Prodrugs of azo compounds and their salts

Abstract

The present invention relates to compounds of formula I and their therapeutic uses. The present invention also discloses pharmaceutical compositions of the compounds of formula I and methods of treatment using same.

Description

[Technical field]

[0001] The present invention relates to compounds of general formula I and their therapeutic uses. The disclosure also relates to pharmaceutical compositions of compounds of general formula I and methods of treatment using same. [Background technology]

[0002] Pain is a complex and multidimensional concept that promotes the initiation of signaling cascades in response to noxious stimuli. In pain sensations, numerous types of receptors with different signaling pathways are activated. These signaling pathways can be considered as sites for the modulation of pain by targeting pain transmitting molecules to induce analgesia from several pain syndromes.

[0003] Interstitial cystitis / bladder pain syndrome (IC / BPS) and overactive bladder (OAB) are often accompanied by other chronic pelvic pain conditions such as IBS and endometriosis, as well as more systemic pain conditions. Peripheral inflammation generates multiple inflammatory mediators, including bradykinin, prostaglandins (PGE2), purines (ATP), proteases, and NGF, which act on their cognate receptors expressed on nociceptive sensory neurons to activate intracellular signaling pathways.

[0004] Thus, the present invention provides compounds useful for the treatment of interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine, pruritus, post-herpetic neuralgia, pain associated with urinary tract infections, osteoarthritis, arthritis, and urinary incontinence. [Brief description of the drawings]

[0005] [Figure 1] Gene expression analysis was performed by quantitative RT-PCR using RNA (following cDNA synthesis) isolated from RT4 cells treated with test drug compounds in combination with cyclophosphamide. Bar graphs represent fold change in gene expression of P2RX3. All values ​​are expressed as mean ± SEM. [Diagram 2] Effect of Compound XI on CFA-induced mechanical allodynia in male SD rats using the up-and-down method %MPE; 2 days after CFA injection. Data are expressed as %MPE (mean ± SEM). ****p<0.0001, n=08, compared to CFA control group by two-way ANOVA followed by Bonferroni multiple comparison test. [Diagram 3] Effect of Compound XI on mean paw withdrawal threshold in mechanical allodynia. Data are expressed as mean ± SEM, n = 8. One-way ANOVA followed by Dunnett's multiple comparison test *P<0.05, ***P<0.0001 vs. vehicle control. [Figure 4] Effects of Compound No. 449 and Compound No. 54 on acute cyclophosphamide (CYP)-induced cystitis model. Data are presented as AUC% pain score (mean±SEM). One-way ANOVA test followed by Dunnett's test, ###p<0.0001 vs. NC and *P<0.05, **P<0.001 vs. CYP group, n=9. [Diagram 5] Effect of Compound XI on chronic cyclophosphamide (CYP)-induced cystitis model. Data are presented as AUC% pain score (mean±SEM). One-way ANOVA test followed by Dunnett's test, ###p<0.0001 vs. NC and **P<0.001, ***P<0.0001 vs. CYP group, n=8. [Figure 6] Effect of Compound No. 43 on acute cyclophosphamide (CYP)-induced cystitis model. Data are presented as AUC% pain score (mean±SE). Two-way RM ANOVA followed by Bonferroni test, ###p<0.001 vs. NC and *p<0.05, **p<0.01 vs. CYP group, n=9. [Figure 7]Effect of Compound XIII on acute cyclophosphamide (CYP)-induced cystitis model. Data are presented as AUC% pain score (mean±SEM). Two-way ANOVA followed by Bonferroni test, ###p<0.001 vs. NC and *P<0.05, **p<0.01, ***p<0.001 vs. CYP group, n=8. [Figure 8] Mean ± SD concentration-time profiles of Compound No. 12 and Compound XI following a single oral dose of Compound No. 12 in Sprague Dawley rats. [Figure 9] Mean ± SD concentration-time profiles of Compound No. 43 and Compound XI following a single oral dose of Compound No. 43 in Sprague Dawley rats. [Figure 10] Mean ± SD concentration-time profiles of Compound No. 446 and Compound XI following a single oral dose of Compound No. 446 in Sprague Dawley rats. [Figure 11] Mean ± SD concentration-time profiles of Compound No. 449 and Compound XI following a single oral dose of Compound No. 449 in Sprague Dawley rats. [Figure 12] Mean ± SD concentration-time profiles of Compound XIII and Compound XI following a single oral dose of Compound XIII in Sprague Dawley rats. [Figure 13] Mean ± SD concentration-time profiles of Compound No. 54 and Compound XI following a single oral dose of Compound No. 54 in Sprague Dawley rats. [Figure 14] Effect of Compound XI on acute cyclophosphamide (CYP)-induced cystitis model. Data are presented as bladder pressure (mm hg) (mean ± SE). One-way ANOVA followed by Dunnett's multiple comparison test, n = 10, *p < 0.05, **p < 0.01 vs. CYP group. Summary of the Invention

[0006] The present invention provides valuable prodrugs that overcome the shortcomings of available active substances, i.e. poor absorption of the active substances by biological membranes or unfavorable metabolism of the parent compounds. Moreover, these novel prodrugs have improved pharmacokinetic properties compared to the parent compounds.

[0007] In one embodiment, the present invention provides a compound of general formula (I), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 and R3 are the same or different and independently represent hydrogen, [ka] Selected from; R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R5 is selected from the group consisting of hydrogen, -OH, OR8, and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R8 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R6 is a phenylene group; the phenylene group is substituted 0 to 4 times by R7, and R7 is hydrogen, OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6) groups; provided that all substitutions at R1, R3, R5, R7 are not hydrogen when R is phenylene; if any substitution at R1 or R3 is other than hydrogen and R6 is phenylene, then R5 and R7 are not hydrogen; if the substitutions at R1, R3, R7 are hydrogen, then R5 is not -OH; if the substitutions at R1, R3, R5 are hydrogen and R6 is phenylene, then the single R7 substitution on the phenylene is -OH or O-(alkyl) in either the ortho or para position. 1~3 ) but not; if R1, R3 substitutions are hydrogen, R5 is -OH, and R6 is phenylene, then the R7 substitution on the phenylene is not -OH para position.

[0008] In one embodiment, the present invention provides a compound of general formula IA, a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 and R3 are the same or different and independently represent hydrogen, [ka] [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R 17 is selected from optionally substituted linear or branched alkylene groups, the alkylene being optionally substituted with amino groups, alkylamino groups, and dialkylamino groups; R 18 , -NH2, -NR20 R 21 Selected from R 20 and R 21 are each independently hydrogen, optionally substituted alkyl, -C(O)-R 22 Selected from R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R5 is hydrogen, -OH, -OR8, and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or an optionally substituted alkyl group, a cycloalkyl group, an aryl group, a heterocycloalkyl group, and a heteroaryl group; R8 is selected from the group consisting of an optionally substituted alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, and a heteroaryl group; R6 is a phenylene group, the phenylene group being substituted 0 to 4 times by R7, and R7 is selected from hydrogen, -OH, -OR 12 ,below: [ka] [ka] [ka] [ka] , and -R 19 Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) groups; R 19 -OR 23 -OC(O)-R 24 , -OC(O)-R 23 -R 27 , and OR 23 -R 28 Selected from; R 23 is an optionally substituted linear or branched alkylene; R 24 is an optionally substituted alkoxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, aryloxy group, and N(R 25 R 26 ) and R 25 , R 26 are each independently selected from hydrogen, optionally substituted alkyl, and aryl, where alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups, or R 25 and R 26taken together form an optionally substituted heterocycloalkyl ring, said heterocycloalkyl ring being optionally substituted with alkyl, hydroxyalkyl, -OH, -SH, F, Cl, Br, I, and optionally substituted amino groups; R 27 is an optionally substituted alkyl group, cycloalkyl group, heterocycloalkyl group, heteroaryl group, aryl group, and N(R 25 R 26 ) groups; R 28 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 28 Heterocycloalkyl, heteroaryl in are optionally substituted with alkyl, hydroxyalkyl, OH, SH, F, Cl, Br, I, and optionally substituted amino and oxo groups; R 29 and R 30 are each independently hydrogen, and R 23 -OC(O)-OR 31 Selected from:R 31 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups; with the proviso that when R6 is phenylene, all substitutions at R1, R3, R5, R7 are not hydrogen; when R1 or R3 substitutions are other than hydrogen and R6 is phenylene, R5 and R7 are not hydrogen; when R1, R3, R7 substitutions are hydrogen, R5 is not -OH; when R1, R3, R5 substitutions are hydrogen and R6 is phenylene, the single R7 substitution on the phenylene is -OH or O-(alkyl) in either the ortho or para position. 1~3 ); if R1, R3 substitutions are hydrogen, R5 is -OH, and R6 is phenylene, then the R7 substitution on the phenylene is not in the -OH para position.

[0009] In another aspect, the present invention provides a method for the treatment of interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, post-herpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, the method comprising administering a compound selected from general formula (I), a pharma- ceutically acceptable salt, or a solvate thereof.

[0010] In another aspect, the present invention provides a method for the treatment of interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, post-herpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, the method comprising administering a compound selected from general formula (IA), a pharma- ceutically acceptable salt, or a solvate thereof.

[0011] In another aspect, the present invention provides a method of use for interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, post-herpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, said method comprising administering a compound selected from general formula (I), a pharma- ceutically acceptable salt, or a solvate thereof.

[0012] In another aspect, the present invention provides a method of use for interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, post-herpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, said method comprising administering a compound selected from general formula (IA), a pharma- ceutically acceptable salt, or a solvate thereof.

[0013] In another aspect, the present invention provides a method for the symptomatic relief of pain, burning, urgency, frequency, and other discomfort resulting from irritation of the lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, or passage of a sound or catheter, said method comprising administering a compound selected from general formula (I), a pharma- ceutically acceptable salt, or a solvate thereof.

[0014] In another aspect, the present invention provides a method for the symptomatic relief of pain, burning, urgency, frequency, and other discomfort resulting from irritation of the lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, or passage of a sound or catheter, said method comprising administering a compound selected from general formula (IA), a pharma- ceutically acceptable salt, or a solvate thereof.

[0015] In one embodiment, the present invention relates to a pharmaceutical composition comprising at least one compound selected from the compounds of general formula (I); a pharma- ceutically acceptable salt or solvate thereof; and a pharma- ceutically acceptable excipient.

[0016] In one embodiment, the present invention relates to a pharmaceutical composition comprising at least one compound selected from the compounds of general formula (IA), a pharma- ceutically acceptable salt, solvate thereof; and a pharma- ceutically acceptable excipient. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] The detailed description and examples provided herein are illustrative, and any modifications or variations within the scope of the present invention will be apparent to those skilled in the art. Furthermore, unless otherwise defined, all technical and scientific terms used herein shall have the meanings understood by those skilled in the art.

[0018] As used herein, the term "prodrug" refers to a precursor compound that, after administration, releases a biologically active compound in vivo through a chemical or physiological process. In one embodiment, the prodrug has a desired biological activity. In another embodiment, the prodrug is converted to a therapeutically active compound that has the desired biological activity.

[0019] The pharmaceutical composition of the present disclosure may be in any form known to those skilled in the art. The pharmaceutical composition of the present invention may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, bucally, or via an implanted reservoir, preferably orally, or by injection. For example, in some embodiments, the pharmaceutical composition is in the form of a product for oral delivery, the product form being selected from the group consisting of tablets, concentrates, dry powders, liquids, capsules, pellets, and pills. The pharmaceutical composition disclosed herein may also further comprise carriers, binders, diluents, and excipients.

[0020] The terms "a" and "an" do not denote a limitation of quantity, but rather denote the presence of at least one of the referenced item.

[0021] As used herein, the term "about" when referring to a measurable value is meant to encompass a variation of ±10%, preferably ±5%, more preferably ±1%, and even more preferably ±0.1% from the stated value.

[0022] As used herein, the term "pharmaceutical composition" for the purposes of the present invention means a composition in the form of a pharmaceutical formulation, said composition can be administered via a route selected from the group consisting of oral, parenteral, nasal, topical, rectal, buccal, ocular, vaginal, otic, or via an implanted reservoir.

[0023] As used herein, the term "pharmaceutical acceptable" means salts, carriers, excipients, and other composition components that are compatible with all other pharmaceutical ingredients of the composition, and not harmful to the individual treated with the composition.

[0024] The term "pharmacologically acceptable carrier" refers to a non-toxic carrier that may be administered to a patient, together with a compound of the invention, and which does not destroy the pharmacological activity thereof.

[0025] As used herein, the term "pharmaceutically acceptable excipient" includes vehicles, adjuvants, or diluents, or other auxiliary substances, such as those conventionally used in the art that are readily available to the public. For example, pharmaceutically acceptable excipients include pH adjusting and buffering agents, tonicity adjusting agents, stabilizers, wetting agents, and the like.

[0026] As used herein, the term "solvate" refers to a physical form of a compound of formula (I) or a pharma- ceutically acceptable salt thereof with a stoichiometric or non-stoichiometric amount of a solvent.

[0027] As used herein, the term "salt" refers to an acid or base salt of a compound of the present invention. Salts of basic compounds are salts formed with mineral acids, organic carboxylic acids, organic sulfonic acids, and the like. Examples of suitable acids include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, formic acid, benzoic acid, malonic acid, naphthalene-2-sulfonic acid, trifluoroacetic acid, benzenesulfonic acid, and the like. Salts of acidic compounds are formed with bases, i.e., cationic species of alkali and alkaline earth metal cations (e.g., sodium, lithium, potassium, calcium, and magnesium ions), and ammonium cations (e.g., ammonium, trimethylammonium, diethylammonium, etc.).

[0028] As used herein, the term "alkyl" refers to a straight or branched chain saturated aliphatic radical having 1 to about 12 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, t-butyl, etc. Additionally, alkyl refers to groups having 1 to about 2 carbon atoms, 1 to about 3 carbon atoms, 1 to about 4 carbon atoms, 1 to about 5 carbon atoms, 1 to about 6 carbon atoms, 1 to about 7 carbon atoms, 1 to about 8 carbon atoms, 1 to about 9 carbon atoms, or 1 to about 10 carbon atoms.

[0029] As used herein, the term "alkylene" refers to a straight-chain or branched saturated divalent aliphatic radical derived from an alkyl group having 1 to about 6 carbon atoms, such as -CH-R or -CH(Me)-R.

[0030] The term "alkenyl" refers to a straight or branched chain hydrocarbon having at least two carbon atoms and at least one carbon-carbon double bond. An alkenyl group can have any suitable number of double bonds, including but not limited to 1, 2, 3, 4, 5 or more. Preferred alkenyl groups include ethenyl (-CH=CH2), 2-propenyl (allyl, -CH2-CH=CH2), and the like.

[0031] The term "alkynyl" refers to alkynyl groups having 2 to 12 carbon atoms and having at least 1 to 2 sites of alkynyl unsaturation, including ethynyl (-C≡CH), propargyl (-CH2-C≡CH), 1-butenyl, 2-butenyl, isobutenyl, butadienyl, and the like.

[0032] The term "cycloalkyl" refers to a saturated carbocyclic group having from 3 to 12 carbon atoms having a single ring (e.g., cyclohexyl) or multiple condensed rings (e.g., norbornyl). Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, and the like.

[0033] The term "heterocycle" refers to a ring containing 3 to 12 carbon atoms, in which up to four carbon atoms are replaced with a heteroatom selected from the group consisting of O, S, or N. Heterocycle further includes "heterocycloalkyl" or "heteroaryl".

[0034] The term "heterocycloalkyl" refers to a cycloalkyl group having 3 to 12 carbon atoms as defined above, where up to four carbon atoms are substituted with a heteroatom selected from the group consisting of O, S, or N. Heterocycloalkyls include pyrrolidine, piperidine, piperazine, morpholine, tetrahydrofuran, tetrahydrothiophenyl, 3-methyl-3,9-diazaspiro[5.5]undecane, 2-methyl-2.6-diazaspiro[3.3]heptane, dioxole, and the like. Heterocycloalkyls can be monocyclic, bicyclic, or spirocyclic.

[0035] The term "aryl" refers to a cyclic aromatic hydrocarbon radical consisting of one or more fused rings containing from 6 to 14 carbon atoms in which at least one ring is aromatic in nature, such as phenyl, naphthyl, 1,2,3,4-tetrahydronaphthalenyl, indanyl, and the like.

[0036] The term "heteroaryl" refers to a cyclic aromatic hydrocarbon radical consisting of one or more fused rings containing 5 to 14 ring atoms, preferably 5 to 10 ring atoms, in which at least one ring is aromatic in nature and contains at least one heteroatom selected from N, O or S, such as pyridyl, pyrrolyl, furyl, thienyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, benzothienyl, benzotriazolyl, isobenzothienyl, indolyl, isoindolyl, benzimidazolyl, imidazo[1,2-a]pyridyl, benzothiazolyl, benzoxazolyl, quinolizinyl, quinazolinyl, benzoquinolyl, and the like.

[0037] The term amino acid as used herein refers to two stereoisomers, designated "D" and "L". The D and L forms of amino acids have the same physical properties and chemical reactivity, but rotate the plane of plane polarized light equally but in opposite directions and react at different rates with asymmetric reagents. All naturally occurring amino acids found in proteins are in the L form. Amino acids include lysine, valine, tryptophan, phenylalanine, methionine, leucine, threonine, isoleucine, arginine, histidine, tyrosine, carnitine, serine, glutamine, aspartic acid, proline, glycine, cysteine, alanine, and glutamic acid. Amino acids may exist as "D" or "L" enantiomers.

[0038] The term "halogen" refers to chlorine, iodine, fluorine and bromine.

[0039] As used herein, the term "leaving group" or "L" or "Li" can be defined as the portion of a substrate that is cleaved by the action of a nucleophile. Examples of leaving groups include, but are not limited to, halogens (F, Cl, Br, I), tosylates, mesylates, triflates, acetates, hydroxyls, camphorsulfonates, aryloxides, and the like.

[0040] The term "amino" refers to the group -NH2.

[0041] The term "alkylamino" refers to the group -NHalkyl.

[0042] The term "dialkylamino" refers to the group -N(alkyl).

[0043] The term "alkoxy" refers to the group -O-alkyl.

[0044] The term "aryloxy" refers to the group -O-aryl.

[0045] The term "cycloalkoxy" refers to the group -O-cycloalkyl.

[0046] The term "heterocycloalkyloxy" refers to the group -O-heterocycloalkyl.

[0047] The term "heteroaryloxy" refers to the group -O-heteraryl.

[0048] The term "alkyl-ester" refers to the group -alkylene-O-(CO)-R.

[0049] The term "aminoaryl" refers to the group -arylene-amino.

[0050] The term "alkyl alcohol" or "hydroxyalkyl" refers to an alkyl group substituted with one or more OH groups.

[0051] The term "amino acid residue" or "amino acid side chain" refers to a fragment of -C(O)-C(H / R)-N(H / R) or N(H / R)-C(H / R)-C(O)(OH / R), or N(H / R)-C(H / R)C(O)(OH / R), where "R" refers to hydrogen or a variable value other than hydrogen.

[0052] The term "optionally" means that the event or circumstance described thereafter may or may not occur, and is meant to include cases where the event or circumstance occurs and cases where it does not occur.

[0053] For purposes of the present invention, the term "substituted" shall be understood to include the addition or replacement of one or more atoms contained within a functional group or compound with one or more different atoms.

[0054] Unless otherwise constrained in the definition of the individual substituents, the above groups, such as "alkyl", "alkenyl", "alkynyl", "cycloalkyl", "heterocycle", "heterocycloalkyl", "substituted heterocycloalkyl", "aryl", and "heteroaryl" groups, are also intended to be used interchangeably with the terms "alkyl having 1 to 8 carbon atoms", "alkenyl having 2 to 8 carbon atoms", "alkynyl having 2 to 8 carbon atoms", "cycloalkyl", "heterocycloalkyl", "aryl", "heteroaryl", "amino", "alkylamino", "dialkylamino", " It may be optionally substituted with one or more substituents selected from the group consisting of "acyl", "acyloxy", "acylamino", "aminocarbonyl", "alkoxycarbonyl", "alkoxyalkyloxy", "alkoxycarbonyloxy", "carbamate", "sulfinyl", "sulfonyl", "alkoxy", "sulfanyl", "halogen", "carboxy", "trihalomethyl", "cyano", "hydroxy", "mercapto", "nitro", "phosphate", "alkylphosphate", and the like. Preferred one or more substituents are selected from 1 to 10; more preferably 1 to 5.

[0055] In one embodiment, the prodrug itself may lack or possess the desired biological activity. In one embodiment of the invention, the compounds as disclosed herein may themselves possess the desired biological activity.

[0056] In one embodiment, the compounds of the present invention contain one or more asymmetric carbon atoms and therefore occur as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. All such isomers of these compounds are expressly included in the present invention. Each stereogenic carbon may be in the R or S configuration. In one embodiment, the enantiomers, diastereomers and racemates of the compounds are expressly included in the present invention.

[0057] In one embodiment, the present invention provides a compound of general formula IA, a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 and R3 are the same or different and independently represent hydrogen, [ka] [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R 17 is selected from optionally substituted linear or branched alkylene groups, the alkylene being optionally substituted with amino groups, alkylamino groups, and dialkylamino groups; R 18 , -NH2, -NR 20 R 21 Selected from R 20 and R 21 are each independently hydrogen, optionally substituted alkyl, -C(O)-R 22 Selected from R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R5 is hydrogen, -OH, -OR8, and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or an optionally substituted alkyl group, a cycloalkyl group, an aryl group, a heterocycloalkyl group, and a heteroaryl group; R8 is selected from the group consisting of an optionally substituted alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group; R6 is a phenylene group, the phenylene group being substituted 0 to 4 times by R7, and R7 is selected from hydrogen, -OH, -OR 12 ,below: [ka] [ka] [ka] [ka] , and -R 19 Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) groups; R 19 -OR 23 -OC(O)-R 24 , -OC(O)-R 23 -R 27 , and OR 23 -R 28 Selected from; R 23 is an optionally substituted linear or branched alkylene; R 24 is an optionally substituted alkoxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, aryloxy group, and N(R 25 R 26 ) and R 25 , R 26 are each independently selected from hydrogen, optionally substituted alkyl, and aryl, where alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups, or R 25 and R 26 taken together form an optionally substituted heterocycloalkyl ring, said heterocycloalkyl ring being optionally substituted with alkyl, hydroxyalkyl, -OH, SH, F, Cl, Br, I, and optionally substituted amino groups; R 27 is an optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, and N(R 25 R26 ) groups; R 28 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 28 Heterocycloalkyl, heteroaryl in are optionally substituted with alkyl, hydroxyalkyl, OH, SH, F, Cl, Br, I, and optionally substituted amino and oxo groups; R 29 and R 30 are each independently hydrogen, and R 23 -OC(O)-OR 31 Selected from; R 31 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups; with the proviso that when R6 is phenylene, all substitutions at R1, R3, R5, R7 are not hydrogen; when R1 or R3 substitutions are other than hydrogen and R6 is phenylene, R5 and R7 are not hydrogen; when R1, R3, R7 substitutions are hydrogen, R5 is not -OH; when R1, R3, R5 substitutions are hydrogen and R6 is phenylene, the single R7 substitution on the phenylene is -OH or O-(alkyl) in either the ortho or para position; 1~3 ); if R1, R3 substitutions are hydrogen, R5 is -OH, and R6 is phenylene, then the R7 substitution on the phenylene is not in the -OH para position.

[0058] In one embodiment, the present invention provides a compound of the general formula IA, a pharma- ceutically acceptable salt or solvate thereof; wherein R4 is an alkyl substituted with a group selected from amino, alkylamino, dialkylamino or an optionally substituted heterocycloalkyl, or R4 is an aryl substituted with an optionally substituted amino acid side chain.

[0059] In one embodiment, the present invention provides a compound of the general formula IA, a pharma- ceutically acceptable salt or solvate thereof; wherein R9 is an alkyl ester, amino, and optionally substituted heterocycloalkyl, alkyl substituted with amino, and optionally substituted heterocycloalkyl; or R9 is a heterocycloalkyl substituted with a group selected from alkyl, amino, alkylamino, dialkylamino, aryl, or an optionally substituted heterocycle, said optionally substituted heterocycle being substituted with alkyl; or R9 is an aryloxy optionally substituted at an amino acid residue or amino acid side chain.

[0060] In one embodiment, the present invention provides a compound of general formula IA, a pharma- ceutically acceptable salt or solvate thereof; R 10 and R 11 is independently selected as alkyl substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl.

[0061] In one embodiment, the present invention provides a compound of general formula IA, a pharma- ceutically acceptable salt or solvate thereof; wherein R 13 is alkyl substituted with a group selected from hydroxy, aryl, amino, alkylamino, dialkylamino, alkylalcohol, heterocycloalkyl, or substituted heterocycloalkyl; or R 13 is alkoxy substituted with a group selected from amino, alkylamino, dialkylamino, heterocycloalkyl, or substituted heterocycloalkyl; or R 13 is hydroxy, amino, carboxy, alkyl, alkylamino, dialkylamino, heterocycle, heterocycloalkyl substituted with substituted heterocycle; said substituted heterocycle is substituted with alkyl; or R 13 is heterocycloalkyloxy substituted with alkyl.

[0062] In one embodiment, the present invention provides a compound of general formula IA, a pharma- ceutically acceptable salt or solvate thereof; wherein R 14and R 15 is independently selected from alkyl substituted with a group selected from carboxy, amino, alkylamino, dialkylamino, heterocycloalkyl, or substituted heterocycloalkyl group; or R 14 and R 15 is independently selected from heterocycloalkyl substituted with alkyl, heterocycle, or substituted heterocycle, wherein said substituted heterocycle is substituted with alkyl.

[0063] In one embodiment, the present invention provides a compound of general formula IA, a pharma- ceutically acceptable salt or solvate thereof; wherein R 14 and R 15 is independently selected from aryl substituted with a group selected from a heterocycle group or a substituted heterocycloalkyl group, said substituted heterocycle being substituted with alkyl.

[0064] In one embodiment, the present invention provides a compound of general formula I, a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 and R3 are the same or different and independently represent hydrogen, [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R5 is selected from the group consisting of hydrogen, -OH, OR8, and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R8 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R6 is a phenylene group, and the phenylene group is substituted 0 to 4 times by R7; R7 is hydrogen, OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) groups; provided that all substitutions at R1, R3, R5, R7 are not hydrogen when R6 is phenylene; when any substitution at R1 or R3 is other than hydrogen and R6 is phenylene, R5 and R7 are not hydrogen; when the substitutions at R1, R3, R7 are hydrogen, R5 is not -OH; when the substitutions at R1, R3, R5 are hydrogen and R6 is phenylene, the single R7 substitution on the phenylene is -OH or O-(alkyl) in either the ortho or para position. 1~3 ); if R1, R3 substitutions are hydrogen, R5 is -OH, and R6 is phenylene, then the R7 substitution on the phenylene is not in the -OH para position.

[0065] In one embodiment, the present invention provides a compound of general formula I, a pharma- ceutically acceptable salt or solvate thereof; wherein R4 is an alkyl substituted with a group selected from amino, alkylamino, dialkylamino or an optionally substituted heterocycloalkyl, or R4 is an aryl substituted with an optionally substituted amino acid side chain.

[0066] In one embodiment, the present invention provides a compound of general formula I, a pharma- ceutically acceptable salt or solvate thereof; wherein R9 is an alkyl ester, an amino, and an optionally substituted heterocycloalkyl, an alkyl substituted with an amino, and an optionally substituted heterocycloalkyl; or R9 is a heterocycloalkyl substituted with a group selected from alkyl, amino, alkylamino, dialkylamino, aryl, or an optionally substituted heterocycle, said optionally substituted heterocycle being substituted with an alkyl; or R9 is an aryloxy optionally substituted with an amino acid residue or an amino acid side chain.

[0067] In one embodiment, the present invention provides a compound of general formula I, a pharma- ceutically acceptable salt or solvate thereof; R 10 and R 11 is independently selected as alkyl substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl.

[0068] In one embodiment, the present invention provides a compound of general formula I, a pharma- ceutically acceptable salt or solvate thereof; wherein R 13 is alkyl substituted with a group selected from hydroxy, aryl, amino, alkylamino, dialkylamino, alkylalcohol, heterocycloalkyl, or substituted heterocycloalkyl; or R 13 is alkoxy substituted with a group selected from amino, alkylamino, dialkylamino, heterocycloalkyl, or substituted heterocycloalkyl; or R 13 is hydroxy, amino, carboxy, alkyl, alkylamino, dialkylamino, heterocycle, heterocycloalkyl substituted with substituted heterocycle; said substituted heterocycle is substituted with alkyl; or R 13 is heterocycloalkyloxy substituted with alkyl.

[0069] In one embodiment, the present invention provides a compound of general formula I, a pharma- ceutically acceptable salt or solvate thereof; wherein R 14 and R 15 is independently selected from alkyl substituted with a group selected from carboxy, amino, alkylamino, dialkylamino, heterocycloalkyl group, or substituted heterocycloalkyl group; or R 14 and R 15 is independently selected from heterocycloalkyl substituted with alkyl, heterocycle, or substituted heterocycle, wherein said substituted heterocycle is substituted with alkyl.

[0070] In one embodiment, the present invention provides a compound of general formula I, a pharma- ceutically acceptable salt or solvate thereof; wherein R 14 and R15 is independently selected from aryl substituted with a group selected from a heterocycle group or a substituted heterocycloalkyl group; said substituted heterocycle being substituted with alkyl.

[0071] In one embodiment, the present invention relates to a compound of general formula (II) or a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 and R3 are independently hydrogen, [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, -(CH2-CH2-O) n -, or heteroaryl; where n is 1 to 20; R5 is selected from the group consisting of hydrogen, OH, -OR8, and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R and R ’ 7 is the same or different and independently represents hydrogen, OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, heterocycloalkyloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group; However, R1, R3, R5, R7 and R ’ All substitutions at R1 or R3 are not hydrogen at the same time; if any one substitution at R5, R7 and R ’ 7 is not hydrogen; R1, R3, R7 and R’ When the substitution at 7 is hydrogen, R5 is not -OH; R1, R3, R5 and R ’ When the substitution at 7 is hydrogen, R7 is -OH or O-(alkyl 1~3 ) instead of; if the substitutions at R, R, R and R are hydrogen, then R ’ 7 is -OH or O-(alkyl 1~3 ) instead of; if the substitutions at R1, R3 and R7 are hydrogen, then R5 and R ’ Neither of 7's are -OH.)

[0072] In one embodiment, the present invention provides a compound of general formula II; a pharma- ceutically acceptable salt or solvate thereof; wherein R4 is an alkyl substituted with a group selected from amino, alkylamino, dialkylamino or optionally substituted heterocycloalkyl; and wherein the aryl group represented by R4 is an aryl substituted with an optionally substituted amino acid side chain.

[0073] In one embodiment, the present invention provides a compound of general formula II; a pharma- ceutically acceptable salt or solvate thereof; wherein the alkyl group represented by R9 is substituted with an alkyl ester, amino, and an optionally substituted heterocycloalkyl; wherein the heterocycloalkyl group represented by R9 is substituted with a group selected from alkyl, amino, alkylamino, dialkylamino, aryl, or an optionally substituted heterocycle; said optionally substituted heterocycle is substituted with an alkyl, and the aryloxy group of R9 is optionally substituted with an amino acid residue or an amino acid side chain.

[0074] In one embodiment, the present invention provides a compound of general formula II; a pharma- ceutically acceptable salt or solvate thereof; wherein R 10 and R 11 is independently selected as alkyl substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl.

[0075] In one embodiment, the present invention provides a compound of general formula II; a pharma- ceutically acceptable salt or solvate thereof; wherein R 13 is alkyl substituted with a group selected from hydroxy, aryl, amino, alkylamino, dialkylamino, alkylalcohol, heterocycloalkyl, or substituted heterocycloalkyl; or R 13 is alkoxy substituted with a group selected from amino, alkylamino, dialkylamino, heterocycloalkyl, or substituted heterocycloalkyl; or R 13 is hydroxy, amino, carboxy, alkyl, alkylamino, dialkylamino, heterocycle, heterocycloalkyl substituted with substituted heterocycle; said substituted heterocycle is substituted with alkyl; or R 13 is heterocycloalkyloxy substituted with alkyl.

[0076] In one embodiment, the present invention provides a compound of general formula II; a pharma- ceutically acceptable salt or solvate thereof; wherein R 14 and R 15 is independently selected from an alkyl substituted with a group selected from a carboxy group, an amino group, an alkylamino group, a dialkylamino group, a heterocycloalkyl group, or a substituted heterocycloalkyl group; or R 14 and R 15 is independently selected from heterocycloalkyl substituted with alkyl, heterocycle, or substituted heterocycle, wherein said substituted heterocycle is substituted with alkyl.

[0077] In one embodiment, the present invention provides a compound of general formula II; a pharma- ceutically acceptable salt or solvate thereof; wherein R 14 and R 15 is independently selected from aryl substituted with a group selected from a heterocyclic group or a substituted heterocyclic alkyl group, said substituted heterocyclic being substituted with alkyl.

[0078] In one embodiment, the present invention relates to a compound of general formula (III), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 is hydrogen, the following: [ka] and [ka] R3 is selected from: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, or heteroaryl, where n is 1 to 20; R5 is -OR8 and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or N 10 R 11 R 10 and R 11 are the same or different and are independently selected from hydrogen, optionally substituted alkyl; where n is 1 to 20; R 10 and R 11The alkyl group represented by the formula (I) may be optionally substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl; R8 is selected from the group consisting of hydrogen; optionally substituted alkylalkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

[0079] In one embodiment, the present invention provides a compound of general formula III: wherein R4 is alkyl substituted with a group selected from amino, alkylamino, dialkylamino, or optionally substituted heterocycloalkyl, or R4 is aryl substituted with an optionally substituted amino acid side chain.

[0080] In one embodiment, the present invention provides a compound of general formula III: wherein R9 is alkyl, amino, and optionally substituted heterocycloalkyl substituted with alkyl esters, amino, and optionally substituted heterocycloalkyl; or R9 is heterocycloalkyl substituted with a group selected from alkyl, amino, alkylamino, dialkylamino, aryl, or optionally substituted heterocycle, wherein said optionally substituted heterocycle is substituted with alkyl; or R9 is aryloxy optionally substituted at an amino acid residue or amino acid side chain.

[0081] In one embodiment, the present invention provides a compound of general formula III: In the formula, R 10 and R 11 is independently selected as alkyl substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl.

[0082] In one embodiment, the present invention provides a compound selected from the group consisting of: [ka] [ka]

[0083] In another embodiment, there is provided a compound of general formula (III-A), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, or heteroaryl, where n is 1 to 20; R5 is -OR8 and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, alkyl-ester, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or N 10 R 11 wherein n is 1 to 20; R 10 and R 11 is independently selected from hydrogen, optionally substituted alkyl; R 10 and R 11The alkyl group represented by the formula (I) may be optionally substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl; R8 is selected from the group consisting of hydrogen; optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

[0084] In one embodiment, the present invention provides a compound selected from the group consisting of: [ka] [ka]

[0085] In another embodiment, a compound of general formula (III-B), a pharma- ceutically acceptable salt or solvate thereof. [ka] (Wherein, R5 is -OR8 and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, alkyl-ester, an amino acid linked via an ester or amide bond at the attachment point, or N 10 R 11 wherein n is 1 to 20; R 10 and R 11 is independently selected from hydrogen, optionally substituted alkyl; R 10 and R 11The alkyl group represented by the formula (I) may be optionally substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl; R8 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

[0086] In one embodiment, the present invention provides a compound selected from the group consisting of: [ka] [ka]

[0087] In another embodiment, a compound of general formula (III-C), a pharma- ceutically acceptable salt or solvate thereof. [ka] (Wherein, R3 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, or heteroaryl, where n is 1 to 20; R5 is -OR8 and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, alkyl-ester, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or N 10 R 11 wherein n is 1 to 20; R 10 and R 11 is independently selected from hydrogen, optionally substituted alkyl; R 10 and R 11 The alkyl group represented by the formula (I) may be optionally substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl; R8 is selected from the group consisting of hydrogen; optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

[0088] In one embodiment, the present invention provides a compound selected from the group consisting of: [ka]

[0089] In one embodiment, the present invention relates to compounds of general formula (IV) or their pharma- ceutically acceptable salts or solvates: [ka] (Wherein, R1 and R3 are independently hydrogen, [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R5 is selected from the group consisting of hydrogen, -OR8, halogen, and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, alkyl-ester, alkoxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 where n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R is selected from the group consisting of hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R is hydrogen, OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group; provided that all substitutions of R1, R3, R5, and R7 are not hydrogen at the same time; if any one substitution of R1 or R3 is not hydrogen, then R5 and R7 are not hydrogen; if substitutions of R1, R3, and R7 are hydrogen, then R5 is not -OH; if substitutions of R1, R3, and R5 are hydrogen, then R7 is -OH or O-(alkyl). 1~3 ) and when R1 and R3 are substituted with hydrogen, R5 and R7 are not both -OH.

[0090] In one embodiment, the present invention relates to a compound of general formula (IV-A), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R5 is -OR8 and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R is selected from the group consisting of hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R is -OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0091] In one embodiment, the present invention provides a compound selected from the group consisting of: [ka]

[0092] In one embodiment, the present invention relates to compounds of general formula (IV-B), pharma- ceutically acceptable salts or solvates thereof: [ka] (Wherein, R3 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n-, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R5 is -OH, -OR8, and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R is -OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0093] In one embodiment, the present invention relates to a compound of general formula (IV-C), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R5 is -OH, -OR8, and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R is -OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group; provided that R5 and R7 are not both -OH.

[0094] In one embodiment, the present invention provides a compound selected from the group consisting of: [ka]

[0095] In one embodiment, the present invention relates to a compound of general formula (V), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 and R3 are the same or different and independently represent hydrogen, [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R5 is hydrogen, OH, OR8, halogen, [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R ’7 is hydrogen, OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group; Where R1, R3, R5 and R ’ All substitutions at R1 or R3 are not hydrogen at the same time; if any one substitution at R5 and R ’ 7 is not hydrogen; R1, R3, R ’ When the substitution at R1, R3, R5 is hydrogen, R ’ 7 is -OH or O-(alkyl 1~3 )isn't it.

[0096] In one embodiment, the present invention relates to a compound of general formula (VA), a pharma- ceutically acceptable salt or solvate thereof. [ka] (In the formula, R1 is as follows: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R5 is -OR8 and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R is selected from the group consisting of hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R ’ 7, -OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, optionally substituted alkyl, heterocycloalkyl, and aryl groups; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0097] In one embodiment, the present invention relates to a compound of general formula (VB), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R3 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R5 is -OR8 and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R is selected from the group consisting of hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R ’ 7, -OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0098] In one embodiment, the present invention relates to a compound of general formula (VC), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R5 is -OH, -OR8, and the following: [ka] R9 is selected from optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH2-CH2-O) n - or NR 10 R 11 wherein R 10 and R 11are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R8 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R ’ 7, -OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0099] In one aspect, the present invention relates to a compound of general formula (VI), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 and R3 are the same or different and independently represent hydrogen, [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R and R ’ 7 is hydrogen, OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group; Where R1, R3, R7 and R ’ All substitutions at R7 and R8 are not hydrogen at the same time; if no substitution at R1 or R3 is hydrogen, then R7 and R ’ 7 is not hydrogen; if R1, R3, and R7 are hydrogen, R ’ 7 is -OH or O-(alkyl 1~3 ) instead of;R1, R3, R ’ When the 7 substitution is hydrogen, R7 is not -OH or O-(alkyl 1-3).

[0100] In one embodiment, the present invention relates to a compound of general formula (VI-A), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R and R ’ 7 is independently selected from -OH, -OR 12 ,the below described: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0101] In one embodiment, the present invention relates to a compound of general formula (VI-B), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R3 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R and R ’ 7 is independently selected from -OH, -OR 12 ,the below described: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0102] In one embodiment, the present invention relates to compounds of general formula (VI-C), pharma- ceutically acceptable salts or solvates thereof. [ka] (Wherein, R7 and R ’ 7 is independently selected from -OH, -OR 12 ,the below described: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0103] In one aspect, the present invention relates to a compound of general formula (VII), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 and R3 are independently hydrogen, [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R7 is hydrogen, OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group; However, all of the substitutions of R1, R3 and R7 are not hydrogen at the same time; when any one of the substitutions of R1 or R3 is not hydrogen, R7 is not hydrogen; when the substitutions of R1 and R3 are hydrogen, R7 is not -OH, -O-(alkyl 1~3 ) is not.

[0104] In one embodiment, the present invention relates to a compound of general formula (VII-A), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n R7 is selected from the group consisting of -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; 12 ,below: [ka] [ka] and [ka] Selected from R 12is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0105] In one embodiment, the present invention provides a compound selected from the group consisting of: [ka]

[0106] In one embodiment, the present invention relates to a compound of general formula (VII-B), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R3 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; n is 1 to 20; R7 is -OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0107] In one embodiment, the present invention relates to a compound of general formula (VII-C), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R7 is -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0108] In one embodiment, the present invention provides a compound selected from the group consisting of: [ka]

[0109] In one aspect, the present invention relates to a compound of general formula (VIII), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 and R3 are independently hydrogen, [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R ’ 7 is hydrogen, OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n- or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group; Where R1, R3 and R ’ All of the substitutions in R1 or R3 are not hydrogen at the same time; if any one of the substitutions in R1 or R3 is not hydrogen, then R ’ 7 is not hydrogen; if the substitutions in R1 and R3 are hydrogen, R ’ 7 is -OH or O-(alkyl 1~3 )isn't it.)

[0110] In one aspect, the present invention provides a compound selected from the group consisting of: [ka] [ka]

[0111] In one embodiment, the present invention relates to a compound of general formula (VIII-A), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R ’ 7, -OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0112] In one aspect, the present invention provides a compound selected from the group consisting of: [ka] [ka]

[0113] In one embodiment, the present invention relates to a compound of formula (VIII-B), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R3 is the following: [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, n being 1 to 20; R ’ 7, -OH, -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) group.

[0114] In one aspect, the present invention provides a compound selected from the group consisting of: [ka]

[0115] In one embodiment, the present invention relates to a compound of general formula (VIII-C), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R'7 is -OR 12 ,below: [ka] [ka] and [ka] Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene (C 1~6 ) groups; provided that when R1 and R3 are substituted with hydrogen, R'7 is -OH or O-(alkyl 1~3 )isn't it.)

[0116] In one aspect, the present invention provides a compound selected from the group consisting of: [ka] [ka] [ka] [ka]

[0117] In one embodiment, the present invention provides a compound selected from the group of compounds shown in Table 1, or a pharma- ceutically acceptable salt or solvate thereof.

[0118] In one embodiment, the present invention provides a method for the treatment of at least one disease state selected from interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, post-herpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, the method comprising administering at least one compound selected from the group consisting of the compounds shown in Table 1, or a pharma- ceutically acceptable salt or solvate thereof.

[0119] In one embodiment, the present invention provides a method of use of a compound selected from the group consisting of the compounds set forth in Table 1, or a pharma- ceutically acceptable salt or solvate thereof, for the treatment of at least one disease state selected from interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headaches, pruritus, post-herpetic neuralgia, urinary tract infection-associated pain, osteoarthritis, arthritis, and urinary incontinence.

[0120] In one embodiment, the serial numbers shown in Tables 1 and 2 are considered compound numbers for purposes of reference herein. [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6] [Table 1-7] [Table 1-8] [Table 1-9] [Table 1-10]

[0121] In one embodiment, the present invention relates to a compound of general formula (IX) or a pharma- ceutically acceptable salt or solvate thereof: [ka] (In the formula, R 17 is selected from optionally substituted linear or branched alkylene groups, the alkylene being optionally substituted by amino groups, alkylamino groups, and dialkylamino groups; R 18 , -NH2, -NR 20 R 21 Selected from R 20 and R 21 are each independently hydrogen, optionally substituted alkyl, -C(O)-R 22 Selected from R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 19 -OR 23 -OC(O)-R 24 , -OC(O)-R 27 , and OR 23 -R 28 Selected from R 23 is an optionally substituted linear or branched alkylene; R 24 is an optionally substituted alkoxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, aryloxy group, and N(R 25 R 26 ) and R 25 , R 26 are each independently selected from hydrogen, optionally substituted alkyl, and aryl, where alkyl and aryl are optionally substituted by OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups, or R25 and R 26 taken together form an optionally substituted heterocycloalkyl ring, said heterocycloalkyl ring being optionally substituted with alkyl, hydroxyalkyl, -OH, -SH, F, Cl, Br, I, and optionally substituted amino groups; R 27 is an optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, and N(R 25 R 26 ) groups; R 28 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 28 The heterocycloalkyl and heteroaryl in are optionally substituted with alkyl, hydroxyalkyl, OH, SH, F, Cl, Br, I, and optionally substituted amino and oxo groups.

[0122] In one embodiment, the present invention relates to a compound of general formula (IX-A), a pharma- ceutically acceptable salt or solvate thereof: [ka] (In the formula, R 17 is selected from optionally substituted linear or branched alkylene groups, the alkylene being optionally substituted by amino groups, alkylamino groups, and dialkylamino groups; R 18 , -NH2, -NR 20 R 21 Selected from; R 20 and R 21 are each independently hydrogen, optionally substituted alkyl, -C(O)-R 22 Selected from; R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 23 is an optionally substituted linear or branched alkylene; R 24 is an optionally substituted alkoxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, aryloxy group, and N(R 25 R 26) and R 25 , R 26 are each independently selected from hydrogen, optionally substituted alkyl, and aryl, where alkyl and aryl are optionally substituted by OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups, or R 25 and R 26 taken together form an optionally substituted heterocycloalkyl ring, said heterocycloalkyl ring being optionally substituted with alkyl, hydroxyalkyl, -OH, -SH, F, Cl, Br, I, and an optionally substituted amino group.

[0123] In one embodiment, the present invention provides at least one compound selected from the group consisting of the following compounds: [ka] [ka] [ka]

[0124] In one embodiment, the present invention relates to a compound of general formula (IX-B), a pharma- ceutically acceptable salt or solvate thereof: [ka] (In the formula, R 17 is selected from optionally substituted linear or branched alkylene groups, the alkylene being optionally substituted with amino groups, alkylamino groups, and dialkylamino groups; R 18 , -NH2, -NR 20 R 21 Selected from R 20 and R 21 are each independently hydrogen, optionally substituted alkyl, -C(O)-R 22 Selected from R 22is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 23 is an optionally substituted linear or branched alkylene; R 25 and R 26 are each independently selected from hydrogen, optionally substituted alkyl and aryl groups, where the alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl and amino groups; or R 25 and R 26 taken together form an optionally substituted heterocycloalkyl ring, which is optionally substituted with optionally substituted alkyl groups, hydroxyalkyl groups, OH, SH, F, Cl, Br, I, and optionally substituted amino groups.

[0125] In one embodiment, the present invention provides at least one compound selected from the group consisting of: [ka] [ka] [ka]

[0126] In one embodiment, the present invention relates to a compound of general formula (IX-C), a pharma- ceutically acceptable salt or solvate thereof: [ka] (In the formula, R 17 is selected from optionally substituted linear or branched alkylene groups, the alkylene being optionally substituted by amino groups, alkylamino groups, and dialkylamino groups; R 18 is -NH2, NR 20 R 21 Selected from R 20 and R 21are each independently hydrogen, optionally substituted alkyl, -C(O)-R 22 Selected from R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 27 is an optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, and N(R 25 R 26 ) groups, R 25 and R 26 are each independently selected from hydrogen, optionally substituted alkyl and aryl groups, where the alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups; or R 25 and R 26 taken together form an optionally substituted heterocycloalkyl ring, said heterocycloalkyl ring being optionally substituted with optionally substituted alkyl, hydroxyalkyl groups, OH, SH, F, Cl, Br, I, and optionally substituted amino groups.

[0127] In one embodiment, the present invention provides at least one compound selected from the group consisting of: [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0128] In one embodiment, the present invention relates to a compound of general formula (IX-D), a pharma- ceutically acceptable salt or solvate thereof: [ka] (In the formula, R 17 is selected from optionally substituted linear or branched alkylene groups, the alkylene being optionally substituted by amino groups, alkylamino groups, and dialkylamino groups; R 18 , -NH2, -NR 20 R 21 Selected from R 20 and R 21 are each independently hydrogen, optionally substituted alkyl, -C(O)-R 22 Selected from R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 23 is an optionally substituted linear or branched alkylene; R 28 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 28 The heterocycloalkyl, heteroaryl are optionally substituted with alkyl, hydroxyalkyl, OH, SH, F, Cl, Br, I, and optionally substituted amino and oxo groups.

[0129] In one embodiment, the present invention provides a compound selected from the group consisting of: [ka]

[0130] In one embodiment, the present invention relates to a compound of general formula (X), a pharma- ceutically acceptable salt or solvate thereof: [ka] (Wherein, R1 is the following: [ka] [ka] and [ka] R2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R4 is optionally substituted alkyl, alkenyl, alkynyl, -(CH2-CH2-O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 17 is selected from optionally substituted linear or branched alkylene groups, the alkylene being optionally substituted by amino groups, alkylamino groups, and dialkylamino groups; R 18 , -NH2, -NR 20 R 21 Selected from R 20 and R 21 are each independently hydrogen, optionally substituted alkyl, and C(O)-R 22 Selected from R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R ’ 7, -OH, -OR 12 ,below: [ka] [ka] [ka] [ka] and R 19 Selected from; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point via an ester or amide bond, -(CH-CH-O) n - or NR 14 R 15 wherein n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, optionally substituted alkyl, heterocycloalkyl, and aryl groups; R 16 is an optionally substituted alkylene (C 1~6 ) groups; R 19 -OR 23 -OC(O)-R 24 , -OC(O)-R 23 -R 27 , and OR 23 -R 28 Selected from; R 23 is an optionally substituted linear or branched alkylene; R 24 is an optionally substituted alkoxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, aryloxy group, and N(R 25 R 26 ) is selected from;R 25 , R 26are each independently selected from hydrogen, optionally substituted alkyl, and aryl, where alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups; or R 25 and R 26 taken together form an optionally substituted heterocycloalkyl ring, said heterocycloalkyl ring being optionally substituted with alkyl, hydroxyalkyl, -OH, -SH, F, Cl, Br, I, and optionally substituted amino groups; R 27 is an optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, and N(R 25 R 26 ) groups; R 28 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 28 Heterocycloalkyl, heteroaryl in are optionally substituted with alkyl, hydroxyalkyl, OH, SH, F, Cl, Br, I, and optionally substituted amino and oxo groups; R 29 and R 30 are each independently hydrogen, and R 23 -OC(O)-OR 31 Selected from; R 31 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups.

[0131] In one embodiment, the present invention provides at least one compound selected from the group consisting of: [ka] [ka] [ka]

[0132] In one embodiment, the present invention provides at least one compound selected from the group consisting of the compounds listed in Table 2, or a pharma- ceutically acceptable salt or solvate thereof.

[0133] In one embodiment, the present invention provides a method for the treatment of at least one disease state selected from interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, post-herpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, comprising administering at least one compound selected from the group consisting of the compounds shown in Table 2, or a pharmaceutically acceptable salt or solvate thereof.

[0134] In one embodiment, the present invention provides a method of use of at least one compound selected from the group consisting of the compounds shown in Table 2, or a pharma- ceutically acceptable salt or solvate thereof, for the treatment of at least one disease state selected from interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine, pruritus, post-herpetic neuralgia, urinary tract infection-associated pain, osteoarthritis, arthritis, and urinary incontinence. compound [Table 2-1] [Table 2-2] [Table 2-3] [Table 2-4] [Table 2-5] [Table 2-6] [Table 2-7] [Table 2-8] [Table 2-9] [Table 2-10] [Table 2-11] [Table 2-12] [Table 2-13] [Table 2-14] [Table 2-15] [Table 2-16] [Table 2-17] [Table 2-18] [Table 2-19] [Table 2-20]

[0135] In another aspect, the present invention provides a method for the treatment of at least one disease state selected from interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, post-herpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, said method comprising administering a compound selected from general formula (I) or (IA), a pharma- ceutically acceptable salt, or solvate thereof.

[0136] In another aspect, the present invention provides a method for treating at least one condition selected from interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, postherpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, comprising administering to a patient a compound of general formula (II), formula (III), formula (III-A), formula (III-B), formula (III-C), formula (IV), formula (IV-A), formula (IV-B), formula (IV-C), formula (IV-D), formula (IV-E), formula (IV-F), formula (IV-G), formula (IV-H), formula (IV-I ... The present invention relates to a method for treating a rheumatoid arthritis, the method comprising administering to a patient a compound selected from the group consisting of compounds of formula (V), formula (VA), formula (VB), formula (VC), formula (VI), formula (VI-A), formula (VI-B), formula (VI-C), formula (VII), formula (VII-A), formula (VII-B), formula (VII-C), formula (VIII), formula (VIII-A), formula (VIII-B), formula (VIII-C), formula (IX), formula (IX-A), formula (IX-B), formula (IX-C), formula (IX-D), formula (X), a pharma- ceutically acceptable salt, or a solvate thereof.

[0137] In another aspect, the present invention provides a method for the symptomatic relief of pain, burning, urgency, frequency, and other discomfort resulting from irritation of the lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, or passage of a sound or catheter, said method comprising administering a therapeutically effective amount of a compound of Formula (I) or Formula (IA), a pharma- ceutically acceptable salt, or solvate thereof.

[0138] In another aspect, the present invention provides a method for symptomatic relief of pain, burning, urgency, frequency, and other discomfort resulting from irritation of the lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, or passage of a sound or catheter, said method comprising administering to a subject a compound represented by general formula (II), (III), (III-A), (III-B), (III-C), (IV), (IV-A), (IV-B), (IV-C), (V), (VA), The method includes administering a compound selected from the group consisting of compounds of formula (VB), formula (VC), formula (VI), formula (VI-A), formula (VI-B), formula (VI-C), formula (VII), formula (VII-A), formula (VII-B), formula (VII-C), formula (VIII), formula (VIII-A), formula (VIII-B), formula (VIII-C), formula (IX), formula (IX-A), formula (IX-B), formula (IX-C), formula (IX-D), formula (X), or a pharma- ceutically acceptable salt or solvate thereof.

[0139] In yet another aspect, the present invention relates to a compound represented by general formula (IA), (I), (II), (III), (III-A), (III-B), (III-C), (IV), (IV-A), (IV-B), (IV-C), (V), (VA), (VB), (VC), (VI), (VI-A), (VI-B), (VI-C), (VII), (VII-A), The present invention relates to a pharmaceutical composition comprising at least one compound selected from the group consisting of compounds of formula (VII-B), formula (VII-C), formula (VIII), formula (VIII-A), formula (VIII-B), formula (VIII-C), formula (IX), formula (IX-A), formula (IX-B), formula (IX-C), formula (IX-D), formula (X), a pharma- ceutically acceptable salt, or solvate thereof, and a pharma- ceutically acceptable excipient.

[0140] In another aspect, the present invention provides a pharmaceutical composition for use in the treatment of at least one disease state selected from interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, post-herpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, the pharmaceutical composition comprising a compound of general formula (IA), formula (I), formula (II), formula (III), formula (III-A), formula (III-B), formula (III-C), formula (IV), formula (IV-A), formula (I), formula (II), formula (III), formula (III-B), formula (III-C), formula (IV ... The present invention includes administering a compound selected from the group consisting of compounds of formula (IV-C), formula (V), formula (VA), formula (VB), formula (VC), formula (VI), formula (VI-A), formula (VI-B), formula (VI-C), formula (VII), formula (VII-A), formula (VII-B), formula (VII-C), formula (VII), formula (VIII), formula (VIII-A), formula (VIII-B), formula (VIII-C), formula (IX), formula (IX-A), formula (IX-B), formula (IX-C), formula (IX-D), formula (X), a pharma- ceutical acceptable salt, or a solvate thereof.

[0141] In another aspect, the present invention provides a method for the treatment of at least one disease state selected from interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, post-herpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, said method comprising administering a compound selected from the following, a pharma- ceutically acceptable salt, or a solvate thereof: [ka]

[0142] In another aspect, the present invention provides a method for treating at least one condition selected from overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine headache, pruritus, post-herpetic neuralgia, urinary tract infection associated pain, osteoarthritis, arthritis, and urinary incontinence, the method comprising administering a compound selected from the following (Compound XIII), a pharma- ceutically acceptable salt, or solvate thereof: [ka]

[0143] The following examples are given for the purpose of illustrating the present invention and should not be construed as limiting the scope of the present invention.

[0144] Example 01: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 1-methyl-L-tryptophanate Step-01: Preparation of N-(tert-butoxycarbonyl)-1-methyl-L-tryptophan [ka]

[0145] To a stirred solution of 1-methyl-L-tryptophan (2.0 g) in 1,4-dioxane (40 mL) was added sodium hydroxide (364 mg / 20 mL water) at a temperature of 0° C., followed by di-tert-butyl dicarbonate (2.7 mL) at the same temperature. The reaction mixture was stirred at 0° C. for 4 h and then stirred at room temperature for another 16 h. After completion of the reaction (monitored by TLC: 20% methanol in dichloromethane), excess solvent was evaporated under reduced pressure, followed by acidification of the reaction mixture using 1N hydrochloric acid. The mixture was extracted with ethyl acetate (3×1500 mL) and then washed with water (3×500 mL). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain the crude product. The crude product was washed with n-pentane and dried under reduced pressure to obtain N-(tert-butoxycarbonyl)-1-methyl-L-tryptophan (1.4 g, 48% yield) as an off-white solid. LCMS: 96.83% (m / z: 317.39), [M-1] + , 1.48 min (10 min run), 214 nm). 1H-NMR (400 MHz, DMSO-d6): δ 12.51 (s, 1H), 7.53 (d, 1H), 7.37 (d, 1H), 7.15-7.11 (m, 2H), 7.02 (t, 1H), 6.93 (d, 1H), 4.15-4.12 (m, 1H), 3.72 (s, 3H), 3.12 (dd, 1H), 3.01-2.95 (m, 1H), 1.33 (s, 9H).

[0146] Step-02: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl (S)-3-(112-indol-3-yl)-2-((tert-butoxycarbonyl)amino)propanoate [ka] To a stirred solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol (0.500 g) in dichloromethane (6.0 mL) was added dicyclohexylcarbodiimide (1.16 g), 4-(dimethylamino)pyridine (0.12 g) and N-(tert-butoxycarbonyl)-1-methyl-L-tryptophan (1.2 g). The reaction mixture was stirred at room temperature for 16 h. Completion of the reaction was monitored by TLC (mobile phase: 50% ethyl acetate in heptane). After completion of the reaction, the reaction mixture was quenched with demineralized water and extracted with 5% methanol in dichloromethane (3×100 mL). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain the crude product. The crude was washed with n-pentane and dried under reduced pressure to give (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl (S)-3-(112-indol-3-yl)-2-((tert-butoxycarbonyl)amino)propanoate (0.1 g. 50% purity) as a yellow solid. LCMS:50.45%(m / z:530.14), [M+1] + , 2.43 min (10 min run), 214 nm)

[0147] Step-03: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 1-methyl-L-tryptophanate [ka] To a stirred solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl (S)-3-(1H-indol-3-yl)-2-((tertbutoxycarbonyl)amino)propanoate (1 g) in dichloromethane (20 mL) was added 4M hydrochloric acid in 1,4-dioxane (2 mL) at a temperature of 0° C., and then the reaction mixture was stirred at room temperature for another 16 h. After completion of the reaction (monitored by TLC: mobile phase: 50% ethyl acetate in heptane), the excess solvent was evaporated under reduced pressure to give the crude material. The crude was purified by preparative HPLC (T3 column, trifluoroacetic acid:acetonitrile, 1:1) to give (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 1-methyl-L-tryptophanate (0.09 g, 11%) as a yellow solid. LCMS: 95.22% (m / z: 430.15 [M+1] + , 4.74 min (10 min run), 214 nm) 1 H-NMR (400 MHz, DMSO-d6): δ 7.80-7.78 (m, 2H), 7.59 (d, 1H), 7.42-7.36 (m, 3H), 7.26-7.11 (m,3H), 7.04 (t, 1H), 6.00 (d, 1H), 4.59 (t, 1H), 3.69 (s, 3H), 3.52 (dd, 1H), 3.40 (dd, 1H)

[0148] Following the reaction conditions of Example 01, step-02 (DCC, DMAP, DCM), the following ester prodrugs were synthesized using the respective acids commercially available. [ka] [ka] [ka] [ka]

[0149] Example 18: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenylpropionate [ka] To a solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol hydrochloride (0.2 g) in dichloromethane (8 mL) was added triethylamine (0.25 mL) and propionyl chloride (0.1 g) at a temperature of 0° C. and the reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction (monitored by TLC), the reaction mass was quenched with cold water (10 mL) and extracted with dichloromethane (3×30 mL). The combined organic layer was washed with water (2×100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude material which was purified by Prep HPLC [(60% acetonitrile:formic acid) to obtain (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenylpropionate. (0.042 g, 19.5%) LCMS: 99.52% (m / z: 286.2, [M+1] + , 4.85 min (10 min run), 214 nm). 1 H NMR (400 MHz, DMSO-d6): δ ppm 7.71-7.69 (m, 1H), 7.64 (d, 1H), 7.31-7.28 (m, 2H), 7.22-7.19(m, 1H), 6.84 (br s, 2H), 6.00 (d, 1H), 2.64 (q. 2H), 1.15 (t, 3H).

[0150] Following the reaction conditions of Example 18 (triethylamine, DCM), the following ester prodrugs were synthesized using the respective acyl chlorides obtained from commercial sources. [ka]

[0151] Example 20: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 1-methylpiperidine-2-carboxylate [ka] To a stirred solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol (0.3 g) in dichloromethane (3 mL) was added pyridine (3 mL), 1,1'-carbonyldiimidazole (0.68 g) and 4-(dimethylamino)pyridine (0.067 g). The resulting reaction mixture was stirred at 0° C. for 30 minutes. To this above stirred solution, 1-methylpiperidine-2-carboxylic acid (0.592 g) was added and the resulting solution was stirred at room temperature for 16 hours. The reaction mixture was monitored by TLC (mobile phase: 70% ethyl acetate in hexane). After completion of the reaction, the reaction mixture was quenched with water, extracted with dichloromethane (3×100 mL), dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain the crude material. The crude material was purified by preparative HPLC [Method: (A) 0.5% TFA in water (B) 100% acetonitrile] and the product fractions were lyophilized to give (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 1-methylpiperidine-2-carboxylate (0.037 g, 9%) as a yellow solid. LCMS:95.00%(m / z:355.25, [M+1] + , 4.02 min (10 min run), 214 nm). 1 H-NMR (400 MHz, DMSO-d6): δ 7.80 (dd, 1H), 7.73 (d, 1H), 7.43-7.36 (m. 3H), 6.05 (d, 1H), 4.41- 4.55 (m, 1H), 3.47-3.44 (m, 1H), 3.12-3.07 (m, 1H), 2.87 (s, 3H), 2.45-2.25 (m, 2H), 1.83-1.59 (m, 4H)

[0152] Example 21: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl diethylcarbamate [ka] To a solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol hydrochloride (0.200 g) in dichloromethane (10 mL), dicyclohexylcarbodiimide (0.466 g) and 4-(dimethylamino)pyridine (0.046 g) were added and stirred at room temperature for 15 minutes. Then diethylcarbamate (0.114 g) was added and the reaction mixture was stirred at room temperature for 24 hours. After completion of the reaction (monitored by TLC), the reaction mass was quenched with cold water (10 mL), extracted with dichloromethane (3×30 mL), washed with water (2×100 mL), dried over anhydrous sodium sulfate and concentrated under vacuum to obtain crude material. The crude material was purified by preparative HPLC [70% acetonitrile / 30% TFA] to give (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl diethylcarbamate (0.025 g, 10.1%) as a yellow solid. LCMS:99.70%(m / z:329.20, [M+1] + , 5.58 min (10 min run), 214 nm) 1 H NMR (400 MHz, DMSO-d6): δ ppm 8.16-7.87 (m, 2H), 7.68-7.63 (m, 2H), 7.30-7.17 (m. 3H), 6.76 (br s, 2H), 5.98 (d, 1H), 3.46-3.41 (m, 2H), 3.28-3.25 (m, 2H), 1.21 (t, 3H), 1.09 (t. 3H)

[0153] Example 22: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 4-methyl-1,4-diazepane-1-carboxylate [ka] To a stirred solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol hydrochloride (0.500 g) in 10 mL of dichloromethane at 0° C. under nitrogen atmosphere, N,N-diisopropylethylamine (2.43 g) and 1,1′-carbonyldiimidazole (0.918 g) were added followed by 4-(dimethylamino)pyridine (0.116 g). The reaction mixture was stirred at a temperature of 0° C. for 10 minutes and 1-methyl-1,4-diazepane (0.861 g) was added. The reaction mixture was stirred at room temperature for 26 hours. After completion of the reaction, the mixture was quenched with water and extracted with dichloromethane (3×50 mL). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain the crude material. The crude was concentrated by flash chromatography and then purified by preparative HPLC [Method: TFA buffer] and the product fractions were lyophilized to give 0.080 g of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 4-methyl-1,4-diazepane-1-carboxylate HCl salt as a red solid. LCMS: 97.21% (m / z: 370.22 [M+1] + , 4.39 min (10 min run), 214 nm) 1 H NMR (400 MHz, DMSO-d6): δ ppm 7.78 (dd, 1H), 7.72 (d, 1H), 7.39-7.25 (m, 3H), 6.10 (d, 1H), 4.08-3.80 (m, 1H), 3.70-3.68 (m, 2H), 3.62-3.54 (m, 3H), 3.31-3.16 (m, 2H), 2.88 (s, 3H), 2.20-2.01 (m. 2H)

[0154] Example 23: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenylmorpholine-4-carboxylate [ka] To a solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol hydrochloride (0.2 g) in dichloromethane:pyridine (1:1, 5 mL), morpholine 4-carbonyl chloride (0.279 g) was added and stirred at room temperature for 24 h. After completion of the reaction (monitored by TLC), the reaction mass was quenched with cold water (10 mL) and extracted with dichloromethane (3×30 mL). The organic layer was washed with water (2×100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude material. The crude was purified using flash chromatography eluting with 9% methanol in dichloromethane to give (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 4-methylpiperazine-1-carboxylate (0.035 g, 13.5%) as a yellow solid. LCMS: 98.18% (m / z: 341.19 [M+1] + , 4.97 min (10 min run), 214 nm) 1 H NMR (400 MHz, DMSO-d6): δ ppm 8.40 (br s, 1H), 7.68-7.65 (m, 2H), 7.31-7.21 (m, 3H), 6.81 (br s. 2H), 6.01 (d, 1H), 3.65 (br s, 6H), 3.41 (br s. 2H)

[0155] Example 24: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 4-methylpiperazine-1-carboxylate [ka] To a solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol hydrochloride (0.2 g) in dichloromethane (10 mL), 4-methylpiperazine-1-carbonyl chloride (0.305 g) and 4-(dimethylamino)pyridine (0.045 g) were added and stirred at room temperature for 24 hours. After completion of the reaction (monitored by TLC), the reaction mass was quenched with cold water (10 mL) and extracted with dichloromethane (3×30 mL). The organic layer was washed with water (2×100 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude material. The crude material was purified using flash chromatography eluting with 10% methanol:dichloromethane to give (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 4-methylpiperazine-1-carboxylate (0.051 g, 19.1%) as a yellow solid. LCMS:96.78%(m / z:356.20, [M+1] + , 4.75 min (10 min run), 214 nm) 1 H NMR (400 MHz, DMSO-d6): δ ppm 7.68-7.65 (m, 2H), 7.30-7.25 (m, 2H), 7.24-7.19 (m, 1H), 6.79 (br s, 2H), 6.00 (d, 1H), 3.63 (br s, 2H), 3.42 (br s, 2H). 2.41 (br s. 4H), 2.27 (br s. 3H)

[0156] According to the reaction conditions of Example 24 (acyl chloride, DMAP, DCM), the following carbamate prodrugs were synthesized using the respective acyl chlorides obtained as commercial products. [ka]

[0157] Example 26: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl(2-(dimethylamino)ethyl)(methyl)carbamate hydrochloride [ka] To a stirred solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol hydrochloride (0.25 g) in dichloromethane (2.5 mL) and pyridine (2.5 mL) at 0° C., 1,1′-carbonyldiimidadiol (0.456 g) and 4-(dimethylamino)pyridine (0.057 g) were added, and the resulting mixture was stirred at 0° C. for 30 min, followed by addition of N 1 ,N 1 ,N 2 -trimethylethane-1,2-diamine (0.385 g) was added. The reaction mixture was stirred at room temperature for 16 h. Completion of the reaction was monitored by TLC (mobile phase: 10% methanol in dichloromethane). After completion of the reaction, the reaction mixture was quenched with DM water and extracted with dichloromethane (3 x 100 mL). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain the crude material. The crude was purified by preparative HPLC [Method: (A) 0.5% TFA in water (B) 100% acetonitrile] and the product fraction was lyophilized to obtain 0.135 g of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl(2-(dimethylamino)ethyl)(methyl)carbamate hydrochloride as a red solid. LCMS: 98.96% (m / z: 358.25 [M+1] + , 4.33 min (10 min run), 214 nm) 1 H NMR (400 MHz, DMSO-d6): δ ppm 9.54-9.46 (m, 1H), 8.20 (br s, 1H), 7.75-7.72 (m, 2H), 7.36- 7.25 (m, 4H), 6.07 (d, 1H), 3.78 (t, 1H), 3.81-3.62 (m, 2H), 3.39-3.30 (m, 2H), 3.11-2,94 (m, 3H), 2.87-2.83 (m, 6H)

[0158] Following the reaction conditions of Example 26 (CDI, pyridine, DMAP, DCM), the following carbamate prodrugs were synthesized using the respective secondary amines obtained from commercial sources. [ka] [ka] [ka]

[0159] Example 35: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 4-morpholinopiperidine-1-carboxylate [ka] To a solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol hydrochloride (0.2 g) in dichloromethane (10 mL) was added pyridine (0.288 g), 1,1'-carbonyldiimidazole (0.6 g) and 4-(dimethylamino)pyridine (0.046 g) at 0° C. and stirred at room temperature for 30 minutes. Then 4-(piperidin-4-yl)morpholine (0.32 g) was added and the reaction mixture was stirred at room temperature for 48 hours. After completion of the reaction (monitored by TLC), the reaction mass was quenched with cold water (10 mL) and extracted with dichloromethane (3×30 mL). The organic layer was washed with water (2×100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude material. The crude material was purified by preparative HPLC using the TFA method to give (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl 4-morpholinopiperidine-1-carboxylate (0.094 g, 28.9%) as a yellow solid. LCMS:99.74%(m / z:426.24, [M+1] + , 4.10 min (10 min run), 214 nm) 1H NMR (400 MHz, DMSO-d6): δ ppm 9.80 (s, 1H), 8.20 (br s. 1H), 7.74-7.70 (m, 2H), 7.36-7.27 (m, 2H), 7.24-7.21 (m, 1H), 7.14 (br s, 1H), 6.06 (d, 1H), 4.35-4.11 (m, 2H), 4.07-4.04 (m. 2H), 3.73-3.67 (m, 2H), 3.48-3.45 (m, 3H), 3.19-3.09 (m, 3H), 2.93 (br s. 1H), 2.14 (br s, 2H), 1.62 (br s, 2H)

[0160] Following the reaction conditions of Example 35 (CDI, DMAP, DCM), the following carbamate prodrugs were synthesized using the respective secondary amines obtained from commercial sources. [ka] [ka]

[0161] Example 39: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenylethyl carbonate [ka] To a solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol hydrochloride (0.3 g) in dichloromethane (8 mL) was added triethylamine (0.4 mL) and ethyl carbonochloridate (0.183 g) at a temperature of 0° C. The resulting reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction (monitored by TLC), the reaction mass was quenched with cold water (10 mL) and extracted with dichloromethane (3×30 mL). The combined organic layers were washed with water (2×100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by flash chromatography (70% ethyl acetate in hexane) to obtain (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenylethyl carbonate (0.095 g, 28%) as an orange solid. LCMS:97.86%(m / z:302.07, [M+1] + , 4.96 min (10 min run), 214 nm). 1 H-NMR (400 MHz, DMSO-d6): δ 7.70-7.67 (m, 1H), 7.65 (d, 1H), 7.34-7.26 (m, 3H), 6.02 (d, 1H), 4.19 (q, 2H), 1.23 (t, 3H).

[0162] Example 40: Preparation of (E)-N-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)acetamide Step-01: Preparation of (E)-3-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridine-2,6-diamine [ka] To a stirred solution of ((E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol (2.0 g) in dichloromethane (25 mL) was added triethylamine (1.98 mL) and tert-butyldimethylsilyl chloride (2.2 g) at a temperature of 0° C. The resulting reaction mixture was stirred at room temperature for another 4 h. After completion of the reaction (monitored by TLC), the mixture was diluted with water (20 mL) and extracted with dichloromethane (3×70 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by CombiFlash chromatography (using 23% ethyl acetate in heptane) to obtain (E)-3-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridine-2,6-diamine (2.6 g, 99%) as a red solid. LCMS:99.69%(m / z:344.46), [M+1] + , 2.47 min (4 min run), 214 nm). 1 H-NMR (400 MHz, DMSO-d6): δ 7.66 (d, 1H), 7.56 (d, 1H), 7.18 (t, 1H), 6.98 (t, 2H), 6.65 (s. 2H), 5.96 (d, 1H), 0.96 (s. 9H), 0.20 (s, 6H).

[0163] Step-02: Preparation of (E)-N-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)acetamide [ka] To a stirred solution of (E)-3-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridine-2,6-diamine (0.4 g) in dichloromethane (6 mL) was added triethylamine (0.32 mL) and acetyl chloride (0.16 mL) at a temperature of 0° C. The resulting reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction (monitored by TLC), the mixture was diluted with water (20 mL) and extracted with dichloromethane (3×70 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by CombiFlash chromatography (18% ethyl acetate in n-heptane) to obtain (E)-N-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)acetamide (0.350 g, 89%) as a yellow solid. Analysis details: LCMS:95.04%(m / z:385.19), [M+1] + , 2.47 min (4 min run), 214 nm).

[0164] Step-03: Preparation of (E)-N-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)acetamide [ka] To a stirred solution of (E)-N-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)acetamide (0.35 g) in dichloromethane (5 mL) was added trifluoroacetic acid (4 mL) at 0° C. and then the reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction (monitored by TLC), the reaction mass was extracted with dichloromethane (2×20 mL) and then washed with water (2×50 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by ether washing to obtain (E)-N-(6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)acetamide (67 mg, 27.9%) as a yellow solid. LCMS:98.69%(m / z:271.11), [M+1] + , 5.14 min (10 min run), 214 nm). 1 H-NMR (400 MHz, DMSO-d6): δ 8.13 (d, 1H), 7.71 (dd, 1H), 7.40 (d, 1H), 7.29 (t, 1H), 7.01 (d, 1H), 6.93 (t, 1H), 2.10 (s, 3H).

[0165] Example 41: Preparation of methyl (E)-(6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)carbamate Step-01: Preparation of (E)-3-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridine-2,6-diamine [ka] To a stirred solution of ((E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol (2 g) in dichloromethane (25 mL) was added triethylamine (1.98 mL) and tert-butyldimethylsilyl chloride (2.2 g) at a temperature of 0° C. The resulting reaction mixture was stirred at room temperature for another 4 h. After completion of the reaction (monitored by TLC), the mixture was diluted with water (20 mL) and extracted with dichloromethane (3×70 mL). The collected organics were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by CombiFlash chromatography (using 23% ethyl acetate in heptane) to obtain (E)-3-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridine-2,6-diamine (2.6 g, 99%) as a red solid. LCMS:99.69%(m / z:344.46), [M+1] + , 2.47 min (4 min run), 214 nm). 1H-NMR (400 MHz, DMSO-d6): δ 7.66 (d, 1H), 7.56 (d, 1H), 7.18 (t, 1H), 6.98 (t, 2H), 6.65 (s, 2H), 5.96 (d, 1H), 0.96 (s. 9H), 0.20 (s, 6H).

[0166] Step-02: Preparation of methyl (E)-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)carbamate [ka] To a stirred solution of (E)-3-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridine-2,6-diamine (0.3 g) in dichloromethane (6 mL) was added triethylamine (0.2 mL) and methyl chloroformate (0.165 mL) at a temperature of 0° C. The resulting reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction (monitored by TLC), the mixture was diluted with water (20 mL) and extracted with dichloromethane (3×70 mL). The collected organics were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by CombiFlash chromatography (18% ethyl acetate in n-heptane) to obtain methyl (E)-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)carbamate (0.16 g, 50.7%) as a yellow solid. Analysis details: LCMS:80.58%(m / z:402.47), [M+1] + , 2.70 min (4 min run), 214 nm).

[0167] Step-03: Preparation of methyl (E)-(6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)carbamate [ka] To a stirred solution of methyl (E)-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)carbamate (0.16 g) in dichloromethane (5 mL) was added trifluoroacetic acid (2 mL) at a temperature of 0° C. and then the reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction (monitored by TLC), the reaction mass was extracted with dichloromethane (2×20 mL) followed by washing with water (2×50 mL). The collected organics were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by Combiflash chromatography (using 25% ethyl acetate in n-hexane) to obtain methyl (E)-(6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)carbamate (40 mg, 36.3%) as a yellow solid. LCMS:98.84%(m / z:288.13), [M+1] + , 5.77 min (10 min run), 214 nm). 1 H NMR (400 MHz, DMSO-d6): δ 8.09 (d, 1H), 7.69 (dd, 1H), 7.30-7.25 (m, 2H), 6.99 (d, 1H), 6.93 (t, 1H), 3.67 (s, 3H).

[0168] Following the reaction conditions of Example 41 (chloroformate, TEA, DCM), the following carbamate prodrugs were synthesized using the respective chloroformate derivatives obtained commercially. [ka] [ka]

[0169] Example 46: Preparation of octyl (E)-(6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)carbamate: Step-01: Preparation of octyl (E)-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)carbamate [ka] To a stirred solution of (E)-3-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridine-2,6-diamine (0.3 g) in dichloromethane (12 mL) was added triphosgene (0.128 g) and N,N'-diisopropylethylamine (0.25 mL) at a temperature of 0° C. The reaction mixture was stirred for further 15 minutes at the same temperature. Then octanol (0.12 g) was added to the above mixture and stirring was continued for further 16 hours at room temperature. After completion of the reaction (monitored by TLC: 30% ethyl acetate in heptane), the mixture was diluted with water (25 mL) followed by extraction with dichloromethane (3×50 mL). The collected organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude material was purified by flash chromatography (15% ethyl acetate in n-heptane) to give octyl (E)-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)carbamate (0.35 g, 85%) as a brown solid. Analysis details: LCMS:97.04%(m / z:500.17), [M+1] + , 3.09 min (4 min run), 214 nm).

[0170] Step-02: Preparation of octyl (E)-(6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)carbamate [ka] To a stirred solution of octyl (E)-(6-amino-5-((2-((tert-butyldimethylsilyl)oxy)phenyl)diazenyl)pyridin-2-yl)carbamate (0.3 g) in dichloromethane (10 mL) was added trifluoroacetic acid (1.1 mL) at a temperature of 0° C. and the resulting solution was stirred at room temperature for 2 hours. Completion of the reaction was monitored by TLC (70% ethyl acetate in heptane). After completion of the reaction, excess solvent was evaporated under reduced pressure to obtain the crude product. The crude product was purified by washing with n-pentane and then diethyl ether to obtain octyl (E)-(6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)carbamate (0.14 g, 31%) as a red solid. LCMS:99.05%(m / z:386.09), [M+1] + , 4.69 min (10 min run), 214 nm). 1 H-NMR (400 MHz, DMSO-d6): δ 8.09 (d, 1H), 7.70 (d, 1H), 7.26-7.27 (m, 2H), 7.01-6.93 (m, 2H), 4.18-4.00 (m, 2H), 1.65-1.53 ​​(m, 2H), 1.33-1.12 (m, 10H), 0.93-0.53 (m, 3H).

[0171] Following the reaction conditions of Example 46 (triphosgene, DIPEA, DCM), the following carbamate prodrugs were synthesized using the respective alcohol derivatives obtained from commercial sources. [ka] [ka]

[0172] Example 49: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl dihydrogen phosphate Step-01: Preparation of (E)-dibenzyl(2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl)phosphate: [ka] To a stirred solution of tert-butyl (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol hydrochloride (1 g) in tetrahydrofuran (20 mL) was added sodium bis(trimethylsilyl)amide (1M in THF) at a temperature of 0° C. and the resulting mixture was stirred at the same temperature for 15 minutes. Then tetrabenzyl diphosphate (4.6 g) was added at the same temperature and the reaction mixture was kept stirring at room temperature for 30 minutes. After completion of the reaction (monitored by TLC: 50% ethyl acetate in heptane), the mixture was quenched with ammonium chloride and extracted with ethyl acetate. The collected organics were dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product (2 g, crude). The crude product was carried forward to the next step without further purification. LCMS:60.69%(m / z:491.20, [M+1] + , 2.25 min (10 min run), 214 nm).

[0173] Step-02: Preparation of (E)-2-((2.6-diaminopyridin-3-yl)diazenyl)phenyl dihydrogen phosphate [ka] To a stirred solution of (E)-dibenzyl(2-((2,6-diaminopyridin-3-yl)diazenyl)phenyl)phosphate (1 g) in dichloromethane was added bromotrimethylsilane (0.86 mL) at a temperature of 0° C., and the resulting reaction mixture was stirred at room temperature for 15 min. After completion of the reaction (monitored by TLC: 50% ethyl acetate in heptane), excess solvent was evaporated under reduced pressure to obtain crude material. The crude was purified by preparative HPLC [(NH4HCO3 65%, ACN 35%) x bridged column] to obtain (E)-2-((2.6-diaminopyridin-3-yl)diazenyl)phenyl dihydrogen phosphate (0.170 g, 27%) as an orange solid. LCMS:95.67%(m / z:310.04, [M+1] + , 4.24 min (10 min run), 214 nm). 1 H-NMR (400 MHz, DMSO-d6): δ 7.84 (d, 1H), 7.60 (d, 1H), 7.33 (d. 1H), 7.27 (t, 1H), 7.11 (t, 1H), 6.08 (d, 1H).

[0174] Example 50: Preparation of (E)-(2-((2,6-diaminopyridin-3-yl)diazenyl)phenoxy)methyl dihydrogen phosphate Step-01: Preparation of (E)-di-tert-butyl((2-((2,6-diaminopyridin-3-yl)diazenyl)phenoxy)methyl)phosphate [ka] To a stirred solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol hydrochloride (0.3 g) in N,N'-dimethylformamide (6 mL) was added potassium carbonate (0.937 g) followed by di-tert-butyl(chloromethyl)phosphate (1.16 g). The solution was stirred for another 6 h at a temperature of 60° C. After completion of the reaction (monitored by LCMS), the mixture was quenched with water (25 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with cold water, dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain (E)-di-tert-butyl((2-((2,6-diaminopyridin-3-yl)diazenyl)phenoxy)methyl)phosphate (0.500 g, crude). The crude was carried forward to the next step without further purification. LCMS:37.14%(m / z:452.51), [M+1] + , 2.14 min (4 min run), 214 nm).

[0175] Step-02: Preparation of (E)-(2-((2,6-diaminopyridin-3-yl)diazenyl)phenoxy)methyl dihydrogen phosphate [ka] A stirred solution of (E)-di-tert-butyl((2-((2,6-diaminopyridin-3-yl)diazenyl)phenoxy)methyl)phosphate (0.5 g) in dichloromethane (10 mL) at a temperature of 0° C. gave trimethyl dihydrogen phosphate (0.012 g, 3.2%) as a yellow solid. LCMS: 95.81% (m / z: 340.05 [M+1] + , 2.67 min (10 min run), 214 nm). 1 H-NMR (400 MHz, DMSO-d6): δ 7.76 (d, 1H), 7.60 (dd, 1H), 7.33 (d, 1H), 7.26 (t, 1H), 7.05 (t, 1H), 6.02 (d, 1H), 5.55 (d, 2H).

[0176] Example 51: Preparation of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-yl butyrate Step-01: Preparation of 2,6-dinitropyridin-3-ol [ka] To a premixed solution of acetic anhydride (14 mL) and nitric acid (6.2 mL), a solution of 2-nitropyridin-3-ol (5 g) was added dropwise at a temperature of 0° C. The resulting solution was stirred at 0° C. for 2 h followed by stirring at room temperature for another 2 h. After completion of the reaction (monitored by TLC), the reaction mass was quenched with ice water and extracted with dichloromethane (3×150 mL). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain the crude product. This crude product was triturated with n-pentane and then dried under reduced pressure to obtain 2,6-dinitropyridin-3-ol (3.4 g, 51%) as a yellow solid. 1 H NMR (400 MHz, DMSO-d6): δ 10.72 (b s. 1H), 8.53 (d, 1H), 7.89-7.85 (m, 1H).

[0177] Step-02: Preparation of 2,6-diaminopyridin-3-yl butyrate [ka] To a stirred solution of 2,6-dinitropyridin-3-ol (1 g) in dichloromethane (100 mL) was added triethylamine (1.7 mL) and butyryl chloride (1.09 g) at a temperature of 0° C. The resulting mixture was stirred at 50° C. for 2.5 hours. After completion of the reaction (monitored by TLC), the reaction mass was cooled to room temperature and poured into ice water (300 mL). The reaction mass was extracted with ethyl acetate (3×150 mL) followed by washing with water (2×100 mL). The combined organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain 3-((4-methoxybenzyl)oxy)-2,6-dinitropyridine (1 g, crude) as a brown oil. The crude product was carried forward to the next step without purification. 1 H NMR (400 MHz, DMSO-d6): δ 8.47 (d, 1H), 7.75 (d, 1H), 2.17 (t, 2H), 1.55-1.46 (m, 2H), 0.88 (t, 3H)

[0178] Step-03: Preparation of 2,6-diaminopyridin-3-yl butyrate [ka] To a stirred solution of 3-((4-methoxybenzyl)oxy)-2,6-dinitropyridine (1 g) in acetic acid (20 mL) was added iron powder (1.5 g) and the resulting mixture was stirred at room temperature for 1 h. After completion of the reaction (monitored by TLC), the reaction was diluted with ethyl acetate (100 mL). The reaction mass was passed through a celite bed to remove inorganics and washed several times with ethyl acetate. The combined organics were washed with water (2×200 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 3-((4-methoxybenzyl)oxy)pyridine-2,6-diamine as a brown oil (0.80 g, crude). The product was carried forward to the next step without further purification. LCMS:42.03%(m / z:195.22), [M+1] + , 1.24 min (4 min run), 214 nm). 1H NMR (400 MHz, DMSO-d6): δ 6.81 (d, 1H), 5.61 (d, 1H), 5.34 (br s, 4H), 2.54 (t, 2H), 1.65-1.58,(m, 2H), 0.95 (m, 3H)

[0179] Step-04: Preparation of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-yl butyrate [ka] To a stirred solution of sodium nitrite (0.28 g) in water (1.5 mL) was added aniline (0.38 g) and 6N hydrochloric acid (0.56 ml). The resulting mixture was stirred at room temperature for 30 minutes. Then 3-((4-methoxybenzyl)oxy)pyridine-2,6-diamine (0.8 g; dissolved in water: 5.0 mL) was added to the reaction mass and stirred at room temperature for another hour. After completion of the reaction (monitored by TLC), it was quenched with sodium acetate and stirred for 15 minutes. The reaction mixture was extracted with ethyl acetate (3×70 mL), washed with water (2×200 mL) and the collected organics were dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain the crude product. The crude product was purified by flash chromatography (50% ethyl acetate in hexane) to obtain (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-yl butyrate (0.063 g, 5.16%) as a red solid. LCMS:99.14%(m / z:300.07, [M+1] + , 5.49 min (10 min run), 214 nm). 1 H NMR (400 MHz, DMSO-d6): δ 10.38 (s, 1H), 9.38 (s, 1H), 7.91 (d, 2H), 7.55-7.52 (m, 3H), 7.48- 7.44 (m, 1H), 6.95 (br s, 2H), 2.52 (t, 2H), 1.67-1.58 (m, 2H), 0.93 (t, 3H)

[0180] procedure: [ka] [ka]

[0181] Example 56: Preparation of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-yl diethylcarbamate Step-01: Preparation of 2,6-dinitropyridin-3-yl diethylcarbamate [ka] To a stirred solution of 2,6-dinitropyridin-3-ol (0.5 g) in dichloromethane (100 mL) was added N,N'-diisopropylethylamine (0.75 mL) followed by triphosgene (0.4 g) at a temperature of 0 °C. The resulting mixture was stirred at room temperature for 10 minutes. Then diethylamine (0.296 g) was added to the above mixture and stirred at room temperature for another 16 hours. After completion of the reaction (monitored by TLC), water (100 mL) was added and the reaction mass was extracted with ethyl acetate (3 x 150 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to obtain the crude product. This crude product was purified by flash chromatography to obtain 2,6-dinitropyridin-3-yl diethylcarbamate (330 mg, 46%) as a yellow solid. This compound was carried forward to the next step without further purification.

[0182] Step-02: Preparation of 2,6-diaminopyridin-3-yl diethylcarbamate [ka] To a stirred solution of 2,6-dinitropyridin-3-yl diethylcarbamate (330 mg) in acetic acid (20 mL), iron powder (0.063 g) was added and the resulting mixture was stirred at room temperature for 1 h. After completion of the reaction (monitored by TLC), the reaction mass was filtered through Celite and concentrated under reduced pressure to obtain the crude product. The crude product was further dried to obtain 2,6-diaminopyridin-3-yl diethylcarbamate (300, crude) as a brown oil. The product was carried forward to the next step without purification. LCMS:76.50%(m / z:225.05), [M+1] + , 1.17 min (4 min run), 214 nm).

[0183] Step-03: Preparation of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-yl diethylcarbamate [ka] To a stirred solution of aniline (0.381 g) and 6N hydrochloric acid (1 mL) in water (5 mL) was added dropwise a solution of sodium nitrite (0.27 g) in water (1.5 mL) at a temperature of 0° C. The resulting mixture was stirred for 30 minutes at a temperature of 0° C. Then 2,6-diaminopyridin-3-yl diethylcarbamate (0.3 g) was added at a temperature of 0° C. and the resulting reaction mass was stirred for further 1 hour at room temperature. After completion of the reaction (monitored by TLC), the reaction mass was quenched with sodium acetate and the reaction was stirred for further 15 minutes. The reaction mixture was extracted with ethyl acetate (3×70 mL) and washed with water (2×50 mL). The collected organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure to obtain the crude product. The crude material was purified by flash chromatography (50% ethyl acetate in hexanes) to give (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-yl butyrate (0.063 g, 5.2%) as a red solid. LCMS:99.96%(m / z:329.23), [M+1] + , 5.30 min (10 min run), 214 nm). 1H NMR (400 MHz, DMSO-d6): δ 8.79 (br s, 1H), 7.75 (d, 2H), 7.46-7.42 (m, 4H), 7.431-7.27 (m, 1H), 6.68 (br s, 2H), 3.46-3.41 (m, 2H), 3.30-3.28 (m, 2H), 1.19 (t, 3H), 1.13 (t, 3H). [ka] [ka]

[0184] Example 60: Preparation of (E)-2-amino-N-(6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)acetamide Step-1: Preparation of tert-butyl (E)-(2-((6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate [ka] To a stirred solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol (2 g) in N,N-dimethylformamide (20 mL) was added sodium hydride (60% w / w dispersion in mineral oil, 0.87 g) at a temperature of 0° C. and then the reaction mixture was stirred at room temperature for 15 minutes. Thereafter, N-boc-glycine N-hydroxysuccinimide ester (9.5 g) was added to the above solution. The resulting reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction (monitored by TLC, 50% ethyl acetate in n-heptane), the mixture was quenched with ice-cold water (50 mL). The reaction mass was extracted with ethyl acetate (2×50 mL) to obtain the crude product. The crude material was purified by flash chromatography to give 0.18 g of tert-butyl (E)-(2-((6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate as a yellow solid. LCMS purity: 95.31% (m / z:387, [M+1], 0.83 min (4 min run), 214 nm).

[0185] Step-2: Preparation of (E)-2-amino-N-(6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)acetamide [ka] To a stirred solution of tert-butyl (E)-(2-((6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (0.25 g) in dichloromethane (5 mL) was added 4M HCl in 1,4-dioxane (1 mL) at a temperature of 0° C. under nitrogen atmosphere. The resulting reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction (monitored by TLC), the mixture was evaporated under reduced pressure to obtain crude mass. The crude compound was purified by preparative HPLC using trifluoroacetic acid as modifier to obtain 0.11 g of (E)-2-amino-N-(6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)acetamide monotrifluoroacetate as a yellow solid. LCMS purity: 99.22% (m / z: 287. [M+1], 4.66 min (10 min run), 214 nm). 1 H-NMR (400 MHz, DMSO-d6): δ 10.79 (s, 1H), 10.49 (s, 1H), 8.19 (d, 1H), 8.09 (br s, 3H), 7.80 (br s, 2H), 7.73 (d, 1H), 7.50 (br s, 1H), 7.33-7.29 (m, 1H), 7.04 (d, 1H), 6.95-6.91 (m, 1H), 3.87 (br s, 2H).

[0186] Example 61: Preparation of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenylcyclopropanecarboxylate Step-1: Preparation of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenylcyclopropanecarboxylate [ka] To a stirred solution of tert-butyl (E)-(2-((6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (0.5 g, prepared in Example 60, step-1) in dichloromethane (7.5 mL) was added triethylamine (0.45 mL) and the resulting mixture was stirred at 0° C. for 5 minutes. Cyclopropylcarbonyl chloride (0.15 mL) was added to the above reaction mixture and stirred at room temperature for an additional hour. After completion of the reaction as monitored by TLC, the reaction mixture was quenched with cold water (10 mL). The reaction was extracted with dichloromethane (3×15 mL) and then washed with water (2×30 mL). The organics were collected, dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude material. The crude was purified by Combiflash chromatography to give 0.32 g of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenylcyclopropanecarboxylate as a yellow solid. LCMS purity: 72.80% (m / z:455.2, [M+1] + , 453.2[M-1] + , 8.11 min (15 min run), 431 nm).

[0187] Step-2: Preparation of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenylcyclopropanecarboxylate [ka] To a stirred solution of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenylcyclopropanecarboxylate (0.30 g) in dichloromethane (6 mL) was added trifluoroacetic acid (0.5 mL) and the resulting reaction mixture was stirred at room temperature for 1 h. After completion of the reaction as monitored by TLC, the solvent was concentrated under reduced pressure. The resulting crude mass was triturated with diethyl ether to give 0.15 g of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenylcyclopropanecarboxylate as a yellow solid. LCMS purity: 83.55%(m / z:355.0[M+1] + , 353.1[M-1] + , 8.16 min (15 min run), 273 nm).

[0188] Example 62: Preparation of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenylcyclopropanecarboxylate Step-1: Preparation of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenylbutyrate [ka] To a solution of (E)-(2-((6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (0.3 g prepared in Example 60, step 1) in dichloromethane (10 ml), dicyclohexylcarbodiimide (0.698 g) and 4-(dimethylamino)pyridine (0.068 g) were added and the reaction mass was stirred at room temperature for 15 minutes, followed by butyric acid (0.118 g) and the resulting reaction mixture was stirred at room temperature for another 2 hours. After completion of the reaction (monitored by TLC), the reaction was quenched with cold water (10 mL) and extracted with dichloromethane (3×30 mL). The combined organic layers were washed with water (2×10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude material which was purified by preparative HPLC to give 0.21 g of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenyl as a yellow solid. LCMS purity: 45.76% (m / z:457.2, [M+1] + , 455.2[M-1] + , 8.38 min (15 min run), 268 nm).

[0189] Step-2: Preparation of ((E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenylbutyrate [ka] To a stirred solution of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenylbutyrate (0.21 g) in dichloromethane (4 mL) was added trifluoroacetic acid (0.3 mL) and the resulting reaction mixture was stirred at room temperature for 1 h. After completion of the reaction as monitored by TLC, the solvent was concentrated under reduced pressure. The resulting crude mass was triturated with diethyl ether to give 0.080 g of ((E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenylbutyrate as a light brown solid. LCMS purity: 94.48%(m / z:357.2[M+1]+ , 355.1[M-1] + , 8.75 min (15 min run), 268 nm).

[0190] Example 63: Preparation of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenylmorpholine-4-carboxylate Step-1: Preparation of morpholine-4-carbonyl chloride [ka] To a stirred solution of morpholine (4 g) in dichloromethane (40 mL) was added triethylamine (11.2 mL) and triphosgene (20.44 g) at a temperature of 0° C. under nitrogen atmosphere. The resulting reaction mixture was stirred at room temperature for 3 hours. After completion of the reaction (monitored by TLC), the reaction mass was diluted with ice-cold water and then extracted with dichloromethane (3×100 mL). The organic layer was washed with water (3×100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by flash chromatography to obtain 4.52 g of morpholine-4-carbonyl chloride as a pale yellow liquid. 1 H NMR(400MHz, DMSO-d6): δ 3.70-3.64 (m, 8H).

[0191] Step-2: Preparation of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenylmorpholine-4-carboxylate [ka] To a stirred solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenol (2 g) in pyridine (15 mL) and dichloromethane (15 mL) was added morpholine-4-carbonyl chloride (5.2 g). The resulting reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction (monitored by TLC), the reaction mass was quenched with 1 M hydrochloric acid solution and then extracted with dichloromethane (2×50 mL). The combined organic layers were washed with water (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude material. The crude was purified by flash chromatography to obtain 1.02 g of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenylmorpholine-4-carboxylate as a yellow solid. LCMS purity: 96.92% (m / z:343.30, [M+1] + , 1.83 min (4 min run), 214 nm). 1 H NMR (400 MHz, DMSO-d6-D20): δ 7.88 (d, 1H), 7.73 (d, 1H), 7.37 (t, 1H), 7.31 (t, 1H), 7.25 (d, 1H), 6.15 (d, 1H), 3.62-3.65 (m, 6H), 3.37-3.39 (m, 2H).

[0192] Step-3: Preparation of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenylmorpholine-4-carboxylate [ka] Sodium hydride (60% w / w dispersion in mineral oil, 0.19 g) was added portionwise to a stirred solution of (E)-2-((2,6-diaminopyridin-3-yl)diazenyl)phenylmorpholine-4-carboxylate (0.65 g) in N,N-dimethylformamide (7.0 mL) at a temperature of 0° C. The resulting reaction mixture was stirred at 0° C. for 15 minutes. Then, boc-glycine N-hydroxysuccinimide ester (2.07 g) was added to the above solution and the reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction (monitored by TLC), the reaction mass was quenched with ice water followed by extraction using ethyl acetate (3×50 mL). The combined organic layer was washed with water (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude material. The crude material was purified by flash chromatography to give 0.34 g of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenylmorpholine-4-carboxylate as a yellow solid. LCMS purity: 93.16% (m / z:500.13[M+1] + , 498.11[M-1] + , 2.06 min (4 min run), 214 nm). Step-4: Preparation of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenylmorpholine-4-carboxylate

[0193] [ka] To a stirred solution of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenylmorpholine-4-carboxylate (0.3 g) in dichloromethane (2 mL) at a temperature of 0° C. was added 4 M hydrochloric acid in dioxane (1 mL). The resulting reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction (monitored by TLC), the reaction mass was evaporated under reduced pressure to obtain crude material. The crude material was triturated with diethyl ether and then purified using preparative HPLC to obtain 0.12 g of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenylmorpholine-4-carboxylate as a yellow solid. LCMS purity: 95.22%(m / z:400.42.[M+1] + , 4.65 min (10 min run), 214 nm). 1 H NMR (400 MHz, DMSO-d6-D2O): 8.09 (d, 1H), 7.73 (d, 1H), 7.47 (t, 2H), 7.29-7.36 (m, 2H), 3.76- 3.96 (m, 2H), 3.50-3.83 (m, 6H), 3.33-3.40 (m, 2H).

[0194] Example 64: Preparation of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenyl acetate Step-1: Preparation of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenyl acetate [ka] To a stirred solution of tert-butyl (E)-(2-((6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (0.11 g) in dichloromethane (3 mL) was added triethylamine (0.11 ml) followed by acetyl chloride (0.026 ml) at 0° C. The resulting reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction by TLC, the reaction mass was diluted with ice water (10 mL) and washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 0.12 g of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenylacetate as an orange solid. LCMS purity: 93.45% (m / z:427.2, [M-1] + , 6.59 min (10 min run), 273 nm). Step-2: Preparation of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenyl acetate [ka] To a stirred solution of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenyl acetate (0.1 g) in dichloromethane (3 mL) was added trifluoroacetic acid (0.2 mL) at a temperature of 0° C. under nitrogen atmosphere. The resulting reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction by TLC, the reaction mass was diluted with ice water (10 mL) and washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 0.075 g of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenyl acetate as a yellow solid. LCMS purity: 94.83%(m / z:329.0[M+1] + , 327.1[M-1] + , 4.17 min (10 min run), 273 nm).

[0195] Example-65: Preparation of (E)-2-amino-N-(6-amino-5-(2-((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)phenyl)diazenyl)pyridin-2-yl)acetamide Step-1: Preparation of tert-butyl (E)-(2-((6-amino-5-((2-((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)phenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate [ka] To a stirred solution of (E)-(2-((6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (0.1 g, prepared in Example-60, step-1) in tetrahydrofuran (3 ml), triphenylphosphine (0.088 g) and diisopropyl azadicarboxylate (0.068 g) were added sequentially at 0° C. under nitrogen atmosphere, and the resulting reaction mixture was stirred at room temperature for 10 minutes, after which 4-(hydroxymethyl)-5-methyl-1,3-dioxol-2-one (0.050 g) was added. After completion of the reaction by TLC, the reaction mass was diluted with ice water (10 mL) and extracted with ethyl acetate (2×10 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to get the crude mass which was purified by column chromatography using 10% ethyl acetate in petroleum ether to give 0.03 g of tert-butyl (E)-(2-((6-amino-5-(2-((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)phenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate as a brown semi-solid. LCMS purity: 31.28% (m / z:497.2, [M-1] + , 6.91 min (10 min run), 273 nm).

[0196] Step-2: Preparation of (E)-2-amino-N-(6-amino-5-((2-((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)phenyl)diazenyl)pyridin-2-yl)acetamide [ka] To a stirred solution of tert-butyl (E)-(2-((6-amino-5-((2-((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)phenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (0.03 g) in dichloromethane (1.5 mL) was added trifluoroacetic acid (0.1 mL) at a temperature of 0° C. The resulting reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction by TLC, the reaction mass was diluted with ice water (10 mL) and washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 0.015 g of (E)-2-amino-N-(6-amino-5-((2-((5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy)phenyl)diazenyl)pyridin-2-yl)acetamide as an orange solid. LCMS purity: 29.11% (m / z:399.0, [M+1] + , 397.1[M-1] + , 4.71 min (10 min run), 273 nm).

[0197] Example 66: Preparation of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenyl isobutyl carbonate Step-1: Preparation of tert-butyl (E)-(2-((6-amino-5-((2-(isobutoxycarbonyl)oxy)phenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate [ka] To a stirred solution of (E)-(2-((6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (0.10 g; prepared in Example 60, step-1) in dichloromethane (3 mL) was added triethylamine (0.1 mL) followed by isobutyl chloroformate (0.045 mL) at a temperature of 0° C. under nitrogen atmosphere. The resulting reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction by TLC, the reaction mass was diluted with ice-cold water (10 mL) and washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 0.10 g of tert-butyl (E)-(2-((6-amino-5-((2-((isobutoxycarbonyl)oxy)phenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate as a light brown solid. LCMS purity: 97.15% (m / z:487.0, [M+1] + , 485.2[M-1]+, 7.48 min (10 min run), 268 nm).

[0198] Step-2: Preparation of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenyl isobutyl carbonate [ka] To a stirred solution of tert-butyl (E)-(2-((6-amino-5-((2-((isobutoxycarbonyl)oxy)phenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (0.1 g) in dichloromethane (3 mL) was added trifluoroacetic acid (0.3 mL) at a temperature of 0° C. under nitrogen atmosphere. The resulting reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction by TLC, the reaction mass was diluted with ice water (10 mL) and washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 0.07 g of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenyl isobutyl carbonate as a yellow solid. LCMS purity: 94.27%(m / z:487.1[M+1] + , 385.1[M-1] + , 5.22 min (10 min run), 273 nm).

[0199] Example 67: Preparation of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-yl methyl carbonate Step-1: (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenyl 2-morpholinoacetate [ka] To a stirred solution of tert-butyl (E)-(2-((6-amino-5-((2-hydroxyphenyl)diazenyl)pyridin-2-yl)amino)-2-oxoethyl)carbamate (0.10 g, prepared in Example 60, step-1) in dichloromethane (4 mL) was added dicyclohexylcarbodiimide (0.13 g) and 4-(dimethylamino)pyridine (0.039 g) sequentially at a temperature of 0° C. The resulting reaction mixture was stirred at the same temperature for 30 minutes, then 2-morpholinoacetic acid (0.056 g) was added and further stirred at room temperature for 2 hours. After completion of the reaction by TLC, the reaction mass was diluted with ice-cold water (50 mL) and extracted with ethyl acetate (3×200 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude material which was subjected to column chromatography using 30% ethyl acetate in petroleum ether as the mobile phase to give 0.11 g of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenyl 2-morpholinoacetate as a yellow solid. LCMS purity: 69%(m / z:514.1[M+1] + , 512.2[M-1] + , 5.23 min (10 min run), 268 nm).

[0200] Step-2: Preparation of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenyl 2-morpholinoacetate [ka] To a stirred solution of (E)-2-((2-amino-6-(2-((tert-butoxycarbonyl)amino)acetamido)pyridin-3-yl)diazenyl)phenyl 2-morpholinoacetate (0.1 g) in dichloromethane (3 mL) was added trifluoroacetic acid (0.3 mL) at a temperature of 0° C. under nitrogen atmosphere. The resulting reaction mixture was stirred at room temperature for 1 hour. After completion of the reaction by TLC, the reaction mass was diluted with ice-cold water (10 mL) and washed with saturated aqueous sodium bicarbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 0.06 g of (E)-2-((2-amino-6-(2-aminoacetamido)pyridin-3-yl)diazenyl)phenyl 2-morpholinoacetate as a dark orange solid. LCMS purity: 35.50%(m / z:412.2[M-1] + , 3.61 min (10 min run), 273 nm).

[0201] Example 68: Preparation of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-yl methyl carbonate Step-1: Synthesis of (E)-3-bromo-5-(phenyldiazenyl)pyridine-2,6-diamine [ka] To a stirred solution of aniline (2.9 g) in water (5 mL), 6N hydrochloric acid (3.01 g) was added followed by sodium nitrite (2.2 g) at a temperature of 0° C., the resulting suspension was stirred for further 30 minutes at 0° C. and then a solution of 3-bromopyridine-2,6-diamine (5 g) in 6N hydrochloric acid (25 mL) was added dropwise. The resulting reaction mixture was stirred for further 2 hours at room temperature. After completion of the reaction as monitored by TLC, the reaction mass was quenched with sodium acetate (30 mL) and stirred for 15 minutes. The reaction mass was extracted with ethyl acetate (100 mL×3) and then washed with water (300 mL×2). The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by flash chromatography to obtain 2.8 g of (E)-3-bromo-5-(phenyldiazenyl)pyridine-2,6-diamine as a red solid. LCMS purity: 86.73% (m / z:293.92.[M+2] + , 2.16 min (4 min run), 214 nm). 1 H NMR (400 MHz, DMSO-d6): δ 7.90 (s, 1H), 7.70 (d, 2H), 7.46 (t, 2H), 7.34 (t, 2H), 6.85 (br s, 2H).

[0202] Step-2: Synthesis of (E)-3-(phenyldiazenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2,6-diamine [ka] To a stirred solution of (E)-3-bromo-5-(phenyldiazenyl)pyridine-2,6-diamine (2.8 g) in dioxane (30 mL) was added bis(pinacolato)diborane (14.4 g), potassium acetate (1.41 g), and tricyclohexylphosphine tetrafluoroborate (0.353 g) at room temperature. The reaction mixture was degassed with a continuous flow of argon gas for next 15 minutes. Then Pd2(dba)3.CHCl3 (0.496 g) was added and the resulting reaction mixture was stirred at 80° C. for 3 hours. After completion of the reaction (monitored by TLC), the reaction mass was cooled to room temperature and diluted with ethyl acetate (100 mL). The organic layer was washed with water (150 mL×2), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude material was purified by flash chromatography to give 2.2 g of (E)-3-(phenyldiazenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2,6-diamine as a yellow solid. LCMS purity: 75% (m / z:340.33, [M+1] + , 2.44 min (4 min run), 214 nm). 1 H NMR (400 MHz, DMSO-d6): δ 8.03 (s, 1H), 7.77 (d, 2H), 7.46 (t, 2H), 7.34 (t, 1H), 6.88 (s, 1H), 6.55 (s, 1H), 6.26 (s, 1H), 1.30 (s. 9H), 1.16 (s, 3H).

[0203] Step-3: Synthesis of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-ol [ka] To a stirred solution of (E)-3-(phenyldiazenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2,6-diamine (2.2 g) in tetrahydrofuran (40 mL), hydrogen peroxide (0.424 g) was added and the resulting solution was stirred at room temperature for 2 hours. After completion of the reaction as monitored by TLC, the reaction mass was diluted with ethyl acetate (40 mL). The organic layer was washed with water (100 mL x 2), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by preparative HPLC using trifluoroacetic acid as a modifier to obtain 0.44 g of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-ol as a red solid. LCMS purity: 97% (m / z:230.03, [M+1] + , 1.43 min (6 min run), 214 nm). 1 H NMR (400 MHz, DMSO-d6): δ 7.68 (d, 2H), 7.37 (t, 2H), 7.10 (t, 1H), 7.06 (s, 1H), (s, 3H). Step-4: Synthesis of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-ylmethyl carbonate [ka] To a stirred solution of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-ol (0.08 g) in dichloromethane (3 mL) was added triethylamine (0.045 g) and methyl chloroformate (0.039 g) at a temperature of 0° C. and the resulting reaction mixture was stirred at room temperature for 10 minutes. After completion of the reaction as monitored by TLC, the reaction mass was quenched with water (3 mL), extracted with dichloromethane (3×30 mL), washed with brine (2×100 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude product. The crude product was purified by preparative HPLC using trifluoroacetic acid as a modifier to obtain 0.018 g of (E)-2,6-diamino-5-(phenyldiazenyl)pyridin-3-ylmethyl carbonate as a brown solid. LCMS purity: 98.09%(m / z:288.10[M+1] + , 4.84 min (10 min run), 214 nm). 1 H NMR (400 MHz, DMSO-d6-D2O): δ 7.81 (d, J = 8.00 Hz, 2H), 7.52-7.49 (m. 3H), 7.42 (t, J = 7.20 Hz, 1H), 3.65 (s. 3H).

[0204] Example 69. Gene expression analysis Study design: To evaluate the effect of the test compound on pain-related markers, human urothelial “RT4 (human bladder cancer cells)” cells were treated with the test compound in combination with cyclophosphamide (CYP) and gene expression analysis of pain-related genes was performed. 6 Cells were treated with cyclophosphamide and test compounds. Cells were cultured at 37°C for 4 hours. Experimental groups: Group 1: untreated cells, Group 2: CYP treatment (100 μM CYP), Group 3: CYP + Compound IX (100 μM CYP + 10 μM Compound IX).

[0205] After 4 hours of incubation, the medium was removed from all wells and the cells were washed once with sterile PBS. RNA isolation was performed using Qiagen RNA mini kit (cat. no. 74104) according to the manufacturer's instructions. Subsequently, cDNA synthesis was performed using 3 μg of total RNA from each sample using Superscript III First strand cDNA synthesis system (Thermo fisher, cat. no. 18080051). qRT-PCR was performed using SYBR green master mix (PCR Biosystems, cat. no.:-PB20.14) and primers specific for the P2RX3 gene. After PCR, the data were analyzed using CFX manager software. The fold change in expression was calculated using the following formula: 2^-ddCT=2^-(CT target-CT internal control).

[0206] Results: As shown in Figure 1, when RT4 cells were treated with CYP for 4 hours, the gene expression of P2RX3 was increased compared to the control cells (untreated). Interestingly, the cells treated with CYP at a concentration of 10 μM of test compound IX showed a decrease in the expression of the P2RX3 gene compared to the CYP control.

[0207] Example 70. Pain assessment - CFA model Study Design: To evaluate the effect of test compounds on inflammatory pain, complete Freund's adjuvant (CFA) was used as an inducer to develop inflammation, and pain responses were measured based on the pain threshold (PWT) of hind paw withdrawal. Mechanical allodynia was induced by injecting CFA emulsion (75ug / 150μl / rat) into the intraplantar surface of the rat hind paw. After CFA injection, baseline ipsilateral PWT (iPWT) was measured using a Von Frey apparatus. Rats were acclimated to the testing room approximately 30 minutes before the start of the experiment and before Von Frey testing. To determine the lowest mechanical threshold, a 2g filament was attached to the hind paw, and if there was no withdrawal response within 3 seconds, the force was increased to prompt the use of the next filament. Conversely, if there was a withdrawal response of the hind paw within 3 seconds, the force was decreased to prompt the use of the next filament. Animals with iPWT≦4g were considered hyperalgesic and were used in the study. Group I: vehicle control, Group 2: CFA control (75 μg / 150 μl, oral (PO)), Group 3: CFA + Compound XI (20 mg / kg, PO), Group 4: CFA + Compound XI (5 mg / kg, IV), Group 5: CFA + naproxen (20 mg / kg, PO), Group 6: CFA + gabapentin (100 mg / kg, IP). Naproxen and gabapentin were used as reference standards. PWTs were recorded at 0.5 and 4 hours after administration. Calculation of % maximum possible effect (MPE) of mechanical allodynia was performed using the following formula: [ka] where 15 = the cut-off threshold (strongest force) of mechanical allodynia in mice. The %MPE is shown in FIG.

[0208] Example 71. Pain assessment - SNL model Study Design: To assess the effect of test compounds on neuropathic pain, the spinal nerve ligation (SNL) technique was used to measure pain responses based on paw withdrawal pain threshold (PWT).

[0209] A longitudinal incision was made at the lower lumbar and sacral levels, and muscles and connective tissues were removed. The L6 transverse process covering the L4 and L5 spinal nerves was excised, and the L5 and L6 spinal nerves were tightly ligated in the SNL group, whereas only a longitudinal incision was made in the sham control group. Antibiotics were administered after surgery. PWT was measured by placing the tip of the transducer on the central part of the hind paw of the rat and applying linear pressure until a clear withdrawal response was observed. Each measurement was repeated three times with a 5-minute interval between each measurement, and the average pressure value was recorded as the final PWT record. On the 6th day after SNL surgery, rats were placed in a dynamic plantar esthesiometer device for 30 min to allow them to acclimate, and baseline responses were measured. Animals corresponding to a pain force of approximately 20 g were selected and randomized into various groups, including group 1: sham control (no SNL), group 2: vehicle control (SNL), group 3: SNL + Compound XI (20 mg / kg, PO), group 4: SNL + Compound XI (5 mg / kg, IV), and group 5: SNL + Gabapentin (100 mg / kg, PO). After a single dose of Compound XI was administered on the 7th day after surgery, rats were allowed to acclimate for 15 min, and mechanical allodynia-hind paw withdrawal pain threshold (PWT) was recorded 1 and 4 hours after administration using a dynamic plantar esthesiometer. The maximum force was 50 g, and the ramp was 20 seconds. After the average PWT recording was completed, the % change in average PWT compared to vehicle control was calculated (Figure 3).

[0210] Example 72 - Efficacy of compounds in acute cyclophosphamide (CYP)-induced cystitis model Experimental system.--Female SD rats (6-8 weeks old) were used in the study. Test protocol - Acute interstitial cystitis was induced in experimental animals by a single intraperitoneal administration of cyclophosphamide at a dose of 150 mg / kg body weight. Test groups, doses, and route of administration (ROA) are shown in the table. The normal control group received saline. Test compounds were administered 30 min before cyclophosphamide administration. The reference compound ibuprofen was administered 1 h before cyclophosphamide administration. The control group received vehicle only. Nociceptive responses were assessed before CYP or saline injection (basal, 0 h) and 4 h after CYP administration. Von Frey filaments of increasing force were applied to the lower abdomen close to the bladder. The animals were sacrificed and the bladder was removed via a low midline laparotomy. [ka]

[0211] FIG. 4 shows the AUC of the nociceptive pain score 4 hours after CYP administration.

[0212] Example 73 - Efficacy of Compound XI in a chronic cyclophosphamide (CYP)-induced cystitis model Experimental system.--Studies were performed in female SD rats (6-7 weeks old). Test Protocol-Chronic interstitial cystitis was induced by intraperitoneal administration of cyclophosphamide at a dose of 50 mg / kg body weight on days 0, 3, and 6. The normal control group was administered saline. On day 7, nociceptive responses were evaluated using Von Frey filaments. Prior to testing, the lower abdomen of each animal was shaved and mechanically stimulated. A Von Frey filament was applied successively with a graded force of 1-60 g, and pain behavior was recorded according to the Pain Behavior Rating Scale. Animals were randomized into different treatment groups based on body weight as the primary criterion, and pain score as the secondary criterion. Animals that showed optimal pain responses were selected for randomization, and the mean pain scores of each group were found to be within ±10%. The test items, doses, number of doses, and route of administration are shown in the table below. The test compound or reference compound was administered for 3 days from day 8 to day 10. The test compound was administered orally once or twice a day as shown in the test design table. Ibuprofen was administered orally once a day for 3 days. The control group received the vehicle only. After the final dose on day 10, nociceptive behavior was recorded 1 h after dosing. [ka] Intraperitoneal, QD - once a day, BID - twice a day FIG. 5 shows the AUC pain scores on day 10 (3 days after treatment).

[0213] Example 74 - Efficacy of compounds in acute cyclophosphamide (CYP)-induced cystitis model Experimental system.--Female SD rats (6-7 weeks old) were used in the study. Test protocol - Acute interstitial cystitis was induced in experimental animals by a single intraperitoneal administration of cyclophosphamide at a dose of 150 mg / kg body weight. Test groups, doses, and route of administration (ROA) are shown in the table. The normal control group received saline. Test compounds were administered 30 min before cyclophosphamide administration. The reference compound ibuprofen was administered 1 h before cyclophosphamide administration. The control group received vehicle only. Nociceptive responses were assessed before CYP or saline injection (basal, 0 h) and 4 h after CYP administration. Von Frey filaments of increasing force were applied to the lower abdomen close to the bladder. The animals were sacrificed and the bladder was removed via a low midline laparotomy. [ka]

[0214] Figure 6 shows the AUC pain score 4 hours after CYP injection. Example - Efficacy of compounds on acute cyclophosphamide (CYP)-induced cystitis model

[0215] Experimental system: Female SD rats (6-7 weeks old) were used in the study. Test protocol - Acute interstitial cystitis was induced in experimental animals by a single intraperitoneal administration of cyclophosphamide at a dose of 150 mg / kg body weight. Test groups, doses, and route of administration (ROA) are shown in the table. The normal control group received saline. Test compounds were administered 30 min before cyclophosphamide administration. The reference compound, ibuprofen, was administered 1 h before cyclophosphamide administration. The control group received vehicle only. Nociceptive responses were assessed before CYP or saline injection (basal, 0 h) and 4 h after CYP administration. Von Frey filaments of increasing force were applied to the lower abdomen close to the bladder. The animals were sacrificed and the bladder was removed via a low midline laparotomy. [ka]

[0216] FIG. 7 shows the AUC pain scores 4 hours after CYP injection.

[0217] Example 75: Pharmacokinetic data in rats The objective of this study is to evaluate the pharmacokinetic exposure of Compound XI along with Compound No. 12 / Compound No. 43 / Compound No. 446 / Compound No. 449 / Compound XIII / Compound No. 54 following oral dosing at 31.2 mg / kg Compound No. 12, 32.8 mg / kg Compound No. 43, 34.8 mg / kg Compound No. 446, 25 mg / kg Compound No. 449, 21.2 mg / kg Compound XIII, and 27 mg / kg Compound No. 54 in female Sprague Dawley rats. The study was conducted in overnight fasted female Sprague Dawley rats. Dose formulations were freshly prepared on the day of dosing. 0.1% tween-80 + 99.9% 0.5% CMC was used as the vehicle to prepare the dose formulations.

[0218] Blood samples were collected by retro orbital plexus puncture before dosing and at 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after dosing. At each time point, blood was drawn and transferred to pre-labeled microcentrifuge tubes containing anticoagulant. Tubes were gently mixed by inversion to facilitate mixing of anticoagulant with blood. All blood / plasma samples were analyzed using a tailored LC-MS / MS method.

[0219] Pharmacokinetic parameters were calculated using standard non-compartmental analysis (Phoenix® software, version 8.3, Pharsight Corporation, Mountain View, California 94040 / USA) by the linear trapezoidal method with linear interpolation.

[0220] Table: Arithmetic mean pharmacokinetic parameters of Compound No. 12 / Compound No. 43 / Compound No. 446 / Compound No. 449 / Compound No. XIII / Compound No. 54 and Compound XI following single oral administration of Compound No. 12 / Compound No. 43 / Compound No. 446 / Compound No. 449 / Compound No. XIII / Compound No. 54 to Sprague Dawley rats [ka] NC - Not calculated

[0221] Example 76 - Effect of Compound XI on bladder pressure Experimental system: Female SD rats (7-9 weeks old) were used for the study. Test protocol - Acute interstitial cystitis was induced in experimental animals by a single intraperitoneal administration of cyclophosphamide at a dose of 150 mg / kg body weight. Test groups, doses and route of administration (ROA) are shown in the table. The normal control group received saline. The test compounds were administered 30 min before cyclophosphamide administration. The control group received vehicle only. The rats were anesthetized and their body temperature was constantly monitored and maintained at 36.5°C ± 0.2°C by a temperature probe and a heat lamp. The bladder was cannulated and connected at one end to a pressure transducer and at the other end to an infusion pump (Harvard Apparatus). The pressure transducer was connected to a data acquisition system and a computer via an amplifier. Lab chart Version 8.8.2 software was used for recording. The infusion pump was started, allowing the infusion of saline at 100 μL / min. In this way, the bladder was filled at a constant rate and the average bladder pressure was recorded and is shown in Figure 14.

Claims

1. A compound of formula I, a pharma- ceutically acceptable salt, or solvate thereof. 【Chemistry 1】 (In the formula, R １ and R ３ are the same or different and independently represent hydrogen, 【Chemistry 2】 and 【Chemistry 3】 is selected from; ２ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R ４ is an optionally substituted alkyl, alkenyl, alkynyl, -(CH ２ -CH ２ -O) ｎ -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R ５ is hydrogen, -OH, -OR ８ , and the following: 【Chemistry 4】 is selected from; ９ is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, or an amino acid linked via an ester or amide bond at the attachment point, -(CH ２ -CH ２ -O) ｎ - or NR １０ R １１ where n is 1 to 20; R １０ and R １１ are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R ８ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R ６ is a phenylene group, and the phenylene group is R ７ is substituted 0 to 4 times by R ７ is hydrogen, -OH, -OR １２ ,below: 【Chemistry 5】 【Chemistry 6】 and 【Chemistry 7】 is selected from; １２ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R １３ is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked through an ester or amide bond at the point of attachment, -(CH ２ -CH ２ -O) ｎ - or NR １４ R １５ where n is 1 to 20; R １４ and R １５ are each independently selected from hydrogen, optionally substituted alkyl, heterocycloalkyl, and aryl groups; R １６ is an optionally substituted alkylene (C １～６ ) groups; １ , R ３ , R ５ , R ７ All substitutions in R ６ is not hydrogen when R is phenylene; １ Or R ３ is other than hydrogen, ６ When R is phenylene, ５ and R ７ is not hydrogen; R １ , R ３ , R ７ When the substituent in is hydrogen, R ５ is not -OH, but R １ , R ３ , R ５ is hydrogen; R ６ When is phenylene, a single R ７ The substitution is at either the ortho or para position by -OH or O-(alkyl １～３ ) but;R １ , R ３ is hydrogen; ５ is —OH, and R ６ When is phenylene, R on the phenylene ７ The substitution is not at the -OH para position.

2. A compound of formula IA, a pharma- ceutically acceptable salt, or solvate thereof. 【Chemistry 8】 (In the formula, R １ and R ３ are the same or different and independently represent hydrogen, 【Chemistry 9】 【Chemistry 10】 and 【Chemistry 11】 is selected from; ２ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R ４ is an optionally substituted alkyl, alkenyl, alkynyl, -(CH ２ -CH ２ -O) ｎ -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R １７ is selected from optionally substituted linear or branched alkylene groups, the alkylene being optionally substituted with amino groups, alkylamino groups, and dialkylamino groups; R １８ NH ２ , -NR ２０ R ２１ is selected from R ２０ and R ２１ are each independently hydrogen, optionally substituted alkyl, -C(O)-R ２２ is selected from R ２２ is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R ５ is hydrogen, -OH, -OR ８ , and the following: 【Chemistry 12】 is selected from; ９ is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked via an ester or amide bond at the attachment point, -(CH ２ -CH ２ -O) ｎ - or NR １０ R １１ where n is 1 to 20; R １０ and R １１ are the same or different and are independently selected from hydrogen or an optionally substituted alkyl group, a cycloalkyl group, an aryl group, a heterocycloalkyl group, and a heteroaryl group; R ８ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R ６ is a phenylene group, and the phenylene group is R ７ is substituted 0 to 4 times by R ７ is hydrogen, -OH, -OR １２ ,below: 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 , and -R １９ is selected from; １２ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R １３ is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked through an ester or amide bond at the point of attachment, -(CH ２ -CH ２ -O) ｎ - or NR １４ R １５ where n is 1 to 20; R １４ and R １５ are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R １６ is an optionally substituted alkylene （Ｃ１～６） R １９ is -O-R ２３ -O-C(O)-R ２４ , -O-C(O)-R ２３ -R ２７ , and O-R ２３ -R ２８ is selected from; ２３ is an optionally substituted linear or branched alkylene; R ２４ is an optionally substituted alkoxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, aryloxy group, and N(R ２５ R ２６ ) selected from R ２５ , R ２６ are each independently selected from hydrogen, optionally substituted alkyl, and aryl, where alkyl and aryl are optionally substituted from OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups, or R ２５ and R ２６ taken together form an optionally substituted heterocycloalkyl ring, said heterocycloalkyl ring being optionally substituted with alkyl, hydroxyalkyl, -OH, -SH, F, Cl, Br, I, and optionally substituted amino groups; R ２７ is an optionally substituted alkyl group, cycloalkyl group, heterocycloalkyl group, heteroaryl group, aryl group, and N(R ２５ R ２６ ) group; R ２８ is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R ２８ Heterocycloalkyl, heteroaryl in are optionally substituted with alkyl groups, hydroxyalkyl groups, OH, SH, F, Cl, Br, I, and optionally substituted amino and oxo groups; R ２９ and R ３０ are each independently hydrogen, and R ２３ -OC(O)-OR ３１ is selected from; ３１ is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups; １ , R ３ , R ５ , R ７ The substitution of R ６ is phenylene, R is not all hydrogen; １ Or R ３ is other than hydrogen, and R ６ When R is phenylene, ５ and R ７ is not hydrogen; R １ , R ３ , R ７ When the substitution of is hydrogen, R ５ is not -OH; １ , R ３ , R ５ is hydrogen; ６ When is phenylene, a single R ７ The substituents are -OH or O-(alkyl) at either the ortho or para positions. １～３ ) but;R １ , R ３ is hydrogen; ５ is —OH, and R ６ When is phenylene, R on the phenylene ７ The substituent is not in the para position of -OH.

3. R ４ is an alkyl group optionally bearing one or more substituents selected from amino, alkylamino, dialkylamino, or optionally substituted heterocycloalkyl; or R ４ 2. The compound of claim 1, wherein is an aryl group optionally bearing one or more substituents selected from optionally substituted amino acid side chains.

4. R ９ is an alkyl group, optionally bearing one or more substituents selected from alkyl ester, amino, and optionally substituted heterocycloalkyl; or R ９ is a heterocycloalkyl group, optionally bearing one or more substituents selected from alkyl, amino, alkylamino, dialkylamino, aryl, or an optionally substituted heterocycle, said optionally substituted heterocycle being substituted with alkyl; or R ９ is an aryloxy group, optionally bearing one or more substituents selected from the group consisting of an amino acid residue or an amino acid side chain; The compound of claim 1.

5. R １０ and R １１ The compound of claim 1 , wherein is an alkyl group, optionally bearing one or more substituents selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl.

6. R １３ is an alkyl group optionally substituted with one or more substituents selected from hydroxy, aryl, amino, alkylamino, dialkylamino, alkylalcohol, heterocycloalkyl, or substituted heterocycloalkyl; or R １３ is an alkoxy group optionally substituted with one or more substituents selected from amino, alkylamino, dialkylamino, heterocycloalkyl, or substituted heterocycloalkyl; or R １３ is heterocycloalkyl optionally substituted with one or more substituents selected from hydroxy, amino, carboxy, alkyl, alkylamino, dialkylamino, heterocycle, substituted heterocycle, said substituted heterocycle being substituted with alkyl; or R １３ The compound of claim 1 , wherein is heterocycloalkyloxy optionally substituted with one or more substituents selected from alkyl groups.

7. R １４ and R １５ is an alkyl group optionally substituted with one or more substituents selected from a carboxy group, an amino group, an alkylamino group, a dialkylamino group, a heterocycloalkyl group, or a substituted heterocycloalkyl group; or R １４ and R １５ is a heterocycloalkyl optionally substituted with one or more substituents selected from alkyl, heterocycle, or substituted heterocycle, said substituted heterocycle being substituted with alkyl; or R １４ and R １５ 2. The compound of claim 1, wherein R is an aryl group optionally substituted with one or more substituents selected from a heterocyclic group or a substituted heterocycloalkyl group, said substituted heterocyclic group being substituted with an alkyl group.

8. 2. The compound of claim 1 which is a compound of formula II, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 17】 (In the formula, R １ and R ３ are independently hydrogen, 【Chemistry 18】 and 【Chemistry 19】 is selected from; ２ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R ４ is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, (CH ２ -CH ２ —O) n-, or heteroaryl; where n is 1 to 20; R ５ is hydrogen, OH, -OR ８ , and the following: 【Chemistry 20】 is selected from; ９ is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked via an ester or amide bond at the attachment point, -(CH ２ -CH ２ -O) ｎ - or NR １０ R １１ where n is 1 to 20; R １０ and R １１ are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R ８ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R ７ and R ’ ７ are the same or different and independently represent hydrogen, OH, -OR １２ ,below: 【Chemistry 21】 【Chemical 22】 and 【Chemistry 23】 is selected from; １２ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R １３ is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, heterocycloalkyloxy, aminoaryl, or an amino acid linked through an ester or amide bond at the point of attachment, -(CH ２ -CH ２ -O) ｎ - or NR １４ R １５ where n is 1 to 20; R １４ and R １５ are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R １６ is an optionally substituted alkylene (C １～６ ) groups; １ , R ３ , R ５ , R ７ and R ’ ７ All the substitutions in R are not hydrogen at the same time; １ Or R ３ If any one of the substitutions in is not hydrogen, then R ５ , R ７ and R ’ ７ is not hydrogen; R １ , R ３ , R ７ and R ’ ７ When the substitution in is hydrogen, R ５ is not -OH; １ , R ３ , R ５ and R ’ ７ When the substitution in is hydrogen, R ７ is -OH or O-(alkyl １～３ ) but;R １ , R ３ , R ５ and R ７ When the substitution in is hydrogen, R ’ ７ is -OH or O-(alkyl １～３ ) but;R １ , R ３ and R ７ When the substitution in is hydrogen, R ５ and R ’ ７ Neither of these is -OH.)

9. 2. The compound of claim 1 which is a compound of formula III, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 24】 (In the formula, R １ is hydrogen, and the following: 【Chemistry 25】 , and 【Chemistry 26】 is selected from; ３ Below: 【Chemistry 27】 , and 【Chemistry 28】 is selected from R ２ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, or heteroaryl; R ４ is an optionally substituted alkyl, alkenyl, alkynyl, (CH ２ -CH ２ —O) n-, cycloalkyl, heterocycloalkyl, or heteroaryl; where n is 1 to 20; R ５ Yes - OR ８ and: 【Chemical 29】 is selected from R ９ is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked via an ester or amide bond at the point of attachment, -(CH ２ -CH ２ -O) ｎ - or N １０ R １１ R １０ and R １１ are the same or different and are independently selected from hydrogen, optionally substituted alkyl; where n is 1 to 20; R １０ and R １１ The alkyl group represented by R may be optionally substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl; ８ is selected from the group consisting of hydrogen; optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

10. 10. The compound of claim 9, which is a compound selected from the group consisting of: a pharma- ceutically acceptable salt or solvate thereof. 【Chemistry 30】

11. The compound of claim 1 which is a compound of formula III-A, a pharma- ceutically acceptable salt or solvate thereof. 【Chemistry 31】 (In the formula, R １ Below: 【Chemistry 32】 and 【Chemical 33】 is selected from; ２ is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, or heteroaryl; R ４ is an optionally substituted alkyl, alkenyl, alkynyl, -(CH ２ -CH ２ -O) ｎ -, cycloalkyl, heterocycloalkyl, or heteroaryl; where n is 1 to 20; R ５ Yes - OR ８ and the following: 【Chemical 34】 is selected from; ９ is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, alkyl-ester, an amino acid linked via an ester or amide bond at the point of attachment, -(CH ２ -CH ２ -O) ｎ - or N １０ R １１ where n is 1 to 20; R １０ and R １１ is independently selected from hydrogen, optionally substituted alkyl; R １０ and R １１ The alkyl group represented by the formula (I) may be optionally substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl; ８ is selected from the group consisting of hydrogen; optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

12. 12. The compound of claim 11, which is a compound selected from the group consisting of: a pharma- ceutically acceptable salt or solvate thereof. 【Chemistry 35】 【Chemical 36】 13. The compound of claim 1, which is a compound of formula III-B, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemical 37】 (wherein R 5 is —OR 8 and the following: 【Chemical 38】 R 9 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, (CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, alkyl-ester, an amino acid linked at the attachment point through an ester or amide bond, or N 10 R 11 , where n is 1-20 and R 10 and R 11 are independently selected from hydrogen, optionally substituted alkyl; the alkyl groups represented by R 10 and R 11 may be optionally substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl; R 8 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

14. The compound described in claim 13, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemical Formula 39】 【Chemistry 40】 15. The compound of claim 1, which is a compound of formula III-C, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 41】 (In the formula, R 3 is the following: 【Chemistry 42】 and 【Chemistry 43】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, or heteroaryl; where n is 1 to 20; R 5 is -OR 8 and the following: 【Chemistry 44】 wherein R 9 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, alkyl-ester, an amino acid linked through an ester or amide bond at the point of attachment, -(CH 2 -CH 2 -O) n -, or R 10 R 11 ; wherein n is 1 to 20; R 10 and R 11 are independently selected from hydrogen, optionally substituted alkyl; the alkyl groups represented by R 10 and R 11 may be optionally substituted with a group selected from amino, alkylamino, dialkylamino, and optionally substituted heterocycloalkyl; and R 8 is selected from the group consisting of hydrogen; optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl.

16. The compound described in claim 15, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 45】 17. The compound of claim 1, which is a compound of formula IV, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 46】 (In the formula, R 1 and R 3 are independently hydrogen, 【Chemistry 47】 and 【Chemistry 48】 wherein R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; and R 5 is selected from the group consisting of hydrogen, -OR 8 , halogen, and the following: 【Chemistry 49】 R 9 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, alkyl-ester, alkoxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH 2 -CH 2 -O) n - or NR 10 R 11 , where n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R 8 is selected from the group consisting of hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 7 is hydrogen, OH, -OR 12 , or the following: 【Chemistry 50】 【Chemistry 51】 and 【Chemistry 52】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is selected from an optionally substituted alkylene(C 1-6 ) group; With the proviso that all substitutions of R 1 , R 3 , R 5 and R 7 are not hydrogen at the same time; when any substitution of R 1 or R 3 is not hydrogen, R 5 and R 7 are not hydrogen; when substitutions of R 1 , R 3 , R 7 are hydrogen, R 5 is not -OH; when substitutions of R 1 , R 3 , R 5 are hydrogen, R 7 is not -OH or O-(alkyl 1-3 ); when substitutions of R 1 , R 3 are hydrogen, R 5 and R 7 are not both -OH.

18. The compound of claim 1, which is a compound of formula IV-A, a pharma- ceutically acceptable salt or solvate thereof. 【Chemistry 53】 (In the formula, R 1 is the following: 【Chemical Formula 54】 and 【Chemistry 55】 wherein R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 5 is -OR 8 and the following: 【Chemistry 56】 R 9 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the point of attachment, -(CH 2 -CH 2 -O) n -, or NR 10 R 11 ; where n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R 8 is selected from the group consisting of hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 7 is -OH, -OR 12 , or the following: 【Chemistry 57】 【Chemistry 58】 and 【Chemistry 59】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 , where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is an optionally substituted alkylene(C 1-6 ) group.

19. The compound of claim 18, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 60】 20. The compound of claim 1, which is a compound of formula IV-B, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 61】 (In the formula, R 3 is the following: 【Chemistry 62】 and 【Chemistry 63】 wherein R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; and R 5 is -OH, -OR 8 , and the following: 【Chemistry 64】 R 9 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the point of attachment, -(CH 2 -CH 2 -O) n -, or NR 10 R 11 ; where n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R 8 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 7 is -OH, -OR 12 , or the following: 【Chemistry 65】 【Chemistry 66】 and 【Chemistry 67】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 , where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is an optionally substituted alkylene(C 1-6 ) group.

21. The compound of claim 1, which is a compound of formula IV-C, a pharma- ceutically acceptable salt or solvate thereof. 【Chemistry 68】 (In the formula, R 5 is —OH, —OR 8 , or the following: 【Chemistry 69】 R 9 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the point of attachment, -(CH 2 -CH 2 -O) n -, or NR 10 R 11 ; where n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R 8 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 7 is -OH, -OR 12 , or the following: 【Chemistry 70】 【Chemistry 71】 and 【Chemical Formula 72】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is an optionally substituted alkylene(C 1-6 ) group; with the proviso that both R 5 and R 7 are not -OH.

22. The compound of claim 21, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemical 73】 23. The compound of claim 1, which is a compound of formula V, a pharma- ceutically acceptable salt or solvate thereof: 【Chemical 74】 (In the formula, R 1 and R 3 are the same or different and independently represent hydrogen, 【Chemistry 75】 and 【Chemical Formula 76】 wherein R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; and R 5 is hydrogen, OH, OR 8 , halogen, 【Chemical 77】 R 9 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the point of attachment, -(CH 2 -CH 2 -O) n -, or NR 10 R 11 ; where n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R 8 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R' 7 is hydrogen, OH, -OR 12 , and the following: 【Chemical 78】 【Chemical Formula 79】 【Chemistry 80】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is selected from an optionally substituted alkylene(C 1-6 ) group; With the proviso that all substitutions at R 1 , R 3 , R 5 and R ' 7 are not hydrogen at the same time; if any one substitution at R 1 or R 3 is not hydrogen, then R 5 and R ' 7 are not hydrogen; if the substitutions at R 1 , R 3 , R ' 7 are hydrogen, then R 5 is not -OH; if the substitutions at R 1 , R 3 , R 5 are hydrogen, then R ' 7 is not -OH or O-(alkyl 1-3 ).

24. The compound of claim 1, which is a compound of formula VA, or a pharma- ceutically acceptable salt or solvate thereof. 【Chemistry 81】 (In the formula, R 1 is the following: 【Chemistry 82】 and 【Chemistry 83】 wherein R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 5 is -OR 8 and the following: 【Chemistry 84】 R 9 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the point of attachment, -(CH 2 -CH 2 -O) n -, or NR 10 R 11 ; where n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R 8 is selected from the group consisting of hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 7 is -OH, -OR 12 , or the following: 【Chemistry 85】 【Chemistry 86】 and 【Chemistry 87】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 , where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

25. The compound of claim 1, which is a compound of formula VB, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 88】 (In the formula, R 3 is the following: 【Chemistry 89】 and 【Chemistry 90】 wherein R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 5 is -OR 8 and the following: 【Chemistry 91】 R 9 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the point of attachment, -(CH 2 -CH 2 -O)n-, or NR 10 R 11 ; where n is 1 to 20; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R 8 is selected from the group consisting of hydrogen, optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 7 is -OH, -OR 12 , or the following: 【Chemistry 92】 【Chemistry 93】 and 【Chemistry 94】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, optionally substituted alkyl, heterocycloalkyl, and aryl groups; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

26. The compound of claim 1, which is a compound of formula VC, a pharma- ceutically acceptable salt or solvate thereof. 【Chemistry 95】 (In the formula, R 5 is —OH, —OR 8 , or the following: 【Chemistry 96】 R 9 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, amino, alkyl-ester, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, an amino acid linked through an ester or amide bond at the attachment point, -(CH 2 -CH 2 -O) n -, or NR 10 R 11 ; R 10 and R 11 are the same or different and are independently selected from hydrogen or optionally substituted alkyl; R 8 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 7 is -OH, -OR 12 , or the following: 【Chemistry 97】 【Chemistry 98】 and 【Chemistry 99】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

27. The compound of claim 1, which is a compound of formula VI, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 100】 (In the formula, R 1 and R 3 are the same or different and independently represent hydrogen, 【Chemistry 101】 and 【Chemistry 102】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 7 and R' 7 are hydrogen, OH, -OR 12 , 【Chemistry 103】 【Chemistry 104】 and 【Chemistry 105】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, an aryl group, and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group; With the proviso that all substitutions at R 1 , R 3 , R 7 and R' 7 are not hydrogen at the same time; if any one substitution at R 1 or R 3 is not hydrogen, then R 7 and R' 7 are not hydrogen; if the substitutions at R 1 , R 3 , R 7 are hydrogen, then R' 7 is not -OH or O-(alkyl 1-3 ); if the substitutions at R 1 , R 3 , R' 7 are hydrogen, then R 7 is not -OH or O-(alkyl 1-3 ).

28. The compound of claim 1, which is a compound of formula VI-A, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 106】 (In the formula, R 1 is the following: 【Chemistry 107】 and 【Chemistry 108】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 7 and R' 7 are, at each substitution point, independently selected from -OH, -OR 12 , 【Chemistry 109】 【Chemistry 110】 and 【Chemistry 111】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

29. The compound of claim 1, which is a compound of formula VI-B as set forth below, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 112】 (In the formula, R 3 is the following: 【Chemistry 113】 and 【Chemistry 114】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 7 and R' 7 are, at each substitution point, independently selected from -OH, -OR 12 , 【Chemistry 115】 【Chemistry 116】 and 【Chemistry 117】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

30. The compound of claim 1, which is a compound of formula VI-C, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 118】 (In the formula, R 7 and R′ 7 are independently, at each substitution point, —OH, —OR 12 , 【Chemistry 119】 【Chemistry 120】 and 【Chemistry 121】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 , where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

31. The compound of claim 1, which is a compound of formula VII, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 122】 (In the formula, R 1 and R 3 are independently hydrogen, 【Chemistry 123】 and 【Chemical 124】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 7 is hydrogen, OH, -OR 12 , or the following: 【Chemistry 125】 【Chemistry 126】 and 【Chemistry 127】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 , where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is selected from an optionally substituted alkylene(C 1-6 ) group; However, all of the substitutions of R 1 , R 3 and R 7 are not hydrogen at the same time; when any one of the substitutions of R 1 or R 3 is not hydrogen, R 7 is not hydrogen; when the substitutions of R 1 and R 3 are hydrogen, R 7 is not -OH, -O-(alkyl 1-3 ).

32. The compound of claim 1, which is a compound of formula VII-A as set forth below, or a pharma- ceutically acceptable salt or solvate thereof. 【Chemistry 128】 (In the formula, R 1 is the following: 【Chemistry 129】 and 【Chemistry 130】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 7 is -OH, -OR 12 , or the following: 【Chemistry 131】 【Chemistry 132】 and 【Chemistry 133】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

33. The compound described in claim 32, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 134】 34. The compound of claim 1, which is a compound of formula VII-B, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 135】 (In the formula, R 3 is the following: 【Chemistry 136】 and 【Chemistry 137】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 7 is -OH, -OR 12 , or the following: 【Chemistry 138】 【Chemistry 139】 and 【Chemistry 140】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

35. The compound of claim 1, which is a compound of formula VII-C, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 141】 (In the formula, R 7 is —OR 12 , 【Chemistry 142】 【Chemistry 143】 and 【Chemistry 144】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1-20 and R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

36. The compound described in claim 35, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 145】 37. The compound of claim 1, which is a compound of formula VIII, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 146】 (In the formula, R 1 and R 3 are independently hydrogen, 【Chemistry 147】 and 【Chemistry 148】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, (CH 2 —CH 2 —O) n —, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R′ 7 is hydrogen, OH, —OR 12 , 【Chemistry 149】 【Chemistry 150】 and 【Chemistry 151】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is selected from an optionally substituted alkylene(C 1-6 ) group; With the proviso that all substitutions at R 1 , R 3 and R ' 7 are not hydrogen at the same time; if any one substitution at R 1 or R 3 is not hydrogen, then R ' 7 is not hydrogen; if the substitutions at R 1 and R 3 are hydrogen, then R ' 7 is not --OH or O-(alkyl 1-3 ).

38. The compound described in claim 37, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 152】 【Chemistry 153】 39. The compound of claim 1, which is a compound of formula VIII-A, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 154】 (In the formula, R 1 is the following: 【Chemistry 155】 and 【Chemistry 156】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 7 is -OH, -OR 12 , 【Chemistry 157】 【Chemistry 158】 and 【Chemistry 159】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

40. The compound described in claim 39, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 160】 【Chemistry 161】 41. The compound of claim 1, which is a compound of formula VIII-B, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 162】 (In the formula, R 3 is the following: 【Chemistry 163】 and 【Chemistry 164】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, where n is 1 to 20; R' 7 is -OH, -OR 12 , or the following: 【Chemistry 165】 【Chemistry 166】 and 【Chemistry 167】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; and R 16 is selected from an optionally substituted alkylene(C 1-6 ) group.

42. The compound described in claim 41, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 168】 43. The compound of claim 1, which is a compound of formula VIII-C, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 169】 (wherein R' 7 is -OR 12 , the following: 【Chemistry 170】 【Chemistry 171】 and 【Chemistry 172】 R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is selected from an optionally substituted alkylene(C 1-6 ) group; provided that if the substitutions at R 1 , R 3 are hydrogen, then R ' 7 is not an optionally substituted alkyl group. is not -OH or O-(alkyl 1-3 ).

44. The compound described in claim 43, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 173】 【Chemistry 174】 【Chemistry 175】 【Chemistry 176】 45. The compound of claim 2, which is a compound of formula IX, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 177】 wherein R 17 is selected from optionally substituted linear or branched alkylene groups, where the alkylene is optionally substituted with an amino group, an alkylamino group, and a dialkylamino group; R 18 is selected from NH 2 , —NR 20 R 21 ; R 20 and R 21 are each independently selected from hydrogen, an optionally substituted alkyl, —C(O)—R 22 , where R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 19 is selected from —O—R 23 —O—C(O)—R 24 , —O—C(O)—R 27 , and O—R 23 —R 28 , where R 23 is an optionally substituted linear or branched alkylene; R 24 is selected from optionally substituted alkoxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, aryloxy groups, and N(R 25 R 26 ); R 25 , R 26 are each independently selected from hydrogen, optionally substituted alkyl, and aryl, where the alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups, or R 25 and R 26 together form an optionally substituted heterocycloalkyl ring, where the heterocycloalkyl ring is optionally substituted with alkyl, hydroxyalkyl, -OH, -SH, F, Cl, Br, I, and optionally substituted amino groups; R 27 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, and N(R 25 R 26 ) groups; R 28 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl and aryl groups; the heterocycloalkyl, heteroaryl in R 28 are optionally substituted with alkyl, hydroxyalkyl, OH, SH, F, Cl, Br, I and optionally substituted amino and oxo groups.

46. ​​The compound of claim 2, which is a compound of formula IX-A, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 178】 wherein R 17 is selected from an optionally substituted linear or branched alkylene group, where the alkylene is optionally substituted by an amino group, an alkylamino group, and a dialkylamino group; R 18 is selected from NH 2 , -NR 20 R 21 ; R 20 and R 21 are each independently selected from hydrogen, an optionally substituted alkyl, -C(O)-R 22 ; R 22 is selected from an optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl group; R 23 is an optionally substituted linear or branched alkylene; R 24 is selected from an optionally substituted alkoxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, aryloxy group, and N(R 25 R 26 ); R 25 , R 26 are each independently selected from hydrogen, optionally substituted alkyl, and aryl, where the alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups; or R 25 and R 26 taken together form an optionally substituted heterocycloalkyl ring, where the heterocycloalkyl ring is optionally substituted with alkyl, hydroxyalkyl, -OH, -SH, F, Cl, Br, I, and optionally substituted amino groups.

47. The compound described in claim 46, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 179】 【Chemistry 180】 【Chemistry 181】 48. The compound of claim 2, which is a compound of formula IX-B, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 182】 wherein R 17 is selected from optionally substituted linear or branched alkylene groups, where the alkylene is optionally substituted with amino groups, alkylamino groups, and dialkylamino groups; R 18 is selected from NH 2 , —NR 20 R 21 ; R 20 and R 21 are each independently selected from hydrogen, optionally substituted alkyl, —C(O)—R 22 , where R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 23 is an optionally substituted linear or branched alkylene; R 25 and R 26 are each independently selected from hydrogen, optionally substituted alkyl and aryl groups, where the alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl groups, amino groups; or R 25 and R 26 taken together form an optionally substituted heterocycloalkyl ring, said heterocycloalkyl ring being optionally substituted with optionally substituted alkyl groups, hydroxyalkyl groups, OH, SH, F, Cl, Br, I, and optionally substituted amino groups.

49. The compound described in claim 48, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 183】 【Chemistry 184】 50. The compound of claim 2, which is a compound of formula IX-C, a pharma- ceutically acceptable salt or solvate thereof. 【Chemistry 185】 wherein R 17 is selected from optionally substituted linear or branched alkylene groups, where the alkylene is optionally substituted by amino, alkylamino, and dialkylamino groups; R 18 is selected from NH 2 , —NR 20 R 21 ; R 20 and R 21 are each independently selected from hydrogen, optionally substituted alkyl, —C(O)—R 22 , where R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 27 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, and N(R 25 R 26 ) groups; R 25 and R 26 are each independently selected from hydrogen, optionally substituted alkyl and aryl groups, where the alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups; or R 25 and R 26 taken together form an optionally substituted heterocycloalkyl ring, where the heterocycloalkyl ring is optionally substituted with optionally substituted alkyl, hydroxyalkyl groups, OH, SH, F, Cl, Br, I, and optionally substituted amino groups.

51. The compound of claim 50, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 186】 【Chemistry 187】 【Chemistry 188】 【Chemistry 189】 【Chemistry 190】 【Chemistry 191】 【Chemistry 192】 【Chemistry 193】 【Chemistry 194】 52. The compound of claim 2, which is a compound of formula IX-D, a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 195】 wherein R 17 is selected from optionally substituted linear or branched alkylene groups, where the alkylene is optionally substituted with amino, alkylamino, and dialkylamino groups; R 18 is selected from NH 2 , —NR 20 R 21 ; R 20 and R 21 are each independently selected from hydrogen, optionally substituted alkyl, —C(O)—R 22 ; R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R 23 is an optionally substituted linear or branched alkylene; R 28 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; and R 28 is an optionally substituted linear or branched alkylene group. The heterocycloalkyl and heteroaryl in are optionally substituted with alkyl groups, hydroxyalkyl groups, OH, SH, F, Cl, Br, I, and optionally substituted amino and oxo groups.

53. The compound of claim 52, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 196】 54. The compound of claim 2, which is a compound of formula X, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 197】 (In the formula, R 1 is the following: 【Chemistry 198】 【Chemistry 199】 and 【Chemistry 200】 R 2 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 4 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, -(CH 2 -CH 2 -O) n -, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; where n is 1 to 20; R 17 is selected from optionally substituted linear or branched alkylene groups, where the alkylene is optionally substituted by amino, alkylamino, and dialkylamino groups; R 18 is selected from NH 2 , -NR 20 R 21 ; R 20 and R 21 are each independently selected from hydrogen, optionally substituted alkyl, and C(O)-R 22 ; R 22 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups; R' 7 is -OH, -OR 12 , 【Chemistry 201】 【Chemistry 202】 【Chemistry 203】 【Chemistry 204】 and R 19 ; R 12 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R 13 is selected from the group consisting of optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkyl-ester, amino, alkoxy, heterocycloalkoxy, heteroaryloxy, cycloalkoxy, aryloxy, aminoaryl, or an amino acid linked at the attachment point through an ester or amide bond, -(CH 2 -CH 2 -O) n -, or NR 14 R 15 ; where n is 1 to 20; R 14 and R 15 are each independently selected from hydrogen, an optionally substituted alkyl group, a heterocycloalkyl group, and an aryl group; R 16 is selected from an optionally substituted alkylene(C 1-6 ) group; R 19 is -O-R 23 R 23 is an optionally substituted linear or branched alkylene; R 24 is an optionally substituted alkoxy, cycloalkoxy, heterocycloalkoxy, heteroaryloxy, aryloxy group, and N(R 25 R 26 ); R 25 , R 26 are each independently selected from hydrogen, optionally substituted alkyl, and aryl, where alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups; or R 25 and R 26 are each independently selected from hydrogen, optionally substituted alkyl, and aryl, where alkyl and aryl are optionally substituted with OH, SH, F, Cl, Br, I, and optionally substituted hydroxyalkyl, amino groups; taken together form an optionally substituted heterocycloalkyl ring, said heterocycloalkyl ring being optionally substituted with alkyl, hydroxyalkyl, -OH, -SH, F, Cl, Br, I, and optionally substituted amino groups; R 27 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, and N(R 25 R 26 ) groups;R 28 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, and aryl groups, and the heterocycloalkyl and heteroaryl in R 28 are optionally substituted with alkyl, hydroxyalkyl, OH, SH, F, Cl, Br, I, and optionally substituted amino and oxo groups; R 29 and R 30 are each independently selected from hydrogen and R 23 -O-C(O)-O-R 31 ; R 31 is selected from optionally substituted alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl groups; 55. The compound of claim 54, which is a compound selected from the group consisting of the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Chemistry 205】 【Chemistry 206】

56. A pharmaceutical composition comprising a compound selected from the group consisting of formula (IA), (I), (II), (III), (III-A), (III-B), (III-C), (IV), (IV-A), (IV-B), (IV-C), (V), (V-A), (V-B), (V-C), (VI), (VI-A), (VI-B), (VI-C), (VII), (VII-A), (VII-B), (VII-C), (VII), (VIII-A), (VIII-B), (VIII-C), (IX), (IX-A), (IX-B), (IX-C), (IX-D) and (X), a pharma- ceutical composition comprising a compound selected from the group consisting of a compound of formula (IA), (I), (II), (III), (III-A), (III-B), (III-C), (III-C), a pharma- ceutical composition comprising a compound of formula (IA), (I), (II), (III), (III-A), (III-B), (III-C), (IX), (IX-A), (IX-B), (IX-C), (IX-D) and (X), a pharma- ceutical composition comprising a compound of formula (IA), (I), (II), (III ...IV-C), (IX), (IX-D) and (X), a pharma- ceutical composition comprising a compound of formula (IA), (I), (II), (III), (III-B), (IV-C), (IX), (IX-D) and (X), a pharma- ceutical composition comprising a compound of formula (IA), (I), (II), (III), (III-B), (IV-C), (IX), (IX-D) and (X), a pha

57. A pharmaceutical composition for treating a symptom selected from interstitial cystitis / bladder pain syndrome (IC / BPS), overactive bladder (OAB), chronic cough, endometriosis, neuropathic pain, migraine, pruritus, postherpetic neuralgia, urinary tract infection-associated pain, osteoarthritis, arthritis, and urinary incontinence, comprising a compound represented by general formula (I), formula (I-A), formula (II), formula (III), formula (III-A), formula (III-B), formula (III-C), formula (IV), formula (IV-A), formula (IV-B), formula (IV-C), formula (V), formula (V A pharmaceutical composition comprising a compound selected from the compounds of formula (V-A), (V-B), (V-C), (VI), (VI-A), (VI-B), (VI-C), (VII), (VII-A), (VII-B), (VII-C), (VIII), (VIII-A), (VIII-B), (VIII-C), (IX), (IX-A), (IX-B), (IX-C), (IX-D), or (X), or a pharma- ceutical composition comprising a compound selected from the compounds of formula (V-A), (V-B), (V-C), (VII), (VII-A), (VII-B), (VII ...VII), (VII-A), (VII-B), (VII-C), (VII), (VII-A), (VII-B), (VII-C), (VII), (VII-A), (VII-B), (VII-C), (VII), (VII-A), (VII-B), (VII-C), (VII), (VII-A), (VII-B), (VII-C), (VII), (VII-A), (VII-B), (VII-C), (VII), (VII-A), (VII-B), (VII-C), (VII), (VII-A), (VII-B), (VII

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