

[0368] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, R10and R14are each independently a phenyl which is substituted or unsubstituted, and R14is optionally hydrogen.

[0369] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, one of R10and R14is an aryl and the other one is a heteroalicyclic or a heteroaryl, and R14is optionally hydrogen.

[0370] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, one of R10and R14is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0371] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of R10and R14is independently an aryl, which can be substituted (e.g., by an alkoxy) or unsubstituted, and R14is optionally hydrogen.

[0372] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, R10and R14are each independently a phenyl which is substituted or unsubstituted, and R14is optionally hydrogen.

[0373] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, one of R10and R14is an aryl and the other one is a heteroalicyclic or a heteroaryl, and R14is optionally hydrogen.

[0374] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, one of R10and R14is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0375] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of X and Y is N.

[0376] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of X and Y is independently N.

[0377] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of X and Y is independently N.

[0378] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, as these are defined herein, and R14is optionally hydrogen.

[0379] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, which can be substituted (e.g., by an alkoxy) or unsubstituted, and R14is optionally hydrogen.

[0380] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each of X and Y is independently N, R10and R11are each independently a phenyl which is substituted or unsubstituted, and R14is optionally hydrogen. According to some embodiments of any of the embodiments described herein, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each of X and Y is independently N, R10and R11are each independently a phenyl which is unsubstituted, and R14is optionally hydrogen.

[0381] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl and the other one is a heteroalicyclic or a heteroaryl, and R14 is optionally hydrogen.

[0382] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0383] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, as these are defined herein, and R14 is optionally hydrogen.

[0384] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, which can be substituted (e.g., by an alkoxy) or unsubstituted, and R14 is optionally hydrogen.

[0385] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl which is substituted or unsubstituted, and R14is optionally hydrogen. According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl which is unsubstituted, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl and the other one is a heteroalicyclic or a heteroaryl, and R14 is optionally hydrogen.

[0386] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0387] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, as these are defined herein, and R14 is optionally hydrogen.

[0388] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, which can be substituted (e.g., by an alkoxy) or unsubstituted, and R14 is optionally hydrogen.

[0389] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl which is substituted or unsubstituted, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl which is unsubstituted, and R14 is optionally hydrogen.

[0390] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl and the other one is a heteroalicyclic or a heteroaryl, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one a pyridine, a piperidine, a morpholine, or a pyrrole, and R14is optionally hydrogen.

[0391] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises urea or thiourea, as described herein in any of the respective embodiments.

[0392] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises a urea moiety, as described herein in any of the respective embodiments.

[0393] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is a urea moiety, and the compounds are collectively represented by Formula VI.2:

[0394] R15R16

[0395]

[0396] R11

[0397] Formula VI.2

[0398] wherein A2 is as described herein in any of the respective embodiments (e.g., for Formulae V-V.4), X, Y and R10-R14 are as described herein in any of the respective embodiments (e.g., for Formula VI), or hereinunder in any of the respective embodiments (e.g., for Formula I); and wherein R15 and R16 are as defined herein in any of the respective embodiments (e.g., for Formula V.2) or hereinunder (e.g., for Formulae II-II***), unless mentioned otherwise.

[0399] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an N-containing heterocyclic moiety (also referred to herein as N-heterocyclic group), as described herein in any of the respective embodiments. According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises a 1,2, 3 -triazole (as an exemplary N-heterocyclic group).

[0400] According to some embodiments of any of the embodiments described herein, the bridging moiety B is a 1,2,3-triazole.

[0401] Exemplary compounds of Formula VI in which the bridging moiety B is a 1,2,3-triazole (as an exemplary N-heterocyclic group) are collectively represented by Formula VI.3 or VI.3a:

[0402]

[0403] wherein A2 is as described herein in any of the respective embodiments (e.g., for Formula V); X, Y and R10-R14 are as described herein in any of the respective embodiments (e.g., for Formula VI) or hereinunder for Formula I; and wherein R17 is as described herein in any of the respective embodiments (e.g., for Formula V.3 or V.3a) or hereinunder (e.g., for Formula III-III*** or Illa-Illa***).

[0404] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide or a thioamide or a sulfonamide, as described herein in any of the respective embodiments.

[0405] According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B is or comprises an amide. According to some embodiments of any of the embodiments described herein for Formula VI, the bridging moiety B comprises an amide, for example, an alkylamide or an amidoalkyl. In some of these embodiments, the alkyl is a lower alkyl, or 1 to 6, or 1 to 4, or 1-2 carbon atoms in length. In some of these embodiments, the alkyl is methylene, and the bridging moiety B is amidomethylene (-CONH-CH2-) or methyleneamido (-CH2-CONH-).

[0406] Exemplary compounds of Formula VI in which the bridging moiety B comprises an amide are collectively represented by Formula VI.4 or VI.4a:

[0407] '20

[0408] N

[0409] A2

[0410] Formula VI.4

[0411] '20

[0412] N

[0413] A2

[0414]

[0415] Formula VI.4a

[0416] wherein A2 is as described herein in any of the respective embodiments (e.g., for Formula V); X, Y, and R10-R14 are as described herein in any of the respective embodiments (e.g., for Formula VI); and wherein R18-R20 are all as described herein in any of the respective embodiments (e.g., for Formula V.4 or V.4a), unless otherwise indicated.

[0417] According to some embodiments of any of the embodiments described herein, the compound is represented by Formula VI**:

[0418]

[0419] Ri i

[0420] Formula VI**

[0421] wherein B is as described herein in any of the respective embodiments (e.g., for Formulae V or VI), unless mentioned otherwise; X and Y are as described herein in any of the respective embodiments (e.g., for Formula VI); and R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino, or, alternatively, two or more of R10-R14 form together a 3-8-membered, or 4-6-membered cyclic or heteroalicyclic ring; and

[0422] A2 is either a substituted or unsubstituted heteroaryl or an aryl, having a 3-8-membered, or 4-6-membered cyclic or heteroalicyclic ring fused thereto.

[0423] In some embodiments of any of the embodiments described herein, e.g., for Formulae VI or VI**, X and Y are each N, and the compound is represented by Formula VI*:

[0424]

[0425] R11

[0426] Formula VI*

[0427] wherein B is described herein in any of the respective embodiments (e.g., for Formula V or VI), A2 is described herein in any of the respective embodiments (e.g., for Formula V or VI or VI**) and R10, R11, and RM are as described herein in any of the respective embodiments (e.g., for Formula VI) or hereinunder in any of the respective embodiments (e.g., for Formula I). According to some embodiments of any of the embodiments described herein for Formula VI*, the bridging moiety B is or comprises urea or thiourea, as described and defined herein in any of the respective embodiments.

[0428] According to some embodiments of any of the embodiments described herein for Formula VI*, the bridging moiety B is or comprises a urea moiety, as described and defined herein in any of the respective embodiments.

[0429] According to some embodiments of any of the embodiments described herein for Formula VI*, the bridging moiety B is a urea moiety, and the compounds are collectively represented by Formula VI.2*:

[0430]

[0431] Formula VI*.2

[0432] wherein A2 is as described herein in any of the respective embodiments (e.g., for Formula V); R10, R11, and RM are as described herein in any of the respective embodiments (e.g., for Formula V or VI) or hereinunder in any of the respective embodiments (e.g., for Formula I); and wherein R15 and Ri6 are as defined for Formula V. II or hereinunder (e.g., for Formulae II-II***).

[0433] According to some embodiments of any of the embodiments described herein for Formula VI*, the bridging moiety B is or comprises an N-containing heterocyclic moiety (also referred to herein as N-heterocyclic group), as described herein in any of the respective embodiments.

[0434] According to some embodiments of any of the embodiments described herein for Formula VI*, the bridging moiety B is or comprises a 1,2, 3 -triazole (as an exemplary N-heterocyclic group).

[0435] According to some embodiments of any of the embodiments described herein for Formula VI*, the bridging moiety B is a 1,2,3-triazole.

[0436] Exemplary compounds of Formula VI* in which the bridging moiety B is a 1,2,3-triazole (as an exemplary N-heterocyclic group) are collectively represented by Formula VI*.3 or VI*.3a:

[0437]

[0438] wherein A2 is as defined for Formula V; R10, R11, and R14, and R12, are as described herein in any of the respective embodiments (e.g., for Formula VI), unless otherwise indicated; and wherein R17 is as described herein in any of the respective embodiments (e.g., for Formula V.3 or V.3a) or as defined hereinunder (e.g., for Formulae III-III*** or Illa-IIIa***).

[0439] According to some embodiments of any of the embodiments described herein for Formula VI*, the bridging moiety B is or comprises an amide or a thioamide or a sulfonamide, as described and defined herein in any of the respective embodiments.

[0440] According to some embodiments of any of the embodiments described herein for Formula VI*, the bridging moiety B is or comprises an amide, as described and defined herein in any of the respective embodiments.

[0441] According to some embodiments of any of the embodiments described herein for Formula VI*, the bridging moiety B comprises an amide, for example, an alkylamide or an amidoalkyl. In some of these embodiments, the alkyl is a lower alkyl, or 1 to 6, or 1 to 4, or 1-2 carbon atoms in length. In some of these embodiments, the alkyl is methylene, and the bridging moiety B is amidomethylene (for example, -CONH-R’R”-) or methyleneamido (for example, -CR’R”-CONH-).

[0442] Exemplary compounds of Formula VI* in which X and Y are N and the bridging moiety B is or comprises an amide are collectively represented by Formula VI*.4 or VI*.4a: Formula VI*.4

[0443]

[0444] wherein A2 is as described herein in any of the respective embodiments (e.g., for Formula V); R10, R11, and RM are as described herein in any of the respective embodiments (e.g., for Formula VI or VI*), unless otherwise indicated; and wherein R18-R20 are all as described hereinunder (e.g., for Formula IV-IV*** or IVa-IVa***).

[0445] In some embodiments of any of the embodiments described herein for Formula V, VI, and subformulae thereof, Al is an aryl or a heteroaryl and A2 is an aryl. In some embodiments of any of the embodiments described herein, Al is a substituted aryl or a substituted heteroaryl as described herein and A2 is an aryl. According to some embodiments of any of the embodiments described herein, Al is an aryl, pyridine or pyrimidine and A2 is an aryl. According to some embodiments of any of the embodiments described herein, Al is an aryl, pyridine or pyrimidine and A2 is a heteroaryl aryl.

[0446] In some embodiments of any of the embodiments described herein, Al is a heteroaryl and A2 is a phenyl. In some embodiments of any of the embodiments described herein, Al is a substituted aryl or substituted heteroaryl as described herein and A2 is a phenyl.

[0447] According to some embodiments of any of the embodiments described herein, Al is a phenyl, pyridine or pyrimidine and A2 is a phenyl, and the compound is represented by Formula I:

[0448]

[0449] wherein B is as defined for Formula V; X, Y and R10-R14 are all as described herein in any of the respective embodiments (e.g., for Formula VI) or as defined hereinunder (e.g., for Formula I); and wherein R1-R5 are as described hereinunder (e.g., for Formula I).

[0450] According to an aspect of some embodiments of the present invention there are provided newly designed compounds, which are represented by Formula I:

[0451]

[0452] wherein:

[0453] B is a bridging moiety, as defined herein in any of the respective embodiments;

[0454] X is N or CR12;

[0455] Y is N or CR13;

[0456] R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R10-R14 or two or more of R10, R11 and R14; and

[0457] R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R1-R5.

[0458] According to some embodiments of any of the embodiments described herein for Formula I: B is a bridging moiety, as defined and described herein in any of the respective embodiments; X is N or CR12;

[0459] Y is N or CR13;

[0460] R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino; and

[0461] R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

[0462] According to some embodiments of any of the embodiments described herein for Formula I: B is a bridging moiety, as defined and described herein in any of the respective embodiments; X is N or CR12;

[0463] Y is N or CR13;

[0464] R10-R14 are as described herein in any of the respective embodiments and any combination thereof; and R1-R5 are as described hereinunder.

[0465] According to some embodiments of any of the embodiments described herein, R1-R5 are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, or amino.

[0466] According to some embodiments of any of the embodiments described herein, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydroxy, thiol, alkoxy, thioalkoxy, aryloxy, and thioaryloxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydroxy, thiol, alkoxy and aryloxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydroxy, alkoxy, thiol and thioalkoxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydroxy, alkoxy and aryloxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently alkoxy or hydroxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or at least three, or all, of Ri-R5 is / are each hydroxy.

[0467] According to some embodiments of any of the embodiments described herein, at least one, or at least two, or all, of R2, R3 and R4 is / are each independently selected from hydroxy, thiol, alkoxy, thioalkoxy, aryloxy, and thioaryloxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or all, of R2, R3 and R4 is / are each independently selected from hydroxy, thiol, alkoxy and aryloxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or all, of R2, R3 and R4 is / are each independently selected from hydroxy, alkoxy, thiol and thioalkoxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or all, of R2, R3 and R4 is / are each independently selected from hydroxy, alkoxy, and aryloxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or all, of R2, R3 and R4 are each selected from alkoxy and hydroxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or all, of R2, R3 and R4 are each independently alkoxy or hydroxy. According to some embodiments of any of the embodiments described herein, at least one, or at least two, or all, of R2, R3 and R4 are each hydroxy.

[0468] According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently selected from hydroxy, thiol, alkoxy, thioalkoxy, aryloxy, and thioaryloxy. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently selected from hydroxy, thiol, alkoxy and aryloxy. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently selected from hydroxy, alkoxy, thiol and thioalkoxy. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently selected from hydroxy, alkoxy, and aryloxy. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently an alkoxy or hydroxy. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently an alkoxy or hydroxy. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently hydroxy.

[0469] According to some embodiments of any of the embodiments described herein, R3 and R4 are each hydroxy.

[0470] Whenever one or more of R1-R5 is / are alkoxy, aryloxy, thioalkoxy or thioaryloxy, these substituents can be further substituted, as described herein, or be unsubstituted.

[0471] According to some embodiments of any of the embodiments described herein, at least one, or each, of Ri and R5 is hydrogen. According to some embodiments of any of the embodiments described herein, at least one, or two, or each, of Ri, R2 and Rs is / are each hydrogen.

[0472] According to some embodiments of any of the embodiments described herein, Ri and Rs are each hydrogen. According to some embodiments of any of the embodiments described herein, Ri, R2 and Rs are each hydrogen.

[0473] According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently hydroxy, at least one, or each, of Ri and Rs is hydrogen, and R2 is optionally hydrogen.

[0474] According to some embodiments of any of the embodiments described herein, R3 and R4 are each hydroxy, Ri and Rs are each hydrogen, and R2 is optionally hydrogen.

[0475] According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently selected from hydroxy, thiol, alkoxy, thioalkoxy, aryloxy, and thioaryloxy; and Ri and Rs are each hydrogen, and R2 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently selected from hydroxy, thiol, alkoxy and aryloxy; Ri and Rs are each hydrogen, and R2 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4is independently selected from hydroxy, alkoxy, thiol and thioalkoxy; Ri and Rs are each hydrogen, and R2 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently selected from hydroxy, alkoxy, and aryloxy; Ri and Rs are each hydrogen, and R2 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently an alkoxy or hydroxy; Ri and Rs are each hydrogen, and R2 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently an alkoxy or hydroxy; Ri and Rs are each hydrogen, and R2 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is independently hydroxy; Ri and Rs are each hydrogen, and R2 is optionally hydrogen.

[0476] According to some embodiments of any of the embodiments described herein, R3 and R4 are each hydroxy; Ri and Rs are each hydrogen, and R2 is optionally hydrogen.

[0477] According to some embodiments of any of the embodiments described herein, two of R1-R5 together form together a cyclic or heterocyclic ring, which can be substituted or unsubstituted, as defined herein in any of the respective embodiments. According to some embodiments of any of the embodiments described herein, two of R1-R5 (e.g., R3 and R4) together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted, as described herein in any of the respective embodiments.

[0478] According to some embodiments of any of the embodiments described herein, R3 and R4 together form a cyclic or heterocyclic ring, which can be substituted or unsubstituted, as described herein in any of the respective embodiments. According to some of these embodiments, Ri, R2 and R5 can be each hydrogen, or can be each independently any of the substituents as described and defined herein. According to some of these embodiments, Ri and R5 are each hydrogen, and R2 is optionally hydrogen.

[0479] According to some embodiments of any of the embodiments described herein, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic as described herein in any of the respective embodiments.

[0480] According to some embodiments of any of the embodiments described herein, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is an N-containing heteroaryl or heteroalicyclic which may be unsubstituted or substituted as described herein in any of the respective embodiments.

[0481] According to some embodiments of any of the embodiments described herein, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy.

[0482] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, and at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy. According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, and at least one, or at least two, or all, of R2, R3, and R4 is / are each independently hydrogen or hydroxy.

[0483] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, and at least one, or each, of R3 and R4 is independently hydroxy.

[0484] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, and at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy.

[0485] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, and at least one, or at least two, or all, of R2, R3, and R4 is / are each independently hydrogen or hydroxy.

[0486] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, and at least one, or each, of R3 and R4 is independently hydroxy.

[0487] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, and at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy.

[0488] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, and at least one, or at least two, or all, of R2, R3, and R4 are each hydroxy.

[0489] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, and at least one, or each, of R3 and R4 is independently hydroxy.

[0490] According to some embodiments of any of the embodiments described herein for Formula I, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10 and R11 are each independently an aryl, and R14 is optionally hydrogen.

[0491] According to some embodiments of any of the embodiments described herein for Formula I, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl which is substituted as described herein or is unsubstituted, and R14is optionally hydrogen. According to some embodiments of any of the embodiments described herein, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl which is unsubstituted, and R14 is optionally hydrogen.

[0492] According to some embodiments of any of the embodiments described herein for Formula I, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently a phenyl which is substituted as described herein or is unsubstituted, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently a phenyl which is unsubstituted, and R14 is optionally hydrogen.

[0493] According to some embodiments of any of the embodiments described herein for Formula I, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 are each hydrogen, at least one, or each, of R10and R11is independently an aryl which is substituted as described herein or is unsubstituted, a heteroaryl, a cycloalkyl or a heteroalicyclic, and R14 is optionally hydrogen.

[0494] According to some embodiments of any of the embodiments described herein for Formula I, at least two of R1-R5 are each hydroxy, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl as described herein, and R14is optionally hydrogen.

[0495] According to some embodiments of any of the embodiments described herein for Formula I, at least two of R2, R3 and R4 are each hydroxy, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, and R14 is optionally hydrogen.

[0496] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R1-R5, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0497] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R1-R5, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0498] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R1-R5, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0499] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 together form the cyclic or heterocyclic ring, which can be substituted or unsubstituted as these are defined herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0500] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 together form the cyclic or heterocyclic ring, which can be substituted or unsubstituted as these are defined herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0501] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 together form the cyclic or heterocyclic ring, which can be substituted or unsubstituted as these are defined herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0502] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R14are each independently a phenyl, and R14is optionally hydrogen.

[0503] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R14is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0504] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, R3 and R4 together form a cyclic or heterocyclic ring as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0505] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, R3 and R4 together form a cyclic or heterocyclic ring as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R14are each independently a phenyl, and R14is optionally hydrogen.

[0506] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, R3 and R4 together form a cyclic or heterocyclic ring as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R14is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11 is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0507] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0508] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0509] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is an N-containing heteroaryl or heteroalicyclic which may be unsubstituted or substituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0510] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is an N-containing heteroaryl or heteroalicyclic which may be unsubstituted or substituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0511] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is an N-containing heteroaryl or heteroalicyclic which may be unsubstituted or substituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0512] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is selected from pyrrole, imidazole, pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine, pyridinone, pyridazine, pyrimidine, pyrazine, morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine, thiazolidine, and pyrazolidine, preferably selected from imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, and pyrazolidinone, each being substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0513] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is selected from pyrrole, imidazole, pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine, pyridinone, pyridazine, pyrimidine, pyrazine, morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine, thiazolidine, and pyrazolidine, preferably selected from imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, and pyrazolidinone, each being substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0514] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is selected from pyrrole, imidazole, pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine, pyridinone, pyridazine, pyrimidine, pyrazine, morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine, thiazolidine, and pyrazolidine, preferably selected from imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, and pyrazolidinone, each being substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0515] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0516] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0517] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0518] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0519] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0520] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and Rs is / are hydrogen, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0521] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and Rs is / are hydrogen, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0522] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and Rs is / are hydrogen, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0523] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and Rs is / are hydrogen, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0524] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of Ri-Rs, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of Ri-R5, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0525] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of Ri-R5, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0526] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 together form the cyclic or heterocyclic ring, which can be substituted or unsubstituted as these are defined herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0527] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 together form the cyclic or heterocyclic ring, which can be substituted or unsubstituted as these are defined herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0528] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 together form the cyclic or heterocyclic ring, which can be substituted or unsubstituted as these are defined herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0529] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0530] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14is optionally hydrogen.

[0531] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0532] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, R3 and R4 together form a cyclic or heterocyclic ring as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and Ri 1 is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0533] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, R3 and R4 together form a cyclic or heterocyclic ring as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0534] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, R3 and R4 together form a cyclic or heterocyclic ring as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0535] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0536] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0537] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0538] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is an N-containing heteroaryl or heteroalicyclic which may be unsubstituted or substituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0539] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is an N-containing heteroaryl or heteroalicyclic which may be unsubstituted or substituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14is optionally hydrogen.

[0540] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is an N-containing heteroaryl or heteroalicyclic which may be unsubstituted or substituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0541] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is selected from pyrrole, imidazole, pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine, pyridinone, pyridazine, pyrimidine, pyrazine, morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine, thiazolidine, and pyrazolidine, preferably selected from imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, and pyrazolidinone, each being substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0542] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is selected from pyrrole, imidazole, pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine, pyridinone, pyridazine, pyrimidine, pyrazine, morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine, thiazolidine, and pyrazolidine, preferably selected from imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, and pyrazolidinone, each being substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0543] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is selected from pyrrole, imidazole, pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine, pyridinone, pyridazine, pyrimidine, pyrazine, morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine, thiazolidine, and pyrazolidine, preferably selected from imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, and pyrazolidinone, each being substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0544] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0545] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0546] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0547] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0548] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14is optionally hydrogen.

[0549] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0550] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0551] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, and R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0552] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, and one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0553] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R1-R5, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0554] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R1-R5, at least one, or each, of X and Y is independently N, and R10and R14are each independently a phenyl, and R14is optionally hydrogen.

[0555] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R1-R5, at least one, or each, of X and Y is independently N, and one of R10and R14is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0556] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 together form the cyclic or heterocyclic ring, which can be substituted or unsubstituted as these are defined herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14is optionally hydrogen.

[0557] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 together form the cyclic or heterocyclic ring, which can be substituted or unsubstituted as these are defined herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and R10and R14are each independently a phenyl, and R14is optionally hydrogen.

[0558] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 together form the cyclic or heterocyclic ring, which can be substituted or unsubstituted as these are defined herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, and one of R10and R14is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0559] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14is optionally hydrogen.

[0560] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, R10and R14are each independently a phenyl, and R14is optionally hydrogen.

[0561] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0562] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, R3 and R4 together form a cyclic or heterocyclic ring as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0563] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, R3 and R4 together form a cyclic or heterocyclic ring as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14is optionally hydrogen.

[0564] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, R3 and R4 together form a cyclic or heterocyclic ring as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0565] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0566] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0567] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0568] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is an N-containing heteroaryl or heteroalicyclic which may be unsubstituted or substituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0569] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is an N-containing heteroaryl or heteroalicyclic which may be unsubstituted or substituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0570] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is an N-containing heteroaryl or heteroalicyclic which may be unsubstituted or substituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is selected from pyrrole, imidazole, pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine, pyridinone, pyridazine, pyrimidine, pyrazine, morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine, thiazolidine, and pyrazolidine, preferably selected from imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, and pyrazolidinone, each being substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0571] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is selected from pyrrole, imidazole, pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine, pyridinone, pyridazine, pyrimidine, pyrazine, morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine, thiazolidine, and pyrazolidine, preferably selected from imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, and pyrazolidinone, each being substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14is optionally hydrogen.

[0572] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, two of R1-R5 (e.g., R3 and R4) together form a cyclic or heterocyclic ring which is selected from pyrrole, imidazole, pyrazole, triazole, tetrazole, oxazole, isoxazole, thiazole, thiadiazole, oxadiazole, pyridine, pyridinone, pyridazine, pyrimidine, pyrazine, morpholine, piperidine, piperazine, pyrrolidine, dioxolane, imidazolidine, thiazolidine, and pyrazolidine, preferably selected from imidazole, imidazolone, triazole, imidazole, imidazolone, pyridine, pyridinone, pyridazine, pyridazinone, pyrimidine, pyriminidinone, pyrazine, pyrazinone, pyrazolidine, and pyrazolidinone, each being substituted or unsubstituted as described herein in any of the respective embodiments, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0573] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14is optionally hydrogen.

[0574] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, at least one, or each, of X and Y is independently N, R10and R14are each independently a phenyl, and R14is optionally hydrogen.

[0575] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, at least one, or each, of X and Y is independently N, one of R10and R14is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14is optionally hydrogen.

[0576] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14is optionally hydrogen.

[0577] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole; at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy, and optionally Ri and Rs is / are hydrogen, at least one, or each, of X and Y is independently N; one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole; and R14 is optionally hydrogen.

[0578] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and Rs is / are hydrogen, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0579] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and Rs is / are hydrogen, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0580] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy; and optionally Ri and Rs is / are hydrogen, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0581] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy, and optionally Ri and Rs is / are hydrogen, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0582] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy, and optionally Ri and Rs is / are hydrogen, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14is optionally hydrogen.

[0583] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy, and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0584] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or all, of R2, R3 and R4 are each selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy, and optionally Rl and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0585] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy, and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0586] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy, and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0587] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of R3 and R4 is independently selected from hydrogen, hydroxy, alkoxy, aryloxy, thiol, thioalkoxy, and thioaryloxy, preferably hydroxy, alkoxy or aryloxy, and optionally Ri and R5 is / are hydrogen, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0588] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0589] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or all, of R2, R3, and R4 are independently selected from hydrogen and hydroxy, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0590] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of R3 and R4 is independently hydroxy, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0591] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0592] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or all, of R2, R3, and R4 are each hydroxy, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0593] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of R3 and R4 is independently hydroxy, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0594] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0595] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or at least two, or all, of R2, R3, and R4 are each hydroxy, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0596] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is devoid of hydrazine or hydrazone, at least one, or each, of R3 and R4 is independently hydroxy, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0597] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0598] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or all, of R2, R3, and R4 are each hydroxy, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0599] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R3 and R4 is independently hydroxy, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0600] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or all, of R2, R3, and R4 are each hydroxy, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0601] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R3 and R4 is independently hydroxy, at least one, or each, of X and Y is independently N, R10and R11are each independently a phenyl, and R14 is optionally hydrogen.

[0602] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0603] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or at least two, or all, of R2, R3, and R4 are each independently hydrogen and hydroxy, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0604] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an N-containing moiety, at least one, or each, of R3 and R4 is independently hydroxy, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0605] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0606] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or all, of R2, R3, and R4 are each hydroxy, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0607] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of R3 and R4 is independently hydroxy, at least one, or each, of X and Y is independently N, at least one, or each, of R10and R14is independently an aryl, a heteroaryl, a cycloalkyl, or a heteroalicyclic, and R14 is optionally hydrogen.

[0608] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy, at least one, or each, of X and Y is independently N, R10and R14are each independently a phenyl, and R14 is optionally hydrogen.

[0609] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or all, of R2, R3, and R4 are each hydroxy, at least one, or each, of X and Y is independently N, R10and R14are each independently a phenyl, and R14 is optionally hydrogen.

[0610] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of R3 and R4 is independently hydroxy, at least one, or each, of X and Y is independently N, R10and R14are each independently a phenyl, and R14 is optionally hydrogen.

[0611] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or at least three, or all, of R1-R5 is / are each independently hydrogen, alkoxy, or hydroxy, at least one, or each, of X and Y is independently N, one of R10and R14is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0612] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or at least two, or all, of R2, R3, and R4 are each hydroxy, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0613] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises an amide, a sulfonamide, a urea, a triazole, a tetrazole, an imidazole, a pyridine, a pyrazole, an oxadiazole, a thiadiazole, a thiazole, or an isoxazole, at least one, or each, of R3 and R4 is independently hydroxy, at least one, or each, of X and Y is independently N, one of R10and R11is an aryl, which can be substituted or unsubstituted, and the other one is independently selected from a pyridine, a piperidine, a morpholine, and a pyrrole, and R14 is optionally hydrogen.

[0614] Additional amide-containing bridging groups B are also contemplated.

[0615] According to some embodiments of any of the embodiments described herein for Formula I, the bridging moiety B is or comprises a sulfonamide. In some embodiments of any of the embodiments described herein, the bridging moiety B is a sulfonamide, and R1-R5 and R10-R14 are as described herein in any of the respective embodiments and in any combination thereof.

[0616] An exemplary such compound is GLB-14 (see, Table 1).

[0617] According to some embodiments of any of the embodiments described herein, at least one, at least two, at least two, or all, of R1-R5 is / are a moiety that is capable to decompose, preferably under physiological environment, to generate hydroxy or thiol, preferably hydroxy. According to some embodiments of any of the embodiments described herein, at least one, or each, of R3 and R4 is a moiety that is capable to decompose, preferably under physiological environment, to generate hydroxy or thiol, preferably hydroxy. According to some of these embodiments, the remaining Ri, R2 and R5 are each independently any of the substituents as described herein, for example, each is hydrogen.

[0618] Such moieties can be, for example, acetylated hydroxy or thiol, amidated hydroxy or thiol, carbamate derivatives of hydroxy or thiol, and alkoxylated or aryloxylated hydroxy or thiol.

[0619] For example, in some embodiments of any of the embodiments described herein for Formula I, at least one, at least two, at least two, or all, of R1-R5, or at least one or each of R3 and R4, is each independently C-carboxy, O-carboxy, C-thiocarboxy, O-thiocarboxy, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, alkoxycarbonyloxy, alkoxy or thioalkoxy.

[0620] Exemplary compounds featuring such moieties can be collectively represented by Formula I**:

[0621]

[0622] wherein B is as described herein in any of the respective embodiments (e.g., for Formula V); X, Y, R10, R11, and R14are as described herein in any of the respective embodiments (e.g., for Formula VI or Formula I) unless mentioned otherwise; and R1-R5 are as described herein in any of the respective embodiments (e.g., for Formula I); and RA and RB are each independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, acyl, carbonyl, thiocarboxy, amido, carboxy, carbamyl, thiocarbamyl, and alkoxycarbonyloxy.

[0623] According to some embodiments of any of the embodiments described herein for Formula I, at least one of X and Y is N. In some embodiments of any of the embodiments described herein for Formula I, at least one, or each, of X and Y is N.

[0624] According to some embodiments of any of the embodiments described herein for Formula I, X and Y are each N, and the compound is represented by Formula I*:

[0625]

[0626] wherein B is as described herein in any of the respective embodiments (e.g., for Formula V, VI or I); R10, R11, and R14 are as described herein in any of the respective embodiments (e.g., for Formula VI or Formula I) unless mentioned otherwise; and R1-R5 are as described herein in any of the respective embodiments (e.g., for Formula I). According to some embodiments of any of the embodiments described herein for Formula I, I* or I**, the bridging moiety B is or comprises a urea, as defined and described herein in any of the respective embodiments.

[0627] Exemplary compounds of Formula I in which the bridging moiety B is or comprises a urea are collectively represented by Formula II:

[0628] R11

[0629]

[0630] wherein R10, R11 and R14 are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); R1-R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); and R15 and Ri6 are as described herein in any of the respective embodiments (e.g., for Formula V.2, VI.2 or VI*.2)

[0631] and / or by Formula II*:

[0632]

[0633] wherein X, Y, R10-R14 are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); R1-R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); and R15 and R16 are as described herein in any of the respective embodiments (e.g., for Formula V.2, VI.2 or VI*.2); and / or by Formula II**:

[0634]

[0635] wherein X, Y, R10-R14 are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); R1, R2 and R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); ORA and ORB are as described herein in any of the respective embodiments (e.g., for Formula I**); and R15 and R16 are as described herein in any of the respective embodiments (e.g., for Formula V.2, VI.2 or VI*.2);

[0636] and / or by Formula II***;

[0637]

[0638] wherein R10, R11 and R14 are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); Ri, R2 and R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); ORA and ORB are as described herein in any of the respective embodiments (e.g., for Formula I**); and R15 and Ri6 are as described herein in any of the respective embodiments (e.g., for Formula V.2, VI.2 or VI*.2).

[0639] Additional urea-containing bridging groups B are also contemplated. According to some embodiments of any of the embodiments described herein for Formula I, I* or I**, the bridging moiety B is or comprises a 1,2,3-triazole (as an exemplary N-heterocyclic group), as defined and described herein in any of the respective embodiments.

[0640] Exemplary compounds of Formula I in which the bridging moiety B is or comprises a 1,2,3-triazole (as an exemplary N-heterocyclic group) are collectively represented by Formula III:

[0641]

[0642] or by Formula Illa:

[0643]

[0644] wherein R10, R11and R14are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); R1-R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); and R17 is as described herein in any of the respective embodiments (e.g., for Formula V.3, V.3a, VI.3, VI.3a, VI*.3 or VI*.3a);

[0645] and / or by Formula III*:

[0646]

[0647] or by Formula Illa*:

[0648]

[0649] wherein X, Y, R10-R14 are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); R1-R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); and R17 is as described herein in any of the respective embodiments (e.g., for Formula V.3, V.3a, VI.3, VI.3a, VI*.3 or VI*.3a);

[0650] and / or by Formula III**:

[0651]

[0652] or by Formula Illa**:

[0653]

[0654] wherein X, Y, R10, R11and R14are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); Ri, R2 and R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); ORA and ORB are as described herein in any of the respective embodiments (e.g., for Formula I**); and R17 is as described herein in any of the respective embodiments (e.g., for Formula V.3, V.3a, VI.3, VI.3a, VI*.3 or VI*.3a);

[0655] and / or by Formula III***;

[0656]

[0657] or by Formula Illa***:

[0658]

[0659] Formula Illa*** wherein R10, R11and R14are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); Ri, Rs and R2, are all as described herein in any of the respective embodiments (e.g., for Formula I); ORA and ORB are as described herein in any of the respective embodiments (e.g., for Formula I**); and R17 is as described herein in any of the respective embodiments (e.g., for Formula V.3, V.3a, VI.3, VI.3a, VI*.3 or VI*.3a).

[0660] Exemplary compounds of Formula I in which the bridging moiety B is or comprises an amide are collectively represented by Formula IV:

[0661]

[0662] Formula IV

[0663] or by Formula IVa:

[0664]

[0665] wherein R10, R11 and R14 are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); R1-R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); and R18-R20 are as described herein in any of the respective embodiments (e.g., for Formula V.4, V.4a, VI.4, VI.4a, VI*.4 or VI*.4a);

[0666] and / or by Formula IV*:

[0667]

[0668] or by Formula IVa*:

[0669]

[0670] wherein X, Y and R10-R14 are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); R1-R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); and R18-R20 are as described herein in any of the respective embodiments (e.g., for Formula V.4, V.4a, VI.4, VI.4a, VI*.4 or VI*.4a);

[0671] and / or by Formula IV**:

[0672]

[0673] or by Formula IVa**:

[0674]

[0675] Formula IVa**

[0676] wherein X, Y and R10-R14 are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); Ri, R2 and R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); ORA and ORB are as described herein in any of the respective embodiments (e.g., for Formula I**); and R18-R20 are as described herein in any of the respective embodiments (e.g., for Formula V.4, V.4a, VI.4, VI.4a, VI*.4 or VI*.4a);

[0677] and / or by Formula IV***:

[0678]

[0679] or by Formula IVa***:

[0680]

[0681] Formula IVa*** wherein R10, R11and R14are as described herein in any of the respective embodiments (e.g., for Formula VI, VI* or I); R1-R5, are all as described herein in any of the respective embodiments (e.g., for Formula I); and R18-R20 are as described herein in any of the respective embodiments (e.g., for Formula V.4, V.4a, VI.4, VI.4a, VI*.4 or VI*.4a).

[0682] According to some embodiments of any of the embodiments described herein for Formula I, V, VI, VI* or VI**, the bridging moiety B is a urea.

[0683] According to an aspect of some embodiments of the present invention there is provided a compound represented by Formulae II- II***, as described herein in any of the respective embodiments and any combination thereof.

[0684] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each independently hydroxy, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, at least one, or each, of R15 and R16 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen.

[0685] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each independently hydroxy, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, at least one, or each, of R15 and R16 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0686] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each independently hydroxy, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, each of R15 and Ri6 is hydrogen, and R14 is optionally hydrogen.

[0687] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, at least one, or each, of R15 and R16 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen.

[0688] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, at least one, or each, of R15 and R16 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, each of R15 and Ri6 is hydrogen, and R14 is optionally hydrogen.

[0689] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 are each hydrogen, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen.

[0690] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 are each hydrogen, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, at least one, or each, of R15 and Ri6 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0691] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 are each hydrogen, at least one, or each, of R10and R11is independently an aryl, a heteroaryl, a cycloalkyl or a heteroalicyclic, each of R15 and R16 is hydrogen, and R14 is optionally hydrogen.

[0692] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10and R11are each independently an aryl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen.

[0693] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10and R11are each independently an aryl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0694] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10and R11are each independently an aryl, each of R15 and Ri6 is hydrogen, and R14 is optionally hydrogen.

[0695] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, R10and R11are each independently an aryl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, R10and R11are each independently an aryl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14is optionally hydrogen.

[0696] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, R10and R11are each independently an aryl, each of R15 and Ri6 is hydrogen, and R14 is optionally hydrogen.

[0697] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently an aryl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen.

[0698] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently an aryl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0699] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently an aryl, each of R15 and Ri6 is hydrogen, and R14 is optionally hydrogen.

[0700] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10and R11are each independently a phenyl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen.

[0701] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10and R11are each independently a phenyl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0702] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10and R11are each independently a phenyl, each of R15 and Ri6 is hydrogen, and R14 is optionally hydrogen.

[0703] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen.

[0704] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0705] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl, each of R15 and Ri6 is hydrogen, and R14 is optionally hydrogen.

[0706] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently a phenyl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen.

[0707] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently a phenyl, at least one, or each, of R15 and Ri6 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0708] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently a phenyl, each of R15 and Ri6 is hydrogen, and R14 is optionally hydrogen.

[0709] An exemplary such compound is GLB-12 (see, Tables 1 and 2).

[0710] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a substituted aryl (e.g., substituted by an alkoxy (e.g., methoxy)), at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen.

[0711] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a substituted aryl (e.g., substituted by an alkoxy (e.g., methoxy)), at least one, or each, of R15 and Ri6 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a substituted aryl (e.g., substituted by an alkoxy (e.g., methoxy)), each of R15 and Ri6 is hydrogen, and R14 is optionally hydrogen.

[0712] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl which is substituted by an alkoxy (e.g., methoxy), at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14is optionally hydrogen.

[0713] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl which is substituted by an alkoxy (e.g., methoxy), at least one, or each, of R15 and Ri6 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14is optionally hydrogen.

[0714] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl which is substituted by an alkoxy (e.g., methoxy), each of R15 and Ri6 is hydrogen, and R14is optionally hydrogen.

[0715] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a substituted aryl (e.g., substituted by an alkoxy (e.g., methoxy)), at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14is optionally hydrogen.

[0716] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a substituted aryl (e.g., substituted by an alkoxy (e.g., methoxy)), at least one, or each, of R15 and R14is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14is optionally hydrogen.

[0717] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a substituted aryl (e.g., substituted by an alkoxy (e.g., methoxy)), each of R15 and R14is hydrogen, and R14is optionally hydrogen.

[0718] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a substituted aryl (e.g., substituted by an alkoxy (e.g., methoxy)), at least one, or each, of R15 and Ri6 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14 is optionally hydrogen.

[0719] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a substituted aryl (e.g., substituted by an alkoxy (e.g., methoxy)), at least one, or each, of R15 and Ri6 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14is optionally hydrogen.

[0720] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a substituted aryl (e.g., substituted by an alkoxy (e.g., methoxy)), each of R15 and Ri6 is hydrogen, and R14is optionally hydrogen.

[0721] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl which is substituted by an alkoxy (e.g., methoxy), at least one, or each, of R15 and R16 is s independently elected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, and R14is optionally hydrogen.

[0722] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl which is substituted by an alkoxy (e.g., methoxy), at least one, or each, of R15 and R16 is independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14is optionally hydrogen.

[0723] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl which is substituted by an alkoxy (e.g., methoxy), each of R15 and R14is hydrogen, and R14is optionally hydrogen.

[0724] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl which is substituted by an alkoxy (e.g., methoxy), at least one, or each, of R15 and R14is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heteroalicyclic, and R14is optionally hydrogen.

[0725] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl which is substituted by an alkoxy (e.g., methoxy), at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0726] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl which is substituted by an alkoxy (e.g., methoxy), each of R15 and Ri6 is hydrogen, and R14 is optionally hydrogen.

[0727] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl ort / zo-substituted by an alkoxy (e.g., methoxy). According to some embodiments of any of the embodiments described herein, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl ort / zo-substituted by an alkoxy (e.g., methoxy), and at least one, or each, of R15 and i6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length). According to some embodiments of any of the embodiments described herein, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl ort / zo-substituted by an alkoxy (e.g., methoxy), and each of R15 and Ri6 is hydrogen.

[0728] An exemplary such compound is Urea 13 (see, Table 2).

[0729] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl meto-substituted by an alkoxy (e.g., methoxy). According to some embodiments of any of the embodiments described herein, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl meto-substituted by an alkoxy (e.g., methoxy), and at least one, or each, of R15 and i6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length). According to some embodiments of any of the embodiments described herein, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl meto-substituted by an alkoxy (e.g., methoxy), and each of R15 and Ri6 is hydrogen.

[0730] An exemplary such compound is Urea 14 (see, Table 2).

[0731] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl para-substituted by an alkoxy (e.g., methoxy). According to some embodiments of any of the embodiments described herein, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl para-substituted by an alkoxy (e.g., methoxy), and at least one, or each, of R15 and i6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length). According to some embodiments of any of the embodiments described herein, R10is an unsubstituted aryl (e.g., unsubstituted phenyl) and R11is a phenyl para-substituted by an alkoxy (e.g., methoxy), and each of R15 and Ri6 is hydrogen.

[0732] An exemplary such compound is Urea 15 (see, Table 2). According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, and at least one of R10and R11is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), and R14 is optionally hydrogen.

[0733] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, and one of R10and R11is an aryl and the other one is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), and R14 is optionally hydrogen.

[0734] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R11is an aryl as described herein, and R10is a heteroaryl or a heteroalicyclic as described herein. According to some embodiments of any of the embodiments described herein, at least two of R1-R5 are each hydroxy, R11is an aryl as described herein, and R10is a heteroaryl or a heteroalicyclic, and R14 is optionally hydrogen.

[0735] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, and at least one of R10and R11is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), and R14 is optionally hydrogen.

[0736] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, and one of R10and R11is an aryl and the other one is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), and R14 is optionally hydrogen.

[0737] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, R11is an aryl as described herein, and R10is a heteroaryl or a heteroalicyclic, and R14 is optionally hydrogen.

[0738] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, and at least one of R10and R11is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), and R14 is optionally hydrogen.

[0739] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, and one of R10and R11is an aryl and the other one is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), and R14 is optionally hydrogen.

[0740] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R11is an aryl as described herein, and R10is a heteroaryl or a heteroalicyclic, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R11is phenyl, and R10is a heteroaryl or a heteroalicyclic, and R14 is optionally hydrogen.

[0741] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, R11is phenyl, and R10is a heteroaryl or a heteroalicyclic, and R14 is optionally hydrogen.

[0742] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R11is phenyl, and R10is a heteroaryl or a heteroalicyclic, and R14 is optionally hydrogen.

[0743] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R1-R5 are each hydroxy, R11is an aryl (e.g., phenyl), and R10is a pyridine, a piperidine, a morpholine, or a pyrrole, and R14 is optionally hydrogen.

[0744] According to some embodiments of any of the embodiments described herein for Formulae II-II***, at least two of R2, R3 and R4 are each hydroxy, R11is an aryl (e.g., phenyl), and R10is a pyridine, a piperidine, a morpholine, or a pyrrole, and R14 is optionally hydrogen.

[0745] According to some embodiments of any of the embodiments described herein for Formulae II-II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R11is an aryl (e.g., phenyl), and R10is a pyridine, a piperidine, a morpholine, or a pyrrole, and R14 is optionally hydrogen.

[0746] According to some embodiments of any of the embodiments described herein for Formulae II-II***, the heteroaryl (R10and / or R11) is a pyridine (e.g., 2-pyridine, 3-pyridine, 4-pyridine). According to some embodiments of any of the embodiments described herein, R11is a pyridine.

[0747] According to some embodiments of any of the embodiments for Formulae II- II***, at least two of R1-R5 are each hydroxy, and at least one of R10and R11is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), R14 is optionally hydrogen, and at least one, or each, of R15 and Rieis independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0748] According to some embodiments of any of the embodiments for Formulae II- II***, at least two of R1-R5 are each hydroxy, and one of R10and R11is an aryl and the other one is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), R14 is optionally hydrogen, and at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0749] According to some embodiments of any of the embodiments for Formulae II-II***, R11is an aryl as described herein, and R10is a heteroaryl or a heteroalicyclic as described herein, and at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length). According to some embodiments of any of the embodiments of Formula Illi***, at least two of R1-R5 are each hydroxy, R11is an aryl as described herein, and R10is a heteroaryl or a heteroalicyclic, R14 is optionally hydrogen and at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0750] According to some embodiments of any of the embodiments for Formulae II- II***, at least two of R2, R3 and R4 are each hydroxy, and at least one of R10and R11is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), R14 is optionally hydrogen, and at least one, or each, of R15 and Rieis independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0751] According to some embodiments of any of the embodiments for Formulae II- II***, at least two of R2, R3 and R4 are each hydroxy, and one of R10and Ri 1 is an aryl and the other one is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), R14 is optionally hydrogen, and at least one, or each, of R15 and Rieis independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0752] According to some embodiments of any of the embodiments for Formulae II- II***, at least two of R2, R3 and R4 are each hydroxy, R11is an aryl as described herein, and R10is a heteroaryl or a heteroalicyclic, R14 is optionally hydrogen, and at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0753] According to some embodiments of any of the embodiments for Formulae II- II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, and at least one of R10and R11is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), R14 is optionally hydrogen, and at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0754] According to some embodiments of any of the embodiments for Formulae II- II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, and one of R10and R11is an aryl and the other one is a heteroalicyclic (e.g., piperidine, morpholine) or a heteroaryl (e.g., pyridine, pyrrole), R14 is optionally hydrogen, and at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0755] According to some embodiments of any of the embodiments for Formulae II- II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R11is an aryl as described herein, and R10is a heteroaryl or a heteroalicyclic, R14 is optionally hydrogen, and at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length). According to some embodiments of any of the embodiments for Formulae II- II***, at least two of R1-R5 are each hydroxy, R11is phenyl, and R10is a heteroaryl or a heteroalicyclic, R14 is optionally hydrogen, and at least one, or each, of R15 and Rieis independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0756] According to some embodiments of any of the embodiments for Formulae II- II***, at least two of R2, R3 and R4 are each hydroxy, R11is phenyl, and R10is a heteroaryl or a heteroalicyclic, R14 is optionally hydrogen, and at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0757] According to some embodiments of any of the embodiments for Formulae II- II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R11is phenyl, and R10is a heteroaryl or a heteroalicyclic, R14 is optionally hydrogen, and at least one, or each, of R15 and R16 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0758] According to some embodiments of any of the embodiments for Formulae II- II***, at least two of R1-R5 are each hydroxy, R11is an aryl (e.g., phenyl), and R10is a pyridine, a piperidine, a morpholine, or a pyrrole, R14 is optionally hydrogen, and at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0759] According to some embodiments of any of the embodiments for Formulae II- II***, at least two of R2, R3 and R4 are each hydroxy, R11is an aryl (e.g., phenyl), and R10is a pyridine, a piperidine, a morpholine, or a pyrrole, R14 is optionally hydrogen, and at least one, or each, of R15 and Ri6 is independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0760] According to some embodiments of any of the embodiments for Formulae II- II***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R11is an aryl (e.g., phenyl), and R10is a pyridine, a piperidine, a morpholine, or a pyrrole, R14 is optionally hydrogen, and at least one, or each, of R15 and Rieis independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0761] According to some embodiments of any of the embodiments for Formulae II- II***, the heteroaryl (R10and / or R11) is a pyridine (e.g., 2-pyridine, 3-pyridine, 4-pyridine). According to some embodiments of any of the embodiments of Formula II- II***, R11is a pyridine, R14 is optionally hydrogen, and at least one, or each, of R15 and Rieis independently hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0762] Exemplary such compounds include Ureal, Urea2 and Urea3 (see, Table 2).

[0763] According to some embodiments of any of the embodiments for Formulae II- II***, the heteroaryl (R10and / or R11) is a pyrrole (e.g., 3-pyrrole). According to some embodiments of any of the embodiments of Formula II-II***, R11is a pyrrole. According to some embodiments of any of the embodiments for Formulae II- II***, the heteroaryl (R10and / or R11) is a pyrrole (e.g., 3-pyrrole), and R15 and Ri6 are independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length). According to some embodiments of any of the embodiments of Formula II-II***, R11is a pyrrole, and R15 and Ri6 are independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0764] According to some embodiments of any of the embodiments for Formulae II-II***, the heteroaryl (R10and / or R11) is a pyrrole (e.g., 3-pyrrole), and each of R15 and Ri6 are hydrogen. According to some embodiments of any of the embodiments of Formula II-II***, R11is a pyrrole, and each of R15 and Ri6 are hydrogen.

[0765] An exemplary such compound is Urea 12 (see, Table 2).

[0766] According to some embodiments of any of the embodiments for Formulae II-II***, the heteroalicyclic (R10and / or R11) is a piperidine. According to some embodiments of any of the embodiments of Formula II-II***, R11is a piperidine.

[0767] According to some embodiments of any of the embodiments for Formulae II-II***, the heteroalicyclic (R10and / or R11) is a piperidine, and R15 and Ri6 are independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length). According to some embodiments of any of the embodiments of Formula II-II***, R11is a piperidine, and R15 and Ri6 are independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length).

[0768] According to some embodiments of any of the embodiments for Formulae II-II***, the heteroalicyclic (R10and / or R11) is a piperidine, and each of R15 and Ri6 is hydrogen. According to some embodiments of any of the embodiments of Formula II-II***, R11is a piperidine, and each of R15 and R16 are hydrogen.

[0769] An exemplary such compound is Urea8 (see, Table 2).

[0770] According to some embodiments of any of the embodiments for Formulae II-II***, the heteroalicyclic (R10and / or R11) is a morpholine (e.g., N-morpholine). According to some embodiments of any of the embodiments of Formula II-II***, R11is a morpholine.

[0771] According to some embodiments of any of the embodiments for Formulae II-II***, the heteroalicyclic (R10and / or R11) is a morpholine (e.g., N-morpholine), and R15 and Ri6 are independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length). According to some embodiments of any of the embodiments of Formula II-II***, R11is a morpholine, and R15 and Ri6 are independently selected from hydrogen and alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length). According to some embodiments of any of the embodiments for Formulae II- II***, the heteroalicyclic (R10and / or R11) is a morpholine (e.g., N-morpholine), and each of R15 and Ri6 are independently hydrogen. According to some embodiments of any of the embodiments of Formula Illi***, R11is a morpholine, and each of R15 and Ri6 are hydrogen.

[0772] An exemplary such compound is Urea9 (see, Table 2).

[0773] According to some embodiments of any of the embodiments described herein for Formula I, V, VI, VI* or VI**, the bridging moiety B is a 1,2,3-triazole.

[0774] According to an aspect of some embodiments of the present invention there is provided a compound represented by Formulae III-III*** or Illa- Illa***, as described herein in any of the respective embodiments and any combination thereof.

[0775] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R1-R5 are each hydroxy, R10and R11are each independently an aryl, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0776] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R2, R3 and R4 are each hydroxy, R10and R11are each independently an aryl, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0777] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently an aryl, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0778] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R10and R11are each independently a phenyl, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0779] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0780] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently a phenyl, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0781] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R1-R5 are each hydroxy, R10and R11are each independently an aryl, R17 is hydrogen or an alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14is optionally hydrogen. According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R1-R5 are each hydroxy, R10and R11are each independently an aryl, R17 is hydrogen, and R14 is optionally hydrogen.

[0782] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R2, R3 and R4 are each hydroxy, R10and R11are each independently an aryl, R17 is hydrogen or an alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0783] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R2, R3 and R4 are each hydroxy, R10and R11are each independently an aryl, R17 is hydrogen, and R14 is optionally hydrogen.

[0784] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently an aryl, R17 is hydrogen or an alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14is optionally hydrogen.

[0785] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently an aryl, R17 is hydrogen, and R14 is optionally hydrogen.

[0786] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R10and R11are each independently a phenyl, R17 is hydrogen or an alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14is optionally hydrogen.

[0787] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R10and R11are each independently a phenyl, R17 is hydrogen, and R14is optionally hydrogen.

[0788] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl, R17 is hydrogen or an alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14is optionally hydrogen.

[0789] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl, R17 is hydrogen, and R14is optionally hydrogen.

[0790] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R3 and R4 are each independently hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently a phenyl, R17 is hydrogen or an alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14is optionally hydrogen. According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently a phenyl, R17 is hydrogen, and R14is optionally hydrogen.

[0791] Exemplary such compound are GLB-15 (see, Tables 1 and 2), which is represented by Formulae I-I** and III-III***, and GLB-16 (see, Table 1), which is represented by Formulae I-I** and Illa- Illa***.

[0792] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, the heteroalicyclic (R10and / or R11) is a morpholine (e.g., N-morpholine). According to some embodiments of any of the embodiments of Formula III-III*** or Illa- Illa***, R11is a morpholine.

[0793] According to some embodiments of any of the embodiments of Formula III-III*** or Illa- Illa***, the compound is represented by Formula III, and R11is a morpholine.

[0794] An exemplary such compound is Triazole9 (see, Table 2).

[0795] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R1-R5 are each hydroxy, at least one of R10and R11is a heteroalicyclic or a heteroaryl that is substituted as described herein in any of the respective embodiments and in any combination thereof, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0796] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R2, R3 and R4 are each hydroxy, at least one of R10and R11is a heteroalicyclic or a heteroaryl that is substituted as described herein in any of the respective embodiments and in any combination thereof, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0797] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 are each independently hydrogen, at least one of R10and R11is a heteroalicyclic or a heteroaryl that is substituted as described herein in any of the respective embodiments and in any combination thereof, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0798] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R1-R5 are each hydroxy, one of R10and R11is an aryl and the other one is a heteroalicyclic or a heteroaryl, which is / are substituted as described herein in any of the respective embodiments and in any combination thereof, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0799] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, at least two of R2, R3 and R4 are each hydroxy, one of R10and R11is an aryl and the other one is a heteroalicyclic or a heteroaryl, which is / are substituted as described herein in any of the respective embodiments and in any combination thereof, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0800] According to some embodiments of any of the embodiments of Formula III-III*** or Illa-Illa***, R3 and R4 are each hydroxy and optionally Ri, R2 and R5 are each independently hydrogen, one of R10and Ri 1 is an aryl and the other one is a heteroalicyclic or a heteroaryl, which is / are substituted as described herein in any of the respective embodiments and in any combination thereof, R17 is hydrogen, alkyl, alkenyl, alkynyl, or cycloalkyl, and R14 is optionally hydrogen.

[0801] According to some embodiments of any of the embodiments described herein for Formula I, V, VI, VI* or VI**, the bridging moiety B is or comprises an amide. According to some embodiments of any of the embodiments described herein for Formula I, V, VI, VI* or VI**, B comprises an amide.

[0802] According to an aspect of some embodiments of the present invention there is provided a compound represented by Formula IV-IV*** or IVa-IV***, as described herein in any of the respective embodiments and any combination thereof.

[0803] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least two of R1-R5 are each hydroxy, R10and R11are each independently an aryl, at least one, or each, of Ris and R19 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, R20 is hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0804] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least two of R1-R5 are each hydroxy, R10and R11are each independently an aryl, at least one, or each, of Ris and R19 is independently hydrogen or an alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R20 and R14 is each optionally hydrogen.

[0805] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least two of R1-R5 are each hydroxy, R10and R11are each independently an aryl, each of Ris and R19 is hydrogen, R20 is hydrogen or alkyl (e.g., an alkyl of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0806] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least two of R2, R3 and R4 are each hydroxy, R10and R11are each independently an aryl, at least one, or each, of Ris and R19 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heteroalicyclic, R20 is hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen. According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least two of R2, R3 and R4 are each hydroxy, R10and R11are each independently an aryl, each of R18-R20 is hydrogen, and R14 is optionally hydrogen.

[0807] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, R3and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently an aryl, at least one, or each, of Ris and R19 is / are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heteroalicyclic, R20 is hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0808] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, R3and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently an aryl, each of R18-R20 is hydrogen, and R14 is optionally hydrogen.

[0809] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, R10and R11are each independently a phenyl, at least one, or each, of Ris and R19 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heteroalicyclic, R20 is hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0810] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, R10and R11are each independently a phenyl, each of Ris and R19 is hydrogen, R20 and R14 is each optionally hydrogen.

[0811] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl, at least one, or each, of Ris and R19 is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic, R20 is hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0812] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least two of R1-R5 are each hydroxy, R10and R11are each independently a phenyl, each of Ris and R19 is hydrogen, and R20 and R14 is each optionally hydrogen.

[0813] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, R3and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently a phenyl, at least one, or each, of Ris and R19 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or heteroalicyclic, R20 is hydrogen or alkyl (e.g., of up to 8, or up to 5, or up to 3 carbon atoms in length), and R14 is optionally hydrogen.

[0814] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, R3and R4 are each hydroxy and optionally Ri, R2 and R5 is / are each independently hydrogen, R10and R11are each independently a phenyl, each of R18-R20 is hydrogen, and R14 is optionally hydrogen.

[0815] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least one of R10and R11is a heteroalicyclic or a heteroaryl, which is substituted as described herein in any of the respective embodiments and in any combination thereof, Ris and R19 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, and R20 is hydrogen or alkyl, and R14 is optionally hydrogen.

[0816] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least one of R10and R11is a heteroalicyclic or a heteroaryl, which is substituted as described herein in any of the respective embodiments and in any combination thereof, Ris and R19 are each independently selected from hydrogen and alkyl, and R20 is hydrogen or alkyl, and R14 is optionally hydrogen.

[0817] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least one of R10and R11is a heteroalicyclic or a heteroaryl, which is substituted as described herein in any of the respective embodiments and in any combination thereof, each of R18-R20 is hydrogen or alkyl, and R14 is optionally hydrogen.

[0818] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least one of R10and R11is a heteroalicyclic or a heteroaryl, which is substituted as described herein in any of the respective embodiments and in any combination thereof, Ris and R19 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, and R20 is hydrogen, and R14 is optionally hydrogen.

[0819] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least one of R10and R11is a heteroalicyclic or a heteroaryl, which is substituted as described herein in any of the respective embodiments and in any combination thereof, Ris and R19 are each independently selected from hydrogen and alkyl, and R20 is hydrogen, and R14 is optionally hydrogen.

[0820] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV***, at least one of R10and R11is a heteroalicyclic or a heteroaryl, which is substituted as described herein in any of the respective embodiments and in any combination thereof, each of R18-R20 is hydrogen, and R14 is optionally hydrogen.

[0821] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV* * *, one of R10and Ri 1 is an aryl and the other one is selected from a heteroalicyclic and a heteroaryl, which is / are substituted as described herein in any of the respective embodiments and in any combination thereof, Ris and R19 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, and R20 is hydrogen or alkyl, and R14 is optionally hydrogen. According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV* * *, one of R10and Ri i is an aryl and the other one is selected from a heteroalicyclic and a heteroaryl, which is / are substituted as described herein in any of the respective embodiments and in any combination thereof, Ris and R19 are each independently selected from hydrogen and alkyl, and R20 is hydrogen or alkyl, and R14 is optionally hydrogen.

[0822] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV* * *, one of R10and Ri 1 is an aryl and the other one is selected from a heteroalicyclic and a heteroaryl, which is / are substituted as described herein in any of the respective embodiments and in any combination thereof, each of R18-R20 is hydrogen or alkyl, and R14 is optionally hydrogen.

[0823] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV* * *, one of R10and Ri 1 is an aryl and the other one is selected from a heteroalicyclic and a heteroaryl, which is / are substituted as described herein in any of the respective embodiments and in any combination thereof, Ris and R19 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, and R20 is hydrogen, and R14 is optionally hydrogen.

[0824] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV* * *, one of R10and Ri 1 is an aryl and the other one is selected from a heteroalicyclic and a heteroaryl, which is / are substituted as described herein in any of the respective embodiments and in any combination thereof, Ris and R19 are each independently selected from hydrogen and alkyl, and R20 is hydrogen, and R14 is optionally hydrogen.

[0825] According to some embodiments of any of the embodiments of Formula IV-IV*** or IVa-IV* * *, one of R10and Ri 1 is an aryl and the other one is selected from a heteroalicyclic and a heteroaryl, which is / are substituted as described herein in any of the respective embodiments and in any combination thereof, each of R18-R20 is hydrogen, and R14 is optionally hydrogen.

[0826] Exemplary such compounds include GLB-12a (see, Table 1), and GLB-14a (see, Table 1). In some embodiments of any of the embodiments described herein, the compound is selected from the compounds presented in Table 1 and / or Table 2. In some embodiments, the compound is GLB-12, GLB-12a, GLB-14, GLB-14a, GLB-15, GLB-16, Ureal4, or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is GLB-12 or GLB-15, or a pharmaceutically acceptable salt thereof.

[0827] Formula V encompasses compounds represented by Formulae I-V4a; compounds represented by Formulae V.2-V4a, wherein B is further defined as described herein in any of the respective embodiments and in any combination thereof; compounds represented by Formulae VI.2-VI.4a and VI*.2-VI*.4a, wherein Al and the bridging moiety B are further defined as described herein in any of the respective embodiments and in any combination thereof. Formula I encompasses compounds represented by Formulae II*-IVa*; compounds represented by Formulae II-IVa, wherein X and Y in Formula I are each N; compounds represented by Formulae II** -IVa** wherein R4 and R3 in Formula I are ORA and ORB, respectively; and compounds represented by Formulae II***-IVa*** wherein X and Y in Formula I are each N and R4 and R3 in Formula I are ORA and ORB, respectively.

[0828] Formula I* encompasses compounds represented by Formulae II-IVa, such that each of the compounds represented by Formulae II-IVa has a different bridging group B.

[0829] Formula I** encompasses compounds represented by Formulae II**-IVa** wherein R4 and R3 in Formula I** are ORA and ORB, respectively such that each of the compounds represented by Formulae II-IVa has a different bridging group B.

[0830] Formulae III and Illa; Formulae III* and Illa*; Formulae III** and Illa**; and Formulae III*** and Illa***, each differ at least in the connectivity of the bridging moiety B thereof.

[0831] Formulae IV and IVa; Formulae IV* and IVa*; Formulae IV** and IVa**; and Formulae IV*** and IVa***, each differ at least in the connectivity of the bridging moiety B thereof.

[0832] Exemplary compounds represented by Formulae I-I** and optionally by II-IVa*** and / or V-VI*.4a and VI** are set forth in Tables 1-4 in the Examples section that follows.

[0833] Process:

[0834] According to an aspect of some embodiments of the present invention there is provided a process or method of preparing any of the compound as described herein (e.g., compounds collectively represented by Formula V-V.4 or VI- VI*.4a), essentially as described herein.

[0835] According to some embodiments of any of the embodiments described herein, the process or method comprises contacting a compound represented by Formula Aii (“Compound Aii” in Scheme A (hereinbelow)) with a compound represented by Formula Bii (“Compound Bii” in Scheme A), under conditions that promote the formation of the bridging moiety B, to thereby provide a solution enriched with a compound represented by Formula V as described herein in any of the respective embodiments and in any combination thereof:

[0836] Scheme A:

[0837] Compound Bn

[0838]

[0839] Compound Aii Formula V In some embodiments of any of these embodiments, Al, A2 and B are as described herein in any of the respective embodiments and in any combination thereof, and Li (a first reactive group) and L2 (a second reactive group) are selected such that a coupling reaction therebetween provides the bridging moiety B (as described herein in any of the respective embodiment...

Claims

1. WHAT IS CLAIMED IS:

1. A compound represented by Formula I:

4. 6.or a pharmaceutically acceptable salt thereof,7.wherein:8.B is a bridging moiety which is or comprises an amide, a sulfonamide, a urea, or an N-heterocyclic group;9.X is N or CR12;10.Y is N or CR13;11.R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R10-R14 or two or more of R10, R11 and R14; and12.R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered or 4-6-membered cyclic or heterocyclic ring formed of two or more of R1-R5.

2. The compound of claim 1, wherein R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

3. The compound of claim 1 or 2, wherein R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

4. The compound of any one of claims 1 to 3, wherein at least one, or each, of X and Y is N.

5. The compound of any one of claims 1 to 4, wherein at least two of R2, R3 and R4 are each hydroxy.

6. The compound of any one of claims 1 to 5, wherein R3 and R4 are each hydroxy.

7. The compound of any one of claims 1 to 6, wherein at least one, or each, of R10and R11is independently selected from an aryl, a heteroaryl, a cycloalkyl, and a heteroalicyclic.

8. The compound of any one of claims 1 to 7, wherein R10and R11are each independently an aryl.

9. The compound of any one of claims 1 to 7, at least one of R10and R11is selected from a heteroalicyclic and a heteroaryl.

10. The compound of any one of claims 1 to 7, wherein one of R10and R11is an aryl and the other one is selected from a heteroalicyclic and a heteroaryl.

11. The compound of any one of claims 1 to 10, wherein said bridging moiety is or comprises an N-heterocyclic group.

12. The compound of claim 11, wherein said N-heterocyclic group is a 1,2,3-triazole.

13. The compound of any one of claims 1 to 10, wherein said bridging moiety is or comprises a urea.

14. The compound of any one of claims 1 to 10, wherein said bridging moiety is or comprises an amide.

15. The compound of claim 14, wherein said bridging moiety comprises an amide.

16. The compound of any one of claims 1 to 10, wherein said bridging moiety B is or comprises urea, the compound being represented by Formula II:

27. 29.Formula II30.or a pharmaceutically acceptable salt thereof,31.wherein R15 and R16 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl.

17. The compound of any one of claims 1 to 10, wherein said bridging moiety B is a 1,2,3-triazole, the compound being represented by Formula III or by Formula Illa:

33. 35.or a pharmaceutically acceptable salt thereof,36.wherein R17 is selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl.

18. The compound of any one of claims 1 to 10, wherein said bridging moiety B comprises an amide, the compound being represented by Formula IV or by Formula IVa:

39.

40. R1141.Formula IV42. 44.or a pharmaceutically acceptable salt thereof,45.wherein R18-R20 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl.

19. A compound represented by Formula V:

48. 50.Formula V51.or a pharmaceutically acceptable salt thereof,52.wherein:53.B is a bridging moiety which is or comprises an amide, a sulfonamide, a urea, or an N-heterocyclic group;54.Al and A2 are each independently selected from an aryl or a heteroaryl, each independently being substituted or unsubstituted;55.wherein each of Al and A2, when substituted, independently features at least one substituent selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered, or 4-6-membered cyclic or heterocyclic ring formed of at least two of said substituents.

20. The compound of claim 19, represented by Formula VI:

57. 59.Rii60.Formula VI61.wherein:62.X is N or CR12;63.Y is N or CR13; and64.R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered, or 4-6-membered cyclic or heteroalicyclic ring formed of two or more of R10-R14 or two or more of R10, R11 and R14.

21. The compound of claim 20, wherein R10-R14 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

22. The compound of any one of claims 19 to 21, wherein at least one, or each, of X and Y is independently N.

23. The compound of any one of claims 19 to 22, wherein at least one, or each, of R10and R11 is independently selected from an aryl, a heteroaryl, a cycloalkyl, and a heteroalicyclic.

24. The compound of any one of claims 1 to 23, wherein R10and R11are each independently an aryl.

25. The compound of any one of claims 1 to 23, at least one of R10and R11is a heteroalicyclic or a heteroaryl.

26. The compound of any one of claims 19 to 23, wherein one of R10and R11is an aryl and the other one is a heteroalicyclic or a heteroaryl.

27. The compound of any one of claims 19 to 26, wherein R14 is hydrogen.

28. The compound of any one of claims 19 to 27, wherein A2 is an aryl.

29. The compound of claim 28, being represented by Formula I:

74. 76.or a pharmaceutically acceptable salt thereof,77.wherein:78.X, Y and R10-R14are each as defined in any one of claims 20 to 27; and79.R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, amino, and a 3-8-membered, or a 4-6-membered cyclic or heterocyclic ring formed of two or more of R1-R5.

30. The compound of claim 28, wherein R1-R5 are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, halo, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, sulfinyl, sulfonyl, sulfonate, sulfate, cyano, nitro, azide, phosphonyl, phosphinyl, carbonyl, thiocarbonyl, a urea group, a thiourea group, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, S -thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, sulfonamide, guanyl, guanidinyl, hydrazine, hydrazide, thiohydrazide, and amino.

31. The compound of claim 28 or 30, wherein at least two of R2, R3 and R4 are each hydroxy.

32. The compound of any one of claims 28 to 31, wherein R3 and R4 are each hydroxy.

33. The compound of claim 28 or 30, wherein two of R1-R5 together form said cyclic or heterocyclic ring, which can be substituted or unsubstituted.

34. The compound of any one of claims 28, 30 and 33, wherein two of R1-R5 together form a five- or six-membered cyclic or heteroalicyclic ring, which can be substituted or unsubstituted.

35. The compound of claims 33 or 34, wherein R3 and R4 together form said cyclic or heterocyclic ring.

36. The compound of any one of claims 30, 30 and 33-35, wherein said cyclic or heterocyclic ring is a heterocyclic ring selected from a substituted or unsubstituted heteroaryl and a substituted or unsubstituted heteroalicyclic.

37. The compound of claim 36, wherein said heteroaryl or heteroalicyclic ring is an N-containing heteroaryl or heteroalicyclic.

38. The compound of any one of claims 19-27, wherein A2 is a substituted or unsubstituted heteroaryl.

39. The compound of claim 38, wherein said heteroaryl is a nitrogen-containing heteroaryl.

40. The compound of any one of claims 19 to 39, wherein said bridging moiety is or comprises an N-heterocyclic group.

41. The compound of claim 40, wherein said N-heterocyclic group is a 1,2,3-triazole.

42. The compound of any one of claims 19 to 39, wherein said bridging moiety is or comprises a urea.

43. The compound of any one of claims 19 to 39, wherein said bridging moiety is or comprises an amide.

44. The compound of claim 43, wherein said bridging moiety comprises an amide.

45. The compound of any one of claims 19 to 39, wherein said bridging moiety B is or comprises urea, the compound being represented by Formula V.2:94.R15R1696. 98.or a pharmaceutically acceptable salt thereof,99.wherein R15 and R16 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl.

46. The compound of any one of claims 19 to 39, wherein said bridging moiety is or comprises a 1,2,3-triazole, the compound being represented by Formula V.3 or V.3a:

102. 104.Formula V.3105. 107.Formula V.3a108.or a pharmaceutically acceptable salt thereof,109.wherein R17 is selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl.

47. The compound of any one of claims 19 to 39, wherein said bridging moiety is or comprises an amide, the compound being represented by Formula V.4 or V.4a:111.Formula V.4113. 115.Formula V.4a116.or a pharmaceutically acceptable salt thereof,117.wherein:118.R18-R20 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, and cycloalkyl.

48. The compound of any one of claims 1 to 47, for use in treating a medical condition in which activating PERK is beneficial; and / or a medical condition associated with an aggregation-prone protein; and / or a medical condition in which upregulating an unfolded protein response is beneficial.

49. The compound for use of claim 48, wherein said medical condition is a viral infection.

50. The compound for use of claim 48, wherein said medical condition is selected from Huntington’s disease, amyloidosis, cataract, type II diabetes, cancer, and memory deficiency.

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