New derivatives for treating TRPM3-mediated disorders

Abstract

The present invention relates to compounds useful for the prevention or treatment of TRPM3-mediated disorders, more particularly disorders selected from pain, epilepsy and inflammatory hypersensitivity. The present invention also relates to a method for the prevention or treatment of said TRPM3-mediated disorders.

Description

[Technical field]

[0001] The present invention relates to compounds useful for the prevention or treatment of TRPM3-mediated disorders, more particularly disorders selected from pain, epilepsy and inflammatory hypersensitivity. The present invention also relates to a method for the prevention or treatment of said TRPM3-mediated disorders. [Background technology]

[0002] The TRP superfamily consists of proteins with six transmembrane domains (6TM) that assemble as homo- or heterotetramers to form cation-permeable ion channels. The name TRP comes from the Drosophila trp (transient receptor potential) mutants that are characterized by a transient receptor potential in fly photoreceptors in response to sustained 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 expressed in virtually all mammalian organs and cell types, and in recent years, great progress has been made in understanding their physiological roles. The customized selectivity of certain TRP channels is due to their ability to selectively bind Ca. 2+ , Mg 2+ , and trace metal ions. Moreover, the sensitivity of TRP channels to a wide range of chemical and physical stimuli allows them to function as dedicated biological sensors involved in processes from vision to taste to touch. Specifically, some members of the TRP superfamily show extremely high sensitivity to temperature. These so-called thermo-TRPs are highly expressed in sensory neurons and / or skin keratinocytes and function as the primary thermosensors for the detection of innocuous and noxious (painful) temperatures.

[0004] It is becoming increasingly clear that TRP channel dysfunction is directly involved in the pathogenesis of various genetic and acquired diseases. In fact, both loss-of-function and gain-of-function mutations in TRP channel genes have been identified as the direct cause of genetic diseases, including brachiolemia, hypomagnesemia with secondary hypocalcemia, polycystic kidney disease, mucolipidosis type IV, and familial focal segmental glomerulosclerosis. Furthermore, TRP channel function / dysfunction is directly related to a wide range of pathological conditions, including chronic pain, hypertension, cancer, epilepsy, 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 the dorsal root and trigeminal ganglion and is involved in heat sensing. The neurosteroid pregnenolone sulfate is a potent known activator of TRPM3 (Wagner et al., 2008). The neurosteroid pregnenolone sulfate caused pain in wild-type mice but not in knockout TRPM3 mice. It was also recently shown that CFA-induced inflammation and inflammatory pain were eliminated in TRPM3 knockout mice. Thus, TRPM3 antagonists could be used as analgesics to counter pain, such as inflammatory pain (Vriens J. et al. Neuron, May 2011). TRPM3 is also expressed in several other tissues, including the brain; reports have shown that two mutations in TRPM3 are associated with developmental and epileptic encephalopathies (Zhao, S., et al. Channels (Austin). 2021).

[0006] Although several TRPM3 antagonists are known, 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 hyperalgesia 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 treatments for the prevention or treatment of TRPM3-mediated disorders such as pain and epilepsy, more specifically for inflammatory pain such as epileptic encephalopathy or pain such as epilepsy. Good efficacy against certain types of pain, low or no side effects (such as no addiction potential and no toxicity as with opiates) and / or good or better pharmacokinetic or -dynamic properties are highly needed.

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

[0008] A first aspect of the present invention relates to compounds of formula (I) (also referred to as benzofuran derivatives according to the invention), their stereoisomers, physiologically acceptable salts, solvates and / or polymorphs thereof, [ka] During the ceremony, R 1 -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)RW , -C(=O)OR W or -C(=O)NR W R X represents Q is -NR 3 R 4 represents R 3 is -OH or -R Y1 represents R 4 But -R Y2 or -S(=O) 2 R Y3 represents Or, R 3 and R 4 together form a saturated or unsaturated, unsubstituted, mono- or polysubstituted 4-, 5-, 6-, 7-, or 8-membered heterocycle containing 1 to 3 heteroatoms selected from N, O, and S; T represents -O- and U represents -(CR 5 R 5 ') n - or T represents -(CR 5 R 5 ') n -, U represents -O-, n is an integer selected from 1, 2, 3, 4, or 5; R 5 and R 5 ', but independently of each other, -R Y4 represents R 6 , R 7 , and R 8 are, independently of each other, -F, -Cl, -Br, -I, -CN, -NO 2 ,-SCIENCE FICTION 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)ORW or -C(=O)NR W R X represents W, a saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl; or In each case, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, During the ceremony, R W and R X but independently of one another, and in each case independently, -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, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl; A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered heterocycloalkyl, R Y1 , RY2 , R Y3 , and R Y4 but independently of one another, and in each case independently, -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, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl; A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; An unsubstituted, mono- or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 6- to 14-membered aryl; An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6-heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 5- to 14-membered heteroaryl, "Mono- or polysubstituted" means, at each occurrence, 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-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)OC 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 , -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -OC 1-6 -Alkylene-OC 1-6 -Alkyl, -OC 1-6 -Alkylene-NH 2 , -OC 1-6 -Alkylene-NH-C 1-6 -Alkyl, -OC 1-6 -Alkylene-N(C 1-6 -alkyl) 2 , -OC(=O)-C 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-C 1-6 -Alkyl, -OC(=O)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-OC 1-6 -Alkyl, -OC(=O)-NH(C 1-6 -alkyl), -C 1-6 -Alkylene-OC(=O)-NH(C 1-6 -alkyl), -OC(=O)-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OC(=O)-N(C 1-6 -alkyl) 2 , -OS(=O) 2 -NH 2 , -C 1-6 -Alkylene-OS(=O) 2 -NH 2 , -OS(=O) 2 -NH(C 1-6 -alkyl), -C 1-6 -Alkylene-OS(=O) 2 -NH(C 1-6-alkyl), -OS(=O) 2 -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OS(=O) 2 -N(C 1-6 -alkyl) 2 , -NH 2 , -NO, -NO 2 , -C 1-6 -Alkylene-NH 2 , -NH(C 1-6 -alkyl), -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)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-C(=O)-OC 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)-OC 1-6-Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-C(=O)-OC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-S(=O) 2 -OC 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) 2N(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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-S(=O) 2 -OC 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 , -SC 1-6 -Alkyl, -C 1-6 -Alkylene-SC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-S(=O) 2 -OC 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- to 14-membered cycloalkyl), 3- to 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 to 14 membered cycloalkyl), -S(=O) 2 -(3-14 membered heterocycloalkyl), -S(=O) 2 -phenyl, or -S(=O) 2 -(5-14 membered heteroaryl), meaning substituted with one or more substituents selected independently from each other from -(5-14 membered heteroaryl), their stereoisomers, physiologically acceptable salts, solvates and / or polymorphs thereof. In particular, the present invention relates to compounds of formula (I), their stereoisomers, physiologically acceptable salts, solvates and / or polymorphs thereof, [ka] During the ceremony, R 1 -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 -NR 3 R 4 represents R 3 is -OH or -R Y1 represents R4 But -R Y2 or -S(=O) 2 R Y3 represents Or, R 3 and R 4 together form a saturated or unsaturated, unsubstituted, mono- or polysubstituted 4-, 5-, 6-, 7-, or 8-membered heterocycle containing 1 to 3 heteroatoms selected from N, O, and S; T represents -O- and U represents -(CR 5 R 5 ') n - or T represents -(CR 5 R 5 ') n -, U represents -O-, n is an integer selected from 1, 2, 3, 4, or 5; R 5 and R 5 ', but independently of each other, -R Y4 represents R 6 , R 7 , and R 8 are, independently of each other, -F, -Cl, -Br, -I, -CN, -NO 2 ,-SCIENCE FICTION 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 W, a saturated or non-aromatically unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl; or In each case, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6-Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, During the ceremony, R W and R X but independently of one another, and in each case independently, -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, A saturated or non-aromatically unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl; A saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; R Y1 , R Y2 , R Y3 , and R Y4 but independently of one another, and in each case independently, -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, A saturated or non-aromatically unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl; A saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; An unsubstituted, mono- or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 6- to 14-membered aryl; An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 5- to 14-membered heteroaryl, "Mono- or polysubstituted" means, at each occurrence, independently, -F, -Cl, -Br, -I, -CN, -C 1-6 -Alkyl, -CF3 , -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 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)OC 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 2Cl, -OCFCl 2 , -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -OC 1-6 -Alkylene-OC 1-6 -Alkyl, -OC 1-6 -Alkylene-NH 2 , -OC 1-6 -Alkylene-NH-C 1-6 -Alkyl, -OC 1-6 -Alkylene-N(C 1-6 -alkyl) 2 , -OC(=O)-C 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-C 1-6 -Alkyl, -OC(=O)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-OC 1-6 -Alkyl, -OC(=O)-NH(C 1-6 -alkyl), -C 1-6 -Alkylene-OC(=O)-NH(C 1-6 -alkyl), -OC(=O)-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OC(=O)-N(C 1-6 -alkyl) 2 , -OS(=O) 2 -NH 2 , -C 1-6 -Alkylene-OS(=O) 2 -NH 2 , -OS(=O) 2 -NH(C 1-6 -alkyl), -C 1-6 -Alkylene-OS(=O) 2 -NH(C 1-6 -alkyl), -OS(=O) 2 -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OS(=O) 2 -N(C 1-6 -alkyl) 2 , -NH2 , -NO, -NO 2 , -C 1-6 -Alkylene-NH 2 , -NH(C 1-6 -alkyl), -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)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-C(=O)-OC 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)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-C(=O)-OC 1-6 -Alkyl, -N(C 1-6 -alkyl)-C(=O)-NH 2 , -C 1-6 -Alkylene-N(C1-6 -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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-S(=O) 2 -OC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-S(=O) 2 -OC 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 , -SC 1-6 -Alkyl, -C 1-6 -Alkylene-SC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-S(=O) 2 -OC 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- to 14-membered cycloalkyl), 3- to 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 to 14 membered cycloalkyl), -S(=O) 2 -(3-14 membered heterocycloalkyl), -S(=O) 2 -phenyl, or -S(=O) 2 -(5- to 14-membered heteroaryl), meaning substituted with one or more substituents independently selected from each other from:

[0009] A second aspect of the invention encompasses a pharmaceutical composition comprising a compound of formula (I) according to the first aspect.

[0010] According to a third aspect, the present invention also provides a compound of formula (I) according to the first aspect or a pharmaceutical composition according to the second aspect for use as a medicament.

[0011] According to a fourth aspect, the present invention also encompasses a compound of formula (I) as defined in the first aspect or a pharmaceutical composition as defined in the second aspect for use in the prevention and / or treatment of a TRPM3 mediated disorder, in particular for use in the prevention and / or treatment of and / or against pain, epilepsy and / or inflammatory hypersensitivity, in particular for use in the prevention and / or treatment of and / or against pain, epilepsy and / or inflammatory hypersensitivity, in particular for use in the prevention and / or treatment of and / or against pain, epilepsy and / or inflammatory hypersensitivity.

[0012] The present invention also provides a method for preventing or treating a TRPM3-mediated disorder by administering a compound of formula (I) according to the first aspect to a subject in need thereof. More specifically, the present invention relates to such a method for preventing and / or treating pain, epilepsy and / or inflammatory hypersensitivity and / or combating pain, epilepsy and / or inflammatory hypersensitivity. More specifically, the present invention relates to such a method for preventing and / or treating pain, epileptic encephalopathy and / or inflammatory hypersensitivity and / or combating pain, epileptic encephalopathy and / or inflammatory hypersensitivity.

[0013] The present invention further provides a process for preparing a compound of formula (I) according to the first aspect, comprising the steps of: -benzoquinone with a suitable β-ketoester or enamine derivative to give a 5-hydroxybenzofuran-3-carboxylate ester derivative; - substitution of the previously obtained 5-hydroxybenzofuran-3-carboxylate ester derivative with a suitable derivative bearing a leaving group or an alcohol derivative under Mitsunobu conditions to obtain a 5-O-substituted benzofuran-3-carboxylate ester derivative; - converting the previously obtained 5-O-substituted benzofuran-3-carboxylate ester derivative into a carboxylic acid to obtain a 5-O-substituted benzofuran-3-carboxylic acid derivative; and - coupling the previously obtained 5-O-substituted benzofuran-3-carboxylic acid derivative with a suitable amine to give the desired derivative of the invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Before the invention is described, it is to be understood that this invention is not limited to the particular processes, methods, and compounds described, as such processes, methods, and compounds may, of course, vary. It is also to be understood that the terms used herein are not intended to be limiting, since the scope of the invention will be limited only by the appended claims.

[0015] When describing the compounds and processes of this invention, the terms used should be construed in accordance with the following definitions, unless the context dictates otherwise.

[0016] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include both singular and plural referents unless the context clearly dictates otherwise. For example, "a compound" means one compound or more than one compound.

[0017] As used herein, the terms "comprising," "comprises," and "comprised of" are synonymous with "including," "includes," or "containing," "contains," and are inclusive or open-ended and do not exclude additional, unrecited components, elements, or method steps. The terms "comprising," "comprises," and "comprised of" include the term "consisting of."

[0018] As used herein, the term "about," when referring to a measurable value such as a parameter, amount, length of time, and the like, is meant to encompass variations of the specified value and therefrom of no more than + / - 10%, preferably no more than + / - 5%, more preferably no more than + / - 1%, and even more preferably no more than + / - 0.1%, provided that such variations are appropriate in the disclosed invention. It is to be understood that the value to which the modifier "about" refers is itself specifically and preferably disclosed.

[0019] As used herein, the term "and / or," when used in a list of two or more items, means that any one of the listed items may be taken alone, or any combination of two or more of the listed items may be taken. For example, if a list is described as including groups A, B, and / or C, the list may include A only, B only, C only, a combination of A and B, a combination of A and C, a combination of B and C, or a combination of A, B, and C.

[0020] The recitation of numerical ranges by endpoints includes all integers and, where appropriate, fractions subsumed within that range (e.g., 1 to 5 can include 1, 2, 3, 4, for example, when referring to several elements, and can also include 1.5, 2, 2.75, and 3.80, for example, when referring to measurements). The recitation of endpoints also includes the endpoint values ​​themselves (e.g., 1.0 to 5.0 includes both 1.0 and 5.0). Any numerical ranges described herein are intended to include all sub-ranges subsumed therein.

[0021] References throughout this specification to "one embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment of the invention. Thus, the phrases "in one embodiment" or "in an embodiment" appearing in various places in this specification do not necessarily all refer to the same embodiment, although they may. Furthermore, particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments, as would be apparent to one of ordinary skill in the art from this disclosure. Moreover, some embodiments described herein include some features but not other features included in other embodiments, and combinations of features of different embodiments are meant to be within the scope of the invention and form different embodiments, as would be understood by one of ordinary skill in the art. For example, in the following claims, any of the claimed embodiments may be used in any combination.

[0022] Similarly, in describing exemplary embodiments of the invention, it will be understood that various features of the invention may be grouped together in a single embodiment, figure, or description thereof in order to streamline the disclosure and to aid in understanding one or more of the various inventive aspects.

[0023] Unless otherwise defined, all terms used in disclosing the present invention, including technical and scientific terms, have the meanings commonly understood by those of ordinary skill in the art to which the present invention belongs. As a further guide, definitions of terms used in the description are included to better understand the teachings of the present invention.

[0024] When describing the present invention, the terms used should be construed in accordance with the following definitions, unless the context dictates otherwise.

[0025] The above terms and other terms used herein are well understood by those of ordinary skill in the art.

[0026] Whenever the term "substituted" is used herein, it is meant to indicate that one or more hydrogen atoms on the atom designated with the phrase "substituted" are replaced with a selection from a designated group, provided that the normal valence of the designated atom is not exceeded, and that the replacement results in a chemically stable compound, i.e., a compound that is robust enough to survive isolation from a reaction mixture.

[0027] In each of the following definitions, the number of carbon atoms represents the maximum number of carbon atoms that are generally optimally present in a substituent or linker. If otherwise indicated in this application, it is understood that the number of carbon atoms represents the optimal maximum number of carbon atoms for that particular substituent or linker.

[0028] The term "leaving group" or "LG" as used herein means a chemical group that is susceptible to displacement by a nucleophile or to cleavage or hydrolysis 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).

[0029] The term "protecting group" refers to a moiety of a compound that masks or alters the properties of a functional group or the overall compound. The chemical substructure of protecting groups varies widely. One function of a protecting group is to serve as an intermediate in the synthesis of a parent drug 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 utilized to mask the reactivity of certain functional groups to aid in the efficiency of a desired chemical reaction, e.g., forming and breaking chemical bonds in an orderly and planned manner. Protection of a functional group of a compound alters other physical properties besides 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 may themselves be biologically active or inactive.

[0030] Protected compounds may also exhibit altered properties, and in some cases, optimized properties in vitro and in vivo (passing cell membranes and resistance to enzymatic degradation or capture). In this role, protected compounds with the intended therapeutic effect may be referred to as prodrugs. 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. Protecting groups are removed either in vitro in the case of chemical intermediates, or in vivo in the case of prodrugs. For chemical intermediates, it is not particularly important that the resulting product (e.g., alcohol) after deprotection is physiologically acceptable, but it is generally more desirable if the product is pharmacologically harmless.

[0031] The term "heteroatom(s)" as used herein means atoms selected from nitrogen, oxygen, and sulfur, including sulfoxide and sulfone, which may be quaternized.

[0032] The term "saturated or unsaturated alkyl" as used herein includes saturated alkyl and unsaturated alkyl such as alkenyl, alkynyl, etc. Suitable examples of saturated or unsaturated alkyl include, but are not limited to, 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. "C 1-6"Alkyl" includes all straight or branched chain alkyl groups having 1 to 6 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl, butyl and its isomers (e.g., n-butyl, i-butyl, and t-butyl), pentyl and its isomers, and hexyl and its isomers. For example, "C 1-5 "Alkyl" is inclusive of all straight or branched chain alkyl groups having from 1 to 5 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl, butyl and its isomers (e.g., n-butyl, i-butyl, and t-butyl), pentyl and its isomers, ethylene or vinyl (-CH=CH 2 ), allyl (-CH 2 CH=CH 2 ), 5-hexenyl (-CH 2 CH 2 CH 2 CH 2 CH=CH 2 ), 2-butenyl, 3-butenyl, 2-pentenyl and its isomers, 2-hexenyl and its isomers, 2,4-pentadienyl, ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 2-pentynyl and its chain isomers, 2-hexynyl and its chain isomers.

[0033] The term "alkyl" as used herein means a normal, secondary or tertiary, straight or branched chain hydrocarbon having no sites of unsaturation. Examples are 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. 1-6"Alkyl" includes all straight or branched chain alkyl groups having 1 to 6 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl, butyl and its isomers (e.g., n-butyl, i-butyl, and t-butyl), pentyl and its isomers, and hexyl and its isomers. For example, "C 1-5 "Alkyl" includes all straight or branched chain alkyl groups having from 1 to 5 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl, butyl and its isomers (e.g., n-butyl, i-butyl, and t-butyl), pentyl and its isomers. For example, "C 1-4 "Alkyl" includes all straight or branched chain alkyl groups having 1 to 4 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl, butyl and their isomers (e.g., n-butyl, i-butyl, and t-butyl). For example, "C 1-3 "Alkyl" includes all straight or branched chain alkyl groups having 1 to 3 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl. "Substituted C 1-6 "Alkyl" refers to a C alkyl group substituted with one or more substituents (e.g., 1 to 3 substituents, e.g., 1, 2, or 3 substituents) at any available point of attachment. 1-6 Refers to an alkyl group.

[0034] As used herein, the term "alkenyl" refers to a normal, secondary or tertiary, straight or branched chain hydrocarbon having at least one site of unsaturation (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) The double bond may be in the cis or trans configuration. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms the named group may contain. For example, "C 2-6 The term "alkenyl" refers to an unsaturated hydrocarbyl group that contains one or more carbon-carbon double bonds and that contains from 2 to 6 carbon atoms, and may be straight or branched. For example, C 2-4 Alkenyl includes all straight or branched alkenyl groups having 2 to 4 carbon atoms. 2-6 Examples of alkenyl groups are ethenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and its isomers, 2-hexenyl and its isomers, 2,4-pentadienyl, and the like.

[0035] The term "alkynyl" as used herein means a normal, secondary, tertiary, straight or branched chain hydrocarbon having at least one site of unsaturation (usually one to three, preferably one), i.e., a carbon-carbon, sp triple bond. Examples include ethynyl (-C≡CH) and 1-propynyl (propargyl, -CH 2 C≡CH). When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms the named group may contain. For example, "C 2-6 The term "alkynyl" refers to an unsaturated hydrocarbyl group that contains one or more carbon-carbon triple bonds and that contains from 2 to 6 carbon atoms, and may be straight or branched. For example, C 2-4 Alkynyl includes all straight or branched chain alkynyl groups having 2 to 4 carbon atoms. 2-6 Non-limiting examples of alkynyl groups include ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 2-pentynyl and chain isomers thereof, 2-hexynyl and chain isomers thereof, and the like.

[0036] As used herein, the term "saturated or unsaturated alkylene" encompasses saturated alkylenes as well as unsaturated alkylenes such as alkenylene, alkynylene, etc. As used herein, the term "alkylene" refers to a saturated, straight-chain, or branched-chain hydrocarbon radical having two monovalent radical centers derived by the removal of two hydrogen atoms from the same or two different carbon atoms of a parent alkane. Exemplary alkylene radicals include methylene (-CH 2 -), ethylene (-CH 2 -CH 2 -), methylmethylene (-CH(CH 3 )-), 1-methyl-ethylene (-CH(CH 3 )-CH 2 -), n-propylene (-CH 2 -CH 2 -CH 2 -), 2-methylpropylene (-CH 2 -CH(CH 3 )-CH 2 -), 3-methylpropylene (-CH 2 -CH 2 -CH(CH 3 )-), n-butylene (-CH 2 -CH 2 -CH 2 -CH 2 -), 2-methylbutylene (-CH 2 -CH(CH 3 )-CH 2 -CH 2 -), 4-methylbutylene (-CH 2 -CH 2 -CH 2 -CH(CH 3 )-), pentylene and its chain isomers, and hexylene and its chain isomers. The term "alkenylene" as used herein means a straight or branched chain hydrocarbon radical having at least one site of unsaturation (usually 1 to 3, preferably 1), i.e., a carbon-carbon, sp2 double bond, and having two monovalent radical centers obtained by the removal of two hydrogen atoms from the same or two different carbon atoms of a parent alkene.2-6 "Alkenylene" by itself or as part of another substituent is a C alkyl group that is divalent, i.e., has two single bonds for attachment to two other groups. 2-6 Refers to an alkenyl group.

[0037] The term "alkynylene" as used herein means a straight or branched chain hydrocarbon radical having at least one site of unsaturation (usually one to three, preferably one), i.e., a carbon-carbon, sp triple bond, and having two monovalent radical centers obtained by removal of two hydrogen atoms from the same or two different carbon atoms of a parent alkyne. 2-6 The term "alkynylene" by itself or as part of another substituent refers to a C alkyl group that is divalent, i.e., has two single bonds for attachment to two other groups. 2-6 Refers to an alkynyl group.

[0038] The term "alkenyl" as a group or part of a group refers to an unsaturated hydrocarbyl group that contains one or more carbon-carbon double bonds, and may be straight or branched. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. For example, "C 2-6 The term "alkenyl" refers to an unsaturated hydrocarbyl group that contains one or more carbon-carbon double bonds and that contains from 2 to 6 carbon atoms, and may be straight or branched. For example, C 2-4 Alkenyl includes all straight or branched alkenyl groups having 2 to 4 carbon atoms. 2-6 Examples of alkenyl groups are ethenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and its isomers, 2-hexenyl and its isomers, 2,4-pentadienyl, and the like.

[0039] The term "alkynyl" by itself or as part of another substituent refers to an unsaturated hydrocarbyl group that contains one or more carbon-carbon triple bonds, and may be straight or branched. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. For example, "C 2-6 The term "alkynyl" refers to an unsaturated hydrocarbyl group that contains one or more carbon-carbon triple bonds and that contains from 2 to 6 carbon atoms, and may be straight or branched. For example, C 2-4 Alkynyl includes all straight or branched chain alkynyl groups having 2 to 4 carbon atoms. 2-6 Non-limiting examples of alkynyl groups include ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 2-pentynyl and chain isomers thereof, 2-hexynyl and chain isomers thereof, and the like.

[0040] "HaloC" as a group or part of a group 1-6 The term "alkyl" refers to a C alkyl group having the meaning defined above, in which one, two or three hydrogen atoms are each replaced by a halogen as defined herein. 1-6 Refers to an alkyl group. Such haloC 1-6 Non-limiting examples of alkyl groups include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, and the like.

[0041] As used herein, the term "saturated or unsaturated heteroalkyl" encompasses saturated heteroalkyls as well as unsaturated heteroalkyls such as heteroalkenyls and heteroalkynyls. As used herein, the term "heteroalkyl" refers to straight or branched chain alkyls in which one or more carbon atoms (usually one, two or three) are replaced by heteroatoms, i.e., oxygen, nitrogen or sulfur atoms, provided that the chain cannot contain two adjacent O atoms or two adjacent S atoms. This means that one or more of the alkyls may have -CH 3 Ga-NH 2and / or one or more of the alkyl groups may be replaced by -CH 2 It means that - can be replaced by -NH-, -O-, or -S-. The S atom in the chain can be optionally oxidized with one or two oxygen atoms to give sulfoxides and sulfones, respectively. Furthermore, the heteroalkyl groups in the benzofuran derivatives of the present invention can contain oxo or thio groups at any carbon or heteroatom that results in a stable compound. Exemplary heteroalkyl groups include, but are not limited to, alcohols, alkyl ethers (e.g., -methoxy, -ethoxy, -butoxy, etc.), primary, secondary, and tertiary alkyl amines, amides, ketones, esters, alkyl sulfides, and alkyl sulfones. The term "heteroalkenyl" refers to straight or branched alkenyl, in which one or more carbon atoms (usually one, two, or three) are replaced by oxygen, nitrogen, or sulfur atoms, with the proviso that the chain must 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 straight or branched chain 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 cannot contain two adjacent O atoms or two adjacent S atoms. Thus, the term heteroalkynyl includes -cyano, -O-alkynyl, -NH-alkynyl, -N(alkynyl), -Cyano, ... 2 , -N(alkyl)(alkynyl), -N(alkenyl)(alkynyl), and -S-alkynyl.

[0042] The term "saturated or unsaturated heteroalkylene" as used herein includes saturated heteroalkylene as well as unsaturated heteroalkylene such as heteroalkenylene and heteroalkynylene. The term "heteroalkylene" as used herein means straight or branched chain alkylene, in which one or more carbon atoms (usually one, two or three) are replaced by heteroatoms, i.e., oxygen, nitrogen or sulfur atoms, with the proviso that the chain may not contain two adjacent O atoms or two adjacent S atoms. The term "heteroalkenylene" as used herein means straight or branched chain alkenylene, in which one or more carbon atoms (usually one, two or three) are replaced by oxygen, nitrogen or sulfur atoms, with the proviso that the chain may not contain two adjacent O atoms or two adjacent S atoms. The term "heteroalkynylene," as used herein, means a straight- or branched-chain alkynylene in which one or more carbon atoms (usually 1, 2, or 3) are replaced by oxygen, nitrogen, or sulfur atoms, provided that the chain cannot contain two adjacent O atoms or two adjacent S atoms.

[0043] The term "saturated or unsaturated cycloalkyl" as used herein includes saturated cycloalkyl and unsaturated cycloalkyl such as cycloalkenyl, cycloalkynyl. In particular, the term "saturated or unsaturated cycloalkyl" as used herein encompasses saturated cycloalkyl and unsaturated non-aromatic cycloalkyl such as cycloalkenyl and cycloalkynyl. In particular, the terms "saturated or unsaturated cycloalkyl" and "saturated or non-aromatic unsaturated cycloalkyl" are synonymous. The term "saturated or unsaturated cycloalkyl" also includes all saturated and unsaturated hydrocarbon groups containing one or more rings, including monocyclic or bicyclic groups. The additional rings of polycyclic cycloalkyls may be fused, bridged, and / or joined through one or more spiro atoms. Suitable examples of saturated or unsaturated cycloalkyl include cyclopropyl, cyclopropanyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,5-cyclooctadienyl, bicyclo[2.2.1]heptane-2, cyclopropyl ... Examples of cycloalkyl include, but are not limited to, norbornyl, (1S,4R)-norbornan-2-yl, (1R,4R)-norbornan-3-yl, (1S,4S)-norbornan-2-yl, (1R,4S)-norbornan-2-yl, decalinyl, adamantyl, spiro[3.3]heptan-2-yl, 3-bicyclo[3.1.0]hexanyl, bicyclo[1.1.1]pentane, and cis-bicyclo[3.1.0]hexane. As used herein, unless otherwise specified, the term "cycloalkyl" refers to a saturated cyclic hydrocarbon radical, including monocyclic or bicyclic groups, where the additional rings of polycyclic cycloalkyls may be fused, bridged, and / or joined through one or more spiro atoms. Examples of cycloalkyl include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornyl, fenchyl, decalinyl, adamantyl, spiro[3.3]heptan-2-yl, 3-bicyclo[3.1.0]hexanyl, and the like.The term "cycloalkenyl" as used herein means a non-aromatic cyclic hydrocarbon radical having at least one site of unsaturation (usually 1-3, preferably 1), i.e., a carbon-carbon, sp2 double bond. The term "cycloalkenyl" also includes monocyclic or bicyclic groups, where the additional rings of polycyclic cycloalkenyls may be fused, bridged, and / or joined through one or more spiro atoms. Examples include, but are not limited to, cyclopentenyl and cyclohexenyl. The double bond may be in a cis or trans configuration. The term "cycloalkynyl" as used herein means a non-aromatic cyclic hydrocarbon radical having at least one site of unsaturation (usually 1-3, preferably 1), i.e., a carbon-carbon, sp triplet. An example is cyclohept-1-ene. A fused system of cycloalkyl rings with a heterocycloalkyl ring is considered to be a heterocycloalkyl, regardless of the ring attached to the core structure. A fused system of cycloalkyl rings with an aryl ring is considered to be an aryl, regardless of the ring attached to the core structure. A fused system of a cycloalkyl ring with a heteroaryl ring is considered heteroaryl, regardless of which ring is attached to the core structure.

[0044] The term "saturated or unsaturated heterocycloalkyl" as used herein includes saturated heterocycloalkyl as well as unsaturated non-aromatic heterocycloalkyl containing at least one heteroatom, i.e., N, O, or S, as a ring member. In particular, the terms "saturated or unsaturated heterocycloalkyl" and "saturated or non-aromatic unsaturated heterocycloalkyl" are synonymous. The term "heterocycloalkyl" as used herein means "cycloalkyl" unless otherwise stated, with the proviso that one or more carbon atoms (usually one, two, or three) are replaced by oxygen, nitrogen, or sulfur atoms, and the chain may not contain two adjacent O atoms or two adjacent S atoms. The term "heterocycloalkenyl" as used herein means "cycloalkenyl" unless otherwise stated, with the proviso that one or more carbon atoms (usually one, two, or three) are replaced by oxygen, nitrogen, or sulfur atoms, and the chain may not contain two adjacent O atoms or two adjacent S atoms. The term "heterocycloalkynyl," as used herein, unless otherwise noted, means "cycloalkynyl" in which one or more carbon atoms (usually 1, 2 or 3) are replaced by oxygen, nitrogen, or sulfur atoms, provided that the chain cannot contain two adjacent O atoms or two adjacent S atoms.Examples of saturated and unsaturated heterocycloalkyls include 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, thiomol. These include, but are not limited to, folin, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-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. Further heterocycloalkyls in the sense of the present invention are described in Paquette, Leo A. "Principles of Modern Heterocyclic Chemistry" (WA 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 to present), especially volumes 13, 14, 16, 19 and 28; Katritzky, Alan R., Rees, CW and Scriven, E. "Comprehensive Heterocyclic Chemistry" (Pergamon Press, 1996), and J. Am. Chem. Soc. (1960) 82: 5566. If the heterocycloalkyl does not contain nitrogen as a ring member, it is typically bonded through carbon. If the heterocycloalkyl contains nitrogen as a ring member, it can be bonded through nitrogen or carbon.A fused system of a heterocycloalkyl ring with a cycloalkyl ring is considered to be a heterocycloalkyl, regardless of the ring that is attached to the core structure. A fused system of a heterocycloalkyl ring with an aryl ring is considered to be a heterocycloalkyl, regardless of the ring that is attached to the core structure. A fused system of a heterocycloalkyl ring with a heteroaryl ring is considered to be a heteroaryl, regardless of the ring that is attached to the core structure.

[0045] The term "aryl" as used herein means an aromatic hydrocarbon. Typical aryl groups include, but are not limited to, radicals derived from 1-membered, or 2- or 3-membered benzene, naphthalene, anthracene, biphenyl, and the like, fused together. A fused system of an aryl ring with a cycloalkyl ring is considered an aryl, regardless of the ring that is attached to the core structure. A fused system of an aryl ring with a heterocycloalkyl ring is considered a heterocycloalkyl, regardless of the ring that is attached to the core structure. Thus, indoline, dihydrobenzofuran, dihydrobenzothiophene, and the like are considered heterocycloalkyl according to the present invention. A fused system of an aryl ring with a heteroaryl ring is considered a heteroaryl, regardless of the ring that is attached to the core structure.

[0046] The term "heteroaryl" as used herein 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, benzoxazole, benzisoxazole, 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.

[0047] As further examples, 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, prazole, 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.

[0048] Preferred carbon-bonded heterocycles 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. By way of example, nitrogen-bonded heterocycles are 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. Preferred nitrogen-bonded heterocycles include 1-aziridyl, 1-azetidyl, 1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, and 1-piperidinyl. Further heteroaryls within the meaning of the present invention are described in Paquette, Leo A. "Principles of Modern Heterocyclic Chemistry" (WA Benjamin, New York, 1968), in particular chapters 1, 3, 4, 6, 7 and 9, "The Chemistry of Heterocyclic Compounds, A series of Monographs" (John Wiley & Sons, New York, 1950 to present), in particular volumes 13, 14, 16, 19 and 28, Katritzky, Alan R., Rees, CW and Scriven, E. "Comprehensive Heterocyclic Chemistry" (Pergamon Press, 1996), and J. Am. Chem. Soc. (1960) 82:5566.

[0049] As used herein with respect to substituents, unless otherwise indicated, the terms "monosubstituted," "disubstituted," "trisubstituted," "polysubstituted," and the like refer to chemical structures as defined herein, each of which is substituted with one or more substituents, and each of which means that one or more hydrogen atoms of the moiety are each independently replaced by a substituent. For example, -C which can be polysubstituted with -F. 1-6 -Alkyl is -CH 2 F, -CHF 2 , -CF 3 , -CH 2 CF 3 , C.F. 2 CF 3 Similarly, -C, which may be polysubstituted with substituents selected from -F and -Cl, independently of each other, 1-6 -Alkyl is -CH 2 F, -CHF 2 , -CF 3 , -CH 2 CF 3 , C.F. 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, etc. Any substituent designation found at more than one site in a compound of the invention is intended to be independently selected.

[0050] As used herein, and unless otherwise specified, the term "solvate" includes any combination that may be formed by the derivatives of the present invention with suitable inorganic solvents (e.g., hydrates) or organic solvents, such as, but not limited to, alcohols, ketones, esters, ethers, nitriles, and the like.

[0051] The term "subject" as used herein refers to an animal, including a human, preferably a mammal, most preferably a human, who has been the object of treatment, observation or experiment.

[0052] As used herein, the term "therapeutically effective amount" refers to that amount of an active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue system, animal, or human that is sought by a researcher, veterinarian, physician, or other clinician, including alleviation or partial alleviation of the symptoms of the disease or disorder being treated.

[0053] As used herein, "composition" is intended to encompass a product containing therapeutically effective amounts of the specified ingredients, as well as any product resulting directly or indirectly from combining the specified ingredients in the specified amounts.

[0054] The terms "antagonist" or "inhibitor" as used herein refer to compounds capable of producing functional antagonists of the TRPM3 ion channel, including competitive antagonists, non-competitive antagonists, desensitizing agonists, and partial agonists, depending on the context.

[0055] For purposes of the present invention, the term "TRPM3 modulated" is used to refer to conditions that are affected by modulation of the TRPM3 ion channel, including conditions mediated by the TRPM3 ion channel.

[0056] The term "TRPM3-mediated disorder" as used herein refers to disorders or diseases consisting of pain and inflammatory hypersensitivity states, the symptoms of which are prevented, treated, (partially) alleviated or ameliorated by the use of antagonists of TRPM3. 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 pain or epilepsy. Preferably, the TRPM3-mediated disorder is epilepsy, preferably selected from epileptic encephalopathies. For the purposes of the present invention, the term "epileptic encephalopathies" refers to a group of severe epilepsies characterized by both seizures and encephalopathy. Preferably, the TRPM3-mediated disorder is pain, preferably selected from nociceptive pain, inflammatory pain, and neuropathic pain. More preferably, the pain is postoperative pain. For purposes of the present invention, the term "inflammatory hypersensitivity" is used to refer to a condition characterized by one or more hallmarks of inflammation, including edema, erythema, hyperpyrexia 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.

[0057] The present invention will occasionally be further described with reference to particular embodiments, but the present invention is not limited thereto.

[0058] Preferred statements (features) and embodiments of the compounds and methods of the present invention are now described. Each statement and embodiment of the invention so defined may be combined with any other statement and / or embodiment, unless expressly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other one or more features indicated as being preferred or advantageous.

[0059] The numbered statements of this invention are as follows: 1. Compounds of formula (I), their stereoisomers, physiologically acceptable salts, solvates and / or polymorphs, [ka] During the ceremony, R 1 -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 -NR 3 R 4 represents R 3 is -OH or -R Y1 represents R 4 But -R Y2 or -S(=O) 2 R Y3 represents Or, R 3 and R 4 together form a saturated or unsaturated, unsubstituted, mono- or polysubstituted 4-, 5-, 6-, 7-, or 8-membered heterocycle containing 1 to 3 heteroatoms selected from N, O, and S; T represents -O- and U represents -(CR 5 R 5 ') n - or T represents -(CR 5 R 5 ') n -, U represents -O-, n is an integer selected from 1, 2, 3, 4, or 5; R 5 and R 5 ', but independently of each other, -R Y4 represents R 6 , R 7 , and R 8are, independently of each other, -F, -Cl, -Br, -I, -CN, -NO 2 ,-SCIENCE FICTION 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 W, saturated or unsaturated 3- to 14-membered cycloalkyl, unsubstituted, mono- or polysubstituted, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, or In each case, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, During the ceremony, R W and R X but independently of one another, and in each case independently, -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, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, or A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case representing a saturated or unsaturated, unsubstituted, mono- or poly-substituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted, 3- to 14-membered heterocycloalkyl, R Y1 , R Y2 , R Y3 , and R Y4 but independently of one another, and in each case independently, -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, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1-C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; An unsubstituted, mono- or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 6- to 14-membered aryl; An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 5- to 14-membered heteroaryl, "Mono- or polysubstituted" means, at each occurrence, 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-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)OC 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 , -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -OC 1-6 -Alkylene-OC 1-6 -Alkyl, -OC 1-6 -Alkylene-NH 2 , -OC 1-6 -Alkylene-NH-C 1-6 -Alkyl, -OC 1-6 -Alkylene-N(C 1-6 -alkyl) 2 , -OC(=O)-C 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-C 1-6 -Alkyl, -OC(=O)-OC 1-6 -Alkyl, -C1-6 -Alkylene-OC(=O)-OC 1-6 -Alkyl, -OC(=O)-NH(C 1-6 -alkyl), -C 1-6 -Alkylene-OC(=O)-NH(C 1-6 -alkyl), -OC(=O)-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OC(=O)-N(C 1-6 -alkyl) 2 , -OS(=O) 2 -NH 2 , -C 1-6 -Alkylene-OS(=O) 2 -NH 2 , -OS(=O) 2 -NH(C 1-6 -alkyl), -C 1-6 -Alkylene-OS(=O) 2 -NH(C 1-6 -alkyl), -OS(=O) 2 -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OS(=O) 2 -N(C 1-6 -alkyl) 2 , -NH 2 , -NO, -NO 2 , -C 1-6 -Alkylene-NH 2 , -NH(C 1-6 -alkyl), -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)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-C(=O)-OC 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)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-C(=O)-OC 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) 2OH, -NH-S(=O) 2 -C 1-6 -Alkyl, -C 1-6 -Alkylene-NH-S(=O) 2 -C 1-6 -Alkyl, -NH-S(=O) 2 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-S(=O) 2 -OC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-S(=O) 2 -OC 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 , -SC 1-6 -Alkyl, -C 1-6 -Alkylene-SC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-S(=O) 2 -OC 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- to 14-membered cycloalkyl), 3- to 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 to 14 membered cycloalkyl), -S(=O) 2 -(3-14 membered heterocycloalkyl), -S(=O) 2 -phenyl, or -S(=O) 2 -(5-14 membered heteroaryl), meaning substituted with one or more substituents independently selected from each other from: 2. T represents -O- and U represents -(CR 5 R 5 ') n - . The compound according to claim 1 , 3.R 1 but, -H, -F, -Cl, -Br, -I, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -OC 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C(=O)C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -C(=O)OC 1-6 -alkyl, -C(=O)NH 2 , Saturated or unsaturated, unsubstituted, mono- or poly-substituted -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 -C 6 -heteroalkyl, or A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C6 -Alkylene- or -C 1 -C 6 3. The compound according to claim 1 or 2, wherein -heteroalkylene- represents, in each case, a saturated or unsaturated, unsubstituted, mono- or poly-substituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted, 3- to 14-membered cycloalkyl, optionally connected through -heteroalkylene-. 4.R 1 but, -H, -F, -Cl, -Br, -I, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -OC 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C(=O)C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -C(=O)OC 1-6 -alkyl, -C(=O)NH 2 , Saturated or unsaturated, unsubstituted, mono- or poly-substituted -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 -C 6 -heteroalkyl, or Unsubstituted, mono- or poly-substituted 3- to 14-membered saturated cycloalkyl, 5- to 14-membered cycloalkenyl, or 8- to 14-membered cycloalkynyl, each of which is, in each occurrence, saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, optionally connected through a 3- to 14-membered saturated cycloalkyl, a 5- to 14-membered cycloalkenyl, an 8- to 14-membered cycloalkynyl, preferably an unsubstituted, mono- or poly-substituted 3- to 12-membered saturated cycloalkyl, a 5- to 12-membered cycloalkenyl, or an 8- to 12-membered cycloalkynyl, each of which is in each case saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, optionally connected through a 3- to 12-membered saturated cycloalkyl, 5- to 12-membered cycloalkenyl, or 8- to 12-membered cycloalkynyl, preferably an unsubstituted, mono- or poly-substituted 3- to 10-membered saturated cycloalkyl, 5- to 10-membered cycloalkenyl, or 8- to 10-membered cycloalkynyl, each of which is in each case saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -Alkylene- or -C 1 -C 6-heteroalkylene- is optionally connected through a 3- to 10-membered saturated cycloalkyl, 5- to 10-membered cycloalkenyl, or 8- to 10-membered cycloalkynyl, preferably an unsubstituted, mono- or poly-substituted 3- to 8-membered saturated cycloalkyl, 5- to 8-membered cycloalkenyl, or 8-membered cycloalkynyl, each of which is in each case saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -Alkylene- or -C 1 -C 6 A compound according to any one of the preceding statements, which represents a 3-8 membered saturated cycloalkyl, a 5-8 membered cycloalkenyl or an 8 membered cycloalkynyl, optionally connected through -heteroalkylene-. 5.R 1 -H, -F, -Cl, -Br, -I, -CN, -C 1-6 -Alkyl, -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC 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 -alkylene)-C 1-6 -Alkylene-CF 3 , -C(=O)C 1-6 -Alkyl, -C(=O)OC1-6 -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, -OC 1-6 A compound according to any one of the preceding statements, wherein R represents -alkyl, unsubstituted -cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, or unsubstituted cyclohexyl. 6.R 1 is -H, unsubstituted, -C 1-6 -Alkyl, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -CHF 2 , -CF 3 or -cyclopentyl, 7.R 3 but, -H, -OH, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -heteroalkyl, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6-Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; An unsubstituted, mono- or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 6- to 14-membered aryl; An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6A compound according to any one of the preceding statements, optionally connected through -heteroalkylene-, in each case representing a saturated or unsaturated, unsubstituted, mono- or poly-substituted, 5- to 14-membered heteroaryl. 8.R 3 but, -H, -OH, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -alkyl, or Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -heteroalkyl. 9.R 3 But -H, -OH, -C 1-6 -Alkyl, -C 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 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 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 20. The compound according to any one of the preceding statements, wherein 10.R3 is -H, -OH, or -C which is saturated, unsubstituted or monosubstituted with -OH; 1-6 A compound according to any one of the preceding statements, wherein: 11.R 3 A compound according to any one of the preceding statements, wherein represents -H. 12.R 4 but, -H, 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 -C 6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -heteroalkyl, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; An unsubstituted, mono- or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 6- to 14-membered aryl; An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 A compound according to any one of the preceding statements, optionally connected through -heteroalkylene-, in each case representing a saturated or unsaturated, unsubstituted, mono- or poly-substituted, 5- to 14-membered heteroaryl. 13.R 4 but, -H, 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 -C 6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -heteroalkyl, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6-heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; Unsubstituted, mono- or polysubstituted -C 1-6 -alkylene-phenyl, unsubstituted, mono- or polysubstituted -phenyl, or An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 A compound according to any one of the preceding statements, optionally connected through -heteroalkylene-, in each case representing a saturated or unsaturated, unsubstituted, mono- or poly-substituted, 5- to 14-membered heteroaryl. 14.R 4 but, Saturated or unsaturated, unsubstituted, independently of each other, -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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6-Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -S(=O) mono- or polysubstituted with a substituent selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 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, each occurrence of which is saturated or unsaturated, 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-OC 1-6-Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -S(=O) mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 2 (3 to 14 membered cycloalkyl), Saturated or unsaturated, 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-OC 1-6-Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -C is mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1-6 -alkyl, Saturated or unsaturated, 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-OC 1-6 -Alkyl, -NH2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -C is mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1 -C 6 -heteroalkyl, 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl) 1-6-alkylene- is unsubstituted or monosubstituted 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, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 1-6-3- 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), 1-6 -alkylene- is unsubstituted or monosubstituted by -OH and the 3 to 14 membered heterocycloalkyl is, in each occurrence, 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, 1,1-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, -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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2, -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -3- to 14-membered heterocycloalkyl, each of which is mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1-6 -alkylene-(3 to 14 membered heterocycloalkyl), Unsubstituted, -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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl)2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -C is mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1-6 -alkylene-phenyl, Unsubstituted, -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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2, -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -phenyl, which is mono- or polysubstituted with substituents independently selected from the group consisting of: -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), 1-6-alkylene- is unsubstituted or monosubstituted by -OH and the 5- to 14-membered heteroaryl is, in each occurrence, benzimidazole, benzisoxazole, benzoxazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furan, furazan, imidazole, imidazopyridine, indazole, indole, indolizine, isobenzofuran, isoindole, iso selected from the group consisting of quinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, oxindole, phthalazine, purine, pyrazine, pyrazole, pyridazine, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, in each case unsubstituted, -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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)-C1-6 -Alkyl, -C(=O)OH, -C(=O)OC 1-6 -Alkyl, -C(=O)OC 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, each of which is mono- or polysubstituted with a substituent selected from the group consisting of: 1-6 -alkylene-(5-14 membered heteroaryl), 15.R 4 but, -H, Saturated, unsubstituted, -S(=O) mono- or polysubstituted with -F 2 C 1-6 -alkyl, Saturated, unsubstituted -S(=O) 2 (3 to 14 membered cycloalkyl), Saturated, unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3- to 14-membered cycloalkyl, unsubstituted phenyl, oxetanyl, or pyrimidinyl, each of which is mono- or polysubstituted with a substituent selected from the group consisting of 1-6 -alkyl, 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl) 1-6 -Alkylene- is unsubstituted or mono- or polysubstituted with -F, -Cl, -Br, -I, or -OH, and the 3- to 14-membered cycloalkyl is saturated, unsubstituted, -F, -Cl, -Br, -I, or -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3, -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3- to 14-membered cycloalkyl, unsubstituted phenyl, oxetanyl, or pyrimidinyl, each of which is mono- or disubstituted with a substituent selected from the group consisting of 3- to 14-membered cycloalkyl, unsubstituted phenyl, oxetanyl, or pyrimidinyl; 1-6 -alkylene-(3 to 14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl or -C1-6 -alkylene-(3- to 14-membered heterocycloalkyl), 1-6 -Alkylene- is unsubstituted or mono- or polysubstituted by -F, -Cl, -Br, -I, -OH, and the 3- to 14-membered heterocycloalkyl is, in each case, azetane, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, -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-dioxothiacylcyclohexane, in each case unsubstituted, -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 , -C1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5-14 membered heteroaryl, or -C 1-6 -alkylene-(3 to 14 membered heterocycloalkyl), 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), 1-6 -alkylene- is unsubstituted or monosubstituted with -F, -Cl, -Br, -I, or -OH, and the 5- to 14-membered heteroaryl, at each occurrence, is selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, at each occurrence, unsubstituted, -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3- to 14-membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl, or -C 1-6 -alkylene-(5-14 membered heteroaryl), 16.R 4 but, -H, Saturated, unsubstituted, -S(=O) mono- or polysubstituted with -F 2 C 1-6 -alkyl, Saturated, unsubstituted -S(=O) 2 (3 to 14 membered cycloalkyl), Saturated, unsubstituted, -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 -C is mono- or disubstituted with substituents independently selected from the group consisting of -alkyl, -phenyl, and unsubstituted -C 1-6 -alkyl, 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl) 1-6 -alkylene- is unsubstituted or monosubstituted with -OH, and the 3- to 14-membered cycloalkyl is saturated, unsubstituted, -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)OC 1-6 -Alkyl, -OH, -OC 1-6 -Alkyl, -NH 2 , -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -C11, -C21, -C31, -C41, -C51, -C61, -C71, -C81, -C91, -C101, -C112, -C121, 1-6 -alkylene-(3 to 14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl or -C 1-6 -alkylene-(3- to 14-membered heterocycloalkyl), 1-6-alkylene- is unsubstituted or monosubstituted by -OH, and the 3- to 14-membered heterocycloalkyl is, in each occurrence, azetane, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octa ... 1,2-dioxothiacylcyclohexane, 4-azabicyclo[3.3]hexane, 5-azabicyclo[3.4]hexane, 6-azabicyclo[3.5]hexane, 7-azabicyclo[3.6]hexane, 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-dioxothiacylcyclohexane, 4-azabicyclo[3.4]hexane, 5-azabicyclo[3.5]hexane, 6-azabicyclo[3.4]hexane, 7-azabicyclo[3.5]hexane, 8-azabicyclo[3.4]hexane, 9-azabicyclo[3.4]hexane, 1,2 ... 1-6 -Alkyl, -C 1-6 -Alkylene-CF 3 , -C 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -3 to 14-membered heterocycloalkyl or -C 1-6 -alkylene-(3 to 14 membered heterocycloalkyl), unsubstituted -phenyl, 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), 1-6 -alkylene- is unsubstituted or monosubstituted with -OH, and the 5 to 14 membered heteroaryl, at each occurrence, is selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, and at each occurrence, is unsubstituted, -C 1-6 -5 to 14-membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), 17. R 3 represents -H, R 4 but, -H, Saturated, unsubstituted, -S(=O) mono- or polysubstituted with -F 2 C 1-6 -alkyl, Saturated, unsubstituted -S(=O) 2 (3 to 14 membered cycloalkyl), Saturated, unsubstituted, -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 -Alkyl, -C(=O)-N(C 1-3 -alkyl) 2 or unsubstituted -phenyl, -C 1-6 -alkyl, 3-14 membered cycloalkyl or -C 1-6-alkylene-(3- to 14-membered cycloalkyl) 1-6 -alkylene- is unsubstituted or monosubstituted with -OH, and the 3- to 14-membered cycloalkyl is saturated, unsubstituted, -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)OC 1-6 -Alkyl, -OH, -OC 1-6 -Alkyl, -NH 2 , -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -C11, -C21, -C31, -C41, -C51, -C61, -C71, -C81, -C91, -C101, -C112, -C121, 1-6 -alkylene-(3 to 14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl or -C 1-6 -alkylene-(3- to 14-membered heterocycloalkyl), 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, and the 3- to 14-membered heterocycloalkyl is, in each occurrence, azetane, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octa ... 1,2-dioxothiacylcyclohexane, 4-azabicyclo[3.3]hexane, 5-azabicyclo[3.4]hexane, 6-azabicyclo[3.5]hexane, 7-azabicyclo[3.6]hexane, 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-dioxothiacylcyclohexane, 4-azabicyclo[3.4]hexane, 5-azabicyclo[3.5]hexane, 6-azabicyclo[3.4]hexane, 7-azabicyclo[3.5]hexane, 8-azabicyclo[3.4]hexane, 9-azabicyclo[3.4]hexane, 1,2 ... 1-6 -Alkyl, -C 1-6 -Alkylene-CF 3 , -C1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -3 to 14-membered heterocycloalkyl or -C 1-6 -alkylene-(3 to 14 membered heterocycloalkyl), unsubstituted -phenyl, 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), 1-6 -alkylene- is unsubstituted or monosubstituted with -OH, and the 5- to 14-membered heteroaryl, at each occurrence, is selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, at each occurrence unsubstituted, independently of each other, -C 1-6 -alkyl, -OH, or -C 1-6 -alkylene-(5-14 membered heteroaryl), 18.R 3 and R 4and R are independently selected from N, O, and S; and R are independently selected from N, O, and S; and R is independently selected from N, O, and S. 19.R 3 and R 4 taken together form a heterocycle selected from the group consisting of pyrrolidine, piperidine, morpholine, and piperazine, in each occurrence unsubstituted or -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)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -alkyl, unsubstituted -pyridyl, and unsubstituted or -C 1-6 -1,2,4-oxadiazole mono- or polysubstituted with substituents independently selected from the group consisting of: 20.R 3 and R 4 But together, Unsubstituted or -N(CH 3 ) 2 a pyrrolidine ring monosubstituted with Unsubstituted or -C 1-6 -Alkyl, -NH 2 , -N(CH 3 ) 2 , -C(=O)NH-C 1-6 -Alkyl, -C(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -alkyl, and unsubstituted or -C 1-6 a piperidine ring, an unsubstituted morpholine ring, or Unsubstituted or -C 1-6A compound according to any one of the preceding statements, forming a piperidine ring, N-substituted with a substituent selected from the group consisting of -alkyl and unsubstituted -pyridyl. 21.R 3 and R 4 together with the nitrogen atom to which they are attached form a residue selected from the group consisting of: [ka] 22. W, saturated or unsaturated, unsubstituted, mono- or di-substituted 3- to 14-membered cycloalkyl; In each case, unsubstituted, monosubstituted or disubstituted -C 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, In particular, W saturated or non-aromatic unsaturated, unsubstituted, mono- or di-substituted 3- to 14-membered cycloalkyl; In each case, unsubstituted, monosubstituted or disubstituted -C 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, 23. W, Saturated or unsaturated, unsubstituted, -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5-14 membered heteroaryl, mono- or polysubstituted with substituents independently selected from, in particular, saturated or aromatically unsaturated, unsubstituted, -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3- to 14-membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl, or In each case, unsubstituted -F, -Cl, -Br, -I, -C1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2, 3- to 14-membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl, mono- or polysubstituted with substituents independently selected from the group consisting of -C 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, 24. W, Saturated or unsaturated, unsubstituted, -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5-14 membered heteroaryl, mono- or polysubstituted with substituents independently selected from 3- to 10-membered cycloalkyl, in particular saturated or aromatically unsaturated, unsubstituted, -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6-Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3- to 14-membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl, or Unsubstituted -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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-C1-6 -Alkylene-CF 3 , -C 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3- to 14-membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl, mono- or polysubstituted with substituents independently selected from the group consisting of -C 1 -C 6 -alkyl. 25.W is Saturated or unsaturated, unsubstituted, -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -OH, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-N(C1-6 -alkyl) 2 , -C 1-6 -Alkylene-OH, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 3- to 14-membered cycloalkyl, mono- or polysubstituted with substituents independently selected from, in particular, saturated or non-aromatically unsaturated, unsubstituted, -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -OH, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OH, -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, -S(=O) 2 -NH 2 , -S(=O) 2-NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 or In each case, unsubstituted -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -OH, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OH, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6-alkynyl, 26. W, Unsubstituted -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -OH, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OH, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 or In each case, unsubstituted -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -OH, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OH, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, 27.R 5 and R 5 ' but 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, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 A compound according to any one of the preceding statements, optionally connected through -heteroalkylene-, in each occurrence representing a saturated or unsaturated, unsubstituted, mono- or poly-substituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted, 3- to 14-membered cycloalkyl. 28. n is an integer selected from 1, 2, or 3; R 5 and R 5 ' but 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, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 A compound according to any one of the preceding statements, optionally connected through -heteroalkylene-, in each occurrence representing a saturated or unsaturated, unsubstituted, mono- or poly-substituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted, 3- to 14-membered cycloalkyl. 29.R 5 and R 5 ', but independently of each other, -H, -C 1 -C 6 -alkyl or -C 1 -C 6 -Alkylene-N(C 1 -C 6 -alkyl) 2 20. The compound according to any one of the preceding statements, wherein 30.R 6 , R 7 , and R 8 But 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- or polysubstituted -C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -OC 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -NHC 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -N(C 1-6-alkyl) 2 , Saturated or unsaturated, unsubstituted, mono- or poly-substituted -C(=O)OC 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -OC(=O)C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1-6 -heteroalkyl. 31.R 6 , R 7 , and R 8 But 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, -OC 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, S.F. 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -NHC 1-6 -alkyl, unsubstituted or, independently of each other, -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 , -CH 2F, -OCF 3 , -OCHF 2 , -OCH 2 F, S.F. 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -N(C 1-6 -alkyl) 2 , 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, S.F. 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -C(=O)OC 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, S.F. 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -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, S.F. 5 , -NO2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -C 1-6 -heteroalkyl. 32.R 6 is -H, -F, -Cl, -CN, or -C 1 -C 6 A compound according to any one of the preceding statements, wherein: 33.R 6 does not represent -H. 34.R 7 is -H, -F, -Cl, -CN, or -C 1 -C 6 A compound according to any one of the preceding statements, wherein: 35.R 7 does not represent -H. 36.R 8 is -H, -F, -Cl, -CN, or -C 1 -C 6 A compound according to any one of the preceding statements, wherein: 37.R 8 does not represent -H. 38. (i)R 6 , R 7 , and R 8 each represents -H, or (ii)R 6 , R 7 , and R 8 Two of them represent -H, and R 6 , R 7 , and R 8 The other of the two is -F, -Cl, -CN, or -CH 3 represents or (iii)R 6 , R 7 , and R 8 One of the groups represents -H, and R 6 , R 7 , and R8 the other of which is independently -F, -Cl, -CN, or -CH 3 20. The compound according to any one of the preceding statements, wherein 39. A compound according to any one of the preceding statements, selected from the group consisting of compounds 001 to 044 as described herein and physiologically acceptable salts thereof. 40. A compound according to any one of the preceding statements, selected from the group consisting of compounds 001 to 062 as described herein and physiologically acceptable salts thereof. 41. R 1 H, -CH 2 F, -CHF 2 , or -CF 3 and / or R 3 represents -H, R 4 but, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -alkyl, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; An unsubstituted, mono- or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 6- to 14-membered aryl; An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 5- to 14-membered heteroaryl, Or, R 3 and R 4together form a saturated or unsaturated, unsubstituted, mono- or polysubstituted 5- or 6-membered heterocycle containing 1 or 2 heteroatoms selected from N, O, and S, R 5 and R 5 ', but independently of each other, -H, -C 1 -C 6 -alkyl or -C 1 -C 6 -Alkylene-N(C 1 -C 6 -alkyl) 2 represents R 6 , R 7 , and R 8 are each independently -H, -F, -Cl, -CN, or -C 1 -C 6 -alkyl, W, saturated or unsaturated 3- to 14-membered cycloalkyl, unsubstituted, mono- or polysubstituted, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, or Unsubstituted, mono- or polysubstituted -C 1 -C 6 -alkyl. 42. A pharmaceutical composition or medicament comprising a compound according to any one of the preceding statements. 43. A compound according to any one of the preceding statements or a pharmaceutical composition according to statement 42 for use as a medicament. 44. A compound according to any one of the preceding statements or a pharmaceutical composition according to statement 42, for use in the treatment of pain or epilepsy, preferably pain and epileptic encephalopathy. 45. The compound for use or pharmaceutical composition for use according to statement 44, wherein the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain. 46. ​​The compound for use or pharmaceutical composition for use according to statement 44, wherein the pain is post-operative pain. 47. A method for preventing and / or treating a TRPM3-mediated disorder, comprising administering to a subject an effective amount of a compound according to any one of claims 1 to 41 or a pharmaceutical composition according to claim 42. 48. A method for the prevention and / or treatment of pain, or epilepsy, such as epileptic encephalopathy, comprising administering to a subject an effective amount of a compound according to any one of the preceding statements 1 to 41, or a pharmaceutical composition according to claim 42. 49. The method of claim 48, wherein the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain.

[0060] A first aspect of the present invention preferably provides a compound of formula (I) (also referred to as a benzofuran derivative according to the present invention), a stereoisomer, a physiologically acceptable salt, a solvate and / or a polymorph thereof, for use in the treatment of pain, [ka] During the ceremony, R 1 -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 -NR 3 R 4 represents R 3 is -OH or -R Y1 represents R 4 But -R Y2 or -S(=O) 2 R Y3 represents Or, R3 and R 4 together form a saturated or unsaturated, unsubstituted, mono- or polysubstituted 4-, 5-, 6-, 7-, or 8-membered heterocycle containing 1 to 3 heteroatoms selected from N, O, and S; T represents -O- and U represents -(CR 5 R 5 ') n - or T represents -(CR 5 R 5 ') n -, U represents -O-, n is an integer selected from 1, 2, 3, 4, or 5; R 5 and R 5 ', but independently of each other, -R Y4 represents R 6 , R 7 , and R 8 are, independently of each other, -F, -Cl, -Br, -I, -CN, -NO 2 ,-SCIENCE FICTION 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 W, saturated or unsaturated 3- to 14-membered cycloalkyl, unsubstituted, mono- or polysubstituted, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, or In each case, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C2 -C 6 -alkynyl, During the ceremony, R W and R X but independently of one another, and in each case independently, -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, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, or A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6-heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; R Y1 , R Y2 , R Y3 , and R Y4 but independently of one another, and in each case independently, -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, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; An unsubstituted, mono- or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 6- to 14-membered aryl; An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6-heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 5- to 14-membered heteroaryl, "Mono- or polysubstituted" means, at each occurrence, 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-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)OC 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 , -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -OC 1-6 -Alkylene-OC 1-6 -Alkyl, -OC 1-6 -Alkylene-NH 2 , -OC 1-6 -Alkylene-NH-C 1-6 -Alkyl, -OC 1-6 -Alkylene-N(C 1-6 -alkyl) 2 , -OC(=O)-C 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-C 1-6 -Alkyl, -OC(=O)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-OC 1-6 -Alkyl, -OC(=O)-NH(C 1-6 -alkyl), -C 1-6 -Alkylene-OC(=O)-NH(C 1-6 -alkyl), -OC(=O)-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OC(=O)-N(C 1-6 -alkyl) 2 , -OS(=O) 2 -NH 2 , -C 1-6 -Alkylene-OS(=O) 2 -NH 2 , -OS(=O) 2 -NH(C 1-6 -alkyl), -C 1-6 -Alkylene-OS(=O) 2 -NH(C 1-6-alkyl), -OS(=O) 2 -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OS(=O) 2 -N(C 1-6 -alkyl) 2 , -NH 2 , -NO, -NO 2 , -C 1-6 -Alkylene-NH 2 , -NH(C 1-6 -alkyl), -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)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-C(=O)-OC 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)-OC 1-6-Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-C(=O)-OC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-S(=O) 2 -OC 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) 2N(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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-S(=O) 2 -OC 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 , -SC 1-6 -Alkyl, -C 1-6 -Alkylene-SC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-S(=O) 2 -OC 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- to 14-membered cycloalkyl), 3- to 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 to 14 membered cycloalkyl), -S(=O) 2 -(3-14 membered heterocycloalkyl), -S(=O) 2 -phenyl, or -S(=O) 2 -(5- to 14-membered heteroaryl) is substituted with one or more substituents independently selected from the group consisting of aryl, aryl, aryl and heteroaryl.

[0061] In some embodiments, T represents -O- and U represents -(CR 5 R 5 ') n -, where n is an integer selected from 1, 2, or 3.

[0062] In some embodiments, R 1 teeth, -H, -F, -Cl, -Br, -I, -CN, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -heteroalkyl, -OH, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -OC 1-6 -alkyl, -NH 2 , Saturated or unsaturated, unsubstituted, mono- or poly-substituted -NHC 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -N(C 1-6 -alkyl) 2 , Saturated or unsaturated, unsubstituted, mono- or polysubstituted -NHC(=O)C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -NC 1-6 -AlkylC(=O)C 1-6 -alkyl, -SH, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -SC 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C(=O)C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -C(=O)OC 1-6 -alkyl, -C(=O)NH 2 , Saturated or unsaturated, unsubstituted, mono- or poly-substituted -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 -C 6 -heteroalkyl, or A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case representing a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered heterocycloalkyl.

[0063] In some embodiments, R 1 teeth, -H, -F, -Cl, -Br, -I, -CN, In each case, unsubstituted -F, -Cl, -Br, -I, -CF 3, -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C 1-6-Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, Unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2-NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C 1 -C 6 -heteroalkyl, -OH, In each case, unsubstituted -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -OC, each of which is mono- or polysubstituted with a substituent selected independently from the group consisting of: 1-6 -Alkyl, -OC 2 -C 6 -Alkenyl, -OC 2 -C 6 -alkynyl, -NH 2 , Unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -NHC, mono- or polysubstituted with substituents independently selected from the group consisting of: 1-6 -alkyl, In each case, unsubstituted -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 , -C1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -N(C 1-6 -alkyl) 2 , Unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -NHC(=O)C mono- or polysubstituted with substituents independently selected from the group consisting of 1-6 -alkyl, In each case, unsubstituted -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-NH-C1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-NH-C 1-6 -Alkylene-CF 3 , -C 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -NC, mono- or polysubstituted with substituents independently selected from the group consisting of: 1-6 -AlkylC(=O)C 1-6 -alkyl, -SH, In each case, unsubstituted -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6-Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -SC, each of which is mono- or polysubstituted with substituents independently selected from the group consisting of: 1-6 -Alkyl, -SC 2 -C 6 -Alkenyl, -SC 2 -C 6 -alkynyl, Unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6-Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C(=O)C mono- or polysubstituted with substituents independently selected from the group consisting of 1-6 -alkyl, Unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2, -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C(=O)OC, mono- or polysubstituted with substituents independently selected from the group consisting of: 1-6 -alkyl, -C(=O)NH 2 , Unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2-C(=O)NHC, mono- or polysubstituted with substituents independently selected from the group consisting of: 1-6 -alkyl, In each case, unsubstituted -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C(=O)N(C 1-6 -alkyl) 2 , Unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -C(=O)NH 2 , -C(=O)-NH-C 1-6 -Alkyl, -C(=O)-N(C 1-6 -alkyl) 2 , -S(=O) 2 C1-6 -Alkyl, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -S(=O)C mono- or polysubstituted with substituents independently selected from the group consisting of 1-6 -alkyl, Unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -S(=O) 2 -C 1-6 -alkyl, Unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6-Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C 1 -C 6 -heteroalkyl, or Unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, optionally connected through, in each case, saturated or unsaturated, unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 a 3- to 14-membered cycloalkyl group, which is mono- or polysubstituted with substituents independently selected from the group consisting of: A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, in particular a saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, which in each case is saturated or unsaturated, unsubstituted, mono- or polysubstituted unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 and represents a 3- to 14-membered heterocycloalkyl which is mono- or polysubstituted with substituents independently selected from the group consisting of:

[0064] In some embodiments, R 1 -H, -F, -Cl, -Br, -I, -CN, -C 1-6 -Alkyl, -C2 -C 6 -alkenyl, -C 2 -C 6 -Alkynyl, -OH, -OC 1-6 -Alkyl, -SH, -NH 2 , -C 1-6 -Alkylene-OC 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, -OC 1-6 -alkyl, unsubstituted 3- to 14-membered cycloalkyl, or unsubstituted 3- to 14-membered heterocycloalkyl. 1 -H, -F, -Cl, -Br, -I, CN, -C 1-6 -Alkyl, -C 2 -C 6 -alkenyl, -C2 -C 6 -Alkynyl, -OH, -OC 1-6 -Alkyl, -SH, -NH 2 , -C 1-6 -Alkylene-OC 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, -OC 1-6 -alkyl, unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, or unsubstituted cyclohexyl.

[0065] In some embodiments, R 1 are -H, CN, and -C 1-6 -Alkyl, -C 1-6 -Alkylene-OC 1-6-Alkyl, -CH 2 F, -CHF 2 , -CF 3 , -C(=O)NH 2 , unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, or unsubstituted cyclohexyl. 1 -H, -CH 2 F, -CHF 2 , -CF 3 , -C(=O)NH 2 , -CN, unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, or unsubstituted cyclohexyl. 1 -H, -C 1-6 -Alkyl, -C(=O)NH 2 , -CHF 2 , unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, or unsubstituted cyclohexyl.

[0066] Preferably, R 1 -H, -CN, -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(=O)NH 2 , or -C 1-3 -Alkylene-CFH 2 , more preferably -H, -CH 3 , or -CF 2 Represents H.

[0067] In some embodiments, R 3 teeth, -H, -OH, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -heteroalkyl, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6-heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; An unsubstituted, mono- or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 6- to 14-membered aryl; An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, which in each case represents a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 5- to 14-membered heteroaryl.

[0068] In some embodiments, R 3 teeth, -H, -OH, In each case, unsubstituted -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -C1-6 -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, Unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C 1 -C 6 -heteroalkyl, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6-heteroalkylene-, which in each case is unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl)2 and in particular, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is selected from the group consisting of: 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, optionally connected through, in each case, unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 a 3- to 14-membered cycloalkyl group, which is mono- or polysubstituted with substituents independently selected from the group consisting of: An unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, optionally connected through, in each case, saturated or unsaturated, unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 a 3- to 14-membered heterocycloalkyl group, which is mono- or polysubstituted with substituents independently selected from the group consisting of An unsubstituted, mono- or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, optionally connected through, in each case, unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl)2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 or a 6- to 14-membered aryl, each of which is mono- or polysubstituted with substituents independently selected from the group consisting of An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, optionally connected through, in each case, saturated or unsaturated, unsubstituted, -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3, -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 and represents a 5- to 14-membered heteroaryl which is mono- or polysubstituted with substituents independently selected from the group consisting of:

[0069] In some embodiments, R 3 teeth, -H, -OH, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -alkyl, or Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -heteroalkyl.

[0070] Preferably, R 3 -H, -OH, -C 1-6 -Alkyl, -C 1-6 -Alkylene-OH, -C 1-6 -Alkylene-C(=O)-NH 2 , -C 1-6 -Alkylene-OC 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 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 More preferably, R 3 -H, -OH, -C 1-6 -Alkyl, -C 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 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 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 Preferably, R 3 is -H, -OH, or -C which is saturated, unsubstituted or monosubstituted with -OH; 1-6 -alkyl. Preferably, R 3 represents -H.

[0071] In some embodiments, R 3 and R 4 do not both represent -H. In some embodiments, R 3 represents -H, R 4 does not represent -H.

[0072] In some embodiments, R 4 teeth, -H, 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 -C 6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1 -C 6 -heteroalkyl, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case optionally connected through a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C 1 -C 6 -Alkylene- or -C1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl; An unsubstituted, mono- or polysubstituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 6- to 14-membered aryl; An unsubstituted, mono- or polysubstituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, which in each case represents a saturated or unsaturated, unsubstituted, mono- or polysubstituted, 5- to 14-membered heteroaryl.

[0073] Preferably, R 4 teeth, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -S(=O) mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 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, each occurrence of which is saturated or unsaturated, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6-Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -S(=O) mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 2 (3 to 14 membered cycloalkyl), 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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, 1-6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl) 1-6 -alkylene- is unsubstituted or monosubstituted 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, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -3- to 14-membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl), in particular 3- to 14-membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl)1-6 -alkylene- is unsubstituted or monosubstituted 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 non-aromatically unsaturated, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 1-6-3- 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), 1-6 -alkylene- is unsubstituted or monosubstituted by -OH and the 3 to 14 membered heterocycloalkyl is, in each occurrence, azepane, 1,4-oxazepane, 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, thio and selected from the group consisting of morpholine, indoline, dihydrobenzofuran, benzodioxole, dihydrobenzothiophene, 1,1-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, -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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2, -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -3- to 14-membered heterocycloalkyl, each of which is mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1-6 -alkylene-(3 to 14 membered heterocycloalkyl), Unsubstituted, -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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl)2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -phenyl, which is mono- or polysubstituted with substituents independently selected from the group consisting of: -alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), 1-6-alkylene- is unsubstituted or monosubstituted with -OH, and the 5- to 14-membered heteroaryl, at each occurrence, is selected from the group consisting of benzimidazole, benzisoxazole, benzoxazole, 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, pyrimidine, pyrrole, quinazoline, quinoline, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, at each occurrence unsubstituted, -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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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, each of which is mono- or polysubstituted with a substituent selected from the group consisting of: 1-6 -alkylene-(5- to 14-membered heteroaryl).

[0074] Preferably, R 4 teeth, -H, -S(=O) mono- or polysubstituted with -F 2 C 1-6 -alkyl, Unsubstituted -S(=O) 2 (3 to 14 membered cycloalkyl), -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 -Alkyl, -C(=O)-N(C 1-3 -alkyl) 2 or unsubstituted -phenyl, -C 1-6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C6 -alkynyl, 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3- to 14-membered cycloalkyl) 1-6 -alkylene- is unsubstituted or monosubstituted with -OH, and the 3- to 14-membered cycloalkyl is saturated, unsubstituted, -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)OC 1-6 -Alkyl, -OH, -OC 1-6 -Alkyl, -NH 2 , -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -C11, -C21, -C31, -C41, -C51, -C61, -C71, -C81, -C91, -C101, -C112, -C121, 1-6 -alkylene-(3 to 14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl or -C 1-6 -alkylene-(3- to 14-membered heterocycloalkyl), 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, and the 3- to 14-membered heterocycloalkyl is, in each occurrence, azetane, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octa ... 1,2-dioxothiacylcyclohexane, 4-azabicyclo[3.3]hexane, 5-azabicyclo[3.4]hexane, 6-azabicyclo[3.5]hexane, 7-azabicyclo[3.6]hexane, 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-dioxothiacylcyclohexane, 4-azabicyclo[3.4]hexane, 5-azabicyclo[3.5]hexane, 6-azabicyclo[3.4]hexane, 7-azabicyclo[3.5]hexane, 8-azabicyclo[3.4]hexane, 9-azabicyclo[3.4]hexane, 1,2 ...1-6 -Alkyl, -C 1-6 -Alkylene-CF 3 , -C 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -3 to 14-membered heterocycloalkyl or -C 1-6 -alkylene-(3 to 14 membered heterocycloalkyl), unsubstituted -phenyl, 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), 1-6 -alkylene- is unsubstituted or monosubstituted with -OH, and the 5 to 14 membered heteroaryl, at each occurrence, is selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, and at each occurrence, is unsubstituted, -C 1-6 -5 to 14-membered heteroaryl or -C 1-6 -alkylene-(5- to 14-membered heteroaryl).

[0075] In some embodiments, R 4 teeth, The following: [ka] or Unsubstituted, mono- or polysubstituted C 1 -C 6 -alkyl, preferably the residue -CR'R''-(CH 2 ) m m is an integer selected from 1, 2, 3, 4, 5, or 6, preferably 1, 2, or 3; R′ and R″ are each independently selected from —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-OC 1-3 -Alkyl, -C 1-3 -Alkylene-OH, -C(=O)-NH 2 , -C(=O)-NH-C 1-3 -Alkyl, or -C(=O)-N(C 1-3 -alkyl) 2 ;-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-OC 1-3 -Alkyl, -C 1-3 -Alkylene-OH, -C(=O)-NH 2 , -C(=O)-NH-C 1-3-Alkyl, or -C(=O)-N(C 1-3 -alkyl) 2 ; preferably -H, -C 1-3 -Alkyl, -C substituted with OH 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-OC 1-3 -Alkyl, -C 1-3 -Alkylene-OH, -C(=O)-NH 2 , -C(=O)-NH-C 1-3 -Alkyl, or -C(=O)-N(C 1-3 -alkyl) 2 ;-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-OC 1-3 -Alkyl, -C 1-3 -Alkylene-OH, -C(=O)-NH 2 , -C(=O)-NH-C 1-3 -Alkyl, or -C(=O)-N(C 1-3 -alkyl) 2 ; preferably -H, -C 1-3 -Alkyl, -C substituted with OH 1-3 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -C 1-3 -Alkylene-CF 3 , -C 1-3 -Alkylene-CF 2 H, -C1-3 -Alkylene-CFH 2 , -C 1-3 -Alkylene-OC 1-3 -Alkyl, -C 1-3 -Alkylene-OH, -C 1-3 -Alkylene(CF 3 )-NH 2 -C(=O)-NH 2 , -C(=O)-NH-C 1-3 -Alkyl, or -C(=O)-N(C 1-3 -alkyl) 2 ;-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-OC 1-3 -Alkyl, -C 1-3 -Alkylene-OH, -C(=O)-NH 2 , -C(=O)-NH-C 1-3 -Alkyl, or -C(=O)-N(C 1-3 -alkyl) 2 ; preferably -H, -CH 3 , -C 1-3 -Alkylene-OH, C(=O)-NH 2 , -C(=O)-NH-C 1-3 -Alkyl, or -C(=O)-N(C 1-3 -alkyl) 2 ; preferably -H, -CH 3 , -CH substituted with OH 3 CH 2 (OH)- -C 1-3 -Alkylene-OH, -C(CF 3 )-NH 2 , -C 1-3 -Alkylene-CF 3 , -C 1-3 -Alkylene-CFH 2 , -C 1-3 -Alkylene-O-CH3 , C(=O)-NH 2 , -C(=O)-NH-C 1-3 -Alkyl, or -C(=O)-N(C 1-3 -alkyl) 2 and preferably at least R' or R'' does not represent -H, preferably neither R' nor R'' represents -H, and preferably the following: [ka] or a residue selected from the group consisting of: represents a saturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, preferably a saturated, unsubstituted, mono- or polysubstituted 3- to 13-membered cycloalkyl, preferably a saturated, unsubstituted, mono- or polysubstituted 3- to 12-membered cycloalkyl, preferably a saturated, unsubstituted, mono- or polysubstituted 3- to 11-membered cycloalkyl, preferably a saturated, unsubstituted, mono- or polysubstituted 3- to 10-membered cycloalkyl, preferably a cycloalkyl residue selected from the group consisting of: [ka] Or, A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably a saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 12-membered cycloalkyl, wherein the 3- to 12-membered cycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably a saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 10-membered cycloalkyl, wherein the 3- to 10-membered cycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C6 -alkylene-, preferably a saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 8-membered cycloalkyl, wherein the 3- to 8-membered cycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, in particular, saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably a saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted 3- to 12-membered cycloalkyl, wherein the 3- to 12-membered cycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably a saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted 3- to 10-membered cycloalkyl, wherein the 3- to 10-membered cycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably a saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted 3- to 8-membered cycloalkyl, wherein the 3- to 8-membered cycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-connected 3-8 membered cycloalkyl, preferably the following: [ka] or Saturated, unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, preferably saturated, unsaturated, unsubstituted, mono- or polysubstituted 3- to 13-membered heterocycloalkyl, preferably saturated, unsaturated, unsubstituted, mono- or polysubstituted 3- to 12-membered heterocycloalkyl, preferably saturated, unsaturated, unsubstituted, mono- or polysubstituted 3- to 11-membered heterocycloalkyl, preferably saturated, unsaturated, unsubstituted, mono- or polysubstituted 3- to 10-membered heterocycloalkyl, in particular saturated, non-aromatic unsaturated, unsubstituted Preferably, the heterocycloalkyl group represents a saturated, non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered heterocycloalkyl, preferably a saturated, non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 13-membered heterocycloalkyl, preferably a saturated, non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 12-membered heterocycloalkyl, preferably a saturated, non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 11-membered heterocycloalkyl, preferably a saturated, non-aromatic unsaturated, unsubstituted, mono- or polysubstituted 3- to 10-membered heterocycloalkyl, preferably the following: [ka] [ka] a heterocycloalkyl residue selected from the group consisting of A saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably a saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 12-membered heterocycloalkyl, wherein the 3- to 12-membered heterocycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6-alkylene-, preferably a saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 10-membered heterocycloalkyl, wherein the 3- to 10-membered heterocycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably a saturated or unsaturated, unsubstituted, mono- or poly-substituted 3- to 8-membered heterocycloalkyl, wherein the hetero 3- to 8-membered cycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-bonded 3- to 8-membered heterocycloalkyl, in particular, saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably a saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted 3- to 12-membered heterocycloalkyl, wherein the 3- to 12-membered heterocycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably a saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted 3- to 10-membered heterocycloalkyl, wherein the 3- to 10-membered heterocycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably a saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted 3- to 8-membered heterocycloalkyl, wherein the 3- to 8-membered heterocycloalkyl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6-alkylene-connected 3-8 membered heterocycloalkyl, preferably the following: [ka] or an unsubstituted, mono- or poly-substituted 6- to 14-membered aryl, preferably an unsubstituted, mono- or poly-substituted 6- to 12-membered aryl, preferably an unsubstituted, mono- or poly-substituted 6- to 10-membered aryl, preferably an unsubstituted, mono- or poly-substituted 6- to 8-membered aryl, or An unsubstituted, mono- or poly-substituted 6- to 14-membered aryl, wherein the 6- to 14-membered aryl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably an unsubstituted, mono- or poly-substituted 6- to 12-membered aryl, wherein the 6- to 12-membered aryl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably an unsubstituted, mono- or poly-substituted 6- to 10-membered aryl, wherein the 6- to 10-membered aryl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-connected 6-10 membered aryl, preferably the following: [ka] or It represents an unsubstituted, mono-substituted or poly-substituted 5-14 membered heteroaryl, preferably an unsubstituted, mono-substituted or poly-substituted 5-12 membered heteroaryl, preferably an unsubstituted, mono-substituted or poly-substituted 5-10 membered heteroaryl, preferably an unsubstituted, mono-substituted or poly-substituted 5-9 membered heteroaryl, preferably the following: [ka] [ka] and more preferably represents a residue selected from the group consisting of: [ka] or An unsubstituted, mono- or poly-substituted 5- to 14-membered heteroaryl, wherein the 5- to 14-membered heteroaryl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, preferably an unsubstituted, mono- or poly-substituted 5- to 12-membered heteroaryl, wherein the 5- to 12-membered heteroaryl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, and an unsubstituted, mono- or poly-substituted 5- to 10-membered heteroaryl, wherein the 5- to 10-membered heteroaryl is a saturated or unsaturated, unsubstituted, mono- or poly-substituted -C 1 -C 6 -alkylene-, and the 5-8 membered heteroaryl is a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted -C 1 -C 6 -alkylene-bonded 5-8 membered heteroaryl, preferably a residue selected from the group consisting of: [ka]

[0076] In some embodiments, R 4 represents a residue according to general formula (A), [ka] During the ceremony, m A is 0 or 1, Y A -O-, -NR A6 - and -CR A7 R A8 - 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 or -3-oxetanyl, or R A7 and R A8 together with the carbon atom to which it is 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 NHCH2 CH 2 -or-CH 2 CH 2 NHCH 2 CH 2 - represents.

[0077] In some embodiments, R 4 represents a residue according to general formula (A) as defined above, m A is 0 or 1, Y A However, -O- and -CR A7 R A8 - selected from R A1 , R A2 , R A3 , R A4 , R A5 , R A7 , and R A8 are, independently of each other, -H, -C 1-3 -Alkylene-OH, -C 1-3 -Alkylene-N(C 1-3 -alkyl) 2 , or -C(=O)NH 2 Preferably, R A1 , R A2 , R A3 , R A4 , R A5 , R A7 , and R A8 represents a residue that is not -H.

[0078] In some embodiments, R 4 represents a residue according to general formula (A) as defined above, m A is 0 or 1, Y A However, -O- and -CR A7 R A8 - selected from R A1 But -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 represents -H.

[0079] In some embodiments, R 4 represents a residue according to general formula (B), [ka] During the ceremony, Y B -O-, -NR B8 - and -CR B9 R B10 - selected from R B1 , R B2 , R B3 , R B4 , R B5 , R B6 , R B7 , R B8 , R B9 , and R B10 are independently -H, -F, -OH, -C(=O)-NH 2 , -C(=O)-NH-C 1-3 -Alkyl, -C(=O)-N(C 1-3 -alkyl) 2 , -C 1-3 -Alkyl, -C 1-3 -Alkylene-OH, -C 1-3 -Alkylene-OC 1-3 -Alkyl, -C 1-3 -Alkylene-CF 3 , -C 1-3 -Alkylene-CO 2 H or -C 1-3 -Alkylene-C(=O)OC 1-3 -alkyl or R B2 and R B3 taken together represent =O or R B4 and R B5 Together, they represent =O.

[0080] In some embodiments, R 4 represents a residue according to general formula (B) as defined above, Y B -O- and -NR B8 - selected from R B1 , R B2 , R B3 , R B4 , R B5 , R B6 , R B7 , R B8 However, independently of each other, -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 R B4 and R B5 taken together represent =O or preferably R A1 , R A2 , R A3 , R A4 , R A5 , R A7 , and R A8 represents a residue that is not -H, preferably A1 , R A2 , R A3 , R A4 , R A5 , R A7 , and R A8 represents a residue that is not -H.

[0081] In some embodiments, R 4 represents a residue according to general formula (C), [ka] During the ceremony, Y C1 But -O-, -S(=O) 2-, -NR C8 - and -CR C9 R C10 - or Y C2 But -CR C11 R C12 - or Y C1 But -CR C9 R C10 - represents Y C2 But -O-, -S(=O) 2 - and -NR C8 - selected from 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 But independently of each other, -H, -F, -OH, -C(=O)OC 1-3 -Alkyl, -NH 2 , -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl) 2 , -C 1-3 -Alkyl, -C 1-3 -Alkylene-OH, -C 1-3 -Alkylene-CF 3 , -C(=O)-NH 2 , -C(=O)-NH-C 1-3 -Alkyl, or -C(=O)N-(C 1-3 -alkyl) 2 or R C2 and R C3 together represent =O or R C4 and R C5 together represent =O or R C9 and R C10 together represent =O or R C11 and R C12 Together they represent =O.

[0082] In some embodiments, R4 represents a residue according to general formula (C) as defined above, Y C1 is -O- or -NR C8 - selected from Y C2 But -CR C11 R C12 - or Y C1 But -CR C9 R C10 - represents Y C2 -O- and -NR C8 - selected from 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 However, independently of each other, -H, -F, -C 1-3 -Alkyl, -C 1-3 -Alkylene-OH or -C(=O)-NH 2 or 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 represents a residue that is not -H, preferably C1 , R C2 , R C3 , R C4 , R C5 , R C6 , R C7 , R C8 , R C9 , R C10 , R C11 , and R C12 represents a residue that is not -H.

[0083] In some embodiments, R 4 teeth, (i) Residue -CR'R''-(CH 2 ) m -OH, in which m is an integer of 1 to 6, preferably an integer of 1 to 3; R' and R'' are each independently -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-OC 1-3 -alkyl or -C 1-3 -alkylene-OH, preferably -H, -CH 3 , or -C 1-3 -Alkylene-OH, the residue -CR'R''-(CH 2 ) m In a preferred embodiment, at least R' or R'' does not represent -H. In a preferred embodiment, neither R' nor R'' represents -H, or (ii) a residue according to general formula (D), [ka] During the ceremony, m D and n D are each independently 0, 1, 2, or 3, preferably m D +n D Provided that ≦3, Y D1 But -O-, -S(=O) 2 -, -NR D8 - and -CR D9 R D10 - selected from Y D2 But -CR D11 R D12 - or Y D1 But -CRD9 R D10 - represents Y D2 But -O-, -S(=O) 2 - and -NR D8 - selected from R D1 , R D2 , R D3 , R D4 , R D5 , R D6 , R D7 , R D8 , R D9 , R D10 , R D11 , and R D12 However, independently of each other, -H, -F, -OH, -C 1-3 -Alkylene-OH, -C(=O)NH 2 , -C 1-3 -Alkylene-C(O)NH 2 , -C(=O)OC 1-3 -Alkyl, -NH 2 , -C 1-3 -Alkylene-NH 2 , -NH(C 1-3 -alkyl), -N(C 1-3 -alkyl) 2 , -NH(C 1-3 -Alkylene-CF 3 ), -C 1-3 -Alkylene-OCH 3 , -C 1-3 -Alkyl, -C 1-3 -Alkylene-CF 3 or R D2 and R D3 together represent =O or R D4 and R D5 together represent =O or R D9 and R D10 together represent =O or R D11 and R D12 together represent =O, Preferably, m D and n D are each independently 0, 1, 2, or 3, preferably m D +n DProvided that ≦3, Y D1 -O-, -NR D8 - and -CR D9 R D10 - selected from Y D2 But -CR D11 R D12 - or Y D1 But -CR D9 R D10 - represents Y D2 -O- and -NR D8 - selected from R D1 , R D2 , R D3 , R D4 , R D5 , R D6 , R D7 , R D8 , R D9 , R D10 , R D11 , and R D12 However, independently of each other, -H, -F, -OH, -C 1-3 -Alkylene-OH, -C(=O)NH 2 , -CH 2 NH 2 , -CH 2 N(CH 3 ) 2 , -NHCH 2 CF 3 , -CH 3 , or -CH 2 CF 3 or R D2 and R D3 together represent =O or R D4 and R D5 together represent =O or R D9 and R D10 together represent =O or R D11 and R D12 taken together represent =O, but preferably R D1 , R D2 , R D3 , R D4 , R D5 , R D6 , R D7 , R D8 , RD9 , R D10 , R D11 , and R D12 represents a residue that is not -H, preferably D1 , R D2 , R D3 , R D4 , R D5 , R D6 , R D7 , R D8 , R D9 , R D10 , R D11 , and R D12 represents a residue that is not -H.

[0084] In some embodiments, R 4 is a residue according to the general formula (A), (B), (C), (D) or the formula -CR'R''-(CH 2 ) m Represents the residue of -OH.

[0085] In some embodiments, R 4 represents a residue selected from the group consisting of: -CH 3 , [ka]

[0086] In some embodiments, R 3 is H and R 4 is any of the embodiments previously described herein.

[0087] In some embodiments, R 5 and R 5 ' are independent 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 -C6 -heteroalkyl, A saturated or unsaturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C 1 -C 6 -Alkylene- or -C 1 -C 6 -heteroalkylene-, optionally connected through, in each case representing a saturated or unsaturated, unsubstituted, mono- or polysubstituted, saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, 3- to 14-membered cycloalkyl.

[0088] Preferably, R 5 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 Shows.

[0089] In some embodiments, R 5 and R 5 At least one of the ' is not -H.

[0090] In some embodiments, R 5 and R 5 ' are both -H.

[0091] In a preferred embodiment, T represents -O- and U represents -(CR5 R 5 ') n represents the resulting moiety -O-(CR 5 R 5 ') n - represents a residue selected from the group consisting of: [ka]

[0092] In some embodiments, R 5 represents -H, R 5 ', -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 , and -C 1-3 -Alkylene-OH, preferably -H or C 1-3 -alkyl.

[0093] In some embodiments, R 6 , R 7 , and R 8 are independent 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- or polysubstituted -C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -OC 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -NHC 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -N(C 1-6 -alkyl) 2 , Saturated or unsaturated, unsubstituted, mono- or poly-substituted -C(=O)OC 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or poly-substituted -OC(=O)C 1-6 -alkyl, Saturated or unsaturated, unsubstituted, mono- or polysubstituted -C 1-6 -heteroalkyl.

[0094] In some embodiments, R 6 , R 7 , and R 8 are independent of each other, -H, -F, -Cl, -Br, -I, -OH, -SH, -SF 5 , -CN, -NO 2 , -C(=O)OH, -NH 2 , In each case, saturated or unsaturated, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -C is mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1-6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, Saturated or unsaturated, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH 2 , -C1-6 -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)OC 1-6 -Alkyl, -C(=O)OC 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 -OC, mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1-6 -alkyl, Saturated or unsaturated, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -NHC mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1-6 -alkyl, Saturated or unsaturated, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-NH-C1-6 -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)OC 1-6 -Alkyl, -C(=O)OC 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 -N(C) mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1-6 -alkyl) 2 , Saturated or unsaturated, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-NH-C1-6 -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)OC 1-6 -Alkyl, -C(=O)OC 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 -C(═O)OC mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl. 1-6 -alkyl, Saturated or unsaturated, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -OC(═O)C mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1-6 -alkyl, Saturated or unsaturated, 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-OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -NHC(=O)OC 1-6 -Alkyl, -N(C 1-6 -alkyl)C(=O)OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 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)OC 1-6 -Alkyl, -C(=O)OC 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 -C is mono- or polysubstituted with substituents independently selected from the group consisting of alkylene-phenyl, saturated or unsaturated, unsubstituted 3- to 14-membered heterocycloalkyl, and unsubstituted 5- to 14-membered heteroaryl; 1-6 -heteroalkyl.

[0095] Preferably, R 6 , R 7 , and R 8 are independent 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, -OC 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 2F, -OCF 3 , -OCHF 2 , -OCH 2 F, S.F. 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -NHC 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, S.F. 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -N(C 1-6 -alkyl) 2 , 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, S.F. 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -C(=O)OC 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, S.F. 5 , -NO 2, -C(=O)OH, -NH 2 , and -C(=O)NH 2 -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, S.F. 5 , -NO 2 , -C(=O)OH, -NH 2 , and -C(=O)NH 2 -C 1-6 -heteroalkyl.

[0096] In some embodiments, R 6 , R 7 , and R 8 are, independently of each other, -H, -F, -Cl, -Br, -I, -CN, C 1-3 -Alkyl, -CF 3 , -CF 2 H, and -CFH 2 , preferably -H or -F.

[0097] In some embodiments, R 6 is -H, -F, -Cl, -CN, or -C 1 -C 6 - represents alkyl.

[0098] In some embodiments, R 6 is -H, -F, -Cl, -CN, or -CH 3 , preferably -H, -F, -CN, or -CH 3 represents a residue selected from the group consisting of:

[0099] In some embodiments, R 6 does not represent -H.

[0100] In some embodiments, R 7 is -H, -F, -Cl, -CN, or -C 1 -C 6 - represents alkyl.

[0101] In a preferred embodiment of the benzofuran derivative according to the invention, R 7 does not represent -H.

[0102] In some embodiments, R 7 is -H, -F, -Cl, -CN, or -CH 3 , preferably -H, -F, -Cl, or -CH 3 represents a residue selected from the group consisting of:

[0103] In some embodiments, R 6 , R 7 , and R 8 are, independently of each other, -H, -F, -Cl, -Br, -I, -CN, C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 or a residue selected from the group consisting of: [ka]

[0104] In some embodiments of the benzofuran derivatives according to the present invention, R 8 is -H, -F, -Cl, -CN, or -C 1 -C 6 - represents alkyl.

[0105] In some embodiments of the benzofuran derivatives according to the present invention, R 8 does not represent -H.

[0106] In some embodiments, R 8 is -H, -F, -Cl, -CN, or CH 3, preferably -F.

[0107] In some embodiments of the benzofuran derivatives according to the present invention, (i)R 6 , R 7 , and R 8 each represents -H, or (ii)R 6 , R 7 , and R 8 Two of the represent -H, and R 6 , R 7 , and R 8 the other is -F, -Cl, -CN, or -CH 3 represents or (iii)R 6 , R 7 , and R 8 One of the groups represents -H, and R 6 , R 7 , and R 8 the other of which is independently -F, -Cl, -CN, or -CH 3 Represents.

[0108] In some embodiments, W is a saturated or unsaturated, unsubstituted, mono- or polysubstituted, preferably unsubstituted, mono- or tri-substituted, preferably unsubstituted, mono- or di-substituted 3- to 14-membered cycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, preferably unsubstituted, mono- or tri-substituted, preferably unsubstituted, mono- or di-substituted 3- to 14-membered cycloalkyl, or a saturated or unsaturated, unsubstituted, mono- or polysubstituted, preferably unsubstituted, mono- or tri-substituted, preferably unsubstituted, mono- or di-substituted 3- to 12-membered cycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, preferably unsubstituted, mono- or tri-substituted, preferably unsubstituted, mono- or di-substituted 3- to 12-membered cycloalkyl, or a saturated or unsaturated, unsubstituted, mono- or polysubstituted, preferably unsubstituted, mono- or tri-substituted, preferably unsubstituted, mono- or di-substituted 3- to 10-membered cycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, preferably unsubstituted, mono- or tri-substituted, preferably unsubstituted, mono- or di-substituted 3- to 10-membered cycloalkyl, or a saturated or unsaturated, unsubstituted, mono- or polysubstituted, preferably unsubstituted, mono- or tri-substituted, preferably unsubstituted, mono- or di-substituted 3- to 8-membered cycloalkyl, in particular a saturated or non-aromatic unsaturated, unsubstituted, mono- or polysubstituted, preferably unsubstituted, mono- or tri-substituted, preferably unsubstituted, mono- or di-substituted 3- to 8-membered cycloalkyl, or saturated or unsaturated, unsubstituted, mono- or poly-substituted, preferably unsubstituted, mono- or tetra-substituted, preferably unsubstituted, mono- or tri-substituted, preferably unsubstituted, mono- or di-substituted 3- to 6-membered cycloalkyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted, preferably unsubstituted, mono- or tetra-substituted, preferably unsubstituted, mono- or tri-substituted, preferably unsubstituted, mono- or di-substituted 3- to 6-membered cycloalkyl, The substituents are -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl)2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5-14 membered heteroaryl, or In each case, unsubstituted -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6-Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C, mono- or di-substituted with substituents independently selected from the group consisting of 3- to 14-membered heterocycloalkyl, unsubstituted -phenyl, and 5- to 14-membered heteroaryl; 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl.

[0109] In some embodiments, W is a saturated or unsaturated, unsubstituted, mono- or di-substituted 3- to 10-membered cycloalkyl, or an unsubstituted, mono- or di-substituted -C 1 -C 6 -Alkyl, haloC 1-6 Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, in particular saturated or non-aromatic unsaturated, unsubstituted, mono- or di-substituted 3- to 10-membered cycloalkyl or unsubstituted, mono- or di-substituted -C 1 -C 6 -Alkyl, haloC 1-6 Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, preferably W is, in each case, unsubstituted, mono- or disubstituted cyclopropyl, cyclopropanyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenylcycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,5-cyclooctadienyl, cyclo[2.2.1]heptyl, a saturated or unsaturated 3- to 10-membered cycloalkyl selected from the group consisting of norbornyl, (1S,4R)-norbornan-2-yl, (1R,4R)-norbornan-3-yl, (1S,4S)-norbornan-2-yl, (1R,4S)-norbornan-2-yl, decalinyl, adamantyl, spiro[3.3]heptan-2-yl, 3-bicyclo[3.1.0]hexanyl, or, in each case, unsubstituted, mono- or disubstituted -C 1 -C 6 -Alkyl, haloC 1-6 Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6-alkynyl, preferably W is, in each case, unsubstituted, mono- or di-substituted cyclopropyl, cyclopropanyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,5-cyclooctadienyl, 1,6-cyclooctyl, 1,7-cyclooctyl, 1,8-cyclooctyl, 1,9-cyclooctyl, 2,2-cyclooctyl, 2,3-cyclooctyl, 2,4-cyclooctyl, 2,5-cyclooctyl, 2,6-cyclooctyl, 2,7-cyclooctyl, 2,8-cyclooctyl, 2,9-cyclooctyl, 2,1 ... enyl, bicyclo[2.2.1]heptan-2-yl, (1S,4R)-norbornan-2-yl, (1R,4R)-norbornan-3-yl, (1S,4S)-norbornan-2-yl, (1R,4S)-norbornan-2-yl, decalinyl, adamantyl, spiro[3.3]heptan-2-yl, 3-bicyclo[3.1.0]hexanyl, bicyclo[1.1.1]pentane, cis-bicyclo[3.1.0]hexane, or, in each case, unsubstituted, mono- or disubstituted -C 1 -C 6 -Alkyl, haloC 1-6 Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, preferably W is a saturated or unsaturated, unsubstituted, mono- or di-substituted 3- to 10-membered cycloalkyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl and t-butyl, pentyl, hexyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -CCl 3 , -C 1-6 -Alkylene-CCl 3 Or -C 1-6 -Alkylene-CF 3Preferably, W is, in each case, unsubstituted, mono- or disubstituted cyclopropyl, cyclopropanyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,5-cyclooctadienyl, cyclocyclopropyl, ... Heptan-2-yl, (1S,4R)-norbornan-2-yl, (1R,4R)-norbornan-3-yl, (1S,4S)-norbornan-2-yl, (1R,4S)-norbornan-2-yl, decalinyl, adamantyl, spiro[3.3]heptan-2-yl, 3-bicyclo[3.1.0]hexanyl; methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl; pentyl, hexyl-CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -CCl 3 , -C 1-6 -Alkylene-CCl 3 , or -C 1-6 -Alkylene-CF 3and preferably W is, in each case, unsubstituted, mono- or di-substituted cyclopropyl, cyclopropanyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,5-cyclooctadienyl, cyclo[2.2.1]heteroaryl, cycloalkyl ... butan-2-yl, (1S,4R)-norbornan-2-yl, (1R,4R)-norbornan-3-yl, (1S,4S)-norbornan-2-yl, (1R,4S)-norbornan-2-yl, decalinyl, adamantyl, spiro[3.3]heptan-2-yl, 3-bicyclo[3.1.0]hexanyl, bicyclo[1.1.1]pentane, cis-bicyclo[3.1.0]hexane; methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, and t-butyl; pentyl, hexyl-CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -CCl 3 , -C 1-6 -Alkylene-CCl 3 , or -C 1-6 -Alkylene-CF 3 It represents a saturated or unsaturated 3- to 10-membered cycloalkyl selected from the group consisting of:

[0110] In some embodiments, W is represents a saturated, unsubstituted, mono- or polysubstituted 3- to 14-membered cycloalkyl, preferably a saturated, unsubstituted, mono- or polysubstituted 3- to 13-membered cycloalkyl, preferably a saturated, unsubstituted, mono- or polysubstituted 3- to 12-membered cycloalkyl, preferably a saturated, unsubstituted, mono- or polysubstituted 3- to 11-membered cycloalkyl, preferably a saturated, unsubstituted, mono- or polysubstituted 3- to 10-membered cycloalkyl, preferably the following: [ka] a cycloalkyl residue selected from the group consisting of In each case, unsubstituted -F, -Cl, -Br, -I, -C 1-6 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -Alkyl, -C(=O)OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -OH, =O, -OC 1-6 -Alkyl, -NH 2 , -NHC 1-6 -Alkyl, -N(C 1-6 -alkyl) 2 , -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 1-6 -Alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -Alkyl, -NHC(=O)OC 1-6 -Alkyl, -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, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 -C, mono- or polysubstituted with substituents independently selected from the group consisting of 3- to 14-membered heterocycloalkyl, unsubstituted -phenyl, and 5- to 14-membered heteroaryl; 1 -C 6 -Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl.

[0111] In some embodiments, the term “mono- or poly-substituted” refers, at each occurrence, independently to —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-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)OC 1-6 -Alkylene-CF 3 , -C(=O)-NH 2 , -C1-6 -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 , -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -OC 1-6 -Alkylene-OC 1-6 -Alkyl, -OC 1-6 -Alkylene-NH 2 , -OC 1-6 -Alkylene-NH-C 1-6 -Alkyl, -OC 1-6 -Alkylene-N(C 1-6 -alkyl) 2 , -OC(=O)-C 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-C 1-6 -Alkyl, -OC(=O)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-OC 1-6 -Alkyl, -OC(=O)-NH(C 1-6 -alkyl), -C 1-6 -Alkylene-OC(=O)-NH(C 1-6 -alkyl), -OC(=O)-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OC(=O)-N(C1-6 -alkyl) 2 , -OS(=O) 2 -NH 2 , -C 1-6 -Alkylene-OS(=O) 2 -NH 2 , -OS(=O) 2 -NH(C 1-6 -alkyl), -C 1-6 -Alkylene-OS(=O) 2 -NH(C 1-6 -alkyl), -OS(=O) 2 -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-OS(=O) 2 -N(C 1-6 -alkyl) 2 , -NH 2 , -NO, -NO 2 , -C 1-6 -Alkylene-NH 2 , -NH(C 1-6 -alkyl), -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)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-C(=O)-OC 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 , -C1-6 -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)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-C(=O)-OC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-S(=O) 2 -OC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-S(=O) 2 -OC 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(C1-6 -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 , -SC 1-6 -Alkyl, -C 1-6 -Alkylene-SC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-S(=O) 2 -OC 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 , -C1-6 -Alkylene-S(=O) 2 -N(C 1-6 -alkyl) 2 , 3-14 membered cycloalkyl, -C 1-6 -Alkylene-(3- to 14-membered cycloalkyl), 3- to 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 to 14 membered cycloalkyl), -S(=O) 2 -(3-14 membered heterocycloalkyl), -S(=O) 2 -phenyl, or -S(=O) 2 -(5- to 14-membered heteroaryl), preferably this term means, at each occurrence, 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-NH-C 1-6 -Alkylene-CF 3 , -C 1-6 -Arki Ren-N(C 1-6 -alkyl)-C 1-6 -Alkylene-CF3 , -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)OC 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 , -OH, -C 1-6 -Alkylene-OH, =O, -OCF 3 , -OCF 2 H, -OCFH 2 , -OCF 2 Cl, -OCFCl 2 , -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -OC(=O)-C 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-C 1-6 -Alkyl, -OC(=O)-NH(C 1-6 -alkyl), -NH 2 , -NO, -NO 2 , -C 1-6 -Alkylene-NH 2 , -NH(C 1-6 -alkyl), -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)-C1-6 -Alkyl, -C 1-6 -Alkylene-NH-C(=O)-C 1-6 -Alkyl, -NH-C(=O)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-C(=O)-OC 1-6 -Alkyl, -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)-OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-C(=O)-OC 1-6 -Alkyl, -N(C 1-6 -alkyl)-C(=O)-NH 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-NH-S(=O) 2 -OC 1-6 -Alkyl, -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(C1-6 -alkyl)-S(=O) 2 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-S(=O) 2 -OC 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 , -SC 1-6 -Alkyl, -C 1-6 -Alkylene-SC 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 -OC 1-6 -Alkyl, -C 1-6-Alkylene-S(=O) 2 -OC 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- to 14-membered cycloalkyl), 3- to 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), -S(=O) 2 -(3 to 14 membered cycloalkyl), -S(=O) 2 -(3-14 membered heterocycloalkyl), -S(=O) 2 -phenyl, or -S(=O) 2 -(5- to 14-membered heteroaryl), preferably this term means, at each occurrence, 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 , -C1-6 -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)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)OC 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 , -OH, -C 1-6 -Alkylene-OH, =O, -OCF 3 , -OCF 2 H, -OCFH 2 , -OCF 2 Cl, -OCFCl 2 , -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -OC(=O)-C 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-C 1-6 -Alkyl, -OC(=O)-NH(C 1-6 -alkyl), -NH 2 , -NO, -NO 2 , -C 1-6-Alkylene-NH 2 , -NH(C 1-6 -alkyl), -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, -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, -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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-N(C 1-6 -alkyl)-S(=O) 2 -OC 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, -SC 1-6 -Alkyl, -C 1-6 -Alkylene-SC 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 -OC 1-6 -Alkyl, -C 1-6 -Alkylene-S(=O) 2 -OC 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- to 14-membered cycloalkyl), 3- to 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, -S(=O) 2 -(3 to 14 membered cycloalkyl), -S(=O) 2 -(3-14 membered heterocycloalkyl), -S(=O) 2 -phenyl, or -S(=O) 2 -(5- to 14-membered heteroaryl), preferably this term means, at each occurrence, 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-NH-C 1-6 -Alkylene-CF 3 , -C 1-6 -Alkylene-N(C 1-6 -alkyl)-C 1-6 -Alkylene-CF 3 , -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)OC 1-6 -Alkylene-CF 3 , -C(=O)-NH 2 , -C 1-6 -Alkylene-C(=O)-NH 2 , -C(=O)-NH(C 1-6 -alkyl), -C1-6 -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 , -OH, -C 1-6 -Alkylene-OH, =O, -OCF 3 , -OCF 2 H, -OCFH 2 , -OCF 2 Cl, -OCFCl 2 , -OC 1-6 -Alkyl, -C 1-6 -Alkylene-OC 1-6 -Alkyl, -OC(=O)-C 1-6 -Alkyl, -C 1-6 -Alkylene-OC(=O)-C 1-6 -Alkyl, -OC(=O)-NH(C 1-6 -alkyl), -NH 2 , -NO 2 , -C 1-6 -Alkylene-NH 2 , -NH(C 1-6 -alkyl), -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, -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)-S(=O) 2 -C 1-6 -Alkyl, -N(C 1-6 -alkyl)-S(=O)2 -OC 1-6 -Alkyl, -SH, -SC 1-6 -Alkyl, -C 1-6 -Alkylene-SC 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 -OC 1-6 -Alkyl, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3 to 12 membered cycloalkyl, -C 1-6 -Alkylene-(3- to 12-membered cycloalkyl), 3- to 12-membered heterocycloalkyl, -C 1-6 -Alkylene-(3-12 membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5-12 membered heteroaryl, -C 1-6 -alkylene-(5- to 12-membered heteroaryl), preferably this term means, at each occurrence, 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-NH-C 1-6 -Alkylene-CF3 , -C(=O)OH, -C 1-6 -Alkylene-C(=O)-OH, -C(=O)-OC 1-6 -Alkyl, -C(=O)OC 1-6 -Alkylene-CF 3 , -C(=O)-NH 2 , -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 , -OH, -C 1-6 -Alkylene-OH, =O, -OCF 3 , -OCF 2 H, -OCFH 2 , -OCF 2 Cl, -OCFCl 2 , -OC 1-6 -Alkyl, -OC(=O)-C 1-6 -Alkyl, -OC(=O)-NH(C 1-6 -alkyl), -NH 2 , -NO 2 , -C 1-6 -Alkylene-NH 2 , -NH(C 1-6 -alkyl), -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 , -N(C 1-6 -alkyl)-S(=O) 2 -C 1-6 -Alkyl, -N(C 1-6 -alkyl)-S(=O) 2 -OC 1-6 -Alkyl, -SH, -SC 1-6 -Alkyl, -S(=O) 2 -C 1-6 -Alkyl, -S(=O) 2 -OH, -S(=O) 2 -OC 1-6-Alkyl, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3 to 12 membered cycloalkyl, -C 1-6 -Alkylene-(3- to 12-membered cycloalkyl), 3- to 12-membered heterocycloalkyl, -C 1-6 -Alkylene-(3-12 membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5-12 membered heteroaryl, -C 1-6 -alkylene-(5- to 12-membered heteroaryl), preferably this term means, at each occurrence, independently, -F, -Cl, -Br, -I, -CN, -C 1-5 -Alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-5 -Alkylene-CF 3 , -C 1-5 -Alkylene-NH-C 1-5 -Alkylene-CF 3 , -C(=O)OH, -C 1-5 -Alkylene-C(=O)-OH, -C(=O)-OC 1-5 -Alkyl, -C(=O)-NH 2 , -C(=O)-NH(C 1-5 -alkyl), C(=O)-N(C 1-5 -alkyl) 2 , -OH, -C 1-5 -Alkylene-OH, =O, -OCF 3 , -OCF 2 H, -OCFH 2 , -OCF 2 Cl, -OCFCl 2 , -OC 1-5 -Alkyl, -OC(=O)-C 1-5 -Alkyl, -OC(=O)-NH(C 1-6 -alkyl), -NH2 , -NO 2 , -C 1-5 -Alkylene-NH 2 , -NH(C 1-5 -alkyl), -C 1-5 -Alkylene-NH(C 1-5 -alkyl), -N(C 1-5 -alkyl) 2 , -C 1-5 -Alkylene-N(C 1-5 -alkyl) 2 , -N(C 1-5 -alkyl)-S(=O) 2 -C 1-5 -Alkyl, -N(C 1-5 -alkyl)-S(=O) 2 -OC 1-5 -Alkyl, -SH, -SC 1-5 Alkyl, -S(=O) 2 -C 1-5 Alkyl, -S(=O) 2 -OH, -S(=O) 2 -OC 1-6 -Alkyl, -S(=O) 2 -NH 2 , -S(=O) 2 -NH(C 1-6 -alkyl), -S(=O) 2 -N(C 1-6 -alkyl) 2 , 3 to 10 membered cycloalkyl, -C 1-5 -alkylene-(3- to 10-membered cycloalkyl), 3- to 10-membered heterocycloalkyl, -C 1-5 -Alkylene-(3 to 10 membered heterocycloalkyl), -phenyl, -C 1-5 -alkylene-phenyl, 5-10 membered heteroaryl, -C 1-5 -alkylene-(5-10 membered heteroaryl) is substituted with one or more substituents independently selected from the group consisting of aryl, aryl, aryl and heteroaryl.

[0112] In a preferred embodiment of the invention, the benzofuran derivative is selected from the group consisting of: Compound 001-(2S)-2-{[5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 00 2-(2S)-2-({5-[(2,2-difluorocyclopropyl)methoxy]-2-methyl-1-benzofuran-3-yl}formamide)-3-hydroxypropanamide, Compound 00 3-(2S)-2-[(5-{[1-(difluoromethyl)cyclopropyl]methoxy}-2-methyl-1-benzofuran-3-yl)formamide]-3-hydroxypropanamide, Compound 00 4-(2S)-2-{[2-cyclopropyl-5-(cyclopropylmethoxy)-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 00 5-(2S)-2-{[5-(2-cyclopropylethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 006-(2S)-2-{[5-(cyclobutylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 007-(2S)-2-{[5-(cyclobutylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}propanamide, Compound 008-(2S)-2-{[5-(cyclopropylmethoxy)-2-(difluoromethyl)-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 009-(2R)-2-{[5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 010-(2S)-2-{[5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}propanamide, Compound 011-(2S,3R)-2-[(5-{[1-(difluoromethyl)cyclopropyl]methoxy}-2-methyl-1-benzofuran-3-yl)formamide]-3-hydroxybutanamide, Compound 01 2-(2S,3R)-2-{[5-(2-cyclopropylethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxybutanamide, Compound 013-2-({5-[(2,2-difluorocyclopentyl)methoxy]-2-methyl-1-benzofuran-3-yl}formamide)-3-hydroxypropanamide, Compound 014-2-[(5-{[1-(difluoromethyl)cyclopropyl]methoxy}-2-methyl-1-benzofuran-3-yl)formamide]-3-hydroxy-2-methylpropanamide, Compound 015-2-{[5-(cyclobutylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-2-methylpropanamide, Compound 016-2-{[5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-2-methylpropanamide, Compound 017-2-{[5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 018-5-(cyclobutylmethoxy)-N-(1,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 019-5-(cyclobutylmethoxy)-N-(3,3-difluoropiperidin-4-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 020-5-(cyclohexylmethoxy)-2-methyl-N-(1-methylpiperidin-4-yl)-1-benzofuran-3-carboxamide, Compound 021-5-(cyclopropylmethoxy)-2-methyl-N-(1-methylpiperidin-4-yl)-1-benzofuran-3-carboxamide, Compound 022-5-(cyclopropylmethoxy)-2-methyl-N-(oxan-4-yl)-1-benzofuran-3-carboxamide, Compound 023-5-(cyclopropylmethoxy)-N-(1,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 024-5-(cyclopropylmethoxy)-N-(3,3-difluoropiperidin-4-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 025-5-(cyclopropylmethoxy)-N-[1-(hydroxymethyl)cyclobutyl]-2-methyl-1-benzofuran-3-carboxamide, Compound 026-5-(cyclopropylmethoxy)-N-[1-(hydroxymethyl)cyclopropyl]-2-methyl-1-benzofuran-3-carboxamide, Compound 027-5-(cyclopropylmethoxy)-N-[3-(hydroxymethyl)-2-oxopiperidin-3-yl]-2-methyl-1-benzofuran-3-carboxamide, Compound 028-5-(cyclopropylmethoxy)-N-[3-(hydroxymethyl)-2-oxopyrrolidin-3-yl]-2-methyl-1-benzofuran-3-carboxamide, Compound 029-5-(cyclopropylmethoxy)-N-[3-(hydroxymethyl)oxetan-3-yl]-2-methyl-1-benzofuran-3-carboxamide, Compound 030-5-(cyclopropylmethoxy)-N-[4-(hydroxymethyl)oxan-4-yl]-2-methyl-1-benzofuran-3-carboxamide, Compound 031-5-[(2,2-difluorocyclopropyl)methoxy]-N-(3,3-difluoropiperidin-4-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 032-N-(3,3-difluoropiperidin-4-yl)-2-methyl-5-[(1-methylcyclopropyl)methoxy]-1-benzofuran-3-carboxamide, Compound 033-N-(3,3-difluoropiperidin-4-yl)-5-[(2,2-dimethylcyclopropyl)methoxy]-2-methyl-1-benzofuran-3-carboxamide, Compound 034-N-(3-carbamoyloxetan-3-yl)-5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 035-N-(3-carbamoyloxolan-3-yl)-5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 036-N-(3-carbamoyloxolan-3-yl)-5-{[1-(difluoromethyl)cyclopropyl]methoxy}-2-methyl-1-benzofuran-3-carboxamide, Compound 037-N-(4-carbamoylxan-4-yl)-5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 038-(2S)-2-{[5-(2,2-difluoroethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 039-(2S)-2-{[5-(2,2-dimethylpropoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 040-(2S,3R)-2-{[5-(2,2-difluoroethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxybutanamide, Compound 041-2-{[5-(2,2-difluoroethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 042-N-(3,3-difluoropiperidin-4-yl)-2-methyl-5-(2-methylpropoxy)-1-benzofuran-3-carboxamide, Compound 043-N-(3,3-difluoropiperidin-4-yl)-5-(2,2-dimethylpropoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 044-N-(3-carbamoyloxolan-3-yl)-5-(2,2-difluoroethoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 045-2-{[5-(cyclopropylmethoxy)-6-fluoro-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 046-5-(cyclopropylmethoxy)-N-(4,4-difluoro-1-hydroxy-2-methylbutan-2-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 047-3-hydroxy-2-methyl-2-{[2-methyl-5-(2,2,2-trifluoroethoxy)-1-benzofuran-3-yl]formamido}propenamide, Compound 048-3-hydroxy-2-methyl-2-[(2-methyl-5-{[1-(trifluoromethyl)cyclopropyl]methoxy}-1-benzofuran-3-yl)formamido]propenamide, Compound 049-2-({5-[(2,2-dimethylcyclopropyl)methoxy]-2-methyl-1-benzofuran-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 050-cis-2-{[5-({bicyclo[3.1.0]hexan-3-yl}methoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 051-trans-2-{[5-({bicyclo[3.1.0]hexan-3-yl}methoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 052-3-hydroxy-2-methyl-2-{[2-methyl-5-({3-methylbicyclo[1.1.1]pentan-1-yl}methoxy)-1-benzofuran-3-yl]formamido}propenamide, Compound 053-2-{[5-(cyclobutylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 054-2-({5-[(3,3-difluorocyclobutyl)methoxy]-2-methyl-1-benzofuran-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 055-5-(cyclopropylmethoxy)-2-methyl-N-(2-oxopiperidin-3-yl)-1-benzofuran-3-carboxamide, Compound 056-N-[(2)-3-amino-4,4,4-trifluoro-1-hydroxybutan-2-yl]-5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 057-5-[(2,2-difluorocyclopropyl)methoxy]-2-methyl-N-(4,4,4-trifluoro-1-hydroxybutan-2-yl)-1-benzofuran-3-carboxamide, Compound 058-cis-3-hydroxy-2-methyl-2-({2-methyl-5-[(3-methylcyclobutyl)methoxy]-1-benzofuran-3-yl}formamido)propenamide, Compound 059-trans-3-hydroxy-2-methyl-2-({2-methyl-5-[(3-methylcyclobutyl)methoxy]-1-benzofuran-3-yl}formamido)propenamide, Compound 060-N-(1-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-{[1-(trifluoromethyl)cyclopropyl]methoxy}-1-benzofuran-3-carboxamide, Compound 061-2-methyl-N-(3-methyl-2-oxopiperidin-3-yl)-5-{[1-(trifluoromethyl)cyclopropyl]methoxy}-1-benzofuran-3-carboxamide, Compound 062-2-{[5-(cyclopentylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, and physiologically acceptable salts thereof.

[0113] The present invention also includes pharmaceutical compositions comprising at least one compound of the present invention.The present invention also includes pharmaceutical compositions comprising at least one compound of the present invention and at least one carrier, excipient or diluent acceptable for pharmaceutical purposes.

[0114] In some embodiments, the present invention relates to the use of at least one compound of formula (I), or any subgroup thereof, in (the preparation of a composition for) the prevention and / or treatment of pain or epilepsy, preferably pain or epileptic encephalopathy.

[0115] In some embodiments, the present invention relates to a method for the prevention and / or treatment of metabolic pain, wherein the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain, preferably post-operative pain.

[0116] Preferred substituents include Q, T, U, W, R 1 , R 3 , R 4 , R 5 , R 5 ', n, R 6 , R 7 , R 8 All definitions, preferred embodiments and preferred meanings of apply equally to the benzofuran derivatives according to the invention, but they are not necessarily limited to use in the treatment of pain or epilepsy. Thus, this aspect of the invention relates to benzofuran derivatives per se, compositions comprising benzofuran derivatives, medicaments comprising benzofuran derivatives, and benzofuran derivatives for use in the prevention and / or treatment of TRPM3-mediated disorders, such as pain, epilepsy and / or inflammatory hypersensitivity, and / or for combating pain, epilepsy and / or inflammatory hypersensitivity. Preferably, the pain is selected from nociceptive pain, inflammatory pain and neuropathic pain. More preferably, the pain is postoperative pain.

[0117] In a preferred embodiment of the present invention, the benzofuran derivative is selected from the group consisting of the above-mentioned compounds 001 to 044 and physiologically acceptable salts thereof. In a preferred embodiment of the present invention, the benzofuran derivative is selected from the group consisting of the above-mentioned compounds 001 to 062 and physiologically acceptable salts thereof.

[0118] Another aspect of the present invention relates to a pharmaceutical composition or medicament comprising a benzofuran derivative according to the present invention as described above.

[0119] The benzofuran derivatives of the invention have been shown to be antagonists of TRPM3 and therefore the invention provides the compounds per se for use as pharmaceuticals, more particularly for use as pharmaceuticals in the prevention or treatment of TRPM3-mediated disorders in a subject having a therapeutically effective amount of a benzofuran derivative of the invention.

[0120] In a preferred embodiment of the invention, the benzofuran derivative of the invention is the only pharmacologically active compound administered for treatment. In another preferred embodiment of the invention, the benzofuran derivative of the invention may be used in combination with other therapeutic agents for the treatment or prevention of TRPM3-mediated disorders. Thus, the invention also relates to - one or more compounds of the formulae and embodiments herein, and - 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.

[0121] The pharmaceutical composition or combined preparation according to the present invention may contain the benzofuran derivative of the present invention over a wide range of contents, depending on the intended use and the expected effect of the preparation. In general, the content of the benzofuran derivative of the present invention in the combined preparation is in the range of 0.1-99.9% by weight, preferably 1-99% by weight, more preferably 5-95% by weight.

[0122] Taking into account the fact that when several active ingredients are used in combination, they do not necessarily exert their joint therapeutic effect directly at the same time in the treated mammal, the corresponding composition can also be in the form of a medical kit or package containing the two ingredients in separate but adjacent containers or compartments.In the latter context, each active ingredient can therefore be formulated in a manner suitable for a route of administration different from that of the other ingredient, for example, one of them can be in the form of an oral or parenteral preparation, whereas the other can be in the form of an ampoule or aerosol for intravenous injection.

[0123] Those skilled in the art will also recognize that the benzofuran derivatives of the present invention can exist in many different protonation states, depending, inter alia, on the pH of their environment. Although the structural formulae provided herein show the compounds in only one of several possible protonation states, it will be understood that these structures are exemplary and that the present invention is not limited to any particular protonation state, and that any and all protonated forms of the compounds are intended to fall within the scope of the present invention.

[0124] The term "pharmaceutically acceptable salts" as used herein refers to the therapeutically active non-toxic salt forms that the compounds of the formulae herein can form. Thus, the compounds of the present invention may optionally be used as salts of the compounds herein, particularly, for example, Na. + , Li + , K + , Ca 2+ , and Mg 2+Such salts may include those derived from suitable cations, such as alkali and alkaline earth metal ions, or ammonium and quaternary amino ions, in combination with an acidic anion moiety, typically a carboxylic acid. The benzofuran derivatives of the present invention may have multiple positive or negative charges. The net charge of the benzofuran derivatives of the present invention may be either positive or negative. Any associated counter ions are typically determined by the synthesis and / or isolation methods by which the compounds are obtained. Exemplary counter ions include, but are not limited to, ammonium, sodium, potassium, lithium, halides, acetates, trifluoroacetates, and the like, and mixtures thereof. It will be understood that the identity of any associated counter ion is not a critical feature of the present invention, and the present invention encompasses compounds associated with any type of counter ion. Furthermore, since the compounds may exist in a variety of different forms, the present invention is intended to encompass not only forms of the compounds associated with a counter ion (e.g., dry salts), but also forms not associated with a counter ion (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 this manner are Li + , Na + , and K +The less soluble metal salts may be precipitated from the solution of a more soluble salt by the addition of a suitable metal compound. In addition, salts may be formed from the acid addition of certain organic and inorganic acids to a basic center, typically an amine, or to an acidic group. Examples of such suitable acids include inorganic acids such as hydrohalogen acids, e.g., hydrochloric or hydrobromic acids, sulfuric acid, nitric acid, phosphoric acid, or organic acids such as, e.g., 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 (i.e., 2-hydroxybenzoic) acid, p-aminosalicylic acid, and the like. Furthermore, the term also includes solvates, such as hydrates, alcoholates, etc., which the compounds of the formulae herein as well as their salts are able to form. Finally, it is to be understood that the compositions herein include the benzofuran derivatives of the present invention in their non-ionized form, as well as in their zwitterionic form and, in the case of hydrates, in combination with a stoichiometric amount of water.

[0125] Also included within the scope of the invention are salts of the parent compounds with one or more amino acids, particularly the naturally occurring amino acids found as protein components. The amino acids are typically those having side chains with basic or acidic groups, e.g., lysine, arginine, or glutamic acid, or neutral groups, such as glycine, serine, threonine, alanine, isoleucine, or leucine.

[0126] The benzofuran derivatives of the present invention also include physiologically acceptable salts thereof. Examples of physiologically acceptable salts of the benzofuran derivatives of the present invention include alkali metal (e.g., sodium), alkaline earth (e.g., magnesium), ammonium and NX4. + (Wherein, X is -C 1-6Physiologically acceptable salts of hydrogen atoms or amino groups include salts of 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 inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid, and sulfamic acid. Physiologically acceptable salts of compounds containing hydroxy groups include salts of Na + and NX4 + (wherein X is typically independently -H or -C 1-4 -alkyl groups). However, salts of acids and bases which are not physiologically acceptable may also find use, for example, in the preparation or purification of a physiologically acceptable compound. All salts are within the scope of the present invention, whether or not they form a physiologically acceptable acid or base.

[0127] As used herein, and unless otherwise specified, the term "enantiomer" means each individual optically active form of a benzofuran derivative of the present invention having an optical purity or enantiomeric excess (as determined by standard methods in the art) 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%.

[0128] The term "isomer" as used herein refers to all possible isomeric forms, including tautomeric and stereochemical forms, that a compound of the formula herein may have, but does not include positional isomers. Typically, the structures shown herein only exemplify one tautomeric or resonance form of a compound, but the corresponding alternative configurations are contemplated as well. Unless otherwise indicated, the chemical names of the compounds refer to a mixture of all possible stereochemically isomeric forms, which mixtures include all diastereomers and enantiomers of basic molecular structures (since the compounds of the formula herein may have at least one chiral center), as well as stereochemically pure or enriched compounds. More specifically, the stereocenters may have either the R or S configuration, and the bonds may have either the cis or trans configuration.

[0129] 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. In particular, the term "stereoisomerically pure" or "chirally pure" refers to a compound having a stereoisomeric excess of at least about 80% (i.e., at least 90% of one isomer and at most 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 "diastereoselectively pure" should be understood in a similar manner, taking into account the enantiomeric excess, respectively the diastereomeric excess, of the mixture in question.

[0130] Separation of stereoisomers is accomplished by standard methods known to those skilled in the art. One enantiomer of the benzofuran derivative of the present invention can be separated substantially free of its opposite enantiomer by methods such as the formation of diastereomers using optically active resolving agents ("Stereochemistry of Carbon Compounds," (1962) by EL Eliel, McGraw Hill, Lochmuller, CH, (1975) J. Chromatogr., 113:(3) 283-302). Separation of isomers in a mixture can be accomplished by any suitable method, including (1) formation of ionic diastereomeric salts with chiral compounds and separation by fractional crystallization or other methods, (2) formation of diastereomeric compounds with chiral derivatizing agents, separation of the diastereomers, and conversion to pure enantiomers, or (3) enantiomers can be directly separated under chiral conditions. In method (1), diastereomeric salts can be formed by reaction of enantiomerically pure chiral bases, such as brucine, quinine, ephedrine, strychnine, a-methyl-b-phenylethylamine (amphetamine), with asymmetric compounds having acidic functionality, such as carboxylic and sulfonic acids. The diastereomeric salts can be induced to separate by fractional crystallization or ionic chromatography. For the separation of optical isomers of amino compounds, the addition of chiral carboxylic or sulfonic acids, such as camphorsulfonic acid, tartaric acid, mandelic acid, or lactic acid, can result in the formation of diastereomeric salts. Alternatively, by method (2), the substrate to be resolved can 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 reaction of the asymmetric compounds with enantiomerically pure chiral derivatizing agents, such as menthyl derivatives, followed by separation and hydrolysis of the diastereomers to give the free enantiomerically enriched compounds.A method for determining the optical purity involves making a chiral ester of the racemic mixture, for example the menthyl ester or Mosher ester, a-methoxy-a-(trifluoromethyl)phenylacetate (Jacob III. (1982) J. Org. Chem. 47:4165), and analyzing the NMR spectrum for the presence of the two atropisomeric diastereomers. The stable diastereomers can be separated and isolated by normal and reverse phase chromatography, following methods for the separation of atropisomeric naphthyl-isoquinolines (Hoye, T., WO 96 / 15111). Under method (3), the racemic mixture of the two asymmetric enantiomers is separated by chromatography using a chiral stationary phase. Suitable chiral stationary phases are, for example, polysaccharides, in particular 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 polysaccharides include hexane, modified with alcohols such as ethanol, isopropanol, etc. ("Chiral Liquid Chromatography" (1989) WJ 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).

[0131] The terms cis and trans are used herein in accordance with chemical information retrieval nomenclature and include reference to the position of substituents on a cyclic moiety. The absolute stereochemical configuration of compounds of the formulae described herein can be readily determined by one skilled in the art using well-known methods such as, for example, X-ray diffraction.

[0132] When a compound is crystallized from a solution or slurry, it can crystallize in different spatial lattice arrangements (this property is called "polymorphism") and form crystals with different crystal forms, each of which is known as a "polymorph". Thus, the term "polymorph" as used herein refers to a crystalline form of a compound of formula (I) in which the molecules are localized in three-dimensional lattice sites. Different polymorphs of a 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 morphology, accumulation mode, flowability, and / or solid-state stability.

[0133] The benzofuran derivatives of the present invention and their physiologically acceptable salts (hereinafter collectively referred to as the active ingredients) may be administered by any route appropriate to the condition to be treated, suitable routes including oral, rectal, nasal, topical (including ophthalmic, buccal, and sublingual), vaginal, and parenteral (including subcutaneous, intramuscular, intranasal, intravenous, intraarterial, intradermal, intrathecal, and epidural). The preferred route of administration may vary, for example, depending on the condition of the recipient.

[0134] In particular, a therapeutically effective amount of a compound(s) preparation for the treatment of TRPM3-mediated disorders in humans and other mammals or animals is preferably a TRPM3 ion channel inhibiting amount of a compound as defined herein, corresponding to an amount ensuring a plasma level of between 1 μg / ml and 100 mg / ml, optionally 10 mg / ml.

[0135] A suitable dose of the compound or composition of the present invention should be used to treat or prevent TRPM3-mediated disorders in a subject. Depending on the pathological condition to be treated and the condition of the patient, the effective amount can be divided into several subunits per day or administered at intervals of more than one day.

[0136] The present invention further provides (pharmaceutical) compositions comprising one or more benzofuran derivatives of the present invention, more particularly all of formula (I) and other formulas and embodiments described herein, and their more specific aspects or embodiments.The present invention further provides compounds or (pharmaceutical) compositions of the present invention, more particularly all of formula (I) and other formulas and embodiments described herein, and their more specific aspects or embodiments, for use as a medicament, more particularly for use in treating pain or epilepsy.The TRPM3-mediated disorder is selected from pain, epilepsy, and inflammatory hypersensitivity conditions.

[0137] The benzofuran derivatives of the present invention may be formulated with conventional carriers and excipients, which are selected according to normal practice. Tablets contain excipients, flow agents, fillers, binders, etc. Aqueous formulations are prepared in sterile form and will generally be isotonic if intended for delivery by other than oral administration. The formulations optionally contain excipients such as those described in the "Handbook of Pharmaceutical Excipients" (1986).

[0138] The term "pharmaceutical acceptable carrier" as used herein thereafter means any material or substance in which an active ingredient is formulated, for example, to facilitate its application or dissemination to the locus to be treated, by dissolving, dispersing, or diffusing the composition, and / or to facilitate its storage, transport, or handling without compromising its effectiveness. A pharmaceutical acceptable carrier can be a solid or liquid, or a gas compressed to form a liquid, i.e., the composition of the present invention can be suitably used as a concentrate, emulsion, solution, granule, dust, spray, aerosol, suspension, ointment, cream, tablet, pellet, or powder.

[0139] Suitable pharmaceutical carriers for use in the pharmaceutical compositions and their formulations are well known to those skilled in the art, and there is no particular restriction on their selection within the present invention. They may also include additives such as wetting agents, dispersants, stickers, adhesives, emulsifiers, surfactants, solvents, coatings, antibacterial and antifungal agents, isotonic agents, etc., provided that the same are consistent 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 active ingredient with the selected carrier material, and, if necessary, other additives such as surfactants, in a one-step or multi-step procedure. They may also be prepared by micronization, for example, for the manufacture of microcapsules for the controlled or sustained release of active ingredients, to obtain them in the form of microspheres, usually with a diameter of about 1 to 10 gm.

[0140] While it is possible for the benzofuran derivatives to be administered alone, it is preferred to present them as pharmaceutical formulations. Both veterinary and human formulations of the present invention contain at least one active ingredient, as described above, therefore together with one or more pharma- ceutically acceptable carriers, and optionally other therapeutic ingredients. The carrier(s) are optimally "acceptable" in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. 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 may conveniently be presented in unit dosage form and may be prepared by any of the methods well known in the art of pharmacy. Such methods include the step of bringing the active ingredient into association with the 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 liquid carriers, or finely divided solid carriers, or both, and then, if necessary, shaping the product.

[0141] Formulations of the present invention suitable for oral administration may each be presented as discrete units (such as a capsule, cachet, or tablet containing a predetermined amount of the active ingredient), as a powder or granules, as a solution or suspension in an aqueous liquid or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion. The active ingredient may also be presented as a bolus, electuary, or paste.

[0142] Tablets can be manufactured by compression or molding, optionally with one or more accessory ingredients. Compressed tablets can be prepared by compressing the active ingredient in a free-flowing form, such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface active agent, or dispersant, in a suitable machine. Molded tablets can be made by molding a mixture of the powdered compound moistened with an inert liquid diluent in a suitable machine. Tablets can be optionally coated or scored, and can be formulated to provide slow or controlled release of the active ingredient therein. For infections of the eye or other external tissues, e.g., mouth and skin, formulations are optionally applied as a topical ointment or cream containing the active ingredient(s) in an amount, for example, of 0.075-20 w / w% (with active ingredient(s) ranging from 0.1% to 20% in increments of 0.1 w / w%, such as 0.6 w / w%, 0.7 w / w%, etc.), preferably 0.2-15 w / w%, most preferably 0.5-10 w / w%. When formulated in an ointment, the active ingredient may be employed with either a paraffinic or a water-miscible ointment base. Alternatively, the active ingredient may be formulated in a cream with an oil-in-water cream base. If desired, the aqueous phase of the cream base may contain, for example, at least 30 w / w% polyhydric alcohol, i.e., alcohols having two or more hydroxyl groups, such as propylene glycol, butane 1,3-diol, mannitol, sorbitol, glycerol, and polyethylene glycol (including PEG 400), and mixtures thereof. It may be desirable for topical formulations to include compounds that enhance absorption or penetration of the active ingredient through the skin or other affected areas. Examples of such skin penetration enhancers include dimethyl sulfoxide and related analogues.

[0143] The oily phase of the emulsion of the present invention can be composed of known ingredients in a known manner. The phase can simply comprise an emulsifier (also known as a diuretic), but desirably comprises a mixture of at least one emulsifier with a fat or oil, or 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 include both an oil and a fat. Together, the emulsifier(s), with or without stabilizer(s), constitute the so-called emulsifying wax, which, together with the oil and fat, constitutes the so-called emulsifying ointment base that forms the oily dispersed phase of the cream formulation.

[0144] The selection of suitable oils or fats for the formulation is based on achieving the desired cosmetic properties, since the solubility of the active compounds in most oils likely to be used in pharmaceutical emulsion formulations is very low. The cream should therefore be a non-greasy, non-staining and washable product, optionally with a suitable consistency to avoid leakage from tubes or other containers. Linear or branched, mono- or dibasic alkyl esters such as diisoadipate of coconut fatty acid, isocetyl stearate, propylene glycol diester, isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate, 2-ethylhexyl palmitate, or a blend of branched esters known as Crodamol CAP may be used, the last three being the preferred esters. These may be used alone or in combination, depending on the properties required. Alternatively, high melting point lipids such as white soft paraffin and / or liquid paraffin or other mineral oils may be used.

[0145] 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, especially an aqueous solvent for the active ingredient. The active ingredient is optionally present in such formulations in a concentration of 0.5 to 20%, advantageously 0.5 to 10%, especially about 1.5 w / w%. Formulations suitable for topical administration in the mouth include lozenges containing the active ingredient in a flavored base, usually sucrose and acacia or tragacanth, pastilles 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.

[0146] Formulations for rectal administration may be presented as a suppository with a suitable base including, for example, cocoa butter or a salicylate. Suitable formulations for nasal administration where the carrier is a solid include coarse powders, for example having a particle size in the range of 20 to 500 microns (with a particle size in the range of 20 to 500 microns in 5 micron increments such as 30 microns, 35 microns), administered in the manner sniffed, i.e. by rapid inhalation via the nasal passage from a container of the powder held close to the nose. Suitable formulations where the carrier is a liquid include aqueous or oily solutions of the active ingredient, for example, for administration as a nasal spray or as nasal drops. Formulations suitable for aerosol administration may be prepared according to conventional methods and may be delivered with other therapeutic agents.

[0147] Formulations suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams, or spray formulations containing in addition to the active ingredient such carriers as are known in the art to be appropriate.

[0148] Preparations suitable for parenteral administration include aqueous and non-aqueous sterile injection solutions that may contain antioxidants, buffers, bacteriostats, and solutes that render the solution isotonic with the blood of the intended recipient, as well as aqueous and non-aqueous sterile suspensions that may contain suspending agents and thickening agents.The preparations 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) condition, requiring only the addition of a sterile liquid carrier (e.g., water) immediately prior to use.Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules, and tablets of the kind previously described.

[0149] Preferred unit dosage formulations are those containing a daily dose or daily sub-dose, as herein described, or an appropriate fraction thereof, of an active ingredient.

[0150] It will be understood that in addition to the ingredients specifically mentioned above, the formulations of the present invention may include other agents conventional in the art having regard to the type of formulation in question (e.g., those suitable for oral administration may include flavoring agents).

[0151] The benzofuran derivatives of the present invention can be used to provide controlled release pharmaceutical formulations ("controlled release formulations") containing one or more benzofuran derivatives of the present invention as active ingredients, where release of the active ingredient can be controlled and regulated to allow less frequent administration or to improve the pharmacokinetic or toxicity profile of a given compound of the present invention. Controlled release formulations adapted for oral administration in which discrete units contain one or more benzofuran derivatives of the present invention can be prepared according to conventional methods.

[0152] Another embodiment of the present invention relates to various precursor or "prodrug" forms of the benzofuran derivatives of the present invention. It may be desirable to formulate the benzofuran derivatives of the present invention in the form of chemical species that are not themselves significantly biologically active, but that when delivered to an animal, mammal, or human undergo a chemical reaction catalyzed by the normal functions of the body, in particular by enzymes present in the stomach or serum, which has the effect of releasing a compound as defined herein. The term "prodrug" therefore relates to those species that are converted in vivo into the active pharmaceutical moiety.

[0153] The prodrug of the benzofuran derivative of the present invention may have any form suitable for the formulation agent, for example, ester is a non-limiting common prodrug form. However, in this case, the prodrug may necessarily be in a form in which the covalent bond is cleaved by the action of an enzyme present at the target locus. For example, the CC covalent bond may be selectively cleaved by one or more enzymes at the target locus, and therefore prodrugs in forms other than easily hydrolyzable precursors, especially esters, amides, etc., may be used. The counterpart of the active pharmaceutical ingredient in the prodrug may have different structures, such as amino acid or peptide structures, alkyl chains, sugar moieties, etc., known in the art.

[0154] For purposes of the present invention, the term "therapeutically suitable prodrug" is defined herein as "a compound that is modified by one or more biological transformations so that, upon contact with the tissues of an animal, mammal, or human to which the prodrug is administered, it is converted in vivo into a therapeutically active form without undue toxicity, irritation, or allergic response, and which achieves an intended therapeutic outcome."

[0155] More specifically, the term "prodrug" as used herein refers to an inactive or significantly less active derivative of a compound as represented by the structural formula described herein, which undergoes spontaneous or enzymatic conversion reaction in the body to release a pharmacologically active form of the compound. For a comprehensive review, see Rautio J. et al. ("Prodrugs: design and clinical applications" Nature Reviews Drug Discovery, 2008, doi:10.1038 / nrd2468).

[0156] Representative benzofuran derivatives of the present invention can be synthesized according to the general synthetic methods described below and are illustrated in the following schemes. The schemes are illustrative and therefore the 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 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 one of ordinary skill in the art. EXAMPLES

[0157] The following examples are provided to further illustrate the present invention and are not intended to limit the scope of the invention in any way.

[0158] Representative compounds of the present invention can be synthesized according to the general synthetic methods described below and are illustrated in the following schemes. The schemes are illustrative, and therefore 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 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.

[0159] Abbreviations used herein, particularly in the schemes and examples, are as follows: ABC-aqueous solution of ammonium bicarbonate, ACN-acetonitrile, AcOH-acetic acid, ADDP-1,1'-(azodicarbonyl)dipiperidide, aq.-aqueous, AIBN-azobisisobutyronitrile, CAN-ceric 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]undeca-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-dimethylsulfoxide, DTBAD-tert-butyl azodicarboxylate, EDCI or EDC-1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, En-enantiomer, Et 2 O-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, MgSO 4 -Magnesium sulfate, min.-min, Na 2 SO 4 -Sodium sulfate, NBS-N-bromosuccinimide, NMP-1-methyl-2-pyrrolidinone, Pd(PPh 3 ) 4 -Tetrakis-(triphenylphosphine)-palladium(0), Pd 2 (dba) 3-Tris(dibenzylideneacetone)dipalladium, Pet ether -Petroleum ether, PPh3 -Triphenylphosphine, PS-DIEA -Polystyrene supported diisopropyl-ethylamine, PS-PPh3 -Polystyrene supported triphenylphosphine, PyBop -Benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate, PTSA -p-Toluenesulfonic acid, RF:frontier ratio, RM -Reaction mixture, RP -Reversed phase, RT -Room temperature, sat. -Saturated, SEM -[2-(T (trimethylsilyl)ethoxy]methyl acetal, SFC-Supercritical fluid chromatography, SPE-Solid phase extraction, TBDMS-Tert-butyldimethylsilyl, TBAF-Tetrabutylammonium fluoride, TBAI-Tetrabutylammonium iodide, TEA-Triethylamine, THF-Tetrahydrofuran, TFA-Trifluoroacetic acid, TLC-Thin layer chromatography, TPP-Triphenylphosphine, IPA-Isopropyl alcohol, TMS-Trimethylsilyl, T3P-Propylphosphonic anhydride.

[0160] Compounds of interest have a structure according to general formula (I), and all other formulae and embodiments thereof described herein, may be prepared as outlined in general chemical Scheme 1. [ka] Scheme 1: All W, R1, R3, R4, and R5 are as described for the compounds of the present invention.

[0161] Para-benzoquinones of formula 1 can be reacted with ketoesters of formula 2, which are commercially available or synthesized by procedures known to those skilled in the art, where R 2can be condensed with an ester protecting group (e.g., methyl, ethyl, t-Bu, etc.) in the presence of a Lewis acid (e.g., titanium(IV) chloride, zinc(II) chloride, etc.) in a polar solvent (e.g., DCM, MeOH, EtOH, etc.) at a temperature range of 0-100° C. to give an intermediate of formula 4. More detailed information can be found in the following references (Bioorg.Med.Chem.2012,20,4237-4244 and FR1319594). Alternatively, para-benzoquinone of formula 1 can be reacted with enamine of formula 3 (commercially available or synthesized by procedures known to those skilled in the art) in the presence of a protic acid (e.g., trifluoroacetic acid, para-toluenesulfonic acid, etc.) in a polar solvent (e.g., DCM, MeOH, EtOH, etc.) at a temperature range of 0-100° C. to give an intermediate of formula 4. More detailed information can be found in the following reference (J. Heterocyclic Chem. 2006, 43, 873). The intermediate of formula 4 can then be converted via nucleophilic substitution using the intermediate of formula 5 (commercially available or synthesized) in a polar solvent (e.g., acetonitrile, DMF, NMP, etc.) with or without a chelating agent (e.g., 18-crown-6, cis-anti-cis-dicyclohexano-18-crown-6, etc.) at a temperature range of 0-100°C. 2 CO 3The intermediate of formula 4 can be converted to the desired compound of formula 7 (wherein LG is a leaving group) 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 range of 0-100° C. to give the desired compound of formula 7. The ester derivative 7 can then be converted to the desired compound of formula 8 by 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 (either commercially available or synthesized by procedures known in the art or as described in the examples below) 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 Examples below, and then reacted with an amine of formula 9 to give the desired compound of formula 10 by procedures known to those skilled in the art or as described in the Examples below.

[0162] In a more specific embodiment, the compounds of the present invention can be synthesized as shown in Scheme 2. [ka] Scheme 2: All W, R1, R3, R4, and R5 are as described for the compounds of the present invention.

[0163] 5-Hydroxy-benzofuran-3-carboxylic acid derivatives 11 (either commercially available or synthesized by procedures known in the art or as described in the Examples below) can be reacted with amine derivatives of formula 9 (either commercially available or synthesized by procedures known in the art or as described in the Examples below) under standard peptide coupling conditions (e.g. DCC, EDCI, HATU, PyBop, etc.) in polar aprotic solvents (e.g. DCM, DMF, etc.) to give intermediates of formula 12. Alternatively, compounds of formula 13 (synthesized as described in Scheme 1) can be converted to intermediates of formula 12 by 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.). The intermediate of formula 12 can then be synthesized via nucleophilic substitution using the intermediate of formula 5 (commercially available or synthesized) in a polar solvent (e.g., acetonitrile, DMF, NMP, etc.) with or without a chelating agent (e.g., 18-crown-6, cis-anti-cis-dicyclohexano-18-crown-6, etc.) at a temperature range of 0-100 °C. 2 CO 3 Alternatively, the compound of formula 12 can also be reacted with an intermediate of formula 6 (commercially available or synthesized) in the presence of an azodicarboxylate reagent (e.g., DEAD, ADDP, DIAD, tert-butyl azodicarboxylate, etc.) and a phosphine (e.g., tributylphosphine, triphenylphosphine, etc.) in a solvent (e.g., THF, toluene, etc.) at a temperature range of 0-100° C. to give the desired compound of formula 10.

[0164] In a more specific embodiment, the compounds of the present invention can be synthesized as shown in Scheme 3. [ka] Scheme 3: All W, R1, R3, R4, and R5 are as described for the compounds of the present invention.

[0165] The intermediate of formula 4 can be halogenated with a suitable halogenating agent (e.g., bromine, N-bromosuccinimide, etc.) in a solvent (e.g., chloroform, water, etc.) to obtain the desired intermediate 23. The desired compound of formula 26 can be obtained by an Ullmann-type reaction with CuCN followed by a Mitsunobu-type reaction with an intermediate of formula 6 (commercially available or synthesized). Alternatively, the desired compound of formula 26 can be obtained by a Mitsunobu-type reaction with an intermediate of formula 6 (commercially available or synthesized) followed by a Suzuki reaction. The ester derivative 26 can then be converted to the desired compound of formula 27 by a standard saponification reaction. The desired compound of formula 28 can be obtained from the acid derivative of formula 27 by reaction with an amine derivative of formula 9 (commercially available or synthesized by procedures known in the art or as described in the examples below) under standard peptide coupling conditions (e.g., DCC, EDCI, HATU, PyBop, etc.) in a polar aprotic solvent (e.g., DCM, DMF, etc.).

[0166] Working Example [Table 1-1] [Table 1-2] [Table 1-3]

[0167] The above examples are provided for the purpose of illustrating the present invention and should not be construed as limiting the scope of the present invention in any way.

[0168] Part A represents the preparation of the compounds and Part B represents the pharmacological examples.

[0169] Part A All starting materials not explicitly mentioned are either commercially available (details of suppliers such as, for example, ABCR, Apollo Scientific Combi-Blocks, Enamine, FluoroChem, MatrixScientific, Maybridge, Merck, TCI can be found, for example, in the SciFinder® database), or their synthesis is already precisely described in the specialist literature (for example, experimental guidelines can be found in the Reaxys® database or the SciFinder® database, respectively), or can be prepared using conventional methods known to the person skilled in the art.

[0170] Reactions were run under an inert atmosphere (mainly argon and N) if necessary. 2 ) under. The number of equivalents of reagents, the amount of solvent used, and the reaction temperature and time may vary slightly between different reactions carried out by the similar method. The processing and purification methods are adapted according to the characteristic properties of each compound and may vary slightly for the similar method. The yield of the prepared compound is not optimized.

[0171] The designation "equivalent" ("eq." or "eq" or "equiv.") means molar equivalent, "RT" or "rt" means room temperature T (23±7°C), "M" is the designation of concentration in mol / l, "sol." means solution, and "conc." means concentration. Solvent mixture ratios are usually expressed as volume / volume ratios.

[0172] Key analytical characterizations were performed for all exemplary compounds and selected intermediates. 1 H-NMR spectroscopy and / or mass spectrometry (MS, [M+H] + and / or [MH] - In certain cases, e.g., where positional isomers and / or diastereomers can be formed, e.g., 13Additional analyses such as C NMR and NOE (Nuclear Overhauser Effect) NMR experiments were performed in some cases.

[0173] The analytical instruments used were, for example, BRUKER 400MHz or BRUKER 500MHz machines (Software Topspin) for NMR analysis, alternatively, BRUKER AVANCE 300MHz and 400Mhz 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, for example, on Waters (Software Empower), Agilent-1200-ELSD (Software Chemistation) or Agilent-1260 (Software OpenLAB). Analytical SFC was performed, for example, with PIC solution (Software: SFC PICLAB ONLINE), WATERS-X5 (Software MASSLYNX), or WATERS-UPC2 (Empower).

[0174] Preparative HPLC was performed, for example, on a Waters 2998 (Software Empower) or YMC (Software K-Prep). Preparative SFC was performed, for example, on a Waters SFC-200 (Software Chromscope or Super chrome), Waters SFC-80 (Super chrome), or PIC, PIC-175 (Software S10-100).

[0175] Structures of exemplary compounds containing stereocenters are drawn and named with absolute stereochemistry, if known. In case of unknown absolute stereochemistry, the compound can be either racemic, a mixture of diastereomers, a pure diastereomer of unknown stereochemistry, or a pure enantiomer of unknown stereochemistry. Dia1 and Dia2 mean that the diastereomers have been separated but the stereochemistry is unknown. En1 and En2 mean that both enantiomers have been separated but the absolute configuration is unknown. Unless the chemical name of the compound specifies the exact stereochemistry, no suffix after the compound code means that the compound containing a stereocenter was obtained as a racemic mixture or a mixture of diastereomers, respectively.

[0176] The LC / MS analyses mentioned in the experimental part were carried out on an Alliance Waters HPLC (equipped with a PDA detector) connected to a mass spectrometer Waters 3100 mass detector in ESI mode, or on an Acquity UPLC Waters (equipped with a PDA detector) connected to a mass spectrometer mass SQD 2 detector in ESI mode, or on an Acquity UPLC Waters (equipped with a PDA detector) connected to a mass spectrometer mass Xevo TQS detector in ESI mode. Column Acquity BEH (50 mm x 2.1 mm) 1.7 μm was used with mobile phase A of 0.05% formic acid in water or 0.05% TFA in water, and mobile phase B of 0.05% formic acid in MeCN or 0.05% TFA in MeCN. Alternatively, column Xbridge C18 (75 mm x 4.6 mm) 3.5 μm was used with mobile phase A of 5 mM ammonium bicarbonate in water and mobile phase B of MeCN.

[0177] Synthesis of (2S)-2-({5-[(2,2-difluorocyclopropyl)methoxy]-2-methyl-1-benzofuran-3-yl}formamide)-3-hydroxypropanamide (Compound 002). [ka] Step 1: To a stirred solution of 5-hydroxy-2-methylbenzofuran-3-carboxylate (500 mg, 2.3 mmol) and (2,2-difluorocyclopropyl)methanol (343 mg, 3.2 mmol) in THF (20 mL) was added ADDP (801 mg, 3.2 mmol), followed by Bu. 3 P (0.7 mL, 3.181 mmol) was added at 0° C. The RM was stirred at room temperature for 16 h. The progress of the reaction was monitored by TLC. The RM was concentrated, diluted with water (50 mL) and extracted with EtOAc (3×80 mL). The combined extracts were washed with brine (40 mL) and washed with anhydrous Na 2 SO 4 The mixture was dried at 40° C., filtered and concentrated under vacuum to give the crude. The crude was purified by Grace flash chromatography using 10% EtOAc in Pet ether as eluent to give ethyl 5-((2,2-difluorocyclopropyl)methoxy)-2-methylbenzofuran-3-carboxylate (200 mg) as a colorless solid. TLC system: 40% ethyl acetate in pet ether; RF: 0.74.

[0178] Step 2: To a stirred solution of ethyl 5-((2,2-difluorocyclopropyl)methoxy)-2-methylbenzofuran-3-carboxylate (1.0 g, 3.3 mmol) in MeOH and THF (1:1, 40 mL) was added 2N aqueous NaOH (4 mL) at 0° C. The RM was refluxed for 3 h. The progress of the reaction was monitored by TLC. The RM was concentrated, acidified to pH ∼2 with 1N HCl, and extracted with EtOAc (3×50 mL). The combined extracts were washed with brine (30 mL) and washed with anhydrous Na 2 SO 4 Drying at 40° C., filtration and concentration in vacuo afforded 5-((2,2-difluorocyclopropyl)methoxy)-2-methylbenzofuran-3-carboxylic acid (1.0 g) as an off-white solid. The crude was used directly in the next step without further purification. TLC system: 80% EtOAc in pet ether; RF: 0.28.

[0179] Step 3: To a stirred solution of 5-((2,2-difluorocyclopropyl)methoxy)-2-methylbenzofuran-3-carboxylic acid (500 mg, 1.8 mmol) in DCM (30 mL) was added DIPEA (1.2 mL, 7.1 mmol), HATU (943 mg, 2.5 mmol) and (S)-2-amino-3-hydroxypropanamide (350 mg, 2.5 mmol) in DCM dropwise at 0° C. The RM was stirred at room temperature for 16 h and the progress of the reaction was monitored by TLC. The RM was diluted with water (50 mL) and extracted with EtOAc (2×100 mL). The combined organic layers were washed with water (30 mL), brine (20 mL) and washed with anhydrous Na 2 SO 4 The mixture was dried at 40° C., filtered and concentrated to give a crude product. The crude product was purified by preparative HPLC to give (2S)-2-({5-[(2,2-difluorocyclopropyl)methoxy]-2-methyl-1-benzofuran-3-yl}formamide)-3-hydroxypropanamide (compound 002) (130 mg, 25%) as an off-white solid. TLC system: 60% EtOAc per ether; RF: 0.31.

[0180] Preparative chiral SFC was performed on a racemic mixture of compound 002 to give compounds 002-En1 and 002-En2.

[0181] The following compounds were prepared in a similar manner as described for compound 002 (using appropriate reagents (chiral or racemic) and purification methods (including chiral HPLC or chiral SFC) known to those skilled in the art): compound 057-En1, compound 057-En2, compound 057-En3, compound 057-En4.

[0182] Synthesis of (2S)-2-[(5-{[1-(difluoromethyl)cyclopropyl]methoxy}-2-methyl-1-benzofuran-3-yl)formamide]-3-hydroxypropanamide (Compound 003). [ka] Step 1: Cesium carbonate (1.77 g, 5.4 mmol) was added to a stirred solution of ethyl 5-hydro...

Claims

1. Equation (I): 【Chemistry 1】 [During the ceremony, R １ is selected from -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 ; Q is -NR ３ R ４ This represents, R ３ is -OH or -R Ｙ１ This represents, R ４ is, -R Ｙ２ or -S (=O) ２ R Ｙ３ This represents, Alternatively, R ３ and R ４ Together, they 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. T represents -O-, and U represents -(CR ５ R ５ ') ｎ - represents, or T is - (CR ５ R ５ ') ｎ - represents, and U represents -O-, n is an integer selected from 1, 2, 3, 4, or 5. R ５ and R ５ ' are independent of each other, -R Ｙ４ This represents, R ６ , R ７ , and R ８ These are -F, -Cl, -Br, -I, -CN, and -NO, which are independent of each other. 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 This represents, W is Saturated or unaromatically unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl groups, In each case, non-substitutive, mono-substitutive or multi-substitutive, -C １ -C ６ -Alkyl, -C ２ -C ６ -Alkenyl, -C ２ -C ６ - Represents Alkinnil, Here, R Ｗ and R Ｘ They are independent of each other, 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 unaromatically unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl group, wherein the 3- to 14-membered cycloalkyl group is -C １ -C ６ -Alkylene- or -C １ -C ６ -Heteroalkylene- is optionally connected, in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, 3- to 14-membered cycloalkyl, or A saturated or unaromatically unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C １ -C ６ -Alkylene- or -C １ -C ６ -Heteroalkylene- is optionally connected, and in each case, saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, 3 to 14-membered heterocycloalkyl, R Ｙ１ , R Ｙ２ , R Ｙ３ , and R Ｙ４ They are independent of each other, 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 unaromatically unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl group, wherein the 3- to 14-membered cycloalkyl group is -C １ -C ６ -Alkylene- or -C １ -C ６ - Heteroalkylene - is optionally connected, and in each case, saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, 3 to 14-membered cycloalkyl, A saturated or non-aromatic unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-member heterocycloalkyl, wherein the 3- to 14-member heterocycloalkyl is -C １ -C ６ -alkylene- or -C １ -C ６ -heteroalkylene- and is optionally connected through, in each case, a saturated or unsaturated, unsubstituted, mono-substituted or multi-substituted 3- to 14-member heterocycloalkyl Unsubstituted, monosubstituted, or polysubstituted 6- to 14-membered aryls, wherein the 6- to 14-membered aryl is -C １ -C ６ -Alkylene- or -C １ -C ６ -Heteroalkylene- is optionally connected, in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, 6- to 14-membered aryl, A non-replaced, mono-replaced or multi-replaced 5- to 14-member heteroaryl, wherein the 5- to 14-member heteroaryl is -C １ -C ６ -alkylene- or -C １ -C ６ -heteroalkylene- and is optionally connected through, and in each case represents, a saturated or unsaturated, non-replaced, mono-replaced or multi-replaced 5- to 14-member heteroaryl, "Single substitution or multiple substitution" in each case independently refers to -F, -Cl, -Br, -I, -CN, and -C １－６ -Alkyl, -CF ３ , -CF ２ H, -CFH ２ , -CF ２ Cl, -CFCl ２ , -C １－６ -Alkilen-CF ３ , -C １－６ -Alkilen-CF ２ H, -C １－６ -Alkilen-CFH ２ , -C １－６ - Alkilen-NH-C １－６ -Alkilen-CF ３ , -C １－６ -Alkylene-N(C) １－６ -Alkyl)-C １－６ -Alkilen-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 -Alkilen-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 -Alkilen-NH ２ , -O-C １－６ - Alkilen-NH-C １－６ -alkyl, -O-C １－６ -Alkylene-N(C) １－６ -Alkyl) ２ , -OC(=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 -Alkilen-O-S (=O) ２ -NH ２ , -O-S (=O) ２ -NH(C) １－６ -Alkyl), -C １－６ -Alkilen-O-S (=O) ２ -NH(C) １－６ -alkyl), -O-S (=O) ２ -N(C) １－６ -Alkyl) ２ , -C １－６ -Alkilen-O-S (=O) ２ -N(C) １－６ -Alkyl) ２ , -NH ２ , -NO, -NO ２ , -C １－６ -Alkilen-NH ２ ,-NH(C １－６ -Alkyl), -C １－６ -Alkilen-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 -Alkilen-NH-C(=O)-C １－６ -Alkyl, -NH-C(=O)-O-C １－６ -Alkyl, -C １－６ -Alkilen-NH-C(=O)-O-C １－６ -alkyl, -NH-C(=O)-NH ２ , -C １－６ -Alkilen-NH-C(=O)-NH ２ , -NH-C(=O)-NH(C １－６ -Alkyl), -C １－６ -Alkilen-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 -Alkilen-NH-S(=O) ２ OH, -NH-S (=O) ２ -C １－６ -Alkyl, -C １－６ -Alkilen-NH-S(=O) ２ -C １－６ -alkyl, -NH-S (=O) ２ -O-C １－６ -Alkyl, -C １－６ -Alkilen-NH-S(=O) ２ -O-C １－６ -alkyl, -NH-S (=O) ２ -NH ２ , -C １－６ -Alkilen-NH-S(=O) ２ -NH ２ , -NH-S (=O) ２ -NH(C) １－６ -Alkyl), -C １－６ -Alkilen-NH-S(=O) ２ -NH(C) １－６ -alkyl), -NH-S (=O) ２ N(C) １－６ -Alkyl) ２ , -C １－６ -Alkilen-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 -Alkilen-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 -Alkilen-S (=O) ２ -C １－６ -alkyl, -S (=O) ２ -OH, -C １－６ -Alkilen-S (=O) ２ -OH, -S (=O) ２ -O-C １－６ -Alkyl, -C １－６ -Alkilen-S (=O) ２ -O-C １－６ -alkyl, -S (=O) ２ -NH ２ , -C １－６ -Alkilen-S (=O) ２ -NH ２ , -S (=O) ２ -NH(C) １－６ -Alkyl), -C １－６ -Alkilen-S (=O) ２ -NH(C) １－６ -alkyl), -S (=O) ２ -N(C) １－６ -Alkyl) ２ , -C １－６ -Alkilen-S (=O) ２ -N(C) １－６ -Alkyl) ２ , 3-14 member cycloalkyl, -C １－６ -Alkylene-(3-14 member cycloalkyl), 3-14 member heterocycloalkyl, -C １－６ -Alkylene-(3-14 member heterocycloalkyl), -phenyl, -C １－６ -alkylene-phenyl, 5-14 member heteroaryl, -C １－６ -alkylene-(5-14 member heteroaryl), -O-(3-14 member cycloalkyl), -O-(3-14 member heterocycloalkyl), -O-phenyl, -O-(5-14 member heteroaryl), -C(=O)-(3-14 member cycloalkyl), -C(=O)-(3-14 member heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5-14 member heteroaryl), -S(=O) ２ - (3-14 member cycloalkyl), -S (=O) ２ - (3-14 member heterocycloalkyl), -S (=O) ２ -phenyl, or -S (=O) ２ [This means that the molecule is substituted with one or more substituents independently selected from (5- to 14-membered heteroaryl groups)] Compounds thereof, or their stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs.

2. T represents -O-, and U represents -(CR ５ R ５ ') ｎ A compound according to claim 1 or its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs that represent -.

3. R ３ However, -H, -OH, -C １－６ -Alkyl, -C １－６ -Alkylene-OH, -C １－６ -Alkylene-O-C １－６ -Alkyl, -C １－６ -Alkilen-NH ２ , -C １－６ -Alkilen-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 -Alkilen-CF ３ , -C １－６ -Alkilen-CF ２ H, -C １－６ -Alkilen-CFH ２ , -C １－６ - Alkilen-NH-C １－６ -Alkilen-CF ３ , or -C １－６ -Alkylene-N(C) １－６ -Alkyl)-C １－６ -Alkilen-CF ３ The compound described in claim 1 or its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs.

4. R ４ but, -H, Saturated, unsubstituted, monosubstituted, or polysubstituted -S (=O) ２ C １－６ - Alkyl, Saturated, monosubstituted or polysubstituted -S (=O) ２ (3-14 member cycloalkyl), 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 unaromatically unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C １ -C ６ -Alkylene- or -C １ -C ６ - Heteroalkylene - is optionally connected, and in each case, saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, 3 to 14-membered cycloalkyl, A saturated or unaromatically unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered heterocycloalkyl, wherein the 3- to 14-membered heterocycloalkyl is -C １ -C ６ -Alkylene- or -C １ -C ６ -Heteroalkylene- is optionally connected, and in each case, saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, 3 to 14-membered heterocycloalkyl, Unsubstituted, monosubstituted, or polysubstituted -C １－６ -Alkylene-phenyl, Unsubstituted, monosubstituted or polysubstituted -phenyl, or Unsubstituted, monosubstituted, or polysubstituted 5- to 14-membered heteroaryls, wherein the 5- to 14-membered heteroaryl is -C １ -C ６ -Alkylene- or -C １ -C ６ The compound according to claim 1 or its stereoisomers, physiologically acceptable salts, solvates and / or polymorphs, optionally linked through a heteroalkylene, in each case representing a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, 5- to 14-membered heteroaryl.

5. R ４ but, -H, Saturated, unsubstituted, monosubstituted or polysubstituted -S (=O) with -F ２ C １－６ - Alkyl, Saturated, unsubstituted -S (=O) ２ (3-14 member cycloalkyl), Saturated, unsubstituted, -F, -Cl, -Br, -I, -CF ３ , -CF ２ H, -CFH ２ , -CF ２ Cl, -CFCl ２ , -C １－６ -Alkilen-CF ３ , -C (=O) -C １－６ -alkyl, -C(=O)OH, -C(=O)-OC １－６ -alkyl, -C(=O)O-C １－６ -Alkilen-CF ３ , -OH, =O, -OC １－６ -alkyl, -NH ２ , - NHC １－６ -alkyl, -N(C) １－６ -Alkyl) ２ , -C １－６ -Alkilen-NH ２ , -C １－６ - Alkilen-NH-C １－６ -Alkyl, -C １－６ -Alkylene-N(C) １－６ -Alkyl) ２ , -C １－６ - Alkilen-NH-C １－６ -Alkilen-CF ３ , -C １－６ -Alkylene-OH, -C １－６ -Alkylene-O-C １－６ -Alkyl, -C １－６ -Alkylene-NHC(=O)O-C １－６ -Alkyl, -NHC(=O)O-C １－６ -alkyl, -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, -S (=O) ２ -NH ２ , -S (=O) ２ -NH(C) １－６ -alkyl), -S (=O) ２ -N(C) １－６ -Alkyl) ２ , a substituent independently selected from the group consisting of 3-14 membered cycloalkyl, unsubstituted -phenyl, oxetanyl, or pyrimidinyl, monosubstituted or polysubstituted, -C １－６ - Alkyl, 3-14 member cycloalkyl or -C １－６ -Alkylene- (3-14 member cycloalkyl), -C １－６ -Alkylene- is unsubstituted, or monosubstituted or polysubstituted with -F, -Cl, -Br, -I, -OH, and the 3- to 14-membered cycloalkyl group is saturated, unsubstituted, -F, -Cl, -Br, -I, -CF ３ , -CF ２ H, -CFH ２ , -CF ２ Cl, -CFCl ２ , -C １－６ -Alkilen-CF ３ , -C (=O) -C １－６ -alkyl, -C(=O)OH, -C(=O)-OC １－６ -alkyl, -C(=O)O-C １－６ -Alkilen-CF ３ , -OH, =O, -OC １－６ -alkyl, -NH ２ , - NHC １－６ -alkyl, -N(C) １－６ -Alkyl) ２ , -C １－６ -Alkilen-NH ２ , -C １－６ - Alkilen-NH-C １－６ -Alkyl, -C １－６ -Alkylene-N(C) １－６ -Alkyl) ２ , -C １－６ - Alkilen-NH-C １－６ -Alkilen-CF ３ , -C １－６ -Alkylene-OH, -C １－６ -Alkylene-O-C １－６ -Alkyl, -C １－６ -Alkylene-NHC(=O)O-C １－６ -Alkyl, -NHC(=O)O-C １－６ -alkyl, -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, -S (=O) ２ -NH ２ , -S (=O) ２ -NH(C) １－６ -alkyl), -S (=O) ２ -N(C) １－６ -Alkyl) ２ , a substituent independently selected from the group consisting of 3-14 member cycloalkyls, unsubstituted -phenyl, oxetanyl, or pyrimidinyl, which is monosubstituted or disubstituted, 3-14 member cycloalkyl or -C １－６ -Alkylene- (3-14 member cycloalkyl), 3-14 member heterocycloalkyl or -C １－６ -Alkylene- (3-14 member heterocycloalkyl), -C １－６ -Alkylene- is unsubstituted, or monosubstituted or polysubstituted with -F, -Cl, -Br, -I, -OH, and the 3- to 14-membered heterocycloalkyl is, in each case, azetane, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole Selected from 1,1-dioxotiacyclohexane, 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, and 1,1-dioxotiacyclohexane, in each case unsubstituted, -F, -Cl, -Br, -I, -C １－６ -Alkyl, -CF ３ , -CF ２ H, -CFH ２ , -CF ２ Cl, -CFCl ２ , -C １－６ -Alkilen-CF ３ , -C (=O) -C １－６ -alkyl, -C(=O)OH, -C(=O)-OC １－６ -alkyl, -C(=O)O-C １－６ -Alkilen-CF ３ , -OH, =O, -OC １－６ -alkyl, -NH ２ , - NHC １－６ -alkyl, -N(C) １－６ -Alkyl) ２ , -C １－６ -Alkilen-NH ２ , -C １－６ - Alkilen-NH-C １－６ -Alkyl, -C １－６ -Alkylene-N(C) １－６ -Alkyl) ２ , -C １－６ - Alkilen-NH-C １－６ -Alkilen-CF ３ , -C １－６ -Alkylene-OH, -C １－６ -Alkylene-O-C １－６ -Alkyl, -C １－６ -Alkylene-NHC(=O)O-C １－６ -Alkyl, -NHC(=O)O-C １－６ -alkyl, -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, -S (=O) ２ -NH ２ , -S (=O) ２ -NH(C) １－６ -alkyl), -S (=O) ２ -N(C) １－６ -Alkyl) ２ , a substituent independently selected from the group consisting of 3-14 member cycloalkyls, 3-14 member heterocycloalkyls, unsubstituted -phenyls, and 5-14 member heteroaryls, which is monosubstituted or polysubstituted, 3-14 member heterocycloalkyl or -C １－６ -Alkylene- (3-14 member heterocycloalkyl), 5-14 member heteroaryl or -C １－６ -Alkilen- (5-14 member heteroaryl), -C １－６ -Alkylene- is unsubstituted or monosubstituted with -F, -Cl, -Br, -I, -OH, and the 5-14 member heteroaryl is selected in each case 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, -F, -Cl, -Br, -I, -C １－６ -Alkyl, -CF ３ , -CF ２ H, -CFH ２ , -CF ２ Cl, -CFCl ２ , -C １－６ -Alkilen-CF ３ , -C (=O) -C １－６ -alkyl, -C(=O)OH, -C(=O)-OC １－６ -alkyl, -C(=O)O-C １－６ -Alkilen-CF ３ , -OH, =O, -OC １－６ -alkyl, -NH ２ , - NHC １－６ -alkyl, -N(C) １－６ -Alkyl) ２ , -C １－６ -Alkilen-NH ２ , -C １－６ - Alkilen-NH-C １－６ -Alkyl, -C １－６ -Alkylene-N(C) １－６ -Alkyl) ２ , -C １－６ - Alkilen-NH-C １－６ -Alkilen-CF ３ , -C １－６ -Alkylene-OH, -C １－６ -Alkylene-O-C １－６ -Alkyl, -C １－６ -Alkylene-NHC(=O)O-C １－６ -Alkyl, -NHC(=O)O-C １－６ -alkyl, -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, -S (=O) ２ -NH ２ , -S (=O) ２ -NH(C) １－６ -alkyl), -S (=O) ２ -N(C) １－６ -Alkyl) ２ , a substituent independently selected from the group consisting of 3-14 member heterocycloalkyls, unsubstituted -phenyls, and 5-14 member heteroaryls, which is monosubstituted or disubstituted, a 5-14 member heteroaryl or -C １－６ A compound according to claim 1, or a stereoisomer, physiologically acceptable salt, solvate, and / or polymorph thereof, representing an alkylene (5-14 member heteroaryl).

6. R ３ However, it represents -H, R ４ but, -H, Saturated, unsubstituted, monosubstituted or polysubstituted -S (=O) with -F ２ C １－６ - Alkyl, Saturated, unsubstituted -S (=O) ２ (3-14 member cycloalkyl), Saturated, unsubstituted, -OH, =O, -OC １－６ -alkyl, -NH ２ , - NHC １－６ -alkyl, -N(C) １－６ -Alkyl) ２ , -C １－６ -Alkilen-NH ２ , -C １－６ - Alkilen-NH-C １－６ -alkyl, -C(=O)NH ２ , -C(=O)-NH-C １－３ -alkyl, -C(=O)-N(C １－３ -Alkyl) ２ -C １－６ - Alkyl, 3-14 member cycloalkyl or -C １－６ -Alkylene- (3-14 member cycloalkyl), -C １－６ -Alkylene- is either unsubstituted or monosubstituted with -OH, and the 3- to 14-membered cycloalkyl group is saturated, unsubstituted, -C １－６ -Alkyl, -C １－６ -Alkilen-NH ２ , -C １－６ - Alkilen-NH-C １－６ -Alkilen-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)OC １－６ - A substituent independently selected from the group consisting of alkyls, which is monosubstituted or disubstituted, and is a 3- to 14-membered cycloalkyl or -C １－６ -Alkylene- (3-14 member cycloalkyl), 3-14 member heterocycloalkyl or -C １－６ -Alkylene- (3-14 member heterocycloalkyl), -C １－６ -Alkylene- is either unsubstituted or monosubstituted with -OH, and the 3- to 14-membered heterocycloalkyl group is, in each case, azetane, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahi Selected from dripyrro[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, and 1,1-dioxotiacyclohexane, in each case unsubstituted -F, -OH, =O, -C １－６ -Alkyl, -C １－６ -Alkilen-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 -Alkilen-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 -Alkilen-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 substituents independently selected from the group consisting of monosubstituted or polysubstituted 3- to 14-membered heterocycloalkyl or -C １－６ -Alkylene- (3-14 member heterocycloalkyl), Unsubstituted -phenyl, 5-14 member heteroaryl or -C １－６ -Alkilen- (5-14 member heteroaryl), -C １－６ -Alkylene- is either unsubstituted or monosubstituted with -OH, and the 5- to 14-membered heteroaryl is selected in each case from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole, and [1,2,4]triazolo[4,3-a]pyrimidine, and in each case, the unsubstituted -C １－６ -alkyl and -OH substituents independently selected from each other, monosubstituted or disubstituted, 5- to 14-membered heteroaryl or -C １－６ A compound according to claim 1, or a stereoisomer, physiologically acceptable salt, solvate, and / or polymorph thereof, representing an alkylene (5-14 member heteroaryl).

7. W is Saturated or unsaturated, unsubstituted, -F, -Cl, -Br, -I, -C １－６ -Alkyl, -CF ３ , -CF ２ H, -CFH ２ , -CF ２ Cl, -CFCl ２ , -C １－６ -Alkilen-CF ３ , -C (=O) -C １－６ -alkyl, -C(=O)OH, -C(=O)-OC １－６ -alkyl, -C(=O)O-C １－６ -Alkilen-CF ３ , -OH, =O, -OC １－６ -alkyl, -NH ２ , - NHC １－６ -alkyl, -N(C) １－６ -Alkyl) ２ , -C １－６ -Alkilen-NH ２ , -C １－６ - Alkilen-NH-C １－６ -Alkyl, -C １－６ -Alkylene-N(C) １－６ -Alkyl) ２ , -C １－６ - Alkilen-NH-C １－６ -Alkilen-CF ３ , -C １－６ -Alkylene-OH, -C １－６ -Alkylene-O-C １－６ -Alkyl, -C １－６ -Alkylene-NHC(=O)O-C １－６ -Alkyl, -NHC(=O)O-C １－６ -alkyl, -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, -S (=O) ２ -NH ２ , -S (=O) ２ -NH(C) １－６ -alkyl), -S (=O) ２ -N(C) １－６ -Alkyl) ２ , 3-14 member heterocycloalkyls, unsubstituted -phenyl, 5-14 member heteroaryls, monosubstituted or polysubstituted 3-14 member cycloalkyls, or In each case, the unsubstituted -F, -Cl, -Br, -I, -C １－６ -Alkyl, -CF ３ , -CF ２ H, -CFH ２ , -CF ２ Cl, -CFCl ２ , -C １－６ -Alkilen-CF ３ , -C (=O) -C １－６ -alkyl, -C(=O)OH, -C(=O)-OC １－６ -alkyl, -C(=O)O-C １－６ -Alkilen-CF ３ , -OH, =O, -OC １－６ -alkyl, -NH ２ , - NHC １－６ -alkyl, -N(C) １－６ -Alkyl) ２ , -C １－６ -Alkilen-NH ２ , -C １－６ - Alkilen-NH-C １－６ -Alkyl, -C １－６ -Alkylene-N(C) １－６ -Alkyl) ２ , -C １－６ - Alkilen-NH-C １－６ -Alkilen-CF ３ , -C １－６ -Alkylene-OH, -C １－６ -Alkylene-O-C １－６ -Alkyl, -C １－６ -Alkylene-NHC(=O)O-C １－６ -Alkyl, -NHC(=O)O-C １－６ -alkyl, -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, -S (=O) ２ -NH ２ , -S (=O) ２ -NH(C) １－６ -alkyl), -S (=O) ２ -N(C) １－６ -Alkyl) ２ -C １ -C ６ -Alkyl, -C ２ -C ６ -Alkenyl, -C ２ -C ６ - The compound according to claim 1 or its stereoisomers, physiologically acceptable salts, solvates and / or polymorphs, representing alkynyl.

8. R １ However, -H, -F, -Cl, -Br, -I, -CN, -C １－６ -alkyl, -O-C １－６ -Alkyl, -C １－６ -Alkylene-O-C １－６ -Alkyl, -C １－６ -Alkilen-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 -Alkilen-CF ３ , -C １－６ -Alkilen-CF ２ H, -C １－６ -Alkilen-CFH ２ , -C １－６ - Alkilen-NH-C １－６ -Alkilen-CF ３ , -C １－６ -Alkylene-N(C) １－６ -Alkyl)-C １－６ -Alkilen-CF ３ , -C(=O)C １－６ -alkyl, -C(=O)OC １－６ -alkyl, -C(=O)NHC １－６ -alkyl, -C(=O)NH ２ , -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 The compound according to claim 1, or its stereoisomers, physiologically acceptable salts, solvates and / or polymorphs, representing an alkyl, unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, or unsubstituted cyclohexyl.

9. R ５ and R ５ 'But, independently of each other, -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 unaromatically unsaturated, unsubstituted, monosubstituted or polysubstituted 3- to 14-membered cycloalkyl, wherein the 3- to 14-membered cycloalkyl is -C １ -C ６ -Alkylene- or -C １ -C ６ The compound according to claim 1 or its stereoisomers, physiologically acceptable salts, solvates and / or polymorphs, optionally linked through a heteroalkylene, in each case representing a saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, 3 to 14-membered cycloalkyl group.

10. R ６ , R ７ , and R ８ However, they are independent 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 ien-CH ２ F, -O-C １－６ -Alkyl, -OCF ３ , -OCHF ２ , -OCH ２ F, Non-substituted, or independently of each other: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF ３ ,-CHF ２ ien-CH ２ F, -OCF ３ , -OCHF ２ , -OCH ２ F, SF ５ , -NO ２ , -C(=O)OH, -NH ２ , and -C(=O)NH ２ -NHC １－６ - Alkyl, Non-substituted, or independently of each other: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF ３ ,-CHF ２ ien-CH ２ F, -OCF ３ , -OCHF ２ , -OCH ２ F, SF ５ , -NO ２ , -C(=O)OH, -NH ２ , and -C(=O)NH ２ -N(C) is substituted with one or more substituents selected from １－６ -Alkyl) ２ , Non-substituted, or independently of each other: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF ３ ,-CHF ２ ien-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 which is substituted with one or more substituents selected from １－６ - Alkyl, Non-substituted, or independently of each other: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF ３ ,-CHF ２ ien-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, which is substituted with one or more substituents selected from １－６ - Alkyl, or Non-substituted, or independently of each other: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF ３ ,-CHF ２ ien-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 is substituted with one or more substituents selected from １－６ - A compound according to claim 1 or its stereoisomers, physiologically acceptable salts, solvates and / or polymorphs representing a heteroalkyl group.

11. Compound 001-(2S)-2-{[5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 002-(2S)-2-({5-[(2,2-difluorocyclopropyl)methoxy]-2-methyl-1-benzofuran-3-yl}formamide)-3-hydroxypropanamide, Compound 003-(2S)-2-[(5-{[1-(difluoromethyl)cyclopropyl]methoxy}-2-methyl-1-benzofuran-3-yl)formamide]-3-hydroxypropanamide, Compound 004-(2S)-2-{[2-cyclopropyl-5-(cyclopropylmethoxy)-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 005-(2S)-2-{[5-(2-cyclopropylethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 006-(2S)-2-{[5-(cyclobutylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 007-(2S)-2-{[5-(cyclobutylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}propanamide, Compound 008-(2S)-2-{[5-(cyclopropylmethoxy)-2-(difluoromethyl)-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 009-(2R)-2-{[5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 010-(2S)-2-{[5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}propanamide, Compound 011-(2S,3R)-2-[(5-{[1-(difluoromethyl)cyclopropyl]methoxy}-2-methyl-1-benzofuran-3-yl)formamide]-3-hydroxybutanamide, Compound 012-(2S,3R)-2-{[5-(2-cyclopropylethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxybutanamide, Compound 013-2-({5-[(2,2-difluorocyclopentyl)methoxy]-2-methyl-1-benzofuran-3-yl}formamide)-3-hydroxypropanamide, Compound 014-2-[(5-{[1-(difluoromethyl)cyclopropyl]methoxy}-2-methyl-1-benzofuran-3-yl)formamide]-3-hydroxy-2-methylpropanamide, Compound 015-2-{[5-(cyclobutylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-2-methylpropanamide, Compound 016-2-{[5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-2-methylpropanamide, Compound 017-2-{[5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 018-5-(cyclobutylmethoxy)-N-(1,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 019-5-(cyclobutylmethoxy)-N-(3,3-difluoropiperidine-4-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 020-5-(cyclohexylmethoxy)-2-methyl-N-(1-methylpiperidine-4-yl)-1-benzofuran-3-carboxamide, Compound 021-5-(cyclopropylmethoxy)-2-methyl-N-(1-methylpiperidine-4-yl)-1-benzofuran-3-carboxamide, Compound 022-5-(cyclopropylmethoxy)-2-methyl-N-(oxan-4-yl)-1-benzofuran-3-carboxamide, Compound 023-5-(cyclopropylmethoxy)-N-(1,3-dihydroxy-2-methylpropan-2-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 024-5-(cyclopropylmethoxy)-N-(3,3-difluoropiperidine-4-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 025-5-(cyclopropylmethoxy)-N-[1-(hydroxymethyl)cyclobutyl]-2-methyl-1-benzofuran-3-carboxamide, Compound 026-5-(cyclopropylmethoxy)-N-[1-(hydroxymethyl)cyclopropyl]-2-methyl-1-benzofuran-3-carboxamide, Compound 027-5-(cyclopropylmethoxy)-N-[3-(hydroxymethyl)-2-oxopiperidine-3-yl]-2-methyl-1-benzofuran-3-carboxamide, Compound 028-5-(cyclopropylmethoxy)-N-[3-(hydroxymethyl)-2-oxopyrrolidine-3-yl]-2-methyl-1-benzofuran-3-carboxamide, Compound 029-5-(cyclopropylmethoxy)-N-[3-(hydroxymethyl)oxetan-3-yl]-2-methyl-1-benzofuran-3-carboxamide, Compound 030-5-(cyclopropylmethoxy)-N-[4-(hydroxymethyl)oxan-4-yl]-2-methyl-1-benzofuran-3-carboxamide, Compound 031-5-[(2,2-difluorocyclopropyl)methoxy]-N-(3,3-difluoropiperidine-4-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 032-N-(3,3-difluoropiperidine-4-yl)-2-methyl-5-[(1-methylcyclopropyl)methoxy]-1-benzofuran-3-carboxamide, Compound 033-N-(3,3-difluoropiperidine-4-yl)-5-[(2,2-dimethylcyclopropyl)methoxy]-2-methyl-1-benzofuran-3-carboxamide, Compound 034-N-(3-carbamoyloxetan-3-yl)-5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 035-N-(3-carbamoyloxolan-3-yl)-5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 036-N-(3-carbamoyloxolan-3-yl)-5-{[1-(difluoromethyl)cyclopropyl]methoxy}-2-methyl-1-benzofuran-3-carboxamide, Compound 037-N-(4-carbamoyloxan-4-yl)-5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 038-(2S)-2-{[5-(2,2-difluoroethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 039-(2S)-2-{[5-(2,2-dimethylpropoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxypropanamide, Compound 040-(2S,3R)-2-{[5-(2,2-difluoroethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxybutanamide, Compound 041-2-{[5-(2,2-difluoroethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 042-N-(3,3-difluoropiperidine-4-yl)-2-methyl-5-(2-methylpropoxy)-1-benzofuran-3-carboxamide, Compound 043-N-(3,3-difluoropiperidine-4-yl)-5-(2,2-dimethylpropoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 044-N-(3-carbamoyloxolan-3-yl)-5-(2,2-difluoroethoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 045-2-{[5-(cyclopropylmethoxy)-6-fluoro-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 046-5-(cyclopropylmethoxy)-N-(4,4-difluoro-1-hydroxy-2-methylbutan-2-yl)-2-methyl-1-benzofuran-3-carboxamide, Compound 047-3-hydroxy-2-methyl-2-{[2-methyl-5-(2,2,2-trifluoroethoxy)-1-benzofuran-3-yl]formamide}propenamide, Compound 048-3-hydroxy-2-methyl-2-[(2-methyl-5-{[1-(trifluoromethyl)cyclopropyl]methoxy}-1-benzofuran-3-yl)formamide]propenamide, Compound 049-2-({5-[(2,2-dimethylcyclopropyl)methoxy]-2-methyl-1-benzofuran-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 050-cis-2-{[5-({bicyclo[3.1.0]hexane-3-yl}methoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide Compound 051-trans-2-{[5-({bicyclo[3.1.0]hexane-3-yl}methoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 052-3-hydroxy-2-methyl-2-{[2-methyl-5-({3-methylbicyclo[1.1.1]pentan-1-yl}methoxy)-1-benzofuran-3-yl]formamide}propenamide, Compound 053-2-{[5-(cyclobutylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, Compound 054-2-({5-[(3,3-difluorocyclobutyl)methoxy]-2-methyl-1-benzofuran-3-yl}formamide)-3-hydroxy-2-methylpropanamide, Compound 055-5-(cyclopropylmethoxy)-2-methyl-N-(2-oxopiperidine-3-yl)-1-benzofuran-3-carboxamide, Compound 056-N-[(2)-3-amino-4,4,4-trifluoro-1-hydroxybutan-2-yl]-5-(cyclopropylmethoxy)-2-methyl-1-benzofuran-3-carboxamide, Compound 057-5-[(2,2-difluorocyclopropyl)methoxy]-2-methyl-N-(4,4,4-trifluoro-1-hydroxybutan-2-yl)-1-benzofuran-3-carboxamide, Compound 058-cis-3-hydroxy-2-methyl-2-({2-methyl-5-[(3-methylcyclobutyl)methoxy]-1-benzofuran-3-yl}formamide)propenamide, Compound 059-trans-3-hydroxy-2-methyl-2-({2-methyl-5-[(3-methylcyclobutyl)methoxy]-1-benzofuran-3-yl}formamide)propenamide, Compound 060-N-(1-hydroxy-3-methoxy-2-methylpropan-2-yl)-2-methyl-5-{[1-(trifluoromethyl)cyclopropyl]methoxy}-1-benzofuran-3-carboxamide, Compound 061-2-methyl-N-(3-methyl-2-oxopiperidine-3-yl)-5-{[1-(trifluoromethyl)cyclopropyl]methoxy}-1-benzofuran-3-carboxamide, and Compound 062-2-{[5-(cyclopentylmethoxy)-2-methyl-1-benzofuran-3-yl]formamide}-3-hydroxy-2-methylpropanamide, The compound according to claim 1 or its stereoisomers, physiologically acceptable salts, solvates, and / or polymorphs, selected from the group consisting of the stereoisomers thereof, physiologically acceptable salts, solvates, and / or polymorphs.

12. A pharmaceutical composition comprising a compound according to any one of claims 1 to 11 or a stereoisomer thereof, a physiologically acceptable salt, solvate, and / or polymorph.

13. A pharmaceutical composition according to claim 12 for use as a medicine.

14. The pharmaceutical composition according to claim 12 for use in the treatment of pain or epilepsy.

15. The pharmaceutical composition according to claim 14, wherein the pain is selected from nociceptive pain, inflammatory pain, and neuropathic pain, and is preferably postoperative pain.

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