Novel derivatives for treatment of TRPM3-mediated disorders
By developing a novel TRPM3 antagonist compound, the problem of difficulty in effectively treating TRPM3-mediated diseases in the prior art is solved, and effective treatment of pain, epilepsy and inflammatory hypersensitivity is achieved, and good safety and Pharmacokinetic properties.
Patent Information
- Application Number
- CN202380047493.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-05-25
- Filing Date
- 2023-05-25
- Publication Date
- 2025-02-11
AI Technical Summary
The prior art is difficult to effectively prevent or treat TRPM3-mediated conditions such as pain, epilepsy, and inflammatory hypersensitivity, and lack therapeutic agents with low side effects and good pharmacokinetic properties.
A novel class of compounds has been developed as antagonists of TRPM3 for the prevention or treatment of TRPM3-mediated conditions. Through specific chemical structure design, this compound can effectively antagonize the TRPM3 channel and alleviate related symptoms.
This compound is able to effectively antagonize the TRPM3 channel, provide therapeutic effects on pain, epilepsy and inflammatory hypersensitivity, and has low side effects and good pharmacokinetic properties.
Smart Images

Figure BDA0005190267110000021 
Figure BDA0005190267110000061 
Figure BDA0005190267110000191
Abstract
Description
Technical Field
[0001] The present invention relates to compounds useful for preventing or treating TRPM3-mediated disorders, more particularly disorders selected from pain, epilepsy and inflammatory hypersensitivity. The present invention also relates to a method for preventing or treating said TRPM3-mediated disorders. Background Art
[0002] The TRP superfamily consists of proteins with six transmembrane domains (6TM) that assemble as homo- or hetero-tetramers to form cation-permeable ion channels. The name TRP is derived from the Drosophila trp (transient receptor potential) mutant, which is characterized by Drosophila photoreceptors having a transient receptor potential in response to sustained light. Over the past 15 years, trp-related channels have been identified in yeast, worms, insects, fish, and mammals, including 27 TRPs in humans. Based on sequence homology, TRP channels can be divided into seven subfamilies: TRPC, TRPV, TRPM, TRPA, TRPP, TRPML, and TRPN.
[0003] Members of the TRP superfamily are likely expressed in all mammalian organs and cell types, and great progress has been made in recent years in understanding their physiological roles. The tailored selectivity of certain TRP channels enables the channels to 2+ Mg 2+ The TRP channels play a key role in the cellular uptake and / or transepithelial transport of trace metal ions. In addition, the sensitivity of TRP channels to a wide range of chemical and physical stimuli allows the channels to act as dedicated biosensors, participating in processes from vision to taste and touch. Specifically, several members of the TRP superfamily show very high sensitivity to temperature. These so-called thermal TRPs are highly expressed in sensory neurons and / or skin keratinocytes, where they act as primary thermal sensors for detecting harmless and harmful (painful) temperatures.
[0004] It is becoming increasingly clear that TRP channel dysfunction is directly related to the etiology of various hereditary and acquired diseases. In fact, both loss-of-function and gain-of-function mutations in TRP channel genes have been identified as direct causes of hereditary diseases, including brachyolmia, hypomagnesemia with secondary hypocalcemia, polycystic kidney disease, mucopolysaccharidosis type IV, and familial focal segmental glomerulosclerosis. In addition, TRP channel function / dysfunction has been directly related to a wide range of pathological conditions, including chronic pain, hypertension, cancer, epilepsy, and neurodegenerative disorders.
[0005] TRPM3 (transient receptor potential M-type 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 thermal sensing. Neurosteroid pregnenolone sulfate is an effective known activator of TRPM3 (Wagner et al., 2008). Neurosteroid pregnenolone sulfate induces pain in wild-type mice, but not in knockout TRPM3 mice. Recently, it has also been shown that CFA-induced inflammation and inflammatory pain are eliminated in TRPM3 knockout mice. Therefore, TRPM3 antagonists can be used as analgesics to combat pain, such as inflammatory pain (Vriens J. et al., Neuron, May 2011). TRPM3 is also expressed in many other tissues including the brain; reports show that two mutations in TRPM3 are associated with developmental and epileptic encephalopathy (Zhao, s. et al., Channels (Austin). 2021).
[0006] Some TRPM3 antagonists are known, but none of them point 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 as reducing mechanical hyperalgesia and cold hyperalgesia in a rat pain model (Chen L et al., Scientific reports, July 2014). There is still a huge medical need for novel, alternative and / or better therapeutic agents for preventing or treating TRPM3-mediated conditions (such as pain and epilepsy), more specifically for pain, such as inflammatory pain or epilepsy (such as epileptic encephalopathy). There is a great need for therapeutic agents with good efficacy, low levels or no side effects (such as unlikely to be addictive, non-toxic like opioids) and / or good or better pharmacokinetic or kinetic properties for certain types of pain.
[0007] The present invention provides a class of novel compounds which are antagonists of TRPM3 and can be used as modulators of TRPM3-mediated disorders. Summary of the invention
[0008] The first aspect of the present invention provides a compound of formula (I), its stereoisomeric form, physiologically acceptable salt, solvate and / or polymorph
[0009]
[0010] in
[0011] R 1Indicates -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 ;
[0012] Q stands for -NR 3 R 4 ;
[0013] R 3 Indicates -OH or -R Y1 ;
[0014] R 4 Indicates -R Y2 or -S(=O) 2 R Y3 ;
[0015] or R 3 and R 4 together form a 4-, 5-, 6-, 7- or 8-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
[0016] T stands for -O-, and U stands for -(CR 5 R 5 ') n -; or T means -(CR 5 R 5 ') n -, and U represents -O-;
[0017] n is an integer selected from 1, 2, 3, 4 or 5;
[0018] R 5 and R 5 'Independently represent -R Y4 ;
[0019] R 6 and R 8 Independently represent -F, -Cl, -Br, -I, -CN, -NO 2 、-SF5 , -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 ;
[0020] W stands for
[0021] 3-14 membered cycloalkyl, which is saturated or unsaturated; unsubstituted, monosubstituted or polysubstituted;
[0022] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted;
[0023] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or polysubstituted;
[0024] 5-14 membered heteroaryl, which is mono- or poly-substituted; or
[0025] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 - alkynyl; which is in each case unsubstituted, monosubstituted or polysubstituted;
[0026] in
[0027] R W and R X Independently of each other, in each case independently
[0028] -H;
[0029] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0030] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0031] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0032] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0033] R Y1 , R Y2 , R Y3 and R Y4 Independently of each other, in each case independently
[0034] -H;
[0035] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0036] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0037] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0038] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6-heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0039] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0040] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0041] and wherein "mono- or poly-substituted" in each case independently means substitution by one or more substituents independently selected from the group consisting of: -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)-OC1-6 -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(C1-6 -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(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-(3-14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl, -C 1-6 -alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 14-membered heteroaryl, -C 1-6-alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -O-(5- to 14-membered heteroaryl), -C(=O)-(3- to 14-membered cycloalkyl), -C(=O)-(3- to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5- to 14-membered heteroaryl), -S(=O) 2 -(3-14 membered cycloalkyl), -S(=O) 2 -(3 to 14 membered heterocycloalkyl), -S(=O) 2 -phenyl or -S(=O) 2 -(5- to 14-membered heteroaryl);
[0042] Alternatively, the compound is 5-(benzyloxy)-2-methylfuro[2,3-c]pyridine-3-carboxylate.
[0043] Specifically, the present invention provides a compound of formula (I), its stereoisomeric form, physiologically acceptable salt, solvate and / or polymorph
[0044]
[0045] in
[0046] R 1 Indicates -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 ;
[0047] Q stands for -NR 3 R 4 ;
[0048] R 3 Indicates -OH or -R Y1 ;
[0049] R 4 Indicates -R Y2 or -S(=O) 2 R Y3;
[0050] or R 3 and R 4 together form a 4-, 5-, 6-, 7- or 8-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
[0051] T stands for -O-, and U stands for -(CR 5 R 5 ') n -; or T means -(CR 5 R 5 ') n -, and U represents -O-;
[0052] n is an integer selected from 1, 2, 3, 4 or 5;
[0053] R 5 and R 5 'Independently represent -R Y4 ;
[0054] R 6 and R 8 Independently represent -F, -Cl, -Br, -I, -CN, -NO 2 、-SF 5 , -R W 、-OR W 、-OC(=O)R W 、-NR W R X 、-NR W C(=O)R X 、-SR W 、-S(=O)R W 、-S(=O) 2 R W 、-C(=O)R W 、-C(=O)OR W or -C(=O)NR W R X ;
[0055] W stands for
[0056] 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated; unsubstituted, monosubstituted or polysubstituted;
[0057] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted;
[0058] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or polysubstituted;
[0059] 5-14 membered heteroaryl, which is mono- or poly-substituted; or
[0060] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 - alkynyl; which is in each case unsubstituted, monosubstituted or polysubstituted;
[0061] in
[0062] R W and R X Independently of each other, in each case independently
[0063] -H;
[0064] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0065] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0066] 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0067] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0068] R Y1 , R Y2 , R Y3 and R Y4 Independently of each other, in each case independently
[0069] -H;
[0070] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0071] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0072] 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0073] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0074] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0075] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0076] and wherein "mono- or poly-substituted" in each case independently means substitution by one or more substituents independently selected from the group consisting of: -F, -Cl, -Br, -I, -CN, -C 1-6 -alkyl, -CF 3 , -CF2 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-OC1-6 -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(C1-6 -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-(3-14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl, -C 1-6 -alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 14-membered heteroaryl, -C 1-6 -alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -O-(5- to 14-membered heteroaryl), -C(=O)-(3- to 14-membered cycloalkyl), -C(=O)-(3- to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5- to 14-membered heteroaryl), -S(=O) 2 -(3-14 membered cycloalkyl), -S(=O) 2 -(3 to 14 membered heterocycloalkyl), -S(=O) 2 -phenyl or -S(=O) 2 -(5- to 14-membered heteroaryl).
[0077] A second aspect of the present invention encompasses a pharmaceutical composition comprising a compound of formula (I) as described in the first aspect.
[0078] According to a third aspect, the present invention also provides a compound of formula (I) as described in the first aspect or a pharmaceutical composition as described in the second aspect for use as a medicament.
[0079] According to a fourth aspect, the present invention also encompasses a compound of formula (I) as described in the first aspect or a pharmaceutical composition as described in the second aspect for use in preventing and / or treating a TRPM3-mediated disorder, in particular for preventing and / or treating pain, epilepsy and / or inflammatory hypersensitivity; and / or for combating pain, epilepsy and / or inflammatory hypersensitivity. Specifically for preventing and / or treating pain, epileptic encephalopathy and / or inflammatory hypersensitivity; and / or for combating pain, epileptic encephalopathy and / or inflammatory hypersensitivity
[0080] The present invention also provides a method for preventing or treating a TRPM3-mediated disorder by administering a compound of formula (I) as described in the first aspect to a subject in need thereof. More specifically, the present invention relates to such methods for preventing and / or treating pain, epilepsy and / or inflammatory hypersensitivity; and / or for combating pain, epilepsy and / or inflammatory hypersensitivity. More specifically, the present invention relates to such methods for preventing and / or treating pain, epileptic encephalopathy and / or inflammatory hypersensitivity; and / or for combating pain, epileptic encephalopathy and / or inflammatory hypersensitivity.
[0081] The present invention further provides a method for preparing a compound of formula (I) as described in the first aspect, the method comprising the following steps:
[0082] - converting a 6-(benzyloxy)-4-iodopyridin-3-ol derivative into a 5-benzyloxyfuro[2,3-c]pyridine-3-carboxylate derivative,
[0083] - Substitution of the previously obtained 5-benzyloxyfuro[2,3-c]pyridine-3-carboxylate derivative with a suitable derivative or alcohol derivative carrying a leaving group under Mitsunobu or alkylation conditions to obtain a 5-O-substituted furo[2,3-c]pyridine-3-carboxylate derivative
[0084] - converting the previously obtained 5-O-substituted furano[2,3-c]pyridine-3-carboxylate derivative into formic acid to obtain a 5-O-substituted furano[2,3-c]pyridine-3-carboxylic acid derivative, and
[0085] - The previously obtained 5-O substituted furo[2,3-c]pyridine-3-carboxylic acid derivatives are coupled with suitable amines to obtain the desired derivatives of the present invention. DETAILED DESCRIPTION
[0086] Before describing the present invention, it should be understood that the present invention is not limited to the specific processes, methods and compounds described, as such processes, methods and compounds may of course vary. It should also be understood that the terminology used herein is not intended to be limiting, as the scope of the present invention will be limited only by the appended claims.
[0087] When describing the compounds or processes of the present invention, the terms used are to be interpreted in accordance with the following definitions, unless the context indicates otherwise.
[0088] As used in the specification and the appended claims, the singular forms "a," "an," and "the" include both singular and plural referents unless the context clearly dictates otherwise. By way of example, "a compound" means one compound or more than one compound.
[0089] 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 members, elements or method steps. The terms "comprising, comprises and comprised of" also include the term "consisting of".
[0090] When referring to a measurable value such as a parameter, amount, time interval, etc., as used herein, the term "about" is intended to encompass variations of + / -10% or less, preferably + / -5% or less, more preferably + / -1% or less, and still more preferably + / -0.1% or less of the specified value, as long as such variations are suitable for implementation in the disclosed invention. It should be understood that the value to which the modifier "about" refers is itself also specifically and preferably disclosed.
[0091] As used herein, when the term "and / or" is used in a list of two or more items, it means that any one of the listed items can be taken alone, or any combination of two or more of the listed items can be taken. For example, if a list is described as containing the group A, B, and / or C, the list can contain A alone; B alone; C alone; 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.
[0092] The description of the numerical range of endpoints includes all integers, and fractions included in the range where appropriate (e.g., when referring to, for example, a plurality of elements, 1 to 5 may include 1, 2, 3, 4, and when referring to, for example, measurements, 1.5, 2, 2.75, and 3.80 may also be included). The description of the endpoints also includes the endpoint values themselves (e.g., 1.0 to 5.0 includes both 1.0 and 5.0). Any numerical range recited herein is intended to include all subranges included therein.
[0093] References throughout this specification to "one embodiment" or "an embodiment" mean that the specific features, structures, or characteristics described in conjunction with the embodiment are included in at least one embodiment of the present invention. Therefore, the appearance of the phrase "in one embodiment" or "in an embodiment" in various places throughout this specification does not necessarily refer to the same embodiment, but may refer to the same embodiment. In addition, in one or more embodiments, the specific features, structures, or characteristics may be combined in any suitable manner, as will be apparent to those skilled in the art based on this disclosure. In addition, although some embodiments described herein include some but not other features included in other embodiments, as will be understood by those skilled in the art, the combination of features of different embodiments is intended to be within the scope of the present invention and to form different embodiments. For example, in the following claims, any of the claimed embodiments may be used in any combination.
[0094] Similarly, it should be understood that in the description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of simplifying the disclosure and aiding in the understanding of one or more of the various inventive aspects.
[0095] Unless otherwise defined, all terms (including technical and scientific terms) used in disclosing the present invention have the meaning commonly understood by those of ordinary skill in the art to which the present invention belongs. By further guidance, definitions of the terms used in the specification are included to better understand the teachings of the present invention.
[0096] When describing the present invention, the terms used are to be interpreted in accordance with the following definitions, unless the context indicates otherwise.
[0097] The terms described above and other terms used in the specification can be well understood by those skilled in the art.
[0098] Whenever the term "substituted" is used herein, it is meant to indicate that one or more hydrogen atoms on the indicated atom in the expression using "substituted" are replaced with a selection from the indicated group, provided that the normal valency of the indicated atom is not exceeded and that the substitution results in a chemically stable compound, i.e., a compound that is sufficiently robust to survive isolation from a reaction mixture.
[0099] In each of the following definitions, the number of carbon atoms represents the maximum number of carbon atoms that is generally optimally present in a substituent or linker; it is understood that where otherwise indicated in this application, the number of carbon atoms represents the optimal maximum number of carbon atoms for that particular substituent or linker.
[0100] As used herein, the term "leaving group" or "LG" means a chemical group that is easily displaced or cleaved or hydrolyzed by a nucleophile under basic or acidic conditions. In a specific embodiment, the leaving group is selected from a halogen atom (e.g., Cl, Br, I) or a sulfonate (e.g., mesylate, tosylate, triflate).
[0101] The term "protecting group" refers to a compound portion that masks or changes the properties of a functional group or the properties of the entire compound. The chemical substructure of a protecting group varies greatly. One function of a protecting group is to act 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 generally used to mask the reactivity of certain functional groups to contribute to the efficiency of the desired chemical reaction, such as forming and disconnecting chemical bonds in an orderly and planned manner. Protection of compound functional groups changes other physical properties other than the reactivity of the protected functional groups, such as polarity, lipophilicity (hydrophobicity) and other properties that can be measured by common analytical tools. The chemically protected intermediate itself can be biologically active or inactive.
[0102] Protected compounds can also show changed, and in some cases optimized in vitro and in vivo properties, such as through cell membrane and resistance to enzymatic degradation or chelation. In this effect, protected compounds with expected therapeutic effects can be referred to as prodrugs. Another function of blocking group is to convert the parent drug into prodrug, thus releasing the parent drug when converting the prodrug in vivo. Because active prodrugs can be absorbed more effectively than the parent drug, prodrugs can have greater effectiveness than the parent drug in vivo. In the case of chemical intermediates, blocking groups are removed in vitro, or in the case of prodrugs, blocking groups are removed in vivo. For chemical intermediates, whether the resulting product (e.g., alcohol) after deprotection is physiologically acceptable is not particularly important, although it is usually more desirable whether the product is pharmacologically harmless.
[0103] As used herein, the term "heteroatom" means an atom selected from: nitrogen (which may be quaternized); oxygen; and sulfur (including sulfoxides and sulfones).
[0104] As used herein, the term "saturated or unsaturated alkyl" encompasses saturated alkyl groups as well as unsaturated alkyl groups, such as alkenyl, alkynyl, and the like. Suitable examples of saturated or unsaturated alkyl groups 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 between 1 and 6 carbon atoms, and thus includes methyl, ethyl, n-propyl, isopropyl, butyl and isomers thereof (e.g., n-butyl, isobutyl and tert-butyl); pentyl and isomers thereof, hexyl and isomers thereof. For example, "C 1-5 The term "alkyl" includes all straight or branched chain alkyl groups having between 1 and 5 carbon atoms, and thus includes methyl, ethyl, n-propyl, isopropyl, butyl and isomers thereof (e.g., n-butyl, isobutyl and tert-butyl); pentyl and isomers thereof; 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.
[0105] As used herein, the term "alkyl" means a straight or branched normal hydrocarbon, secondary hydrocarbon or tertiary hydrocarbon without unsaturated sites. 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. "C 1-6 "Alkyl" includes all straight or branched chain alkyl groups having between 1 and 6 carbon atoms, and thus includes methyl, ethyl, n-propyl, isopropyl, butyl and isomers thereof (e.g., n-butyl, isobutyl and tert-butyl); pentyl and isomers thereof, hexyl and isomers thereof. For example, "C 1-5 "Alkyl" includes all straight or branched chain alkyl groups having between 1 and 5 carbon atoms, and thus includes methyl, ethyl, n-propyl, isopropyl, butyl and isomers thereof (e.g., n-butyl, isobutyl and tert-butyl); pentyl and isomers thereof. For example, "C 1-4 "Alkyl" includes all straight or branched chain alkyl groups having between 1 and 4 carbon atoms, and thus includes methyl, ethyl, n-propyl, isopropyl, butyl, and isomers thereof (e.g., n-butyl, isobutyl, and tert-butyl). For example, "C 1-3 "Alkyl" includes all straight or branched chain alkyl groups having between 1 and 3 carbon atoms, and thus includes methyl, ethyl, n-propyl, isopropyl. "Substituted C 1-6 "Alkyl" refers to a C 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 alkyl.
[0106] As used herein, the term "alkenyl" means a straight or branched normal, secondary or tertiary hydrocarbon having at least one unsaturated site (usually 1 to 3, preferably 1), i.e., a carbon-carbon sp2 double bond. Examples include, but are not limited to, 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). Double bonds can be in either the cis or trans configuration. When a subscript is used after a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. For example, the term "C 2-6 "Alkenyl" refers to an unsaturated hydrocarbon group which may be straight or branched, containing one or more carbon-carbon double bonds and containing 2 to 6 carbon atoms. For example, C 2-4 Alkenyl includes all straight-chain 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 isomers thereof, 2-hexenyl and isomers thereof, 2,4-pentadienyl and the like.
[0107] As used herein, the term "alkynyl" means a straight or branched normal hydrocarbon, secondary hydrocarbon, or tertiary hydrocarbon having at least one unsaturated site (usually 1 to 3, preferably 1), i.e., a carbon-carbon sp triple bond. Examples include, but are not limited to, ethynyl (-C≡CH) and 1-propynyl (propargyl, -CH 2 C≡CH). When a subscript is used after a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. For example, the term "C 2-6 "Alkynyl" refers to an unsaturated hydrocarbon group which may be straight or branched chain containing one or more carbon-carbon triple bonds and containing 2 to 6 carbon atoms. For example, C 2-4 Alkynyl includes all straight-chain or branched 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.
[0108] As used herein, the term "saturated or unsaturated alkylene" encompasses saturated alkylene as well as unsaturated alkylene, such as alkenylene, alkynylene, etc. As used herein, the term "alkylene" means a saturated, straight or branched hydrocarbon group having two monovalent radical centers derived from the same or two different carbon atoms of a parent alkane by removing two hydrogen atoms. Typical alkylene groups include, but are not limited to, 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, hexylene and its chain isomers.
[0109] As used herein, the term "alkenylene" 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 derived by removing two hydrogen atoms from the same or two different carbon atoms of a parent olefin. 2-6 "Alkenylene" by itself or as part of another substituent refers to a divalent C 2-6 An alkenyl group, that is, has two single bonds to attach two other groups.
[0110] As used herein, the term "alkynylene" 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 sp triple bond, and having two monovalent radical centers derived by removing two hydrogen atoms from the same or two different carbon atoms of a parent alkyne. As used herein, the term "C 2-6 "Alkynylidene" by itself or as part of another substituent refers to a divalent C 2-6 Alkynyl groups, that is, have two single bonds to attach two other groups.
[0111] The term "alkenyl" as a group or part of a group refers to an unsaturated hydrocarbon group that may be straight or branched and that contains one or more carbon-carbon double bonds. When a subscript is used after a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. For example, the term "C 2-6 "Alkenyl" refers to an unsaturated hydrocarbon group which may be straight or branched, containing one or more carbon-carbon double bonds and containing 2 to 6 carbon atoms. For example, C 2-4 Alkenyl includes all straight-chain 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 isomers thereof, 2-hexenyl and isomers thereof, 2,4-pentadienyl and the like.
[0112] The term "alkynyl" by itself or as part of another substituent refers to an unsaturated hydrocarbon radical which may be straight or branched chain containing one or more carbon-carbon triple bonds. When a subscript is used after a carbon atom herein, the subscript refers to the number of carbon atoms the named group may contain. For example, the term "C 2-6 "Alkynyl" refers to an unsaturated hydrocarbon group which may be straight or branched chain containing one or more carbon-carbon triple bonds and containing 2 to 6 carbon atoms. For example, C 2-4 Alkynyl includes all straight-chain or branched 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.
[0113] The term "halogenated C 1-6 "Alkyl" as a group or part of a group refers to a C 1-6 Alkyl wherein one, two or three hydrogen atoms are each substituted by halogen as defined herein. 1-6 Non-limiting examples of alkyl groups include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, and the like.
[0114] As used herein, the term "saturated or unsaturated heteroalkyl" encompasses saturated heteroalkyl as well as unsaturated heteroalkyl, such as heteroalkenyl, heteroalkynyl, etc. As used herein, the term "heteroalkyl" means a straight or branched chain alkyl in which one or more carbon atoms (usually 1, 2 or 3) are replaced by heteroatoms (i.e., oxygen, nitrogen or sulfur atoms), provided that the chain may not contain two adjacent O atoms or two adjacent S atoms. This means that one or more -CH 3 Can be -NH 2 Substitution and / or one or more -CH 2- can be substituted with -NH-, -O- or -S-. The S atom in the chain can be optionally oxidized with one or two oxygen atoms to provide sulfoxides and sulfones, respectively. In addition, the heteroalkyl in the compounds of the present invention can contain oxo or thio groups at any carbon or heteroatom, which will produce stable compounds. Exemplary heteroalkyls include, but are not limited to, alcohols, alkyl ethers (e.g., -methoxy, -ethoxy, -butoxy ...), primary alkylamines, secondary alkylamines and tertiary alkylamines, amides, ketones, esters, alkyl sulfides and alkyl sulfones. The term "heteroalkenyl" means a straight or branched alkenyl group in which one or more carbon atoms (usually 1, 2 or 3) are substituted with oxygen, nitrogen or sulfur atoms, provided that the chain may not contain two adjacent O atoms or two adjacent S atoms. Therefore, the term heteroalkenyl includes imines, -O-alkenyls, -NH-alkenyls, -N(alkenyls) 2 , -N(alkyl)(alkenyl) and -S-alkenyl. As used herein, the term "heteroalkynyl" means a straight or branched chain alkynyl group in which one or more carbon atoms (usually 1, 2 or 3) are replaced by oxygen, nitrogen or sulfur atoms, provided that the chain may not contain two adjacent O atoms or two adjacent S atoms. Thus, the term heteroalkynyl includes -cyano, -O-alkynyl, -NH-alkynyl, -N(alkynyl) 2 , -N(alkyl)(alkynyl), -N(alkenyl)(alkynyl), and -S-alkynyl.
[0115] As used herein, the term "saturated or unsaturated heteroalkylene" encompasses saturated heteroalkylene and unsaturated heteroalkylene, such as heteroalkenylene, heteroalkynylene, etc. As used herein, the term "heteroalkylene" means a straight or branched chain alkylene, wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by heteroatoms (i.e., oxygen, nitrogen or sulfur atoms), provided that the chain may not contain two adjacent O atoms or two adjacent S atoms. As used herein, the term "heteroalkenylene" means a straight or branched chain alkenylene, wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by oxygen, nitrogen or sulfur atoms, provided that the chain may not contain two adjacent O atoms or two adjacent S atoms. As used herein, the term "heteroalkynylene" means a straight or branched chain alkynylene, wherein one or more carbon atoms (usually 1, 2 or 3) are replaced by oxygen, nitrogen or sulfur atoms, provided that the chain may not contain two adjacent O atoms or two adjacent S atoms.
[0116] As used herein, the term "saturated or unsaturated cycloalkyl" encompasses saturated cycloalkyl and unsaturated cycloalkyl, such as cycloalkenyl, cycloalkynyl, etc. Specifically, as used herein, the term "saturated or unsaturated cycloalkyl" encompasses saturated cycloalkyl and unsaturated non-aromatic cycloalkyl, such as cycloalkenyl and cycloalkynyl. Specifically, 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 other rings of the polycyclic cycloalkyl can be fused, bridged and / or joined by one or more spiro atoms. Suitable examples of saturated or unsaturated cycloalkyl groups include, but are not limited to, cyclopropyl, cyclopropenyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, 1,3-cyclohexadienyl, 1,4-cyclohexadienyl, 1,5-cyclooctadienyl, bicyclo[2.2.1]hept-2yl, (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]hept-2-yl, 3-bicyclo[3.1.0]hexanyl. Unless otherwise indicated, as used herein, the term "cycloalkyl" means a saturated cyclic hydrocarbon group, including a monocyclic or bicyclic group; the other rings of polycyclic cycloalkyl groups can be fused, bridged and / or connected by one or more spiral atoms. Examples of cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornyl, fenchyl, decalinyl, adamantyl, spiro [3.3] hept-2-yl, 3-bicyclo [3.1.0] hexyl, etc. As used herein, the term "cycloalkenyl" means a non-aromatic cyclic hydrocarbon group having at least one unsaturated site (usually 1 to 3, preferably 1), i.e., a carbon-carbon sp2 double bond. The term "cycloalkenyl" also includes a monocyclic or bicyclic group; the other rings of polycyclic cycloalkenyl groups can be fused, bridged and / or connected by one or more spiral atoms. Examples include, but are not limited to, cyclopentenyl and cyclohexenyl. The double bond can be a cis or trans configuration. As used herein, the term "cycloalkynyl" means a non-aromatic cyclic hydrocarbon radical having at least one unsaturated site (usually 1 to 3, preferably 1), i.e., a carbon-carbon sp triple atom. An example is cyclohept-1-yne. A fused system of a cycloalkyl ring and a heterocycloalkyl ring is considered to be a heterocycloalkyl, regardless of the ring bound to the core structure. A fused system of a cycloalkyl ring and an aryl ring is considered to be an aryl, regardless of the ring bound to the core structure. A fused system of a cycloalkyl ring and a heteroaryl ring is considered to be a heteroaryl, regardless of the ring bound to the core structure.
[0117] As used herein, the term "saturated or unsaturated heterocycloalkyl" encompasses saturated heterocycloalkyl and unsaturated non-aromatic heterocycloalkyl including at least one heteroatom, i.e., N, O or S as a ring member. Specifically, the terms "saturated or unsaturated heterocycloalkyl" and "saturated or non-aromatic unsaturated heterocycloalkyl" are synonymous. Unless otherwise specified, as used herein, the term "heterocycloalkyl" means a "cycloalkyl" in which one or more carbon atoms (usually 1, 2 or 3) are replaced by oxygen, nitrogen or sulfur atoms, provided that the chain may not contain two adjacent O atoms or two adjacent S atoms. Unless otherwise specified, as used herein, the term "heterocycloalkenyl" means a "cycloalkenyl" in which one or more carbon atoms (usually 1, 2 or 3) are replaced by oxygen, nitrogen or sulfur atoms, provided that the chain may not contain two adjacent O atoms or two adjacent S atoms. Unless otherwise indicated, as used herein, the term "heterocycloalkynyl" means a "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 may not contain two adjacent O atoms or two adjacent S atoms. Examples of saturated and unsaturated heterocycloalkyls include, but are not limited to, azepane, 1,4-oxazepane, azetane, azetidine, aziridine, azooctane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxazolidine, morpholine, oxazolidine, oxetane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran
[0013] 1,2-dihydro-1,2-dihydro-2-pyrrolidine, ...Additional heterocycloalkyl groups 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. When the heterocycloalkyl group does not contain nitrogen as a ring member, it is usually bonded through carbon. When the heterocycloalkyl group 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 group, regardless of the ring to which the core structure is attached. A fused system of a heterocycloalkyl ring with an aryl ring is considered to be a heterocycloalkyl group, regardless of the ring to which the core structure is attached. A fused system of a heterocycloalkyl ring with a heteroaryl ring is considered to be a heteroaryl group, regardless of the ring to which the core structure is attached.
[0118] As used herein, the term "aryl" means an aromatic hydrocarbon. Typical aryl includes, but is not limited to, 1 ring or 2 or 3 rings fused together, derived from groups such as benzene, naphthalene, anthracene, biphenyl, etc. The fused system of an aryl ring and a cycloalkyl ring is considered to be an aryl, regardless of the ring combined with the core structure. The fused system of an aryl ring and a heterocycloalkyl ring is considered to be a heterocycloalkyl, regardless of the ring combined with the core structure. Therefore, indoline, dihydrobenzofuran, dihydrobenzothiophene, etc. are considered to be heterocycloalkyl according to the present invention. The fused system of an aryl ring and a heteroaryl ring is considered to be a heteroaryl, regardless of the ring combined with the core structure.
[0119] As used herein, the term "heteroaryl" means an aromatic ring system that includes at least one heteroatom (i.e., N, O, or S) as a ring member of the aromatic ring system. Examples of heteroaryl groups include, but are not limited to, benzimidazole, benzisoxazole, benzoxazole, 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.
[0120] By way of further example, the carbon-bonded heterocycle is bonded at position 2, 3, 4, 5, or 6 of a pyridine, at position 3, 4, 5, or 6 of a pyridazine, at position 2, 4, 5, or 6 of a pyrimidine, at position 2, 3, 5, or 6 of a pyrazine, at position 2, 3, 4, or 5 of a furan, tetrahydrofuran, thiophene, pyrrole, or tetrahydropyrrole, at position 2, 4, or 5 of an oxazole, imidazole, or thiazole, at position 3, 4, or 5 of an isoxazole, pyrazole, or isothiazole, at position 2 or 3 of an aziridine, at position 2, 3, or 4 of an azetidine, at position 2, 3, 4, 5, 6, 7, or 8 of a quinoline, or at position 1, 3, 4, 5, 6, 7, or 8 of an isoquinoline.
[0121] 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. For example, the nitrogen-bonded heterocycle is bonded to 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 at position 1, isoindole or isoindoline at position 2, morpholine at position 4, and carbazole or β-carboline at position 9. Preferred nitrogen-bonded heterocycles include 1-aziridine, 1-azetidinyl, 1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, and 1-piperidinyl. Additional heteroaryl groups within the meaning of the present invention are described in Paquette, Leo A. "Principles of Modern Heterocyclic Chemistry" (W. A. Benjamin Publishers, New York, 1968), in particular Chapters 1, 3, 4, 6, 7 and 9; "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, C. W. and Scriven, E. "Comprehensive Heterocyclic Chemistry" (Pergamon Publishers, 1996); and Journal of the American Chemical Society (1960) 82:5566.
[0122] As used herein with respect to substituents, and unless otherwise indicated, the terms "monosubstituted," "disubstituted," "trisubstituted," "polysubstituted," and the like refer to chemical structures as defined herein in which the corresponding moiety is substituted with one or more substituents, meaning that one or more hydrogen atoms of the moiety are each independently replaced with a substituent. For example, -C 1-6 -Alkyl capping -CH 2 F, -CHF 2 , -CF 3 、-CH 2 CF 3 CF 2 CF 3 Likewise, -C may be polysubstituted by substituents independently selected from -F and -Cl. 1-6 -Alkyl capping -CH 2 F, -CHF 2 , -CF 3 、-CH 2 CF 3 CF 2 CF 3、-CH 2 Cl, -CHCl 2 , -CCl 3 、-CH 2 CCl 3 , CCl 2 CCl 3 , -CHClF, -CClF 2 , -CCl 2 CF 3 , -CF 2 CCl 3 、-CClFCCl 2 F, etc. The name of any substituent found in more than one site in the compounds of the invention should be selected independently.
[0123] Unless otherwise indicated, as used herein, the term "solvate" includes any combination that can be formed by a derivative of the present invention and a suitable inorganic solvent (e.g., hydrate) or organic solvent (such as but not limited to alcohols, ketones, esters, ethers, nitriles, etc.).
[0124] As used herein, the term "subject" refers to an animal, including a human, preferably a mammal, most preferably a human, that has been the object of treatment, observation or experiment.
[0125] As used herein, the term "therapeutically effective amount" means the amount of an active compound or agent that elicits the biological or medical response sought by a researcher, veterinarian, medical doctor or other clinician in a tissue system, animal or human, including alleviation or partial alleviation of the symptoms of the disease or condition being treated.
[0126] As used herein, the term "composition" is intended to encompass a product comprising the specified ingredients in therapeutically effective amounts, as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts.
[0127] As used herein, the term "antagonist" or "inhibitor" refers to a compound that can produce a functional antagonistic effect on the TRPM3 ion channel, including competitive antagonists, non-competitive antagonists, desensitizing agonists and partial agonists.
[0128] For the 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 states mediated by the TRPM3 ion channel.
[0129] As used herein, the term "TRPM3-mediated disorder" refers to a disorder or disease consisting of pain and inflammatory hypersensitivity symptoms that can be prevented, treated, (partially) alleviated or improved using an antagonist of TRPM3. According to the International Association for the Study of Pain and for the purposes of the present invention, pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described with such damage. Preferably, the disorder mediated by TRPM3 is pain or epilepsy. Preferably, the disorder mediated by TRPM3 is epilepsy, and the epilepsy is preferably selected from epileptic encephalopathy. For the purposes of the present invention, the term "epileptic encephalopathy" refers to a group of severe epilepsy characterized by epileptic seizures and encephalopathy. Preferably, the disorder mediated by TRPM3 is pain, and the pain is preferably selected from nociceptive pain, inflammatory pain and neuropathic pain. More preferably, pain is postoperative pain. For the purposes of the present invention, the term "inflammatory hypersensitivity" is used to refer to a condition characterized by one or more of the hallmarks of inflammation (including edema, erythema, hyperthermia and pain) and / or an exaggerated physiological or pathophysiological response to one or more types of stimulation (including thermal, mechanical and / or chemical stimulation).
[0130] The invention will be further described and in some cases described with respect to specific embodiments but the invention is not limited thereto.
[0131] Preferred claims (features) and embodiments of the compounds and methods of the present invention are now described. Each claim and embodiment of the present invention so defined may be combined with any other claim and / or embodiment, unless expressly indicated to the contrary. Specifically, any feature indicated as preferred or advantageous may be combined with any one or more other features indicated as preferred or advantageous.
[0132] The numbered claims of this invention are:
[0133] 1. A compound of formula (I), its stereoisomeric form, physiologically acceptable salt, solvate and / or polymorph
[0134]
[0135]
[0136] in
[0137] R 1 Indicates -F, -Cl, -Br, -I, -CN, -R W 、-OR W 、-OC(=O)R W 、-NR W RX 、-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 ;
[0138] Q stands for -NR 3 R 4 ;
[0139] R 3 Indicates -OH or -R Y1 ;
[0140] R 4 Indicates -R Y2 or -S(=O) 2 R Y3 ;
[0141] or R 3 and R 4 together form a 4-, 5-, 6-, 7- or 8-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
[0142] T stands for -O-, and U stands for -(CR 5 R 5 ') n -; or T means -(CR 5 R 5 ') n -, and U represents -O-;
[0143] n is an integer selected from 1, 2, 3, 4 or 5;
[0144] R 5 and R 5 'Independently represent -R Y4 ;
[0145] R 6 and R 8 Independently represent -F, -Cl, -Br, -I, -CN, -NO 2 、-SF 5 , -R W 、-OR W 、-OC(=O)R W 、-NR W R X、-NR W C(=O)R X 、-SR W 、-S(=O)R W 、-S(=O) 2 R W 、-C(=O)R W 、-C(=O)OR W or -C(=O)NR W R X ;
[0146] W stands for
[0147] 3-14 membered cycloalkyl, which is saturated or unsaturated; unsubstituted, monosubstituted or polysubstituted; specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated; unsubstituted, monosubstituted or polysubstituted;
[0148] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted;
[0149] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or polysubstituted;
[0150] 5-14 membered heteroaryl, which is mono- or poly-substituted; or
[0151] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 - alkynyl; which is in each case unsubstituted, monosubstituted or polysubstituted;
[0152] in
[0153] R W and R X Independently of each other, in each case independently
[0154] -H;
[0155] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0156] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0157] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0158] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0159] R Y1 , R Y2 , R Y3 and R Y4 Independently of each other, in each case independently
[0160] -H;
[0161] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0162] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0163] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0164] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0165] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0166] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0167] and wherein "mono- or poly-substituted" in each case independently means substitution by one or more substituents independently selected from the group consisting of: -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 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, -C1-6 -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) 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-(3-14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl, -C 1-6 -alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 14-membered heteroaryl, -C 1-6 -alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -O-(5- to 14-membered heteroaryl), -C(=O)-(3- to 14-membered cycloalkyl), -C(=O)-(3- to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5- to 14-membered heteroaryl), -S(=O) 2 -(3-14 membered cycloalkyl), -S(=O) 2 -(3 to 14 membered heterocycloalkyl), -S(=O) 2 -phenyl or -S(=O) 2 -(5- to 14-membered heteroaryl);
[0168] Alternatively, the compound is 5-(benzyloxy)-2-methylfuro[2,3-c]pyridine-3-carboxylate.
[0169] 2. A compound according to statement 1, wherein T represents -O-, and U represents -(CR 5 R 5 ') n -.
[0170] 3. A compound according to any one of statements 1 or 2, wherein R 1 express
[0171] -H, -F, -Cl, -Br, -I;
[0172] -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0173] -OC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0174] -C(=O)C 1-6- alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0175] -C(=O)OC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0176] -C(=O)NH 2 ;
[0177] -C(=O)NHC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0178] -C(=O)N(C 1-6 -alkyl) 2 , which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0179] -S(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0180] -S(=O) 2 -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0181] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0182] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0183] 4. A compound according to any one of the preceding statements, wherein R 1 express
[0184] -H, -F, -Cl, -Br, -I;
[0185] -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0186] -OC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0187] -C(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0188] -C(=O)OC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0189] -C(=O)NH 2 ;
[0190] -C(=O)NHC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0191] -C(=O)N(C 1-6 -alkyl) 2 , which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0192] -S(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0193] -S(=O) 2 -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0194] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0195] 3-14 membered saturated cycloalkyl, 5-14 membered cycloalkenyl, 8-14 membered cycloalkynyl, which is unsubstituted, mono-, poly- or poly-substituted; wherein the 3-14 membered cycloalkyl, 5-14 membered cycloalkenyl or 8-14 membered cycloalkynyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6-heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably, a 3-12-membered saturated cycloalkyl, a 5-12-membered cycloalkenyl or an 8-12-membered cycloalkynyl, which is unsubstituted, monosubstituted or polysubstituted, wherein the 3-12-membered cycloalkyl, 5-12-membered cycloalkenyl or 8-12-membered cycloalkynyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably, a 3-10 membered saturated cycloalkyl, a 5-10 membered cycloalkenyl or an 8-10 membered cycloalkynyl, which is unsubstituted, mono- or polysubstituted, wherein the 3-10 membered cycloalkyl, the 5-10 membered cycloalkenyl or the 8-10 membered cycloalkynyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably, a 3-8 membered saturated cycloalkyl, a 5-8 membered cycloalkenyl or an 8 membered cycloalkynyl, which is unsubstituted, mono- or polysubstituted, wherein the 3-8 membered cycloalkyl, the 5-8 membered cycloalkenyl or the 8 membered cycloalkynyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0196] 5. A compound according to any one of the preceding statements, wherein R 1 Indicates -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 , -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)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.
[0197] 6. A compound according to any one of the preceding statements, wherein R 1 Indicates -H, -C 1-6 -alkyl, -C 1-6 -Alkylene-OC 1-6 -alkyl, -CHF 2 , -CF 3 or unsubstituted-cyclopentyl.
[0198] 7. A compound according to any one of the preceding statements, wherein R 3 express
[0199] -H;
[0200] -OH;
[0201] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0202] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0203] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0204] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0205] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0206] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0207] 8. A compound according to any one of the preceding statements, wherein R 3 express
[0208] -H;
[0209] -OH;
[0210] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0211] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0212] 9. A compound according to any one of the preceding statements, wherein R 3 Indicates -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 .
[0213] 10. A compound according to any one of the preceding statements, wherein R 3 represents -H, -OH or saturated, unsubstituted or monosubstituted -C 1-6 -alkyl.
[0214] 11. A compound according to any one of the preceding statements, wherein R 3 Indicates -H.
[0215] 12. A compound according to any one of the preceding statements, wherein R4 express
[0216] -H;
[0217] -S(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0218] -S(=O) 2 -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0219] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0220] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0221] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0222] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0223] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1 -C6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0224] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0225] 13. A compound according to any one of the preceding statements, wherein R 4 express
[0226] -H;
[0227] -S(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0228] -S(=O) 2 -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0229] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0230] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0231] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6-heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0232] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0233] -C 1-6 - alkylene-phenyl which is unsubstituted, monosubstituted or polysubstituted;
[0234] - phenyl, which is unsubstituted, monosubstituted or polysubstituted; or
[0235] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0236] 14. A compound according to any one of the preceding statements, wherein R 4 express
[0237] -S(=O) 2 C 1-6 -alkyl, which is saturated or unsaturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0238] -S(=O) 2 (3-14 membered cycloalkyl), wherein the 3-14 membered cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, which are in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted independently of one another by substituents selected from the group consisting of -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)OC1-6 -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 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0239] -C 1-6 -alkyl, which is saturated or unsaturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0240] -C 1 -C 6 -heteroalkyl, which is saturated or unsaturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0241] 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3-14 membered cycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3- to 14-membered cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, which are in each case saturated or unsaturated, which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0242] 3-14 membered heterocycloalkyl or -C 1-6 -alkylene-(3-14 membered heterocycloalkyl), wherein -C 1-6 -Alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3- to 14-membered heterocycloalkyl is in each case selected from the group consisting of azepane, 1,4-oxazepane, azetidine, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxazolidine, morpholine, oxazolidine, oxetane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiacyclopent ... pentane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiocyclohexane, 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-pyrrolizine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole and octahydropyrrolo[1,2-a]pyrazine; which are in each case unsubstituted, monosubstituted or polysubstituted, independently of one another, by substituents selected from the group consisting of: -F, -Cl, -C 1-6 -alkyl, -C 1-6 -Alkylene-CF 3 、-OH、=O、-OC 1-6 -alkyl, -C1-6 -alkylene-OH, -C 1-6 -Alkylene-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 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0243] -C 1-6 -alkylene-phenyl, which is unsubstituted, mono-substituted or poly-substituted independently of one another by substituents selected from the group consisting of: -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 、-NHC1-6 -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 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0244] -phenyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0245] 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), wherein -C 1-6 -Alkylene- is unsubstituted or monosubstituted by -OH, wherein the 5- to 14-membered heteroaryl is in each case selected from the group consisting of benzimidazole, benzisoxazole, benzoxazole, benzodioxole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furan, furan, imidazole, imidazopyridine, indazole, indole, indolizine, isobenzofuran, isoindole, isoquinoline, isothiazole , isoxazole, naphthylidine, 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; which are in each case unsubstituted, monosubstituted or polysubstituted, independently of one another, by substituents selected from the group consisting of: -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 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl.
[0246] 15. A compound according to any one of the preceding statements, wherein R 4 express
[0247] -H;
[0248] -S(=O) 2 C 1-6 -alkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted by -F;
[0249] -S(=O) 2(3-14 membered cycloalkyl), which is saturated and unsubstituted;
[0250] -C 1-6 -alkyl, which is saturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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 , 3-14 membered cycloalkyl, unsubstituted-phenyl, oxetanyl or pyrimidinyl;
[0251] 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3-14 membered cycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or mono- or polysubstituted by -F, -Cl, -Br, -I, -OH, wherein the 3- to 14-membered cycloalkyl is saturated, unsubstituted, mono- or di-substituted independently of one another by substituents selected from the group consisting of: -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 , 3-14 membered cycloalkyl, unsubstituted-phenyl, oxetanyl or pyrimidinyl;
[0252] 3-14 membered heterocycloalkyl or -C 1-6 -alkylene-(3-14 membered heterocycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or mono- or polysubstituted by -F, -Cl, -Br, -I, -OH, wherein the 3- to 14-membered heterocycloalkyl is in each case selected from azetidine, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahydropyrrolo[1,2-a]pyrrole, oxazine, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, quinuclidine, hexahydro-1H-pyrrolizine, 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 1,1-dioxothiocyclohexane, which are in each case unsubstituted, monosubstituted or polysubstituted, independently of one another, by substituents selected from the group consisting of: -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 , -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 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- to 14-membered heteroaryl;
[0253] 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -F, -Cl, -Br, -I, -OH, wherein the 5- to 14-membered heteroaryl is in each case selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole and [1,2,4]triazolo[4,3-a]pyrimidine, which are in each case unsubstituted, monosubstituted or disubstituted independently of one another by substituents selected from the group consisting of -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 cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted-phenyl, 5- to 14-membered heteroaryl.
[0254] 16. A compound according to any one of the preceding statements, wherein R 4 express
[0255] -H;
[0256] -S(=O) 2 C 1-6 -alkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted by -F;
[0257] -S(=O) 2 (3-14 membered cycloalkyl), which is saturated and unsubstituted;
[0258] -C 1-6 -alkyl, which is saturated, unsubstituted, mono- or di-substituted independently of one another by substituents selected from the group consisting of: OH, -OC 1-6 -alkyl, -N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-NH 2 , -C 1-6 -Alkylene-NH-C 1-6 -alkyl, unsubstituted-phenyl;
[0259] 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3-14 membered cycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3-14 membered cycloalkyl is saturated, unsubstituted, monosubstituted or disubstituted independently of one another by substituents selected from the group consisting of: 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 -alkyl;
[0260] 3-14 membered heterocycloalkyl or -C 1-6 -alkylene-(3-14 membered heterocycloalkyl), wherein -C 1-6-alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3- to 14-membered heterocycloalkyl is in each case selected from azetidine, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, 8-azabis[c]pyrrole ... 1,4-oxazepane, pyrrolidine, cyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, quinuclidine, hexahydro-1H-pyrrolizine, 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 1,1-dioxothiocyclohexane, which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -F, -OH, =O, -C 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 -alkylene-phenyl;
[0261] unsubstituted-phenyl;
[0262] 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), wherein -C 1-6-alkylene- is unsubstituted or monosubstituted by -OH, wherein the 5- to 14-membered heteroaryl is in each case selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole and [1,2,4]triazolo[4,3-a]pyrimidine, which are in each case unsubstituted, monosubstituted or disubstituted independently of one another by substituents selected from the group consisting of: -C 1-6 -alkyl, -OH.
[0263] 17. A compound according to any of the preceding statements, wherein
[0264] R 3 indicates -H; and
[0265] R 4 express
[0266] -H;
[0267] -S(=O) 2 C 1-6 -alkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted by -F;
[0268] -S(=O) 2 (3-14 membered cycloalkyl), which is saturated and unsubstituted;
[0269] -C 1-6 -alkyl, which is saturated, unsubstituted, mono- or di-substituted independently of one another by substituents selected from the group consisting of: -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;
[0270] 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3-14 membered cycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3-14 membered cycloalkyl is saturated, unsubstituted, monosubstituted or disubstituted independently of one another by substituents selected from the group consisting of: C1-6 -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 -alkyl;
[0271] 3-14 membered heterocycloalkyl or -C 1-6 -alkylene-(3-14 membered heterocycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3- to 14-membered heterocycloalkyl is in each case selected from azetidine, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, 8-azabis[c]pyrrole ... 1,4-oxazepane, pyrrolidine, cyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, quinuclidine, hexahydro-1H-pyrrolizine, 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 1,1-dioxothiocyclohexane, which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -F, -OH, =O, -C 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 -alkylene-phenyl;
[0272] unsubstituted-phenyl;
[0273] 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 5- to 14-membered heteroaryl is in each case selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole and [1,2,4]triazolo[4,3-a]pyrimidine, which are in each case unsubstituted, monosubstituted or disubstituted independently of one another by substituents selected from the group consisting of: -C 1-6 -alkyl, -OH.
[0274] 18. A compound according to any one of the preceding statements, wherein R 3 and R 4 Together they form a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N, O and S, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted.
[0275] 19. A compound according to any one of the preceding statements, wherein R 3 and R 4 together form a heterocycle selected from the group consisting of pyrrolidine, piperidine, morpholine and piperazine, which are in each case unsubstituted, independently of one another, mono- or polysubstituted by substituents selected from the group consisting of: 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 substituted-C 1-6 -alkyl monosubstituted 1,2,4-oxadiazole.
[0276] 20. A compound according to any one of the preceding statements, wherein R3 and R 4 Together we form
[0277] The pyrrolidine ring is unsubstituted or substituted with -N(CH 3 ) 2 Single substituted;
[0278] A piperidine ring which is unsubstituted or monosubstituted with a substituent selected from the group consisting of: -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 substituted with -C 1-6 - alkyl monosubstituted 1,2,4-oxadiazole;
[0279] a morpholine ring which is unsubstituted; or
[0280] A piperazine ring which is unsubstituted or N-substituted with a substituent selected from the group consisting of: -C 1-6 -alkyl and unsubstituted-pyridyl.
[0281] 21. A compound according to any one of the preceding statements, wherein R 3 and R 4 Together with the nitrogen atom to which it is attached, it forms a residue selected from the group consisting of:
[0282]
[0283] 22. A compound according to any one of the preceding statements, wherein W represents
[0284] 3-14 membered cycloalkyl, which is saturated or unsaturated; unsubstituted, monosubstituted or disubstituted;
[0285] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted;
[0286] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or polysubstituted;
[0287] 5-14 membered heteroaryl, which is mono- or poly-substituted; or
[0288] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C6 - alkynyl; which is in each case unsubstituted, monosubstituted or disubstituted;
[0289] Specifically, W represents
[0290] 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or disubstituted;
[0291] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted;
[0292] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or polysubstituted;
[0293] 5-14 membered heteroaryl, which is mono- or poly-substituted; or
[0294] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl; which is in each case unsubstituted, monosubstituted or disubstituted.
[0295] 23. A compound according to any one of the preceding statements, wherein W represents
[0296] 3-14 membered saturated cycloalkyl, 5-14 membered cycloalkenyl, 8-14 membered cycloalkynyl, which are unsubstituted, monosubstituted or disubstituted;
[0297] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted;
[0298] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or polysubstituted;
[0299] 5-14 membered heteroaryl, which is mono- or poly-substituted; or
[0300] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl; which is in each case unsubstituted, monosubstituted or disubstituted.
[0301] 24. A compound according to any one of the preceding statements, wherein W represents
[0302] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted independently by substituents selected from the group consisting of: -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 cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5 to 14 membered heteroaryl, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted by substituents independently selected from the group consisting of: -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 cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl;
[0303] 6-14 membered aryl, which is unsubstituted, independently selected from the following mono- or poly-substituted: -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 cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl;
[0304] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, independently selected from the following mono- or poly-substituted: -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) 2C 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 cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl;
[0305] 5-14 membered heteroaryl, which is unsubstituted, independently selected from the following mono- or poly-substituted: -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(C1-6 -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 cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5 to 14 membered heteroaryl; or
[0306] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl; which is in each case unsubstituted, monosubstituted or polysubstituted independently by substituents selected from the group consisting of: -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-OC1-6 -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 cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted-phenyl, 5- to 14-membered heteroaryl.
[0307] 25. A compound according to any one of the preceding statements, wherein W represents
[0308] 3-10 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted independently by substituents selected from the group consisting of: -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 to 14 membered heteroaryl, specifically 3-10 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted by substituents independently selected from: -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- to 14-membered heteroaryl; or
[0309] 6-12 membered aryl, which is unsubstituted, independently selected from the following mono- or poly-substituted: -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 cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl;
[0310] 3-10 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, independently selected from the following mono- or poly-substituted: -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 cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl;
[0311] 5-10 membered heteroaryl, which is unsubstituted, independently selected from the following mono- or poly-substituted: -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 cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5 to 14 membered heteroaryl; or
[0312] -C 1 -C 6 -alkyl, which is unsubstituted, monosubstituted or polysubstituted independently by substituents selected from the group consisting of: -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- to 14-membered heteroaryl.
[0313] 26. A compound according to any one of the preceding statements, wherein W represents
[0314] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted independently by substituents selected from the group consisting of: -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)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 , specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, mono- or poly-substituted independently by substituents selected from: -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 ;
[0315] 6-14 membered aryl, which is unsubstituted, independently selected from the following mono- or poly-substituted: -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 ;
[0316] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, independently selected from the following mono- or poly-substituted: -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 ;
[0317] 5-14 membered heteroaryl, which is unsubstituted, independently selected from the following mono- or poly-substituted: -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, -OC1-6 -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
[0318] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl; which is in each case unsubstituted, monosubstituted or polysubstituted independently by substituents selected from the group consisting of: -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 .
[0319] 27. A compound according to any one of the preceding statements, wherein W represents
[0320] 3-10 membered cycloalkyl, which is saturated, unsubstituted, mono- or di-substituted independently by substituents selected from: -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 ,
[0321] 6-14 membered aryl, which is unsubstituted, independently selected from the following mono- or poly-substituted: -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 ;
[0322] 3-10 membered heterocycloalkyl, which is saturated, unsubstituted, independently selected from the following mono- or di-substituted: -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)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 ;
[0323] 5-10 membered heteroaryl, which is unsubstituted, independently selected from the following mono- or di-substituted: -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
[0324] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl; which is unsubstituted, monosubstituted or disubstituted independently by substituents selected from the group consisting of: -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 .
[0325] 28. A compound according to any one of the preceding statements, wherein R 5 and R 5 'Independently express
[0326] -H;
[0327] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0328] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0329] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0330] 29. A compound according to any of the preceding statements, wherein n is an integer selected from 1, 2 or 3, and
[0331] R 5 and R 5 'Independently express
[0332] -H;
[0333] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0334] -C1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0335] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0336] 30. A compound according to any of the preceding statements, wherein R 5 and R 5 ' represents -H, -C independently of each other 1 -C 6 -alkyl or -C 1 -C 6 -alkylene-N(C 1 -C 6 -alkyl) 2 .
[0337] 31. A compound according to any of the preceding statements, wherein R 6 and R 8 Independently express
[0338] -H;
[0339] -F, -Cl, -Br, -I, -OH, -SH, -SF 5 、-CN、-NO 2 , -C(=O)OH, -NH 2 ;
[0340] -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0341] -OC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0342] -NHC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0343] -N(C 1-6 -alkyl) 2 , which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0344] -C(=O)OC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0345] -OC(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0346] -C 1-6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0347] 32. A compound according to any one of the preceding statements, wherein R 6 and R 8 Independently express
[0348] -H, -F, -Cl, -Br, -I, -OH, -SH, -SF 5 、-CN、-NO 2 , -C(=O)OH, -NH 2 ,
[0349] -C 1-6 -alkyl, -CF 3 , -CHF 2 、-CH 2 F,
[0350] -OC 1-6 -alkyl, -OCF 3 、-OCHF 2 、-OCH 2 F,
[0351] -NHC 1-6 -alkyl, which is unsubstituted or substituted by one or more substituents independently selected from the group consisting of: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F. SF 5 、-NO2 , -C(=O)OH, -NH 2 and -C(=O)NH 2 ;
[0352] -N(C 1-6 -alkyl) 2 , which is unsubstituted or substituted by one or more substituents independently selected from the following: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F. SF 5 、-NO 2 , -C(=O)OH, -NH 2 and -C(=O)NH 2 ;
[0353] -C(=O)OC 1-6 -alkyl, which is unsubstituted or substituted by one or more substituents independently selected from the group consisting of: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F. SF 5 、-NO 2 , -C(=O)OH, -NH 2 and -C(=O)NH 2 ;
[0354] -OC(=O)C 1-6 -alkyl, which is unsubstituted or substituted by one or more substituents independently selected from the group consisting of: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F. SF 5 、-NO 2 , -C(=O)OH, -NH 2 and -C(=O)NH 2 ;or
[0355] -C 1-6 -heteroalkyl, which is unsubstituted or substituted by one or more substituents independently selected from the group consisting of: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F. SF 5 、-NO 2 , -C(=O)OH, -NH 2 and -C(=O)NH 2 .
[0356] 33. A compound according to any of the preceding statements, wherein R 6 Indicates -H, -F, -Cl, -CN or -C 1 -C 6 -alkyl.
[0357] 34. A compound according to any of the preceding statements, wherein R 6 -H is not indicated.
[0358] 35. A compound according to any of the preceding statements, wherein R 8 Indicates -H, -F, -Cl, -CN or -C 1 -C 6 -alkyl.
[0359] 36. A compound according to any of the preceding statements, wherein R 8 -H is not indicated.
[0360] 37. A compound according to any of the preceding statements, wherein
[0361] (i)R 6 and R 8 Each represents -H; or
[0362] (ii) R 6 and R 8 independently represent -F, -Cl, -CN or -CH 3 ;or
[0363] (iii) R 6 and R 8 One of them represents -H, and R 6 and R 8 The other one of the above represents -F, -Cl, -CN or -CH 3 .
[0364] 38. A compound according to any of the preceding statements, selected from the group consisting of Cpd 001 to Cpd 036 as mentioned herein, or a physiologically acceptable salt thereof.
[0365] 39. A compound according to any of the preceding statements, wherein
[0366] R 1 Indicates H, -CH 2 F, -CHF 2 or -CF 3 ;
[0367] R 3 Indicates -H;
[0368] R 4 express
[0369] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0370] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0371] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0372] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1-C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0373] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0374] or R 3 and R 4 together form a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N, O and S, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
[0375] R 5 and R 5 ' represents -H, -C independently of each other 1 -C 6 -alkyl or -C 1 -C 6 -alkylene-N(C 1 -C 6 -alkyl) 2 ;
[0376] R 6 and R 8 independently represent -H, -F, -Cl, -CN or -C 1 -C 6 -alkyl;
[0377] W stands for
[0378] 3-14 membered cycloalkyl, which is saturated or unsaturated; unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated; unsubstituted, monosubstituted or polysubstituted;
[0379] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted;
[0380] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or polysubstituted;
[0381] 5-14 membered heteroaryl, which is mono- or poly-substituted; or
[0382] -C 1 -C6 - alkyl; which is unsubstituted, monosubstituted or polysubstituted.
[0383] 40. A compound according to any of the preceding statements, wherein
[0384] R 1 Indicates H, -CH 2 F, -CHF 2 or -CF 3 ;
[0385] R 3 Indicates -H;
[0386] R 4 express
[0387] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0388] 3-14 membered saturated cycloalkyl, 5-14 membered cycloalkenyl, 8-14 membered cycloalkynyl, which is unsubstituted, monosubstituted or polysubstituted; wherein each of the 3-14 membered cycloalkyl, 5-14 membered cycloalkenyl, 8-14 membered cycloalkynyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0389] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0390] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0391] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0392] or R 3 and R 4 together form a 5- or 6-membered heterocyclic ring containing 1 or 2 heteroatoms selected from N, O and S, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
[0393] R 5 and R 5 ' represents -H, -C independently of each other 1 -C 6 -alkyl or -C 1 -C 6 -alkylene-N(C 1 -C 6 -alkyl) 2 ;
[0394] R 6 and R 8 independently represent -H, -F, -Cl, -CN or -C 1 -C 6 -alkyl;
[0395] W stands for
[0396] 3-14 membered saturated cycloalkyl, 5-14 membered cycloalkenyl, 8-14 membered cycloalkynyl, which are unsubstituted, monosubstituted or polysubstituted;
[0397] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted;
[0398] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or polysubstituted;
[0399] 5-14 membered heteroaryl, which is mono- or poly-substituted; or
[0400] -C 1 -C 6 - alkyl; which is unsubstituted, monosubstituted or polysubstituted.
[0401] 41. A pharmaceutical composition or medicament comprising a compound according to any one of the preceding statements.
[0402] 42. A compound according to any of the preceding statements or a pharmaceutical composition according to statement 41 for use as a medicament.
[0403] 43. A compound according to any of the preceding statements or a pharmaceutical composition according to statement 41 for use in the treatment of pain or epilepsy; preferably pain and epileptic encephalopathy.
[0404] 44. The compound for use or pharmaceutical composition for use according to statement 43, wherein the pain is selected from nociceptive pain, inflammatory pain and neuropathic pain.
[0405] 45. The compound for use or pharmaceutical composition for use according to statement 43, wherein the pain is postoperative pain.
[0406] 46. A method for preventing and / or treating a TRPM3-mediated disorder, the method comprising administering to a subject an effective amount of a compound according to any one of statements 1 to 40 or a pharmaceutical composition according to claim 41.
[0407] 47. A method for preventing and / or treating pain or epilepsy; such as epileptic encephalopathy, the method comprising administering to a subject an effective amount of a compound according to any one of statements 1 to 40 or a pharmaceutical composition according to claim 41.
[0408] 48. The method of statement 47, wherein the pain is selected from the group consisting of nociceptive pain, inflammatory pain, and neuropathic pain.
[0409] The first aspect of the present invention is to provide a compound of formula (I), its stereoisomeric form, physiologically acceptable salt, solvate and / or polymorph
[0410]
[0411] in
[0412] R 1 Indicates -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 ;
[0413] Q stands for -NR3 R 4 ;
[0414] R 3 Indicates -OH or -R Y1 ;
[0415] R 4 Indicates -R Y2 or -S(=O) 2 R Y3 ;
[0416] or R 3 and R 4 together form a 4-, 5-, 6-, 7- or 8-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted;
[0417] T stands for -O-, and U stands for -(CR 5 R 5 ') n -; or T means -(CR 5 R 5 ') n -, and U represents -O-;
[0418] n is an integer selected from 1, 2, 3, 4 or 5;
[0419] R 5 and R 5 'Independently represent -R Y4 ;
[0420] R 6 and R 8 Independently represent -F, -Cl, -Br, -I, -CN, -NO 2 、-SF 5 , -R W 、-OR W 、-OC(=O)R W 、-NR W R X 、-NR W C(=O)R X 、-SR W 、-S(=O)R W 、-S(=O) 2 R W 、-C(=O)R W 、-C(=O)OR W or -C(=O)NR W R X ;
[0421] W stands for
[0422] 3-14 membered cycloalkyl, which is saturated or unsaturated; unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated; unsubstituted, monosubstituted or polysubstituted;
[0423] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted;
[0424] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or polysubstituted;
[0425] 5-14 membered heteroaryl, which is mono- or poly-substituted; or
[0426] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 - alkynyl; which is in each case unsubstituted, monosubstituted or polysubstituted;
[0427] in
[0428] R W and R X Independently of each other, in each case independently
[0429] -H;
[0430] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0431] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0432] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6-heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0433] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0434] R Y1 , R Y2 , R Y3 and R Y4 Independently of each other, in each case independently
[0435] -H;
[0436] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0437] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0438] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0439] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0440] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0441] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0442] and wherein "mono- or poly-substituted" in each case independently means substitution by one or more substituents independently selected from the group consisting of: -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, -C1-6 -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 -NH2 、-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 , -C1-6 -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-(3-14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl, -C 1-6 -alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 14-membered heteroaryl, -C1-6 -alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -O-(5- to 14-membered heteroaryl), -C(=O)-(3- to 14-membered cycloalkyl), -C(=O)-(3- to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5- to 14-membered heteroaryl), -S(=O) 2 -(3-14 membered cycloalkyl), -S(=O) 2 -(3 to 14 membered heterocycloalkyl), -S(=O) 2 -phenyl or -S(=O) 2 -(5- to 14-membered heteroaryl);
[0443] Alternatively, the compound is 5-(benzyloxy)-2-methylfuro[2,3-c]pyridine-3-carboxylate.
[0444] In some embodiments, T represents -O-, U represents -(CR 5 R 5 ') n -; and n is an integer selected from 1, 2 or 3.
[0445] In some embodiments, R 1 express
[0446] -H, -F, -Cl, -Br, -I, CN;
[0447] -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0448] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0449] -OH;
[0450] -OC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0451] -NH 2 ;
[0452] NHC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0453] -N(C 1-6 -alkyl) 2 , which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0454] -NHC(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0455] -NC 1-6 -alkylC(=O)C 1-6 - alkyl, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0456] -SH;
[0457] -SC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0458] -C(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0459] -C(=O)OC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0460] -C(=O)NH 2 ;
[0461] -C(=O)NHC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0462] -C(=O)N(C 1-6 -alkyl) 2 , which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0463] -S(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0464] -S(=O) 2 -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0465] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0466] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0467] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0468] In some embodiments, R 1 express
[0469] -H, -F, -Cl, -Br, -I, CN;
[0470] -C 1-6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, which is in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0471] -C 1 -C 6 -heteroalkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0472] -OH;
[0473] -OC 1-6 -alkyl, -OC 2 -C 6 -Alkenyl, -OC 2 -C 6 -alkynyl, which is in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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)-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 ;
[0474] -NH 2 ;
[0475] -NHC 1-6 -alkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 , -C 1-6 -Alkylene-CF3 , -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 ;
[0476] -N(C 1-6 -alkyl) 2 , which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl2 , -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 ;
[0477] -NHC(=O)C 1-6 -alkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH 2 , -CF2 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 ;
[0478] -NC 1-6 -alkylC(=O)C 1-6 -alkyl, which is in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0479] -SH;
[0480] -SC 1-6 -alkyl, -SC 2 -C6 -Alkenyl, -SC 2 -C 6 -alkynyl, which is in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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(C1-6 -alkyl) 2 ;
[0481] -C(=O)C 1-6 -alkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0482] -C(=O)OC 1-6 -alkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0483] -C(=O)NH 2 ;
[0484] -C(=O)NHC 1-6 -alkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0485] -C(=O)N(C 1-6 -alkyl) 2 , which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0486] -S(=O)C 1-6 -alkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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(C1-6 -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 ;
[0487] -S(=O) 2 -C 1-6 -alkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0488] -C 1 -C 6 -heteroalkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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
[0489] 3-14 membered cycloalkyl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0490] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 , -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 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 .
[0491] In some embodiments, R 1 Indicates -H, -F, -Cl, -Br, -I, -CN, -C 1-6 -alkyl, -C 2 -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-CF3 , -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 3-14 membered cycloalkyl or unsubstituted 3-14 membered heterocycloalkyl. 1 Indicates -H, -F, -Cl, -Br, -I, CN, -C 1-6 -alkyl, -C 2 -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-cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl or unsubstituted cyclohexyl.
[0492] In some embodiments, R 1 Indicates -H, CN, -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. Preferably, R 1 Indicates -H, -CH 2 F, -CHF 2 , -CF 3 、-C(=O)NH 2 , -CN, unsubstituted-cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl or unsubstituted cyclohexyl. Preferably, R 1 Indicates H, -C 1-6 -alkyl, -C(=O)NH 2 , -CHF 2 , unsubstituted-cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl or unsubstituted cyclohexyl.
[0493] Preferably, R 1 Indicates -H, -CN, -C 1-3 -alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2Cl, -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 specifically -H, -CH 3 or -CF 2 H,.
[0494] In some embodiments, R 3 express
[0495] -H;
[0496] -OH;
[0497] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0498] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0499] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0500] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6-heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0501] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0502] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0503] In some embodiments, R 3 express
[0504] -H;
[0505] -OH;
[0506] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, which is in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0507] -C 1 -C 6 -heteroalkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 ;
[0508] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkages, which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 , specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkages, which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -F, -Cl, -Br, -I, -CF 3 , -CF 2 H, -CFH2 , -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 ;
[0509] 3-14 membered heterocycloalkyl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted independently of one another by substituents selected from the group consisting of: -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;;
[0510] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkages, which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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
[0511] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted independently of one another by substituents selected from the group consisting of: -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)NH2 , -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 .
[0512] In some embodiments, R 3 express
[0513] -H;
[0514] -OH;
[0515] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0516] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0517] Preferably, R 3 Indicates -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 2H, -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 Indicates -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 represents -H, -OH or saturated, unsubstituted or monosubstituted -C 1-6 -alkyl. Preferably, R 3 Indicates -H.
[0518] In some embodiments, R 3 and R 4 Neither represents -H. In some embodiments, R 3 Indicates -H, and R 4 -H is not indicated.
[0519] In some embodiments, R4 express
[0520] -H;
[0521] -S(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0522] -S(=O) 2 -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0523] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0524] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0525] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0526] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0527] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally substituted by -C 1 -C6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or
[0528] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0529] Preferably, R 4 express
[0530] -S(=O) 2 C 1-6 -alkyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0531] -S(=O) 2 (3-14 membered cycloalkyl), wherein the 3-14 membered cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, which are in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted independently of one another by substituents selected from the group consisting of -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)OC1-6 -Alkylene-CF 3 、-C(=O)NH 2 、-C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 、-S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0532] -C 1-6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, which is unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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-CF3 、-C(=O)NH 2 、-C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 、-S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0533] 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3-14 membered cycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3- to 14-membered cycloalkyl is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, which are in each case saturated or unsaturated, which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0534] 3-14 membered heterocycloalkyl or -C 1-6 -alkylene-(3-14 membered heterocycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3- to 14-membered heterocycloalkyl is in each case selected from the group consisting of azepane, 1,4-oxazepane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxazolidine, morpholine, oxazolidine, oxetane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, Thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiocyclohexane, 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-pyrrolizine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole and octahydropyrrolo[1,2-a]pyrazine; which are in each case unsubstituted, monosubstituted or polysubstituted, independently of one another, by substituents selected from the group consisting of: -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0535] -phenyl, which is unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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-NH2 , -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl) 2 , -C 1-6 -Alkylene-NH-C 1-6 -Alkylene-CF 3 , -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)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 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0536] 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), wherein -C 1-6 -Alkylene- is unsubstituted or monosubstituted by -OH, wherein the 5- to 14-membered heteroaryl is in each case selected from the group consisting of benzimidazole, benzisoxazole, benzoxazole, benzofuran, benzothiadiazole, benzothiazole, benzothiophene, carbazole, cinnoline, dibenzofuran, furan, furan, 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; which are in each case unsubstituted, monosubstituted or polysubstituted, independently of one another, by substituents selected from the group consisting of: -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 、-NHC1-6 -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 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl.
[0537] Preferably, R 4 express
[0538] -H;
[0539] -S(=O) 2 C 1-6 -alkyl, which is mono- or polysubstituted by -F;
[0540] -S(=O) 2 (3-14 membered cycloalkyl), which is unsubstituted;
[0541] -C 1-6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6-alkynyl, which is mono- or di-substituted independently of one another by substituents selected from the group consisting of: -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;
[0542] 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3-14 membered cycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3-14 membered cycloalkyl is saturated, unsubstituted, monosubstituted or disubstituted independently of one another by substituents selected from the group consisting of: 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 -alkyl;
[0543] 3-14 membered heterocycloalkyl or -C 1-6 -alkylene-(3-14 membered heterocycloalkyl), wherein -C 1-6-alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3- to 14-membered heterocycloalkyl is in each case selected from azetidine, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, 8-azabis[c]pyrrole ... 1,4-oxazepane, pyrrolidine, cyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, quinuclidine, hexahydro-1H-pyrrolizine, 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 1,1-dioxothiocyclohexane, which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -F, -OH, =O, -C 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 -alkylene-phenyl;
[0544] unsubstituted-phenyl;
[0545] 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), wherein -C 1-6-alkylene- is unsubstituted or monosubstituted by -OH, wherein the 5- to 14-membered heteroaryl is in each case selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole and [1,2,4]triazolo[4,3-a]pyrimidine, which are in each case unsubstituted, monosubstituted or disubstituted independently of one another by substituents selected from the group consisting of: -C 1-6 -alkyl, -OH.
[0546] In some embodiments, R 4 express
[0547] A residue selected from the group consisting of:
[0548]
[0549] or
[0550] C 1 -C 6 -alkyl, which is unsubstituted, monosubstituted or polysubstituted; preferably represents the residue -CR'R"-(CH 2 ) m -OH, wherein m is an integer selected from 1, 2, 3, 4, 5 or 6, preferably selected from 1, 2 or 3; and wherein R' and R" independently represent -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) 2Preferably, at least R' or R" does not represent -H; preferably, neither R' or R" represents -H; preferably represents a residue selected from the group consisting of:
[0551]
[0552] or;
[0553] 3-14 membered cycloalkyl which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-13 membered cycloalkyl which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered cycloalkyl which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-11 membered cycloalkyl which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered cycloalkyl which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably represents a cycloalkyl residue selected from the group consisting of:
[0554]
[0555]
[0556] or;
[0557] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is connected by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-12 membered cycloalkyl is linked by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-10 membered cycloalkyl is linked by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-8 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-8 membered cycloalkyl is connected by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is connected by -C 1 -C 6-alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-12 membered cycloalkyl is connected by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-10 membered cycloalkyl is connected by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-8 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-8 membered cycloalkyl is connected by -C 1 -C 6 - an alkylene-linkage, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably represents a residue selected from the group consisting of:
[0558] or
[0559] 3-14 membered heterocycloalkyl, which is saturated, unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-13 membered heterocycloalkyl, which is saturated, unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered heterocycloalkyl, which is saturated, unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-11 membered heterocycloalkyl, which is saturated, unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered heterocycloalkyl, which is saturated, unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably represents a heterocycloalkyl residue selected from the group consisting of:
[0560]
[0561]
[0562] More preferably selected from the group consisting of:
[0563]
[0564]
[0565] or
[0566] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is substituted by -C 1-C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-12 membered heterocycloalkyl is linked by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-10 membered heterocycloalkyl is connected by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-8 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-8 membered heterocycloalkyl is connected by -C 1 -C 6 - an alkylene-linkage, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably represents a residue selected from the group consisting of:
[0567]
[0568] or
[0569] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-12 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-10 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-8 membered aryl which is unsubstituted, monosubstituted or polysubstituted; or
[0570] 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is substituted by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 6-12 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-12 membered aryl is connected by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 6-10 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-10 membered aryl is connected by -C 1 -C 6 - an alkylene-linkage, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably represents a residue selected from the group consisting of:
[0571]
[0572] or
[0573] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-12 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-10 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-9 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably represents a residue selected from the group consisting of:
[0574]
[0575]
[0576] More preferably represents a residue selected from the group consisting of:
[0577]
[0578] or
[0579] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is substituted by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 5-12 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-12 membered heteroaryl is connected by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; 5-10 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-10 membered heteroaryl is connected by -C 1 -C 6 -alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; 5-8 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-8 membered heteroaryl is linked via -C1-C6-alkylene-linked, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably represents a residue selected from the group consisting of:
[0580]
[0581] In some embodiments, R 4 represents a residue according to the general formula (A),
[0582]
[0583] in
[0584] m A is 0 or 1;
[0585] Y A Selected from -O-, -NR A6 -and-CR A7 R A8 -;and
[0586] R A1 , R A2 , R A3 , R A4 , R A5 , R A6 , R A7 and R A8 Independently represent -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, it forms a ring and represents -CH 2 OCH 2 -、-CH 2 OCH 2 CH 2 -or-CH 2 CH 2 OCH 2 CH 2 -、-CH 2 NHCH 2 -、-CH 2 NHCH 2 CH 2 -or-CH 2CH 2 NHCH 2 CH 2 -.
[0587] In some embodiments, R 4 represents a residue according to the general formula (A) as defined above, wherein
[0588] m A is 0 or 1;
[0589] Y A Selected from -O- and -CR A7 R A8 -;and
[0590] R A1 , R A2 , R A3 , R A4 , R A5 , R A7 and R A8 Independently represent -H, -C 1-3 -alkylene-OH, -C 1-3 -alkylene-N(C 1-3 -alkyl) 2 or -C(=O)NH 2 ; preferably the condition is R A1 , R A2 , R A3 , R A4 , R A5 , R A7 and R A8 Only one of them represents a residue other than -H.
[0591] In some embodiments, R 4 represents a residue according to the general formula (A) as defined above, wherein
[0592] m A is 0 or 1;
[0593] Y A Selected from -O- and -CR A7 R A8 -;and
[0594] R A1 Indicates -C 1-3 -alkylene-OH, -C 1-3 -alkylene-N(C 1-3 -alkyl) 2 or -C(=O)NH 2 ;and
[0595] R A2 , R A3 , RA4 , R A5 , R A7 and R A8 Indicates -H.
[0596] In some embodiments, R 4 represents a residue according to the general formula (B),
[0597]
[0598] in
[0599] Y B Selected from -O-, -NR B8 -and-CR B9 R B10 -;and
[0600] R B1 , R B2 , R B3 , R B4 , R B5 , R B6 , R B7 , R B8 , R B9 and R B10 independently represent -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 Together they represent =O; or R B4 and R B5 Together they represent =O.
[0601] In some embodiments, R 4 represents a residue according to the general formula (B) as defined above, wherein
[0602] Y B Selected from -O- and -NR B8 -;and
[0603] R B1 , R B2 , R B3 , R B4 , R B5 , R B6 , R B7 , R B8 Independently represent -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 they represent =O; or R B4 and R B5 Together they represent =O; preferably the condition is R A1 , R A2 , R A3 , R A4 , R A5 , R A7 and R A8 Only 1, 2 or 3 of them represent residues other than -H; preferably, the condition is that R A1 , R A2 , R A3 , R A4 , R A5 , R A7 and R A8 At least one of represents a residue other than -H.
[0604] In some embodiments, R 4 represents a residue according to the general formula (C),
[0605]
[0606] in
[0607] Y C1 Selected from -O-, -S(=O) 2 -、-NR C8 -and-CR C9 R C10 -, and Y C2 Indicates -CR C11 R C12 -; or Y C1 Indicates -CR C9 R C10 -, and Y C2 Selected from -O-, -S(=O) 2 -and-NR C8 -;
[0608] 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 Independently express
[0609] -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 they represent =O; or R C4 and R C5 Together they represent =O; or R C9 and R C10 Together they represent =O; or R C11 and R C12 Together they represent =O.
[0610] In some embodiments, R 4 represents a residue according to the general formula (C) as defined above, wherein
[0611] Y C1 Selected from -O- or -NR C8 -, and Y C2 Indicates -CR C11 R C12 -; or Y C1 Indicates -CR C9 R C10 -, and Y C2 Selected from -O- and -NR C8 -;
[0612] R C1 , R C2 , R C3 , RC4 , R C5 , R C6 , R C7 , R C8 , R C9 , R C10 , R C11 and R C12 Independently represent -H, -F, -C 1-3 -alkyl, -C 1-3 -alkylene-OH or -C(=O)-NH 2 ; preferably the condition is 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 Only 1, 2 or 3 of them represent residues other than -H; preferably, the condition is that 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 At least one of represents a residue other than -H.
[0613] In some embodiments, R 4 express
[0614] (i) Residue -CR'R"-(CH 2 ) m -OH, wherein m is an integer from 1 to 6, preferably from 1 to 3; and wherein R' and R" independently represent -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 -C1-3 -alkylene-OH, preferably -H, -CH 3 or -C 1-3 -alkylene-OH. In a preferred embodiment, at least R' or R" does not represent -H. In a preferred embodiment, both R' and R" do not represent -H; or
[0615] (ii) a residue according to formula (D),
[0616]
[0617] in
[0618] m D and n D are independently 0, 1, 2 or 3; preferably, m D +n D ≤3;
[0619] Y D1 Selected from -O-, -S(=O) 2 -、-NR D8 -and-CR D9 R D10 -, and Y D2 Indicates -CR D11 R D12 -; or Y D1 Indicates -CR D9 R D10 -, and Y D2 Selected from -O-, -S(=O) 2 -and-NR D8 -;
[0620] 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 Independently represent -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(C1-3 -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 they represent =O; or R D4 and R D5 Together they represent =O; or R D9 and R D10 Together they represent =O; or R D11 and R D12 Together they represent =O;
[0621] Preferably,
[0622] m D and n D are independently 0, 1, 2 or 3; preferably, m D +n D ≤3;
[0623] Y D1 Selected from -O-, -NR D8 -and-CR D9 R D10 -, and Y D2 Indicates -CR D11 R D12 -; or Y D1 Indicates -CR D9 R D10 -, and Y D2 Selected from -O- and -NR D8 -;
[0624] 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 Independently represent -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 they represent =O; or R D4 and R D5 Together they represent =O; or R D9 and R D10 Together they represent =O; or R D11 and R D12 Together they represent =O; preferably the condition is 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 Only 1, 2 or 3 of them represent residues other than -H; preferably, the condition is that 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 At least one of represents a residue other than -H.
[0625] In some embodiments, R 4 represents a residue according to the general formula (A), (B), (C), (D) or the formula -CR'R"-(CH 2 ) m -OH residue.
[0626] In some embodiments, R 4 represents a residue selected from the group consisting of: -CH 3 ,
[0627]
[0628]
[0629] In some embodiments, R 3 is H, and R 4 Any embodiment described above.
[0630] In some embodiments, R 5 and R 5 'Independently express
[0631] -H;
[0632] -C 1 -C 6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0633] -C 1 -C 6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0634] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally substituted by -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linked, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally connected via -C 1 -C 6 -alkylene- or -C 1 -C 6 -heteroalkylene-linkage, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0635] Preferably, R 5 and R 5 ' represents -H, -C independently of each other 1 -C 6 -alkyl or -C 1 -C 6 -alkylene-N(C 1 -C 6 -alkyl) 2 .
[0636] In some embodiments, R 5 and R 5 At least one of ' is not -H.
[0637] In some embodiments, R 5 and R 5'Both are -H.
[0638] In a preferred embodiment, T represents -O-, and U represents -(CR 5 R 5 ') n , and the resulting portion -O-(CR 5 R 5 ') n - represents a residue selected from the group consisting of:
[0639]
[0640] In some embodiments, R 5 Indicates -H, and R 5 ' represents a residue selected from the group consisting of: -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.
[0641] In some embodiments, R 6 and R 8 Independently express
[0642] -H;
[0643] -F, -Cl, -Br, -I, -OH, -SH, -SF 5 、-CN、-NO 2 , -C(=O)OH, -NH 2 ;
[0644] -C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0645] -OC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0646] -NHC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0647] -N(C 1-6 -alkyl)2 , which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0648] -C(=O)OC 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0649] -OC(=O)C 1-6 - alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted;
[0650] -C 1-6 - heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
[0651] In some embodiments, R 6 and R 8 Independently express
[0652] -H;
[0653] -F, -Cl, -Br, -I, -OH, -SH, -SF 5 、-CN、-NO 2 , -C(=O)OH, -NH 2 ;
[0654] -C 1-6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl, which is in each case saturated or unsaturated, unsubstituted, mono- or polysubstituted independently of one another by substituents selected from the group consisting of: -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0655] -OC 1-6 -alkyl, which is saturated or unsaturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0656] -NHC 1-6 -alkyl, which is saturated or unsaturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0657] -N(C 1-6 -alkyl) 2 , which is saturated or unsaturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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)OC1-6 -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 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0658] -C(=O)OC 1-6 -alkyl, which is saturated or unsaturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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)NH2 、-C(=O)NH(C 1-6 -alkyl), -C(=O)N(C 1-6 -alkyl) 2 、-S(=O) 2 C 1-6 -alkyl, -phenyl, -C 1-6 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl;
[0659] -OC(=O)C 1-6 -alkyl, which is saturated or unsaturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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 -alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14 membered heterocycloalkyl; and unsubstituted 5-14 membered heteroaryl
[0660] -C 1-6 -heteroalkyl, which is saturated or unsaturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -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-alkylene-phenyl, saturated or unsaturated, unsubstituted 3-14-membered heterocycloalkyl; and unsubstituted 5-14-membered heteroaryl. .
[0661] Preferably, R 6 and R 8 Independently express
[0662] -H, -F, -Cl, -Br, -I, -OH, -SH, -SF 5 、-CN、-NO 2 , -C(=O)OH, -NH 2 ,
[0663] -C 1-6 -alkyl, -CF 3 , -CHF 2 、-CH 2 F,
[0664] -OC 1-6 -alkyl, -OCF 3 、-OCHF 2 、-OCH 2 F,
[0665] -NHC 1-6 -alkyl, which is unsubstituted or substituted by one or more substituents independently selected from the group consisting of: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F. SF 5 、-NO 2 , -C(=O)OH, -NH 2 and -C(=O)NH 2 ;
[0666] -N(C 1-6 -alkyl)2, which is unsubstituted or substituted by one or more substituents independently selected from the following: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F. SF 5 、-NO 2 , -C(=O)OH, -NH2 and -C(=O)NH 2 ;
[0667] -C(=O)OC 1-6 -alkyl, which is unsubstituted or substituted by one or more substituents independently selected from the group consisting of: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F. SF 5 、-NO 2 , -C(=O)OH, -NH 2 and -C(=O)NH 2 ;
[0668] -OC(=O)C 1-6 -alkyl, which is unsubstituted or substituted by one or more substituents independently selected from the group consisting of: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F. SF 5 、-NO 2 , -C(=O)OH, -NH 2 and -C(=O)NH 2 ;or
[0669] -C 1-6 -heteroalkyl, which is unsubstituted or substituted by one or more substituents independently selected from the group consisting of: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF 3 , -CHF 2 、-CH 2 F, -OCF 3 、-OCHF 2 、-OCH 2 F. SF 5 、-NO 2 , -C(=O)OH, -NH 2 and -C(=O)NH 2 .
[0670] In some embodiments, R 6 and R8 independently of one another represent a residue selected from the group consisting of: -H, -F, -Cl, -Br, -I, -CN, C 1-3 -alkyl, -CF 3 , -CF 2 H and -CFH 2 ; preferably -H or -F.
[0671] In some embodiments, R 6 Indicates -H, -F, -Cl, -CN or -C 1 -C 6 -alkyl.
[0672] In some embodiments, R 6 represents a residue selected from the group consisting of: -H, -F, -Cl, -CN or -CH 3 ; preferably -H, -F, -CN or -CH 3 .
[0673] In some embodiments, R 6 -H is not indicated.
[0674] In some embodiments, R 6 and R 8 independently of one another represent a residue selected from the group consisting of: -H, -F, -Cl, -Br, -I, -CN, C 1-6 -alkyl, -CF 3 , -CF 2 H, -CFH 2 ;or
[0675]
[0676] In some embodiments, R 8 Indicates -H, -F, -Cl, -CN or -C 1 -C 6 -alkyl.
[0677] In some embodiments, R 8 -H is not indicated.
[0678] In some embodiments, R 8 represents a residue selected from the group consisting of: -H, -F, -Cl, -CN or CH 3 ; preferably -F.
[0679] In some embodiments
[0680] (i)R 6 and R 8 Each represents -H; or
[0681] (ii) R 6 and R 8 independently represent -F, -Cl, -CN or -CH 3 ;or
[0682] (iii) R 6 and R 8 One of them represents -H, and R 6 and R 8 The other one of the above represents -F, -Cl, -CN or -CH 3 .
[0683] In some embodiments, W represents
[0684] 3-14 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-8 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-6 membered cycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the cycloalkyl is unsubstituted, monosubstituted or trisubstituted; preferably the cycloalkyl is unsubstituted, monosubstituted or disubstituted, specifically 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, mono-substituted or poly-substituted; preferably 3-12 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, mono-substituted or poly-substituted; preferably 3-10 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, mono-substituted or poly-substituted; preferably 3-8 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, mono-substituted or poly-substituted; preferably 3-6 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, mono-substituted or poly-substituted; wherein the cycloalkyl is unsubstituted, mono-substituted or tri-substituted; preferably the cycloalkyl is unsubstituted, mono-substituted or di-substituted;
[0685] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-12 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-10 membered aryl which is unsubstituted, monosubstituted or polysubstituted; wherein the aryl is unsubstituted, monosubstituted or trisubstituted; preferably the aryl is unsubstituted, monosubstituted or disubstituted; or
[0686] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-8 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-6 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the heterocycloalkyl is unsubstituted, monosubstituted or trisubstituted; preferably the heterocycloalkyl is unsubstituted, monosubstituted or disubstituted;
[0687] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-12 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-10 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-9 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-8 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the heteroaryl is unsubstituted, monosubstituted or trisubstituted; preferably the heteroaryl is unsubstituted, monosubstituted or disubstituted;
[0688] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl; wherein the alkyl, alkenyl or alkynyl is unsubstituted, monosubstituted or trisubstituted; preferably the alkyl, alkenyl or alkynyl is unsubstituted, monosubstituted or disubstituted.
[0689] In some embodiments, W represents
[0690] 3-14-membered cycloalkyl, 3-14-membered cycloalkenyl, 3-14-membered cycloalkynyl, each of which is unsubstituted, monosubstituted or polysubstituted; preferably 3-12-membered cycloalkyl, 3-12-membered cycloalkenyl, 3-12-membered cycloalkynyl, each of which is unsubstituted, monosubstituted or polysubstituted; preferably 3-10-membered cycloalkyl, 3-10-membered cycloalkenyl, 3-10-membered cycloalkynyl, each of which is unsubstituted, monosubstituted or polysubstituted. polysubstituted; preferably 3-8 membered cycloalkyl, 3-8 membered cycloalkenyl, 3-8 membered cycloalkynyl, each of which is unsubstituted, monosubstituted or polysubstituted; preferably 3-6 membered cycloalkyl, 3-6 membered cycloalkenyl, 3-6 membered cycloalkynyl, each of which is unsubstituted, monosubstituted or polysubstituted; wherein the cycloalkyl is unsubstituted, monosubstituted or trisubstituted; preferably the cycloalkyl is unsubstituted, monosubstituted or disubstituted;
[0691] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-12 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-10 membered aryl which is unsubstituted, monosubstituted or polysubstituted; wherein the aryl is unsubstituted, monosubstituted or trisubstituted; preferably the aryl is unsubstituted, monosubstituted or disubstituted; or
[0692] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-8 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-6 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the heterocycloalkyl is unsubstituted, monosubstituted or trisubstituted; preferably the heterocycloalkyl is unsubstituted, monosubstituted or disubstituted;
[0693] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-12 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-10 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-9 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-8 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the heteroaryl is unsubstituted, monosubstituted or trisubstituted; preferably the heteroaryl is unsubstituted, monosubstituted or disubstituted;
[0694] -C 1 -C 6-alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl; wherein the alkyl, alkenyl or alkynyl is unsubstituted, monosubstituted or trisubstituted; preferably the alkyl, alkenyl or alkynyl is unsubstituted, monosubstituted or disubstituted.
[0695] In some embodiments, W represents
[0696] 3-14 membered cycloalkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered cycloalkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered cycloalkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-8 membered cycloalkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-6 membered cycloalkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted; wherein the cycloalkyl is unsubstituted, monosubstituted or trisubstituted; preferably the cycloalkyl is unsubstituted, monosubstituted or disubstituted;
[0697] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-12 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-10 membered aryl which is unsubstituted, monosubstituted or polysubstituted; wherein the aryl is unsubstituted, monosubstituted or trisubstituted; preferably the aryl is unsubstituted, monosubstituted or disubstituted; or
[0698] 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-8 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-6 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the heterocycloalkyl is unsubstituted, monosubstituted or trisubstituted; preferably the heterocycloalkyl is unsubstituted, monosubstituted or disubstituted;
[0699] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-12 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-10 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-9 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-8 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the heteroaryl is unsubstituted, monosubstituted or trisubstituted; preferably the heteroaryl is unsubstituted, monosubstituted or disubstituted;
[0700] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl; which is in each case unsubstituted, monosubstituted or disubstituted
[0701] wherein the substituents are independently selected from the group consisting of: -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- to 14-membered heteroaryl.
[0702] In some embodiments, W represents a 3-10 membered cycloalkyl group which is unsubstituted, monosubstituted or polysubstituted, a 6-12 membered aryl group which is unsubstituted, monosubstituted or polysubstituted, a 3-10 membered heterocycloalkyl group which is saturated or unsaturated, monosubstituted or polysubstituted, a 5-12 membered heteroaryl group which is monosubstituted or polysubstituted, -C 1 -C 6 -alkyl, halogenated C 1-6 Alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl; preferably W represents 3-10 membered cycloalkyl, which is unsubstituted, monosubstituted or disubstituted, 6-12 membered aryl, which is unsubstituted, monosubstituted or disubstituted, 3-10 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or disubstituted, 5-12 membered heteroaryl, which is monosubstituted or substituted, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl and tert-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 .
[0703] In some embodiments, W represents
[0704] 3-14 membered cycloalkyl which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-13 membered cycloalkyl which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered cycloalkyl which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-11 membered cycloalkyl which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered cycloalkyl which is saturated, unsubstituted, monosubstituted or polysubstituted; preferably represents a cycloalkyl residue selected from the group consisting of:
[0705]
[0706] 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-12 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-10 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably 6-8 membered aryl which is unsubstituted, monosubstituted or polysubstituted; preferably represents a phenyl residue selected from the group consisting of:
[0707]
[0708] or
[0709] 3-14 membered heterocycloalkyl, which is saturated, unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-13 membered heterocycloalkyl, which is saturated, unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-12 membered heterocycloalkyl, which is saturated, unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-11 membered heterocycloalkyl, which is saturated, unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably 3-10 membered heterocycloalkyl, which is saturated, unsaturated, unsubstituted, monosubstituted or polysubstituted; preferably represents a heterocycloalkyl residue selected from the group consisting of:
[0710]
[0711]
[0712] More preferably selected from the group consisting of:
[0713]
[0714] or
[0715] 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-12 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-10 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; preferably 5-9 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; more preferably represents a residue selected from the group consisting of:
[0716]
[0717]
[0718] More preferably represents a residue selected from the group consisting of:
[0719]
[0720]
[0721] or
[0722] -C 1 -C 6 -alkyl, -C 2 -C 6 -alkenyl, -C 2 -C 6 -alkynyl; which is in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -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(C1-6 -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- to 14-membered heteroaryl.
[0723] In some embodiments, the 5-14 membered heteroaryl group within the definition of W is selected from benzimidazole, benzisoxazole, benzoxazole, 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, pyrimidine, oxadiazole, oxazole, triazine, triazole and [1,2,4]triazolo[4,3-a]pyrimidine; which are in each case unsubstituted, monosubstituted or polysubstituted; preferably defined as being selected from the group consisting of benzimidazole, benzisoxazole, benzodioxole, benzofuran, benzothiazole, benzothiophene, cinnoline, dibenzofuran, furan, thiophene, furazan, imidazole, imidazopyridine, indole, isobenzofuran, isoindole, isoquinoline, isoxazole, oxadiazole, oxazole, oxindole, pyrazine, pyrazole, pyridazine, pyridine , pyrimidine, pyrrole, quinoline, tetrazole, thiadiazole, thiazole, thiophene, triazine, triazole and [1,2,4]triazolo[4,3-a]pyrimidine; which are in each case unsubstituted, monosubstituted or polysubstituted; preferably defined in the group consisting of furan, thiophene, imidazole, pyrazole, oxazole, isoxazole, thiazole, triazole, pyridine, isoquinoline, benzothiazole, pyridazine, pyrimidine, imidazopyridine; which are in each case unsubstituted, monosubstituted or polysubstituted; preferably defined in the group consisting of furan-2-yl, furan-3-yl, thiophene- 2-yl, thiophen-3-yl, pyrazol-5-yl, oxazol-5-yl, isoxazol-4-yl, thiazol-2-yl, thiazol-5-yl, 1,2,4-triazol-3-yl, 1,2,3-triazol-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, isoquinolin-1-yl, isoquinolin-5-yl, benzo[d]thiazol-2-yl, pyridazin-3-yl, pyrimidin-5-yl and imidazo[1,2-a]pyridin-6-yl, which are in each case unsubstituted, monosubstituted or polysubstituted.
[0724] In some embodiments, the 3-14 membered heterocycloalkyl group within the definition of W is selected from azepane, 1,4-oxazepane, azetidine, aziridine, azocane, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isothiazolidine, isoxazolidine, morpholine, oxazolidine, oxetane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, thiazolidine, thietane, thiirane, thiolane, thiomorpholine, indoline, dihydrobenzofuran, dihydrobenzothiophene, 1,1-dioxothiocyclohexane, 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-pyrrolizine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole and octahydropyrrolo[1,2-a]pyrazine; which are in each case unsubstituted, monosubstituted or polysubstituted; preferably defined as selected from the group consisting of azepane, azetidine, aziridine, diazepane, dioxane, dioxolane, dithiane, dithiolane, imidazolidine, isoxazolidine, morpholine, oxazolidine, oxetane, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, tetracycline, substituted, monosubstituted or polysubstituted; preferably defined as azepane, azetidine, aziridine, diazepane, dioxane, dioxolane, dithiolane, imidazolidine, isoxazolidine, morpholine, oxazolidine, oxetane, oxetane, oxirane, piperazine, piperazine, oxadiaz ... 1-yl, 1-dihydrofuran, 1-dihydropyran, 1-dihydropyran-2-yl, 1-dihydropyran-3-yl, 1-dihydropyran-4-yl, 1-dihydrothiolane, 1-dihydrobenzofuran, 1-dihydrobenzothiophene, which are in each case unsubstituted, monosubstituted or polysubstituted; preferably defined as azetidine, dioxane, imidazolidine, isoxazolidine, morpholine, oxazolidine, oxetane, oxirane, piperazine, piperidine, pyrazolidine, pyrrolidin-1-yl, pyrrolidin-2-yl, tetrahydrofuran-1-yl, tetrahydrofuran-2-yl, tetrahydropyran-1-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, tetrahydropyran-4-yl, thiazolidine, thiolane and indoline, which are in each case unsubstituted, monosubstituted or polysubstituted.
[0725] In some embodiments, the 5-14 membered heteroaryl group within the definition of W represents a residue according to the general formula (E):
[0726]
[0727] in
[0728] Y E1 Indicates -N=, -NR E2 -, S, O, or -CR E3 =; Y E2 Indicates -N=, -NR E3 -, S, O, or -CR E4 =, and Y E3 Indicates -N=, -NR E4 -, S, O, or -CR E5 =; condition is Y E1 , Y E2 and Y E3 At least one of them is not -CR E3 =, -CR E4 = and -CR E5 = In another preferred embodiment, W represents a residue according to the general formula (E)
[0729] Wherein YE1 represents -N=, -NRE2-, S or -CRE3=; YE2 represents -N=, -NRE3-, S or -CRE4=; and YE3 represents -N=, -NRE4-, S or -CRE5=; provided that at least one of YE1, YE2 and YE3 is not -CRE3=, -CRE4= and -CRE5=, respectively.
[0730] R E1 , R E2 , R E3 and R E4 Independently represent -H, -CH 3 、-CH 2 -cyclopropyl, -CH 2 CF 3 、-CH 2 CHF 2 or -CF 3 More specifically R E1 , R E2 , R E3 and R E4 Independently represent -H, -CH 3 or -CF 3 ; preferably the condition is R E1 , R E2 , R E3 and R E4 Only one of them represents a residue other than -H.
[0731] In some embodiments, the 5-14 membered heteroaryl group within the definition of W represents a residue according to the general formula (F'):
[0732]
[0733] in
[0734] Y F1 Indicates -N= or -CR F4 =; and Y F2 Indicates -N= or -CR F5 =; and Y F3 Indicates -N= or -CR F3 =; condition is Y F1 and Y F2 At least one of them is not -CR F4 = and -CR F5 =;
[0735] R F1 , R F2 , R F3 , R F4 and R F5 Independently represent -H, -CH 3 , -CF 3 ,-OH, -OCH 3 、-OCH 2 CH 3 , -Cl or -azetidinyl; preferably, R F1 , R F2 , R F3 , R F4 and R F5 Only one of them represents a residue other than -H.
[0736] In some embodiments, the 5-14 membered heteroaryl group within the definition of W represents a residue according to the general formula (F):
[0737]
[0738] in
[0739] Y F1 Indicates -N= or -CR F4 =; and Y F2 Indicates -N= or -CR F5 =; condition is Y F1 and Y F2 At least one of them is not -CR F4 = and -CR F5 =;
[0740] R F1 , R F2 , RF3 , R F4 and R F5 Independently represent -H, -CH 3 , -CF 3 ,-OH, -OCH 3 、-OCH 2 CH 3 , -Cl or -azetidinyl; preferably, R F1 , R F2 , R F3 , R F4 and R F5 Only one of them represents a residue other than -H.
[0741] In some embodiments, the 5-14 membered heteroaryl group within the definition of W represents a residue according to formula (G) or (H):
[0742]
[0743] Where R G1 and R H1 Selected from the group consisting of: -H, -CH 3 , -CF 3 、-OH、-OCH 3 、-OCH 2 CH 3 , -Cl, azetidinyl, -cyclopropyl, -O-cyclopropyl and -CHF 2 ; or where R G1 and R H1 Selected from the group consisting of: -H, -CH 3 , -CF 3 、-OH、-OCH 3 、-OCH 2 CH 3 , -Cl and azetidinyl.
[0744] In some embodiments, the 5-14 membered heteroaryl group within the definition of W represents a residue according to the general formula (G') or (H'):
[0745]
[0746] Where R G1 and R H1 Selected from the group consisting of: -H, -CH 3 , -CF 3 、-OH、-OCH 3 、-OCH 2 CH 3 , -Cl, azetidinyl, -cyclopropyl, -O-cyclopropyl and -CHF 2; or where R G1 and R H1 Selected from the group consisting of: -H, -CH 3 , -CF 3 、-OH、-OCH 3 、-OCH 2 CH 3 , -Cl and azetidinyl;
[0747] In some embodiments, 5-14 membered heteroaryl within the definition of W represents a residue according to formula (E), (F), (F'), (G), (H), (G') or (H') as defined above.
[0748] In some embodiments, the term "mono- or poly-substituted" independently in each instance means substituted by one or more substituents independently selected from the group consisting of: -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(C1-6 -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(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-(3-14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl, -C 1-6 -alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 14-membered heteroaryl, -C 1-6 -alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -O-(5- to 14-membered heteroaryl), -C(=O)-(3- to 14-membered cycloalkyl), -C(=O)-(3- to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5- to 14-membered heteroaryl), -S(=O) 2-(3-14 membered cycloalkyl), -S(=O) 2 -(3 to 14 membered heterocycloalkyl), -S(=O) 2 -phenyl or -S(=O) 2 -(5- to 14-membered heteroaryl); preferably the term independently in each case means substituted by one or more substituents independently selected from the following: -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), -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 、-OCF2 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, -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(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) 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-(3-14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl, -C 1-6 -alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 14-membered heteroaryl, -C 1-6 -alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -O-(5- to 14-membered heteroaryl), -S(═O) 2 -(3-14 membered cycloalkyl), -S(=O) 2 -(3 to 14 membered heterocycloalkyl), -S(=O) 2 -phenyl or -S(=O) 2-(5- to 14-membered heteroaryl); preferably the term independently in each case means substituted by one or more substituents independently selected from the following: -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), -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(C1-6 -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-(3-14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl, -C 1-6 -alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 14-membered heteroaryl, -C 1-6 -alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -S(═O) 2 -(3-14 membered cycloalkyl), -S(=O) 2 -(3 to 14 membered heterocycloalkyl), -S(=O) 2 -phenyl or -S(=O) 2 -(5- to 14-membered heteroaryl); preferably the term independently in each case means substituted by one or more substituents independently selected from the following: -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), -C 1-6 -alkylene-C(=O)-NH(C 1-6 -alkyl), -C(=O)-N(C1-6 -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 -C1-6 -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 , 3-12 membered cycloalkyl, -C 1-6 -alkylene-(3-12 membered cycloalkyl), 3 to 12 membered heterocycloalkyl, -C 1-6 -alkylene-(3 to 12 membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 12-membered heteroaryl, -C 1-6 -alkylene-(5- to 12-membered heteroaryl); preferably the term independently in each case means substituted by one or more substituents independently selected from the group consisting of: -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(=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 , -C1-6 -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 , 3-12 membered cycloalkyl, -C 1-6 -alkylene-(3-12 membered cycloalkyl), 3 to 12 membered heterocycloalkyl, -C 1-6 -alkylene-(3 to 12 membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 12-membered heteroaryl, -C 1-6-alkylene-(5- to 12-membered heteroaryl); preferably the term independently in each case means substituted by one or more substituents independently selected from the group consisting of: -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), -NH 2 、-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, -SC1-5 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 , 3-10 membered cycloalkyl, -C 1-5 -alkylene-(3-10 membered cycloalkyl), 3- to 10-membered heterocycloalkyl, -C 1-5 -alkylene-(3 to 10 membered heterocycloalkyl), -phenyl, -C 1-5 -alkylene-phenyl, 5- to 10-membered heteroaryl, -C 1-5 -alkylene-(5- to 10-membered heteroaryl).
[0749] In some embodiments, the 3-14 membered cycloalkyl group within the definition of W is unsubstituted, monosubstituted or disubstituted with a substituent selected from the group consisting of: -F, -Cl, -Br, -I, -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 1-3 -Alkylene-CFH 2、 -OCF 3 、-OCF 2 H, -OCFH 2 、-OCF 2 Cl, -OCFCl 2 、-OC 1-3 -alkyl, -C 1-3 -Alkylene-OC 1-3 -alkyl and -C 1-3 -alkylene-OH; preferably -F, -Cl, -Br, -I, -CN, -CH 3 , -CF 3 , -CF 2 H, -CFH 2 、-OCF 3and -OCH 3 .
[0750] In some embodiments, the 6-14 membered aryl group within the definition of W is unsubstituted, monosubstituted or disubstituted with a substituent selected from the group consisting of: -F, -Cl, -Br, -I, -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 1-3 -Alkylene-CFH 2、 -OCF 3 、-OCF 2 H, -OCFH 2 、-OCF 2 Cl, -OCFCl 2 、-OC 1-3 -alkyl, -C 1-3 -Alkylene-OC 1-3 -alkyl and -C 1-3 -alkylene-OH; preferably -F, -Cl, -Br, -I, -CN, -CH 3 , -CF 3 , -CF 2 H, -CFH 2 、-OCF 3 and -OCH 3 .
[0751] In some embodiments, the 5-14 membered heteroaryl group within the definition of W is unsubstituted, monosubstituted or disubstituted with a substituent selected from the group consisting of: -F, -Cl, -Br, -I, -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 1-3 -Alkylene-CFH 2、 -OCF 3 、-OCF 2 H, -OCFH2 、-OCF 2 Cl, -OCFCl 2 、-OC 1-3 -alkyl, -C 1-3 -Alkylene-OC 1-3 -alkyl and -C 1-3 -alkylene-OH; preferably -F, -Cl, -Br, -I, -CN, -CH 3 , -CF 3 , -CF 2 H, -CFH 2 、-OCF 3 and -OCH 3 .
[0752] In some embodiments, the -C 1 -C 6 -Alkyl is unsubstituted, monosubstituted or disubstituted by a substituent selected from the group consisting of: -F, -Cl, -Br, -I, -CN, C 1-3 -alkyl, -CF 3 , -CF 2 H, -CFH 2 , -CF 2 Cl, -CFCl 2 、-OCF 3 、-OCF 2 H, -OCFH 2 、-OCF 2 Cl, -OCFCl 2 、-OC 1-3 -alkyl and -OH; preferably -F, -Cl, -Br, -I, -CN, -CH 3 , -CF 3 , -CF 2 H, -CFH 2 、-OCF 3 and -OCH 3 .
[0753] In some embodiments, the 3-14 membered heterocycloalkyl group within the definition of W is unsubstituted, monosubstituted or disubstituted with a substituent selected from the group consisting of: -F, -Cl, -Br, -I, -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 1-3 -Alkylene-CFH 2、 -OCF 3 、-OCF 2 H, -OCFH 2 、-OCF 2 Cl, -OCFCl 2 、-OC 1-3 -alkyl, -C 1-3 -Alkylene-OC 1-3 -alkyl and -C 1-3 -alkylene-OH; preferably -F, -Cl, -Br, -I, -CN, -CH 3 , -CF 3 , -CF 2 H, -CFH 2 、-OCF 3 and -OCH 3 .
[0754] In some embodiments of the invention, the compound is selected from the group consisting of:
[0755] Cpd 001-(2S)-3-hydroxy-2-({2-methyl-5-[(2-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide;
[0756] Cpd 002-(2S,3R)-2-({5-[(2-fluorophenyl)methoxy]-2-methylfuro[2,3-c]pyridin-3-yl}carboxamido)-3-hydroxybutanamide;
[0757] Cpd 003-(2S,3R)-3-hydroxy-2-({2-methyl-5-[(2-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}formamido)butanamide;
[0758] Cpd 004-(2S,3R)-3-hydroxy-2-({2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}formamido)butanamide;
[0759] Cpd 005-2-({2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}formamido)propanamide;
[0760] Cpd 006-2-({2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide;
[0761] Cpd 007-2-({5-[(2-fluorophenyl)methoxy]-2-methylfuro[2,3-c]pyridin-3-yl}formamido)-2-methylpropanamide;
[0762] Cpd 008-2-({5-[(2-fluorophenyl)methoxy]-2-methylfuro[2,3-c]pyridin-3-yl}carboxamido)-3-hydroxypropanamide;
[0763] Cpd 009-2-({5-[(2-fluorophenyl)methoxy]-2-methylfuro[2,3-c]pyridin-3-yl}formamido)propanamide;
[0764] Cpd 010-2-{[5-(Benzyloxy)-2-methylfuro[2,3-c]pyridin-3-yl]formamido}propanamide;
[0765] Cpd 011-2-methyl-2-({2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide;
[0766] Cpd 012-2-methyl-2-({2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide;
[0767] Cpd 013-3-hydroxy-2-({2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide;
[0768] Cpd 014-3-hydroxy-2-({2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide;
[0769] Cpd 015-5-(Benzyloxy)-N-(4,4-difluoropyrrolidin-3-yl)-2-methylfuro[2,3-c]pyridine-3-carboxamide;
[0770] Cpd 016-5-(Benzyloxy)-N-[4-(hydroxymethyl)oxan-4-yl]-2-methylfuro[2,3-c]pyridine-3-carboxamide;
[0771] Cpd 017-5-[(2-fluorophenyl)methoxy]-N-[1-(2-hydroxyethyl)-2-oxopyrrolidin-3-yl]-2-methylfuro[2,3-c]pyridine-3-carboxamide;
[0772] Cpd 018-5-[(2-fluorophenyl)methoxy]-N-[1-(hydroxymethyl)cyclopropyl]-2-methylfuro[2,3-c]pyridine-3-carboxamide;
[0773] Cpd 019-N-(3-carbamoyloxetan-3-yl)-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0774] Cpd 020-N-(3-carbamoyloxetan-3-yl)-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0775] Cpd 021-N-(4,4-difluoropyrrolidin-3-yl)-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0776] Cpd 022-N-(4,4-difluoropyrrolidin-3-yl)-2-methyl-5-(2-phenylethoxy)furo[2,3-c]pyridine-3-carboxamide;
[0777] Cpd 023-N-(4,4-difluoropyrrolidin-3-yl)-2-methyl-5-[2-(4-methyl-1,3-thiazol-5-yl)ethoxy]furo[2,3-c]pyridine-3-carboxamide;
[0778] Cpd 024-N-(4-carbamoyloxan-4-yl)-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0779] Cpd 025-N-[(4R)-3,3-difluoropiperidin-4-yl]-2-methyl-5-{[2-(trifluoromethyl)pyridin-3-yl]methoxy}furo[2,3-c]pyridine-3-carboxamide;
[0780] Cpd 026-N-[(4S)-3,3-difluoropiperidin-4-yl]-2-methyl-5-{[2-(trifluoromethyl)pyridin-3-yl]methoxy}furo[2,3-c]pyridine-3-carboxamide;
[0781] Cpd 027-N-[1-(2-hydroxyethyl)-2-oxopyrrolidin-3-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0782] Cpd 028-N-[1-(Hydroxymethyl)cyclobutyl]-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0783] Cpd 029-N-[1-(Hydroxymethyl)cyclobutyl]-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0784] Cpd 030-N-[1-(Hydroxymethyl)cyclopropyl]-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0785] Cpd 031-N-[1-(Hydroxymethyl)cyclopropyl]-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0786] Cpd 032-N-[1-(Hydroxymethyl)cyclopropyl]-5-[(2-methoxypyridin-3-yl)methoxy]-2-methylfuro[2,3-c]pyridine-3-carboxamide;
[0787] Cpd 033-N-[3-(Hydroxymethyl)oxetan-3-yl]-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0788] Cpd 034-N-[3-(Hydroxymethyl)oxetan-3-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0789] Cpd 035-N-[4-(Hydroxymethyl)oxan-4-yl]-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide;
[0790] or a physiologically acceptable salt thereof.
[0791] The present invention also encompasses pharmaceutical compositions comprising at least one compound of the present invention.The present invention also encompasses a pharmaceutical composition comprising at least one compound of the present invention and at least one acceptable carrier, excipient or diluent for pharmaceutical purposes.
[0792] In some embodiments, the present invention relates to the use of at least one compound of formula (I) or any subgroup thereof in the prevention and / or treatment of pain or epilepsy; preferably pain or epileptic encephalopathy (for the preparation of a composition thereof).
[0793] In some embodiments, the present invention relates to a method for preventing and / or treating metabolic pain, wherein the pain is selected from nociceptive pain, inflammatory pain and neuropathic pain; preferably postoperative pain.
[0794] Q, T, U, W, R 1 , R 3 , R 4 , R 5 , R 5 ',n,R 6 , R 8 All definitions, preferred embodiments and preferred meanings, including preferred substituents, also apply similarly to the compounds according to the present invention, which are not necessarily limited to the treatment of pain or epilepsy. Therefore, this aspect of the present invention relates to the compounds of the present invention themselves, compositions comprising the compounds of the present invention, medicaments comprising the compounds of the present invention, and compounds of the present invention for preventing and / or treating TRPM3-mediated conditions such as pain, epilepsy and / or inflammatory hypersensitivity; and / or compounds of the present invention for combating pain and / or inflammatory hypersensitivity. Preferably, pain is selected from nociceptive pain, inflammatory pain and neuropathic pain. More preferably, pain is postoperative pain.
[0795] In some embodiments of the present invention, the compound is selected from the group consisting of the above-mentioned Cpd 001 to Cpd 036 and physiologically acceptable salts thereof.
[0796] Another aspect of the present invention relates to a pharmaceutical composition or a medicament comprising a compound according to the invention as described above.
[0797] The compounds of the invention have been shown to be antagonists of TRPM3, and thus the invention provides the compounds themselves for use as medicaments, more particularly for use as medicaments for preventing or treating a TRPM3-mediated disorder in a subject using a therapeutically effective amount of a compound of the invention.
[0798] In some embodiments, the compound of the present invention is the only pharmacologically active compound for the administered therapy. In another embodiment of the present invention, the compound of the present invention can be used in combination with other therapeutic agents to treat or prevent TRPM3-mediated disorders. Therefore, the present invention also relates to the use of a composition comprising:
[0799] - one or more compounds of the formulae and examples herein, and
[0800] - One or more additional therapeutic or prophylactic agents for the prevention or treatment of a TRPM3-mediated disorder as biologically active agents in the form of a combined preparation for simultaneous, separate or sequential use.
[0801] Pharmaceutical composition or combined preparation according to the present invention can contain compound of the present invention in a wide content range according to the intended use and the expected effect of the preparation. Usually, the content of the compound of the present invention of the combined preparation is in the range of 0.1 to 99.9% by weight, preferably 1 to 99% by weight, more preferably 5 to 95% by weight.
[0802] In view of the fact that, when several active ingredients are used in combination, the several active ingredients do not necessarily produce their combined therapeutic effect directly at the same time in the mammal to be treated, the corresponding composition can also be in the form of a medical kit or package containing two components in separate but adjacent reservoirs or compartments. In the latter case, each active ingredient can therefore be formulated in a manner suitable for a route of administration different from that of the other ingredients, for example, one of the active ingredients can be in the form of an oral or parenteral formulation, while the other active ingredient is in the form of an ampoule or aerosol for intravenous injection.
[0803] Those skilled in the art will also recognize that the compounds of the present invention can exist in many different protonation states, depending, among other things, on the pH of their environment. While the structural formulas provided herein depict compounds in only one of several possible protonation states, it should be understood that these structures are merely illustrative, and the present invention is not limited to any particular protonation state - any and all protonated forms of the compounds are intended to fall within the scope of the present invention.
[0804] As used herein, the term "pharmaceutically acceptable salt" refers to the therapeutically active non-toxic salt forms that the compounds of the formulae herein are able to form. Therefore, the compounds of the present invention optionally include salts of the compounds herein, especially those containing, for example, Na + , Li + , K + , Ca 2+ and Mg 2+Pharmaceutically acceptable non-toxic salts. Such salts may include salts derived from a combination of appropriate cations (such as alkali and alkaline earth metal ions or ammonium and quaternary amino ions) with an acid anion moiety (usually a carboxylic acid). The compounds of the present invention may carry multiple positive or negative charges. The net charge of the compounds of the present invention may be positive or negative. Any relevant counterions are generally determined by the synthesis and / or separation methods used to obtain the compounds. Typical counterions include, but are not limited to, ammonium, sodium, potassium, lithium, halides, acetates, trifluoroacetates, and the like, and mixtures thereof. It should be understood that the identity of any associated counterions is not a key feature of the present invention, and the present invention encompasses compounds associated with any type of counterions. In addition, since the compounds may exist in a variety of different forms, the present invention is intended to encompass not only forms of compounds associated with counterions (e.g., dry salts), but also forms not associated with counterions (e.g., aqueous solutions or organic solutions). Metal salts are typically prepared by reacting metal hydroxides with compounds of the present invention. Examples of metal salts prepared in this manner are Li-containing + 、Na + and K + Salts. Metal salts with lower solubility can be precipitated from solutions of salts with higher solubility by adding suitable metal compounds. In addition, salts can be formed by acid addition of certain organic and inorganic acids with basic centers (usually amines) or with acidic groups. Examples of such suitable acids include, for example, inorganic acids (such as hydrohalic acids), such as hydrochloric acid or hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or organic acids, such as acetic acid, propionic acid, glycolic acid, 2-hydroxypropionic acid, 2-oxopropionic acid, lactic acid, pyruvic acid, oxalic acid (i.e., oxalic acid), malonic acid, succinic acid (i.e., succinic acid), maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, cyclohexylaminosulfonic acid, salicylic acid (i.e., 2-hydroxybenzoic acid), p-aminosalicylic acid, etc. In addition, this term also includes solvates that compounds of the formula herein and their salts can form, such as hydrates, alcoholates, etc. Finally, it is to be understood that the compositions herein comprise the compounds of the present invention in their unionized as well as zwitterionic forms, and in the form of hydrates in combination with a stoichiometric amount of water.
[0805] Also included within the scope of the invention are salts of the parent compound with one or more amino acids, especially salts of naturally occurring amino acids found as protein components. Amino acids are typically amino acids that carry side chains with basic or acidic groups (e.g., lysine, arginine or glutamic acid) or neutral groups (e.g., glycine, serine, threonine, alanine, isoleucine or leucine).
[0806] The compounds of the present invention also include physiologically acceptable salts thereof. Examples of physiologically acceptable salts of the compounds of the present invention include salts derived from appropriate bases, such as alkali metals (e.g., sodium), alkaline earth metals (e.g., magnesium), ammonium and NX4. + (Where X is -C 1-6 -alkyl). Physiologically 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 aminosulfonic acid). Physiologically acceptable salts of compounds containing hydroxyl groups include salts of the anion of the compound with a suitable cation (such as Na + and NX4 + (wherein X is generally independently selected from -H or -C 1-4 -alkyl)). However, salts that are not physiologically acceptable acids or bases can also be used, for example, to prepare or purify physiologically acceptable compounds. All salts, whether or not derived from physiologically acceptable acids or bases, are within the scope of the present invention.
[0807] Unless otherwise indicated, as used herein, the term "enantiomer" means each individual optically active form of a compound of the invention having an optical purity or enantiomeric excess (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%, and more preferably at least 98%.
[0808] As used herein, the term "isomer" means all possible isomeric forms that a compound of the formula herein may have, including tautomers and stereochemical forms, but excluding positional isomers. Typically, the structures shown herein only illustrate one tautomer or resonance form of a compound, but corresponding alternative configurations are also envisioned. Unless otherwise indicated, the chemical name of a compound represents a mixture of all possible stereochemical isomeric forms, containing all diastereomers and enantiomers of the basic molecular structure (because the compound of the formula herein may have at least one chiral center), as well as stereochemically pure or enriched compounds. More specifically, a stereocenter may have an R configuration or an S configuration, and multiple bonds may have a cis configuration or a trans configuration.
[0809] 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" relates to a compound having a stereoisomer excess of at least about 80% (i.e. at least 90% of one isomer and up to 10% of other possible isomers), preferably at least 90%, more preferably at least 94%, most preferably at least 97%. The terms "enantiomerically pure" and "diastereomerically pure" should be understood in a similar manner, taking into account the enantiomeric excess, diastereomeric excess, respectively, of a mixture.
[0810] Separation of stereoisomers is accomplished by standard methods known to those skilled in the art. One enantiomer of a compound of the invention may be separated by methods such as forming diastereomers using an optically active resolving agent ("Stereochemistry of Carbon Compounds", (1962) L. Eliel, McGraw Hill; Lochmuller, CH, (1975) "Journal of Chromatography", 113: (3) 283-302), substantially free of its opposite enantiomer. Separation of isomers in a mixture may be achieved by any suitable method, including: (1) forming ionic diastereomeric salts with a chiral compound and separating by fractional crystallization or other methods, (2) forming diastereomeric compounds with a chiral derivatizing agent, separating the diastereomers and converting them into pure enantiomers, or (3) enantiomers may be separated directly under chiral conditions. In method (1), diastereomeric salts can be formed by reacting an enantiomerically pure chiral base (such as brucine, quinine, ephedrine, strychnine, a-methyl-b-phenylethylamine (amphetamine), etc.) with an asymmetric compound carrying an acidic functional group (such as carboxylic acid and sulfonic acid). Diastereomeric salts can be induced to separate by fractional crystallization or ion chromatography. In order to separate the optical isomers of amino compounds, the addition of chiral carboxylic acids or sulfonic acids (such as camphorsulfonic acid, tartaric acid, mandelic acid or lactic acid) can lead to the formation of diastereomeric salts. Alternatively, by method (2), the substrate to be resolved can be reacted with one enantiomer of the chiral compound to form a diastereomeric pair (Eliel, E. and Wilen, S. (1994) Stereochemistry of Organic Compounds, John Wiley & Sons, Inc. Wiley & Sons, Inc.), p. 322). Diastereomeric compounds can be formed by reacting an asymmetric compound with an enantiomerically pure chiral derivatizing agent such as a menthyl derivative, followed by separation of the diastereomers and hydrolysis to produce the free enantiomerically enriched compound. A method for determining optical purity involves preparing a chiral ester of the racemic mixture, such as the menthyl ester or Mosher ester, a-methoxy-a-(trifluoromethyl)phenyl acetate (Jacob III. (1982) J. Org. Chem. 47:4165), and analyzing the NMR spectrum for the presence of the two atropisomeric diastereomers.According to the method for separating atropisomers naphthyl-isoquinolines (Hoye, T., WO 96 / 15111), stable diastereomers can be separated and isolated by normal phase chromatography and reverse phase chromatography. Under method (3), the racemic mixture of 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 chiral stationary phases based on polysaccharides are. CA, OA, OB5, OC5, OD, OF, OG, OJ, and OK, and AD, AS, OP(+) and OT(+). Suitable eluents or mobile phases used in combination with the polysaccharide chiral stationary phase are hexane modified with alcohols (such as ethanol, isopropanol, etc.). (Chiral Liquid Chromatography (1989) WJLough, ed., Chapman and Hall, New York; Okamoto Co., Ltd., (1990) "Optical resolution of dihydropyridine enantiomers by High-performance liquid chromatography using phenylcarbamates of polysaccharides as a chiral stationary phase", Journal of Chromatogr. 513: 375-378).
[0811] The terms cis and trans are used herein according to Chemical Abstracts nomenclature and include reference to the position of substituents on ring moieties. 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 X-ray diffraction.
[0812] When a compound is crystallized from a solution or slurry, it can crystallize in different spatially arranged lattices (this property is called "polymorphism") to form crystals with different crystalline forms, each of which is called a "polymorph". Therefore, as used herein, the term "polymorph" refers to a crystalline form of a compound of formula (I) in which the molecules are located in a three-dimensional lattice site. Different polymorphs of a compound of formula (I) may differ from one another in one or more physical properties, such as solubility and dissolution rate, true specific gravity, crystal form, accumulation pattern, flowability and / or solid state stability, etc.
[0813] The compounds of the present invention and their physiologically acceptable salts (hereinafter collectively referred to as active ingredients) can be administered by any route suitable for the condition to be treated, including oral, rectal, nasal, topical (including ocular, buccal and sublingual), vaginal and parenteral (including subcutaneous, intramuscular, intranasal, intravenous, intraarterial, intradermal, intrathecal and epidural). The preferred route of administration may vary with, for example, the condition of the recipient.
[0814] A therapeutically effective amount of a preparation of a compound, in particular for the treatment of TRPM3-mediated disorders in humans and other mammals or animals, is preferably a TRPM3 ion channel inhibiting amount of the compound as defined herein and corresponds to an amount ensuring plasma levels between 1 μg / ml and 100 mg / ml, optionally 10 mg / ml.
[0815] Suitable dosages of the compounds or compositions of the present invention are applied 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 may be divided into several subunits / day or may be administered at intervals of more than one day.
[0816] The present invention further provides (pharmaceutical) compositions comprising one or more compounds of the present invention, more specifically compounds of all formula (I) and other formulas and embodiments described herein and more specific aspects or embodiments thereof. In addition, the present invention provides compounds or (pharmaceutical) compositions of the present invention, more specifically compounds or (pharmaceutical) compositions of all formula (I) and other formulas and embodiments described herein and more specific aspects or embodiments thereof, for use as a medicament, more specifically for the treatment of pain or epilepsy. TRPM3-mediated conditions are selected from pain, epilepsy and inflammatory hypersensitivity conditions.
[0817] The compounds of the present invention can be formulated with conventional carriers and excipients, which will be selected according to conventional practice. Tablets will contain excipients, glidants, fillers, binding agents, etc. Aqueous formulations are prepared in sterile form and will generally be isotonic when intended to be delivered by means other than oral administration. The formulations optionally contain excipients such as those described in the Handbook of Pharmaceutical Excipients (1986).
[0818] Subsequently, as used herein, the term "pharmaceutically acceptable carrier" means any material or substance with which the active ingredient is formulated to facilitate its application or spreading to the site to be treated, for example by dissolving, dispersing or diffusing the composition, and / or facilitating its storage, transportation or handling without impairing its effectiveness. A pharmaceutically acceptable carrier may be a solid or a liquid or a gas that has been compressed to form a liquid, i.e., the composition of the present invention may be suitably used as a concentrate, emulsion, solution, granule, powder, spray, aerosol, suspension, ointment, cream, tablet, pill or powder.
[0819] Suitable pharmaceutical carriers for the pharmaceutical composition and its formulation are well known to those skilled in the art, and are not particularly limited in their selection within the present invention. It may also include additives, such as wetting agents, dispersants, adhesives, binders, emulsifiers, surfactants, solvents, coatings, antibacterial and antifungal agents, isotonic agents, etc., provided that it is consistent with pharmaceutical practice, i.e., carriers and additives will not produce permanent damage to mammals. The pharmaceutical composition of the present invention may be prepared in any known manner, such as by uniformly mixing, coating and / or grinding the active ingredient with selected carrier materials and other additives (such as surfactants) when appropriate in one or more step procedures. It may also be prepared by micronization, such as in order to obtain the pharmaceutical composition in the form of microspheres generally having a diameter of about 1 to 10 gm, i.e., for the preparation of microcapsules for the controlled or sustained release of active ingredients.
[0820] Although the compounds of the present invention can be administered alone, it is preferred that the compounds exist as pharmaceutical formulations. The formulations of the present invention for both veterinary and human use comprise at least one active ingredient as described above and therefore one or more pharmaceutically acceptable carriers and optionally other therapeutic ingredients. The carrier is optimally "acceptable" in the sense that it is compatible with the other ingredients of the formulation and harmless to its recipient. The formulations include formulations suitable for oral, rectal, nasal, topical (including buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal and epidural) administration. The formulations can be conveniently presented in unit dosage form and can be prepared by any method well known in the pharmaceutical industry. Such methods include the step of associating the active ingredient with a carrier constituting one or more auxiliary ingredients. Typically, the formulation is prepared by uniformly and closely associating the active ingredient with a liquid carrier or a finely dispersed solid carrier or both and then forming the product when necessary.
[0821] Formulations of the present invention suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The active ingredient may also be presented as a bolus, electuary or paste.
[0822] Tablets can be prepared by compressing or molding optionally with one or more auxiliary ingredients. Compressed tablets can be prepared...
Claims
1. A compound of formula (I), its stereoisomeric form, physiologically acceptable salt, solvate and / or polymorph in R 1 represents -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)2R W 、 -C(=O)R W 、 -C(=O)OR W or -C(=O)NR W R X ; Q stands for -NR 3 R 4 ; R 3 Indicates -OH or -R Y1 ; R 4 Indicates -R Y2 or -S(=O)2R Y3 ; or R 3 and R 4 together form a 4-, 5-, 6-, 7- or 8-membered heterocyclic ring containing 1 to 3 heteroatoms selected from N, O and S, which is saturated or unsaturated, unsubstituted or mono- or polysubstituted; T stands for -O-, and U stands for -(CR 5 R 5 ') n -; or T means -(CR 5 R 5 ') n -, and U represents -O-; n is an integer selected from 1, 2, 3, 4 or 5; R 5 and R 5 'Independently represent -R Y4 ; R 6 and R 8 Independently represent -F, -Cl, -Br, -I, -CN, -NO2, -SF5, -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)2R W 、-C(=O)R W 、-C(=O)OR W or -C(=O)NR W R X ; W stands for 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated; unsubstituted, monosubstituted or polysubstituted; 6-14 membered aryl which is unsubstituted, monosubstituted or polysubstituted; 3-14 membered heterocycloalkyl, which is saturated or unsaturated, monosubstituted or polysubstituted; 5-14 membered heteroaryl, which is mono- or poly-substituted; or -C1-C6-alkyl, -C2-C6-alkenyl, -C2-C6-alkynyl; which are in each case unsubstituted, monosubstituted or polysubstituted; in R W and R X Independently of each other, in each case independently -H; - C1-C6-alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; - C1-C6-heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally attached via -C1-C6-alkylene- or -C1-C6-heteroalkylene-, which in each case is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally linked via -C1-C6-alkylene- or -C1-C6-heteroalkylene-, which in each case is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; R Y1 , R Y2 , R Y3 and R Y4 Independently of each other, in each case independently -H; - C1-C6-alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; - C1-C6-heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally attached via -C1-C6-alkylene- or -C1-C6-heteroalkylene-, which in each case is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally linked via -C1-C6-alkylene- or -C1-C6-heteroalkylene-, which in each case is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; 6-14 membered aryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 6-14 membered aryl is optionally attached via -C1-C6-alkylene- or -C1-C6-heteroalkylene-, which in each case is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; or 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally attached via -C1-C6-alkylene- or -C1-C6-heteroalkylene-, which in each case is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; and wherein "mono- or polysubstituted" in each case independently means substitution by one or more substituents independently selected from the group consisting of: -F, -Cl, -Br, -I, -CN, -C 1-6 -alkyl, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C 1-6 -alkylene-CF2H, -C 1-6 -alkylene-CFH2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -C 1-6 -alkylene-N(C 1-6 -alkyl)-C 1-6 -alkylene-CF3, -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-CF3, -C(=O)-NH2, -C 1-6 -alkylene-C(=O)-NH2, -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, -OCF3, -OCF2H, -OCFH2, -OCF2Cl, -OCFCl2, -OC 1-6 -alkyl, -C 1-6 -Alkylene-OC 1-6 -alkyl, -OC 1-6 -Alkylene-OC 1-6 -alkyl, -OC 1-6 -Alkylene-NH2, -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-NH2, -C 1-6 -alkylene-OS(=O)2-NH2, -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, -NO2, -C 1-6 -alkylene-NH2, -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)-NH2, -C 1-6 -alkylene-NH-C(=O)-NH2, -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)-NH2, -C 1-6 -alkylene-N(C 1-6 -alkyl)-C(=O)-NH2, -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)2OH, -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-NH2, -C 1-6 -alkylene-NH-S(=O)2-NH2, -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)2N(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-NH2, -C 1-6 -alkylene-N(C 1-6 -alkyl)-S(=O)2-NH2, -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, -SF5, -SCF3, -SCF2H, -SCFH2, -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-NH2, -C 1-6 -alkylene-S(=O)2-NH2, -S(=O)2-NH(C 1-6 -alkyl), -C 1-6 -alkylene-S(=O)2-NH(C 1-6 -alkyl), -S(=O)2-N(C 1-6 -alkyl)2, -C 1-6 -alkylene-S(=O)2-N(C 1-6 -alkyl)2,3-14-membered cycloalkyl, -C 1-6 -alkylene-(3-14 membered cycloalkyl), 3 to 14 membered heterocycloalkyl, -C 1-6 -alkylene-(3 to 14-membered heterocycloalkyl), -phenyl, -C 1-6 -alkylene-phenyl, 5- to 14-membered heteroaryl, -C 1-6 -alkylene-(5- to 14-membered heteroaryl), -O-(3- to 14-membered cycloalkyl), -O-(3- to 14-membered heterocycloalkyl), -O-phenyl, -O-(5- to 14-membered heteroaryl), -C(=O)-(3- to 14-membered cycloalkyl), -C(=O)-(3- to 14-membered heterocycloalkyl), -C(=O)-phenyl, -C(=O)-(5- to 14-membered heteroaryl), -S(=O)2-(3- to 14-membered cycloalkyl), -S(=O)2-(3- to 14-membered heterocycloalkyl), -S(=O)2-phenyl, or -S(=O)2-(5- to 14-membered heteroaryl).
2. The compound according to claim 1, wherein T represents -O-, and U represents -(CR 5 R 5 ') n -.
3. The compound according to any one of claims 1 or 2, wherein R 3 Indicates -H, -OH, -C 1-6 -alkyl, -C 1-6 -alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -alkyl, -C 1-6 -alkylene-NH2, -C 1-6 -alkylene-NH(C 1-6 -alkyl), -C 1-6 -alkylene-N(C 1-6 -alkyl)2, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C 1-6 -alkylene-CF2H, -C 1-6 -alkylene-CFH2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3 or -C 1-6 -alkylene-N(C 1-6 -alkyl)-C 1-6 -Alkylene-CF3.
4. A compound according to any one of claims 1 to 3, wherein R 4 express -H; -S(=O)2C 1-6 - alkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted; -S(=O)2(3-14 membered cycloalkyl), which is saturated, monosubstituted or polysubstituted; - C1-C6-alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; - C1-C6-heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally linked via -C1-C6-alkylene- or -C1-C6-heteroalkylene-, which is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered heterocycloalkyl is optionally linked via -C1-C6-alkylene- or -C1-C6-heteroalkylene-, which in each case is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; -C 1-6 - alkylene-phenyl which is unsubstituted, monosubstituted or polysubstituted; - phenyl, which is unsubstituted, monosubstituted or polysubstituted; or 5-14 membered heteroaryl, which is unsubstituted, monosubstituted or polysubstituted; wherein the 5-14 membered heteroaryl is optionally attached via -C1-C6-alkylene- or -C1-C6-heteroalkylene-, which in each case is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
5. A compound according to any one of claims 1 to 4, wherein R 4 express -H; -S(=O)2C 1-6 -alkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted by -F; -S(=O)2(3-14 membered cycloalkyl), which is saturated and unsubstituted; -C 1-6 -alkyl, which is saturated, unsubstituted, mono- or poly-substituted independently of one another by substituents selected from the group consisting of: -F, -Cl, -Br, -I, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)-OC 1-6 -alkyl, -C(=O)OC 1-6 -alkylene-CF3, -OH, =O, -OC 1-6 -alkyl, -NH2, -NHC 1-6 -alkyl, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl)2, -C 1-6 -Alkylene -NH-C 1-6 -alkylene-CF3, -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)NH2, -C(=O)-NH-C 1-6 -alkyl, -C(=O)-N(C 1-6 -alkyl)2, -S(=O)2C 1-6 -alkyl, -S(=O)2-NH2, -S(=O)2-NH(C 1-6 -alkyl), -S(=O)2-N(C 1-6 -alkyl) 2, 3-14 membered cycloalkyl, unsubstituted -phenyl, oxetanyl or pyrimidinyl; 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3-14 membered cycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or mono- or poly-substituted by -F, -Cl, -Br, -I, -OH, wherein the 3- to 14-membered cycloalkyl is saturated, unsubstituted, mono- or di-substituted independently of one another by substituents selected from the group consisting of: -F, -Cl, -Br, -I, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)-OC 1-6 -alkyl, -C(=O)OC 1-6 -alkylene-CF3, -OH, =O, -OC 1-6 -alkyl, -NH2, -NHC 1-6 -alkyl, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl)2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -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)NH2, -C(=O)-NH-C 1-6 -alkyl, -C(=O)-N(C 1-6 -alkyl)2, -S(=O)2C 1-6 -alkyl, -S(=O)2-NH2, -S(=O)2-NH(C 1-6 -alkyl), -S(=O)2-N(C 1-6 -alkyl) 2, 3-14 membered cycloalkyl, unsubstituted -phenyl, oxetanyl or pyrimidinyl; 3-14 membered heterocycloalkyl or -C 1-6 -alkylene-(3-14 membered heterocycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or mono- or polysubstituted by -F, -Cl, -Br, -I, -OH, wherein the 3- to 14-membered heterocycloalkyl is in each case selected from azetidine, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahydropyrrolo[1,2-a]pyrrole, oxazine, 8-azabicyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, quinuclidine, hexahydro-1H-pyrrolizine, 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 1,1-dioxothiocyclohexane, which are in each case unsubstituted, monosubstituted or polysubstituted, independently of one another, by substituents selected from the group consisting of: -F, -Cl, -Br, -I, -C 1-6 -alkyl, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)-OC 1-6 -alkyl, -C(=O)OC 1-6 -alkylene-CF3, -OH, =O, -OC 1-6 -alkyl, -NH2, -NHC 1-6 -alkyl, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl)2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -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)NH2, -C(=O)-NH-C 1-6 -alkyl, -C(=O)-N(C 1-6 -alkyl)2, -S(=O)2C 1-6 -alkyl, -S(=O)2-NH2, -S(=O)2-NH(C 1-6 -alkyl), -S(=O)2-N(C 1-6 -alkyl)2, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl; 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -F, -Cl, -Br, -I, -OH, wherein the 5- to 14-membered heteroaryl is in each case selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole and [1,2,4]triazolo[4,3-a]pyrimidine, which are in each case unsubstituted, monosubstituted or disubstituted independently of one another by substituents selected from the group consisting of -F, -Cl, -Br, -I, -C 1-6 -alkyl, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)-OC 1-6 -alkyl, -C(=O)OC 1-6 -alkylene-CF3, -OH, =O, -OC 1-6 -alkyl, -NH2, -NHC 1-6 -alkyl, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl)2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -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)NH2, -C(=O)-NH-C 1-6 -alkyl, -C(=O)-N(C 1-6 -alkyl)2, -S(=O)2C 1-6 -alkyl, -S(=O)2-NH2, -S(=O)2-NH(C 1-6 -alkyl), -S(=O)2-N(C 1-6 -alkyl)2, 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5 to 14 membered heteroaryl.
6. A compound according to any one of claims 1 to 5, wherein R 3 indicates -H; and R 4 express -H; -S(=O)2C 1-6 -alkyl, which is saturated, unsubstituted, monosubstituted or polysubstituted by -F; -S(=O)2(3-14 membered cycloalkyl), which is saturated and unsubstituted; -C 1-6 -alkyl, which is saturated, unsubstituted, mono- or di-substituted independently of one another by substituents selected from the group consisting of: -OH, =O, -OC 1-6 -alkyl, -NH2, -NHC 1-6 -alkyl, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C(=O)NH2, -C(=O)-NH-C 1-3 -alkyl, -C(=O)-N(C 1-3 -alkyl)2 or unsubstituted -phenyl; 3-14 membered cycloalkyl or -C 1-6 -alkylene-(3-14 membered cycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3-14 membered cycloalkyl is saturated, unsubstituted, monosubstituted or disubstituted independently of one another by substituents selected from the group consisting of: C 1-6 -alkyl, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -C 1-6 -alkylene-OH, -C 1-6 -Alkylene-NHC(=O)OC 1-6 -alkyl, -OH, -OC 1-6 -alkyl, -NH2, -N(C 1-6 -alkyl)2, -NHC(=O)OC 1-6 -alkyl; 3-14 membered heterocycloalkyl or -C 1-6 -alkylene-(3-14 membered heterocycloalkyl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 3- to 14-membered heterocycloalkyl is in each case selected from azetidine, 1,4-oxazepane, pyrrolidine, piperidine, azepane, diazepane, tetrahydrofuran, tetrahydropyran, oxetane, morpholine, piperazine, hexahydrocyclopenta[c]pyrrole, octahydrocyclopenta[c]pyrrole, octahydropyrrolo[1,2-a]pyrazine, 8-azabis[c]pyrrole ... 1,4-oxazepane, pyrrolidine, cyclo[3.2.1]octane, 9-azabicyclo[3.3.1]nonane, quinuclidine, hexahydro-1H-pyrrolizine, 2-oxaspiro[3.3]heptane, 2-azaspiro[3.3]heptane, 7-azaspiro[3.5]nonane, 1,1-dioxothiocyclohexane, which are in each case unsubstituted, monosubstituted or polysubstituted independently of one another by substituents selected from the group consisting of: -F, -OH, =O, -C 1-6 -alkyl, -C 1-6 -alkylene-CF3, -C 1-6 -alkylene-OH, -C 1-6 -Alkylene-OC 1-6 -alkyl, -NH2, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -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-CF3, -C(=O)NH2, -C(=O)NH(C 1-6 -alkyl), -S(=O)2C 1-6 -alkyl, oxetanyl, pyrimidinyl, -C 1-6 -alkylene-phenyl; unsubstituted-phenyl; 5-14 membered heteroaryl or -C 1-6 -alkylene-(5-14 membered heteroaryl), wherein -C 1-6 -alkylene- is unsubstituted or monosubstituted by -OH, wherein the 5- to 14-membered heteroaryl is in each case selected from the group consisting of pyridine, pyridazine, pyrazine, pyrazole, isoxazole, triazole and [1,2,4]triazolo[4,3-a]pyrimidine, which are in each case unsubstituted, monosubstituted or disubstituted independently of one another by substituents selected from the group consisting of: -C 1-6 -alkyl, -OH.
7. A compound according to any one of claims 1 to 6, wherein W represents 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, mono-substituted or poly-substituted independently by substituents selected from the group consisting of -F, -Cl, -Br, -I, -C 1-6 -alkyl, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)-OC 1-6 -alkyl, -C(=O)OC 1-6 -alkylene-CF3, -OH, =O, -OC 1-6 -alkyl, -NH2, -NHC 1-6 -alkyl, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl)2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -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)NH2, -C(=O)-NH-C 1-6 -alkyl, -C(=O)-N(C 1-6 -alkyl)2, -S(=O)2C 1-6 -alkyl, -S(=O)2-NH2, -S(=O)2-NH(C 1-6 -alkyl), -S(=O)2-N(C 1-6 -alkyl)2, 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl; 6-14 membered aryl, which is unsubstituted, independently selected from the following mono- or poly-substituted: -F, -Cl, -Br, -I, -C 1-6 -alkyl, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)-OC 1-6 -alkyl, -C(=O)OC 1-6 -alkylene-CF3, -OH, =O, -OC 1-6 -alkyl, -NH2, -NHC 1-6 -alkyl, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl)2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -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)NH2, -C(=O)-NH-C 1-6 -alkyl, -C(=O)-N(C 1-6 -alkyl)2, -S(=O)2C 1-6 -alkyl, -S(=O)2-NH2, -S(=O)2-NH(C 1-6 -alkyl), -S(=O)2-N(C 1-6 -alkyl)2, 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl; 3-14 membered heterocycloalkyl, which is saturated or unsaturated, unsubstituted, independently selected from the following mono- or poly-substituted: -F, -Cl, -Br, -I, -C 1-6 -alkyl, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)-OC 1-6 -alkyl, -C(=O)OC 1-6 -alkylene-CF3, -OH, =O, -OC 1-6 -alkyl, -NH2, -NHC 1-6 -alkyl, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl)2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -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)NH2, -C(=O)-NH-C 1-6 -alkyl, -C(=O)-N(C 1-6 -alkyl)2, -S(=O)2C 1-6 -alkyl, -S(=O)2-NH2, -S(=O)2-NH(C 1-6 -alkyl), -S(=O)2-N(C 1-6 -alkyl)2, 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5- to 14-membered heteroaryl; 5-14 membered heteroaryl, which is unsubstituted, independently selected from the following mono- or poly-substituted: -F, -Cl, -Br, -I, -C 1-6 -alkyl, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)-OC 1-6 -alkyl, -C(=O)OC 1-6 -alkylene-CF3, -OH, =O, -OC 1-6 -alkyl, -NH2, -NHC 1-6 -alkyl, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl)2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -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)NH2, -C(=O)-NH-C 1-6 -alkyl, -C(=O)-N(C 1-6 -alkyl)2, -S(=O)2C 1-6 -alkyl, -S(=O)2-NH2, -S(=O)2-NH(C 1-6 -alkyl), -S(=O)2-N(C 1-6 -alkyl)2, 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5 to 14 membered heteroaryl; or -C1-C6-alkyl, -C2-C6-alkenyl, -C2-C6-alkynyl; which are in each case unsubstituted, monosubstituted or polysubstituted independently by substituents selected from the group consisting of: -F, -Cl, -Br, -I, -C 1-6 -alkyl, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C(=O)-C 1-6 -alkyl, -C(=O)OH, -C(=O)-OC 1-6 -alkyl, -C(=O)OC 1-6 -alkylene-CF3, -OH, =O, -OC 1-6 -alkyl, -NH2, -NHC 1-6 -alkyl, -N(C 1-6 -alkyl)2, -C 1-6 -alkylene-NH2, -C 1-6 -Alkylene-NH-C 1-6 -alkyl, -C 1-6 -alkylene-N(C 1-6 -alkyl)2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -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)NH2, -C(=O)-NH-C 1-6 -alkyl, -C(=O)-N(C 1-6 -alkyl)2, -S(=O)2C 1-6 -alkyl, -S(=O)2-NH2, -S(=O)2-NH(C 1-6 -alkyl), -S(=O)2-N(C 1-6 -alkyl)2, 3-14 membered cycloalkyl, 3-14 membered heterocycloalkyl, unsubstituted -phenyl, 5 to 14 membered heteroaryl.
8. A compound according to any one of claims 1 to 7, wherein R 1 Indicates -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, -CF3, -CF2H, -CFH2, -CF2Cl, -CFCl2, -C 1-6 -alkylene-CF3, -C 1-6 -alkylene-CF2H, -C 1-6 -alkylene-CFH2, -C 1-6 -Alkylene-NH-C 1-6 -alkylene-CF3, -C 1-6 -alkylene-N(C 1-6 -alkyl)-C 1-6 -alkylene-CF3, -C(=O)C 1-6 -alkyl, -C(=O)OC 1-6 -alkyl, -C(=O)NHC 1-6 -alkyl, -C(=O)NH2, -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.
9. A compound according to any one of claims 1 to 8, wherein R 5 and R 5 'Independently express -H; - C1-C6-alkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; - C1-C6-heteroalkyl, which is saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted; 3-14 membered cycloalkyl, which is saturated or non-aromatic unsaturated, unsubstituted, monosubstituted or polysubstituted; wherein the 3-14 membered cycloalkyl is optionally linked via -C1-C6-alkylene- or -C1-C6-heteroalkylene-, It is in each case saturated or unsaturated, unsubstituted, monosubstituted or polysubstituted.
10. A compound according to any one of claims 1 to 9, wherein R 6 and R 8 Independently express -H, -F, -Cl, -Br, -I, -OH, -SH, -SF5, -CN, -NO2, -C(=O)OH, -NH2, -C 1-6 -alkyl, -CF3, -CHF2, -CH2F, -OC 1-6 -alkyl, -OCF3, -OCHF2, -OCH2F, -NHC 1-6 -alkyl, which is unsubstituted or substituted by one or more substituents independently selected from the following: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2 and -C(=O)NH2; -N(C 1-6 -alkyl)2, which is unsubstituted or substituted by one or more substituents independently selected from the following: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2 and -C(=O)NH2; -C(=O)OC 1-6 -alkyl, which is unsubstituted or substituted by one or more substituents independently selected from the following: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2 and -C(=O)NH2; -OC(=O)C 1-6 -alkyl, which is unsubstituted or substituted by one or more substituents independently selected from the following: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2 and -C(=O)NH2; or -C 1-6 -heteroalkyl, which is unsubstituted or substituted by one or more substituents independently selected from the following: -OH, =O, -F, -Cl, -Br, -I, -SH, =S, -CN, -CF3, -CHF2, -CH2F, -OCF3, -OCHF2, -OCH2F, SF5, -NO2, -C(=O)OH, -NH2 and -C(=O)NH2.
11. A compound according to any one of claims 1 to 10, selected from the group consisting of: Cpd 001-(2S)-3-hydroxy-2-({2-methyl-5-[(2-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide; Cpd 002-(2S,3R)-2-({5-[(2-fluorophenyl)methoxy]-2-methylfuro[2,3-c]pyridin-3-yl}carboxamido)-3-hydroxybutanamide; Cpd 003-(2S,3R)-3-hydroxy-2-({2-methyl-5-[(2-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}formamido)butanamide; Cpd 004-(2S,3R)-3-hydroxy-2-({2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}formamido)butanamide; Cpd 005-2-({2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}formamido)propanamide; Cpd 006-2-({2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide; Cpd 007-2-({5-[(2-fluorophenyl)methoxy]-2-methylfuro[2,3-c]pyridin-3-yl}formamido)-2-methylpropanamide; Cpd 008-2-({5-[(2-fluorophenyl)methoxy]-2-methylfuro[2,3-c]pyridin-3-yl}carboxamido)-3-hydroxypropanamide; Cpd 009-2-({5-[(2-fluorophenyl)methoxy]-2-methylfuro[2,3-c]pyridin-3-yl}formamido)propanamide; Cpd 010-2-{[5-(Benzyloxy)-2-methylfuro[2,3-c]pyridin-3-yl]formamido}propanamide; Cpd 011-2-methyl-2-({2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide; Cpd 012-2-methyl-2-({2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide; Cpd 013-3-hydroxy-2-({2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide; Cpd 014-3-hydroxy-2-({2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridin-3-yl}carboxamido)propanamide; Cpd 015-5-(Benzyloxy)-N-(4,4-difluoropyrrolidin-3-yl)-2-methylfuro[2,3-c]pyridine-3-carboxamide; Cpd 016-5-(Benzyloxy)-N-[4-(hydroxymethyl)oxan-4-yl]-2-methylfuro[2,3-c]pyridine-3-carboxamide; Cpd 017-5-[(2-fluorophenyl)methoxy]-N-[1-(2-hydroxyethyl)-2-oxopyrrolidin-3-yl]-2-methylfuro[2,3-c]pyridine-3-carboxamide; Cpd 018-5-[(2-fluorophenyl)methoxy]-N-[1-(hydroxymethyl)cyclopropyl]-2-methylfuro[2,3-c]pyridine-3-carboxamide; Cpd 019-N-(3-carbamoyloxetan-3-yl)-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 020-N-(3-carbamoyloxetan-3-yl)-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 021-N-(4,4-difluoropyrrolidin-3-yl)-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 022-N-(4,4-difluoropyrrolidin-3-yl)-2-methyl-5-(2-phenylethoxy)furo[2,3-c]pyridine-3-carboxamide; Cpd 023-N-(4,4-difluoropyrrolidin-3-yl)-2-methyl-5-[2-(4-methyl-1,3-thiazol-5-yl)ethoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 024-N-(4-carbamoyloxan-4-yl)-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 025-N-[(4R)-3,3-difluoropiperidin-4-yl]-2-methyl-5-{[2-(trifluoromethyl)pyridin-3-yl]methoxy}furo[2,3-c]pyridine-3-carboxamide; Cpd 026-N-[(4S)-3,3-difluoropiperidin-4-yl]-2-methyl-5-{[2-(trifluoromethyl)pyridin-3-yl]methoxy}furo[2,3-c]pyridine-3-carboxamide; Cpd 027-N-[1-(2-hydroxyethyl)-2-oxopyrrolidin-3-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 028-N-[1-(Hydroxymethyl)cyclobutyl]-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 029-N-[1-(Hydroxymethyl)cyclobutyl]-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 030-N-[1-(Hydroxymethyl)cyclopropyl]-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 031-N-[1-(Hydroxymethyl)cyclopropyl]-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 032-N-[1-(Hydroxymethyl)cyclopropyl]-5-[(2-methoxypyridin-3-yl)methoxy]-2-methylfuro[2,3-c]pyridine-3-carboxamide; Cpd 033-N-[3-(Hydroxymethyl)oxetan-3-yl]-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 034-N-[3-(Hydroxymethyl)oxetan-3-yl]-2-methyl-5-[(pyridin-2-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide; Cpd 035-N-[4-(Hydroxymethyl)oxan-4-yl]-2-methyl-5-[(4-methyl-1,3-thiazol-5-yl)methoxy]furo[2,3-c]pyridine-3-carboxamide.
12. A pharmaceutical composition comprising a compound according to any one of claims 1 to 11.
13. A compound according to any one of claims 1 to 11 or a pharmaceutical composition according to claim 12 for use as a medicament.
14. A compound according to any one of claims 1 to 11 or a pharmaceutical composition according to claim 12 for use in the treatment of pain or epilepsy.
15. The compound for use or pharmaceutical composition for use according to claim 14, wherein the pain is selected from nociceptive pain, inflammatory pain and neuropathic pain; preferably postoperative pain.