Pyrazolo[1,5-a]pyridine derivatives for treating TRPM3-mediated disorders

Abstract

The present invention relates to a compound useful for the prevention or treatment of a TRPM3-mediated disorder, more specifically a disorder selected from pain and inflammatory hypersensitivity. The present invention also relates to a method for the prevention or treatment of such TRPM3-mediated disorders.

Description

Technical Field

[0001] The present invention relates to compounds useful for the prevention or treatment of TRPM3-mediated disorders, more specifically, disorders selected from pain, inflammatory hypersensitivity, and epilepsy. The present invention also relates to methods for the prevention or treatment of such TRPM3-mediated disorders.

Background Art

[0002] The TRP superfamily consists of proteins having six transmembrane domains (6TM) that are assembled as homo- or hetero-tetramers to form cation-permeable ion channels. The name TRP is derived from the Drosophila trp (transient receptor potential) mutant that characterizes the transient receptor potential in the fly photoreceptor in response to continuous light. In the past 15 years, trp-related channels have been identified in yeast, parasites, insects, fish, and mammals, including 27 TRPs in humans. Based on sequence homology, TRP channels can be divided into seven subfamilies: TRPC, TRPV, TRPM, TRPA, TRPP, TRPML, and TRPN.

[0003] Members of the TRP superfamily are likely expressed in all mammalian organs and cell types, and there have been great advances in understanding their physiological roles in recent years. The customized selectivity of certain TRP channels enables them to play important roles in the cellular uptake and / or trans-epithelial transport of Ca 2+ , Mg 2+ , and trace metal ions. Furthermore, the sensitivity of TRP channels to a wide range of chemical and physical stimuli enables them to function as dedicated biological sensors involved in processes from vision to taste and touch. In particular, some members of the TRP superfamily exhibit very high sensitivity to temperature. These so-called thermoTRPs are highly expressed in sensory neurons and / or skin keratinocytes and function as major thermosensors for the detection of harmless and harmful (painful) temperatures.

[0004] It is becoming increasingly clear that dysfunction of TRP channels is directly involved in the etiology of various hereditary and acquired diseases. In fact, mutations causing both loss-of-function and gain-of-function of TRP channel genes have been identified as the direct causes of hereditary diseases including brachyolmia, hypomagnesemia with secondary hypocalcemia, polycystic kidney disease, mucolipidosis type IV, and familial focal segmental glomerulosclerosis. Furthermore, the function / dysfunction of TRP channels is directly related to a wide range of pathological conditions including chronic pain, hypertension, cancer, and neurodegenerative disorders.

[0005] TRPM3 (transient receptor potential melastatin 3) represents a promising pharmacological target. TRPM3 is expressed in a large subset of small-diameter sensory neurons from dorsal root and trigeminal ganglia and is involved in thermosensation. Pregnenolone sulfate, a neurosteroid, is a known potent activator of TRPM3 (Wagner et al., 2008). The neurosteroid pregnenolone sulfate caused pain in wild-type mice but not in knockout TRPM3 mice. Also, recently, it has been shown that CFA-induced inflammation and inflammatory pain are abolished in TRPM3 knockout mice. Therefore, TRPM3 antagonists can be used as analgesics to counteract pain such as inflammatory pain (Vriens J. et al. Neuron, May 2011). The relationship between TRPM3 and epilepsy has also been established (see, for example, Eur J Hum Genet. 2019 Oct;27(10):1611-1618; Elife 2020 May 19;9:e57190.doi:10.7554 / eLife.57190.DOI:10.7554 / eLife.57190; Channels(Austin).2021;15(1):386-397). Therefore, TRPM3 is also a potential target for the treatment of epilepsy.

[0006] Several TRPM3 antagonists are known, but none of them refer to the compounds of the present invention (Straub I et al. Mol Pharmacol, November 2013). For example, liquiritigenin, a putative TRPM3 blocker, has been described to reduce mechanical and cold allodynia in a rat pain model (Chen L et al. Scientific reports, July 2014). There remains a great medical need for new, alternative, and / or better therapies for the prevention or treatment of TRPM3-mediated disorders, more specifically for pain such as inflammatory pain and epilepsy. There is a strong demand for therapies that have good efficacy against a particular type of pain, have low or no side effects (such as no potential for dependence like opioids and no toxicity), and / or have good or better pharmacokinetic or pharmacodynamic properties.

[0007] The present invention provides novel compounds that are antagonists of TRPM3 and can be used as modulators of TRPM3-mediated disorders.

Summary of the Invention

[0008] The present invention provides pyrazolo[1,5-a]pyridine derivatives and pharmaceutical compositions containing such pyrazolo[1,5-a]pyridine derivatives. The present invention also provides pyrazolo[1,5-a]pyridine derivatives for use as a medicament, more specifically for use in the prevention and / or treatment of TRPM3-mediated disorders, particularly for use in the prevention and / or treatment of pain and / or inflammatory hypersensitivity and / or epilepsy, and / or for combating pain and / or inflammatory hypersensitivity and / or for combating epilepsy.

[0009] The present invention also provides the use of a pyrazolo[1,5-a]pyridine derivative for the prevention and / or treatment of TRPM3-mediated disorders, in particular for the prevention and / or treatment of pain and / or inflammatory hypersensitivity and / or epilepsy, and / or for the manufacture of a pharmaceutical composition or medicament for combating pain and / or inflammatory hypersensitivity and / or epilepsy.

[0010] The present invention also provides a method for the prevention or treatment of a TRPM3-mediated disorder by administering a pyrazolo[1,5-a]pyridine derivative according to the invention to a subject in need thereof. More specifically, the present invention relates to such a method for the prevention and / or treatment of pain and / or inflammatory hypersensitivity and / or epilepsy, and / or for combating pain and / or inflammatory hypersensitivity and / or epilepsy.

[0011] The present invention further provides a method for preparing the pyrazolo[1,5-a]pyridine derivative of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0012] The present invention will be further described and, in some cases, described with respect to specific embodiments, but the present invention is not limited thereto.

[0013] A first aspect of the present invention is the provision of a compound of formula (I), its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs,

CHEMICAL FORMULA

[0014] In some embodiments of the pyrazolo[1,5-a]pyridine derivatives according to the present invention, (a-1) Q is -NR 3 R 4 represents, R 1 is R W represents, R W is -C 1 -C 6 -alkyl, and / or (a-2) Q is -NR 3 R 4 represents, R 5 and R 5 ’ among at least one represents -H, and / or (a-3) Q is -NR 3 R 4 represents, R 6 is -H, and / or (a-4) Q is -NR 3 R 4 represents, R 8 is -H, or or (b-1) (b-1) Q is -NR 3 R 4 represents, R 1 is -CH 2 F, -CHF 2 、-CF3 represents -CN, -methyl, -ethyl, -propyl, or -cyclopropyl, and / or (b-2) Q is -NR 3 R 4 represents, and R 5 and R 5 ’ in which at least one does not represent -H, and / or (b-3) Q is -NR 3 R 4 represents, and R 3 represents -H.

[0015] In one embodiment of the pyrazolo[1,5-a]pyridine derivative according to the present invention, T represents -O-, and U represents -CR 5 R 5 ’-. According to this embodiment, the pyrazolo[1,5-a]pyridine derivative according to the present invention is a compound of formula (II), a stereoisomer, a physiologically acceptable salt, a solvate, and / or a polymorph

Chemical formula

[0016] In another embodiment of the pyrazolo[1,5-a]pyridine derivative according to formula I, T represents -CR 5 R 5 ’-, and U represents -O-.

[0017] In one embodiment of the pyrazolo[1,5-a]pyridine derivative according to formula I or formula II, R 1 is methyl, ethyl, or another C 1 -C 6 alkyl. In another preferred embodiment, R 1 is methyl.

[0018] In one embodiment of the pyrazolo[1,5-a]pyridine derivative according to the present invention, Q represents -NR 3 R 4 .

[0019] In one embodiment of the pyrazolo[1,5-a]pyridine derivative according to the present invention, Q represents -OR2 represents

[0020] In some embodiments of the pyrazolo[1,5-a]pyridine derivatives according to the present invention, V is a saturated or unsaturated 3- to 14-membered cycloalkyl; 3- to 14-membered heterocycloalkyl, saturated or unsaturated 5- to 14-membered aryl, C 1 -C 6 alkyl, or 5- to 14-membered heteroaryl, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z and is mono- or polysubstituted with substituents selected from

[0021] .

[0022] In some embodiments, the 5- to 14-membered heteroaryl within the definition of V is selected from benzimidazole, benzisoxazole, benzazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furan, furazan, imidazole, imidazopyridine, pyrazolo[1,5-a]pyridine, indole, indolizine, isobenzofuran, isoindole, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, oxindole, phthalazine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, and in each case, unsubstituted or, independently of one another, mono- or polysubstituted by substituents selected from -F, -Cl, -Br, -I, -CF 3 、-CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 、=O, =S, -SF 5 、-R Y 、-OR Y 、-OC(=O)R Y 、-NR Y R Z 、-NR Y C(=O)R Z 、-SR Y 、-S(=O)R Y 、-S(=O) 2 R Y 、-C(=O)R Y 、-C(=O)OR Y 、or -C(=O)NR Y R Z and is mono- or polysubstituted by substituents selected from

[0023] Preferably, the 5- to 14-membered heteroaryl within the definition of V is selected from the group consisting of furan, thiophene, imidazole, pyrazole, oxazole, isoxazole, thiazole, triazole, pyridine, isoquinoline, benzothiazole, pyridazine, pyrimidine, imidazopyridine, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 、-CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 、=O, =S, -SF 5 、-R Y 、-OR Y 、-OC(=O)R Y 、-NR Y R Z 、-NR Y C(=O)R Z 、-SR Y 、-S(=O)R Y 、-S(=O) 2 R Y 、-C(=O)R Y 、-C(=O)OR Y 、or -C(=O)NR Y R Z and is monosubstituted or polysubstituted with substituents selected from the group consisting of

[0024] Preferably, the 5- to 14-membered heteroaryl within the definition of V is selected from the group consisting of furan-2-yl, furan-3-yl, thiophene-2-yl, thiophene-3-yl, pyrazole-3-yl, pyrazole-4-yl, pyrazole-5-yl, oxazole-5-yl, isoxazole-4-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, 1,2,4-triazol-3-yl, 1,2,3-triazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, isoquinolin-1-yl, isoquinolin-5-yl, benzo[d]thiazol-2-yl, pyridazin-3-yl, pyrimidin-5-yl, and imidazo[1,2-a]pyridin-6-yl, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I,, CF 3 、-CF2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z is monosubstituted or polysubstituted with substituents selected from

[0025] In some embodiments, the 5- to 14-membered heteroaryl within the definition of V is selected from the group consisting of pyrazol-3-yl, pyrazol-4-yl, thiazol-4-yl, thiazol-5-yl, pyridin-2-yl, pyridin-3-yl, and pyridin-4-yl, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I,, CF 3 , -CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Zmono- or polysubstituted with a substituent selected from

[0026] In one embodiment, the saturated or unsaturated 3- to 14-membered cycloalkyl within the definition of V is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, or cyclodecyl, including non-condensed or non-bridged, condensed, or bridged cycloalkyl, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I,, CF 3 , -CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z mono- or polysubstituted with a substituent selected from

[0027] In one embodiment, the 5- to 14-membered aryl within the definition of V is unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 , -CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y, -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z It is phenyl or other 5- to 14-membered aryl that is mono- or polysubstituted with a substituent selected from

[0028] In a further embodiment of the pyrazolo[1,5-a]pyridine derivative according to the present invention, V is saturated or unsaturated, unsubstituted, and independently of one another, -F, -Cl, -Br, -I, CF 3 , -CF 2 H, C 1 , -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z It represents 3- to 14-membered heterocycloalkyl that is mono- or polysubstituted with a substituent selected from

[0029] In some embodiments, the 3- to 14-membered heterocycloalkyl within the definition of V is azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxazolidine, morpholine, oxazolidine, oxane, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiacyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, hexahydro-1H-pyrrolidine, hexahydro-cyclopenta[c]pyrrole, octahydro-cyclopenta[c]pyrrole, and octahydropyrrolo[1,2-a]pyrazine, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 、-CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 、=O, =S, -SF 5 、-R Y 、-OR Y 、-OC(=O)R Y 、-NR Y R Z 、-NR Y C(=O)R Z 、-SR Y 、-S(=O)R Y 、-S(=O) 2 R Y 、-C(=O)R Y 、-C(=O)OR Y 、or -C(=O)NR Y R Z and is monosubstituted or polysubstituted with substituents selected from

[0030] In some embodiments, the 3- to 14-membered heterocycloalkyl within the definition of V is oxane, oxan-4-yl, oxetane, or oxetan-3-yl, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 、-CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 、=O, =S, -SF 5 、-R Y 、-OR Y 、-OC(=O)R Y 、-NR Y R Z 、-NR Y C(=O)R Z 、-SR Y 、-S(=O)R Y 、-S(=O) 2 R Y 、-C(=O)R Y 、-C(=O)OR Y 、or -C(=O)NR Y R Z and is monosubstituted or polysubstituted with substituents selected from

[0031] In another preferred embodiment of the pyrazolo[1,5-a]pyridine derivative according to the present invention, V is saturated or unsaturated, unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 、-CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 、=O, =S, -SF 5 、-R Y 、-OR Y 、-OC(=O)R Y 、-NR Y R Z 、-NR Y C(=O)R Z 、-SR Y 、-S(=O)R Y 、-S(=O) 2 R Y 、-C(=O)R Y 、-C(=O)OR Y、 or -C(=O)NR Y R Z mono- or polysubstituted with a substituent selected from 1 -C 6 alkyl or C 1 -C 6 represents heteroalkyl.

[0032] In some embodiments of the pyrazolo[1,5-a]pyridine derivatives according to the present invention, V is unsubstituted, independently of one another, -F, -Cl, -Br, -I, -CN, -C(=O)OH, -NH 2 , -NO 2 , -OH, =O, -SF 5 ; saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -C(=O)O-C 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -NHC 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -N(C 1-6 -alkyl) 2 ; saturated or unsaturated, unsubstituted, mono- or polysubstituted -O-C 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -S(=O) 2 -C 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally, -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-(in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted) via which is connected, 3- to 14-membered cycloalkyl; or A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted) and is mono- or polysubstituted by a substituent selected from 3- to 14-membered heterocycloalkyl.

[0033] In some embodiments, V is unsubstituted and, independently of one another, -OH, -F, -Cl, -Br, -I, -SH, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -CN, -NO 2 , -C(=O)OH, -NH 2 , or -N(CH 3 ) 2 ; A saturated or unsaturated, unsubstituted, independently of one another, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 and is mono- or polysubstituted by a substituent selected from the group consisting of -C 1-6 -alkyl; A saturated or unsaturated, unsubstituted, independently of one another, -F, -Cl, -Br, -I, -C1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 -, -CHF 2 -, -CH 2 F, -OCF 3 -, -OCHF 2 -, -OCH 2 F, SF 5 -, -NO 2 -, -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 mono- or polysubstituted with a substituent selected from the group consisting of -C 1-6 -heteroalkyl; unsubstituted, independently of one another, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 mono- or polysubstituted with a substituent selected from the group consisting of -OC 1-6 -alkyl; unsubstituted, independently of one another, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2, -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 -O(C=O)C substituted mono- or polysubstituted with a substituent selected from the group consisting of 1-6 -alkyl; unsubstituted, independently of one another, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 -C(=O)OC substituted mono- or polysubstituted with a substituent selected from the group consisting of 1-6 -alkyl; a 3- to 14-membered cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, in each case unsubstituted, independently of one another, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 a 3- to 14-membered cycloalkyl substituted mono- or polysubstituted with a substituent selected from the group consisting of; Azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxalidine, morpholine, oxazolidine, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1, 3- to 14-membered heterocycloalkyl selected from the group consisting of 1-dioxothiacylcyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, hexahydro-1H-pyrrolidine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, and octahydropyrrolo[1,2-a]pyrazine, in each case unsubstituted and independently of each other, -F, -Cl, -Br, -I, -C 1-6 -Alkyl, C 2-6 -alkenyl, -C 2-6 -Alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, S.F. 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 and 3- to 14-membered heterocycloalkyl which is mono- or polysubstituted with a substituent selected from the group consisting of:

[0034] In some embodiments, V is unsubstituted, independently of each other, -F, -Cl, -CN, -OH, ═O, -C 1-6 -Alkyl, methyl, ethyl, -CHF 2, -CF 3 , -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-NHC(=O)-O-C 1-6 -alkyl, -C(=O)O-C 1-6 , -N(C 1-6 -alkyl) 2 , -OC 1-6 -alkyl, -OCF 3 , -O-C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -S(=O) 2 , -C 1-6 -alkyl, -azetidine, -C 1-6 -alkylene-O-tetrahydropyran, or -C 1-6 -piperazine substituted with -alkyl, and is monosubstituted or polysubstituted with a substituent selected from them.

[0035] In some embodiments of the pyrazolo[1,5-a]pyridine derivative according to the present invention, V is (i) unsubstituted, or (ii) monosubstituted, or (iii) disubstituted, or (iv) trisubstituted, or (v) tetrasubstituted.

[0036] In some embodiments of the pyrazolo[1,5-a]pyridine derivative according to the present invention, V is (i) unsubstituted, or (ii) monosubstituted, or (iii) disubstituted.

[0037] In some embodiments, V is a saturated or unsaturated 3- to 14-membered heterocycloalkyl (preferably 3- to 5-membered heterocycloalkyl), 5- to 14-membered heteroaryl (preferably 5- to 6-membered heteroaryl), saturated or unsaturated 3- to 14-membered cycloalkyl, 5- to 14-membered aryl, or C 1 -C 6 represents alkyl, and in each case, is unsubstituted, mono-substituted or multi-substituted, and is preferably a residue selected from the group consisting of the following.

Chemical formula

[0038] In one embodiment, V represents unsubstituted, mono-substituted or multi-substituted -oxetanyl, preferably

Chemical formula

[0039] In some embodiments, V represents a residue according to general formula (E),

Chemical formula

[0040] In some embodiments, V represents unsubstituted, monosubstituted, or polysubstituted 2-pyridine. In some embodiments, V represents a residue selected from the group consisting of.

Chemical formula

[0041] In some embodiments, V represents unsubstituted, monosubstituted, or polysubstituted 3-pyridine. In preferred embodiments, V represents a residue selected from the group consisting of.

Chemical formula

[0042] In some embodiments, V represents an unsubstituted, mono-substituted, or multi-substituted 4-pyridine. In preferred embodiments, V represents a residue selected from the group consisting of the following.

Chemical formula

[0043] In some embodiments, optionally, U-CH 2 in the case of, V represents a residue selected from the group consisting of the following.

Chemical formula

[0044] In alternative embodiments, V represents a residue selected from the group consisting of the following.

Chemical formula

[0045] In some embodiments, V represents an unsubstituted, mono-substituted or multi-substituted bicyclic heteroaryl, preferably selected from the group consisting of the following.

Chemical formula

[0046] In some embodiments, V represents a residue according to general formula (F’),

Chemical formula

Chemical formula

[0047] In some embodiments, V represents a residue according to general formula (G) or (H), [Chemical formula] wherein R G1 and R H1 are selected from the group consisting of -H, -CH 3 , -CF 3 , -OH, -OCH 3 , -OCH 2 CH 3 , -Cl, azetidinyl, -cyclopropyl, -O-cyclopropyl, and -CHF 2 ; or R G1 and R H1 are selected from the group consisting of -H, -CH 3 , -CF 3 , -OH, -OCH 3 , -OCH 2 CH 3 , -Cl, and azetidinyl. In other embodiments, V represents a residue according to general formula (G') or (H'), [Chemical formula] wherein R G1 and R H1 are selected from the group consisting of -H, -CH 3 , -CF 3 , -OH, -OCH 3 , -OCH 2 CH 3 , -Cl, azetidinyl, -cyclopropyl, -O-cyclopropyl, and -CHF 2 ; or R G1 and R H1 are selected from the group consisting of -H, -CH 3 , -CF 3 , -OH, -OCH 3 , -OCH 2 CH 3 , -Cl, and azetidinyl. 、

[0048] In one embodiment of the pyrazolo[1,5-a]pyridine derivative according to the present invention, R 1is -H, -F, -Cl, -Br, -I, -CN; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 - 6 -alkyl; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -O-C 1 - 6 -alkyl; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C(=O)C 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C(=O)OC 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C(=O)NHC 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C(=O)N(C 1-6 -alkyl) 2 ; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -S(=O)C 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -S(=O) 2 -C 1 - 6 -alkyl; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -heteroalkyl; or saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, wherein said 3- to 14-membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted), representing a 3- to 14-membered cycloalkyl.

[0049] In some embodiments, R 1is -H, -F, -Cl, -Br, -I, -C 1-6 -alkyl, -O-C 1-6 -alkyl, -C 1-6 -alkylene-O-C 1-6 -alkyl, -C 1-6 -alkylene-NH(C 1-6 -alkyl), -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -alkylene-CF 3 , -C 1-6 -alkylene-CF 2 , -C 1-6 -alkylene-CFH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , -C 1-6 -alkylene-N(C 1-6 -alkyl)-C 1-6 -alkylene-CF 3 , -C(=O)C 1-6 -alkyl, -C(=O)OC 1-6 -alkyl, -C(=O)NH 2 , -C(=O)NHC 1-6 , -C(=O)N(C 1-6 -alkyl) 2 , -S(=O)-C 1-6 , -S(=O) 2 -C 1-6 , -O-C 1-6 -alkyl, unsubstituted -cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, or unsubstituted cyclohexyl.

[0050] In some embodiments, R 1 is -H, -C 1-6 -alkyl, -C 1-6 -alkylene-O-C 1-6 -alkyl, -CH 2F, -CHF 2 , -CF 3 , -unsubstituted cyclopentyl, or -cyclopropyl. Preferably, R 1 is, -H, -C 1-6 -alkyl, -C 1-6 -alkylene - O - C 1-6 -alkyl, -CH 2 F, -CHF 2 , -CF 3 , -cyclopentyl, or unsubstituted. In some embodiments, R 1 is, -CH 3 .

[0051] In some embodiments, R 1 is, -CH 2 F, -CHF 2 , -CH 3、 or -cyclopropyl. Preferably, R 1 is, -CH 2 F, -CHF 2 , or -CH 3 . In some embodiments, R 1 is, -C(=O)NH 2 , or -CHF 2 .

[0052] In some embodiments, R 1 is, -H, -C 1-3 -alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-3 -alkylene - CF 3 , -C 1-3 -alkylene - CF 2 H, -C 1-3 -alkylene - CFH 2、 or -cyclopropyl, and preferably, R 1 is, -H, -C 1-3 -alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl2 , -C 1-3 -alkylene-CF 3 , -C 1-3 -alkylene-CF 2 H, or -C 1-3 -alkylene-CFH 2 represents, for example, -CH 3 is the case.

[0053] In some embodiments of the pyrazolo[1,5-a]pyridine derivatives according to the present invention, R 2 is -H; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -alkyl; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -heteroalkyl; a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted), a 3- to 14-membered cycloalkyl; or a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted), a 3- to 14-membered heterocycloalkyl.

[0054] In some embodiments, R 2 is -H, -C 1-6 -alkyl, -C 1-6 -alkylene-O-C1-6 -alkyl, -C 1-6 -alkylene-NH(C 1-6 -alkyl), -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -alkylene-CF 3 , -C 1-6 -alkylene-CF 2 H, -C 1-6 -alkylene-CFH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , or -C 1-6 -alkylene-N(C 1-6 -alkyl)-C 1-6 -alkylene-CF 3 represents.

[0055] In some embodiments, R 2 represents -H or -C 1-6 -alkyl.

[0056] In one embodiment of the pyrazolo[1,5-a]pyridine derivative according to the present invention, R 3 is -H; -OH; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -alkyl; or saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -heteroalkyl.

[0057] In some embodiments, R 3 is -H, -OH, -C 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C1-6 -Alkyl, -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-NH(C 1-6 -Alkyl), -C 1-6 -Alkylene-N(C 1-6 -Alkyl) 2 , -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C 1-6 -Alkylene-CF 2 H, -C 1-6 -Alkylene-CFH 2 , -C 1-6 -Alkylene-NH-C 1-6 -Alkylene-CF 3 , or -C 1-6 -Alkylene-N(C 1-6 -Alkyl)-C 1-6 -Alkylene-CF 3 represents.

[0058] In some embodiments, R 3 represents -H, -OH, or saturated, unsubstituted, or -OH monosubstituted -C 1-6 -Alkyl. Preferably, R 3 represents -H.

[0059] In some embodiments, R 3 represents -H, and R 4 represents a residue other than -H.

[0060] In one embodiment of the pyrazolo[1,5-a]pyridine derivative according to the present invention, R 4 is -H; Saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -S(=O)C 1-6 -Alkyl; Saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -S(=O) 2 -C1 - 6 -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -heteroalkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted), a 3- to 14-membered cycloalkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted), a 3- to 14-membered heterocycloalkyl; An unsubstituted, mono-substituted or multi-substituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted), a 6- to 14-membered aryl, or An unsubstituted, mono-substituted or multi-substituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6Represents a 5- to 14-membered heteroaryl connected via -heteroalkylene- (in each case, saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted).

[0061] In some embodiments, R 4 is saturated or unsaturated, unsubstituted, and independently of one another, -F, -Cl, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 , -OH, =O, -OC 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 , -NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)O-C 1-6 -alkyl, -N(C 1-6 -alkyl)C(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 , -C(=O)NH 2 , -C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 , -S(=O) 2 C 1-6-Alkyl, -phenyl, -C 1-6 -Alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, mono- or polysubstituted with a substituent selected from the group consisting of: -S(=O) 2 C 1-6 -Alkyl; -S(=O) 2 (3- to 14-membered cycloalkyl), wherein the 3- to 14-membered cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, and in each case, saturated or unsaturated, unsubstituted, and independently of one another, -F, -Cl, -C 1-6 -Alkyl, -C 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OH, -C 1-6 -Alkylene-O-C 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -Alkyl) 2 , -NHC(=O)O-C 1-6 -Alkyl, -N(C 1-6 -Alkyl)C(=O)O-C 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)O-C 1-6 -Alkyl, -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-NH-C 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -Alkyl) 2 , -C 1-6 -Alkylene-NH-C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)O-C 1-6 -Alkyl, -C(=O)O-C 1-6 -Alkylene-CF 3 , -C(=O)NH2 、 -C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 、 -S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, monosubstituted or polysubstituted with a substituent selected from the group consisting of, -S(=O) 2 (3- to 14-membered cycloalkyl); Saturated or unsaturated, unsubstituted, independently of one another, -F, -Cl, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 、 -OH, =O, -OC 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 、 -NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 、 -NHC(=O)O-C 1-6 -alkyl, -N(C 1-6 -alkyl)C(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 、 -C 1-6 -alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 、 -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 、 -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 、 -C(=O)NH2 ,-C(=O)NH(C 1-6 -alkyl),-C(=O)N(C 1-6 -alkyl) 2 ,-S(=O) 2 C 1-6 -alkyl,-phenyl,-C 1-6 -alkylene-phenyl,a saturated or unsaturated,unsubstituted 3- to 14-membered heterocycloalkyl,and an unsubstituted 5- to 14-membered heteroaryl,mono- or polysubstituted with a substituent selected from the group consisting of,-C 1-6 -alkyl; 3- to 14-membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl)wherein,-C 1-6 -alkylene-is unsubstituted or mono-substituted with -OH,and said 3- to 14-membered cycloalkyl is selected from the group consisting of cyclopropyl,cyclobutyl,cyclopentyl,cyclohexyl,and cycloheptyl,and in each case is saturated or unsaturated,and in each case is unsubstituted,independently of one another,-F,-Cl,-C 1-6 -alkyl,-C 1-6 -alkylene-CF 3 ,-OH,=O,-OC 1-6 -alkyl,-C 1-6 -alkylene-OH,-C 1-6 -alkylene-O-C 1-6 -alkyl,-NH 2 ,-NHC 1-6 -alkyl,-N(C 1-6 -alkyl) 2 ,-NHC(=O)O-C 1-6 -alkyl,-N(C 1-6 -alkyl)C(=O)O-C 1-6 -alkyl,-C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl,-C 1-6 -alkylene-NH 2 ,-C 1-6 -alkylene-NH-C 1-6 -alkyl,-C 1-6 -alkylene-N(C 1-6 -alkyl) 2 ,-C1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 , -C(=O)NH 2 , -C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 , -S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, monosubstituted or polysubstituted with a substituent selected from the group consisting of, 3- to 14-membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl); 3- to 14-membered heterocycloalkyl or -C 1-6 -alkylene-(3- to 14-membered heterocycloalkyl) wherein -C 1-6-alkylene- is unsubstituted or mono-substituted with -OH, and the 3- to 14-membered heterocycloalkyl is in each case azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxazolidine, morpholine, oxazolidine, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thietan, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiacyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, hexahydro-1H-pyrrolidine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, and octahydropyrrolo[1,2-a]pyrazine, and is in each case unsubstituted, -F, -Cl, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 、-OH、=O、-OC 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 、-NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 、-NHC(=O)O-C 1-6 -alkyl, -N(C 1-6 -alkyl)C(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 、-C 1-6 -alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C1-6 -alkyl) 2 ,-C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 ,-C(=O)-C 1-6 -alkyl,-C(=O)OH,-C(=O)O-C 1-6 -alkyl,-C(=O)O-C 1-6 -alkylene-CF 3 ,-C(=O)NH 2 ,-C(=O)NH(C 1-6 -alkyl),-C(=O)N(C 1-6 -alkyl) 2 ,-S(=O) 2 C 1-6 -alkyl,-phenyl,-C 1-6 -alkylene-phenyl,a saturated or unsaturated,unsubstituted 3- to 14-membered heterocycloalkyl,and an unsubstituted 5- to 14-membered heteroaryl,monosubstituted or polysubstituted with a substituent selected from the group consisting of,a 3- to 14-membered heterocycloalkyl or -C 1-6 -alkylene-(3- to 14-membered heterocycloalkyl); unsubstituted,independently of one another,-F,-Cl,-CN,-C 1-6 -alkyl,-C 1-6 -alkylene-CF 3 ,-OH,=O,-OC 1-6 -alkyl,-C 1-6 -alkylene-OH,-C 1-6 -alkylene-O-C 1-6 -alkyl,-NH 2 ,-NHC 1-6 -alkyl,-N(C 1-6 -alkyl) 2 ,-NHC(=O)O-C 1-6 -alkyl,-N(C 1-6 -alkyl)C(=O)O-C 1-6 -alkyl,-C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl,-C 1-6 -alkylene-NH 2 ,-C 1-6 -alkylene-NH-C 1-6 -alkyl,-C1-6 -alkylene-N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 、-C(=O)-C 1-6 -alkyl、-C(=O)OH、-C(=O)O-C 1-6 -alkyl、-C(=O)O-C 1-6 -alkylene-CF 3 、-C(=O)NH 2 、-C(=O)NH(C 1-6 -alkyl)、-C(=O)N(C 1-6 -alkyl) 2 、-S(=O) 2 C 1-6 -alkyl、-phenyl、-C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, mono- or polysubstituted with a substituent selected from the group consisting of: -phenyl; 5- to 14-membered heteroaryl or -C 1-6 -alkylene-(5- to 14-membered heteroaryl), wherein -C 1-6 -alkylene- is unsubstituted or mono-substituted with -OH, and the 5- to 14-membered heteroaryl is in each case selected from the group consisting of benzimidazole, benzisoxazole, benzazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furan, furazan, imidazole, imidazopyridine, pyrazolo[1,5-a]pyridine, indole, indolizine, isobenzofuran, isoindole, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, oxyindole, phthalazine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, and is in each case unsubstituted, -F, -Cl, -CN, -C1-6 -Alkyl, -C 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OH, -C 1-6 -Alkylene-O-C 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -Alkyl) 2 , -NHC(=O)O-C 1-6 -Alkyl, -N(C 1-6 -Alkyl)C(=O)O-C 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)O-C 1-6 -Alkyl, -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-NH-C 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -Alkyl) 2 , -C 1-6 -Alkylene-NH-C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)O-C 1-6 -Alkyl, -C(=O)O-C 1-6 -Alkylene-CF 3 , -C(=O)NH 2 , -C(=O)NH(C 1-6 -Alkyl), -C(=O)N(C 1-6 -Alkyl) 2 , -S(=O) 2 C 1-6 -Alkyl, -phenyl, -C 1-6 -Alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, monosubstituted or polysubstituted with a substituent selected from the group consisting of, 5- to 14-membered heteroaryl or -C 1-6 -Alkylene-(5- to 14-membered heteroaryl), represents.

[0062] In some embodiments, R 4 is -H; saturated, unsubstituted, mono- or poly-substituted with -F, -S(=O) 2 C 1-6 -alkyl; saturated, unsubstituted -S(=O) 2 (3- to 14-membered cycloalkyl); saturated, unsubstituted, and independently of one another, -OH, =O, -NH 2 , -NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 , -OC 1-6 -alkyl, -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkyl, -C(=O)NH 2 , -C(=O)-NH-C 1-3 , -C(=O)-N(C 1-3 -alkyl) 2 , or mono- or di-substituted with a substituent selected from the group consisting of unsubstituted -phenyl, -C 1-6 -alkyl; 3- to 14-membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or mono-substituted with -OH, and the 3- to 14-membered cycloalkyl is saturated, unsubstituted, and independently of one another, -C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , -C 1-6 -alkylene-OH, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -OH, -OC 1-6 -alkyl, -NH 2 , -N(C 1-6 -alkyl) 2 , -NHC(=O)O-C1-6 3- to 14-membered cycloalkyl or -C, monosubstituted or disubstituted with a substituent selected from the group consisting of -alkyl 1-6 -alkylene-(3- to 14-membered cycloalkyl); 3- to 14-membered heterocycloalkyl or -C 1-6 -alkylene-(3- to 14-membered heterocycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted with -OH, and the 3- to 14-membered heterocycloalkyl is in each case selected from azetane, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, quinuclidine, hexahydro-1H-pyrrolidine, 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 1,1-dioxothiacyclohexane, and is in each case unsubstituted, independently of one another, with -F, -OH, =O, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 、-C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 、-N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-NH 2 、-C 1-6 -alkylene-N(C 1-6 -alkyl) 2 、-C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 、-C(=O)NH 2 、-C(=O)NH(C 1-6 -alkyl), -S(=O)2 C 1-6 - alkyl, oxetanyl, pyrimidinyl, -C 1-6 - alkylene - phenyl, and is mono - or polysubstituted with a substituent selected from the group consisting of 3 - to 14 - membered heterocycloalkyl or -C1 - 6 - alkylene-(3 - to 14 - membered heterocycloalkyl); unsubstituted - phenyl; 5 - to 14 - membered heteroaryl or -C 1-6 - alkylene-(5 - to 14 - membered heteroaryl), wherein -C 1-6 - alkylene - is unsubstituted or mono - substituted with -OH, and the 5 - to 14 - membered heteroaryl is in each case selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole, and [1,2,4]triazolo[4,3 - a]pyrimidine, and in each case is unsubstituted, independently of one another, and is mono - or disubstituted with a substituent selected from the group consisting of -C 1-6 - alkyl, -OH, and represents 5 - to 14 - membered heteroaryl or -C 1-6 - alkylene-(5 - to 14 - membered heteroaryl).

[0063] In one embodiment of the pyrazolo[1,5 - a]pyridine derivative according to the present invention, R 3 and R 4 together form a saturated or unsaturated, unsubstituted, or mono - or polysubstituted 5 - or 6 - membered heterocyclic ring containing one or two heteroatoms selected from N, O, and S.

[0064] In some embodiments, R 3 and R 4 together form a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, morpholine, and piperazine, and in each case is unsubstituted, independently of one another, and is -F, -C 1-6 - alkyl, -NH 2 -, -NHCH 3 -, -N(CH 3 ) 2 -, -C(=O)NH - C 1-6 - alkyl, -C(=O)N(C 1-6-(alkyl) 2 、-C(=O)O-C 1-6 -alkyl, -NHC(=O)O-C 1-6 -alkyl, -unsubstituted pyridyl, and a substituent selected from the group consisting of 1,2,4-oxadiazole monosubstituted or polysubstituted with -alkyl. In one embodiment, R 1-6 and R 3 and R 4 do not together form an unsubstituted, monosubstituted or polysubstituted morpholine.

[0065] In some embodiments, R 3 and R 4 together form an unsubstituted, or -N(CH 3 ) 2 monosubstituted pyrrolidine ring; an unsubstituted or -C 1-6 -alkyl, -NH 2 , -N(CH 3 ) 2 , -C(=O)NH-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkyl, -NHC(=O)O-C 1-6 -alkyl, and a piperidine ring monosubstituted with a substituent selected from the group consisting of unsubstituted or -C 1-6 -alkyl monosubstituted 1,2,4-oxadiazole; an unsubstituted morpholine ring; or an N-substituted piperazine ring formed with a substituent selected from the group consisting of unsubstituted or -C 1-6 -alkyl and -unsubstituted pyridyl.

[0066] In some embodiments, both R 3 and R 4 do not represent -H. In some embodiments, R 3 and R 4 together with the nitrogen atom to which they are attached form a residue selected from the group consisting of the following.

Chemical formula

[0067] In other embodiments, R 3 represents -H, and R 4 does not represent -H.

[0068] In some embodiments, R 3 represents -H, and R 4 represents a saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -alkyl. In some embodiments, R 3 represents -H, and R 4 represents a residue selected from the group consisting of.

Chemical formula

[0069] In a further embodiment, R 3 represents -H, and R 4 represents the residue -CR’R’’-(CH 2 ) m -OH, where m is an integer from 1 to 6, preferably from 1 to 3, and where R’ and R’’ are, independently of each other, -H, -C 1-3 -alkyl, -CF 3 、-CF 2 H, -CFH 2 、-C 1-3 -alkylene-CF 3 、-C 1-3 -alkylene-CF 2 H, -C 1-3 -alkylene-CFH 2 、-C 1-3 -alkylene-O-C 1-3 -alkyl, -C 1-3 -alkylene-OH, -C(=O)-NH 2 、or C(=O)-NH-C 1-3 -alkyl, preferably -H, -CH 3 、-C 1-3 -alkylene-OH, -C(=O)-NH 2 、or C(=O)-NH-C 1-3-Alkyl is represented. In one embodiment, at least R' or R'' does not represent -H. In an alternative embodiment, neither R' nor R'' represents -H.

[0070] In a further embodiment, R 3 represents -H, and R 4 represents a saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, or a saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered heterocycloalkyl.

[0071] In a further embodiment, R 3 represents -H, and R 4 represents a saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3-membered cycloalkyl, or a saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3-membered heterocycloalkyl. In some embodiments, R 3 represents -H, and R 4 represents a residue selected from the group consisting of.

Chemical formula

[0072] In some embodiments, R 3 represents -H, and R 4 represents a saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 4-membered cycloalkyl), or a saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered heterocycloalkyl (preferably, a 4-membered heterocycloalkyl). In some embodiments, R 3 represents -H, and R 4 represents a residue selected from the group consisting of.

Chemical formula

[0073] In some embodiments, R 3 represents -H, and R 4 represents a residue according to general formula (A), [Chemical] In the formula, m A is 0 or 1, Y A is -O-, -NR A6 -, and -CR A7 R A8 - is selected from, R A1 , R A2 , R A3 , R A4 , R A5 , R A6 , R A7 , and R A8 are, independently of each other, -H, F, -C 1-3 -alkyl, -C 1-3 -alkylene-OH, -C 1-3 -alkylene-NH 2 , -C 1-3 -alkylene-NH(C 1-3 -alkyl), -C 1-3 -alkylene-N(C 1-3 -alkyl) 2 , -C 1-3 -alkylene-NH(C 1-3 -alkylene-CF 3 ), -C 1-3 -alkylene-C(=O)NH 2 , -C 1-3 -alkylene-NH-C(=O)OC 1-4 -alkyl, -C(=O)NH 2 , -C(=O)-NH-C 1-3 -alkyl, -C(=O)-N(C 1-3 -alkyl) 2 , -3-oxetanyl, or -CHF 2 represents, preferably, R A1 , R A2 , R A3 , R A4 , R A5 , R A6 , R A7 , and R A8 are, independently of each other, -H, F, -C 1-3 -alkyl, -C 1-3 -alkylene-OH, -C1-3 -alkylene-NH 2 、-C 1-3 -alkylene-NH(C 1-3 -alkyl)、-C 1-3 -alkylene-N(C 1-3 -alkyl) 2 、-C 1-3 -alkylene-NH(C 1-3 -alkylene-CF 3 )、-C 1-3 -alkylene-C(=O)NH 2 、-C 1-3 -alkylene-NH-C(=O)OC 1-4 -alkyl、-C(=O)NH 2 、-C(=O)-NH-C 1-3 -alkyl、-C(=O)-N(C 1-3 -alkyl) 2 、or -3-oxetanyl, or R A7 and R A8 together with the carbon atom to which they are attached form a ring, -CH 2 OCH 2 -, -CH 2 OCH 2 CH 2 -, or -CH 2 CH 2 OCH 2 CH 2 -, -CH 2 NHCH 2 -, -CH 2 NHCH 2 CH 2 -, or -CH 2 CH 2 NHCH 2 CH 2 -.

[0074] In some embodiments, R 3 represents -H, R 4 represents a residue according to general formula (A) as defined above, wherein m A is 0 or 1, Y A is selected from -O- and -CR A7 R A8 -, R A1 、R A2 、R A3 、R A4 、R A5 、R A7 、and R A8 are, independently of one another, -H, -C 1-3 -alkylene-OH, -C 1-3 -alkylene-N(C 1-3 -alkyl) 2 , -C(=O)NH 2、 or -CHF 2 and preferably, R A1 , R A2 , R A3 , R A4 , R A5 , R A7 , and R A8 are, independently of one another, -H, -C 1-3 -alkylene-OH, -C 1-3 -alkylene-N(C 1-3 -alkyl) 2 , or -C(=O)NH 2 and preferably, R A1 , R A2 , R A3 , R A4 , R A5 , R A7 , and R A8 on condition that only one of them represents a residue other than -H.

[0075] In some embodiments, R 3 represents -H, R 4 represents a residue according to general formula (A) as defined above, in which m A is 0 or 1, Y A is selected from -O- and -CR A7 R A8 -, R A1 is -C 1-3 -alkylene-OH, -C 1-3 -alkylene-N(C 1-3 -alkyl) 2 , -C(=O)NH 2 , or -CHF2 represents, preferably, R A1 is -C 1-3 -alkylene-OH, -C 1-3 -alkylene-N(C 1-3 -alkyl) 2 , or -C(=O)NH 2 represents, R A2 , R A3 , R A4 , R A5 , R A7 , and R A8 represent -H.

[0076] In some embodiments, R 3 represents -H, and R 4 represents a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl (preferably 5-membered cycloalkyl), or a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered heterocycloalkyl (preferably 5-membered heterocycloalkyl), or an unsubstituted, monosubstituted or polysubstituted 5- to 14-membered heteroaryl (preferably 5-membered heteroaryl). In a preferred embodiment, R 3 represents -H, and R 4 represents a residue selected from the group consisting of.

Chemical formula

[0077] In some embodiments, R 3 represents -H, and R 4 represents a residue according to general formula (B),

Chemical formula

[0078] In some embodiments, R 3 represents -H, and R 4 represents a residue according to general formula (B) as defined above, where Y B is selected from -O- and -NR B8 -, and R B1 , R B2 , R B3 , R B4 , R B5 , R B6 , R B7 , R B8 are, independently of one another, -H, -F, -C 1-3 -alkyl, -C 1-3 -alkylene-OH, -C 1-3 -alkylene-CF 3 , or -C(=O)NH 2 or R B2 and R B3 together represent =O, or RB4 and R B5 together represent =O, and preferably, R A1 , R A2 , R A3 , R A4 , R A5 , R A7 , and R A8 only one, two, or three of, represent residues other than -H, and preferably, R A1 , R A2 , R A3 , R A4 , R A5 , R A7 , and R A8 only one of, represents a residue other than -H, provided that.

[0079] In some embodiments, R 3 represents -H, and R 4 represents a saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl (preferably, 6-membered cycloalkyl), or a saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl (preferably 6-membered heterocycloalkyl), or an unsubstituted, mono- or polysubstituted 6- to 14-membered aryl (preferably 6-membered aryl), or an unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl (preferably 6-membered heteroaryl). In a preferred embodiment, R 3 represents -H, and R 4 represents a residue selected from the group consisting of.

Chemical formula

[0080] In some embodiments, R 3 represents -H, and R 4 represents a residue according to general formula (C),

Chemical formula

[0081] In some embodiments, R 3 represents, -H, R 4represents a residue according to the general formula (C) defined above, wherein Y C1 is selected from -O- or -NR C8 -, and Y C2 is -CR C11 R C12 -, or Y C1 is -CR C9 R C10 -, and Y C2 is selected from -O- and -NR C8 -; R C1 、R C2 、R C3 、R C4 、R C5 、R C6 、R C7 、R C8 、R C9 、R C10 、R C11 、and R C12 each independently represent -H, -F, -C 1-3 -alkyl, -C 1-3 -alkylene-OH, or -C(=O)NH 2 -, preferably, R C1 、R C2 、R C3 、R C4 、R C5 、R C6 、R C7 、R C8 、R C9 、R C10 、R C11 、and R C12 represent non-H residues only on the condition that one, two, or three of them do, preferably, R C1 、R C2 、R C3 、R C4 、R C5 、R C6 、R C7 、R C8 、R C9 、R C10 、R C11 and R C12 represent non-H residues on the condition that at least one of them does.

[0082] In some embodiments, R 3 represents -H, and R 4 represents a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 7-membered cycloalkyl, or a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 7-membered heterocycloalkyl. In some embodiments, R 3 represents -H, and R 4 represents the following residue.

Chemical formula

[0083] In some embodiments, R 3 represents -H, and R 4 is a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl (preferably 3, 4, 5 or 6-membered cycloalkyl), where the 3- to 14-membered cycloalkyl is a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -alkylene-connected 3- to 14-membered cycloalkyl; or a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered heterocycloalkyl (preferably 4, 5 or 6-membered heterocycloalkyl), where the 3- to 14-membered heterocycloalkyl is a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -alkylene-connected 3- to 14-membered heterocycloalkyl; or an unsubstituted, monosubstituted or polysubstituted 6- to 14-membered aryl (preferably 6-membered aryl), where the 6- to 14-membered aryl is a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -alkylene-connected 6- to 14-membered aryl; or an unsubstituted, monosubstituted or polysubstituted 5- to 14-membered heteroaryl (preferably 5- or 6-membered heteroaryl), where the 5- to 14-membered heteroaryl is a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6Represents a 5- to 14-membered heteroaryl connected via -alkylene-. In a preferred embodiment, R 3 represents -H, and R 4 represents a residue selected from the group consisting of.

Chemical formula

[0084] In some embodiments, R 3 represents -H, and R 4 is a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 5-membered heterocycloalkyl, wherein the 5-membered heterocycloalkyl is a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -alkylene-connected 5-membered heterocycloalkyl; or a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 5-membered heteroaryl, wherein the 5-membered heteroaryl is a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -alkylene-connected 5-membered heteroaryl.

[0085] In some embodiments, R 3 represents -H, and R 4 represents a residue selected from the group consisting of.

Chemical formula

[0086] In some embodiments, R 3 represents -H, and R 4 is (i) the residue -CR’R’’-(CH 2 ) m- OH, wherein m is an integer from 1 to 6, preferably an integer from 1 to 3, and R’ and R’’ are independently of each other -H, -C 1-3 -alkyl, -CF 3 , -CF 2 H, -CFH2 , -C 1-3 -alkylene - CF 3 , -C 1-3 -alkylene - CF 2 H, -C 1-3 -alkylene - CFH 2 , -C 1-3 -alkylene - O - C 1-3 -alkyl, or -C 1-3 -alkylene - OH, preferably -H, -CH 3 , or -C 1-3 -alkylene - OH. In one embodiment, at least R' or R'' does not represent -H. In one embodiment, neither R' nor R'' represents -H, or (ii) a residue according to general formula (D),

Chemical formula

[0087] In some embodiments, R 3 represents -H, and R 4 represents a residue selected from the group consisting of.

Chemical formula

Chemical formula

[0088] In some embodiments of the pyrazolo[1,5-a]pyridine derivative according to the present invention, R 5 and R 5 ' are, independently of each other, -H; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -alkyl; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -heteroalkyl; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted) and represents a 3- to 14-membered cycloalkyl connected via.

[0089] In some embodiments, R5 and R 5 ’ are, independently of each other, -H, -C 1 -C 6 -alkyl, or -C 1 -C 6 -alkylene-N(C 1 -C 6 -alkyl) 2 represents.

[0090] In some embodiments of the pyrazolo[1,5-a]pyridine derivative according to the present invention, R 5 and R 5 ’ at least one of which is not -H.

[0091] In some embodiments of the pyrazolo[1,5-a]pyridine derivative according to the present invention, R 5 and R 5 ’ are both -H.

[0092] In some embodiments, T represents -O-, U represents -CR 5 R 5 ’-, and the resulting moiety -O-CR 5 R 5 ’- represents a residue selected from the group consisting of the following.

Chemical formula

[0093] In some embodiments, T represents -CR 5 R 5 ’-, U represents -O-, and the resulting moiety -CR 5 R 5 ’-O- represents the following residue.

Chemical formula

[0094] In some embodiments, R 5 represents -H, R 5 ’ represents -H, -C 1-3 -alkyl, -CF3 , -CF 2 H, -CFH 2 , -C 1-3 -alkylene - CF 3 , -C 1-3 -alkylene - CF 2 H, -C 1-3 -alkylene - CFH 2、 and -C 1-3 -alkylene - OH, preferably, -H or C 1-3 -alkyl represents a residue selected from the group consisting of.

[0095] In some embodiments of the pyrazolo[1,5 - a]pyridine derivatives according to the present invention, R 6 , R 7 , and R 8 are, independently of each other, -H; -F, -Cl, -Br, -I, -OH, -SH, -SF 5 , -CN, -NO 2 , -C(=O)OH, -NH 2 ; Saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -C 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -O - C 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -NHC 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -N(C 1-6 -alkyl) 2 ; Saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -C(=O)OC 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -OC(=O)C 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -C 1-6 -heteroalkyl, represents.

[0096] In some embodiments, R 6 , R 7 and R 8 are, independently of each other, -H, -F, -Cl, -Br, -I, -OH, -SH, -SF 5 , -CN, -NO 2 , -C(=O)OH, -NH 2 , -C 1-6 -alkyl, -CF 3 , -CHF 2 , -CH 2 F, -O-C 1-6 -alkyl, -OCF 3 , -OCHF 2 , -OCH 2 F, unsubstituted or, independently of each other, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 substituted with one or more substituents selected from 1-6 -NHC unsubstituted or, independently of each other, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 substituted with one or more substituents selected from 1-6 -N(C 2 -alkyl) Unsubstituted, or independently of each other, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -C(=O)OC substituted with one or more substituents selected from 1-6 -alkyl; Unsubstituted, or independently of each other, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -OC(=O)C substituted with one or more substituents selected from 1-6 -alkyl; or Unsubstituted, or independently of each other, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -C substituted with one or more substituents selected from 1-6 -heteroalkyl, represents.

[0097] In some embodiments, R 6 , R 7 , and R 8are, independently of one another, -H, -F, -Cl, -Br, -I, -CN, C 1-3 -alkyl, -CF 3 -, -CF 2 H, and -CFH 2 and preferably represent a residue selected from the group consisting of -H or -F.

[0098] In some embodiments of the pyrazolo[1,5-a]pyridine derivatives according to the invention, R 6 is -H, -F, -Cl, -CN, or -C 1 -C 6 -alkyl.

[0099] In some embodiments of the pyrazolo[1,5-a]pyridine derivatives according to the invention, R 6 does not represent -H.

[0100] In some embodiments, R 6 is -H, -F, -Cl, -CN, or -CH 3 , preferably a residue selected from the group consisting of -H, -F, -CN, or -CH 3 .

[0101] In some embodiments of the pyrazolo[1,5-a]pyridine derivatives according to the invention, R 7 is -H, -F, -Cl, -CN, or -C 1 -C 6 -alkyl.

[0102] In some embodiments of the pyrazolo[1,5-a]pyridine derivatives according to the invention, R 7 does not represent -H.

[0103] In some embodiments, especially when Q represents -NR 3 R 4 , R 7 is a residue selected from the group consisting of -H, -F, -Cl, -CN, or CH 3 .

[0104] In some embodiments, especially when Q is -OR2 When representing, R 7 represents -H or a residue selected from the group consisting of the following.

Chemical formula

[0105] In some embodiments of the pyrazolo[1,5-a]pyridine derivative according to the present invention, R 8 is -H, -F, -Cl, -CN, or -C 1 -C 6 -alkyl.

[0106] In some embodiments of the pyrazolo[1,5-a]pyridine derivative according to the present invention, R 8 does not represent -H.

[0107] In some embodiments, R 8 is a residue preferably selected from the group consisting of -H, -F, -Cl, -CN, or CH 3 and preferably -F.

[0108] In some embodiments of the pyrazolo[1,5-a]pyridine derivative according to the present invention, (i) R 6 , R 7 , and R 8 each represent -H, or (ii) Two of R 6 , R 7 , and R 8 represent -H, and the remaining of R 6 , R 7 , and R 8 represent -F, -Cl, -CN, or -CH 3 , or (iii) One of R 6 , R 7 , and R 8 represents -H, and the remaining of R 6 , R 7 , and R 8 independently of one another represent -F, -Cl, -CN, or -CH 3 .

[0109] In some embodiments, the compound is according to general formula (I), -R 1 represents -CH 3 and / or -R 6 , R 7 , and R 8 each represents -H, and / or -T represents -O-, and / or -U represents -CH 2 - and / or -V represents thiazolyl, pyridyl, or pyrazolyl, and the thiazolyl, pyridyl, and pyrazolyl are each independently unsubstituted, -CH 3 , -F, -CH 2 CHF 2 , and -CF 3 and may be mono-substituted or di-substituted with substituents selected from the group consisting of, and / or -Q represents NR 3 R 4 and / or -R 3 represents H, and / or -R 4 is

Chemical formula

Chemical formula

[0110] In an exemplary embodiment of the present invention, the pyrazolo[1,5-a]pyridine derivative is selected from the group consisting of: Compound 001 - 2 - ({5 - [(2 - fluorophenyl)methoxy] - 2 - methylpyrazolo[1,5 - a]pyridin - 3 - yl}formamide) - 2 - (hydroxymethyl)butanamide, Compound 002 - N-(1,3 - Dihydroxy - 2 - methylpropan - 2 - yl)-5-[(2 - fluorophenyl)methoxy]-2 - methylpyrazolo[1,5 - a]pyridine - 3 - carboxamide, Compound 003 - (2S)-2 - ({5-[(2 - fluorophenyl)methoxy]-2 - methylpyrazolo[1,5 - a]pyridine - 3 - yl}formamido)-3 - hydroxypropanamide, Compound 004 - 2 - ({5-[(2 - fluorophenyl)methoxy]-2 - methylpyrazolo[1,5 - a]pyridine - 3 - yl}formamido)-2 - methylpropanamide, Compound 005 - 5-[(2 - fluorophenyl)methoxy]-N-(2 - methanesulfonamidoethyl)-2 - methylpyrazolo[1,5 - a]pyridine - 3 - carboxamide, Compound 006 - N-(2,2 - Difluoroethyl)-5-[(2 - fluorophenyl)methoxy]-2 - methylpyrazolo[1,5 - a]pyridine - 3 - carboxamide, Compound 007 - (2S,3R)-2 - ({5-[(2 - fluorophenyl)methoxy]-2 - methylpyrazolo[1,5 - a]pyridine - 3 - yl}formamido)-3 - hydroxybutanamide, Compound 008 - N-(1,3 - Dihydroxy - 2 - methylpropan - 2 - yl)-2 - methyl - 5-[(4 - methyl - 1,3 - thiazol - 5 - yl)methoxy]pyrazolo[1,5 - a]pyridine - 3 - carboxamide, Compound 009 - 2 - ({5-[(2 - fluorophenyl)methoxy]-2 - methylpyrazolo[1,5 - a]pyridine - 3 - yl}formamido)-3 - hydroxy - N - methylpropanamide, Compound 010:(2S)-3 - Hydroxy - 2 - ({2 - methyl - 5-[(4 - methyl - 1,3 - thiazol - 5 - yl)methoxy]pyrazolo[1,5 - a]pyridine - 3 - yl}formamido)propanamide, Compound 011:2 - ({5-[(2 - fluorophenyl)methoxy]-2 - methylpyrazolo[1,5 - a]pyridine - 3 - yl}formamido)-3 - hydroxy - N,2 - dimethylpropanamide, Compound 012: (2S)-2-({5-[(2-chlorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamido)-3-hydroxypropanamide, Compound 013: 2-({5-[(2-chlorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamido)-2-methylpropanamide, Compound 014: 5-[(2-chlorophenyl)methoxy]-N-(1,3-dihydroxy-2-methylpropan-2-yl)-2-methylpyrazolo[1,5-a]pyridine-3-carboxamide, Compound 015: 2-{[5-(2,2-difluoroethoxy)-2-methylpyrazolo[1,5-a]pyridin-3-yl]formamido}-3-hydroxy-2-methylpropanamide, Compound 016: 2-{[5-(benzyloxy)-2-methylpyrazolo[1,5-a]pyridin-3-yl]formamido}-3-hydroxy-2-methylpropanamide, Compound 017: 2-({5-[(2-fluorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamido)-3-hydroxy-N,N,2-trimethylpropanamide, Compound 018: 5-[(2-fluorophenyl)methoxy]-N-[3-(hydroxymethyl)-2-oxopyrrolidin-3-yl]-2-methylpyrazolo[1,5-a]pyridine-3-carboxamide, Compound 019: 2-({5-[(2-chlorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamido)-3-hydroxy-2-methylpropanamide, Compound 020: 2-({5-[(2-fluorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamido)-3-hydroxy-2-methylpropanamide, Compound 021: 3-hydroxy-2-methyl-2-({2-methyl-5-[(6-methylpyridin-3-yl)methoxy]pyrazolo[1,5-a]pyridin-3-yl}formamido)propanamide, Compound 022: 2-{[5-(Cyclopropylmethoxy)-2-methylpyrazolo[1,5-a]pyridin-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 023: 2-[(5-{[2-(Difluoromethyl)phenyl]methoxy}-2-methylpyrazolo[1,5-a]pyridin-3-yl)formamide]-3-hydroxy-2-methylpropanamide, Compound 024: 2-(1-{5-[(2-Fluorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}-N-methylformamide)-3-hydroxy-2-methylpropanamide, Compound 025: N-(4,4-Difluoro-1-hydroxy-2-methylbutan-2-yl)-5-[(2-fluorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxamide, Compound 026: 2-({5-[(2,4-Difluorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 027: 2-({5-[(2,3-Difluorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 028: 2-({5-[(2-Fluoro-4-methylphenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 029: 2-({5-[(2-Fluoro-3-methylphenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 030: 2-({5-[(2,5-Difluorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 031: 2-({5-[(2-Fluoro-6-methylphenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 032: 2-({5-[(2,6-Difluorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridin-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 033: 5-(Benzyloxy)-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid, Compound 034: 5-(Cyclopropylmethoxy)-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid, Compound 035: 5-[(2-Fluorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid, Compound 036: 5-[(2-Chlorophenyl)methoxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid, Compound 037: N-(4,4-Difluoro-1-hydroxy-2-methylbutan-2-yl)-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 038: N-(4,4-Difluoro-1-hydroxy-2-methylbutan-2-yl)-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 042: 2-Methyl-5-[(pyridin-2-yl)methoxy]-N-(2,2,2-trifluoroethyl)pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 043: N-(2-Hydroxyethyl)-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 044: N-[(1H-Imidazol-2-yl)methyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 045: N-[3-(dimethylamino)-2,2-dimethylpropyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 046: N-(2,2-difluoro-2-phenylethyl)-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 047: N-{[2-fluoro-6-(trifluoromethyl)phenyl]methyl}-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 048: N-{[3-(difluoromethoxy)phenyl]methyl}-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 049: N-(4,4-difluoropiperidin-3-yl)-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 050: N-(4,4-difluoropiperidin-3-yl)-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 051: N-(5,5-difluoropiperidin-3-yl)-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 052: N-(5,5-difluoropiperidin-3-yl)-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 053: 2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]-N-(pyrrolidin-3-yl)pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 054: 2-methyl-5-[(pyridin-2-yl)methoxy]-N-(pyrrolidin-3-yl)pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 055: N-[3,3-difluoro-1-(hydroxymethyl)cyclobutyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 056: N-[2-hydroxy-5-(trifluoromethyl)pyridin-3-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 057: N-[5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-5-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 058: N-[1-(4-fluorophenyl)-2-hydroxyethyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 059: N-[2-hydroxy-1-(pyridin-2-yl)ethyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 061: N-[1-(4-fluorophenyl)-3-hydroxypropyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 062: 2-methyl-5-[(pyridin-2-yl)methoxy]-N-(4,4,4-trifluoro-1-hydroxybutan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 063: 2-methyl-5-[(pyridin-2-yl)methoxy]-N-[4,4,4-trifluoro-1-hydroxy-3-(trifluoromethyl)butan-2-yl]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 064: N-(4,4-difluoro-1-hydroxybutan-2-yl)-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 066: N-(4,4-difluoro-1-methoxy-2-methylbutan-2-yl)-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 068: N-(1-hydroxy-2-methyl-3-oxobutan-2-yl)-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 071: N-[2,2-difluoro-1-(hydroxymethyl)cyclopropyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 071A: N-[cis-2,2-difluoro-1-(hydroxymethyl)cyclopropyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 071B: N-[trans-2,2-difluoro-1-(hydroxymethyl)cyclopropyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 072: N-[cis-2-(difluoromethyl)-1-(hydroxymethyl)cyclopropyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 074: N-[1-(1-cyclopropyl-1H-imidazol-2-yl)-2-hydroxyethyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 075: N-[1-hydroxy-2-(1-methyl-1H-pyrazol-3-yl)propan-2-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 076: (R)-4-hydroxy-3-({2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridin-3-yl}formamido)butanamide, Compound 077: N-[2-Hydroxy-1-(oxan-4-yl)ethyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 079: N-[1-Hydroxy-3-(pyrimidin-2-yl)propan-2-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 079A: (R)-N-[1-Hydroxy-3-(pyrimidin-2-yl)propan-2-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 079B: (S)-N-[1-Hydroxy-3-(pyrimidin-2-yl)propan-2-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 081: 2-Methyl-5-[(pyridin-2-yl)methoxy]-N-(4,4,4-trifluoro-2-hydroxybutyl)pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 082: 2-Methyl-5-[(pyridin-2-yl)methoxy]-N-[4-(trifluoromethyl)pyrrolidin-3-yl]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 082A: 2-Methyl-5-[(pyridin-2-yl)methoxy]-N-[cis-4-(trifluoromethyl)pyrrolidin-3-yl]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 082B: 2-Methyl-5-[(pyridin-2-yl)methoxy]-N-[trans-4-(trifluoromethyl)pyrrolidin-3-yl]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 084: N-[3-(2,2-Difluoroethyl)piperidin-3-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 087: N-[2-Hydroxy-1-(1-methyl-1H-pyrazol-3-yl)ethyl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 088: N-[1-Hydroxy-3-(pyridin-2-yl)propan-2-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 089: 3-Hydroxy-2-methyl-2-({2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridin-3-yl}formamido)propanamide, Compound 090: 2-Methyl-5-[(pyridin-2-yl)methoxy]-N-(1,1,1-trifluoro-3-hydroxypropan-2-yl)pyrazolo[1,5-a]pyridine-3-carboxamide, Compound 091: N-[3-(Hydroxymethyl)-2-oxopyrrolidin-3-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]pyrazolo[1,5-a]pyridine-3-carboxamide,

[0111] The pyrazolo[1,5-a]pyridine derivatives according to the present invention are preferably for use in the treatment of pain selected from nociceptive pain, inflammatory pain, and neuropathic pain. More preferably, the pain is postoperative pain. The pyrazolo[1,5-a]pyridine derivatives according to the present invention are for use in the treatment of epilepsy.

[0112] In some embodiments, the pyrazolo[1,5-a]pyridine derivative is selected from the group consisting of Compounds 001 to 091 shown in Table 1 below, including its stereoisomers and pharmaceutically acceptable salts.

Table 1-1

Table 1-2

[0113] In some embodiments, the pyrazolo[1,5-a]pyridine derivative is selected from the group consisting of Compounds 037 to 088 shown in Table 2 below, including its stereoisomers and pharmaceutically acceptable salts.

Table 2-1

Table 2-2

Table 2-3

Table 2-4

Table 2-5

[0114] Q, T, U, V, R including the disclosed substituents 1 , R 2 , R 3 , R 4 , R 5 , R 5 ’, R 6 , R 7 , and R 8 All definitions, embodiments, and meanings of are also applicable to the pyrazolo[1,5-a]pyridine derivatives according to the present invention, including but not limited to (a-1), (a-2), (a-3), (b-1), (b-2), and (b-3), but these are not necessarily limited to being used for the treatment of pain. Therefore, this aspect of the present invention relates to the pyrazolo[1,5-a]pyridine derivative itself, a composition containing the pyrazolo[1,5-a]pyridine derivative, a medicament containing the pyrazolo[1,5-a]pyridine derivative, and a pyrazolo[1,5-a]pyridine derivative for use in the prevention and / or treatment of TRPM3-mediated disorders such as pain and / or inflammatory hypersensitivity and / or epilepsy, and / or for counteracting pain and / or inflammatory hypersensitivity and / or epilepsy. Preferably, the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain. More preferably, the pain is postoperative pain.

[0115] In some embodiments of the present invention, the pyrazolo[1,5-a]pyridine derivative is selected from the group consisting of the above-described Compound 001 to Compound 036 and their physiologically acceptable salts.

[0116] In some embodiments of the present invention, the pyrazolo[1,5-a]pyridine derivative is selected from the group consisting of the above-described Compound 037 to Compound 091 and their physiologically acceptable salts.

[0117] Another aspect of the present invention relates to a pharmaceutical composition or a medicament containing the compound according to the present invention described above.

[0118] Throughout this specification, references to "one embodiment" or "an embodiment" mean that the particular features, structures, or characteristics described in connection with that embodiment are included in at least one embodiment of the present invention. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" in various places in this specification are not necessarily all referring to the same embodiment, but may be. Further, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments, as will be apparent to those skilled in the art from this disclosure. Also, the embodiments described for aspects of the present invention may be used and combined in other aspects of the present invention. When an indefinite or definite article is used in reference to a singular noun (e.g., "a" or "an", "the"), unless otherwise specified, this includes the plural form of that noun.

[0119] Similarly, in the description of the exemplary embodiments of the present invention, it should be understood that various aspects of the present invention may be grouped together in a single embodiment, figure, or their description for the purpose of rationalizing the present disclosure and facilitating the understanding of one or more of the various aspects of the present invention.

[0120] In each of the following definitions, the number of carbon atoms represents the maximum number of carbon atoms that is generally optimal for a substituent or linker. Unless otherwise indicated in this application, the number of carbon atoms is understood to represent the optimal maximum number of carbon atoms for that particular substituent or linker.

[0121] As used herein, the term "leaving group" or "LG" means a chemical group that is readily substituted by a nucleophile or readily cleaved or hydrolyzed under basic or acidic conditions. In certain embodiments, the leaving group is selected from a halogen atom (e.g., Cl, Br, I) or a sulfonate (e.g., mesylate, tosylate, triflate).

[0122] The term "protecting group" refers to a moiety of a compound that masks or modifies the properties of a functional group or the properties of the compound as a whole. The chemical substructures of protecting groups are diverse. One function of a protecting group is to function as an intermediate in the synthesis of a prodrug substance. Chemical protecting groups and strategies for protection / deprotection are well known in the art. See: “Protective Groups in Organic Chemistry”, Theodora W. Greene (John Wiley & Sons, Inc., New York, 1991). Protecting groups are often used to hide the reactivity of a particular functional group and to assist in the efficiency of desired chemical reactions, such as creating and breaking chemical bonds in an ordered and planned manner. The protection of a functional group of a compound changes other physical properties of the compound other than the reactivity of the protected functional group, such as polarity, lipophilicity (hydrophobicity), and other properties that can be measured by common analytical tools. Chemically protected intermediates can themselves be biologically active or inactive.

[0123] The protected compound may also exhibit modified properties in vitro and in vivo and, in some cases, may exhibit optimized properties (such as cell membrane permeability and resistance to enzymatic degradation or capture). In this role, a protected compound having the intended therapeutic effect may be referred to as a prodrug. Another function of the protecting group is to convert the parent drug into a prodrug, whereby the parent drug is released upon conversion of the prodrug in vivo. Since the active prodrug may be absorbed more effectively than the parent drug, the prodrug may have greater potency in vivo than the parent drug. The protecting group is removed either in vitro in the case of a chemical intermediate or in vivo in the case of a prodrug. With respect to a chemical intermediate, it is not particularly important that the resulting product (e.g., an alcohol) after deprotection be physiologically acceptable, although it is generally more desirable if this product is pharmacologically innocuous.

[0124] As used herein, the term "heteroatom" means an atom selected from nitrogen, which can be quaternized or can exist as an oxide, oxygen, sulfur in the form of sulfoxide and sulfone, including sulfur in some cases including sulfonate. In some cases, the compound and / or synthetic intermediate may contain heteroatoms such as boron, phosphorus, and silicon.

[0125] As used herein, the term "saturated or unsaturated alkyl" includes saturated alkyl as well as unsaturated alkyl such as alkenyl and alkynyl. As used herein, the term "alkyl" means a normal, secondary or tertiary, linear or branched hydrocarbon having no unsaturated moieties. Examples include methyl, ethyl, 1-propyl (n-propyl), 2-propyl (iPr), 1-butyl, 2-methyl-1-propyl (i-Bu), 2-butyl (s-Bu), 2-dimethyl-2-propyl (t-Bu), 1-pentyl (n-pentyl), 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl, and 3,3-dimethyl-2-butyl. As used herein, the term "alkenyl" means a normal, secondary or tertiary, linear or branched hydrocarbon having at least one unsaturated moiety (usually 1 to 3, preferably 1), i.e., a carbon-carbon, sp2 double bond. Examples include ethylene or vinyl (-CH=CH 2 ), allyl (-CH 2 CH=CH 2 ), and 5-hexenyl (-CH 2 CH 2 CH 2 CH 2 CH=CH 2 ), but are not limited thereto. The double bond may be in a cis or trans configuration. As used herein, the term "alkynyl" means a normal, secondary, tertiary, linear or branched hydrocarbon having at least one unsaturated moiety (usually 1 to 3, preferably 1), i.e., a carbon-carbon, sp triple bond. Examples include ethynyl (-C≡CH), and 1-propynyl (propargyl, -CH 2 C≡CH), but are not limited thereto.

[0126] As used herein, the term "saturated or unsaturated alkylene" includes saturated alkylene and unsaturated alkylene such as alkenylene, alkynylene, alkenynylene. As used herein, the term "alkylene" means a saturated, linear, or branched hydrocarbon radical having two monovalent radical centers obtained by removal of two hydrogen atoms from the same or two different carbon atoms of a parent alkane. Typical alkylene radicals include, but are not limited to, methylene (-CH 2 -), 1,2-ethylene (-CH 2 CH 2 -), 1,3-propylene (-CH 2 CH 2 CH 2 -), 1,4-butylene (-CH 2 CH 2 CH 2 CH 2 -), etc. As used herein, the term "alkenylene" means a linear or branched hydrocarbon radical having two monovalent radical centers obtained by removing two hydrogen atoms from the same or two different carbon atoms of a parent alkene and having at least one site of unsaturation (usually 1 to 3, preferably 1), i.e., a carbon-carbon, sp2 double bond. As used herein, the term "alkynylene" means a linear or branched hydrocarbon radical having two monovalent radical centers obtained by removing two hydrogen atoms from the same or two different carbon atoms of a parent alkene and having at least one site of unsaturation (usually 1 to 3, preferably 1), i.e., a carbon-carbon, sp triple bond.

[0127] As used herein, the term "saturated or unsaturated heteroalkyl" includes saturated heteroalkyl as well as unsaturated heteroalkyl such as heteroalkenyl, heteroalkynyl, heteroalkenynyl. As used herein, the term "heteroalkyl" means a linear or branched alkyl in which one or more carbon atoms (usually one, two, or three) are replaced by a heteroatom, i.e., an oxygen, nitrogen, or sulfur atom, provided that the chain does not contain two adjacent O atoms or two adjacent S atoms. This means that one or more -CH 3 can be replaced by -NH 2 and / or one or more -CH 2 - of the alkyl can be replaced by -NH-, -O-, or -S-. The S atom in the chain can optionally be oxidized by one or two oxygen atoms to give sulfoxide and sulfone, respectively. Further, the heteroalkyl group in the pyrazolo[1,5-a]pyridine derivative of the present invention can contain an oxo or thio group on any carbon or heteroatom that would result in a stable compound. Exemplary heteroalkyl groups include, but are not limited to, alcohol, alkyl ether (e.g., -methoxy, -ethoxy, -butoxy, etc.), primary, secondary, and tertiary alkylamine, amide, ketone, ester, alkyl sulfide, and alkyl sulfone. The term "heteroalkenyl" means a linear or branched alkenyl in which one or more carbon atoms (usually one, two, or three) are replaced by an oxygen, nitrogen, or sulfur atom, provided that the chain does not contain two adjacent O atoms or two adjacent S atoms. Thus, the term heteroalkenyl includes imine, -O-alkenyl, -NH-alkenyl, -N(alkenyl) 2, -N(alkyl)(alkenyl), and -S-alkenyl. As used herein, the term "heteroalkynyl" means a linear or branched alkynyl in which one or more carbon atoms (usually one, two, or three) are replaced by an oxygen, nitrogen, or sulfur atom, provided that the chain does not contain two adjacent O atoms or two adjacent S atoms. Thus, the term heteroalkynyl includes -cyano, -O-alkynyl, -NH-alkynyl, -N(alkynyl) 2 , -N(alkyl)(alkynyl), -N(alkenyl)(alkynyl), and -S-alkynyl.

[0128] As used herein, the term "saturated or unsaturated heteroalkylene" includes saturated heteroalkylene and unsaturated heteroalkylene such as heteroalkenylene, heteroalkynylene, heteroalkenynylene. As used herein, the term "heteroalkylene" means a linear or branched alkylene in which one or more carbon atoms (usually one, two, or three) are replaced by a heteroatom, i.e., an oxygen, nitrogen, or sulfur atom, provided that the chain does not contain two adjacent O atoms or two adjacent S atoms. As used herein, the term "heteroalkenylene" means a linear or branched alkenylene in which one or more carbon atoms (usually one, two, or three) are replaced by an oxygen, nitrogen, or sulfur atom, provided that the chain does not contain two adjacent O atoms or two adjacent S atoms. As used herein, the term "heteroalkynylene" means a linear or branched alkynylene in which one or more carbon atoms (usually one, two, or three) are replaced by an oxygen, nitrogen, or sulfur atom, provided that the chain does not contain two adjacent O atoms or two adjacent S atoms.

[0129] As used herein, the term "saturated or unsaturated cycloalkyl" includes saturated cycloalkyl, as well as unsaturated cycloalkyl such as cycloalkenyl and cycloalkynyl. As used herein, the term "cycloalkyl", unless otherwise specified, means a saturated cyclic hydrocarbon radical such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornyl, fenchyl, decalinyl, adamantyl, etc. As used herein, the term "cycloalkenyl" means a non-aromatic cyclic hydrocarbon radical having at least one site of unsaturation (usually 1 to 3, preferably 1), i.e., a carbon-carbon, sp2 double bond. Examples include, but are not limited to, cyclopentenyl and cyclohexenyl. The double bond may be in the cis or trans configuration. As used herein, the term "cycloalkynyl" means a non-aromatic cyclic hydrocarbon radical having at least one site of unsaturation (usually 1 to 3, preferably 1), i.e., a carbon-carbon, sp triple bond. One example is cyclohepta-1-yne. A fused system of a cycloalkyl ring having a heterocycloalkyl ring is considered a heterocycloalkyl regardless of the ring attached to the core structure. A fused system of a cycloalkyl ring having an aryl ring is considered an aryl regardless of the ring attached to the core structure. A fused system of a cycloalkyl ring having a heteroaryl ring is considered a heteroaryl regardless of the ring attached to the core structure.

[0130] As used herein, the term "saturated or unsaturated heterocycloalkyl" includes saturated heterocycloalkyl, which contains at least one heteroatom, i.e., N, O, or S as a ring member, and unsaturated non-aromatic heterocycloalkyl. As used herein, the term "heterocycloalkyl" means "cycloalkyl" in which one or more carbon atoms (usually one, two, or three) are replaced by oxygen, nitrogen, or sulfur atoms, provided that the chain does not contain two adjacent O atoms or two adjacent S atoms, unless otherwise specified. As used herein, the term "heterocycloalkenyl" means "heterocycloalkenyl" in which one or more carbon atoms (usually one, two, or three) are replaced by oxygen, nitrogen, or sulfur atoms, provided that the chain does not contain two adjacent O atoms or two adjacent S atoms, unless otherwise specified. As used herein, the term "heterocycloalkynyl" means "heterocycloalkynyl" in which one or more carbon atoms (usually one, two, or three) are replaced by oxygen, nitrogen, or sulfur atoms, provided that the chain does not contain two adjacent O atoms or two adjacent S atoms, unless otherwise specified.Examples of saturated and unsaturated heterocycloalkyls include, but are not limited to, azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxazolidine, morpholine, oxazolidine, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiacyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, hexahydro-1H-pyrrolidine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, and octahydropyrrolo[1,2-a]pyrazine. Further heterocycloalkyls in the meaning of the present invention are described in Paquette, Leo A. “Principles of Modern Heterocyclic Chemistry” (W.A. Benjamin, New York, 1968), especially Chapters 1, 3, 4, 6, 7, and 9, “The Chemistry of Heterocyclic Compounds, A series of Monographs” (John Wiley & Sons, New York, 1950 - present), especially Volumes 13, 14, 16, 19, and 28, Katritzky, Alan R., Rees, C.W. and Scriven, E. “Comprehensive Heterocyclic Chemistry” (Pergamon Press, 1996), and J. Am. Chem. Soc. (1960) 82:5566. When the heterocycloalkyl does not contain nitrogen as a ring member, it is typically bonded via carbon. When the heterocycloalkyl contains nitrogen as a ring member, it can be bonded via nitrogen or carbon.A fused system of a heterocycloalkyl ring having a cycloalkyl ring is regarded as a heterocycloalkyl regardless of the ring bonded to the core structure. A fused system of a heterocycloalkyl ring having an aryl ring is regarded as a heterocycloalkyl regardless of the ring bonded to the core structure. A fused system of a heterocycloalkyl ring having a heteroaryl ring is regarded as a heteroaryl regardless of the ring bonded to the core structure.

[0131] As used herein, the term "aryl" means an aromatic hydrocarbon. Typical aryl groups include, but are not limited to, radicals derived from benzene, naphthalene, anthracene, biphenyl, etc., which are monocyclic or two- or three-ring fused together. A fused system of an aryl ring having a cycloalkyl ring is regarded as an aryl regardless of the ring bonded to the core structure. A fused system of an aryl ring having a heterocycloalkyl ring is regarded as a heterocycloalkyl regardless of the ring bonded to the core structure. Thus, indoline, dihydrobenzofuran, dihydrobenzothiophene, etc. are regarded as heterocycloalkyls according to the present invention. A fused system of an aryl ring having a heteroaryl ring is regarded as a heteroaryl regardless of the ring bonded to the core structure.

[0132] As used herein, the term "heteroaryl" means an aromatic ring system containing at least one heteroatom, i.e., N, O, or S, as a ring member of the aromatic ring system. Examples of heteroaryl include, but are not limited to, benzimidazole, benzisoxazole, benzazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furan, furazan, imidazole, imidazopyridine, indazole, indole, indolizine, isobenzofuran, isoindole, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, oxyindole, phthalazine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine.

[0133] As a further example, the carbon-bonded heterocycle is bonded at the 2-, 3-, 4-, 5-, or 6-position of pyridine, the 3-, 4-, 5-, or 6-position of pyridazine, the 2-, 4-, 5-, or 6-position of pyrimidine, the 2-, 3-, 5-, or 6-position of pyrazine, the 2-, 3-, 4-, or 5-position of furan, tetrahydrofuran, thiophene, pyrrole, or tetrahydropyrrole, the 2-, 4-, or 5-position of oxazole, imidazole, or thiazole, the 3-, 4-, or 5-position of isoxazole, pyrazole, or isothiazole, the 2- or 3-position of aziridine, the 2-, 3-, or 4-position of azetidine, the 2-, 3-, 4-, 5-, 6-, 7-, or 8-position of quinoline, or the 1-, 3-, 4-, 5-, 6-, 7-, or 8-position of isoquinoline.

[0134] Examples of the carbon-bonded heterocyclic ring include 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl, 6-pyridyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4-thiazolyl, or 5-thiazolyl. As an example, the nitrogen-bonded heterocyclic ring is bonded to the 1-position of aziridine, azetidine, pyrrole, pyrrolidine, 2-pyrroline, 3-pyrroline, imidazole, imidazolidine, 2-imidazoline, 3-imidazoline, pyrazole, pyrazoline, 2-pyrazoline, 3-pyrazoline, piperidine, piperazine, indole, indoline, 1H-indazole, the 2-position of isoindole or isoindoline, the 4-position of morpholine, and the 9-position of carbazole or β-carboline. Examples of the nitrogen-bonded heterocyclic ring include 1-aziridyl, 1-azetedyl, 1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, and 1-piperidinyl. Further heteroaryl in the meaning of the present invention is described in Paquette, Leo A. “Principles of Modern Heterocyclic Chemistry” (W.A. Benjamin, New York, 1968), particularly Chapters 1, 3, 4, 6, 7, and 9, “The Chemistry of Heterocyclic Compounds, A series of Monographs” (John Wiley & Sons, New York, 1950 - present), particularly Volumes 13, 14, 16, 19, and 28, Katritzky, Alan R., Rees, C.W. and Scriven, E. “Comprehensive Heterocyclic Chemistry” (Pergamon Press, 1996), and J. Am. Chem. Soc. (1960) 82:5566.

[0135] As used herein with respect to substituents, unless otherwise specified, terms such as "monosubstituted", "disubstituted", "trisubstituted", "polysubstituted", etc. mean chemical structures defined herein, each part being substituted with one or more substituents, meaning that one or more hydrogen atoms of the part are each independently replaced with a substituent. For example, -C which may be polysubstituted with -F 1-6 -alkyl is -CH 2 F, -CHF 2 , -CF 3 , -CH 2 CF 3 , CF 2 CF 3 and the like. Similarly, -C which may be polysubstituted with substituents independently selected from -F and -Cl 1-6 -alkyl is -CH 2 F, -CHF 2 , -CF 3 , -CH 2 CF 3 , CF 2 CF 3 , -CH 2 Cl, -CHCl 2 , -CCl 3 , -CH 2 CCl 3 , CCl 2 CCl 3 , -CHClF, -CClF 2 , -CCl 2 CF 3 , -CF 2 CCl 3 , -CClFCCl 2 F and the like. The designation of any substituent found at multiple sites in the compounds of the present invention is to be independently selected.

[0136] As used herein, unless otherwise specified, the term "solvate" includes any combination that can be formed by a derivative of the present invention with a suitable inorganic solvent (e.g., hydrate) or an organic solvent such as, but not limited to, alcohol, ketone, ester, ether, nitrile, etc.

[0137] As used herein, the term "subject" refers to an animal, preferably a mammal, most preferably a human, who is the subject of treatment, observation, or experiment.

[0138] As used herein, the term "therapeutically effective amount" means an amount of an active compound or pharmaceutical that elicits a biological or pharmaceutical response in a tissue system, animal, or human, as determined by a researcher, veterinarian, physician, or other clinician, including alleviation or partial alleviation of the symptoms of a disease or disorder being treated.

[0139] As used herein, the term "composition" is intended to encompass a product containing a therapeutically effective amount of a designated ingredient, as well as any product directly or indirectly obtained from a combination of the designated amount of the designated ingredients.

[0140] As used herein, the term "antagonist" or "inhibitor" refers to a compound capable of producing a functional antagonism of the TRPM3 ion channel, including competitive antagonists, non-competitive antagonists, desensitizing agonists, and partial agonists, depending on the situation. Generally, "antagonist" and "inhibitor" can be understood to modulate TRPM3.

[0141] For the purposes of the present invention, the term "TRPM3-regulated" is used to refer to a state that is affected by the regulation of the TRPM3 ion channel, including states mediated by the TRPM3 ion channel.

[0142] As used herein, the term "TRPM3-mediated disorder" refers to a disorder or disease consisting of pain, inflammatory hypersensitivity conditions, and epilepsy, where the use of an antagonist or modulator of TRPM3 prevents, treats, (partially) alleviates, or improves the symptoms. According to the International Association for the Study of Pain, for the purposes of the present invention, pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. Preferably, the TRPM3-mediated disorder is preferably pain selected from nociceptive pain, inflammatory pain, and neuropathic pain. More preferably, the pain is postoperative pain. For the purposes of the present invention, the term "inflammatory hypersensitivity" is used to refer to a condition characterized by one or more features of inflammation including edema, erythema, hyperthermia and pain, and / or by an exaggerated physiological or pathophysiological response to one or more types of stimuli including thermal, mechanical, and / or chemical stimuli.

[0143] The pyrazolo[1,5-a]pyridine derivatives of the present invention have been shown or are understood to be antagonists or modulators of TRPM3, and thus the present invention provides the compound itself, the compound for use as a medicament, more specifically, the compound for use as a medicament in the prevention or treatment of TRPM3-mediated disorders in a subject using a therapeutically effective amount of the pyrazolo[1,5-a]pyridine derivative of the present invention.

[0144] In one embodiment of the present invention, the pyrazolo[1,5-a]pyridine derivative of the present invention is the only pharmacologically active compound administered for treatment. In another embodiment of the present invention, the pyrazolo[1,5-a]pyridine derivative of the present invention can be used in combination with other therapeutic agents for the treatment or prevention of TRPM3-mediated disorders. Thus, the present invention also - one or more compounds of the formulas and embodiments herein, and -Regarding the use of a composition comprising one or more further therapeutic or prophylactic agents used as biologically active agents in the form of a combined preparation for simultaneous, separate or sequential use for the prevention or treatment of TRPM3-mediated disorders.

[0145] The pharmaceutical composition or combined preparation according to the invention may contain the pyrazolo[1,5-a]pyridine derivative of the invention over a wide range of contents, depending on the intended use and the expected effect of the preparation. Generally, the content of the pyrazolo[1,5-a]pyridine derivative of the invention in the combined preparation is in the range of 0.1 to 99.9% by weight, preferably 1 to 99% by weight, more preferably 5 to 95% by weight.

[0146] When several active ingredients are used in combination, taking into account the fact that they do not necessarily directly exert their combined therapeutic effect simultaneously in the mammal to be treated, the corresponding composition may also be in the form of a medical kit or package containing two components in separate but adjacent reservoirs or compartments. Thus, in the latter situation, each active ingredient can be formulated in a manner suitable for an administration route different from that of the other ingredients. For example, one of them can be in the form of an oral or parenteral preparation, while the other can be in the form of an ampoule for intravenous injection or an aerosol.

[0147] Those skilled in the art will also recognize that the pyrazolo[1,5-a]pyridine derivatives of the invention can exist in many different protonation states, especially depending on the pH of their environment. The structural formulas provided herein show compounds in only one of several possible protonation states, but these structures are illustrative and the invention is not limited to any particular protonation state, and it will be understood that any and all protonated forms of the compounds are intended to fall within the scope of the invention.

[0148] As used herein, the terms "pharmaceutically acceptable salt" or "physiologically acceptable salt" mean therapeutically active non-toxic salt forms that can be formed by the compounds of the formulas herein. Thus, the compounds of the present invention optionally include salts of the compounds herein, particularly, for example, Na + , Li + , K + , Ca 2+ , and Mg 2+ -containing pharmaceutically acceptable non-toxic salts. Such salts can include those derived by the combination of a suitable cation, such as an alkali metal and alkaline earth metal ion, or ammonium and quaternary amino ions, with an acidic anion moiety, typically a carboxylic acid. The pyrazolo[1,5-a]pyridine derivatives of the present invention can have multiple positive or negative charges. The net charge of the pyrazolo[1,5-a]pyridine derivatives of the present invention can be either positive or negative. Any associated counterion is typically determined by the synthetic and / or isolation methods by which the compound is obtained. Typical counterions include, but are not limited to, ammonium, sodium, potassium, lithium, halides, acetic acid, trifluoroacetic acid, etc., and mixtures thereof. The identity of any associated counterion is not an important feature of the present invention, and it will be understood that the present invention includes compounds that associate with any type of counterion. Further, since the compounds can exist in various different forms, the present invention is intended to include not only forms of the compounds that associate with a counterion (e.g., dry salts), but also forms that do not associate with a counterion (e.g., aqueous or organic solutions). Metal salts are typically prepared by reacting a metal hydroxide with the compounds of the present invention. Examples of metal salts prepared in such a manner are Li + , Na + , and K +It is a salt containing. Less soluble metal salts can be precipitated from a solution of a more soluble salt by the addition of a suitable metal compound. In addition, the salt can be formed from the acid addition of certain organic and inorganic acids to basic centers, typically amines, or acidic groups. Examples of such suitable acids include, for example, hydrohalogen acids such as hydrochloric acid or hydrobromic acid, inorganic acids such as sulfuric acid, nitric acid, phosphoric acid, or organic acids such as acetic acid, propanoic acid, hydroxyacetic acid, 2-hydroxypropanoic acid, 2-oxopropanoic acid, lactic acid, pyruvic acid, oxalic acid (i.e., ethanedioic acid), malonic acid, succinic acid (i.e., butanedioic acid), maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, cyclohexanesulfamic acid, salicylic acid (i.e., 2-hydroxybenzoic acid), p-aminosalicylic acid, and the like. Furthermore, the term also includes solvates, such as hydrates, alcoholates, etc., that the compounds of the formulas herein and their salts can form. Finally, it should be understood that the compositions herein include the pyrazolo[1,5-a]pyridine derivatives of the present invention in their non-ionized form, as well as zwitterionic forms, and in combination with a stoichiometric amount of water as hydrates.

[0149] Salts of the parent compounds with one or more amino acids, particularly natural amino acids found as protein components, are also included within the scope of the present invention. Amino acids typically have side chains with basic or acidic groups such as, for example, lysine, arginine, or glutamic acid, or neutral groups such as glycine, serine, threonine, alanine, isoleucine, or leucine.

[0150] The pyrazolo[1,5-a]pyridine derivatives of the present invention also include their physiologically acceptable salts. Examples of physiologically acceptable salts of the pyrazolo[1,5-a]pyridine derivatives of the present invention include alkali metals (e.g., sodium), alkaline earths (e.g., magnesium), ammonium, and NX4 + (wherein X is -C 1-6-alkyl), and salts derived from suitable bases such as. Physiologically acceptable salts of a hydrogen atom or an amino group include organic carboxylic acids such as acetic acid, benzoic acid, lactic acid, fumaric acid, tartaric acid, maleic acid, malonic acid, malic acid, isethionic acid, lactobionic acid, and succinic acid, organic sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid, and salts of inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, and sulfamic acid. Physiologically acceptable salts of a compound containing a hydroxy group include the anion of the compound combined with a suitable cation such as Na + and NX4 + including (wherein X is typically independently selected from -H or -C 1-4 -alkyl group). However, salts of acids and bases that are not physiologically acceptable may also be recognized for use, for example, in the preparation or purification of physiologically acceptable compounds. All salts are within the scope of the present invention, regardless of whether they are in a form derived from a physiologically acceptable acid or base.

[0151] As used herein, the term "enantiomer" means, unless otherwise specified, each optically active form of the pyrazolo[1,5-a]pyridine derivative of the present invention having an optical purity or enantiomeric excess of at least 80% (i.e., at least 90% of one enantiomer and at most 10% of the other enantiomer), preferably at least 90%, more preferably at least 98% (determined by standard methods in the art).

[0152] As used herein, the term "isomer" means all possible isomeric forms, including tautomeric and stereochemical forms, that a compound of the formulas herein may have, but does not include positional isomers. Typically, the structures shown herein illustrate only one tautomer or resonance form of a compound, but the corresponding alternative configurations are equally contemplated. Unless otherwise specified, the chemical name of a compound denotes a mixture of all possible stereochemical isomeric forms, which mixture contains all diastereomers and enantiomers of the basic molecular structure (since the compounds of the formulas herein may have at least one chiral center), as well as stereochemically pure or enriched compounds. More specifically, a stereocenter may have either an R or S configuration, and a multiple bond may have either a cis or trans configuration.

[0153] A pure isomeric form of the compound is defined as an isomer that is substantially free of other enantiomeric or diastereomeric forms of the same basic molecular structure. Specifically, the terms "stereoisomerically pure" or "chiral pure" relate to compounds having a stereoisomer excess of at least about 80% (i.e., at least 90% of one isomer and a maximum of 10% of the other possible isomers), preferably at least 90%, more preferably at least 94%, and most preferably at least 97%. The terms "enantiomerically pure" and "diastereomerically pure" should be understood in a similar manner, taking into account the enantiomeric excess and diastereomeric excess, respectively, of the mixture in question.

[0154] The separation of stereoisomers is achieved by standard methods known to those skilled in the art. One enantiomer of the pyrazolo[1,5-a]pyridine derivatives of the present invention can be separated to substantially exclude its opposite enantiomer by methods such as the formation of diastereomers using an optically active resolving agent (“Stereochemistry of Carbon Compounds,” (1962) E.L. Eliel, McGraw Hill, Lochmuller, C.H., (1975) J. Chromatogr., 113: (3) 283-302). The separation of isomers in a mixture can be achieved by any suitable method including (1) the formation of ionic diastereomeric salts with chiral compounds and separation by fractional crystallization or other methods, (2) the formation of diastereomeric compounds with chiral derivatizing reagents, separation of the diastereomers, and conversion to pure enantiomers, or (3) the ability of enantiomers to be directly separated under chiral conditions. In method (1), diastereomeric salts can be formed by the reaction of enantiomerically pure chiral bases such as brucine, quinine, ephedrine, strychnine, a-methyl-b-phenylethylamine (amphetamine), etc. with asymmetric compounds having acidic functionalities such as carboxylic acids and sulfonic acids. Diastereomeric salts can be induced to separate by fractional crystallization or ion chromatography. The addition of chiral carboxylic acids or sulfonic acids such as camphorsulfonic acid, tartaric acid, mandelic acid, or lactic acid can result in the formation of diastereomeric salts for the separation of optical isomers of amino compounds. Alternatively, by method (2), the substrate to be resolved may be reacted with one enantiomer of a chiral compound to form a diastereomeric pair (Eliel, E. and Wilen, S. (1994) Stereochemistry of Organic Compounds, John Wiley & Sons, Inc., p. 322). Diastereomeric compounds can be formed by reacting an asymmetric compound with an enantiomerically pure chiral derivatizing reagent such as a methyl derivative, followed by separation and hydrolysis of the diastereomers to obtain a free enantiomerically enriched compound.Methods for determining optical purity include preparing chiral esters such as menthyl esters or Mosher esters, a-methoxy-a-(trifluoromethyl)phenylacetate (Jacob III. (1982) J. Org. Chem. 47:4165) from a racemic mixture, purifying by, and analyzing the NMR spectrum for the presence of two atropisomeric diastereomers. Stable diastereomers can be separated and isolated by normal and reverse phase chromatography according to methods for the separation of atropisomeric naphthyl-isoquinolines (Hoye, T., WO96 / 15111). In method (3), a racemic mixture of two asymmetric enantiomers is separated by chromatography using a chiral stationary phase. Suitable chiral stationary phases are, for example, polysaccharides, especially cellulose or amylose derivatives. Commercially available polysaccharide-based chiral stationary phases are ChiralCel® CA, OA, OB5, OC5, OD, OF, OG, OJ and OK, and Chiralpak® AD, AS, OP(+) and OT(+). Suitable eluents or mobile phases for use in combination with the polysaccharide chiral stationary phase are hexanes, etc. modified with alcohols such as ethanol, isopropanol, etc. (“Chiral Liquid Chromatography” (1989) W.J. Lough, Ed. Chapman and Hall, New York, Okamoto, (1990) “Optical resolution of dihydropyridine enantiomers by High-performance liquid chromatography using phenylcarbamates of polysaccharides as a chiral stationary phase”, J. of Chromatogr. 513:375-378).

[0155] The terms cis and trans are used herein in accordance with Chemical Abstracts nomenclature and include reference to the position of substituents on the cyclic moiety. The absolute stereochemical configuration of the compounds of the formulas described herein can be readily determined by one skilled in the art using well-known methods such as, for example, X-ray diffraction.

[0156] When a compound crystallizes from solution or slurry, it can crystallize in different spatial lattice arrangements (this property is called "polymorphism") and form crystals with different crystal morphologies, each of which is known as a "polymorph". Thus, the term "polymorph" as used herein refers to the crystal form of the compound of formula (I), where the molecules are localized at the three-dimensional lattice sites. Different polymorphs of the compound of formula (I) can differ from each other in one or more physical properties such as solubility and dissolution rate, true specific gravity, crystal form, packing mode, fluidity, and / or solid-state stability.

[0157] The pyrazolo[1,5-a]pyridine derivatives of the present invention and their physiologically acceptable salts (hereinafter collectively referred to as the active ingredients) can be administered by any suitable route appropriate for the condition being treated, including oral, rectal, nasal, topical (including ocular, oral, and sublingual), vaginal, and parenteral (including subcutaneous, intramuscular, intranasal, intravenous, intraarterial, intradermal, intrathecal, and epidural). The preferred route of administration can vary, for example, depending on the condition of the recipient.

[0158] In particular, for the treatment of TRPM3-mediated disorders in humans and other mammals, or animals, a therapeutically effective amount for the preparation of the compound is preferably the amount that inhibits the TRPM3 ion channel of the compound as defined herein and corresponds to the amount that ensures a plasma level of 1 μg / ml to 100 mg / ml.

[0159] A suitable dosage of the compound or composition of the present invention should be used to treat or prevent a TRPM3-mediated disorder in a subject. Depending on the pathological condition being treated and the condition of the patient, the effective amount can be divided into several subunits per day or administered at intervals over more than one day.

[0160] The present invention further provides a (pharmaceutical) composition comprising one or more pyrazolo[1,5-a]pyridine derivatives of the present invention, more specifically, all formulas (I) and other formulas and embodiments described herein, and their more specific aspects or embodiments. Further, the present invention provides the compounds or (pharmaceutical) compositions of the present invention, more specifically, all formulas (I) and other formulas and embodiments described herein, and their more specific aspects or embodiments, for use as a drug, more specifically, for use in the treatment of pain. The TRPM3-mediated disorder is selected from pain and inflammatory hypersensitivity conditions and epilepsy.

[0161] The pyrazolo[1,5-a]pyridine derivatives of the present invention can be formulated with conventional carriers and excipients, which are selected according to normal practice. Tablets contain excipients, glidants, fillers, binders, etc. Aqueous formulations are prepared in a sterile form and are generally isotonic when intended for delivery other than oral administration. The formulations optionally contain excipients as described in the "Handbook of Pharmaceutical Excipients" (1986).

[0162] Thereafter, the term "pharmaceutically acceptable carrier" as used herein means any material or substance in which the active ingredient is formulated to facilitate the application or dispersion of the composition to the site to be treated, e.g., by dissolving, dispersing, or diffusing the composition, and / or to facilitate its storage, transport, or handling without impairing its effectiveness. A pharmaceutically acceptable carrier can be a solid, a liquid, or a gas compressed to form a liquid, i.e., the compositions of the present invention can be suitably used as concentrates, emulsions, solutions, granules, dusts, sprays, aerosols, suspensions, ointments, creams, tablets, pellets, or powders.

[0163] Suitable pharmaceutical carriers for use in the pharmaceutical composition and its formulations are well-known to those skilled in the art and are not particularly limited in their selection within the present invention. They may also include additives such as wetting agents, dispersants, stickers, adhesives, emulsifiers, surfactants, solvents, coating agents, antibacterial and antifungal agents, and isotonic agents, provided that these are compatible with pharmaceutical practice, i.e., carriers and additives that do not cause permanent damage to mammals. The pharmaceutical compositions of the present invention can be prepared by any known method, for example, by uniformly mixing, coating, and / or grinding the selected carrier material, and optionally other additives such as surfactants, with the active ingredient in a one-step or multi-step procedure. They can also be prepared by micronization to obtain them in the form of microspheres having a diameter of usually about 1 to 10 gm, for example, for the production of microcapsules for the controlled or sustained release of the active ingredient.

[0164] Pyrazolo[1,5-a]pyridine derivatives can be administered alone, but it is preferred that they be presented as pharmaceutical formulations. The formulations of the present invention for both veterinary and human use include, as described above, at least one active ingredient together with one or more pharmaceutically acceptable carriers therefor and optionally other therapeutic ingredients. The carrier is "acceptable" in the sense that it is most preferably compatible with the other ingredients of the formulation and not harmful to its recipient. The formulations include those suitable for oral, rectal, nasal, topical (including buccal and sublingual), vaginal, or parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural) administration. The formulations can conveniently be presented in unit dosage form and can be prepared by any of the methods well-known in the pharmaceutical art. Such methods include the step of bringing the active ingredient into association with a carrier which constitutes one or more accessory ingredients. In general, the formulations are prepared by uniformly and intimately bringing the active ingredient into association with a liquid carrier, or a finely divided solid carrier, or both, and optionally shaping the product.

[0165] The pharmaceutical preparations of the present invention suitable for oral administration may be presented as individual units such as capsules, cachets, or tablets, each containing a predetermined amount of the active ingredient, as powders or granules, as solutions or suspensions in aqueous or non-aqueous liquids, or as oil-in-water or water-in-oil liquid emulsions. The active ingredient may also be presented as a bolus, lozenge, or paste.

[0166] Tablets can be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared by compressing, in a suitable machine, the active ingredient in free-flowing form, such as a powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surfactant, or dispersing agent. Molded tablets can be produced by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent. Tablets can optionally be coated or scored and formulated to provide for the slow or controlled release of the active ingredient therein. In the case of infections of the eye or other external tissues, such as the mouth and skin, the preparation can be applied optionally as a topical ointment or cream containing the active ingredient in an amount of, for example, 0.075 to 20 w / w% (including the active ingredient in the range of 0.1% to 20% in increments of 0.1 w / w% such as 0.6 w / w%, 0.7 w / w%, etc.), preferably 0.2 to 15 w / w%, most preferably 0.5 to 10 w / w%. When formulated as an ointment, the active ingredient can be used with either a paraffin-based or water-miscible ointment base. Alternatively, the active ingredient can be formulated into a cream having an oil-in-water cream base. Optionally, the aqueous phase of the cream base can contain, for example, at least 30 w / w% of a polyhydric alcohol, i.e., an alcohol having two or more hydroxyl groups such as propylene glycol, butane 1,3-diol, mannitol, sorbitol, glycerol, and polyethylene glycol (including PEG400), and mixtures thereof. The topical preparation can desirably contain a compound that enhances the absorption or penetration of the active ingredient through the skin or other affected area. Examples of such skin penetration enhancers include dimethyl sulfoxide and related analogs.

[0167] The oily phase of the emulsion of the present invention can be composed of known components by known methods. The phase may simply contain an emulsifier (also known as an emulgent), but preferably contains a mixture of at least one emulsifier and a fat or an oil, or a mixture with both a fat and an oil. Optionally, a hydrophilic emulsifier is included together with a lipophilic emulsifier that acts as a stabilizer. It is also preferred to contain both an oil and a fat. Regardless of the presence or absence of a stabilizer, the emulsifiers together constitute a so-called emulsifying wax, and the wax, together with the oil and the fat, constitutes a so-called emulsifying ointment base that forms the oily dispersed phase of the cream preparation.

[0168] Since the solubility of the active compound in most oils that are likely to be used in pharmaceutical emulsion preparations is very low, the selection of a suitable oil or fat for the preparation is based on achieving the desired cosmetic properties. Thus, the cream should be a non-greasy, non-staining and washable product with a suitable consistency to avoid leakage from tubes or other containers. Straight-chain or branched-chain, mono- or dibasic alkyl esters such as diisoadipate, isocetyl stearate, propylene glycol diester of coconut fatty acid, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate, or a blend of branched-chain esters known as Crodamol CAP can be used, with the last three being preferred esters. These can be used alone or in combination depending on the required properties. Alternatively, high melting point lipids such as white soft paraffin and / or liquid paraffin or other mineral oils can be used.

[0169] Formulations suitable for topical administration to the eye also include eye drops in which the active ingredient is dissolved or suspended in a suitable carrier, particularly an aqueous solvent for the active ingredient. The active ingredient is optionally present in such formulations at a concentration of 0.5 to 20%, preferably 0.5 to 10%, particularly about 1.5 w / w%. Formulations suitable for topical administration to the oral cavity usually include lozenges containing the active ingredient in a flavoring base such as sucrose and acacia or tragacanth; troches containing the active ingredient in an inert base such as gelatin and glycerin, or sucrose and acacia; and mouthwashes containing the active ingredient in a suitable liquid carrier.

[0170] Formulations for rectal administration can be presented, for example, as suppositories using a suitable base containing cocoa butter or salicylate. Formulations suitable for nasal administration in which the carrier is solid are administered in the manner of sniffing tobacco, i.e., by rapid inhalation through the nasal cavity from a container of powder maintained close to the nose, and include, for example, a coarse powder having a particle size in the range of 20 to 500 microns (including particle sizes in the range of 20 to 500 microns in 5-micron units such as 30 microns, 35 microns, etc.). Formulations suitable for administration as a nasal spray or as nasal drops in which the carrier is liquid include an aqueous or oily solution of the active ingredient. Formulations suitable for aerosol administration can be prepared according to conventional methods and can be delivered together with other therapeutic agents.

[0171] Formulations suitable for vaginal administration can be presented as pessaries, tampons, creams, gels, pastes, foams, or spray formulations containing, in addition to the active ingredient, a carrier as is known in the art to be suitable.

[0172] Compositions suitable for parenteral administration may include aqueous and non-aqueous sterile injection solutions which may contain antioxidants, buffers, bacteriostats, and solutes which render the formulation isotonic with the blood of the intended recipient, as well as aqueous and non-aqueous sterile suspensions which may include suspending and thickening agents. The formulations may be presented in unit dose or multi-dose containers (e.g., sealed ampoules and vials) and may be stored in a freeze-dried (i.e., lyophilized) state which requires only the addition of a sterile liquid carrier (e.g., water) immediately prior to use. Immediate injection solutions and suspensions may be prepared from sterile powders, granules, and tablets of the previously described types.

[0173] Preferred unit dose formulations contain, as described above herein, the daily dose or unit sub-dose of the active ingredient, or an appropriate fraction thereof.

[0174] It should be understood that, in addition to the ingredients particularly mentioned above, the formulations of the present invention may include other conventional agents in the art, taking into account the type of formulation in question (e.g., those suitable for oral administration may include flavoring agents).

[0175] Using the pyrazolo[1,5-a]pyridine derivatives of the present invention, controlled release pharmaceutical formulations (the "controlled release formulations") containing one or more pyrazolo[1,5-a]pyridine derivatives of the present invention as the active ingredient can be provided, and the release of the active ingredient can be controlled and adjusted to allow for less frequent dosing or to improve the pharmacokinetic or toxicity profile of a given compound of the present invention. Separate units containing one or more pyrazolo[1,5-a]pyridine derivatives of the present invention and adapted for oral administration can be prepared according to conventional methods.

[0176] Another embodiment of the present invention relates to various precursors or “prodrug” forms of the pyrazolo[1,5-a]pyridine derivatives of the present invention. The pyrazolo[1,5-a]pyridine derivatives of the present invention, which are not themselves significantly biologically active, may, when delivered to an animal, mammal, or human, undergo chemical reactions catalyzed by enzymes present in the normal functions of the body, particularly in the stomach or serum, and it may be desirable to formulate such chemical reactions in the form of chemical species that have the effect of releasing the compounds defined herein. Thus, the term “prodrug” relates to these species that are converted in vivo to the active pharmaceutical ingredient.

[0177] The prodrugs of the pyrazolo[1,5-a]pyridine derivatives of the present invention can have any form suitable for a formulation, for example, esters are a non-limiting general prodrug form. However, in this case, the prodrug can necessarily exist in a form in which the covalent bond is cleaved by the action of an enzyme present at the target site. For example, a C-C covalent bond can be selectively cleaved by one or more enzymes at the target site, and thus prodrugs in forms other than readily hydrolysable precursors, particularly esters, amides, etc., can be used. The counterparts of the active pharmaceutical ingredient in the prodrug can have different structures such as amino acid or peptide structures, alkyl chains, sugar moieties, etc., as known in the art.

[0178] For the purposes of the present invention, the term “therapeutically suitable prodrug” is defined herein as “a compound that, when contacted with the tissues of an animal, mammal, or human to which the prodrug has been administered, is converted in vivo to a therapeutically active form by one or more biological conversions and is modified to achieve the intended therapeutic outcome without undue toxicity, irritation, or allergic reaction”.

[0179] More specifically, as used herein, the term "prodrug" refers to an inactive or significantly less active derivative of a compound represented by the structural formulas described herein that undergoes spontaneous or enzymatic conversion reactions in the body to release the pharmacologically active form of the compound. For a comprehensive overview, see Rautio J. et al. ("Prodrugs: design and clinical applications" Nature Reviews Drug Discovery, 2008, doi:10.1038 / nrd2468).

[0180] Representative pyrazolo[1,5-a]pyridine derivatives of the present invention are described below and can be synthesized according to the general synthetic methods exemplified in the following schemes. Since the schemes are illustrative, the present invention should not be construed as being limited by the specific chemical reactions and specific conditions described in the schemes and examples. The various starting materials used in the schemes can be commercially available or can be prepared by methods well known to those skilled in the art. The variables are as defined herein and are within the skill of those skilled in the art.

[0181] Exemplary embodiments of the present invention are summarized as the following clauses 1 to 51. 1. A compound of formula (I), its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs, [Chemical formula] Preferably, optionally, a compound of formula (I), its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs for use in the treatment of pain or epilepsy or in a method for treating pain or epilepsy, wherein, R 1 is -F, -Cl, -Br, -I, -CN, -R W , -OR W , -OC(=O)R W , -NR W R X , -NR W C(=O)RX 、 -SR W 、 -S(=O)R W 、 -S(=O) 2 R W 、 -C(=O)R W 、 -C(=O)OR W 、 or -C(=O)NR W R X represents, Q is, -OR 2 or -NR 3 R 4 represents, R 2 is, -R Y represents, R 3 is, -OH or -R Y represents, R 4 is, -R Y or -S(=O) 2 R Y represents, or alternatively R 3 and R 4 together form a saturated or unsaturated, unsubstituted, or mono- or polysubstituted 4-, 5-, 6-, 7-, or 8-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N, O, and S, T represents -O-, U represents -CR 5 R 5 ’-, or T represents -CR 5 R 5 ’-, U represents -O-, R 5 and R 5 ’ are independently of each other, -R Y represents, R 6 、R 7 、 and R 8 are independently of each other, -F, -Cl, -Br, -I, -CN, -NO 2 、 -SF 5 、 -R W 、 -OR W 、 -OC(=O)R W 、 -NR W R X 、 -NR W C(=O)R X 、 -SR W、 -S(=O)R W 、 -S(=O) 2 R W 、 -C(=O)R W 、 -C(=O)OR W 、 or -C(=O)NR W R X represents, V is a saturated or unsaturated 3 - to 14 - membered heterocycloalkyl, a saturated or unsaturated 3 - to 14 - membered cycloalkyl, a 5 - to 14 - membered aryl, C 1 -C 6 alkyl, or a 5 - to 14 - membered heteroaryl, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, -CF 3 、 -CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 、 =O, =S, -SF 5 、 -R Y 、 -OR Y 、 -OC(=O)R Y 、 -NR Y R Z 、 -NR Y C(=O)R Z 、 -SR Y 、 -S(=O)R Y 、 -S(=O) 2 R Y 、 -C(=O)R Y 、 -C(=O)OR Y 、 or -C(=O)NR Y R Z and is monosubstituted or polysubstituted with substituents selected from, R W and R X are, independently of one another, in each case independently, -H; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -alkyl; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -heteroalkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted); or A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted), representing a 3- to 14-membered heterocycloalkyl, R Y and R Z are, independently of each other in each case, -H; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -alkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -heteroalkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted); A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally connected via -C1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted) via which is connected, a 3- to 14-membered heterocycloalkyl; unsubstituted, monosubstituted or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is optionally, -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted) via which is connected, a 6- to 14-membered aryl, or unsubstituted, monosubstituted or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is optionally, -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted) via which is connected, a 5- to 14-membered heteroaryl, or alternatively R Y and R Z together form a saturated or unsaturated, unsubstituted, or monosubstituted or polysubstituted 4-, 5-, 6-, 7- or 8-membered heterocycle containing 1 to 3 heteroatoms selected from N, O and S, wherein, "monosubstituted or polysubstituted" in each case independently, -F, -Cl, -Br, -I, -CN, -C 1-6 -alkyl, -CF 3 -, -CF 2 H, -CFH 2 -, -CF 2 Cl, -CFCl 2 -, -C 1-6 -alkylene-CF 3 -, -C 1-6 -alkylene-CF 2 H, -C 1-6 -alkylene-CFH 2 -, -C 1-6-alkylene-O-CF 3 、-C 1-6 -alkylene-O-CF 2 H、-C 1-6 -alkylene-O-CFH 2 、-C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 、-C 1-6 -alkylene-N(C 1-6 -alkyl)-C 1-6 -alkylene-CF 3 、-C(=O)-C 1-6 -alkyl、-C 1-6 -alkylene-C(=O)-C 1-6 -alkyl、-C(=O)OH、-C 1-6 -alkylene-C(=O)-OH、-C(=O)-OC 1-6 -alkyl、-C 1-6 -alkylene-C(=O)-OC 1-6 -alkyl、-C(=O)O-C 1-6 -alkylene-CF 3 、-C(=O)-NH 2 、-C 1-6 -alkylene-C(=O)-NH 2 、-C(=O)-NH(C 1-6 -alkyl)、-C 1-6 -alkylene-C(=O)-NH(C 1-6 -alkyl)、-C(=O)-N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-C(=O)-N(C 1-6 -alkyl) 2 、-C(=O)-NH(OH)、-C 1-6 -alkylene-C(=O)-NH(OH)、-OH、-C 1-6 -alkylene-OH、=O、-OCF 3 、-OCF 2 H、-OCFH 2 、-OCF 2 Cl、-OCFCl 2 、-O-C 1-6 -alkyl、-C 1-6 -alkylene-O-C 1-6 -alkyl、-O-C1-6 -alkylene-O-C 1-6 -alkyl, -O-C 1-6 -alkylene-NH 2 、-O-C 1-6 -alkylene-NH-C 1-6 -alkyl, -O-C 1-6 -alkylene-N(C 1-6 -alkyl) 2 、-O-C(=O)-C 1-6 -alkyl, -C 1-6 -alkylene-O-C(=O)-C 1-6 -alkyl, -O-C(=O)-O-C 1-6 -alkyl, -C 1-6 -alkylene-O-C(=O)-O-C 1-6 -alkyl, -O-C(=O)-NH(C 1-6 -alkyl)、-C 1-6 -alkylene-O-C(=O)-NH(C 1-6 -alkyl)、-O-C(=O)-N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-O-C(=O)-N(C 1-6 -alkyl) 2 、-O-S(=O) 2 -NH 2 、-C 1-6 -alkylene-O-S(=O) 2 -NH 2 、-O-S(=O) 2 -NH(C 1-6 -alkyl)、-C 1-6 -alkylene-O-S(=O) 2 -NH(C 1-6 -alkyl)、-O-S(=O) 2 -N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-O-S(=O) 2 -N(C 1-6 -alkyl) 2 、-NH 2 、-NO、-NO 2 、-C 1-6 -alkylene-NH 2 、-NH(C 1-6-alkyl), -N(3- to 14-membered cycloalkyl)(C 1-6 -alkyl), -N(C 1-6 -alkyl)-C 1-6 -alkylene-OH, -N(H)-C 1-6 -alkylene-OH, -C 1-6 -alkylene-NH(C 1-6 -alkyl), -N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-N(C 1-6 -alkyl) 2 、-NH-C(=O)-C 1-6 -alkyl, -C 1-6 -alkylene-NH-C(=O)-C 1-6 -alkyl, -NH-C(=O)-O-C 1-6 -alkyl, -C 1-6 -alkylene-NH-C(=O)-O-C 1-6 -alkyl, -NH-C(=O)-NH 2 、-C 1-6 -alkylene-NH-C(=O)-NH 2 、-NH-C(=O)-NH(C 1-6 -alkyl)、-C 1-6 -alkylene-NH-C(=O)-NH(C 1-6 -alkyl)、-NH-C(=O)-N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-NH-C(=O)-N(C 1-6 -alkyl) 2 、-N(C 1-6 -alkyl)-C(=O)-C 1-6 -alkyl、-C 1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-C 1-6 -alkyl、-N(C 1-6 -alkyl)-C(=O)-O-C 1-6 -alkyl、-C 1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-O-C 1-6 -alkyl、-N(C 1-6 -alkyl)-C(=O)-NH 2 、-C1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-NH 2 、-N(C 1-6 -alkyl)-C(=O)-NH(C 1-6 -alkyl)、-C 1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-NH(C 1-6 -alkyl)、-N(C 1-6 -alkyl)-C(=O)-N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-N(C 1-6 -alkyl) 2 、-NH-S(=O) 2 OH、-C 1-6 -alkylene-NH-S(=O) 2 OH、-NH-S(=O) 2 -C 1-6 -alkyl、-C 1-6 -alkylene-NH-S(=O) 2 -C 1-6 -alkyl、-NH-S(=O) 2 -O-C 1-6 -alkyl、-C 1-6 -alkylene-NH-S(=O) 2 -O-C 1-6 -alkyl、-NH-S(=O) 2 -NH 2 、-C 1-6 -alkylene-NH-S(=O) 2 -NH 2 、-NH-S(=O) 2 -NH(C 1-6 -alkyl)、-C 1-6 -alkylene-NH-S(=O) 2 -NH(C 1-6 -alkyl)、-NH-S(=O) 2 N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-NH-S(=O) 2 N(C 1-6 -alkyl) 2 、-N(C 1-6-(alkyl)-S(=O) 2 -OH, -C 1-6 -alkylene-N(C 1-6 -(alkyl)-S(=O) 2 -OH, -N(C 1-6 -(alkyl)-S(=O) 2 -C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -(alkyl)-S(=O) 2 -C 1-6 -alkyl, -N(C 1-6 -(alkyl)-S(=O) 2 -O-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -(alkyl)-S(=O) 2 -O-C 1-6 -alkyl, -N(C 1-6 -(alkyl)-S(=O) 2 -NH 2 , -C 1-6 -alkylene-N(C 1-6 -(alkyl)-S(=O) 2 -NH 2 , -N(C 1-6 -(alkyl)-S(=O) 2 -NH(C 1-6 -alkyl), -C 1-6 -alkylene-N(C 1-6 -(alkyl)-S(=O) 2 -NH(C 1-6 -alkyl), -N(C 1-6 -(alkyl)-S(=O) 2 -N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-N(C 1-6 -(alkyl)-S(=O) 2 -N(C 1-6 -alkyl) 2 , -SH, =S, -SF 5 , -SCF 3 , -SCF 2 H, -SCFH 2 , -S-C 1-6 -alkyl, -C 1-6 -alkylene-S-C1-6 -alkyl, -S(=O)-C 1-6 -alkyl, -C 1-6 -alkylene-S(=O)-C 1-6 -alkyl, -S(=O) 2 -C 1-6 -alkyl, -C 1-6 -alkylene-S(=O) 2 -C 1-6 -alkyl, -S(=O) 2 -OH, -C 1-6 -alkylene-S(=O) 2 -OH, -S(=O) 2 -O-C 1-6 -alkyl, -C 1-6 -alkylene-S(=O) 2 -O-C 1-6 -alkyl, -S(=O) 2 -NH 2 , -C 1-6 -alkylene-S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -C 1-6 -alkylene-S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-S(=O) 2 -N(C 1-6 -alkyl) 2 , 3- to 14-membered cycloalkyl, -C 1-6 -alkylene-(3- to 14-membered cycloalkyl), 3- to 14-membered heterocycloalkyl, -C 1-6 -alkylene-(3- to 14-membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 14-membered heteroaryl, -C 1-6-alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -O-(5- to 14-membered heteroaryl), -C(=O)-(3- to 14-membered cycloalkyl), -C(=O)-(3- to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5- to 14-membered heteroaryl), -S(=O) 2 -(3- to 14-membered cycloalkyl), -S(=O) 2 -(3- to 14-membered heterocycloalkyl), -S(=O) 2 -phenyl, -S(=O) 2 A compound, its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs, which means being substituted with one or more substituents independently selected from -(5- to 14-membered heteroaryl). 2. T represents -O-, and U represents -CR 5 R 5 ’-, the compound itself described in item 1, or a compound for use. 3. T represents -CR 5 R 5 ’-, and U represents -O-, the compound itself described in item 1, or a compound for use. 4. Q represents -NR 3 R 4 The compound itself described in any one of items 1 to 3, or a compound for use. 5. Q represents -OR 2 The compound itself described in any one of items 1 to 3, or a compound for use. 6. V represents a saturated or unsaturated 3- to 14-membered heterocycloalkyl, a saturated or unsaturated 3- to 14-membered cycloalkyl, a 5- to 14-membered aryl, C 1 -C 6 alkyl, or a 5- to 14-membered heteroaryl, and in any case, unsubstituted, independently of each other, -F, -Cl, -Br, -I, -CF 3 ,-CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 ,, =O, =S, -SF 5 ,-RY , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z The compound itself described in any one of Clauses 1 to 5, or the compound for use, which is mono- or polysubstituted with a substituent selected from The compound itself described in Clause 6, or the compound for use, wherein the 7.5- to 14-membered heteroaryl is mono- or polysubstituted The 8.5- to 14-membered heteroaryl is selected from benzimidazole, benzisoxazole, benzazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furan, furazan, imidazole, imidazopyridine, indazole, indole, indolizine, isobenzofuran, isoindole, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, oxyindole, phthalazine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 , -CF 2 H, C 1 , -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y RZ 、 -NR Y C(=O)R Z 、 -SR Y 、 -S(=O)R Y 、 -S(=O) 2 R Y 、 -C(=O)R Y 、 -C(=O)OR Y 、 or -C(=O)NR Y R Z The compound itself according to clause 6 or 7, or the compound for use, which is mono- or polysubstituted with a substituent selected from 9.5 - to 14-membered heteroaryl is selected from the group consisting of furan, thiophene, imidazole, pyrazole, oxazole, isoxazole, thiazole, triazole, pyridine, isoquinoline, benzothiazole, pyridazine, pyrimidine, imidazopyridine, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 、 -CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 、 =O, =S, -SF 5 、 -R Y 、 -OR Y 、 -OC(=O)R Y 、 -NR Y R Z 、 -NR Y C(=O)R Z 、 -SR Y 、 -S(=O)R Y 、 -S(=O) 2 R Y 、 -C(=O)R Y 、 -C(=O)OR Y 、 or -C(=O)NR Y R Z The compound itself according to any one of clauses 6 - 8, or the compound for use, which is mono- or polysubstituted with a substituent selected from The 10.5- to 14-membered heteroaryl is selected from the group consisting of furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, oxazol-5-yl, isoxazol-4-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, 1,2,4-triazol-3-yl, 1,2,3-triazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, isoquinolin-1-yl, isoquinolin-5-yl, benzo[d]thiazol-2-yl, pyridazin-3-yl, pyrimidin-5-yl, and imidazo[1,2-a]pyridin-6-yl, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 、-CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 、=O, =S, -SF 5 、-R Y 、-OR Y 、-OC(=O)R Y 、-NR Y R Z 、-NR Y C(=O)R Z 、-SR Y 、-S(=O)R Y 、-S(=O) 2 R Y 、-C(=O)R Y 、-C(=O)OR Y 、or -C(=O)NR Y R Z The compound itself according to any one of clauses 6 to 9, or a compound for use, which is mono- or polysubstituted with substituents selected from 11. V is saturated or unsaturated, unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 、-CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 、=O, =S, -SF 5 、-R Y 、-ORY 、 -OC(=O)R Y 、 -NR Y R Z 、 -NR Y C(=O)R Z 、 -SR Y 、 -S(=O)R Y 、 -S(=O) 2 R Y 、 -C(=O)R Y 、 -C(=O)OR Y 、 or -C(=O)NR Y R Z A compound as described in any one of clauses 1 to 5, or a compound for use, which is monosubstituted or polysubstituted with a substituent selected from 12. A 3- to 14-membered heterocycloalkyl is selected from azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxazolidine, morpholine, oxazolidine, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiacyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, hexahydro-1H-pyrrolidine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, and octahydropyrrolo[1,2-a]pyrazine, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 、 -CF 2 H, C 1 ~C 6 alkyl, -CN, -NO, -NO 2 、 =O, =S, -SF 5 、 -R Y 、 -OR Y 、 -OC(=O)RY , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z The compound itself according to clause 11, or a compound for use, which is mono- or polysubstituted with a substituent selected from 13.3 - 14-membered heterocycloalkyl is oxane, or oxetanyl, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, CF 3 , -CF 2 H, C 1 , -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z The compound itself according to clause 11 or 12, or a compound for use, which is mono- or polysubstituted with a substituent selected from 14.3 - 14-membered heterocycloalkyl is oxan-4-yl or oxetan-3-yl, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y, -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z The compound itself according to any one of clauses 11 to 13, or the compound for use, which is mono- or polysubstituted with a substituent selected from 15. A saturated or unsaturated 3- to 14-membered cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, or cyclodecyl, including non-condensed or non-bridged, condensed, or bridged cycloalkyl, and in each case is unsubstituted, -F, -Cl, -Br, -I,, CF 3 , -CF 2 H, C 1 , -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z The compound itself according to any one of clauses 1 to 5, or the compound for use, which is mono- or polysubstituted with a substituent selected from 16. A 5- to 14-membered aryl is unsubstituted, and independently of one another, -F, -Cl, -Br, -I, CF 3 , -CF2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z The compound itself according to any one of clauses 1 to 5, or the compound for use, which is phenyl or other 5- to 14-membered aryl, mono- or polysubstituted with substituents selected from C representing V 1 -C 6 alkyl or C 1 -C 6 heteroalkyl is saturated or unsaturated, unsubstituted, and independently of one another, -F, -Cl, -Br, -I, CF 3 , -CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R ZThe compound itself according to any one of clauses 1 to 6, or the compound for use, which is mono-substituted or multi-substituted with a substituent selected from 18. V is unsubstituted and, independently of one another, -F, -Cl, -Br, -I, CF 3 , -CF 2 H, -CN, -C(=O)OH, -NH 2 , -NO 2 , -OH, =O, -SF 5 ; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C(=O)O-C 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -NHC 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -N(C 1-6 -alkyl) 2 ; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -O-C 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -S(=O) 2 -C 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted), a 3- to 14-membered cycloalkyl; or Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally -C 1 -C 6 -alkylene- or -C1 -C 6 -heteroalkylene-(in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted), a 3- to 14-membered heterocycloalkyl, monosubstituted or polysubstituted with a substituent selected from, the compound itself according to any one of the preceding clauses, or a compound for use. 19. V is, independently of one another, unsubstituted, -OH, -F, -Cl, -Br, -I, -SH, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -CN, -NO 2 , -C(=O)OH, -NH 2 , -N(CH 3 ) 2 , -cyclopropyl, or -O-cyclopropyl (preferably, -OH, -F, -Cl, -Br, -I, -SH, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -CN, -NO 2 , -C(=O)OH, -NH 2 , or -N(CH 3 ) 2 selected from); saturated or unsaturated, unsubstituted, independently of one another, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2, C(=O)CHF 2 , -C(=O)NH 2 , and selected from the group consisting of -cyclopropyl, preferably, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 , is mono- or polysubstituted with a substituent selected from the group consisting of -C 1-6 -alkyl; Saturated or unsaturated, unsubstituted, independently of one another, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 , is mono- or polysubstituted with a substituent selected from the group consisting of -C 1-6 -heteroalkyl; Unsubstituted, independently of one another, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 -OC substituted with a substituent selected from the group consisting of mono- or multi-substitutions 1-6 -alkyl; Unsubstituted, independently of each other, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 -O(C=O)C substituted with a substituent selected from the group consisting of mono- or multi-substitutions 1-6 -alkyl; Unsubstituted, independently of each other, -F, -Cl, -Br, -I, -C 1-6 -alkyl, C 2-6 -alkenyl, -C 2-6 -alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 -C(=O)OC substituted with a substituent selected from the group consisting of mono- or multi-substitutions1-6 -alkyl; 3-14 membered cycloalkyl selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, each of which is unsubstituted and independently selected from -F, -Cl, -Br, -I, -C 1-6 -Alkyl, C 2-6 -alkenyl, -C 2-6 -Alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, S.F. 5 , -NO 2 , -C(=O)OH, -NH 2 , C(=O)CHF 2 , and -C(=O)NH 2 3 to 14-membered cycloalkyl mono- or polysubstituted with substituents selected from the group consisting of: Azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxalidine, morpholine, oxazolidine, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1, 3- to 14-membered heterocycloalkyl selected from the group consisting of 1-dioxothiacylcyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, hexahydro-1H-pyrrolidine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, and octahydropyrrolo[1,2-a]pyrazine, in each case unsubstituted and independently of each other, -F, -Cl, -Br, -I, -C 1-6-Alkyl, C 2-6 -Alkenyl, -C 2-6 -Alkynyl, -OH, =O, -SH, =S, -CN, -CF 3 、-CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F, SF 5 、-NO 2 、-C(=O)OH, -NH 2 、C(=O)CHF 2 、and -C(=O)NH 2 A 3- to 14-membered heterocycloalkyl mono- or polysubstituted with a substituent selected from the group consisting of; a compound as described in any one of the preceding paragraphs, itself, or a compound for use, mono- or polysubstituted with a substituent selected from the group consisting of. 20. V is, independently of one another, unsubstituted, -F, -Cl, -CN, -OH, =O, -C 1-6 -Alkyl, -CHF 2 、-CF 3 、-C 1-6 -Alkylene-NH 2 、-C 1-6 -Alkylene-NHC(=O)O-C 1-6 -Alkyl, -C 1-6 -Alkylene-OH, -C 1-6 -Alkylene-NHC(=O)-O-C 1-6 -Alkyl, -C(=O)O-C 1-6 -Alkyl, -N(C 1-6 -Alkyl) 2 、-OC 1-6 -Alkyl, -OCF 3 、-O-C 1-6 -Alkylene-N(C 1-6 -Alkyl) 2 、-S(=O) 2 -C 1-6 -Alkyl, -azetidine, -C 1-6 -Alkylene-O-tetrahydropyran, or -C 1-6The compound itself according to any one of the preceding clauses, or a compound for use, which is mono- or polysubstituted with a substituent selected from -alkyl-substituted -piperazine, or represents unsubstituted, mono- or polysubstituted oxetanyl. 21. V is (i) unsubstituted, (ii) mono-substituted, (iii) di-substituted, (iv) tri-substituted, or (v) tetra-substituted, the compound itself according to any one of the preceding clauses, or a compound for use. 22. R 1 is -H, -F, -Cl, -Br, -I; saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 - 6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -O-C 1 - 6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -C(=O)C 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -C(=O)OC 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -C(=O)NHC 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -C(=O)N(C 1-6 -alkyl) 2 ; saturated or unsaturated, unsubstituted, mono- or polysubstituted -S(=O)C 1-6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -S(=O) 2 -C 1 - 6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C6 -heteroalkyl, or a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally, via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted), a compound as defined in any one of the preceding clauses, or a compound for use. 23.R 1 is -H, -F, -Cl, -Br, -I, -C 1-6 -alkyl, -O-C 1-6 -alkyl, -C 1-6 -alkylene-O-C 1-6 -alkyl, -C 1-6 -alkylene-NH(C 1-6 -alkyl), -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -alkylene-CF 3 , -C 1-6 -alkylene-CF 2 H, -C 1-6 -alkylene-CFH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , -C 1-6 -alkylene-N(C 1-6 -alkyl)-C 1-6 -alkylene-CF 3 , -C(=O)C 1-6 -alkyl, -C(=O)OC 1-6 -alkyl, -C(=O)NHC 1-6 -alkyl, -C(=O)N(C 1-6 -alkyl) 2, -S(=O)-C 1-6 -alkyl, -S(=O) 2 -C 1-6 -alkyl, -O-C 1-6 -alkyl, unsubstituted -cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, or unsubstituted cyclohexyl, the compound itself as described in any one of the preceding clauses, or a compound for use. 24.R 1 is, -H, -C 1-6 -alkyl, -C 1-6 -alkylene-O-C 1-6 -alkyl, -CH 2 F, -CHF 2 , -CF 3 , -unsubstituted cyclopentyl, or -unsubstituted cyclopropyl, preferably, R 1 is, -H, -C 1-6 -alkyl, -C 1-6 -alkylene-O-C 1-6 -alkyl, -CH 2 F, -CHF 2 , -CF 3 , or unsubstituted -cyclopentyl, the compound itself as described in any one of the preceding clauses, or a compound for use. 25.R 1 is, -CH 2 F, -CHF 2 , -CH 3 , or unsubstituted -cyclopropyl, preferably, R 1 is, -CH 2 F, -CHF 2 , -CH 3 , or -CH 2 CH 3 represents, the compound itself as described in any one of the preceding clauses, or a compound for use. 26.R 2 is -H; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -alkyl; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6-heteroalkyl; a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted), a 3- to 14-membered cycloalkyl; or a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted), a 3- to 14-membered heterocycloalkyl, representing the compound itself according to any one of the preceding clauses, or a compound for use. 27.R 2 is -H, -C 1-6 -alkyl, -C 1-6 -alkylene-O-C 1-6 -alkyl, -C 1-6 -alkylene-NH(C 1-6 -alkyl), -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -alkylene-CF 3 , -C 1-6 -alkylene-CF 2 H, -C 1-6 -alkylene-CFH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , or -C 1-6-alkylene-N(C 1-6 -alkyl)-C 1-6 -alkylene-CF 3 represents the compound itself according to any one of the preceding clauses, or a compound for use. 28. R 2 is -H or -C 1-6 -alkyl represents the compound itself according to any one of the preceding clauses, or a compound for use. 29. R 3 is -H; -OH; saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -alkyl; or saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -heteroalkyl, represents the compound itself according to any one of the preceding clauses, or a compound for use. 30. R 3 is -H, -OH, -C 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NH(C 1-6 -alkyl), -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -alkylene-CF 3 , -C 1-6 -alkylene-CF 2 , -C 1-6 -alkylene-CFH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3、 or -C 1-6 - alkylene -N(C 1-6 - alkyl)-C 1-6 - alkylene -CF 3 represents the compound itself according to any one of the preceding clauses, or the compound for use. 31.R 3 is -H, -OH, or -C which is saturated, unsubstituted, or mono - substituted with -OH 1-6 - alkyl represents the compound itself according to any one of the preceding clauses, or the compound for use. 32.R 4 is -H; saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -S(=O)C 1-6 - alkyl; saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -S(=O) 2 -C 1 - 6 - alkyl; saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -C 1 -C 6 - alkyl; saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted -C 1 -C 6 - heteroalkyl; saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted 3 - to 14 - membered cycloalkyl, wherein the 3 - to 14 - membered cycloalkyl is optionally connected via -C 1 -C 6 - alkylene - or -C 1 -C 6 - heteroalkylene - (in each case saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted) is a 3 - to 14 - membered cycloalkyl; saturated or unsaturated, unsubstituted, mono - substituted or multi - substituted 3 - to 14 - membered heterocycloalkyl, wherein the 3 - to 14 - membered heterocycloalkyl is optionally connected via -C 1 -C 6 - alkylene - or -C 1 -C 63- to 14-membered heterocycloalkyl connected via -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted); unsubstituted, monosubstituted or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is optionally -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted) connected, or unsubstituted, monosubstituted or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is optionally -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted) connected, representing a compound according to any one of the preceding clauses, or a compound for use 33.R 4 is saturated or unsaturated, unsubstituted, and independently of one another, -F, -Cl, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 、-OH、=O、-OC 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 、-NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 、-NHC(=O)O-C 1-6 -alkyl, -N(C 1-6 -alkyl)C(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NH2 ,-C 1-6 -alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 ,-C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 ,-C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 ,-C(=O)NH 2 ,-C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 ,-S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, mono- or polysubstituted with a substituent selected from the group consisting of: -S(=O) 2 C 1-6 -alkyl; -S(=O) 2 (3- to 14-membered cycloalkyl), wherein the 3- to 14-membered cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, and in each case, saturated or unsaturated, unsubstituted, independently of one another, -F, -Cl, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 ,-OH, =O, -OC 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 ,-NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 ,-NHC(=O)O-C 1-6 -alkyl, -N(C1-6 -(alkyl)C(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 , -C(=O)NH 2 , -C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 , -S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, mono- or polysubstituted with a substituent selected from the group consisting of; -S(=O) 2 (3- to 14-membered cycloalkyl); saturated or unsaturated, unsubstituted, independently of one another, -F, -Cl, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 , -OH, =O, -OC 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 , -NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)O-C 1-6 -alkyl, -N(C1-6 -(alkyl)C(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 , -C(=O)NH 2 , -C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 , -S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, mono- or polysubstituted with a substituent selected from the group consisting of, -C 1-6 -alkyl; 3- to 14-membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl) wherein, -C 1-6 -alkylene- is unsubstituted or mono-substituted with -OH, and the 3- to 14-membered cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl, in each case saturated or unsaturated, and in each case unsubstituted, independently of one another, -F, -Cl, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 , -OH, =O, -OC 1-6 -alkyl, -C1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 , -NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)O-C 1-6 -alkyl, -N(C 1-6 -alkyl)C(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 , -C(=O)NH 2 , -C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 , -S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, mono- or polysubstituted with substituents selected from the group consisting of, 3- to 14-membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl); 3- to 14-membered heterocycloalkyl or -C 1-6 -alkylene-(3- to 14-membered heterocycloalkyl) wherein -C 1-6-alkylene- is unsubstituted or mono-substituted with -OH, and the 3- to 14-membered heterocycloalkyl is in each case azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxazolidine, morpholine, oxazolidine, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiacyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, hexahydro-1H-pyrrolidine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, and octahydropyrrolo[1,2-a]pyrazine, and is in each case unsubstituted, -F, -Cl, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 、-OH、=O、-OC 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 、-NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 、-NHC(=O)O-C 1-6 -alkyl, -N(C 1-6 -alkyl)C(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 、-C 1-6 -alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C1-6 -(alkyl) 2 、 -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 、 -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 、 -C(=O)NH 2 、 -C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 、 -S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3 - 14 membered heterocycloalkyl, and unsubstituted 5 - 14 membered heteroaryl, mono - or polysubstituted with substituents selected from the group consisting of, 3 - 14 membered heterocycloalkyl or -C 1-6 -alkylene-(3 - 14 membered heterocycloalkyl); unsubstituted, independently of one another, -F, -Cl, -CN, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 、 -OH, =O, -OC 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 、 -NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 、 -NHC(=O)O-C 1-6 -alkyl, -N(C 1-6 -alkyl)C(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 、 -C 1-6 -alkylene-NH-C 1-6 -alkyl, -C1-6 -alkylene-N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 、-C(=O)-C 1-6 -alkyl、-C(=O)OH、-C(=O)O-C 1-6 -alkyl、-C(=O)O-C 1-6 -alkylene-CF 3 、-C(=O)NH 2 、-C(=O)NH(C 1-6 -alkyl)、-C(=O)N(C 1-6 -alkyl) 2 、-S(=O) 2 C 1-6 -alkyl、-phenyl、-C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, monosubstituted or polysubstituted with a substituent selected from the group consisting of: -phenyl; 5- to 14-membered heteroaryl or -C 1-6 -alkylene-(5- to 14-membered heteroaryl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted with -OH, and the 5- to 14-membered heteroaryl is in each case selected from the group consisting of benzimidazole, benzisoxazole, benzazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furan, furazan, imidazole, imidazopyridine, indazole, indole, indolizine, isobenzofuran, isoindole, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, oxyindole, phthalazine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, and is in each case unsubstituted, -F, -Cl, -CN, -C1-6 -alkyl, -C 1-6 -alkylene-CF 3 , -OH, =O, -OC 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 , -NHC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)O-C 1-6 -alkyl, -N(C 1-6 -alkyl)C(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 , -C(=O)NH 2 , -C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 , -S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl, monosubstituted or polysubstituted with a substituent selected from the group consisting of, 5- to 14-membered heteroaryl or -C 1-6-alkylene-(5- to 14-membered heteroaryl), the compound itself as described in any one of the preceding clauses, or a compound for use. 34.R 4 is -H; saturated, unsubstituted, mono- or polysubstituted with -F -S(=O) 2 C 1-6 -alkyl; saturated, unsubstituted -S(=O) 2 (3- to 14-membered cycloalkyl); saturated, unsubstituted, independently of one another, -OH, -OC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkyl, unsubstituted -phenyl, mono- or disubstituted with a substituent selected from the group consisting of, -C 1-6 -alkyl, 3- to 14-membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or mono-substituted with -OH, and the 3- to 14-membered cycloalkyl is saturated, unsubstituted, independently of one another, -C 1-6 -alkyl, -C 1-6 -alkylene-NH 2 , -C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 , -C 1-6 -alkylene-OH, -C 1-6 -alkylene-NHC(=O)O-C 1-6 -alkyl, -OH, -OC 1-6 -alkyl, -NH 2 , -N(C 1-6 -alkyl) 2 , -NHC(=O)O-C 1-6 -alkyl, mono- or disubstituted with a substituent selected from the group consisting of, 3- to 14-membered cycloalkyl or -C 1-6-alkylene-(3- to 14-membered cycloalkyl); 3- to 14-membered heterocycloalkyl or -C 1-6 -alkylene-(3- to 14-membered heterocycloalkyl), provided that -C 1-6 -alkylene- is unsubstituted or mono-substituted with -OH, and in each case, the 3- to 14-membered heterocycloalkyl is selected from azetane, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, quinuclidine, hexahydro-1H-pyrrolidine, 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 1,1-dioxothiacyclohexane, and in each case, is unsubstituted, and independently of one another, is -F, -OH, =O, -C 1-6 -alkyl, -C 1-6 -alkylene-CF 3 、-C 1-6 -alkylene-OH, -C 1-6 -alkylene-O-C 1-6 -alkyl, -NH 2 、-N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-NH 2 、-C 1-6 -alkylene-N(C 1-6 -alkyl) 2 、-C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)O-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkylene-CF 3 、-C(=O)NH 2 、-C(=O)NH(C 1-6 -alkyl), -S(=O) 2 C 1-6 -alkyl, oxetanyl, pyrimidinyl, -C 1-6-alkylene-phenyl, or a 3- to 14-membered heterocycloalkyl or -C mono- or polysubstituted with a substituent selected from the group consisting of 1-6 -alkylene-(3- to 14-membered heterocycloalkyl); unsubstituted -phenyl; a 5- to 14-membered heteroaryl or -C 1-6 -alkylene-(5- to 14-membered heteroaryl), wherein -C 1-6 -alkylene- is unsubstituted or mono-substituted with -OH, and the 5- to 14-membered heteroaryl is in each case selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, and in each case is unsubstituted, independently of one another, and is mono- or disubstituted with a substituent selected from the group consisting of -C 1-6 -alkyl, -OH, or a 5- to 14-membered heteroaryl or -C 1-6 -alkylene-(5- to 14-membered heteroaryl), as defined in any one of the preceding clauses, the compound itself, or a compound for use. 35.R 3 and R 4 together form a saturated or unsaturated, unsubstituted, or mono- or polysubstituted 5- or 6-membered heterocycle containing 1 or 2 heteroatoms selected from N, O, and S, as defined in any one of the preceding clauses, the compound itself, or a compound for use. 36.R 3 and R 4 together form a heterocycle selected from the group consisting of pyrrolidine, piperidine, morpholine, and piperazine, and in each case is unsubstituted, independently of one another, and is -C 1-6 -alkyl, -NH 2 , -NHCH 3 , -N(CH 3 ) 2 , -C(=O)NH-C 1-6 -alkyl, -C(=O)N(C 1-6 -alkyl) 2 , -C(=O)O-C 1-6 -alkyl, -NHC(=O)O-C 1-6-Alkyl, -unsubstituted pyridyl, and unsubstituted or -C 1-6 The compound itself according to any one of the preceding clauses, or a compound for use, which is mono- or polysubstituted with a substituent selected from the group consisting of 1,2,4-oxadiazole mono-substituted with -alkyl, -unsubstituted pyridyl, and -alkyl. 37.R 3 and R 4 together form unsubstituted, or -N(CH 3 ) 2 mono-substituted pyrrolidine ring; unsubstituted or -C 1-6 -alkyl, -NH 2 , -N(CH 3 ) 2 , -C(=O)NH-C 1-6 -alkyl, -C(=O)O-C 1-6 -alkyl, -NHC(=O)O-C 1-6 -alkyl, and a piperidine ring mono-substituted with a substituent selected from the group consisting of unsubstituted or -C 1-6 -alkyl mono-substituted 1,2,4-oxadiazole; unsubstituted morpholine ring; or unsubstituted, or a compound itself according to any one of the preceding clauses, or a compound for use, which forms an N-substituted piperazine ring with a substituent selected from the group consisting of -alkyl and -unsubstituted pyridyl. 1-6 -alkyl 38.R 5 and R 5 ’ are, independently of each other, -H; saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -alkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -heteroalkyl; saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, where the 3- to 14-membered cycloalkyl is optionally -C 1 -C 6-alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted), the compound itself as described in any one of the preceding clauses, or a compound for use, representing a 3- to 14-membered cycloalkyl connected via 39.R 5 and R 5 ’ are, independently of one another, -H, -C 1 -C 6 -alkyl, or -C 1 -C 6 -alkylene-N(C 1 -C 6 -alkyl) 2 the compound itself as described in any one of the preceding clauses, or a compound for use 40.R 5 and R 5 ’ in which at least one does not represent -H, the compound itself as described in any one of the preceding clauses, or a compound for use 41.R 6 , R 7 and R 8 are, independently of one another, -H; -F, -Cl, -Br, -I, -OH, -SH, -SF 5 , -CN, -NO 2 , -C(=O)OH, -NH 2 ; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1-6 -alkyl; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -O-C 1-6 -alkyl; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -NHC 1-6 -alkyl; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -N(C 1-6 -alkyl) 2 ; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C(=O)OC 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -OC(=O)C 1-6 -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1-6 -heteroalkyl, a compound as described in any one of the preceding paragraphs, or a compound for use. 42.R 6 , R 7 and R 8 are, independently of one another, -H, -F, -Cl, -Br, -I, -OH, -SH, -SF 5 , -CN, -NO 2 , -C(=O)OH, -NH 2 , -C 1-6 -alkyl, -CF 3 , -CHF 2 , -CH 2 F, -O-C 1-6 -alkyl, -OCF 3 , -OCHF 2 , -OCH 2 F, Unsubstituted, or independently of one another, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 substituted with one or more substituents selected from -NHC 1-6 -alkyl; Unsubstituted, or independently of one another, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5, -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 substituted with one or more substituents selected from -N(C 1-6 -alkyl) 2 ; unsubstituted or, independently of one another, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 substituted with one or more substituents selected from -C(=O)OC 1-6 -alkyl; unsubstituted or, independently of one another, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 substituted with one or more substituents selected from -OC(=O)C 1-6 -alkyl; or unsubstituted or, independently of one another, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2 F, -OCF 3 , -OCHF 2 , -OCH 2 F, SF 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2-C substituted with one or more substituents selected from 1-6 -heteroalkyl, the compound itself according to any one of the preceding clauses, or a compound for use. 43.R 6 is -H, -F, -Cl, -CN, or -C 1 -C 6 -alkyl, the compound itself according to any one of the preceding clauses, or a compound for use. 44.R 6 does not represent -H, the compound itself according to any one of the preceding clauses, or a compound for use. 45.R 7 is -H, -F, -Cl, -CN, or -C 1 -C 6 -alkyl, the compound itself according to any one of the preceding clauses, or a compound for use. 46.R 7 does not represent -H, the compound itself according to any one of the preceding clauses, or a compound for use. 47.R 8 is -H, -F, -Cl, -CN, or -C 1 -C 6 -alkyl, the compound itself according to any one of the preceding clauses, or a compound for use. 48.R 8 does not represent -H, the compound itself according to any one of the preceding clauses, or a compound for use. 49. (i) R 6 , R 7 , and R 8 each represents -H, or (ii) two of R 6 , R 7 , and R 8 represent -H, and the remaining of R 6 , R 7 , and R 8 represent -F, -Cl, -CN, or -CH 3 , or (iii) R 6 , R 7 , and R 8One of them represents -H, and R 6 , R 7 , and R 8 The remainder of are, independently of one another, -F, -Cl, -CN, or -CH 3 , a compound itself, or a compound for use according to any one of the preceding clauses. 50. A compound itself, or a compound for use, according to any one of the preceding clauses, selected from the group consisting of the above-described compounds 001 to 036, or compounds 037 to 091, and a physiologically acceptable salt thereof. 51. A compound itself, or a compound for use, according to any one of the preceding clauses, wherein the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain. 52. A compound itself, or a compound for use, according to any one of the preceding clauses, wherein the pain is postoperative pain. 53. In a compound of formula (I), its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs, (a-1) Q represents -NR 3 R 4 , R 1 represents R W , R W represents -C 1 -C 6 -alkyl, and / or (a-2) Q represents -NR 3 R 4 , at least one of R 5 and R 5 ’ represents -H, and / or (a-3) Q represents -NR 3 R 4 , R 6 represents -H, and / or (a-4) Q represents -NR 3 R 4 , R 8 represents -H, or alternatively (b-1) (b-1) Q represents -NR 3 R 4 , R 1 represents -CH 2F, -CHF 2 , -CF 3 , -CN, -methyl, -ethyl, -propyl, or -cyclopropyl, and / or (b-2) Q is -NR 3 R 4 represents, and R 5 and R 5 ’s at least one does not represent -H, and / or (b-3) Q is -NR 3 R 4 represents, and R 3 represents -H, a compound of formula (I) defined by any one of the preceding clauses, its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs. 54. A pharmaceutical composition or medicine containing the compound according to any one of the preceding clauses. The further exemplary embodiments of the present invention are summarized as Items 1 to 68 below. 1. A compound of formula (I), its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs, wherein [Chemical formula] In the formula, R 1 is -F, -Cl, -Br, -I, -CN, -R W , -OR W , -OC(=O)R W , -NR W R X , -NR W C(=O)R X , -SR W , -S(=O)R W , -S(=O) 2 R W , -C(=O)R W , -C(=O)OR W , or -C(=O)NR W R X represents, Q is -OR 2 or -NR 3 R 4 represents, R 2 is -R Y represents, R 3 is -OH or -R Y and represents R 4 is -R Y or -S(=O) 2 R Y and represents, or alternatively R 3 and R 4 together form a saturated or unsaturated, unsubstituted, or mono - or poly - substituted 4, 5, 6, 7, or 8 - membered heterocyclic ring containing 1 to 3 heteroatoms selected from N, O, and S T represents -O-, U represents -CR 5 R 5 ’-, or T represents -CR 5 R 5 ’- and U represents -O- R 5 and R 5 ’ are independently of each other -R Y and represent R 6 , R 7 and R 8 are independently of each other -F, -Cl, -Br, -I, -CN, -NO 2 -SF 5 -R W -OR W -OC(=O)R W -NR W R X -NR W C(=O)R X -SR W -S(=O)R W -S(=O) 2 R W -C(=O)R W -C(=O)OR W or -C(=O)NR W R X and represent V is a saturated or unsaturated 3 - to 14 - membered heterocycloalkyl, a saturated or unsaturated 3 - to 14 - membered cycloalkyl, a 5 - to 14 - membered aryl, C 1 -C 6represents alkyl or 5- to 14-membered heteroaryl, and in each case, unsubstituted, independently of one another, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, C 1 -C 6 alkyl, -CN, -NO, -NO 2 , =O, =S, -SF 5 , -R Y , -OR Y , -OC(=O)R Y , -NR Y R Z , -NR Y C(=O)R Z , -SR Y , -S(=O)R Y , -S(=O) 2 R Y , -C(=O)R Y , -C(=O)OR Y , or -C(=O)NR Y R Z and is monosubstituted or polysubstituted with substituents selected from R W and R X are, independently of one another, in each case independently -H; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -alkyl; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -heteroalkyl; saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl, where the 3- to 14-membered cycloalkyl is optionally, via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted) connected, 3- to 14-membered cycloalkyl; or A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted), a 3- to 14-membered heterocycloalkyl, represents R Y and R Z are, independently of each other, in each case independently -H; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -alkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C 1 -C 6 -heteroalkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted), a 3- to 14-membered cycloalkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted), a 3- to 14-membered heterocycloalkyl; An unsubstituted, mono-substituted or multi-substituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is optionally -C 1 -C6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted) via which is connected a 6- to 14-membered aryl, or an unsubstituted, monosubstituted or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is optionally -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted) via which is connected a 5- to 14-membered heteroaryl, or alternatively R Y and R Z together form a saturated or unsaturated, unsubstituted, or monosubstituted or polysubstituted 4-, 5-, 6-, 7- or 8-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S, wherein "monosubstituted or polysubstituted" in each case independently is -F, -Cl, -Br, -I, -CN, -C 1-6 -alkyl, -CF 3 、-CF 2 H、-CFH 2 、-CF 2 Cl、-CFCl 2 、-C 1-6 -alkylene-CF 3 、-C 1-6 -alkylene-CF 2 H、-C 1-6 -alkylene-CFH 2 、-C 1-6 -alkylene-O-CF 3 、-C 1-6 -alkylene-O-CF 2 H、-C 1-6 -alkylene-O-CFH 2 、-C 1-6 -alkylene-NH-C 1-6 -alkylene-CF 3 、-C 1-6 -alkylene-N(C 1-6 -alkyl)-C 1-6-alkylene-CF 3 、-C(=O)-C 1-6 -alkyl、-C 1-6 -alkylene-C(=O)-C 1-6 -alkyl、-C(=O)OH、-C 1-6 -alkylene-C(=O)-OH、-C(=O)-OC 1-6 -alkyl、-C 1-6 -alkylene-C(=O)-OC 1-6 -alkyl、-C(=O)O-C 1-6 -alkylene-CF 3 、-C(=O)-NH 2 、-C 1-6 -alkylene-C(=O)-NH 2 、-C(=O)-NH(C 1-6 -alkyl)、-C 1-6 -alkylene-C(=O)-NH(C 1-6 -alkyl)、-C(=O)-N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-C(=O)-N(C 1-6 -alkyl) 2 、-C(=O)-NH(OH)、-C 1-6 -alkylene-C(=O)-NH(OH)、-OH、-C 1-6 -alkylene-OH、=O、-OCF 3 、-OCF 2 H、-OCFH 2 、-OCF 2 Cl、-OCFCl 2 、-O-C 1-6 -alkyl、-C 1-6 -alkylene-O-C 1-6 -alkyl、-O-C 1-6 -alkylene-O-C 1-6 -alkyl、-O-C 1-6 -alkylene-NH 2 、-O-C 1-6 -alkylene-NH-C 1-6 -alkyl、-O-C 1-6 -alkylene-N(C 1-6 -alkyl) 2 、-O-C(=O)-C 1-6 -alkyl、-C 1-6-alkylene-O-C(=O)-C 1-6 -alkyl, -O-C(=O)-O-C 1-6 -alkyl, -C 1-6 -alkylene-O-C(=O)-O-C 1-6 -alkyl, -O-C(=O)-NH(C 1-6 -alkyl), -C 1-6 -alkylene-O-C(=O)-NH(C 1-6 -alkyl), -O-C(=O)-N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-O-C(=O)-N(C 1-6 -alkyl) 2 , -O-S(=O) 2 -NH 2 , -C 1-6 -alkylene-O-S(=O) 2 -NH 2 , -O-S(=O) 2 -NH(C 1-6 -alkyl), -C 1-6 -alkylene-O-S(=O) 2 -NH(C 1-6 -alkyl), -O-S(=O) 2 -N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-O-S(=O) 2 -N(C 1-6 -alkyl) 2 , -NH 2 , -NO, -NO 2 , -C 1-6 -alkylene-NH 2 , -NH(C 1-6 -alkyl), -N(3 - 14 membered cycloalkyl)(C 1-6 -alkyl), -N(C 1-6 -alkyl)-C 1-6 -alkylene-OH, -N(H)-C 1-6 -alkylene-OH, -C 1-6 -alkylene-NH(C 1-6 -alkyl), -N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-N(C 1-6-(alkyl) 2 、 -NH-C(=O)-C 1-6 -alkyl, -C 1-6 -alkylene-NH-C(=O)-C 1-6 -alkyl, -NH-C(=O)-O-C 1-6 -alkyl, -C 1-6 -alkylene-NH-C(=O)-O-C 1-6 -alkyl, -NH-C(=O)-NH 2 、 -C 1-6 -alkylene-NH-C(=O)-NH 2 、 -NH-C(=O)-NH(C 1-6 -alkyl)、 -C 1-6 -alkylene-NH-C(=O)-NH(C 1-6 -alkyl)、 -NH-C(=O)-N(C 1-6 -alkyl) 2 、 -C 1-6 -alkylene-NH-C(=O)-N(C 1-6 -alkyl) 2 、 -N(C 1-6 -alkyl)-C(=O)-C 1-6 -alkyl、 -C 1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-C 1-6 -alkyl、 -N(C 1-6 -alkyl)-C(=O)-O-C 1-6 -alkyl、 -C 1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-O-C 1-6 -alkyl、 -N(C 1-6 -alkyl)-C(=O)-NH 2 、 -C 1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-NH 2 、 -N(C 1-6 -alkyl)-C(=O)-NH(C 1-6 -alkyl)、 -C 1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-NH(C 1-6 -alkyl)、 -N(C 1-6 -alkyl)-C(=O)-N(C 1-6 -alkyl)2 , -C 1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-N(C 1-6 -alkyl) 2 , -NH-S(=O) 2 OH, -C 1-6 -alkylene-NH-S(=O) 2 OH, -NH-S(=O) 2 -C 1-6 -alkyl, -C 1-6 -alkylene-NH-S(=O) 2 -C 1-6 -alkyl, -NH-S(=O) 2 -O-C 1-6 -alkyl, -C 1-6 -alkylene-NH-S(=O) 2 -O-C 1-6 -alkyl, -NH-S(=O) 2 -NH 2 , -C 1-6 -alkylene-NH-S(=O) 2 -NH 2 , -NH-S(=O) 2 -NH(C 1-6 -alkyl), -C 1-6 -alkylene-NH-S(=O) 2 -NH(C 1-6 -alkyl), -NH-S(=O) 2 N(C 1-6 -alkyl) 2 , -C 1-6 -alkylene-NH-S(=O) 2 N(C 1-6 -alkyl) 2 , -N(C 1-6 -alkyl)-S(=O) 2 , -OH, -C 1-6 -alkylene-N(C 1-6 -alkyl)-S(=O) 2 , -OH, -N(C 1-6 -alkyl)-S(=O) 2 -C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl)-S(=O) 2 -C 1-6-Alkyl, -N(C 1-6 -Alkyl)-S(=O) 2 -O-C 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -Alkyl)-S(=O) 2 -O-C 1-6 -Alkyl, -N(C 1-6 -Alkyl)-S(=O) 2 -NH 2 、-C 1-6 -Alkylene-N(C 1-6 -Alkyl)-S(=O) 2 -NH 2 、-N(C 1-6 -Alkyl)-S(=O) 2 -NH(C 1-6 -Alkyl), -C 1-6 -Alkylene-N(C 1-6 -Alkyl)-S(=O) 2 -NH(C 1-6 -Alkyl), -N(C 1-6 -Alkyl)-S(=O) 2 -N(C 1-6 -Alkyl) 2 、-C 1-6 -Alkylene-N(C 1-6 -Alkyl)-S(=O) 2 -N(C 1-6 -Alkyl) 2 、-SH, =S, -SF 5 、-SCF 3 、-SCF 2 H, -SCFH 2 、-S-C 1-6 -Alkyl, -C 1-6 -Alkylene-S-C 1-6 -Alkyl, -S(=O)-C 1-6 -Alkyl, -C 1-6 -Alkylene-S(=O)-C 1-6 -Alkyl, -S(=O) 2 -C 1-6 -Alkyl, -C 1-6 -Alkylene-S(=O) 2 -C 1-6 -Alkyl, -S(=O) 2 -OH, -C 1-6-alkylene-S(=O) 2 -OH, -S(=O) 2 -O-C 1-6 -alkyl, -C 1-6 -alkylene-S(=O) 2 -O-C 1-6 -alkyl, -S(=O) 2 -NH 2 、-C 1-6 -alkylene-S(=O) 2 -NH 2 、-S(=O) 2 -NH(C 1-6 -alkyl), -C 1-6 -alkylene-S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 、-C 1-6 -alkylene-S(=O) 2 -N(C 1-6 -alkyl) 2 、3 - 14 membered cycloalkyl, -C 1-6 -alkylene-(3 - 14 membered cycloalkyl), 3 - 14 membered heterocycloalkyl, -C 1-6 -alkylene-(3 - 14 membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5 - 14 membered heteroaryl, -C 1-6 -alkylene-(5 - 14 membered heteroaryl), -O-(3 - 14 membered cycloalkyl), -O-(3 - 14 membered heterocycloalkyl), -O-phenyl, -O-(5 - 14 membered heteroaryl), -C(=O)-(3 - 14 membered cycloalkyl), -C(=O)-(3 - 14 membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5 - 14 membered heteroaryl), -S(=O) 2 -(3 - 14 membered cycloalkyl), -S(=O) 2 -(3 - 14 membered heterocycloalkyl), -S(=O) 2 -phenyl, -S(=O) 2A compound, its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs, which means being substituted with one or more substituents independently selected from -(5 to 14-membered heteroaryl). 2. The preferred compound of formula (I), stereoisomeric form, physiologically acceptable salt, solvate, and / or polymorph according to item 1, wherein

Chemical formula

Chemical formula

Chemical formula

Chemical formula

Chemical Structure

Chemical Structure

Chemical Structure

Chemical Structure

Chemical Structure

Chemical Structure

Examples

[0182] The following examples are provided to further illustrate the present invention and are not intended to limit the scope of the present invention in any way.

[0183] Representative compounds of the present invention can be synthesized according to the general synthetic methods described below and are exemplified in the following schemes. Since the schemes are illustrative, the present invention should not be construed as being limited by the specific chemical reactions and specific conditions described in the schemes and examples. The various starting materials used in the schemes are either commercially available or can be prepared by methods well known to those skilled in the art. The variables are as defined herein and are within the skill of those skilled in the art.

[0184] As used herein, particularly in the schemes and examples, the abbreviations are as follows: ABC - aqueous solution of ammonium bicarbonate, ACN - acetonitrile, AcOH - acetic acid, ADDP - 1,1'-(azodicarbonyl)dipiperidide, aq. - aqueous, AIBN - azobisisobutyronitrile, CAN - cerium(IV) ammonium nitrate, COMU - (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate, DABCO - 1,4-diazabicyclo[2.2.2]octane, DAST - diethylaminosulfur trifluoride, DBU - 1,8-diazabicyclo[5.4.0]undec-7-ene, DCC - N,N'-dicyclohexylcarbodiimide, DCM - dichloromethane, DEAD - diethyl azodicarboxylate, DIA - diastereomer, DIAD - diisopropyl azodicarboxylate, DEA - diethylamine, DIPEA - diisopropyl-ethylamine, DME - 1,2-dimethoxyethane, DMF - N,N-dimethylformamide, DMSO - dimethyl sulfoxide, DPPA - diphenylphosphoryl azide, 2,4-DNPH - 2,4-dinitrophenylhydrazine, DTBAD - tert-butyl azodicarboxylate, EDCI or EDC - 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, En - enantiomer, Et2O - diethyl ether, EtOH - ethanol, EtOAc - ethyl acetate, Eq. - equivalent, FA - formic acid, FCC - flash column chromatography, h - hour, HATU - O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate, HPLC - high performance liquid chromatography, IPA - isopropyl alcohol, LAH - lithium aluminum hydride, LG - leaving group, MeOH - methanol, MgSO4 - magnesium sulfate, min. - minute, Ms - methanesulfonyl, Na 2 SO 4- Sodium sulfate, NBS - N - Bromosuccinimide, nBuLi - n - Butyllithium, NMP - 1 - Methyl - 2 - pyrrolidinone, Pd(PPh3)4 - Tetrakis - (triphenylphosphine) - palladium(0), Pd2(dba)3 - Tris(dibenzylideneacetone)dipalladium, Pet ether - Petroleum ether, PPh3 - Triphenylphosphine, PS - DIEA - Diisopropylethylamine supported on polystyrene, PS - PPh3 - Triphenylphosphine supported on polystyrene, PyBop - Benzotriazol - 1 - yloxytrispyrrolidinophosphonium hexafluorophosphate, PTSA - p - Toluenesulfonic acid, RF: ratio of frontiers, RM - Reaction mixture, RP - Reverse phase, RT - Room temperature, sat. - Saturated, SEM - [2 - (Trimethylsilyl)ethoxy]methyl acetal, SFC - Supercritical fluid chromatography, SPE - Solid phase extraction, TBDMS - tert - Butyldimethylsilyl ether, TBAF - Tetrabutylammonium fluoride hydrate, TBAI - Tetrabutylammonium iodide, TEA - Triethylamine, THF - Tetrahydrofuran, TFA - Trifluoroacetic acid, TLC - Thin layer chromatography, TPP - Triphenylphosphine, IPA - Isopropyl alcohol, TMS - Trimethylsilyl, T3P - Propylphosphonic anhydride.

[0185] The compounds of the general formula (A) and all other general formulas described herein, and the subject compounds having structures according to their embodiments, can be prepared as outlined in General Chemical Scheme 1.

Chemical formula

[0186] Scheme 1: All V, R 1 , R 2 , R 3 , R 4 , and R 5 are as described for the compounds of the present invention. R 5In each occurrence of, up to two independent substituents are contemplated (i.e., R 5 and R 5’ ).

[0187] 4-(Benzyloxy)pyridine of formula 1 can be reacted with a reagent carrying an electrophilic amine (e.g., 2,4-DNPH, O-(mesitylsulfonyl)hydroxylamine, etc.) in a suitable solvent (e.g., MeCN, DMF, NMP, etc.) to obtain the N-aminopyridinium salt of formula 2. The intermediate of formula 2 can be condensed with an alkyne ester derivative 3 (either commercially available or synthesized by procedures known to those skilled in the art) at a temperature in the range of 0 to 100 °C in the presence of a base (e.g., potassium carbonate, DBU, etc.) in a polar solvent (e.g., DMF, DCM, MeCN, etc.) to obtain pyrazolo[1,5-a]pyridine of formula 4 (wherein R2 is an ester protecting group (e.g., methyl, ethyl, t-Bu, etc.)). Then, the ester derivative 4 can be converted to an intermediate compound of formula 5 via a hydrogenation reaction with a reducing agent (e.g., hydrogen gas, ammonium formate, cyclohexadiene, etc.) using a catalyst (more preferably Pd or Pt) in a solvent (e.g., THF, EtOH, etc.). Subsequently, the intermediate of formula 5 can be reacted with an intermediate of formula 6a (either a commercial product or a synthetic product) (wherein LG is a leaving group) in a polar solvent (e.g., MeCN, DMF, NMP, etc.) in the presence of a base (e.g., DIPEA, DBU, triethylamine, Cs 2 CO 3In the presence of, for example, a chelating agent (e.g., 18-crown-6, cis-anti-cis-dicyclohexano-18-crown-6, etc.), it can be converted to the desired compound of formula 7 via nucleophilic substitution at a temperature in the range of 0 to 100 °C, with or without the chelating agent. Alternatively, the intermediate of formula 5 can be reacted with an intermediate of formula 6b (commercially available or synthesized) in the presence of an azodicarboxylate reagent (e.g., DEAD, DIAD, ADDP, etc.) and a phosphine (e.g., tributylphosphine, triphenylphosphine, etc.) in a solvent (e.g., THF, toluene, etc.) at a temperature in the range of 0 to 100 °C to obtain the desired compound of formula 7. Then, the ester derivative 7 can be converted to the desired compound of formula 8 via a standard saponification reaction. Alternatively, the benzyl derivative 4 can then be converted to the desired compound of formula 8 via a standard saponification reaction. The desired compound of formula 10 can be obtained from the acid derivative of formula 8 by reaction with an amine derivative of formula 9 (commercially available or synthesized by procedures known in the art or as described in the following examples) under standard peptide coupling conditions (e.g., DCC, EDCI, HATU, PyBop, etc.) in a polar aprotic solvent (e.g., DCM, DMF, etc.). Alternatively, the carboxylic acid derivative of formula 8 can be converted to an acid chloride derivative by procedures known to those skilled in the art or as described in the procedures of the following examples, and then reacted with an amine of formula 9 by procedures known to those skilled in the art or as described in the procedures of the following examples to obtain the desired pyrazolo[1,5-a]pyridine of formula 10.

[0188] The compounds of interest having the structures according to the general formula (A) and all other general formulas described herein, and their embodiments, can be prepared as outlined in General Chemical Scheme 2.

Chemical formula

[0189] Scheme 2: All V, n, R 1 、R 2 R 3 、R4 and R 5 is as described for the compounds of the present invention. For each occurrence of R 5 , up to two independent substituents are contemplated (i.e., R 5 and R 5’ ). The integer n can range from 1 to 10 in some embodiments.

[0190] 4-(Benzyloxy)pyridine of formula 11 is reacted with a reagent carrying an electrophilic amine (e.g., 2,4-DNPH, O-(mesitylsulfonyl)hydroxylamine, etc.) in a suitable solvent (e.g., MeCN, DMF, NMP, etc.) to obtain an N-aminopyridinium salt of formula 12. The intermediate of formula 12 is condensed with an alkyne ester derivative 13 (either commercially available or synthesized by procedures known to those skilled in the art) at a temperature in the range of 0 to 100 °C in the presence of a base (e.g., potassium carbonate, DBU, etc.) in a polar solvent (e.g., DMF, DCM, MeCN, etc.) to obtain a pyrazolo[1,5-a]pyridine of formula 14 (wherein R2 is an ester protecting group (e.g., methyl, ethyl, t-Bu, etc.)). Then, the ester derivative 14 can be converted to an intermediate compound of formula 15 via a hydrogenation reaction with a reducing agent (e.g., hydrogen gas, ammonium formate, cyclohexadiene, etc.) using a catalyst (more preferably Pd or Pt) in a solvent (e.g., THF, EtOH, etc.). Then, the intermediate of formula 15 is reacted with an intermediate of formula 16a (either a commercial product or a synthetic product) (wherein LG is a leaving group) in a polar solvent (e.g., MeCN, DMF, NMP, etc.) in the presence of a base (e.g., DIPEA, DBU, triethylamine, Cs 2 CO 3In the presence of (such as), it can be converted into the desired compound of Formula 17 through nucleophilic substitution at a temperature in the range of 0 to 100 °C, with or without a chelating agent (such as 18-crown-6, cis-anti-cis-dicyclohexano-18-crown-6, etc.). Alternatively, the intermediate of Formula 15 can be reacted with an intermediate of Formula 16b (commercially available or synthetic) in the presence of an azodicarboxylate reagent (such as DEAD, DIAD, ADDP, etc.) and a phosphine (such as tributylphosphine, triphenylphosphine, etc.) in a solvent (such as THF, toluene, etc.) at a temperature in the range of 0 to 100 °C to obtain the desired compound of Formula 17. Then, the ester derivative 17 can be converted into the desired compound of Formula 18 through a standard saponification reaction. Alternatively, then, the benzyl derivative 14 can be converted into the desired compound of Formula 18 through a standard saponification reaction. The desired compound of Formula 20 can be obtained from the acid derivative of Formula 18 by reaction with an amine derivative of Formula 19 (commercially available or synthesized by procedures known in the art or as described in the following examples) under standard peptide coupling conditions (such as DCC, EDCI, HATU, PyBop, etc.) in a polar aprotic solvent (such as DCM, DMF, etc.). Alternatively, the carboxylic acid derivative of Formula 18 can be converted into an acid chloride derivative by procedures known to those skilled in the art or as described in the procedures of the following examples, and then reacted with the amine of Formula 9 by procedures known to those skilled in the art or as described in the procedures of the following examples to obtain the desired pyrazolo[1,5-a]pyridine of Formula 20.

Table 3-1

Table 3-2

Table 4-1

Table 4-2

Table 4-3

Table 4-4

Table 4-5

[0191] The following examples are provided to illustrate the present invention and are not intended to limit the scope of the present invention in any way.

[0192] Part A represents the preparation of compounds, and Part B represents pharmacological examples.

[0193] Part A All starting materials not explicitly described are commercially available (for example, details of suppliers such as ABCR, Apollo Scientific Combi-Blocks, Enamine, FluoroChem, Matrix Scientific, Maybridge, Merck, TCI, etc. can be found in, for example, the SciFinder® database), or their synthesis has already been accurately described in the specialized literature (for example, experimental guidelines can be found in the Reaxys® database or the SciFinder® database respectively), or they can be prepared using conventional methods known to those skilled in the art.

[0194] The reactions were carried out under an inert atmosphere (mainly argon and N 2 ) as required. The number of equivalents of reagents and the amount of solvent used, as well as the reaction temperature and time, may vary slightly between different reactions carried out by similar methods. The processing and purification methods are adapted according to the characteristic properties of each compound and may vary slightly in similar methods. The yields of the prepared compounds have not been optimized.

[0195] The notation "equivalent" ("eq.", "eq", or "equiv.") means molar equivalent, "RT" or "rt" means room temperature T (23 ± 7 °C), "M" is the notation for concentration in mol / l, "sol." means solution, and "conc." means concentrated. The mixing ratio of solvents is usually expressed as volume / volume ratio.

[0196] The major analytical characterizations were performed for all exemplary compounds and selected intermediate products 1 by 1H-NMR spectroscopy and / or mass spectrometry (MS, m / z for + [M+H] - and / or [M−H]). In certain cases, for example, when positional isomers and / or diastereomers could have been / had been formed during the reaction, additional analyses such as 13 13C NMR and NOE (nuclear Overhauser effect) NMR experiments were performed in some cases.

[0197] The analytical instruments used were, for example, for NMR analysis, BRUKER 400 MHz or BRUKER 500 MHz machines (software Topspin), alternatively, BRUKER AVANCE 300 MHz and 400 MHz were used. For LC / MS analysis, for example, Agilent 1290 infinity, Mass: 6150 SQD (ESI / APCI), or Agilent 1200 SERIES, Mass: 6130 SQD (ESI / APCI) (software Chemistation) were used. Analytical HPLC was measured with, for example, Waters (software Empower), Agilent-1200-ELSD (software Chemistation), or Agilent-1260 (software OpenLAB). Analytical SFC was performed with, for example, PIC solution (software: SFC PICLAB ONLINE), WATERS-X5 (software MASSLYNX), or WATERS-UPC2 (Empower).

[0198] Preparative HPLC was performed, for example, using Waters 2998 (software Empower) or YMC (software K-Prep). Preparative SFC was performed, for example, using Waters, SFC-200 (software Chromscope or Super chrome), Waters, SFC-80 (Super chrome), or PIC, PIC-175 (software S10-100).

[0199] For compounds containing a stereocenter, if the structure is known, the absolute stereochemistry is depicted and named. For compounds of unknown absolute stereochemistry, the compound can be either a racemate, a mixture of diastereomers, a pure diastereomer of unknown stereochemistry, or a pure enantiomer of unknown stereochemistry. Dia1 and Dia2 mean that the diastereoisomers were separated, but the stereochemistry is unknown. En1 and En2 mean that both enantiomers were separated, but the absolute configuration is unknown. When no suffix is attached after the compound code, it means that compounds containing a stereocenter were obtained as a racemic mixture or a mixture of diastereomers respectively, unless the chemical name of the compound specifies the exact stereochemistry.

[0200] Synthesis of ethyl 5-(benzyloxy)-2-methylpyrazolo[1,5-a]pyridine-3-carboxylate (Int-01).

Chemical Structure

[0201] Step 1: To a stirred solution of 4-benzyloxy-pyridine (60 g, 324.3 mmol) in MeCN (600 mL) was added 2,4-DNPH (64.5 g, 324.3 mmol) at room temperature. The reaction mixture was heated to 40 °C and stirred at 40 °C for 16 h. The reaction mixture was concentrated under reduced pressure while maintaining the water bath temperature below 40 °C to obtain 1-amino-4-benzyloxy-pyridinium. To a solution of 1-amino-4-benzyloxy-pyridinium in DMF (600 mL) was added potassium carbonate (447.5 g, 3243.2 mmol), followed by addition of methyl but-2-enoate (56.6 mL, 486.4 mmol) at room temperature. The reaction mixture was stirred at room temperature for 16 h. The RM was quenched with ice-cold water and extracted with EtOAc:MTBE (1:3, 3 L). The combined organic layers were washed with brine (900 mL×2) and dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (100 - 200 mesh) using 20 - 25% EtOAc in Pet ether as the eluent to give ethyl 5-(benzyloxy)-2-methylpyrazolo[1,5-a]pyridine-3-carboxylate (Int-01) (20 g, 19.8% over 2 steps) as an off-white solid. 1 1H-NMR (400 MHz, CDCl3) δ [ppm]: 8.21 - 8.23 (m, 1H), 7.26 - 7.47 (m, 7H), 6.60 - 6.62 (m, 1H), 5.15 (s, 2H), 4.36 (q, 3H), 2.62 (s, 3H), 1.40 (t, 3H).

[0202] Synthesis of 2-amino-3-((tert-butyldimethylsilyl)oxy)-2-methylpropanamide (Int-02).

Chemical Structure

[0203] Step 1: To a stirred solution of 1-(tert-butyl-dimethyl-silanilyloxy)-propan-2-one (25 g, 132.7 mmol) in EtOH (250 ml) was added 4-methoxybenzylamine (19.08 ml, 146 mmol) at room temperature. Trimethylsilyl cyanide (19.93 ml, 159.286 mmol) and then ammonium chloride (2.13 g, 39.8 mmol) were added to the RM at room temperature. The RM was stirred at 80 °C for 16 h. The RM was concentrated. The crude was partitioned between EtOAc and saturated sodium bicarbonate solution. The organic layer was washed with brine solution, dried over sodium sulfate and concentrated. The crude was purified by FCC (using 100 - 200 silica gel, eluting with 10% EtOAc - hexane) to give 3-(tert-butyl-dimethyl-silanilyloxy)-2-(4-methoxy-benzylamino)-2-methyl-propionitrile (25 g, 57%) as a yellow liquid. 1 H-NMR (400 MHz, DMSO) δ [ppm]: 7.25 - 7.23 (d, 2H), 6.68 - 6.86 (d, 2H), 3.72 - 3.68 (m, 6H), 3.51 - 3.48 (m, 1H), 1.36 (s, 3H), 0.87 (s, 9H), 0.06 (s, 6H).

[0204] Step 2: To a stirred solution of 3-(tert-butyl-dimethyl-silanilyloxy)-2-(4-methoxy-benzylamino)-2-methyl-propionitrile (10 g, 29.9 mmol) in DMSO (100 ml) was added potassium carbonate (28.92 g, 209.243 mmol) at room temperature. Hydrogen peroxide (14.03 ml, 298.92 mmol) was added dropwise to the reaction at 0 °C. The RM was stirred at room temperature for 16 h. The RM was quenched with ice cold water and extracted with MTBE. The organic portion was dried over Na 2 SO 4 and concentrated. The resulting crude material was purified by FCC (using 100 - 200 silica gel, eluting with 50% EtOAc - hexane) to give 3-(tert-butyl-dimethyl-silanilyloxy)-2-(4-methoxy-benzylamino)-2-methyl-propionamide (3.4 g, 33%) as an oily liquid. 1H-NMR (400 MHz, DMSO) δ [ppm]: 7.26 - 7.24 (d, 3H), 7.06 (s, 1H), 6.87 - 6.85 (d, 2H), 3.72 (s, 3H), 3.70 - 3.68 (m, 1H), 3.58 - 3.56 (m, 1H), 3.51 - 3.50 (d, 2H), 2.04 (m, 1H), 1.15 (s, 3H), 0.85 (s, 9H), 0.03 (s, 6H).

[0205] Step 3: To a stirred solution of -(tert-Butyl-dimethyl-silanyloxy)-2-(4-methoxy-benzylamino)-2-methyl-propionamide (3 g, 8.509 mmol) in MeOH (60 ml) was added palladium hydroxide (1.5 g) at room temperature. The RM was stirred at room temperature under H 2 gas balloon pressure for 4 h. The RM was filtered through a celite bed and washed with 10% MeOH-DCM. The combined filtrates were concentrated to afford 2-amino-3-((tert-butyldimethylsilyl)oxy)-2-methylpropanamide (Int-02) (1.5 g, 76%) as an off-white solid. 1 H-NMR (400 MHz, DMSO) δ [ppm]: 7.25 (s, 1H), 6.95 (s, 1H), 3.77 - 3.74 (d, 1H), 3.70 - 3.68 (m, 1H), 3.27 - 3.24 (d, 1H), 1.82 (s, 2H), 1.04 (s, 3H), 0.85 (s, 9H), 0.02 (s, 6H).

[0206] Synthesis of ethyl 5-hydroxy-2-methylpyrazolo[1,5-a]pyridine-3-carboxylate (Int-03).

Chemical Structure

[0207] Step 1: To a stirred solution of ethyl 5-benzyloxy-2-methyl-pyrazolo[1,5-a]pyridine-3-carboxylate (int-01) (10.0 g) in MeOH (650 mL) was added 10% Pd / C (2.5 g) at room temperature. The RM was stirred under balloon pressure with H 2It was stirred in gas for 4 hours. The RM was filtered through a celite bed, and the celite bed was washed with 10% MeOH in dichloromethane (50 mL). The combined filtrate was concentrated under reduced pressure. The crude product was triturated with MTBE and n-pentane (1:9, 100 mL) to give ethyl 5-hydroxy-2-methylpyrazolo[1,5-a]pyridine-3-carboxylate (Int-03) (5.0 g, 70%) as an off-white solid. 1 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 10.89 (s, 1H), 8.49 - 8.51 (m, 1H), 7.20 (s, 1H), 6.59 - 6.62 (m, 1H), 4.24 (q, 2H), 2.47 (s, 3H), 1.32 (t, 3H).

[0208] Synthesis of 2-amino-2-(hydroxymethyl)butanamide (Int-04).

Chemical formula

[0209] Step 1: A mixture of sodium cyanide (4.45 g, 90.90 mmol), ammonium chloride (4.9 g, 90.90 mmol), and ammonia solution (7 M in methanol, 120 mL) in methanol (65 ml) was stirred at room temperature, stirred for 10 minutes, and then 1-hydroxybutan-2-one (4.0 g, 45.45 mmol) was added. The reaction mixture was stirred at room temperature for 24 hours, filtered through a celite bed, and the celite bed was washed with methanol (50 mL). The combined filtrate was concentrated under vacuum. Ethyl acetate (80 mL) was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum. The residue was co-distilled with dichloromethane (2 × 50 mL) to give 2-amino-2-(hydroxymethyl)butanenitrile (4.2 g) as a pale yellow residue. TLC system: 100% ethyl acetate, RF: 0.3.

[0210] Step 2: To a stirred solution of 2-amino-2-(hydroxymethyl)butanenitrile (2.0 g, 17.54 mmol) in ethanol (20 mL) cooled to 0 °C, KOH (1.47 g, 26.31 mmol) was added, followed by 30% H2 O 2 (2 mL) was added dropwise at 0 °C. The reaction mixture was stirred at room temperature for 1 hour. The progress of the reaction was monitored by TLC, and the reaction mixture was concentrated under vacuum. The crude product was diluted with 10% methanol in dichloromethane (2 × 50 mL), stirred for 20 minutes, and filtered. The filtrate was concentrated under reduced pressure to obtain 2-amino-2-(hydroxymethyl)butanamide (Int-04) (1.8 g) as a thick residue. TLC system: 10% methanol in dichloromethane, RF: 0.1.

[0211] Synthesis of 2-amino-4,4-difluorobutan-1-ol (Int-05).

Chemical Structure

[0212] Step 1: To a solution of t-BuOK (13.2 g, 117.836 mmol) in DMF (150 mL) was added ethyl 2-((diphenylmethylene)amino)acetate (30 g, 112.225 mmol) at 0 °C. After 30 minutes, 1,1-difluoro-2-iodoethane (24.9 g, 130.181 mmol) was added over 10 minutes while maintaining the temperature at -5 °C to 5 °C. The reaction mixture (RM) was stirred at 5 °C for 1 hour. After completion, the RM was diluted with saturated NH 4 Cl solution (100 mL) and extracted with EtOAc (3 × 100 mL). The combined organic layers were washed with brine (100 mL), dried over Na 2 SO 4 and filtered, then concentrated under reduced pressure. The residue was purified by FCC on silica gel using 5% EtOAc in pet ether as the eluent to obtain ethyl 2-((diphenylmethylene)amino)-4,4-difluorobutanoate (30 g, 80.67%) as a pale yellow liquid. 1 1H NMR (400 MHz, CDCl 3)δ ppm: 7.64 (d, 2 H), 7.42 - 7.48 (m, 4 H), 7.31 - 7.39 (m, 2 H), 7.18 - 7.25 (m, 2 H), 5.75 - 5.91 (tt, 1 H), 4.27 - 4.30 (m, 1 H), 4.12 - 4.21 (m, 2 H), 2.45 - 2.53 (m, 2 H), 1.25 (t, 3 H)

[0213] Step 2: 1N HCl (80 ml) was added to a solution of ethyl 2 - ((diphenylmethylene)amino)-4,4 - difluorobutanoate (8.0 g, 24.143 mmol) in hexane (40 ml) at room temperature. The RM was stirred at room temperature for 4 hours. After completion, the RM was washed with hexane (2 × 40 mL). The aqueous solution was basified with NaHCO 3 (pH about 8) and extracted with EtOAc (2 × 100 mL). The combined organic layers were dried over Na 2 SO 4 and concentrated under reduced pressure to obtain the desired product as a brown liquid (2.5 g). 1 1H NMR (400 MHz, CDCl 3 )δ ppm: 5.91 - 6.22 (m, 1 H), 4.20 (q, 2 H), 3.61 - 3.65 (m, 1 H), 2.24 - 2.36 (m, 1 H), 1.98 - 2.00 (m, 1 H), 1.27 (t, 3 H).

[0214] Step 3: Sodium borohydride (1.697 g, 44.868 mmol) was added to a solution of ethyl 2 - amino - 4,4 - difluorobutanoate (2.5 g, 14.956 mmol) in EtOH (30 mL) at 0 °C. The RM was stirred at room temperature for 6 hours. The RM was diluted with saturated NH 4 Cl (20.0 mL) and extracted with EtOAc (3 × 50 mL). The combined organic layers were washed with brine (20.0 mL), dried over anhydrous Na 2 SO 4 filtered, and concentrated under reduced pressure to obtain 2 - amino - 4,4 - difluorobutan - 1 - ol (Int - 05) as a yellow liquid (1.2 g, 64.13%).

[0215] Synthesis of 4,4-difluoro-1-methoxy-2-methylbutan-2-amine hydrochloride (Int-06). [Chemical formula]

[0216] Step 1: Anhydrous phthalic acid (2.66 g, 17.96 mmol) was added to a solution of 2-amino-4,4-difluoro-2-methylbutan-1-ol (2.5 g, 17.96 mmol) in toluene (25 mL). The RM was stirred at 120 °C for 24 h in a sealed tube. After consumption, the RM was concentrated under reduced pressure. The residue was purified by FCC on silica gel using 25% EtOAc in pet ether as the eluent to give 2-(4,4-difluoro-1-hydroxy-2-methylbutan-2-yl)isoindoline-1,3-dione (2.0 g, yield 41.34%) as a pale yellow gum. 1 H NMR (400 MHz, CDCl 3 ) δ ppm: 7.79 - 7.84 (m, 2 H), 7.71 - 7.75 (m, 2 H), 6.06 - 6.37 (dt, 1 H), 4.03 - 4.12 (m, 2 H), 3.62 (t, 1 H), 2.87 - 3.00 (m, 1 H), 2.29 - 2.43 (m, 1 H), 1.66 (s, 3 H).

[0217] Step 2: NaH (60% in mineral oil) (463.51 mg, 19.313 mmol) and iodomethane (1.194 mL, 19.31 mmol) were added to a solution of 2-(4,4-difluoro-1-hydroxy-2-methylbutan-2-yl)isoindoline-1,3-dione (2.6 g, 9.657 mmol) in DMF (26 mL) at 0 °C. The RM was stirred at room temperature for 2 h. After consumption, the RM was quenched with ice-cold water (20 mL) and extracted with EtOAc (2 × 40 mL). The organic layer was washed with Na 2 SO 4It was dried, filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 25% EtOAc in pet ether as the eluent to obtain 2-(4,4-difluoro-1-methoxy-2-methylbutan-2-yl)isoindoline-1,3-dione (1.1 g, yield: 40.21%) as a pale yellow gum. 1 H NMR (400 MHz, CDCl 3 ) δ ppm: 7.76 - 7.81 (m, 2 H), 7.67 - 7.72 (m, 2 H), 5.87 - 6.17 (dt, 1 H), 3.99 (d, 1 H), 3.79 (d, 2 H), 3.36 (d, 3 H), 2.77 - 2.90 (m, 1 H), 2.40 - 2.53 (m, 1 H), 1.82 (s, 3 H).

[0218] Step 3: To a solution of 2-(4,4-difluoro-1-methoxy-2-methylbutan-2-yl)isoindoline-1,3-dione (1.1 g, 3.883 mmol) in IPA (22 mL) and water (2.2 mL), NaBH 4 (733.9 mg, 19.41 mmol) was added at 0 °C. The reaction mixture was stirred at room temperature for 16 h. After completion, the reaction mixture was concentrated, and the resulting residue was quenched with cold water (30 mL) and extracted with EtOAc (2 × 30 mL). The organic layer was washed with brine (20 mL), dried over anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure. The residue was treated with 6N HCl (22 mL) and heated at 80 °C for 2 h. The reaction mixture was concentrated under reduced pressure, and the resulting residue was triturated with diethyl ether (2 × 30 mL). The solid was filtered and dried under vacuum to obtain 4,4-difluoro-1-methoxy-2-methylbutan-2-amine hydrochloride (Int-06) (650 mg, yield: 88.27%) as an off-white solid. 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 8.40 (s, 3 H), 6.20 - 6.50 (dt, 1 H), 3.43 (s, 2 H), 3.33 (s, 3 H), 2.19 - 2.30 (m, 2 H), 1.29 (s, 3 H).

[0219] Synthesis of methyl 1-amino-2,2-difluorocyclopropane-1-carboxylate hydrobromide (Int-07). [Chemical formula]

[0220] Step 1: To a solution of methyl 2-(((benzyloxy)carbonyl)amino)acrylate (2.5 g, 10.627 mmol) in toluene (50 mL), NaF (44.61 mg, 1.063 mmol) was added at room temperature and the mixture was heated to 110 °C. After 10 minutes, a solution of trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)acetate (5.236 mL, 26.56 mmol) in toluene (50 mL) was added dropwise to the RM over 4 hours. The RM was stirred at 110 °C for 18 hours. After completion, the RM was cooled to 0 °C and quenched with saturated Na 2 CO 3 solution (70 mL) and extracted with EtOAc (2 × 70 mL). The combined organic layers were washed with brine solution (50 mL), dried over Na 2 SO 4 and filtered, then concentrated under reduced pressure. The residue was purified by FCC on silica gel using 15% EtOAc in pet ether as the eluent to give methyl 1-(((benzyloxy)carbonyl)amino)-2,2-difluorocyclopropane-1-carboxylate (1.4 g, yield 46.18%) as a pale yellow liquid. 1 1H NMR (400 MHz, CDCl 3 ) δ ppm: 7.32 - 7.38 (m, 5 H), 5.57 (s, 1 H), 5.14 (s, 2 H), 3.77 (s, 3 H), 2.66 - 2.71 (m, 1 H), 1.75 - 1.95 (m, 1 H).

[0221] Step 2: Methyl 1-(((benzyloxy)carbonyl)amino)-2,2-difluorocyclopropane-1-carboxylate (1.4 g, 4.908 mmol) and HBr in acetic acid (33%) (7.5 mL) were stirred at room temperature for 2 hours. After consumption, the reaction mixture was concentrated under reduced pressure, and the resulting residue was triturated with diethyl ether (2 × 30 mL). The obtained solid was filtered and dried under vacuum to give methyl 1-amino-2,2-difluorocyclopropane-1-carboxylate hydrobromide (Int-07) as a light brown solid (1.0 g, yield: 87.81%). 1 H NMR(400 MHz,DMSO-d 6 )δ ppm:9.15(s,2 H),3.82(s,3 H),2.69-2.78(m,1 H),2.43-2.51(m,1 H).

[0222] Synthesis of (cis-1-amino-2-(difluoromethyl)cyclopropyl)methanol hydrochloride (Int-08).

Chemical Structure

[0223] Step 1: 4M HCl in dioxane (5.0 mL) was added to a solution of tert-butyl (cis-2-(difluoromethyl)-1-(hydroxymethyl)cyclopropyl)carbamate (880 mg, 3.318 mmol) in DCM (10 mL) at room temperature. The reaction mixture was stirred at room temperature for 1 hour. After consumption, the reaction mixture was concentrated under reduced pressure, and the resulting residue was triturated with diethyl ether (2 × 20 mL). The residue was dried under vacuum to give (cis-1-amino-2-(difluoromethyl)cyclopropyl)methanol hydrochloride (Int-08) as a pale yellow gum (700 mg). 1 H NMR(400 MHz,CDCl 3 )δ ppm:9.19(s,2 H),6.00-5.70(dt,1 H),3.70(s,3 H),2.80-2.70(m,1 H),2.23-2.18(m,1 H),1.90-1.86(m,1 H).

[0224] Synthesis of 2-amino-2-(1-cyclopropyl-1H-imidazol-2-yl)ethan-1-ol hydrochloride (Int-09).

Chem.

[0225] Step 1: To a solution of 2-((tert-butyldimethylsilyl)oxy)acetaldehyde (2 g, 11.47 mmol) in DCM (30 mL) were added 2-methylpropan-2-sulfinamide (1.53 g, 12.62 mmol) and copper(II) sulfate (3.66 g, 22.94 mmol) under N 2 atmosphere at room temperature. The reaction mixture (RM) was stirred at room temperature for 12 h. After completion, the RM was filtered and washed with DCM (50 mL). The filtrate was concentrated under reduced pressure. The residue was purified by FCC on silica gel using 10% EtOAc in Pet. ether as the eluent to afford (E / Z)-N-(2-((tert-butyldimethylsilyl)oxy)ethylidene)-2-methylpropan-2-sulfinamide (1.5 g, yield 47.11%) as a pale yellow gum. 1 H NMR (400 MHz, CDCl 3 ) δ ppm: 7.96 (s, 1 H), 4.44 (s, 2H), 1.10 (s, 9H), 0.82 (s, 9H).

[0226] Step 2: To a solution of 1-cyclopropyl-1H-imidazole (500 mg, 4.62 mmol) in THF (22 mL) was added dropwise nBuLi (5 mL, 2.5 M) at -78 °C. The RM was stirred at -78 °C for 2 h. After 2 h, a solution of (E)-N-(2-((tert-butyldimethylsilyl)oxy)ethylidene)-2-methylpropan-2-sulfinamide (1.54 g, 5.54 mmol) in THF (2 mL) was added dropwise to the RM. The RM was stirred for 1.5 h. After completion, the RM was quenched with saturated NH 4 Cl (25 mL) at 0 °C and extracted with EtOAc (3 × 30 mL). The combined organic layers were washed with brine (30 mL) and concentrated to afford the compound (1.5 g, 84%).

[0227] Step 3: To a q solution of N-(2-((tert-butyldimethylsilyl)oxy)-1-(1-cyclopropyl-1H-imidazol-2-yl)ethyl)-2-methylpropane-2-sulfinamide (1.3 g, 3.37 mmol) in 1,4-dioxane (10 mL) was added 4M HCl in 1,4-dioxane (5 mL) at 0 °C. The RM was stirred at room temperature for 16 h. After consumption, the RM was concentrated under reduced pressure. The residue was triturated with DCM (2 × 5 mL) and dried under vacuum to give 2-amino-2-(1-cyclopropyl-1H-imidazol-2-yl)ethan-1-ol hydrochloride (Int-09) (800 mg, 88%) as a brown gum.

[0228] Synthesis of ethyl 2-amino-2-(1-methyl-1H-pyrazol-3-yl)propanoate (Int-10).

Chemical formula

[0229] Step 1: To a solution of ethyl 2-((diphenylmethylene)amino)acetate (5.0 g, 18.704 mmol) and 3-bromo-1-methyl-1H-pyrazole (2.850 mL, 28.056 mmol) in toluene (50 mL, taken up in a 100 mL sealed tube) was added K 3 PO 4 (11.907 g, 56.113 mmol). The RM was degassed with argon for 20 min. Pd(t-Bu3P)2 (955.87 mg, 1.870 mmol) was added at room temperature. The resulting RM was stirred at 100 °C for 16 h. After completion, the RM was diluted with cold water (100 mL) and extracted with EtOAc (2 × 100 mL). The combined organic layers were washed with brine (100 mL), dried over Na 2 SO 4 and filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 12% EtOAc in pet ether as the eluent to give ethyl 2-((diphenylmethylene)amino)-2-(1-methyl-1H-pyrazol-3-yl)acetate (2.5 g, yield 38.47%) as a pale yellow gum.1 1H NMR (400 MHz, CDCl 3 ) δ ppm: 7.68 - 7.71 (q, 2 H), 7.42 - 7.44 (m, 3 H), 7.36 - 7.38 (m, 1 H), 7.30 - 7.33 (m, 3 H), 7.17 - 7.20 (m, 2 H), 6.45 (d, 1 H), 5.34 (s, 1 H), 4.15 - 4.19 (m, 2 H), 3.84 (s, 3 H), 1.22 (t, 3 H).

[0230] Step 2: To a solution of ethyl 2 - ((diphenylmethylene)amino)-2-(1 - methyl - 1H - pyrazol - 3 - yl)acetate (1.8 g, 5.181 mmol) in DMF (20 mL, taken in a sealed tube), NaH (60%) (621 mg, 15.543 mmol) was added portionwise at 0 °C. The RM was stirred at 0 °C for 30 minutes. After 30 minutes, iodomethane (1.613 mL, 25.90 mmol) was added. The RM was stirred at room temperature for 16 hours. After completion, the RM was quenched with cold water (50 mL) and extracted with EtOAc (2 × 50 mL). The combined organic layers were washed with brine (50 mL) and dried over anhydrous Na 2 SO 4 , filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 20% EtOAc in pet ether as the eluent to give ethyl 2 - ((diphenylmethylene)amino)-2-(1 - methyl - 1H - pyrazol - 3 - yl)propanoate (1.0 g, yield 53.40%) as a light brown gummy substance. 1 1H NMR (400 MHz, DMSO - d 6 ) δ ppm: 7.48 - 7.52 (m, 3 H), 7.34 - 7.42 (m, 6 H), 6.34 (d, 2 H), 5.75 (s, 1 H), 3.63 - 3.75 (m, 5 H), 1.62 (s, 3 H), 1.00 (t, 3 H).

[0231] Step 3: To a solution of ethyl 2-((diphenylmethylene)amino)-2-(1-methyl-1H-pyrazol-3-yl)propanoate (1.6 g, 4.427 mmol) in hexane (15 mL) was added 1N HCl (aqueous solution) (30 mL) at room temperature. The RM was stirred for 16 h. After completion, the RM was extracted with EtOAc (3 × 20 mL). The aqueous layer was basified with saturated NaHCO 3 solution (pH ca. 0.8) and extracted with 10% MeOH in DCM (3 × 30 mL). The combined organic layers were dried over Na 2 SO 4 and filtered, and concentrated under reduced pressure to give ethyl 2-amino-2-(1-methyl-1H-pyrazol-3-yl)propanoate (Int-10) (630 mg, 72.24%) as a brown liquid. 1 H NMR (400 MHz, DMSO-d 6 ) δ ppm: 7.54 (s, 1 H), 6.18 (s, 1 H), 4.00 - 4.07 (m, 2 H), 3.99 (s, 3 H), 2.21 (s, 2 H), 1.50 (s, 3 H), 1.12 (t, 3 H).

[0232] Synthesis of trans-3-amino-4-(trifluoromethyl)pyrrolidine-1-carboxylic acid tert-butyl (Int-11).

Chemical Structure

[0233] Step 1: To a solution of trans-1-(tert-butoxycarbonyl)-4-(trifluoromethyl)pyrrolidine-3-carboxylic acid (3 g, 10.591 mmol) in xylene (25 mL), TEA (1.771 mL, 12.710 mmol) and DPPA (2.505 mL, 11.651 mmol) were added dropwise at room temperature. The reaction mixture (RM) was heated to 130 °C and stirred for 1 h. After 1 h, phenylmethanol (1.211 mL, 11.651 mmol) was added to the RM and the mixture was stirred at 130 °C for 3 h. After cooling to room temperature, the RM was quenched with 1 N NaOH solution (80.0 mL) and washed with EtOAc (2 × 50 mL). The aqueous layer was acidified with aqueous citric acid (pH ca. 5) and extracted with DCM (2 × 80 mL). The organic layer was washed with brine (50 mL) and dried over Na 2 SO 4 , filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using 15% EtOAc in pet ether as eluent to afford tert-butyl trans-3-(((benzyloxy)carbonyl)amino)-4-(trifluoromethyl)pyrrolidine-1-carboxylate (2.2 g, 53.48%) as a yellow solid. 1 1H NMR (400 MHz, DMSO-d 6 ) δ ppm: 7.32 - 7.38 (m, 7 H), 5.10 (s, 3 H), 4.69 (d, 1 H), 4.35 - 4.40 (m, 1 H), 3.77 - 3.82 (m, 1 H), 3.49 (s, 2 H), 2.94 (s, 2 H), 1.45 (s, 9 H).

[0234] Step 2: 10% Pd / C (1.315 g, 12.359 mmol) was added to a solution of tert-butyl trans-3-(((benzyloxy)carbonyl)amino)-4-(trifluoromethyl)pyrrolidine-1-carboxylate (2.4 g, 6.179 mmol) in EtOAc (20 mL). The reaction mixture (RM) was stirred at room temperature for 16 h under a hydrogen balloon pressure. After completion, the RM was filtered through a Celite pad, washed with EtOAc (2 × 100 mL), and the filtrate was concentrated under reduced pressure. The residue was purified by FCC on silica gel using 45% EtOAc in pet ether as the eluent to give tert-butyl trans-3-amino-4-(trifluoromethyl)pyrrolidine-1-carboxylate (Int-11) (1.3 g, 82.74%) as a colorless liquid. 1 H NMR(400 MHz,DMSO-d 6 )δ ppm: 3.49 - 3.62(m, 3 H), 3.26 - 3.31(m, 2 H), 2.96(s, 1 H), 2.85(s, 1 H), 1.82 - 1.98(m, 2 H), 1.39(s, 9 H).

[0235] Synthesis of benzyl 3-amino-3-(2,2-difluoroethyl)piperidine-1-carboxylate (Int-12).

Chemical Structure

[0236] Step 1: TEA (1.704 mL, 12.228 mmol) and DPPA (1.446 mL, 6.725 mmol) were added dropwise to a solution of 1-((benzyloxy)carbonyl)-3-(2,2-difluoroethyl)piperidine-3-carboxylic acid (2.0 g, 6.114 mmol) in toluene (20 mL) at room temperature. The RM was heated at 100 °C for 2 h. After cooling to room temperature, the RM was diluted with water and extracted with EtOAc (2 × 100 mL). The combined organic layers were washed with brine (50 mL) and Na 2 SO 4It was dried, filtered, and concentrated under reduced pressure to obtain benzyl 3-(2,2-difluoroethyl)-3-isocyanatopiperidine-1-carboxylate (1.8 g, 90.78%) as a pale yellow liquid.

[0237] Step 2: 6M aqueous HCl solution (18 mL) was added to a solution of benzyl 3-(2,2-difluoroethyl)-3-isocyanatopiperidine-1-carboxylate (1.8 g, 5.550 mmol) in 1,4-dioxane (18 mL). The RM was heated at 45 °C for 16 h. After completion, the RM was concentrated. The residue was diluted with water (50 mL) and washed with EtOAc (100 mL). The aqueous layer was basified with 1N NaOH solution (50 mL) and extracted with DCM (2 × 100 mL). The combined organic layers were washed with brine (10 mL) and dried over 2 SO 4 Na, filtered, and concentrated under reduced pressure to obtain benzyl 3-amino-3-(2,2-difluoroethyl)piperidine-1-carboxylate (Int-12) as a pale yellow liquid (900 mg, 54.36%). 1 1H NMR (400 MHz, DMSO d 6 6) δ ppm: 7.37 - 7.30 (m, 5 H), 6.37 - 6.07 (m, 1 H), 5.06 (s, 2 H), 3.56 (s, 4 H), 3.38 - 3.16 (m, 3 H), 1.90 - 1.79 (m, 2 H), 1.65 - 1.55 (m, 4 H), 1.43 - 1.38 (m, 2 H).

[0238] Synthesis of ethyl 2-amino-2-(1-methyl-1H-pyrazol-3-yl)acetate (Int-13).

Chemical formula

[0239] Step 1: To a solution of ethyl 2-((diphenylmethylene)amino)-2-(1-methyl-1H-pyrazol-3-yl)acetate (2.4 g, 6.908 mmol, 1.0 equiv) in hexane (10 mL) was added 1N HCl (aqueous solution) (25 mL) at room temperature. The reaction mixture (RM) was stirred for 16 h. After completion, the RM was extracted with EtOAc (2 × 30 mL). The aqueous layer was basified with saturated NaHCO 3 solution (pH ca. 0.8) and extracted with 10% MeOH in DCM (3 × 50 mL). The combined organic layers were dried over Na 2 SO 4 , filtered, and concentrated under reduced pressure to give ethyl 2-amino-2-(1-methyl-1H-pyrazol-3-yl)acetate (Int-13) (900 mg, 71.11%). 1 1H NMR (400 MHz, DMSO-d 6 ) δ ppm: 7.57 (d, 1 H), 6.15 (d, 1 H), 4.43 (s, 1 H), 4.11 - 4.01 (m, 2 H), 3.70 (s, 3 H), 2.07 (s, 2 H), 1.14 (t, 3 H).

[0240] Synthesis of 2-amino-3-hydroxy-2-methylpropanamide (Int-14).

Chemical formula

[0241] Step 1: To a mixture of sodium cyanide (3.97 g, 81.08 mmol), ammonium chloride (4.29 g, 81.08 mmol), and ammonia solution (7M in methanol, 30 mL) was added 1-hydroxyacetone (3.0 g, 40.54 mmol) after 10 min. The reaction mixture (RM) was stirred at room temperature under nitrogen for 23 h and then concentrated under vacuum. EtOAc (200 mL) was added to the residue and the solid was filtered off. The filtrate was concentrated under vacuum and DCM (1 × 50 mL) was added to the residue. The solution was cooled to -20 °C and left standing at room temperature for 60 h. The precipitate was collected by filtration, washed with cold DCM, and dried under vacuum to give 2-amino-3-hydroxy-2-methylpropanenitrile (2.0 g, 50%).

[0242] Step 2: To a stirred solution of amino-3-hydroxy-2-methylpropanenitrile (2.0 g, 20 mmol) in ethanol (30 mL) at 0 °C was added KOH (1.62 g, 30 mmol, 1.5 equiv), followed by H 2 O 2 (2 mL) dropwise at 0 °C. The RM was stirred at room temperature for 18 h. The RM was concentrated under reduced pressure. The residue was diluted with 10% MeOH in DCM (2 × 100 ml), stirred for 20 min, then filtered, and the filtrate was concentrated under reduced pressure to give 2-amino-3-hydroxy-2-methylpropanamide (Int-14) (0.6 g, 26%).

[0243] Synthesis of ethyl 3-amino-2-oxopyrrolidine-3-carboxylate hydrochloride (Int-15).

Chemical formula

[0244] Step 1: Boc anhydride (35.8 mL, 155.9 mmol) was added to a solution of diethyl 2-aminomalonate hydrochloride (30 g, 141.7 mmol) and TEA (60.18 mL, 425.25 mmol) in DCM (400 mL) at 0 °C. The RM was stirred at room temperature for 16 h. The RM was diluted with ice water (500 mL), the organic layer was separated, the organic layer was washed with brine (200 mL), dried over Na 2 SO 4 and concentrated under reduced pressure to give diethyl 2-((tert-butoxycarbonyl)amino)malonate (35.8 g) as a colorless solid.

[0245] Step 2: A solution of nitroethene (6.64 g, 90.90 mmol) dissolved in diethyl ether (15 mL) was added to a solution of diethyl 2-((tert-butoxycarbonyl)amino)malonate (10 g, 36.36 mmol) and sodium ethoxide (1.97 g, 29.08 mmol) in ethanol (300 mL) cooled to 0 °C. The reaction mixture (RM) was slowly allowed to reach room temperature. Then, the RM was stirred for 2 h. The RM was diluted with ice water (500 mL), the organic layer was separated, washed with brine (100 mL), dried over Na 2 SO 4 and filtered, and concentrated under reduced pressure to obtain a residue. The residue was purified by reverse-phase GRACE flash chromatography using 0.1% FA in water and ACN as the eluent. The fractions were collected and concentrated under vacuum to obtain diethyl 2-((tert-butoxycarbonyl)amino)-2-(2-nitroethyl)malonate (4.1 g).

[0246] Step 3: Raney-Ni (5.3 g) was added to a solution of diethyl 2-((tert-butoxycarbonyl)amino)-2-(2-nitroethyl)malonate (4.0 g, 11.49 mmol) in ethanol (50 mL) in a Parr hydrogenation vessel under an inert atmosphere. The RM was hydrogenated at room temperature under 70 psi for 16 h. The RM was filtered through a Celite pad, and the Celite pad was washed with ethanol. The combined filtrates were concentrated under reduced pressure to obtain ethyl 3-((tert-butoxycarbonyl)amino)-2-oxopyrrolidine-3-carboxylate (1.6 g) as a colorless oil.

[0247] Step 4: HCl (4 M in dioxane, 3.6 mL) was added to a stirred solution of ethyl 3-((tert-butoxycarbonyl)amino)-2-oxopyrrolidine-3-carboxylate (1.6 g, 5.9 mmol) in DCM (30 mL) at 0 °C. The RM was stirred at room temperature for 2 h. The RM was concentrated under vacuum. The residue was triturated with diethyl ether (10 mL), filtered, and dried under vacuum to obtain ethyl 3-amino-2-oxopyrrolidine-3-carboxylate hydrochloride (1.03 g) as an off-white solid.

[0248] Synthesis of 3 - amino - 3-(hydroxymethyl)pyrrolidin - 2 - one (Int - 16 - En1) and (Int - 16 - En2).

Chemical formula

[0249] Step 1: To a stirred solution of diethyl 2-(2-(1,3 - dioxoisoindolin - 2 - yl)ethyl)malonate (60 g, 179.99 mmol) in 1,4 - dioxane (600 mL) was added TEA (49.90 mL, 359.99 mmol) at 0 °C. After 15 minutes, formaldehyde (29.18 g, 359.99 mmol) was added at 0 °C. The reaction mixture was warmed to room temperature and stirred at 80 °C for 16 hours. After completion, the reaction mixture was diluted with ice - cold water (200 mL) and extracted with EtOAc (2×300 mL). The combined organic layers were washed with brine (150 mL), dried over Na 2 SO 4 and filtered, and concentrated under reduced pressure. The residue was purified by FCC on silica gel using a gradient of 0 - 40% EtOAc in pet ether to give diethyl 2-(2-(1,3 - dioxoisoindolin - 2 - yl)ethyl)-2-(hydroxymethyl)malonate (59 g, 90%) as a pale yellow gum. 1 1H NMR (400 MHz, CDCl 3 ) δ ppm: 7.86 - 7.82 (m, 2 H), 7.74 - 7.69 (m, 2 H), 4.25 - 4.18 (m, 4 H), 4.07 (d, 2 H), 3.83 - 3.79 (m, 2 H), 2.79 (t, 1 H), 2.33 - 2.30 (m, 2 H), 1.28 (t, 6 H).

[0250] Step 2: To a stirred solution of diethyl 2-(2-(1,3-dioxoisoindolin-2-yl)ethyl)-2-(hydroxymethyl)...

Claims

1. A compound of formula (I), its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs, wherein 【Chemical 1】 wherein R １ is - F, - Cl, - Br, - I, - CN, - R Ｗ , - OR Ｗ , - OC(=O)R Ｗ , - NR Ｗ R Ｘ , - NR Ｗ C(=O)R Ｘ , - SR Ｗ , - S(=O)R Ｗ , - S(=O) ２ R Ｗ , - C(=O)R Ｗ , - C(=O)OR Ｗ , or - C(=O)NR Ｗ R Ｘ represents, Q is -OR ２ or -NR ３ R ４ and represents R ２ represents -R Ｙ and R ３ represents -OH or -R Ｙ , and R ４ is -R Ｙ or -S(=O) ２ R Ｙ represents, or Alternatively, R ３ and R ４ together form a saturated or unsaturated, unsubstituted, or mono- or polysubstituted 4-, 5-, 6-, 7-, or 8-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N, O, and S. T represents -O-, and U represents -CR ５ R ５ ’-, or T represents -CR ５ R ５ ’-, and U represents -O- R ５ and R ５ ’ are, independently of each other, -R Ｙ to represent, R ６ 、 R ７ 、 and R ８ are, independently of one another, -F, -Cl, -Br, -I, -CN, -NO ２ 、 -SF ５ 、 -R Ｗ 、 -OR Ｗ 、 -OC(=O)R Ｗ 、 -NR Ｗ R Ｘ 、 -NR Ｗ C(=O)R Ｘ 、 -SR Ｗ 、 -S(=O)R Ｗ 、 -S(=O) ２ R Ｗ 、 -C(=O)R Ｗ 、 -C(=O)OR Ｗ 、 or -C(=O)NR Ｗ R Ｘ represent, V is a saturated or unsaturated 3- to 14-membered heterocycloalkyl, a saturated or unsaturated 3- to 14-membered cycloalkyl, a 5- to 14-membered aryl, C １ -C ６ alkyl or a 5- to 14-membered heteroaryl, and in each case, unsubstituted or, independently of one another, -F, -Cl, -Br, -I, -CF ３ , -CF ２ H, C １ -C ６ alkyl, -CN, -NO, -NO ２ , =O, =S, -SF ５ , -R Ｙ , -OR Ｙ , -OC(=O)R Ｙ , -NR Ｙ R Ｚ , -NR Ｙ C(=O)R Ｚ , -SR Ｙ , -S(=O)R Ｙ , -S(=O) ２ R Ｙ , -C(=O)R Ｙ , -C(=O)OR Ｙ , or -C(=O)NR Ｙ R Ｚ and is monosubstituted or polysubstituted with substituents selected from R Ｗ and R Ｘ are, independently of each other and in each case independently, -H; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C １ -C ６ -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C １ -C ６ -heteroalkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally connected via -C １ -C ６ -alkylene- or -C １ -C ６ -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted), a 3- to 14-membered cycloalkyl; or A saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally, -C １ -C ６ -alkylene- or -C １ -C ６ -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted) is represented by a 3- to 14-membered heterocycloalkyl connected via R Ｙ and R Ｚ are, independently of each other and in each case independently, -H; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C １ -C ６ -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C １ -C ６ -heteroalkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally connected via -C １ -C ６ -alkylene- or -C １ -C ６ -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted) to a 3- to 14-membered cycloalkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is optionally connected via -C １ -C ６ -alkylene- or -C １ -C ６ -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted) to a 3- to 14-membered heterocycloalkyl; Unsubstituted, monosubstituted or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is optionally -C １ -C ６ -alkylene- or -C １ -C ６ -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted) connected via a 6- to 14-membered aryl, or A non-replaced, mono-replaced or multi-replaced 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is optionally -C １ -C ６ -alkylene- or -C １ -C ６ -heteroalkylene- (in each case saturated or unsaturated, non-replaced, mono-replaced or multi-replaced) and represents a 5- to 14-membered heteroaryl connected via Alternatively, R Ｙ and R Ｚ together form a saturated or unsaturated, unsubstituted, or mono- or polysubstituted 4-, 5-, 6-, 7- or 8-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S, Here, "monosubstituted or polysubstituted" in each case independently represents -F, -Cl, -Br, -I, -CN, -C １－６ -alkyl, -CF ３ 、-CF ２ H, -CFH ２ 、-CF ２ Cl, -CFCl ２ 、-C １－６ -alkylene-CF ３ 、-C １－６ -alkylene-CF ２ H, -C １－６ -alkylene-CFH ２ 、-C １－６ -alkylene-O-CF ３ 、-C １－６ -alkylene-O-CF ２ H, -C １－６ -alkylene-O-CFH ２ 、-C １－６ -alkylene-NH-C １－６ -alkylene-CF ３ 、-C １－６ -alkylene-N(C １－６ -alkyl)-C １－６ -alkylene-CF ３ 、-C(=O)-C １－６ -alkyl, -C １－６ -alkylene-C(=O)-C １－６ -alkyl, -C(=O)OH, -C １－６ -alkylene-C(=O)-OH, -C(=O)-OC １－６ -alkyl, -C １－６ -alkylene-C(=O)-OC １－６ -alkyl, -C(=O)O-C １－６ -alkylene-CF ３ 、-C(=O)-NH ２ 、-C １－６ -alkylene-C(=O)-NH ２ 、-C(=O)-NH(C １－６ -alkyl), -C １－６ -alkylene-C(=O)-NH(C １－６ -alkyl), -C(=O)-N(C １－６ -alkyl) ２ 、-C １－６ -alkylene-C(=O)-N(C １－６ -alkyl) ２ , -C(=O)-NH(OH), -C １－６ -alkylene-C(=O)-NH(OH), -OH, -C １－６ -alkylene-OH, =O, -OCF ３ , -OCF ２ H, -OCFH ２ , -OCF ２ Cl, -OCFCl ２ , -O-C １－６ -alkyl, -C １－６ -alkylene-O-C １－６ -alkyl, -O-C １－６ -alkylene-O-C １－６ -alkyl, -O-C １－６ -alkylene-NH ２ , -O-C １－６ -alkylene-NH-C １－６ -alkyl, -O-C １－６ -alkylene-N(C １－６ -alkyl) ２ , -O-C(=O)-C １－６ -alkyl, -C １－６ -alkylene-O-C(=O)-C １－６ , -O-C(=O)-O-C １－６ -alkyl, -C １－６ -alkylene-O-C(=O)-O-C １－６ , -O-C(=O)-NH(C １－６ -alkyl), -C １－６ -alkylene-O-C(=O)-NH(C １－６ -alkyl), -O-C(=O)-N(C １－６ -alkyl) ２ , -C １－６ -alkylene-O-C(=O)-N(C １－６ -alkyl) ２ , -O-S(=O) ２ -NH ２ , -C １－６ -alkylene-O-S(=O) ２ -NH ２ , -O-S(=O) ２ -NH(C １－６ -alkyl), -C １－６ -alkylene-O-S(=O) ２ -NH(C １－６ -alkyl), -O-S(=O) ２ -N(C １－６ -alkyl) ２ , -C １－６ -alkylene-O-S(=O) ２ -N(C １－６ -alkyl) ２ , -NH ２ , -NO, -NO ２ , -C １－６ -alkylene-NH ２ , -NH(C １－６ -alkyl), -N(3- to 14-membered cycloalkyl)(C １－６ -alkyl), -N(C １－６ -alkyl)-C １－６ -alkylene-OH, -N(H)-C １－６ -alkylene-OH, -C １－６ -alkylene-NH(C １－６ -alkyl), -N(C １－６ -alkyl) ２ , -C １－６ -alkylene-N(C １－６ -alkyl) ２ , -NH-C(=O)-C １－６ -alkyl, -C １－６ -alkylene-NH-C(=O)-C １－６ -alkyl, -NH-C(=O)-O-C １－６ -alkyl, -C １－６ -alkylene-NH-C(=O)-O-C １－６ -alkyl, -NH-C(=O)-NH ２ , -C １－６ -alkylene-NH-C(=O)-NH ２ , -NH-C(=O)-NH(C １－６ -alkyl), -C １－６ -alkylene-NH-C(=O)-NH(C １－６ -alkyl), -NH-C(=O)-N(C １－６ -alkyl) ２ , -C １－６ -alkylene-NH-C(=O)-N(C １－６ -alkyl) ２ , -N(C １－６ -alkyl)-C(=O)-C １－６ -alkyl, -C １－６ -alkylene-N(C １－６ -alkyl)-C(=O)-C １－６ -alkyl, -N(C １－６ -alkyl)-C(=O)-O-C １－６ -alkyl, -C １－６ -alkylene-N(C １－６ -alkyl)-C(=O)-O-C １－６ -alkyl, -N(C １－６ -alkyl)-C(=O)-NH ２ , -C １－６ -alkylene-N(C １－６ -alkyl)-C(=O)-NH ２ , -N(C １－６ -alkyl)-C(=O)-NH(C １－６ -alkyl), -C １－６ -alkylene-N(C １－６ -alkyl)-C(=O)-NH(C １－６ -alkyl), -N(C １－６ -alkyl)-C(=O)-N(C １－６ -alkyl) ２ , -C １－６ -alkylene-N(C １－６ -alkyl)-C(=O)-N(C １－６ -alkyl) ２ , -NH-S(=O) ２ OH, -C １－６ -alkylene-NH-S(=O) ２ OH, -NH-S(=O) ２ , -C １－６ -alkyl, -C １－６ -alkylene-NH-S(=O) ２ , -C １－６ , -alkyl), -NH-S(=O) ２ , -O-C １－６ , -alkyl), -C １－６ -alkylene-NH-S(=O) ２ , -O-C １－６ , -alkyl), -NH-S(=O) ２ , -NH ２ , -C １－６ -alkylene-NH-S(=O) ２ -NH ２ 、-NH-S(=O) ２ -NH(C １－６ -alkyl), -C １－６ -alkylene-NH-S(=O) ２ -NH(C １－６ -alkyl), -NH-S(=O) ２ N(C １－６ -alkyl) ２ 、-C １－６ -alkylene-NH-S(=O) ２ N(C １－６ -alkyl) ２ 、-N(C １－６ -alkyl)-S(=O) ２ -OH、-C １－６ -alkylene-N(C １－６ -alkyl)-S(=O) ２ -OH、-N(C １－６ -alkyl)-S(=O) ２ -C １－６ -alkyl、-C １－６ -alkylene-N(C １－６ -alkyl)-S(=O) ２ -C １－６ -alkyl、-N(C １－６ -alkyl)-S(=O) ２ -O-C １－６ -alkyl、-C １－６ -alkylene-N(C １－６ -alkyl)-S(=O) ２ -O-C １－６ -alkyl、-N(C １－６ -alkyl)-S(=O) ２ -NH ２ 、-C １－６ -alkylene-N(C １－６ -alkyl)-S(=O) ２ -NH ２ 、-N(C １－６ -alkyl)-S(=O) ２ -NH(C １－６ -alkyl), -C １－６ -alkylene-N(C １－６ -alkyl)-S(=O) ２ -NH(C １－６ -alkyl), -N(C １－６ -(alkyl)-S(=O) ２ -N(C １－６ -alkyl) ２ 、-C １－６ -alkylene-N(C １－６ -alkyl)-S(=O) ２ -N(C １－６ -alkyl) ２ 、-SH、=S、-SF ５ 、-SCF ３ 、-SCF ２ H、-SCFH ２ 、-S-C １－６ -alkyl、-C １－６ -alkylene-S-C １－６ -alkyl、-S(=O)-C １－６ -alkyl、-C １－６ -alkylene-S(=O)-C １－６ -alkyl、-S(=O) ２ -C １－６ -alkyl、-C １－６ -alkylene-S(=O) ２ -C １－６ -alkyl、-S(=O) ２ -OH、-C １－６ -alkylene-S(=O) ２ -OH、-S(=O) ２ -O-C １－６ -alkyl、-C １－６ -alkylene-S(=O) ２ -O-C １－６ -alkyl、-S(=O) ２ -NH ２ 、-C １－６ -alkylene-S(=O) ２ -NH ２ 、-S(=O) ２ -NH(C １－６ -alkyl)、-C １－６ -alkylene-S(=O) ２ -NH(C １－６ -alkyl)、-S(=O) ２ -N(C １－６ -alkyl) ２ 、-C １－６ -alkylene-S(=O) ２ -N(C １－６ -alkyl) ２ , 3- to 14-membered cycloalkyl, -C １－６ -alkylene-(3- to 14-membered cycloalkyl), 3- to 14-membered heterocycloalkyl, -C １－６ -alkylene-(3- to 14-membered heterocycloalkyl), -phenyl, -C １－６ -alkylene-phenyl, 5- to 14-membered heteroaryl, -C １－６ -alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -O-(5- to 14-membered heteroaryl), -C(=O)-(3- to 14-membered cycloalkyl), -C(=O)-(3- to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5- to 14-membered heteroaryl), -S(=O) ２ -(3- to 14-membered cycloalkyl), -S(=O) ２ -(3- to 14-membered heterocycloalkyl), -S(=O) ２ -phenyl, -S(=O) ２ means being substituted with one or more substituents independently selected from -(3- to 14-membered cycloalkyl), -C-alkylene-(3- to 14-membered cycloalkyl), 3- to 14-membered heterocycloalkyl, -C-alkylene-(3- to 14-membered heterocycloalkyl), -phenyl, -C-alkylene-phenyl, 5- to 14-membered heteroaryl, -C-alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -O-(5- to 14-membered heteroaryl), -C(=O)-(3- to 14-membered cycloalkyl), -C(=O)-(3- to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5- to 14-membered heteroaryl), -S(=O)-(3- to 14-membered cycloalkyl), -S(=O)-(3- to 14-membered heterocycloalkyl), -S(=O)-phenyl, -S(=O)-(5- to 14-membered heteroaryl); a compound, its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs.

2. R ３ The compound according to claim 1, wherein R represents -H.

3. 。R ４ The compound according to claim 2, wherein R represents a residue other than -H.

4. R １ The compound according to any one of claims 1 to 3, wherein R represents -methyl or ethyl.

5. T represents -O-, and U represents -CR ５ R ５ '- A compound according to any one of claims 1 to 3.

6. R ５ and R ５’ each of the Rs representing Ｙ a compound according to any one of claims 1 to 5, wherein each of said Rs is H.

7. V is a 5- to 14-membered heteroaryl selected from (i) benzimidazole, benzisoxazole, benzazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furan, furazan, imidazole, imidazopyridine, indazole, indole, indolizine, isobenzofuran, isoindole, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, oxindole, phthalazine, purine, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, and in each case, unsubstituted, independently of one another, -F, -Cl, -CN, -OH, =O, -C １－６ -alkyl, -CHF ２ 、-CF ３ 、-C １－６ -alkylene-NH ２ 、-C １－６ -alkylene-NHC(=O)O-C １－６ -alkyl, -C １－６ -alkylene-OH, -C １－６ -alkylene-CHF ２ 、-C １－６ -alkylene-CF ３ 、-C １－６ -alkylene-cyclopropyl, -cyclopropyl, -O-cyclopropyl, -C １－６ -alkylene-NHC(=O)-O-C １－６ -alkyl, -C(=O)O-C １－６ -alkyl, -N(C １－６ -alkyl) ２ 、-OC １－６ -alkyl, -OCF ３ 、-O-C １－６ -alkylene-N(C １－６ -alkyl) ２ 、-S(=O) ２ -C １－６ -alkyl, -azetidine, -C １－６ -alkylene-O-tetrahydropyran, or -C １－６ -substituted with a substituent selected from -alkyl-substituted -piperazine, and in particular, in any case, unsubstituted, independently of one another, -F, -Cl, -CN, -OH, =O, -C １－６ -alkyl, -CHF ２ , -CF ３ , -C １－６ -alkylene-NH ２ , -C １－６ -alkylene-NHC(=O)O-C １－６ -alkyl, -C １－６ -alkylene-OH, -C １－６ -alkylene-NHC(=O)-O-C １－６ -alkyl, -C(=O)O-C １－６ -alkyl, -N(C １－６ -alkyl) ２ , -OC １－６ -alkyl, -OCF ３ , -O-C １－６ -alkylene-N(C １－６ -alkyl) ２ , -S(=O) ２ -C １－６ -alkyl, -azetidine, -C １－６ -alkylene-O-tetrahydropyran or -C １－６ -substituted with a substituent selected from -alkyl-substituted -piperazine, or (ii) represents unsubstituted, monosubstituted or polysubstituted -oxetanyl, a compound according to any one of claims 1 to 6.

8. The saturated or unsaturated 3- to 14-membered cycloalkyl within the definition of V is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, or cyclodecyl, which includes non-condensed or non-bridged, condensed, or bridged cycloalkyl, and in each case, is unsubstituted or, independently of one another, mono- or polysubstituted with substituents selected from ３ , -CF ２ H, C １ , -C ６ alkyl, -CN, -NO, -NO ２ , =O, =S, -SF ５ , -R Ｙ , -OR Ｙ , -OC(=O)R Ｙ , -NR Ｙ R Ｚ , -NR Ｙ C(=O)R Ｚ , -SR Ｙ , -S(=O)R Ｙ , -S(=O) ２ R Ｙ , -C(=O)R Ｙ , -C(=O)OR Ｙ , or -C(=O)NR Ｙ R Ｚ The compound according to any one of claims 1 to 6, which is mono- or polysubstituted with substituents selected from

9. The 5- to 14-membered aryl within the definition of V is unsubstituted or, independently of one another, is -F, -Cl, -Br, -I, CF ３ , -CF ２ H, C １ -C ６ alkyl, -CN, -NO, -NO ２ , =O, =S, -SF ５ , -R Ｙ , -OR Ｙ , -OC(=O)R Ｙ , -NR Ｙ R Ｚ , -NR Ｙ C(=O)R Ｚ , -SR Ｙ , -S(=O)R Ｙ , -S(=O) ２ R Ｙ , -C(=O)R Ｙ , -C(=O)OR Ｙ , or -C(=O)NR Ｙ R Ｚ and is phenyl or another 5- to 14-membered aryl which is monosubstituted or polysubstituted by substituents selected from, a compound according to any one of claims 1 to 6.

10. The 3- to 14-membered heterocycloalkyl within the definition of V is selected from azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxazolidine, morpholine, oxazolidine, oxane, oxepane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiacyclohexane, 2-azaspiro[3.3]heptane, 2-oxaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, hexahydro-1H-pyrrolidine, hexahydro-cyclopenta[c]pyrrole, octahydro-cyclopenta[c]pyrrole, and octahydro-pyrrolo[1,2-a]pyrazine, and in each case, unsubstituted or, independently of one another, mono- or polysubstituted with substituents selected from -F, -Cl, -Br, -I, CF ３ 、 -CF ２ H, C １ -C ６ alkyl, -CN, -NO, -NO ２ 、 =O, =S, -SF ５ 、 -R Ｙ 、 -OR Ｙ 、 -OC(=O)R Ｙ 、 -NR Ｙ R Ｚ 、 -NR Ｙ C(=O)R Ｚ 、 -SR Ｙ 、 -S(=O)R Ｙ 、 -S(=O) ２ R Ｙ 、 -C(=O)R Ｙ 、 -C(=O)OR Ｙ 、 or -C(=O)NR Ｙ R Ｚ and is mono- or polysubstituted with substituents selected from, a compound according to any one of claims 1 to 6.

11. V is saturated or unsaturated, unsubstituted, and independently of one another, -F, -Cl, -Br, -I, CF ３ , -CF ２ H, C １ , -C ６ alkyl, -CN, -NO, -NO ２ , =O, =S, -SF ５ , -R Ｙ , -OR Ｙ , -OC(=O)R Ｙ , -NR Ｙ R Ｚ , -NR Ｙ C(=O)R Ｚ , -SR Ｙ , -S(=O)R Ｙ , -S(=O) ２ R Ｙ , -C(=O)R Ｙ , -C(=O)OR Ｙ , or -C(=O)NR Ｙ R Ｚ and is monosubstituted or polysubstituted with substituents selected from C １ , -C ６ alkyl or C １ , -C ６ heteroalkyl, a compound according to any one of claims 1 to 6.

12. The compound according to any one of claims 1 to 6, wherein V is a residue selected from the group consisting of [Chemical 2]

13. R １ is -H, -F, -Cl, -Br, -I, -C １－６ -alkyl, -O-C １－６ -alkyl, -C １－６ -alkylene-O-C １－６ -alkyl, -C １－６ -alkylene-NH(C １－６ -alkyl), -C １－６ -alkylene-N(C １－６ -alkyl) ２ , -CF ３ , -CF ２ H, -CFH ２ , -CF ２ Cl, -CFCl ２ , -C １－６ -alkylene-CF ３ , -C １－６ -alkylene-CF ２ H, -C １－６ -alkylene-CFH ２ , -C １－６ -alkylene-NH-C １－６ -alkylene-CF ３ , -C １－６ -alkylene-N(C １－６ -alkyl)-C １－６ -alkylene-CF ３ , -C(=O)C １－６ -alkyl, -C(=O)OC １－６ -alkyl, -C(=O)NH ２ , -C(=O)NHC １－６ -alkyl, -C(=O)N(C １－６ -alkyl) ２ , -S(=O)-C １－６ -alkyl, -S(=O) ２ -C １－６ -alkyl, -O-C １－６ -alkyl, unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl or unsubstituted cyclohexyl, the compound according to claim 1.

14. R ３ is -H, -OH, -C １－６ -alkyl, -C １－６ -alkylene-OH, -C １－６ -alkylene-O-C １－６ -alkyl, -C １－６ -alkylene-NH ２ , -C １－６ -alkylene-NH(C １－６ -alkyl), -C １－６ -alkylene-N(C １－６ -alkyl) ２ , -CF ３ , -CF ２ H, -CFH ２ , -CF ２ Cl, -CCl ２ , -C １－６ -alkylene-CF ３ , -C １－６ -alkylene-CF ２ H, -C １－６ -alkylene-CFH ２ , -C １－６ -alkylene-NH-C １－６ -alkylene-CF ３ , or -C １－６ -alkylene-N(C １－６ -alkyl)-C １－６ -alkylene-CF ３ The compound according to claim 1, wherein it represents

15. R ４ is -H; Saturated, unsubstituted, monosubstituted or polysubstituted with -F, -S(=O) ２ C １－６ -alkyl; Saturated, unsubstituted -S(=O)- ２ (3- to 14-membered cycloalkyl); Saturated, unsubstituted, mono-substituted or poly-substituted -C １－６ -alkyl; Each of unsubstituted, mono-substituted, or multi-substituted 3- to 14-membered cycloalkyl or -C １－６ -alkylene-(3- to 14-membered cycloalkyl); Unsubstituted, monosubstituted, or polysubstituted 3- to 14-membered heterocycloalkyl or -C １－６ -alkylene-(3- to 14-membered heterocycloalkyl); Each of unsubstituted, mono-substituted, or poly-substituted, -phenyl, or -C １－６ -alkylene-phenyl; or Each unsubstituted, mono-substituted, or multi-substituted 5- to 14-membered heteroaryl or -C １－６ -alkylene-(5- to 14-membered heteroaryl), the compound according to any one of claims 1 to 14.

16. R ４ is a saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered cycloalkyl (preferably 3, 4, 5 or 6-membered cycloalkyl), wherein the 3- to 14-membered cycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C １ -C ６ -alkylene- connected 3- to 14-membered cycloalkyl; or a saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl (preferably 4, 5 or 6-membered heterocycloalkyl), wherein the 3- to 14-membered heterocycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C １ -C ６ -alkylene- connected 3- to 14-membered heterocycloalkyl; or an unsubstituted, mono- or poly-substituted 6- to 14-membered aryl (preferably 6-membered aryl), wherein the 6- to 14-membered aryl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C １ -C ６ -alkylene- connected 6- to 14-membered aryl; or an unsubstituted, mono- or poly-substituted 5- to 14-membered heteroaryl (preferably 5- or 6-membered heteroaryl), wherein the 5- to 14-membered heteroaryl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C １ -C ６ -alkylene- connected 5- to 14-membered heteroaryl, a compound according to any one of claims 1 to 14.

17. R ３ is H, and R ４ is a residue selected from the group consisting of the following, the compound according to any one of claims 1 to 16. 【Chemical Formula 3-1】 【Chemical Formula 3-2】

18. R ３ and R ４ together form a heterocyclic ring selected from the group consisting of pyrrolidine, piperidine, morpholine, and piperazine, and in each case, unsubstituted, independently of one another, -F, -C １－６ -alkyl, -NH ２ , -NHCH ３ , -N(CH ３ ) ２ , -C(=O)NH-C １－６ -alkyl, -C(=O)N(C １－６ -alkyl) ２ , -C(=O)O-C １－６ -alkyl, -NH-C(=O)O-C １－６ -alkyl, -unsubstituted pyridyl, and 1,2,4-oxadiazole unsubstituted or monosubstituted with -C １－６ -alkyl and monosubstituted or polysubstituted with a substituent selected from the group consisting of monosubstituted 1,2,4-oxadiazole, the compound according to claim 1.

19. R ５ and R ５ ’ are each independently -H; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C １ -C ６ -alkyl; Saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted -C １ -C ６ -heteroalkyl; A saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is optionally -C １ -C ６ -alkylene- or -C １ -C ６ -heteroalkylene- (in each case saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted) and is connected via the 3- to 14-membered cycloalkyl represented by the compound according to claim 1.

20. R ６ 、R ７ 、and R ８ are, independently of one another, -H, -F, -Cl, -Br, -I, -OH, -SH, -SF ５ , -CN, -NO ２ , -C(=O)OH, -NH ２ , -C １－６ -alkyl, -CF ３ -, -CHF ２ -, -CH ２ F, -O-C １－６ -alkyl, -OCF ３ -OCHF ２ -OCH ２ F Non-replaced or independently of each other, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF ３ , -CHF ２ , -CH ２ F, -OCF ３ , -OCHF ２ , -OCH ２ F, SF ５ , -NO ２ , -C(=O)OH, -NH ２ , and -C(=O)NH ２ substituted with one or more substituents selected from -NHC １－６ -alkyl; Non-replaced, or independently of each other, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF ３ , -CHF ２ , -CH ２ F, -OCF ３ , -OCHF ２ , -OCH ２ F, SF ５ , -NO ２ , -C(=O)OH, -NH ２ , and -C(=O)NH ２ substituted with one or more substituents selected from -N(C １－６ -alkyl) ２ ; Non-replaceable, or independently of each other, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF ３ , -CHF ２ , -CH ２ F, -OCF ３ , -OCHF ２ , -OCH ２ F, SF ５ , -NO ２ , -C(=O)OH, -NH ２ , and -C(=O)NH ２ substituted with one or more substituents selected from -C(=O)OC １－６ -alkyl; Non-replaced, or independently of one another, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF ３ , -CHF ２ , -CH ２ F, -OCF ３ , -OCHF ２ , -OCH ２ F, SF ５ , -NO ２ , -C(=O)OH, -NH ２ , and -C(=O)NH ２ substituted with one or more substituents selected from -OC(=O)C １－６ -alkyl; or Unsubstituted, or independently of each other, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF ３ , -CHF ２ , -CH ２ F, -OCF ３ , -OCHF ２ , -OCH ２ F, SF ５ , -NO ２ , -C(=O)OH, -NH ２ , and -C(=O)NH ２ substituted with one or more substituents selected from -C １－６ -heteroalkyl, a compound according to any one of claims 1 to 19.

21. The compound according to claim 1, selected from the group consisting of Compounds 001 to 036 shown in the following table 【Chemical Formula 4-1】 【Chemical Formula 4-2】

22. The compound according to claim 1, selected from the group consisting of Compounds 037 to 091 shown in the following table 【Chemical Formula 5-1】 【Chemical Formula 5-2】 [[Chemical Formula 5-3]] 【Chemical Formula 5-4】 ​

23. A pharmaceutical composition comprising the compound according to any one of claims 1 to 22

24. The compound according to any one of claims 1 to 22, or the pharmaceutical composition according to claim 23, for use in the treatment of pain

25. The compound or pharmaceutical composition for use in the treatment of pain according to claim 24, wherein the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain, preferably postoperative pain

26. A method of treating pain, comprising administering to a subject in need thereof the compound according to any one of claims 1 to 22, or the pharmaceutical composition according to any one of claims 23 to 25

27. The method according to claim 26, wherein the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain, preferably postoperative pain

28. The compound according to any one of claims 1 to 22, or the pharmaceutical composition according to claim 23, for use in the treatment of epilepsy

29. A method of treating epilepsy, comprising administering to a subject in need thereof the compound according to any one of claims 1 to 22, or the pharmaceutical composition according to claim 23

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