Bumetanib derivatives for treatment of hyperhidrosis

Abstract

The present invention relates to bumetanib derivatives for use in the treatment of hyperhidrosis. The present invention relates to bumetanib derivatives of formula (I) and pharmaceutical compositions comprising these compounds for use in the treatment or prevention of diseases / disorders involving Na +-K +-2Cl-co-transporter (NKCC), and in particular for use in the treatment or prevention of hyperhidrosis. # imgabs0 #

Description

[0001] This application is a divisional application. The filing date of the original application is April 5, 2019, the application number is 201980037183.5, and the invention title is "Bumetanide derivatives for the treatment of hyperhidrosis", which is hereby incorporated by reference in its entirety. Technical Field

[0002] The present invention relates to bumetanide derivatives of formula (I) and pharmaceutical compositions comprising these compounds, which are used for the treatment or prevention of diseases / disorders involving the Na + -K + -2Cl - -cotransporter (NKCC), and specifically for the treatment or prevention of hyperhidrosis. Background Art

[0003] Na + -K + -Cl - cotransporter

[0004] The intracellular chloride concentration ([Cl - ) i ) is mainly controlled by the chloride-cation cotransporters (CCC) of the SLC12 gene family (Maa et al., 2011). These transporters are one of the most important ion transporters in multicellular organisms and are essential for survival (Alessi et al., 2014). The Na + -K + -2Cl - -cotransporter (NKCC) transports Cl - into the cell, while the K + -Cl - -cotransporter (KCC) directs it outwards (Munoz, DeFelipe, & Alvarez-Leefmans, 2007). These CCCs are integral membrane proteins that use the energy-favorable transmembrane gradients of potassium and sodium ions to transport Cl - across the membrane. These gradients are established by the active primary transport of ouabain-sensitive Na + -K + -adenosine triphosphatase (Alessi et al., 2014). Therefore, Cl - transport occurs electro-neutrally, so there is no net charge movement across the membrane (Payne et al., 2003). NKCC1 and NKCC2 use the inward sodium current to transport Cl - into the cell to a level higher than its equilibrium level. KCC1, KCC2, KCC3, and KCC4 use the potassium gradient to transport Cl - out of the cell, keeping Cl -The concentration drops below the equilibrium level (Maa et al., 2011). NKCC1 is widely distributed throughout the body and is expressed in neurons, glial cells, choroid plexus, and vascular endothelium, while NKCC2 is mainly expressed in the kidney (Maa et al., 2011). NKCC1 and NKCC2 have 60% homology at the protein level (Markadieu, N., Delpire, E., 2014). Cellular Cl - efflux and influx are also regulated by two serine-threonine kinases, SPAK and OSR1, which phosphorylate key N- and C-residues of NKCC and KCC. Thus, they activate NKCC and cause Cl - influx, but at the same time they inhibit KCC and Cl - efflux (Alessi et al., 2014). In the mammalian central nervous system (CNS), the intracellular Cl - concentration ([Cl - i ) determines the strength and direction of GABAergic neurotransmission (Kahle & Staley, 2008). In the adult central nervous system, there is a very low level of [Cl - i , and activation of GABA A receptors causes Cl - influx into the cell, resulting in hyperpolarization and inhibition (Khanna, Walcott and Kahle, 2013). On the other hand, the immature brain of newborns exhibits a much higher [Cl - i , such that activation of GABA A receptors causes Cl - efflux, which depolarizes neurons and leads to synaptic excitation (Kahle & Staley, 2008).

[0005] NKCC2

[0006] ​​​NKCC2 is expressed at the apical membrane of epithelial cells in the ascending limb of the loop of Henle, where it reabsorbs approximately 20–30% of the NaCl filtered by the glomerulus (Ares G., Caceres P., Ortiz P., 2011). The main function of the ascending limb of the loop of Henle is NaCl reabsorption, but not water absorption. This results in further dilution of the urine formed in the renal tubular lumen. NKCC2 is also expressed in the macula densa. Macula densa cells act as NaCl sensors and are able to regulate glomerular filtration by vasoconstriction or vasodilation of the afferent arteriole. A decrease in the renal tubular NaCl concentration will lead to vasodilation of the afferent arteriole and release of renin from granular cells. Conversely, an increase in the renal tubular NaCl concentration will lead to vasoconstriction of the afferent arteriole and thus a decrease in glomerular filtration. This mechanism is called tubuloglomerular feedback, and it has been shown that NKCC2 plays a very important role in sensing high NaCl concentrations (Peti-Peterdi, J., Harris, R., 2010).

[0007] NKCC1

[0008] In contrast to NKCC2, NKCC1 is widely distributed throughout the body and has many different functions. It is highly expressed in the cochlear and vestibular ganglia of the inner ear. Regulation of [Cl - i levels seems to be an important function of NKCC1 in adult neurons not located in the CNS. However, in the immature brain, the expression of NKCC1 increases, and these elevated [Cl - i levels seem to have a developmental role (Dzhala et al., 2005). NKCC1 is also highly expressed in the salivary glands, where it is involved in the secretion of fluid and mucin. It is also expressed in the intestine, where it is also involved in fluid excretion. The most obvious defects in NKCC1 knockout mice are deafness and imbalance, which result from the fact that NKCC1 is highly expressed in the inner ear. It plays a major role in afferent neurons. In the CNS, it is only elevated in immature neurons and plays an important role in neuronal maturation. NKCC1 knockout mice also suffer from hypotension and male infertility. Hypotension results from decreased vascular tone (Markadieu, N., Delpire, E., 2014).

[0009] GABA

[0010] γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the adult mammalian brain (Dzhala et al., 2005). However, GABA-mediated signaling also plays a crucial role in all important developmental steps such as cell proliferation (Owens & Kriegstein, 2002). GABA​​A The receptor is a ligand-gated chloride channel that is opened by the docking of GABA to its binding site. The receptor undergoes a conformational change, which allows Cl - to passively flow into or out of the cell, depending on the equilibrium concentration of chloride ions (Maa et al., 2011). The channel also allows bicarbonate to permeate the pore, but with lower efficiency than chloride (Owens & Kriegstein, 2002). The influx of Cl - causes hyperpolarization, while on the other hand, the efflux of Cl - results in depolarization. In the immature brain, GABA has a depolarizing effect, which can excite neurons and thus cause seizures (Dzhala et al., 2005). The depolarizing effect of GABA is crucial for brain development. It has been shown that GABA A receptors can affect DNA synthesis, proliferation, and neuronal migration (Owens & Kriegstein, 2002). In immature neurons, there is a delicate balance between inhibition and excitation. This balance plays an important role in the early stages of brain development. Excessive inhibition can lead to the inability of neurons to grow and synapses to mature, while excessive excitation can cause seizures and even excitotoxic death (Maa et al., 2011).

[0011] Anxiety disorder

[0012] Anxiety disorders affect approximately 18% of adults and are the most common type of mental illness (Le′pine, J., 2002). Anxiety disorders are currently treated with psychotherapy and medications such as serotonin reuptake inhibitors (SSRI), antidepressants, monoamine oxidase inhibitors, benzodiazepines, and anticonvulsants. However, 20 - 40% of patients do not respond to any of the above medications (Denys D., de Geus F. 2005). Another drawback of these medications is that they can cause severe side effects in the central nervous system. Long-term use of SSRI may lead to sexual dysfunction and weight gain (Hirschfeld, R., 2003). Since most patients with anxiety disorders are non-responders and due to the severe side effects that current medications may cause, there is a great need for new drugs. It has been shown that bumetanide has an anxiolytic effect in a rat model of state anxiety. The percentage of freezing during the test period in the fear conditioning model was significantly lower in rats treated with bumetanide than in those treated with vehicle alone. Bumetanide also plays an important role in the fear-potentiated startle model (Krystal AD, Sutherland J, Hochman DW 2012).

[0013] Autism spectrum disorder

[0014] Autism spectrum disorder (ASD) is a complex series of neurodevelopmental disorders characterized by repetitive and characteristic patterns of behavior and difficulties with social interaction and communication. ASD consists of a range of different disorders, with autism being the most severe form. Other forms are Asperger syndrome, childhood disintegrative disorder, and pervasive developmental disorder, which are part of ASD. One in 68 children is affected by ASD, and boys are much more likely to have ASD than girls. It occurs in all racial and ethnic groups and at all socioeconomic levels (NINDS Autism Spectrum Disorder Fact Sheet 2016). Parturition in rodents plays a very important role, inducing neuroprotection and analgesia in neonates. These effects are mediated by oxytocin [Cl - i reduced. In two models of rodent autism (VPA rats and FRX mice), this sequence is abolished in CA3 pyramidal neurons. It can be restored by administering bumetanide, leading to the restoration of the GABA developmental sequence, and those rats do not show any autistic phenotype in the rodent offspring (Tyzio R. et al., 2014). Bumetanide has also been used in an open-label trial in which 7 patients were diagnosed with autism. The patients received bumetanide treatment for 10 months, and bumetanide caused an improvement in emotion recognition and enhanced activation of brain regions involved in social and emotional perception (Hadjikhani N. et al., 2015). Since there is no cure yet and only very limited treatment options are available for ASD, there is an urgent need for improved therapies.

[0015] Hyperhidrosis

[0016] ​Hyperhidrosis is a medical condition that causes excessive sweating. It is classified as primary or secondary hyperhidrosis. Primary hyperhidrosis is an idiopathic disorder caused by overactivity of the sympathetic nervous system. It only affects limited body areas, mainly the armpits, palms, soles of the feet, or the head. While most of the body remains dry, one or two areas will sweat. Secondary hyperhidrosis is a side effect caused by certain medications or underlying medical conditions such as diabetes or gout (Website of American Academy of Dermatology (2016)). Hyperhidrosis can have a significant impact on daily life, such as work limitations, social interactions, physical activities, and psychological and emotional well-being. Available treatments include topical use of aluminum chloride hexahydrate, oral anticholinergics, injection of botulinum toxin, or surgery. Their efficacy, side effects, cost, and ease of use vary. In the United States, 15.3 million people have hyperhidrosis, accounting for 4.8% of the population. Only 51% of the affected population discuss their condition with a healthcare professional. 75% of respondents said that their condition had a negative impact on their social life, well-being, mood, or mental health. Most people agreed that excessive sweating was embarrassing and caused anxiety (Doolittle J. et al., 2016). Given the negative impacts reported by patients, there is clearly a need for a better understanding and treatment of hyperhidrosis. Excessive sweating can be treated by blocking NKCC in the sweat glands. Bumetanide has been shown to be somewhat effective in treating hyperhidrosis (Louie et al., 2016).

[0017] Spinal cord injury

[0018] Worldwide, 250,000 to 500,000 people suffer from spinal cord injury (SCI) each year. 90% of the causes of SCI are traumatic causes, such as road traffic accidents, falls, or violence. People affected by SCI have a 2- to 5-fold increased risk of premature death and reduced school enrollment and economic participation. The symptoms of SCI depend on the severity and location of the injury, but most patients experience chronic pain (WHO (2013) Spinal Cord Injury Fact Sheet N°384). Injury and noxious input can lead to a persistent increase in spinal nerve excitability, which may cause chronic pain. Spinal cord injury (SCI) can shift the activation of GABA channels from hyperpolarization to depolarization. The effect of SCI is associated with the downregulation of KCC2, which results in a shift in GABAergic activation. Nerve injury seems to push the spinal system into an early developmental state, in which GABA has a depolarizing effect. This depolarizing effect may cause the development of chronic pain and spasticity. Bumetanide can restore normal [Cl - i by blocking NKCC - i ​​The concentration is used to restore normal GABAergic function (Huang Y. et al., 2016). There is a great need for improved therapies for patients suffering from chronic pain caused by SCI.

[0019] Post-stroke recovery

[0020] Stroke is the fifth leading cause of death in the United States, and 795,000 people in the United States suffer from stroke each year. A stroke is caused by a blocked or ruptured blood vessel that supplies blood to the brain. Stroke is also a major cause of disability, reducing the mobility of more than half of stroke survivors over the age of 65 (Centers for Disease Control and Prevention, (2016) Stroke Fact Sheet). Ischemic stroke promotes adult neurogenesis, but these new neurons have a rather limited ability to survive in the long term. Ischemic stroke can cause an imbalance in the expression of NKCC and KCC, leading to - i an increase in [Cl

[0021] Schizophrenia

[0022] Schizophrenia is characterized by distortions of emotion, perception, thought, behavior, self-awareness, and language. Many patients experience hearing voices and delusions. More than 21 million people worldwide are affected, and this is associated with considerable disability. Patients are 2-2.5 times more likely to die prematurely, and discrimination and stigma are very common (WHO (2016) Schizophrenia Fact Sheet). The neurophysiological basis of schizophrenia is still poorly understood, but many studies suggest that abnormal cortical GABA regulation may be the cause of schizophrenia. In a recent study, a missense variant with enhanced function in SLC12A2 was found in human schizophrenia, which encodes the bumetanide-sensitive NKCC1 cotransporter. Functional experiments showed that this variant of NKCC1 is a gain-of-function variant that increases Cl - ​Dependent activity (Merner, N.D. et al., 2016). Another study found loss-of-function variants of KCC in human schizophrenia (Merner, N.D. et al., 2015). In both cases (gain of function of NKCC, loss of function of KCC), - i both increase, which may lead to disruption of GABA neurotransmission. Blocking NKCC will lead to - i normalization and reverse GABA signaling to hyperpolarization.

[0023] Parasite

[0024] In a recent study, it has been found that furosemide (another loop diuretic that blocks NKCC) exhibits submicromolar inhibitory effects on the rAceMIF tautomerase activity and is able to produce positive effects in various assays (Cho Y. et al., 2011). Since bumetanide and its derivatives are also inhibitors of NKCC, they are thought to exhibit similar effects as furosemide, if not stronger.

[0025] Soil-transmitted helminth infection

[0026] ​​More than 1.5 billion people worldwide are infected with soil-transmitted helminth infections. That is 24% of the world's population. These helminth infections are caused by three different parasites: hookworms, roundworms, and whipworms. Adult worms live in the intestines of infected people, where they lay thousands of eggs every day. These eggs are passed in the feces of infected people, for example by attaching to vegetables that are neither cooked nor peeled. Another way of getting infected is by drinking from contaminated water sources or children playing in contaminated soil. In addition, hookworm eggs hatch in the soil, releasing larvae that are able to penetrate the skin, and infect humans by walking barefoot on contaminated soil. Symptoms and morbidity largely depend on the number of worms people are infected with. Mild infections usually do not show any symptoms, while severe infections can cause diarrhea, abdominal pain, general weakness, impaired cognitive and physical development, and blood loss, which may lead to anemia (WHO (2016) Soil-transmitted helminth infections Fact Sheet). Recent studies have found that furosemide, another aryl-sulfonamide derivative that is also used as a high-ceiling loop diuretic that blocks NKCC, has anthelmintic activity. Human MIF is a pro-inflammatory protein with multiple functions. Furosemide targets AceMIF, which is similar to human MIF, and is thought to help worms evade the host's immune response (Cho Y. et al., 2011). Bumetanide derivatives may be effective inhibitors of hookworm MIF and have excellent insecticidal potential. In particular, lipophilic derivatives with enhanced pharmacokinetic properties are promising derivatives for better treatment of helminth infections.

[0027] Other parasites

[0028] The novel compound may also help treat other worms, such as tapeworms, whipworms, guinea worms, pinworms, Toxocara, Strongyloides stercoralis, and Ascaris lumbricoides. In addition to worms, it can also be used to treat diseases caused by parasitic flukes, such as schistosomiasis, gnathostomiasis, paragonimiasis, fascioliasis, and schistosome dermatitis. Additionally, the compound can be used to treat diseases caused by protozoa, such as malaria, amebiasis, giardiasis, African trypanosomiasis, toxoplasmosis, Acanthamoeba keratitis, leishmaniasis, babesiosis, granulomatous amebic encephalitis, cryptosporidiosis, cyclosporiasis, and primary amebic meningoencephalitis. The compound can also be used to treat ectoparasites, such as Sarcoptes scabiei, head lice, pubic lice, human botfly maggots, Tunga penetrans, Ixodidae, etc. The compound can also be used to control plant pests, such as nematodes, arthropods, ectoparasites, and mollusks.

[0029] Edema

[0030] Edema is the result of an imbalance between capillaries and the intestinal lumen. The kidneys regulate the extracellular volume by adjusting the excretion of sodium and water. Venous obstruction, increased plasma volume, and increased capillary permeability may cause edema. The treatment of edema includes sodium restriction, the use of diuretics, and the treatment of the underlying disease. Edema may be confined to the extremities or spread throughout the body (generalized) and become massive. Since bumetanide is a loop diuretic and blocks NKCC, it prevents the reabsorption of sodium in the loop of Henle and leads to the excretion of sodium and water. Bumetanide and its derivatives can be used to treat edema (O’Brien, O.G. et al., 2005).

[0031] Cerebral edema

[0032] Cerebral edema (brain edema) causes intracranial hypertension (ICH), which leads to poor patient prognosis in a clinical setting. Effective anti-edema treatment can significantly reduce the mortality rate of various neurological disorders. Currently, drug treatment is the cornerstone of treating cerebral edema. Osmotherapy is the mainstay of pharmacological therapy. Mannitol and hypertonic saline (HS) are the most commonly used osmotic agents. The inhibitor of the Na / H exchanger, NKCC, attenuates the formation of cerebral edema by inhibiting the excessive transport of ions and water from the blood to the brain tissue (Deng Y. et al., 2016). Therefore, NKCC inhibitors can be used to treat cerebral edema.

[0033] Down syndrome

[0034] Down syndrome is the most common genetic cause of intellectual disability. Adults and children with Down syndrome present with an IQ lower than the normal IQ, learning disabilities, and memory impairments. It is caused by extra genetic material on chromosome 21. This may be due to a process called non-disjunction, in which the genetic material fails to separate, resulting in an extra chromosome (trisomy 21). The prevalence worldwide is approximately 1 in 1000 cases, which means that approximately 3000 to 5000 children are born with this disorder each year (WHO (2017), Genes and chromosomal diseases). Altered GABAergic transmission contributes significantly to the learning and memory deficits in mouse models. Recent publications have shown that bumetanide is able to restore normal GABA 能 transmission and reduce cognitive impairment (Deidda, G. et al., 2015). Based on this research, bumetanide and its derivatives are a promising approach for treating the intellectual disabilities of patients with Down syndrome.

[0035] Glaucoma

[0036] As the population ages, glaucoma is the second leading cause of blindness globally. Glaucoma is a term for a group of different diseases: in primary open-angle glaucoma, the fluid in the eye cannot drain due to blocked channels. This causes increased intraocular pressure and leads to blindness. Since there are few symptoms, patients are not initially aware of the loss of vision. The cause of angle-closure glaucoma is similar to that of open-angle glaucoma, but it has a faster onset and is accompanied by symptoms such as headache, blurred vision, and eye pain. With the aging of the world's population, the demand for additional treatment is increasing annually. (WHO(2004)Glaucoma is the second leading cause of blindness globally).

[0037] Bumetanide and its derivatives

[0038] Bumetanide, namely 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid, is a loop diuretic (high-ceiling diuretic) that blocks both NKCC1 and NKCC2 and has been approved by the FDA and EMA for the treatment of edema, particularly edema associated with congestive heart failure, liver disease, and kidney disease (including nephrotic syndrome); bumetanide and / or certain of its derivatives have also been proposed for various other therapeutic applications (Lykke K et al., Br J Pharmacol. 2015, 172(18):4469-80; K et al., Eur J Pharmacol. 2015, 746:78-88; K et al., Ann Neurol. 2014, 75(4):550-62; Erker T et al., Epilepsia. 2016, 57(5):698-705; Louie JC et al., Physiol Rep. 2016, 4(22).pii: e13024). However, due to the very polar carboxylic acid group of bumetanide, it can hardly penetrate cell membranes, which severely limits the therapeutic potential of the drug. Given the weak therapeutic activity of bumetanide and the undesired strong diuretic effect, there is thus an urgent and unmet need for new and / or improved therapeutic agents that can be used for the treatment of NKCC-related disorders and do not have the drawbacks associated with bumetanide.

[0039] Certain other (hetero)aryl sulfonamides, benzoic acids, thiophenes, pyrazolopyrimidines or other derivatives are described in, for example, Feit PW et al., J Med Chem. 1976, 19(3):402-6; Feit PW et al., J Med Chem. 1977, 20(12):1687-91; Consiglio G et al., ARKIVOC. 2002, 11:104-17; Hauck S et al., Bioorg Med Chem. 2016, 24(22):5717-29; Moni L et al., Synthesis. 2016, 48(23):4050-9; Moni L et al., Molecules. 2016, 21(9):1153 / 1-1153 / 9; Palfrey HC et al., American Journal of Physiology. 1984, 246(3, Pt.1):C242-C246; Englert H et al., Archiv der Pharmazie (Weinheim, Germany). 1983, 316(5):460-3; Nielsen OT et al., Am Chem Soc Symp Ser, Diuretic Agents. 1978, 83:12-23; Petzinger E et al., Am J Physiol. 1993, 265(5Pt 1):G942-54; AU-A-521892; CN-A-104926804, DE-A-1966878; DE-A-2654795; GB-A-1523632; US3,985,777; US 4,010,273; US2014 / 066504; WO 2008 / 052190; WO 2010 / 083442; WO 2010 / 085352; WO 2012 / 018635; WO 2013 / 087090; WO 2014 / 157635; WO 2014 / 196793; and WO 2014 / 039454. SUMMARY OF THE INVENTION

[0040] Accordingly, an object of the present invention is to provide novel and / or improved active agents for the treatment of hyperhidrosis or other diseases / disorders involving NKCC, in particular NKCC1.

[0041] In the context of the present invention, it has been found that bumetanide derivatives of formula (I) as described and defined herein can be used as Na + -K + -2Cl -- Inhibitors of cotransporters (NKCC), especially used as NKCC1 inhibitors. In addition, bumetanide derivatives of formula (I) have been found to exhibit significantly improved properties, especially in terms of permeability, diuresis, and metabolic stability. Thus, the compounds provided herein show increased lipophilicity and improved skin permeability, significantly reduced diuretic activity, improved metabolic stability, and generally enhanced therapeutic effects. This makes the compounds according to the invention highly advantageous for therapeutic applications, including for the treatment or prevention of diseases or disorders involving NKCC, especially NKCC1. Therefore, the compounds of formula (I) according to the invention can be advantageously used for the treatment or prevention of hyperhidrosis (Louie JC et al., Physiol Rep. 2016, 4(22). pii: e13024; Bovell DL et al., Exp Dermatol. 2011, 20(12):1017 - 20; Cui CY et al., J Dermatol Sci. 2016, 81(2):129 - 31) or other diseases / disorders involving NKCC, including any of the diseases / disorders described above in the introduction of this specification. The present invention also provides compounds of formula (I) that are selective inhibitors of NKCC1, especially compounds that are more effective in inhibiting NKCC1 compared to NKCC2, which makes these compounds particularly suitable for the treatment or prevention of NKCC1 - related diseases / disorders and for therapeutic applications where a high - efficacy diuretic effect is not desired, especially hyperhidrosis. In addition, some compounds of the present invention show favorable water solubility. The present invention also provides compounds of formula (I) that contain a carboxylic acid ester group and can be hydrolyzed by esterases in the patient's skin to release more polar therapeutically active compounds, which, due to their increased polarity, are not easily transported back to the skin surface and will thus accumulate at the desired target site ("metabolic trapping"), resulting in a more pronounced and / or longer - lasting therapeutic effect. All of these properties make the compounds provided herein highly suitable as drugs for inhibiting NKCC, especially NKCC1, and thus for therapeutic intervention in diseases / disorders involving NKCC, especially for the treatment or prevention of hyperhidrosis.

[0042] Accordingly, the present invention provides a compound of formula (I) below, or a pharmaceutically acceptable salt or solvate thereof, for the treatment or prevention of hyperhidrosis.

[0043]

[0044] In formula (I), the ring moiety is

[0045] R x is R 1 or R 3 .

[0046] R 1 selected from -COOH, -COO-(C 1-15 alkyl), -COO-(C 0-15 alkylene)-carbocyclic group, -COO-(C 0-15 alkylene)-heterocyclic group, -O-CHO, -O-CO-(C 1-15 alkyl), -O-CO-(C 0-15 alkylene)-carbocyclic group, -O-CO-(C 0-15 alkylene)-heterocyclic group, -CHO, -CO-(C 1-15 alkyl), -CO-(C 0-15 alkylene)-carbocyclic group, -CO-(C 0-15 alkylene)-heterocyclic group, -CO-NH2, -CO-N(R 11 )(C 1-15 alkyl), -CO-N(R 11 )(C 0-15 alkylene)-carbocyclic group, -CO-N(R 11 )(C 0-15 alkylene)-heterocyclic group, -N(R 11 )(CHO, -N(R 11 )(CO-(C 1-15 alkyl), -N(R 11 )(CO-(C 0-15 alkylene)-carbocyclic group, -N(R 11 )(CO-(C 0-15 alkylene)-heterocyclic group, C 1-15 alkyl, -(C 0-15 alkylene)-carbocyclic group, -(C 0-15 alkylene)-heterocyclic group, C 2-15 alkenyl, -(C 2-15 alkenylene)-carbocyclic group, -(C 2-15 alkenylene)-heterocyclic group, C 2-15 alkynyl, -(C 2-15 alkynylene)-carbocyclic group and -(C 2-15 alkynylene)-heterocyclic group,

[0047] wherein the alkyl moiety of any of the above groups, the alkylene moiety of any of the above groups, the alkenylene moiety of any of the above groups, the alkynylene moiety of any of the above groups, the C 1-15 alkyl, the C 2-15 alkenyl and the C 2-15 alkynyl are each optionally and independently selected from halogen, -CF3, -CN, -NO2, -N(R 11 )(R11 ), -O(R 11 ), -S(R 11 ) and one or more groups selected from -SO3H,

[0048] including in the alkyl moiety of any of the above groups, in the alkylene moiety of any of the above groups, in the alkenylene moiety of any of the above groups, in the alkynylene moiety of any of the above groups, said C 1-15 alkyl, said C 2-15 alkenyl or said C 2-15 alkynyl, one or more -CH2- units are each optionally and independently replaced by a group selected from -O-, -CO-, -COO-, -O-CO-, -N(R 11 ), -N(R 11 )-CO-, -CO-N(R 11 ), -S-, -SO-, -SO2-, -SO2-N(R 11 ), -N(R 11 )-SO2-,

[0049] and further, wherein the carbocyclic moiety of any of the above groups and the heterocyclic moiety of any of the above groups are each optionally and independently replaced by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ), -SO3H, carbocyclic and heterocyclic groups.

[0050] Each R 11 is independently hydrogen or C 1-6 alkyl.

[0051] R 2 is selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl).

[0052] R 3 is selected from -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -SO2-N=(C 1-6 alkylidene) and -SO2-halogen, wherein the alkyl moiety of the -SO2-NH(C 1-6 alkyl), one or both of the alkyl moieties of the -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), and the alkylidene moiety of the -SO2-N=(C 1-6 alkylidene) are each optionally independently substituted with one or more groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH and -S(C 1-6 alkyl).

[0053] R 4 is the group R 4a , and R 5 is the group R 5a , or R 4 and R 5 are connected to each other to form a group -R5b -.

[0054] R 4a selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 alkyl)-R 41 , halogen, hydrogen, carbocyclic group and heterocyclic group, wherein the carbocyclic group and the heterocyclic group are each optionally substituted by one or more groups R 42 .

[0055] R 41 selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the carbocyclic group part of the -(C 0-4 alkylene)-carbocyclic group and the heterocyclic group part of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted by one or more groups R 42 , and wherein the C 1-6 alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl, the alkylene part of the -(C 0-4 alkylene)-carbocyclic group and the alkylene part of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted by one or more groups R 43 .

[0056] Each R 42 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl).

[0057] Each R 43 is independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3, -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl) and -N(C 1-6 alkyl)-CO-(C 1-6 alkyl).

[0058] R 5a is selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -NO2 and hydrogen, wherein the alkyl moiety of the -NH(C 1-6 alkyl) and one or both of the alkyl moieties of the -N(C 1-6 alkyl)(C 1-6 alkyl) are each optionally independently selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6(alkyl), -OH, -O(C 1-6 (alkyl), -SH, -S(C 1-6 (alkyl), a carbocyclic group, and a heterocyclic group, where each of the carbocyclic group and the heterocyclic group is optionally substituted with one or more groups R 51 Substituted.

[0059] Each R 51 Is independently selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -OH, -O(C 1-6 (alkyl), -O(C 1-6 (alkylene)-OH, -O(C 1-6 (alkylene)-O(C 1-6 (alkyl), -SH, -S(C 1-6 (alkyl), -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), halogen, C 1-6 Halogenated alkyl, -O-(C 1-6 Halogenated alkyl), -CN, -NO2, -CHO, -CO-(C 1-6 (alkyl), -COOH, -COO-(C 1-6 (alkyl), -O-CO-(C 1-6 (alkyl), -CO-NH2, -CO-NH(C 1-6 (alkyl), -CO-N(C 1-6 (alkyl)(C 1-6 (alkyl), -NH-CO-(C 1-6 (alkyl), -N(C 1-6 (alkyl)-CO-(C 1-6 (alkyl), -SO2-NH2, -SO2-NH(C 1-6 (alkyl), -SO2-N(C 1-6 (alkyl)(C 1-6 (alkyl), -NH-SO2-(C 1-6 And -N(C 1-6 (alkyl)-SO2-(C 1-6 (alkyl).

[0060] R 5b Is selected from -R 5b1 -R 5b2 -R 5b1 -, -N=C(R 53 ))-R 5b3 -R 5b1 -, -R 5b1 -R 5b3-C(R 53 )=N- and -N=C(R 53 )-R 5b4 -C(R 53 )=N-.

[0061] Each R 5b1 is independently selected from -N(R 52 )-, -O-, and -S-.

[0062] R 5b2 is selected from -C(R 53 )(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )(R 53 )-, -C(R 53 )=C(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-, and -C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-.

[0063] R 5b3 is selected from a covalent bond, -C(R 53 )(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )(R 53 )-, and -C(R 53 )=C(R 53 )-.

[0064] R 5b4 is selected from a covalent bond and -C(R 53 )(R 53 )-.

[0065] Each R 52 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -(C 0-4 )-aryl, and -(C 0-4 )-heteroaryl.

[0066] Each R 53 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6Alkynyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl), -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl), -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, and any two groups R 53 attached to the same carbon atom may also together form the group =O, and any two groups R 53 attached to adjacent carbon atoms connected by a double bond may also be connected to each other to form the group -C(R 54 )=C(R 54 )-C(R 54 )=C(R 54 ).

[0067] Each R 54 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6Halogenoalkyl, -O-(C 1-6 halogenoalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl).

[0068] R 6 is selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 halogenoalkyl, -O-(C 1-6 halogenoalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl).

[0069] Optionally, R 1 and R 6 are connected to each other to form a group -R 16 -, where:

[0070] -R 16 is the group -C(R 161 )(R 161 )(R 161 )(R 161 )-C(R 161 )(R 161 )-C(R 161 )(R 161 )-, where one or two -C(R 161 )(R 161 )- units included in the said group are each replaced by -R 163 -;

[0071] - Each R 161 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -(C 0-6 alkylene)-CF3, -(C 0-6 alkylene)-CN, -(C 0-6 alkylene)-NO2, -(C 0-6 alkylene)-N(R 162 )(R 162 ), -(C 0-6 alkylene)-O(R 162 ), -(C 0-6 alkylene)-S(R 162 ), -(C 0-6 alkylene)-SO3H,

[0072] -(C 0-6 alkylene)-carbocyclic group and -(C 0-6 alkylene)-heterocyclic group;

[0073] - Each R 162 is independently hydrogen or C 1-6 alkyl; and

[0074] - Each R 163 is independently selected from -N(R 161 )-, -O-, and -S-.

[0075] According to the present invention, if the ring moiety in formula (I) is R 2 is hydrogen, R 3 is -SO2-NH2, R 4 is -O-phenyl, R 5 is -NH-CH2CH2CH2CH3 and R 6 is hydrogen, then R 1 is different from -COOH.

[0076] The present invention also relates to a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in combination with a pharmaceutically acceptable excipient, which is used for treating or preventing hyperhidrosis.

[0077] Furthermore, the present invention relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in the preparation of a drug for treating or preventing hyperhidrosis.

[0078] The present invention also relates to a method for treating or preventing hyperhidrosis, which method comprises administering to a subject (preferably a human) in need thereof a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising any of the above entities in combination with a pharmaceutically acceptable excipient. It should be understood that a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition, is administered according to the method.

[0079] In addition, the present invention relates to the use of a compound of formula (I) or a pharmaceutically / physiologically acceptable salt or solvate thereof for inhibiting or reducing non-pathological sweating in a subject (e.g., a human). Thus, the present invention relates to the non-therapeutic use of a compound of formula (I) or a pharmaceutically / physiologically acceptable salt or solvate thereof for inhibiting or reducing sweating in a subject (e.g., a human). The present invention also relates to a method (especially a non-therapeutic method) for inhibiting or reducing sweating in a subject (e.g., a human), which method comprises administering to the subject a compound of formula (I) or a pharmaceutically / physiologically acceptable salt or solvate thereof. The subject in need of inhibiting or reducing sweating is preferably a healthy subject, especially a subject not suffering from hyperhidrosis. The present invention particularly relates to inhibiting or reducing sweating in a subject, wherein the sweating is caused or occurs due to physical stress or physical exercise (e.g., exercise).

[0080] For the treatment or prophylaxis of hyperhidrosis and also for the inhibition or reduction of non-pathological sweating, it is preferred to topically apply a compound of formula (I) or a pharmaceutically / physiologically acceptable salt or solvate thereof, in particular to those skin parts which are (or are strongly) affected by sweating and / or to those skin parts where a reduction in sweating is desired. For topical application, the compound of formula (I) or a pharmaceutically / physiologically acceptable salt or solvate thereof can be provided as such or, for example, in the form of a composition (e.g., in the form of a pharmaceutical composition for the treatment or prophylaxis of hyperhidrosis comprising the compound and a pharmaceutically acceptable excipient or in the form of a cosmetic composition for the inhibition or reduction of non-pathological sweating comprising the compound and a cosmetic / physiologically acceptable excipient). The compound of formula (I) or a pharmaceutically / physiologically acceptable salt or solvate thereof can also be provided in the form of a wipe (or a wiping cloth) comprising the compound, in the form of an insole (or a shoe insert or an arch support; in particular an orthotic insole, an orthotic shoe insert or an orthotic arch support) comprising the compound or in the form of a garment (or a piece of clothing) comprising the compound. Each of the above articles (i.e., the wipe, the wiping cloth, the insole, the shoe insert, the arch support, the garment or the piece of clothing) can be treated, coated or impregnated, for example, with the compound. Preferably, at least one surface of the above article (in particular at least one body-facing surface) is (or has been) treated, coated or impregnated with a compound of formula (I) or a pharmaceutically / physiologically acceptable salt or solvate thereof. The invention also relates to such articles comprising a compound provided herein. Accordingly, the invention specifically includes articles comprising a compound of formula (I) or a pharmaceutically / physiologically acceptable salt or solvate thereof, wherein the article is (i) a wipe (or a wiping cloth), (ii) an insole (or a shoe insert or an arch support; e.g., an orthotic insole, an orthotic shoe insert or an orthotic arch support), or (iii) a garment (or a piece of clothing).

[0081] According to the invention, the use of a compound of formula (I) can not only treat or prophylax hyperhidrosis but also treat or prophylax other diseases / disorders involving NKCC (or mediated thereby), in particular diseases / disorders involving NKCC1 (or mediated thereby).

[0082] Accordingly, the invention also relates to a compound of formula (I) as described and defined above, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising any of the above entities and a pharmaceutically acceptable excipient, for the treatment or prophylaxis of a disease or disorder involving NKCC, in particular a disease or disorder involving NKCC1.

[0083] The present invention further relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in the preparation of a medicament for the treatment or prophylaxis of a disease or disorder involving NKCC, in particular a disease or disorder involving NKCC1.

[0084] The present invention also provides a method for the treatment or prophylaxis of a disease or disorder involving NKCC (in particular a disease or disorder involving NKCC1), which method comprises administering to a subject in need thereof (preferably a human) a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising any of the foregoing entities in combination with a pharmaceutically acceptable excipient. It is to be understood that a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition, is administered according to the method.

[0085] The disease or disorder to be treated or prevented according to the present invention, specifically a disease or disorder involving NKCC (preferably NKCC1), is not particularly limited and is preferably selected from hyperhidrosis (e.g., primary hyperhidrosis, secondary hyperhidrosis or night sweats), anxiety disorders, autism spectrum disorders (e.g., autism, Asperger's syndrome, childhood disintegrative disorder or pervasive developmental disorder as part of the autism spectrum disorder), traumatic brain injury, spinal cord injury (also including chronic pain caused by spinal cord injury), peripheral nerve injury, stroke (e.g., ischemic stroke; specifically including the use of the compounds according to the present invention in promoting recovery after stroke, or the use of said compounds in reducing post-stroke brain injury and / or neurological deficits), Alzheimer's disease, schizophrenia, asthma, edema (e.g., cerebral edema), Down syndrome (in particular intellectual disability in Down syndrome patients), glaucoma (e.g., primary open-angle glaucoma or angle-closure glaucoma) or parasitic infections. Parasitic infections can be, for example, (i) helminth infections, also including soil-transmitted helminth infections, in particular hookworm infection, ascariasis, trichuriasis, taeniasis, guinea worm infection, enterobiasis, toxocariasis, strongyloidiasis or ascariasis lumbricoides (or diseases caused thereby); (ii) parasitic trematode infections or diseases caused by parasitic trematodes, in particular schistosomiasis, gnathostomiasis, paragonimiasis, fascioliasis or schistosome dermatitis; (iii) protozoan infections or diseases caused by protozoa, such as, for example, malaria, amoebiasis, giardiasis, African trypanosomiasis, toxoplasmosis, acanthamoeba keratitis, leishmaniasis, babesiosis, granulomatous amoebic encephalitis, cryptosporidiosis, cyclosporiasis or primary amoebic meningoencephalitis; or (iv) ectoparasite infections, in particular scabies mite infection, head louse infection, pubic louse infection, human botfly maggot infection, tungiasis or ixodidae infection (or diseases caused thereby).

[0086] Thus, preferably, the diseases or disorders to be treated or prevented according to the present invention are selected from hyperhidrosis, primary hyperhidrosis, secondary hyperhidrosis, night sweats, anxiety disorders, autism spectrum disorder, autism, Asperger's syndrome, childhood disintegrative disorder, pervasive developmental disorder as part of the autism spectrum disorder, traumatic brain injury, spinal cord injury (also including chronic pain caused by spinal cord injury), peripheral nerve injury, stroke (e.g., ischemic stroke), Alzheimer's disease, schizophrenia, asthma, edema (e.g., cerebral edema), Down syndrome, intellectual disability in patients with Down syndrome, glaucoma, primary open-angle glaucoma, angle-closure glaucoma, or parasitic infections. Parasitic infections are preferably selected from: (i) worm infections, especially hookworm infection, ascariasis, trichuriasis, taeniasis, guinea worm infection, enterobiasis, toxocariasis, strongyloidiasis, or human ascariasis; (ii) parasitic trematode infections, especially schistosomiasis, gnathostomiasis, paragonimiasis, fascioliasis, or schistosome dermatitis; (iii) protozoan infections, especially malaria, amebiasis, giardiasis, African trypanosomiasis, toxoplasmosis, Acanthamoeba keratitis, leishmaniasis, babesiosis, granulomatous amebic encephalitis, cryptosporidiosis, cyclosporiasis, or primary amebic meningoencephalitis; or (iv) ectoparasite infections, especially scabies infection, head lice infection, pubic lice infection, human botfly maggot infection, tungiasis, or Ixodidae infection (or diseases caused by them). Particularly preferably, the diseases or disorders to be treated or prevented according to the present invention are hyperhidrosis (e.g., primary hyperhidrosis, secondary hyperhidrosis, or night sweats).

[0087] The diseases or disorders to be treated or prevented according to the present invention may also be, for example, neurological diseases or disorders involving NKCC (or mediated thereby), especially neurological diseases or disorders involving NKCC1 (or mediated thereby). Specific examples include stroke (e.g., ischemic stroke), traumatic brain injury, spinal cord injury, peripheral nerve injury, or cerebral edema.

[0088] The compound of formula (I) can further be used as a pest control agent, especially, for example, by applying the compound of formula (I) or its salt or solvate to plants or soil for controlling plant pests (such as, for example, nematodes, arthropods, ectoparasites, and / or mollusks).

[0089] Furthermore, as described in more detail below, the present invention also provides novel compounds that can be used as drugs, and pharmaceutical compositions comprising such compounds and pharmaceutically acceptable excipients.

[0090] In addition, the present invention relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as an NKCC inhibitor, in particular as a research tool compound for inhibiting NKCC (in particular NKCC1), in research. Accordingly, the present invention relates to the in vitro use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as an NKCC inhibitor (in particular as an NKCC1 inhibitor), and similarly to the in vitro use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as a research tool compound for use as an NKCC inhibitor (in particular as an NKCC1 inhibitor). The present invention also relates to an in vitro method of inhibiting NKCC (in particular NKCC1), comprising administering a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. The present invention further provides an in vitro method of inhibiting NKCC (in particular NKCC1), comprising using a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof as an NKCC inhibitor (in particular as an NKCC1 inhibitor). It should be understood that the term "in vitro" is used in this particular context in the sense of "outside a living human or animal", which specifically includes experiments that can be carried out in an artificial environment such as an aqueous solution or a culture medium provided in, for example, a flask, test tube, petri dish, microtiter plate, etc., using cells, cell extracts or subcellular extracts and / or biomolecules. Detailed Description

[0091] The compound of formula (I) and its pharmaceutically acceptable salt or solvate will be described in more detail below:

[0092]

[0093] In formula (I), the ring moiety is

[0094] It should be understood that if the ring moiety is then the compound of formula (I) has the following structure:

[0095]

[0096] Conversely, if the ring moiety is then the compound of formula (I) has the following structure:

[0097]

[0098] R 1 is selected from -COOH, -COO-(C 1-15 alkyl), -COO-(C 0-15 alkylene)-carbocyclic group, -COO-(C 0-15alkylene)-heterocyclic group, -O-CHO, -O-CO-(C 1-15 alkyl), -O-CO-(C 0-15 alkylene)-carbocyclic group, -O-CO-(C 0-15 alkylene)-heterocyclic group, -CHO, -CO-(C 1-15 alkyl), -CO-(C 0-15 alkylene)-carbocyclic group, -CO-(C 0-15 alkylene)-heterocyclic group, -CO-NH2, -CO-N(R 11 )(C 1-15 alkyl), -CO-N(R 11 )(C 0-15 alkylene)-carbocyclic group, -CO-N(R 11 )(C 0-15 alkylene)-heterocyclic group, -N(R 11 )(CHO), -N(R 11 )(CO-(C 1-15 alkyl), -N(R 11 )(CO-(C 0-15 alkylene)-carbocyclic group, -N(R 11 )(CO-(C 0-15 alkylene)-heterocyclic group, C 1-15 alkyl, -(C 0-15 alkylene)-carbocyclic group, -(C 0-15 alkylene)-heterocyclic group, C 2-15 alkenyl, -(C 2-15 alkenylene)-carbocyclic group, -(C 2-15 alkenylene)-heterocyclic group, C 2-15 alkynyl, -(C 2-15 alkynylene)-carbocyclic group and -(C 2-15 alkynylene)-heterocyclic group,

[0099] wherein the alkyl portion of any one of the above groups, the alkylene portion of any one of the above groups, the alkenylene portion of any one of the above groups, the alkynylene portion of any one of the above groups, the C 1-15 alkyl, the C 2-15 alkenyl and the C 2-15 alkynyl are each optionally independently substituted by one or more (e.g., one, two or three) groups selected from halogen, -CF3, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ) and -SO3H,

[0100] Including in the alkyl moiety of any of the above groups, in the alkylene moiety of any of the above groups, in the alkenylene moiety of any of the above groups, in the alkynylene moiety of any of the above groups, the C 1-15 alkyl, the C 2-15 alkenyl or the C 2-15 alkynyl, one or more (e.g., one or two) -CH2- units are each optionally independently replaced by a group selected from -O-, -CO-, -COO-, -O-CO-, -N(R 11 ), -N(R 11 )-CO-, -CO-N(R 11 ), -S-, -SO-, -SO2-, -SO2-N(R 11 ), and -N(R 11 )-SO2-.

[0101] And further, wherein the carbocyclic moiety of any of the above groups and the heterocyclic moiety of any of the above groups are each optionally independently substituted by one or more (e.g., one, two or three) groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ), -SO3H, carbocyclic and heterocyclic groups.

[0102] Each R 11 is independently hydrogen or C 1-6 alkyl. Preferably, each R 11 is independently hydrogen or C 1-4 alkyl (e.g., methyl or ethyl).

[0103] R 1 can be, for example, any of the specific groups R 1 included in any of the compounds described in the Examples section.

[0104] Specifically, R 1 can be, for example, -COO-(C 1-15 alkyl), wherein the alkyl moiety of the -COO-(C 1-15 alkyl) is optionally independently selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-4 alkyl), -N(C 1-4 alkyl)(C 1-4 alkyl), -OH, -O(C1-4 alkyl), -SH and -S(C 1-4 alkyl) of one or more (e.g., one, two or three) groups, and further, wherein including in the -COO-(C 1-15 alkyl) of the alkyl moiety, one or two -CH2- units are each optionally independently selected from -O-, -CO-, -COO-, -O-CO-, -NH-, -N(C 1-4 alkyl)-, -NH-CO-, -N(C 1-4 alkyl)-CO-, -CO-NH-, -CO-N(C 1-4 alkyl)-, -S-, -SO-, -SO2-, -SO2-NH-, -SO2-N(C 1-4 alkyl)-, -NH-SO2- and -N(C 1-4 alkyl)-SO2-. The -COO-(C 1-15 alkyl) of the alkyl moiety has 1 to 15 carbon atoms, especially 1 to 10 carbon atoms. Such R 1 group preferred examples include the corresponding groups R of the compounds described in the Examples section 1 (including, for example, -COO-CH3 or -COO-CH2CH3; especially -COO-CH3).

[0105] R 1 Another preferred example of R is -COOH.

[0106] R 1 Another preferred example of R is -(C 1-4 alkylene)-NH-(C 1-4 alkylene)-R 12 (such as, for example, -CH2-NH-CH2-R 12 ), -COO-(C 1-4 alkylene)-R 12 (e.g., -COO-CH2-R 12 ), -O-CO-(C 1-4 alkylene)-R 12 , -CO-(C 1-4 alkylene)-R 12 , -CO-NH-(C 1-4 alkylene)-R 12 (e.g., -CO-NH-CH2-R 12 ), -CO-N(C 1-4 alkyl)-(C 1-4 alkylene)-R 12 , -NH-CO-(C 1-4 alkylene)-R 12or -N(C 1-4 alkyl)-CO-(C 1-4 alkylene)-R 12 , wherein R 12 is independently selected from -CF3, -CN and halogen (e.g., -F, -Cl, -Br or -I); preferably, R 12 is independently selected from -CF3 and -CN; more preferably, R 12 is -CF3. Specific examples of such R 1 groups include the corresponding R 1 groups of the compounds described in the Examples section. Particularly preferred examples of R 1 are -(C 1-4 alkylene)-NH-(C 1-4 alkylene)-CF3, and even more preferred examples are -CH2-NH-CH2-CF3.

[0107] R 1 's additional examples are -(C 1-4 alkylene)-S-heterocyclic group, especially -(C 1-4 alkylene)-S-heteroaryl (such as for example -CH2-S-heteroaryl), wherein the heterocyclic group part of the -(C 1-4 alkylene)-S-heterocyclic group or the heteroaryl part of the -(C 1-4 alkylene)-S-heteroaryl or the heteroaryl part of the -CH2-S-heteroaryl is optionally substituted by one or more (e.g., one, two or three) groups independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ), -SO3H, carbocyclic group and heterocyclic group. Specific examples of such R 1 groups include the corresponding R 1 groups of the compounds described in the Examples section.

[0108] R 1 's additional examples are -(C 1-4 alkylene)-O-(C 0-4 alkylene)-carbocyclic group, especially -(C 1-4 alkylene)-O-(C 0-4 alkylene)-phenyl (such as for example -CH2-O-phenyl or -CH2-O-CH2-phenyl), wherein the -(C 1-4 alkylene)-O-(C 0-4- (alkylene)-carbocyclic moiety of the carbocyclic group or said -(C 1-4 alkylene)-O-(C 0-4 alkylene)-phenyl (or said -CH2-O-phenyl or -CH2-O-CH2-phenyl) is optionally substituted on the phenyl moiety independently by one or more (e.g., one, two or three) groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ), -SO3H, carbocyclic group and heterocyclic group. Specific examples of such R 1 groups include the corresponding groups R of the compounds described in the Examples section 1 .

[0109] R 1 Another example of is -(C 1-4 alkylene)-heterocyclic group, especially -CH2-heterocyclic group, wherein the -(C 1-4 alkylene)-heterocyclic group or the heterocyclic moiety of the -CH2-heterocyclic group is optionally substituted independently by one or more (e.g., one, two or three) groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ), -SO3H, carbocyclic group and heterocyclic group. The heterocyclic moiety can be, for example, heterocycloalkyl (such as, for example, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl), heterocycloalkenyl (such as, for example, tetrahydropyridyl) or heteroaryl. Specific examples of such R 1 groups include the corresponding groups R of the compounds described in the Examples section 1 .

[0110] R 2 is selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl).

[0111] Preferably, R 2 is selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN. More preferably, R 2 is hydrogen or C 1-4 alkyl. Even more preferably, R 2 is hydrogen.

[0112] R 3 is selected from -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6(alkyl), -SO2-N=(C 1-6 alkylidene) and -SO2-halogen, wherein the alkyl moiety of the -SO2-NH(C 1-6 (alkyl), the -SO2-N(C 1-6 (alkyl)(C 1-6 (alkyl), and one or both of the alkyl moieties of the -SO2-N=(C 1-6 alkylidene) and the alkylidene moiety of the -SO2-N=(C 1-6 alkylidene) are each optionally independently substituted by one or more (e.g., one, two, or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), -OH, -O(C 1-6 (alkyl), -SH, and -S(C

[0113] Preferably, R 3 is selected from -SO2-NH2, -SO2-NH(C 1-4 (alkyl), -SO2-N(C 1-4 (alkyl)(C 1-4 (alkyl), and -SO2-N=(C 1-4 alkylidene), wherein the alkyl moiety of the -SO2-NH(C 1-4 (alkyl), the -SO2-N(C 1-4 (alkyl)(C 1-4 (alkyl), and one or both of the alkyl moieties of the -SO2-N=(C 1-4 alkylidene) and the alkylidene moiety of the -SO2-N=(C 1-6 alkylidene) are each optionally independently substituted by one or more groups (especially one group) selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), -OH, -O(C 1-6 (alkyl), -SH, and -S(C 3 is selected from -SO2-NH2, -SO2-NH(C 1-4 (alkyl), -SO2-N(C 1-4 (alkyl)(C 1-4 (alkyl), and -SO2-N=(C 1-4 alkylidene), wherein the alkyl moiety of the -SO2-NH(C 1-4 (alkyl), the -SO2-N(C 1-4 (alkyl)(C 1-4 (alkyl), and one or both of the alkyl moieties of the -SO2-N=(C1-4 The alkylidene moiety of the alkylidene group is each optionally substituted with a group selected from -NH2, -NH(C 1-4 alkyl), and -N(C 1-4 alkyl)(C 1-4 alkyl). Even more preferably, R 3 is selected from -SO2-NH2, -SO2-NH(C 1-4 alkyl), -SO2-N(C 1-4 alkyl)(C 1-4 alkyl), -SO2-NH-(C 1-4 alkylene)-NH2, -SO2-NH-(C 1-4 alkylene)-NH(C 1-4 alkyl), -SO2-NH-(C 1-4 alkylene)-N(C 1-4 alkyl)(C 1-4 alkyl), -SO2-N=(C 1-4 alkylidene)-NH2, -SO2-N=(C 1-4 alkylidene)-NH(C 1-4 alkyl), and -SO2-N=(C 1-4 alkylidene)-N(C 1-4 alkyl)(C 1-4 alkyl). Even still more preferably, R 3 is selected from -SO2-NH2, -SO2-NH-CH3, -SO2-N(CH3)2, -SO2-NH-(C 1-4 alkylene)-NH2, -SO2-NH-(C 1-4 alkylene)-NH-CH3, -SO2-NH-(C 1-4 alkylene)-N(CH3)2 (e.g., -SO2-NH-CH2CH2-N(CH3)2), -SO2-N=(C 1-4 alkylidene)-NH2, -SO2-N=(C 1-4 alkylidene)-NH-CH3, and -SO2-N=(C 1-4 alkylidene)-N(CH3)2 (e.g., -SO2-N=CH-N(CH3)2). A particularly preferred example of R 3 is -SO2-NH2. A further particularly preferred example of R 3 is -SO2-N=CH-N(CH3)2.

[0114] R x is R 1 or R 3 (as defined above, also including the preferred definitions of R 1 and R 3 ).

[0115] Preferably, R x is selected from -COOH, -COO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-4 alkyl), -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and -SO2-N=(C 1-4 alkylidene), wherein the alkyl moiety of the -SO2-NH(C 1-4 alkyl), one or both of the alkyl moieties of the -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and the alkylidene moiety of the -SO2-N=(C 1-4 alkylidene) are each optionally substituted with a group selected from -NH2, -NH(C 1-4 alkyl) and -N(C 1-4 alkyl)(C 1-4 alkyl). More preferably, R x is selected from -COOH, -COOCH3, -SO2-NH2 and -SO2-N=CH-N(CH3)2.

[0116] R 4 is the group R 4a , and R 5 is the group R 5a ; or alternatively, R 4 and R 5 are connected to each other to form the group -R 5b -.

[0117] R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 alkyl)-R 41 , halogen (e.g., -Cl), hydrogen, carbocyclic group and heterocyclic group, wherein the carbocyclic group and the heterocyclic group are each optionally substituted with one or more (e.g., one, two or three) groups R 42 .

[0118] Preferably, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 alkyl)-R 41 , halogen, carbocyclic group and heterocyclic group, wherein the carbocyclic group and the heterocyclic group are each optionally substituted with one or more groups R 42is substituted. More preferably, R 4a is selected from -O-R 41 、-S-R 41 、-NH-R 41 、-N(C 1-6 alkyl)-R 41 、a carbocyclic group (e.g., aryl, cycloalkyl or cycloalkenyl) and a heterocyclic group (e.g., heteroaryl, heterocycloalkyl or heterocycloalkenyl), wherein each of the carbocyclic group and the heterocyclic group is optionally substituted by one or more groups R 42 is substituted. Even more preferably, R 4a is selected from -O-R 41 、-S-R 41 、-NH-R 41 、-N(C 1-4 alkyl)-R 41 、aryl and heteroaryl, wherein each of the aryl and the heteroaryl is optionally substituted by one or more groups R 42 is substituted.

[0119] R 41 is selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the carbocyclic group portion of the -(C 0-4 alkylene)-carbocyclic group and the heterocyclic group portion of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted by one or more (e.g., one, two or three) groups R 42 is substituted, and wherein the C 1-6 alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl, the alkylene portion of the -(C 0-4 alkylene)-carbocyclic group and the alkylene portion of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted by one or more (e.g., one, two or three) groups R 43 is substituted.

[0120] Preferably, R 41 is selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the carbocyclic group portion of the -(C 0-4 alkylene)-carbocyclic group is selected from cycloalkyl, cycloalkenyl and aryl, wherein the -(C 0-4The heterocyclic moiety of the -(C-alkylene)-heterocyclic group is selected from heterocycloalkyl, heterocycloalkenyl, and heteroaryl, wherein the -(C 0-4 The carbocyclic moiety of the -(C-alkylene)-carbocyclic group and the -(C 0-4 The heterocyclic moiety of the -(C-alkylene)-heterocyclic group is each optionally substituted by one or more (e.g., one, two, or three) groups R 42 And further, wherein the C 1-6 Alkyl, the C 2-6 Alkenyl, the C 2-6 Alkynyl, the -(C 0-4 The alkylene moiety of the -(C-alkylene)-carbocyclic group and the -(C 0-4 The alkylene moiety of the -(C-alkylene)-heterocyclic group is each optionally substituted by one or more (e.g., one, two, or three) groups R 43 Substituted. More preferably, R 41 Is selected from -(C 0-4 Alkylene)-aryl and -(C 0-4 Alkylene)-heteroaryl, wherein the aryl moiety of the -(C 0-4 Alkylene)-aryl and the heteroaryl moiety of the -(C 0-4 Alkylene)-heteroaryl are each optionally substituted by one or more (e.g., one, two, or three) groups R 42 Substituted, and further, wherein the alkylene moiety of the -(C 0-4 Alkylene)-aryl and the alkylene moiety of the -(C 0-4 Alkylene)-heteroaryl are each optionally substituted by one or more (e.g., one, two, or three) groups R 43 Substituted. Even more preferably, R 41 Is selected from -(C 0-4 Alkylene)-aryl and -(C 0-4 Alkylene)-heteroaryl, wherein the aryl moiety of the -(C 0-4 Alkylene)-aryl and the heteroaryl moiety of the -(C 0-4 Alkylene)-heteroaryl are each optionally substituted by one or more (e.g., one, two, or three) groups R 42 Substituted. Preferred examples of the aryl moiety of the -(C 0-4 Alkylene)-aryl are phenyl. Preferred examples of the heteroaryl moiety of the -(C 0-4 Alkylene)-heteroaryl are 5- or 6-membered monocyclic heteroaryls having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (where the remaining ring atoms are carbon atoms), such as, for example, imidazolyl, phenylthio, or pyrimidinyl. Still more preferably, R 41Selected from phenyl and heteroaryl, wherein the heteroaryl is a 5- or 6-membered monocyclic heteroaryl having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (the remaining ring atoms of the monocyclic heteroaryl are carbon atoms), and further, wherein the phenyl or the heteroaryl is optionally substituted with one or more (e.g., one, two, or three) groups R 42 substituted.

[0121] Each R 42 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl).

[0122] Preferably, each R 42 is independently selected from C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0123] Each R 43 independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3, -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl) and -N(C 1-6 alkyl)-CO-(C 1-6 alkyl).

[0124] Preferably, each R 43 independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3 and -CN.

[0125] According to the above definition, particularly preferably, R 4a selected from -O-(C 0-4 alkylene)-aryl, -O-(C 0-4 alkylene)-heteroaryl, -S-(C 0-4 alkylene)-aryl, -S-(C 0-4 alkylene)-heteroaryl, -NH-(C 0-4 alkylene)-aryl, -NH-(C 0-4 alkylene)-heteroaryl, -N(C 1-4 alkyl)-(C 0-4 alkylene)-aryl, -N(C1-4 alkyl)-(C 0-4 alkylene)-heteroaryl, aryl and heteroaryl, wherein the aryl moiety of any of the above groups, the heteroaryl moiety of any of the above groups, the aryl and the heteroaryl are each optionally substituted by one or more (e.g., one, two or three) groups R 42 Substituted. Even more preferably, R 4a is selected from -O-aryl, -O-heteroaryl, -S-aryl, -S-heteroaryl, -NH-aryl, -NH-heteroaryl, -N(C 1-4 alkyl)-aryl, -N(C 1-4 alkyl)-heteroaryl, aryl and heteroaryl, wherein the aryl moiety of any of the above groups, the heteroaryl moiety of any of the above groups, the aryl and the heteroaryl are each optionally independently substituted by a group selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl and -CN. Even yet more preferably, R 4a is selected from -O-phenyl, -O-heteroaryl, -S-phenyl, -S-heteroaryl, -NH-phenyl, -NH-heteroaryl, -N(C 1-4 alkyl)-phenyl, -N(C 1-4 alkyl)-heteroaryl, phenyl and heteroaryl, wherein the heteroaryl or the heteroaryl moiety of any of the above groups is a 5- or 6-membered monocyclic heteroaryl having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen and sulfur (the remaining ring atoms of the monocyclic heteroaryl are carbon atoms), and further, wherein the phenyl moiety of any of the above groups, the heteroaryl moiety of any of the above groups, the phenyl and the heteroaryl are each optionally independently substituted by a group selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6(alkyl), -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), halogen, C 1-6 substituted by one or more groups of haloalkyl and -CN. R 4a Particularly preferred examples of are -O-phenyl.

[0126] R 5a is selected from -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), -NO2 and hydrogen, wherein the alkyl moiety of the -NH(C 1-6 (alkyl) and the one or two alkyl moieties of the -N(C 1-6 (alkyl)(C 1-6 (alkyl) are each optionally independently substituted by one or more groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), -OH, -O(C 1-6 (alkyl), -SH, -S(C 1-6 (alkyl), carbocyclic group and heterocyclic group, and one or more (e.g., one, two or three) groups, wherein the carbocyclic group and the heterocyclic group are each optionally substituted by one or more (e.g., one, two or three) groups R 51 substituted.

[0127] Preferably, R 5a is selected from -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), -NO2, wherein the alkyl moiety of the -NH(C 1-6 (alkyl) and the one or two alkyl moieties of the -N(C 1-6 (alkyl)(C 1-6 (alkyl) are each optionally independently substituted by one or more groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), -OH, -O(C 1-6 (alkyl), -SH and -S(C 1-6 (alkyl), and one or more (e.g., one, two or three) groups. More preferably, R 5a is selected from -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C1-6 alkyl) and -NO2. R 5a Particularly preferred examples of are -NH2, -NH-CH2CH2CH2CH3 or -NO2.

[0128] Each R 51 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl).

[0129] Preferably, each R 51 is independently selected from C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0130] R 5b is selected from -R 5b1 -R 5b2 -R 5b1 -, -N=C(R 53 )-R 5b3 -R 5b1 -, -R 5b1 -R 5b3 -C(R 53 )=N- and -N=C(R 53 )-R 5b4 -C(R 53 )=N-.

[0131] Each R 5b1 is independently selected from -N(R 52 )-, -O- and -S-.

[0132] R 5b2 is selected from -C(R 53 )(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )(R 53 )-, -C(R 53 )=C(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )=C(R 53 )- and -C(R 53 )=C(R 53 )-C(R 53 )(R 53 ).

[0133] R 5b3 is selected from a covalent bond, -C(R 53 )(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )(R 53 )- and -C(R 53 )=C(R 53 ).

[0134] R 5b4 is selected from a covalent bond and -C(R 53 )(R53 )-.

[0135] Each R 52 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl.

[0136] Preferably, each R 52 is independently selected from hydrogen, C 1-4 alkyl (e.g., n-butyl), C 2-4 alkenyl and C 2-4 alkynyl (e.g., -CH2-C≡CH). Even more preferably, each R 52 is hydrogen.

[0137] Each R 53 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl), -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl), -(C 0-4 alkylene)-aryl and -(C 0-4alkylene)-heteroaryl; in addition, any two groups R attached to the same carbon atom 53 may also together form a group =O; and any two groups R attached to adjacent carbon atoms linked by a double bond 53 (i.e., including any two groups R in the moiety -C(R 53 )=C(R 53 )) may also be linked to each other to form a group -C(R 53 )=C(R 54 )-C(R 54 )=C(R 54 )=C(R 54 )-.

[0138] Preferably, each R 53 is independently selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN, and any two groups R attached to the same carbon atom 53 may also together form a group =O, and any two groups R attached to adjacent carbon atoms linked by a double bond 53 may also be linked to each other to form a group -C(R 54 )=C(R 54 )-C(R 54 )=C(R 54 )-. More preferably, each R 53 is independently selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN, and any two groups R attached to the same carbon atom 53 may also together form a group =O. Even more preferably, each R 53 is independently selected from hydrogen, C 1-4 alkyl, -OH, -O(C 1-4 alkyl), -NH2, -NH(C 1-4 alkyl), -N(C1-4 (alkyl)(C 1-4 alkyl), halogen, C 1-4 haloalkyl, -O-(C 1-4 haloalkyl) and -CN, and any two groups R attached to the same carbon atom 53 may also together form the group =O.

[0139] Each R 54 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl).

[0140] Preferably, each R 54 is independently selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6(haloalkyl) and -CN. More preferably, each R 54 is hydrogen.

[0141] Particularly preferably, R 5b is selected from -N(R 52 )(R 53 )(R 53 )-N(R 52 )-, -N=C(R 53 )(R 52 )-N(R 52 )-, -N(R 53 )(R 52 )=N-, -N(R 53 )(R 53 )(R 53 )(R 53 )-N(R 52 )-, -N=C(R 53 )(R 53 )(R 53 )-N(R 52 )-, -N(R 52 )(R 53 )=C(R 53 )(R 52 )-N(R 52 )-, -N(R 53 )(R 53 )(R 53 )=N-, -N=C(R 53 )(R 53 )=N-, -N(R 52 )(R 53 )(R 53 )(R 53 )(R 53 )-N(R 53 )(R 53 )-, -N=C(R 52 )(R 53 )(R 53 )(R 53 )-N(R 53 )(R 53 )-, -N(R 52 )(R 52 )(R 53 )(R 53 )-C(R 53 )=C(R 53 )(R 52 )-, -N(R 52 )(R 53 )=C(R53 )-C(R 53 )(R 53 )-N(R 52 )-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )=N-、-N=C(R 53 )-C(R 53 )(R 53 )-C(R 53 )=N-、-O-C(R 53 )(R 53 )-N(R 52 )-、-O-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-O-C(R 53 )=C(R 53 )-N(R 52 )-、-O-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-O-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-N(R 52 )-、-O-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-N(R 52 )-C(R 53 )(R 53 )-O-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-O-、-N(R 52 )-C(R 53 )=C(R 53 )-O-、-N(R 52 )-C(R 53)(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-O-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-O-、-N(R 52 )-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-O-、-S-C(R 53 )(R 53 )-N(R 52 )-、-S-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-S-C(R 53 )=C(R 53 )-N(R 52 )-、-S-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-S-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-N(R 52 )-、-S-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-N(R 52 )-C(R 53 )(R 53 )-S-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-S-、-N(R 52 )-C(R 53 )=C(R 53 )-S-、-N(R52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-S-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-S-, -N(R 52 )-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-S-, -N(R 52 )-C(R 53 )(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )=C(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-N(R 52 )- and -N(R 52 )-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-N(R 52 ).

[0142] In addition, if the ring moiety is and if R 4 and R 5Connected to each other to form a group -R 5b -, then even more preferably, R is selected 5b such that the compound of formula (I) has any one of the following structures:

[0143]

[0144]

[0145] R 6 is selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl).

[0146] Preferably, R 6 is selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN. More preferably, R 6 is hydrogen or C 1-4 alkyl. Even more preferably, R 6 is hydrogen.

[0147] Optionally (i.e., as an alternative to the above meanings of R 1 and R 6 ), the groups R 1 and R 6 are joined to form a group -R 16 -, where:

[0148] -R 16 is the group -C(R 161 )(R 161 )-C(R 161 )(R 161 )-C(R 161 )(R 161 )-C(R 161 )(R 161 )-, where one or two -C(R 161 )(R 161 )- units included in said group are each replaced by -R 163 -;

[0149] - each R 161 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -(C 0-6 alkylene)-CF3, -(C 0-6 alkylene)-CN, -(C 0-6 alkylene)-NO2, -(C 0-6 alkylene)-N(R 162 )(R 162 ), -(C 0-6 alkylene)-O(R 162 ), -(C 0-6 alkylene)-S(R 162 ), -(C 0-6 alkylene)-SO3H,

[0150] -(C0-6 (alkylene)-carbocyclic group and -(C 0-6 (alkylene)-heterocyclic group;

[0151] - Each R 162 is independently hydrogen or C 1-6 alkyl group; and

[0152] - Each R 163 is independently selected from -N(R 161 )-, -O-, and -S-.

[0153] Preferably, R 16 is the group -CH2-CH2-CH2-CH2-, wherein one or two -CH2- units included in said group are each replaced by -R 163 -. More preferably, R 16 is the group -CH2-CH2-CH2-CH2-, wherein one -CH2- unit included in said group is replaced by -R 163 -. Even more preferably, R 16 is -CH2-R 163 -CH2-CH2- or -CH2-CH2-R 163 -CH2.

[0154] Preferably, each R 163 is independently -N(R 161 )-. A preferred example of the corresponding group R 163 is -N(-CH2-CF3)-. Thus, particularly preferably, R 16 is -CH2-N(R 161 )-CH2-CH2- or -CH2-CH2-N(R 161 )-CH2- (for example, -CH2-N(-CH2-CF3)-CH2-CH2- or -CH2-CH2-N(-CH2-CF3)-CH2-).

[0155] According to the present invention, if the ring moiety in formula (I) is R 2 is hydrogen, R 3 is -SO2-NH2, R 4 is -O-phenyl, R 5 is -NH-CH2CH2CH2CH3 and R 6 is hydrogen, then R 1 is different from -COOH.

[0156] Therefore, in other words, if all of the following conditions are satisfied, then R 1 is different from -COOH (i.e., R 1Not - COOH): (i) Ring moiety is (ii) R 2 is hydrogen, (iii) R 3 is - SO2 - NH2, (iv) R 4 is - O - phenyl, (v) R 5 is - NH - CH2CH2CH2CH3, and (vi) R 6 is hydrogen.

[0157] The compound of formula (I) can be, for example, any of the specific compounds described in the Examples section of this specification, which are in non - salt form (e.g., free base / acid form) or as a pharmaceutically acceptable salt or solvate of the corresponding compound.

[0158] Specifically, the compound of formula (I) can be a compound of any of the following formulas, or a pharmaceutically acceptable salt or solvate thereof:

[0159]

[0160]

[0161]

[0162]

[0163]

[0164]

[0165]

[0166]

[0167]

[0168]

[0169] In the first embodiment, the ring moiety in the compound of formula (I) is

[0170] Thus, in this first embodiment, the compound of formula (I) is a compound of the following formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0171]

[0172] wherein the groups and variables in formula (Ia), specifically including R 1 、R2 , R 3 , R 4 , R 5 and R 6 , having the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0173] In a second embodiment, the ring moiety in the compound of formula (I) is

[0174] Thus, in this second embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0175]

[0176] wherein the groups and variables in formula (Ib), specifically including R x , R 4 , R 5 and R 6 , having the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0177] In a third embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0178]

[0179] wherein R 4 is the group R 4a , wherein R 5 is the group R 5a , and wherein the further groups and variables in formula (Ia), specifically including R 1 , R 2 , R 3 and R 6 , having the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0180] In this third embodiment, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 alkyl)-R 41 , halogen (e.g., -Cl), carbocyclic group and heterocyclic group, wherein the carbocyclic group and the heterocyclic group are each optionally substituted by one or more (e.g., one, two or three) groups R 42 . Preferably, R4a Selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 (alkyl)-R 41 , a carbocyclic group (e.g., aryl, cycloalkyl or cycloalkenyl) and a heterocyclic group (e.g., heteroaryl, heterocycloalkyl or heterocycloalkenyl), wherein each of the carbocyclic group and the heterocyclic group is optionally substituted by one or more groups R 42 . More preferably, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-4 (alkyl)-R 41 , aryl and heteroaryl, wherein each of the aryl and the heteroaryl is optionally substituted by one or more groups R 42 .

[0181] R 41 is selected from -(C 0-4 (alkylene)-carbocyclic group, -(C 0-4 (alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the carbocyclic group portion of the -(C 0-4 (alkylene)-carbocyclic group and the heterocyclic group portion of the -(C 0-4 (alkylene)-heterocyclic group are each optionally substituted by one or more (e.g., one, two or three) groups R 42 , and wherein the C 1-6 alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl, the alkylene portion of the -(C 0-4 (alkylene)-carbocyclic group and the alkylene portion of the -(C 0-4 (alkylene)-heterocyclic group are each optionally substituted by one or more (e.g., one, two or three) groups R 43 . Preferably, R 41 is selected from -(C 0-4 (alkylene)-carbocyclic group, -(C 0-4 (alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the carbocyclic group portion of the -(C 0-4 (alkylene)-carbocyclic group is selected from cycloalkyl, cycloalkenyl and aryl, wherein the heterocyclic group portion of the -(C 0-4 (alkylene)-heterocyclic group is selected from heterocycloalkyl, heterocycloalkenyl and heteroaryl, wherein the -(C0-4 The carbocyclic moiety of the -(C-alkylene)-carbocyclic group and the 0-4 heterocyclic moiety of the -(C-alkylene)-heterocyclic group are each optionally 42 substituted by one or more (e.g., one, two or three) groups R 1-6 alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl, the -(C 0-4 alkylene)-carbocyclic alkylene moiety and the -(C 0-4 alkylene)-heterocyclic alkylene moiety are each optionally 43 substituted by one or more (e.g., one, two or three) groups R 41 More preferably, R 0-4 is selected from -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, wherein the aryl moiety of the -(C 0-4 alkylene)-aryl and the heteroaryl moiety of the -(C 42 alkylene)-heteroaryl are each optionally 0-4 substituted by one or more (e.g., one, two or three) groups R 0-4 and further, wherein the alkylene moiety of the -(C 43 alkylene)-aryl and the alkylene moiety of the -(C 41 alkylene)-heteroaryl are each optionally 0-4 substituted by one or more (e.g., one, two or three) groups R 0-4 Even more preferably, R 0-4 is selected from -(C 0-4 alkylene)-aryl and -(C 42 alkylene)-heteroaryl, wherein the aryl moiety of the -(C 0-4 alkylene)-aryl and the heteroaryl moiety of the -(C 0-4 alkylene)-heteroaryl are each optionally 41Selected from phenyl and heteroaryl, wherein the heteroaryl is a 5- or 6-membered monocyclic heteroaryl having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (the remaining ring atoms of the monocyclic heteroaryl are carbon atoms), and further, wherein the phenyl or the heteroaryl is optionally substituted with one or more (e.g., one, two, or three) groups R 42 substituted.

[0182] Each R 42 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, each R 42 is independently selected from C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0183] Each R 43 is independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3, -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl) and -N(C 1-6 alkyl)-CO-(C 1-6 alkyl). Preferably, each R 43 is independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3 and -CN.

[0184] According to the above definition, particularly preferably, R 4a is selected from -O-(C 0-4 alkylene)-aryl, -O-(C 0-4 alkylene)-heteroaryl, -S-(C 0-4 alkylene)-aryl, -S-(C 0-4 alkylene)-heteroaryl, -NH-(C 0-4 alkylene)-aryl, -NH-(C 0-4 alkylene)-heteroaryl, -N(C 1-4 alkyl)-(C 0-4 alkylene)-aryl, -N(C 1-4 alkyl)-(C 0-4an alkylene)-heteroaryl, aryl and heteroaryl, wherein the aryl moiety of any of the above groups, the heteroaryl moiety of any of the above groups, the aryl and the heteroaryl are each optionally substituted by one or more (e.g., one, two or three) groups R 42 substituted. Even more preferably, R 4a is selected from -O-aryl, -O-heteroaryl, -S-aryl, -S-heteroaryl, -NH-aryl, -NH-heteroaryl, -N(C 1-4 alkyl)-aryl, -N(C 1-4 alkyl)-heteroaryl, aryl and heteroaryl, wherein the aryl moiety of any of the above groups, the heteroaryl moiety of any of the above groups, the aryl and the heteroaryl are each optionally independently substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl and -CN. Even even more preferably, R 4a is selected from -O-phenyl, -O-heteroaryl, -S-phenyl, -S-heteroaryl, -NH-phenyl, -NH-heteroaryl, -N(C 1-4 alkyl)-phenyl, -N(C 1-4 alkyl)-heteroaryl, phenyl and heteroaryl, wherein the heteroaryl or the heteroaryl moiety of any of the above groups is a 5- or 6-membered monocyclic heteroaryl having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen and sulfur (the remaining ring atoms of the monocyclic heteroaryl are carbon atoms), and further, wherein the phenyl moiety of any of the above groups, the heteroaryl moiety of any of the above groups, the phenyl and the heteroaryl are each optionally independently substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C1-6 (alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, and one or more groups of -CN. R 4a Particularly preferred examples of are -O-phenyl.

[0185] In this third embodiment, R 5a is selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -NO2, and hydrogen, wherein the alkyl moiety of the -NH(C 1-6 alkyl) and one or both alkyl moieties of the -N(C 1-6 alkyl)(C 1-6 alkyl) are each optionally independently substituted with one or more (e.g., one, two, or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), carbocyclic group, and heterocyclic group, wherein the carbocyclic group and the heterocyclic group are each optionally substituted with one or more (e.g., one, two, or three) groups R 51 substituted. Preferably, R 5a is selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), and -NO2, wherein the alkyl moiety of the -NH(C 1-6 alkyl) and one or both alkyl moieties of the -N(C 1-6 alkyl)(C 1-6 alkyl) are each optionally independently substituted with one or more (e.g., one, two, or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH, and -S(C 1-6 alkyl). More preferably, R 5a is selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), and -NO2. R 5aParticularly preferred examples are -NH2, -NH-CH2CH2CH2CH3 or -NO2.

[0186] Each R 51 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, each R 51 is independently selected from C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C1-6 haloalkyl) and -CN.

[0187] In a fourth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof

[0188]

[0189] wherein R 4 and R 5 are connected to each other to form a group -R 5b -, and wherein the further groups and variables in formula (Ia), specifically including R 1 , R 2 , R 3 and R 6 , have the same meanings as described and defined above for the compound of formula (I), including the same preferred meanings.

[0190] In this fourth embodiment, R 4 and R 5 are connected to each other to form a group -R 5b -. The group R 5b is selected from -R 5b1 -R 5b2 -R 5b1 -, -N=C(R 53 )-R 5b3 -R 5b1 -, -R 5b1 -R 5b3 -C(R 53 )=N- and -N=C(R 53 )-R 5b4 -C(R 53 )=N-.

[0191] Each R 5b1 is independently selected from -N(R 52 )-, -O- and -S-. R 5b2 is selected from -C(R 53 )(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )(R 53 )-, -C(R 53 )=C(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )=C(R 53 )- and -C(R 53 )=C(R 53 )-C(R53 )(R 53 )-.R 5b3 Selected from a covalent bond, -C(R 53 )(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )(R 53 )- and -C(R 53 )=C(R 53 )-.R 5b4 Selected from a covalent bond and -C(R 53 )(R 53 )-.

[0192] Each R 52 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl. Preferably, each R 52 is independently selected from hydrogen, C 1-4 alkyl (e.g., n-butyl), C 2-4 alkenyl and C 2-4 alkynyl (e.g., -CH2-C≡CH). Even more preferably, each R 52 is hydrogen.

[0193] Each R 53 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6(alkyl)-CO-(C 1-6 (alkyl), -SO2-NH2, -SO2-NH(C 1-6 (alkyl), -SO2-N(C 1-6 (alkyl)(C 1-6 (alkyl), -NH-SO2-(C 1-6 (alkyl), -N(C 1-6 (alkyl)-SO2-(C 1-6 (alkyl), -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl; in addition, any two groups R 53 connected to the same carbon atom may also together form the group =O; and any two groups R 53 (i.e., including in the moiety -C(R 53 )=C(R 53 ))- in any two groups R 53 ) may also be connected to each other to form the group -C(R 54 )=C(R 54 )-C(R 54 )=C(R 54 ))-. Preferably, each R 53 is independently selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN, and any two groups R 53 connected to the same carbon atom may also together form the group =O, and any two groups R 53 connected to adjacent carbon atoms linked by a double bond may also be connected to each other to form the group -C(R 54 )=C(R 54 )-C(R 54 )=C(R 54 ))-. More preferably, each R 53 is independently selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C1-6 haloalkyl, -O-(C 1-6 haloalkyl), and -CN, and any two groups R attached to the same carbon atom 53 may also together form the group =O. Even more preferably, each R 53 is independently selected from hydrogen, C 1-4 alkyl, -OH, -O(C 1-4 alkyl), -NH2, -NH(C 1-4 alkyl), -N(C 1-4 alkyl)(C 1-4 alkyl), halogen, C 1-4 haloalkyl, -O-(C 1-4 haloalkyl), and -CN, and any two groups R attached to the same carbon atom 53 may also together form the group =O.

[0194] Each R 54 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl), and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, each R 54 is independently selected from hydrogen, C1-6 alkyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN. More preferably, each R 54 is hydrogen.

[0195] Particularly preferably, R 5b is selected from -N(R 52 )(R 53 )(R 53 )-N(R 52 )-, -N=C(R 53 )(R 52 )-N(R 52 )-, -N(R 53 )-C(R 52 )(R 53 )-N(R 53 )-, -N=C(R 53 )(R 53 )-N(R 52 )-, -N(R 53 )-C(R 53 )(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )=C(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )=N-, -N=C(R 53 )-C(R 53 )=N-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-, -N=C(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53)-N(R 52 )-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-N(R 52 )-、-N(R 52 )-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )=N-、-N=C(R 53 )-C(R 53 )(R 53 )-C(R 53 )=N-、-O-C(R 53 )(R 53 )-N(R 52 )-、-O-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-O-C(R 53 )=C(R 53 )-N(R 52 )-、-O-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-O-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-N(R 52 )-、-O-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-N(R 52 )-C(R 53 )(R 53 )-O-、-N(R52 )(R 53 )(R 53 )(R 53 )(R 53 )-O-, -N(R 52 )(R 53 )=C(R 53 )-O-, -N(R 52 )(R 53 )(R 53 )(R 53 )(R 53 )(R 53 )(R 53 )-O-, -N(R 52 )(R 53 )(R 53 )(R 53 )=C(R 53 )-O-, -N(R 52 )(R 53 )=C(R 53 )(R 53 )(R 53 )-O-, -S-C(R 53 )(R 53 )-N(R 52 )-, -S-C(R 53 )(R 53 )(R 53 )(R 53 )-N(R 52 )-, -S-C(R 53 )=C(R 53 )-N(R 52 )-, -S-C(R 53 )(R 53 )(R 53 )(R 53 )(R 53 )(R 53 )-N(R 52 )-, -S-C(R 53 )(R 53 )(R 53 )=C(R 53 )-N(R 52 )-, -S-C(R 53 )=C(R 53 )(R 53 )(R 53 )-N(R 52 )-, -N(R 52 )(R 53 )(R53 )-S-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-S-, -N(R 52 )-C(R 53 )=C(R 53 )-S-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-S-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-S-, -N(R 52 )-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-S-, -N(R 52 )-C(R 53 )(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )=C(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-N(R 52 )- and -N(R 52 )-C(R53 )=C(R 53 )-C(R 53 )(R 53 )-N(R 52 )-.

[0196] In this fourth embodiment, even more preferably, R is selected 5b such that the compound of formula (Ia) has any of the following structures:

[0197]

[0198]

[0199] In a fifth embodiment, the compound of formula (I) is a compound of formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0200]

[0201] wherein R 4 is the group R 4a , wherein R 4a is -O-phenyl, wherein R 5 is the group R 5a , and wherein the further groups and variables in formula (Ia), specifically including R 1 , R 2 , R 3 , R 5a and R 6 , have the same meanings as described and defined above for the compound of formula (I), including the same preferred meanings.

[0202] In a sixth embodiment, the compound of formula (I) is a compound of formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0203]

[0204] wherein R 4 is the group R 4a , wherein R 5 is the group R 5a , wherein R 5a is -NH2, and wherein the further groups and variables in formula (Ia), specifically including R 1 , R 2 , R 3 , R 4a and R 6 , have the same meanings as described and defined above for the compound of formula (I), including the same preferred meanings.

[0205] In a seventh embodiment, a compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0206]

[0207] wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 3 、R 4a and R 6 have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0208] In an eighth embodiment, a compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0209]

[0210] wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NO2, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 3 、R 4a and R 6 have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0211] In a ninth embodiment, a compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0212]

[0213] wherein R 3 is -SO2-NH2, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 4 、R 5 and R 6, having the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0214] In a tenth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0215]

[0216] wherein R 3 is -SO2-N=CH-N(CH3)2, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 4 、R 5 and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0217] In an eleventh embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0218]

[0219] wherein R 3 is -SO2-NH2, wherein R 4 is the group R 4a wherein R 4a is -O-phenyl, wherein R 5 is the group R 5a , and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 5a and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0220] In a twelfth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0221]

[0222] wherein R 3 is -SO2-NH2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5ais -NH2, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 4a and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0223] In a thirteenth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0224]

[0225] wherein R 3 is -SO2-NH2, wherein R 4 is the group R 4a , wherein R 5 is the group R 5a , wherein R 5a is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 4a and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0226] In a fourteenth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0227]

[0228] wherein R 3 is -SO2-NH2, wherein R 4 is the group R 4a , wherein R 5 is the group R 5a , wherein R 5a is -NO2, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 4a and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0229] In a fifteenth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0230]

[0231] wherein R 3 is -SO2-N=CH-N(CH3)2, wherein R 4 is the group R 4a wherein R 4a is -O-phenyl, wherein R 5 is the group R 5a and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 5a and R 6 have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0232] In a sixteenth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0233]

[0234] wherein R 3 is -SO2-N=CH-N(CH3)2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NH2, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 4a and R 6 have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0235] In a seventeenth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0236]

[0237] wherein R 3 is -SO2-N=CH-N(CH3)2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R4a and R 6 , which has the same meaning as described and defined above for the compound of formula (I), including the same preferred meanings.

[0238] In the eighteenth embodiment, the compound of formula (I) is a compound of the following formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0239]

[0240] wherein R 3 is -SO2-N=CH-N(CH3)2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NO2, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 4a and R 6 , which has the same meaning as described and defined above for the compound of formula (I), including the same preferred meanings.

[0241] In the nineteenth embodiment, the compound of formula (I) is a compound of the following formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0242]

[0243] wherein R 4 is -O-phenyl, wherein R 5 is -NH2, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2 、R 3 and R 6 , which has the same meaning as described and defined above for the compound of formula (I), including the same preferred meanings.

[0244] In the twentieth embodiment, the compound of formula (I) is a compound of the following formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0245]

[0246] wherein R 4 is -O-phenyl, wherein R 5 is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ia), specifically including R 1 、R 2, R 3 and R 6 , having the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0247] In a twenty-first embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0248]

[0249] wherein R 4 is -O-phenyl, wherein R 5 is -NO2, and wherein the further groups and variables in formula (Ia), specifically including R 1 , R 2 , R 3 and R 6 , having the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0250] In a twenty-second embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0251]

[0252] wherein R 1 is as defined below, and wherein the further groups and variables in formula (Ia), specifically including R 2 , R 3 , R 4 , R 5 and R 6 , having the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0253] In this twenty-second embodiment, R 1 is -COO-(C 1-15 alkyl), wherein the alkyl moiety of said -COO-(C 1-15 alkyl) is optionally independently substituted by one or more (e.g., one, two or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-4 alkyl), -N(C 1-4 alkyl)(C 1-4 alkyl), -OH, -O(C 1-4 alkyl), -SH and -S(C 1-4 alkyl), and further, wherein included in said -COO-(C 1-15One or two -CH2- units in the alkyl moiety of (alkyl) are each optionally independently selected from -O-, -CO-, -COO-, -O-CO-, -NH-, -N(C 1-4 alkyl)-, -NH-CO-, -N(C 1-4 alkyl)-CO-, -CO-NH-, -CO-N(C 1-4 alkyl)-, -S-, -SO-, -SO2-, -SO2-NH-, -SO2-N(C 1-4 alkyl)-, -NH-SO2- and -N(C 1-4 alkyl)-SO2-. The alkyl moiety of the -COO-(C 1-15 alkyl) has 1 to 15 carbon atoms, especially 1 to 10 carbon atoms. Such an R 1 group's preferred examples include the corresponding group R of the compounds described in the Examples section 1 , specifically including -COO-CH3 or -COO-CH2CH3. A particularly preferred group R 1 is -COO-CH3.

[0254] In the twenty-third embodiment, the compound of formula (I) is a compound of the following formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0255]

[0256] wherein R 1 is -COOH, and wherein the other groups and variables in formula (Ia), specifically including R 2 , R 3 , R 4 , R 5 and R 6 , have the same meanings as described and defined above for the compound of formula (I), including the same preferred meanings.

[0257] In the twenty-fourth embodiment, the compound of formula (I) is a compound of the following formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0258]

[0259] wherein R 1 is as defined below, and wherein the other groups and variables in formula (Ia), specifically including R 2 , R 3 , R 4 , R 5 and R 6, having the same meaning as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0260] In this twenty-fourth embodiment, R 1 is selected from -(C 1-4 alkylene)-NH-(C 1-4 alkylene)-R 12 (e.g., -CH2-NH-CH2-R 12 ), -COO-(C 1-4 alkylene)-R 12 (e.g., -COO-CH2-R 12 ), -O-CO-(C 1-4 alkylene)-R 12 , -CO-(C 1-4 alkylene)-R 12 , -CO-NH-(C 1-4 alkylene)-R 12 (e.g., -CO-NH-CH2-R 12 ), -CO-N(C 1-4 alkyl)-(C 1-4 alkylene)-R 12 , -NH-CO-(C 1-4 alkylene)-R 12 and -N(C 1-4 alkyl)-CO-(C 1-4 alkylene)-R 12 , where R 12 is independently selected from -CF3, -CN and halogen (e.g., -F, -Cl, -Br or -I). Preferably, R 12 is independently selected from -CF3 and -CN; more preferably, R 12 is -CF3. Specific examples of such R 1 groups include the corresponding groups R 1 of the compounds described in the Examples section. More preferably, R 1 is -(C 1-4 alkylene)-NH-(C 1-4 alkylene)-CF3, and even more preferably, R 1 is -CH2-NH-CH2-CF3.

[0261] Thus, according to this twenty-fourth embodiment, the present invention provides a compound of the following formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0262]

[0263] In this twenty-fourth embodiment, R in formula (Ia)1 selected from -(C 1-4 alkylene)-NH-(C 1-4 alkylene)-R 12 (e.g., -CH2-NH-CH2-R 12 ), -COO-(C 1-4 alkylene)-R 12 (e.g., -COO-CH2-R 12 ), -O-CO-(C 1-4 alkylene)-R 12 , -CO-(C 1-4 alkylene)-R 12 , -CO-NH-(C 1-4 alkylene)-R 12 (e.g., -CO-NH-CH2-R 12 ), -CO-N(C 1-4 alkyl)-(C 1-4 alkylene)-R 12 , -NH-CO-(C 1-4 alkylene)-R 12 and -N(C 1-4 alkyl)-CO-(C 1-4 alkylene)-R 12 , where R 12 is independently selected from -CF3, -CN, and halogen (e.g., -F, -Cl, -Br, or -I). Preferably, R 12 is independently selected from -CF3 and -CN; more preferably, R 12 is -CF3. Specific examples of such R 1 groups include the corresponding R 1 groups of the compounds described in the Examples section. Particularly preferably, R 1 is -(C 1-4 alkylene)-NH-(C 1-4 alkylene)-CF3, and even more preferably, R 1 is -CH2-NH-CH2-CF3.

[0264] In the twenty-fourth embodiment, R 2 is selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, R 2 is selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN. More preferably, R 2 is hydrogen or C 1-4 alkyl. Even more preferably, R 2 is hydrogen.

[0265] In the twenty-fourth embodiment, R 3 is selected from -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -SO2-N=(C 1-6 alkylidene) and -SO2-halogen, wherein the -SO2-NH(C1-6 the alkyl moiety of the alkyl), the -SO2-N(C 1-6 alkyl)(C 1-6 one or two alkyl moieties of the alkyl) and the -SO2-N=(C 1-6 the alkylidene moiety of the alkylidene) is each optionally independently substituted by one or more (e.g., one, two or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH and -S(C 1-6 alkyl). Preferably, R 3 is selected from -SO2-NH2, -SO2-NH(C 1-4 alkyl), -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and -SO2-N=(C 1-4 alkylidene), wherein the alkyl moiety of the -SO2-NH(C 1-4 alkyl), the one or two alkyl moieties of the -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and the alkylidene moiety of the -SO2-N=(C 1-4 alkylidene) is each optionally independently substituted by one or more groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH and -S(C 1-6 alkyl). More preferably, R 3 is selected from -SO2-NH2, -SO2-NH(C 1-4 alkyl), -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and -SO2-N=(C 1-4 alkylidene), wherein the alkyl moiety of the -SO2-NH(C 1-4 alkyl), the one or two alkyl moieties of the -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and the alkylidene moiety of the -SO2-N=(C 1-4 alkylidene) is each optionally substituted by -NH2, -NH(C 1-4 alkyl) and -N(C 1-4 alkyl)(C1-4 is substituted by one group of (alkyl). Even more preferably, R 3 is selected from -SO2-NH2, -SO2-NH(C 1-4 alkyl), -SO2-N(C 1-4 alkyl)(C 1-4 alkyl), -SO2-NH-(C 1-4 alkylene)-NH2, -SO2-NH-(C 1-4 alkylene)-NH(C 1-4 alkyl), -SO2-NH-(C 1-4 alkylene)-N(C 1-4 alkyl)(C 1-4 alkyl), -SO2-N=(C 1-4 alkylidene)-NH2, -SO2-N=(C 1-4 alkylidene)-NH(C 1-4 alkyl) and -SO2-N=(C 1-4 alkylidene)-N(C 1-4 alkyl)(C 1-4 alkyl). Even even more preferably, R 3 is selected from -SO2-NH2, -SO2-NH-CH3, -SO2-N(CH3)2, -SO2-NH-(C 1-4 alkylene)-NH2, -SO2-NH-(C 1-4 alkylene)-NH-CH3, -SO2-NH-(C 1-4 alkylene)-N(CH3)2 (for example, -SO2-NH-CH2CH2-N(CH3)2), -SO2-N=(C 1-4 alkylidene)-NH2, -SO2-N=(C 1-4 alkylidene)-NH-CH3 and -SO2-N=(C 1-4 alkylidene)-N(CH3)2 (for example, -SO2-N=CH-N(CH3)2). Still more preferably, R 3 is -SO2-NH2.

[0266] In the twenty-fourth embodiment, R 4 is selected from -O-R 41 、-S-R 41 、-NH-R 41 、-N(C 1-6 alkyl)-R 41 、halogen (for example, -Cl), hydrogen, carbocyclic group and heterocyclic group, wherein each of the carbocyclic group and the heterocyclic group is optionally substituted by one or more (for example, one, two or three) groups R 42 substituted. Preferably, R 4 is selected from -O-R41 、 -S-R 41 、 -NH-R 41 、 -N(C 1-6 alkyl)-R 41 、 a halogen, a carbocyclic group, and a heterocyclic group, wherein each of the carbocyclic group and the heterocyclic group is optionally substituted with one or more groups R 42 . More preferably, R 4 is selected from -O-R 41 、 -S-R 41 、 -NH-R 41 、 -N(C 1-6 alkyl)-R 41 、 a carbocyclic group (e.g., an aryl, cycloalkyl, or cycloalkenyl group) and a heterocyclic group (e.g., a heteroaryl, heterocycloalkyl, or heterocycloalkenyl group), wherein each of the carbocyclic group and the heterocyclic group is optionally substituted with one or more groups R 42 . Even more preferably, R 4 is selected from -O-R 41 、 -S-R 41 、 -NH-R 41 、 -N(C 1-4 alkyl)-R 41 、 an aryl group and a heteroaryl group, wherein each of the aryl group and the heteroaryl group is optionally substituted with one or more groups R 42 .

[0267] In the twenty-fourth embodiment, R 41 is selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl, and C 2-6 alkynyl, wherein the carbocyclic group portion of the -(C 0-4 alkylene)-carbocyclic group and the heterocyclic group portion of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted with one or more (e.g., one, two, or three) groups R 42 , and wherein the C 1-6 alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl, the alkylene portion of the -(C 0-4 alkylene)-carbocyclic group, and the alkylene portion of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted with one or more (e.g., one, two, or three) groups R 43 . Preferably, R 41 is selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4(Alkylene)-heterocyclyl, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein said -(C 0-4 alkylene)-carbocyclic moiety of the carbocyclic group is selected from cycloalkyl, cycloalkenyl and aryl, wherein said -(C 0-4 alkylene)-heterocyclic moiety of the heterocyclic group is selected from heterocycloalkyl, heterocycloalkenyl and heteroaryl, wherein said -(C 0-4 alkylene)-carbocyclic moiety of the carbocyclic group and said -(C 0-4 alkylene)-heterocyclic moiety of the heterocyclic group are each optionally substituted by one or more (e.g., one, two or three) groups R 42 and further, wherein said C 1-6 alkyl, said C 2-6 alkenyl, said C 2-6 alkynyl, said -(C 0-4 alkylene)-carbocyclic moiety of the alkylene part and said -(C 0-4 alkylene)-heterocyclic moiety of the alkylene part are each optionally substituted by one or more (e.g., one, two or three) groups R 43 . More preferably, R 41 is selected from -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, wherein said -(C 0-4 alkylene)-aryl moiety of the aryl part and said -(C 0-4 alkylene)-heteroaryl moiety of the heteroaryl part are each optionally substituted by one or more (e.g., one, two or three) groups R 42 and further, wherein said -(C 0-4 alkylene)-aryl moiety of the alkylene part and said -(C 0-4 alkylene)-heteroaryl moiety of the alkylene part are each optionally substituted by one or more (e.g., one, two or three) groups R 43 . Even more preferably, R 41 is selected from -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, wherein said -(C 0-4 alkylene)-aryl moiety of the aryl part and said -(C 0-4 alkylene)-heteroaryl moiety of the heteroaryl part are each optionally substituted by one or more (e.g., one, two or three) groups R 42 . Preferred examples of the aryl moiety of said -(C 0-4 alkylene)-aryl are phenyl. Said -(C 0-4Preferred examples of the heteroaryl moiety of the (alkylene)-heteroaryl are 5- or 6-membered monocyclic heteroaryls having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (where the remaining ring atoms are carbon atoms), such as, for example, imidazolyl, phenylthio, or pyrimidinyl. Still more preferably, R 41 is selected from phenyl and heteroaryl, where the heteroaryl is a 5- or 6-membered monocyclic heteroaryl having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (the remaining ring atoms of the monocyclic heteroaryl are carbon atoms), and further, where the phenyl or the heteroaryl is optionally substituted by one or more (e.g., one, two, or three) groups R 42 substituted.

[0268] In the twenty-fourth embodiment, each R 42 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl), and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, each R 42 is independently selected from C 1-6Alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0269] In the twenty-fourth embodiment, each R 43 is independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3, -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl) and -N(C 1-6 alkyl)-CO-(C 1-6 alkyl). Preferably, each R 43 is independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3 and -CN.

[0270] In the twenty-fourth embodiment, according to the above definitions, particularly preferably, R 4 is selected from -O-(C 0-4 alkylene)-aryl, -O-(C 0-4 alkylene)-heteroaryl, -S-(C 0-4 alkylene)-aryl, -S-(C 0-4 alkylene)-heteroaryl, -NH-(C 0-4-alkylene)-aryl, -NH-(C 0-4 -alkylene)-heteroaryl, -N(C 1-4 -alkyl)-(C 0-4 -alkylene)-aryl, -N(C 1-4 -alkyl)-(C 0-4 -alkylene)-heteroaryl, aryl and heteroaryl, wherein the aryl moiety of any of the above groups, the heteroaryl moiety of any of the above groups, the aryl and the heteroaryl are each optionally substituted by one or more (e.g., one, two or three) groups R 42 Even more preferably, R 4 is selected from -O-aryl, -O-heteroaryl, -S-aryl, -S-heteroaryl, -NH-aryl, -NH-heteroaryl, -N(C 1-4 -alkyl)-aryl, -N(C 1-4 -alkyl)-heteroaryl, aryl and heteroaryl, wherein the aryl moiety of any of the above groups, the heteroaryl moiety of any of the above groups, the aryl and the heteroaryl are each optionally independently selected from C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, -OH, -O(C 1-6 -alkyl), -O(C 1-6 -alkylene)-OH, -O(C 1-6 -alkylene)-O(C 1-6 -alkyl), -SH, -S(C 1-6 -alkyl), -NH2, -NH(C 1-6 -alkyl), -N(C 1-6 -alkyl)(C 1-6 -alkyl), halogen, C 1-6 -haloalkyl and -CN. Even even more preferably, R 4 is selected from -O-phenyl, -O-heteroaryl, -S-phenyl, -S-heteroaryl, -NH-phenyl, -NH-heteroaryl, -N(C 1-4 -alkyl)-phenyl, -N(C 1-4 -alkyl)-heteroaryl, phenyl and heteroaryl, wherein the heteroaryl or the heteroaryl moiety of any of the above groups is a 5- or 6-membered monocyclic heteroaryl having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen and sulfur (the remaining ring atoms of the monocyclic heteroaryl are carbon atoms), and further, wherein the phenyl moiety of any of the above groups, the heteroaryl moiety of any of the above groups, the phenyl and the heteroaryl are each optionally independently selected from C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, -OH, -O(C 1-6 -alkyl), -O(C1-6 -OH, -O(C 1-6 -O(C 1-6 -SH, -S(C 1-6 -NH2, -NH(C 1-6 -N(C 1-6 -N(C 1-6 -halogen, C 1-6 -haloalkyl, and one or more groups selected from -CN. Still more preferably, R 4 is -O-phenyl.

[0271] In a twenty-fourth embodiment, R 5 is selected from -NH2, -NH(C 1-6 -N(C 1-6 -N(C 1-6 -NO2, and hydrogen, wherein the alkyl moiety of the -NH(C 1-6 -alkyl) and one or both of the alkyl moieties of the -N(C 1-6 -alkyl)(C 1-6 -alkyl) are each optionally independently substituted with one or more (e.g., one, two, or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 -alkyl), -N(C 1-6 -alkyl)(C 1-6 -alkyl), -OH, -O(C 1-6 -alkyl), -SH, -S(C 1-6 -alkyl), carbocyclic group, and heterocyclic group, and wherein the carbocyclic group and the heterocyclic group are each optionally substituted with one or more (e.g., one, two, or three) groups R 51 -substituted. Preferably, R 5 is selected from -NH2, -NH(C 1-6 -alkyl), -N(C 1-6 -alkyl)(C 1-6 -alkyl), and -NO2, wherein the alkyl moiety of the -NH(C 1-6 -alkyl) and one or both of the alkyl moieties of the -N(C 1-6 -alkyl)(C 1-6 -alkyl) are each optionally independently substituted with one or more (e.g., one, two, or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 -alkyl), -N(C 1-6 -alkyl)(C 1-6 -alkyl), -OH, -O(C 1-6 -alkyl), -SH, and -S(C 1-6 -alkyl). More preferably, R5 selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl) and -NO2. Even more preferably, R 5 is selected from -NH2, -NH(C 1-6 alkyl) and -N(C 1-6 alkyl)(C 1-6 alkyl). Even even more preferably, R 5 is -NH(C 1-6 alkyl). Still more preferably, R 5 is -NH-CH2CH2CH2CH3.

[0272] In the twenty-fourth embodiment, each R 51 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, each R 51Independently selected from C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0273] In a twenty-fourth embodiment, R 6 is selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, R 6 is selected from hydrogen, C1-6 Alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN. More preferably, R 6 is hydrogen or C 1-4 alkyl. Even more preferably, R 6 is hydrogen.

[0274] According to the twenty-fourth embodiment, the compound of formula (Ia) may specifically be a compound of any one of the following formulas, or a pharmaceutically acceptable salt or solvate thereof:

[0275]

[0276] The present invention also relates to a compound of formula (Ia) as defined in the twenty-fourth embodiment, or a pharmaceutically acceptable salt or solvate thereof, for use as a medicament. The present invention also relates to a pharmaceutical composition comprising the compound of formula (Ia) or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient. In addition, the present invention relates to the compound of formula (Ia) or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising any of the foregoing entities and a pharmaceutically acceptable excipient, for treating or preventing a disease or disorder involving NKCC (especially a disease or disorder involving NKCC1), specifically including any one of the specific diseases / disorders mentioned in this specification. The present invention also relates to the use of the compound of formula (Ia) or a pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for treating or preventing a disease or disorder involving NKCC (especially a disease or disorder involving NKCC1), specifically including any one of the specific diseases / disorders mentioned in this specification. In addition, the present invention provides a method for treating or preventing a disease or disorder involving NKCC (especially a disease or disorder involving NKCC1), specifically including any one of the specific diseases / disorders mentioned in this specification, the method comprising administering to a subject in need thereof (preferably a human) a compound of formula (Ia) as defined in the twenty-fourth embodiment, or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising any of the foregoing entities in combination with a pharmaceutically acceptable excipient. It should be understood that a therapeutically effective amount of the compound of formula (Ia) or a pharmaceutically acceptable salt or solvate thereof, or the pharmaceutical composition, will be administered according to the method.

[0277] In the twenty-fifth embodiment, the compound of formula (I) is a compound of formula (Ia) as follows or a pharmaceutically acceptable salt or solvate thereof:

[0278]

[0279] wherein R 1 is as defined below, and wherein the further groups and variables in formula (Ia), specifically including R 2 , R 3 , R 4 , R 5 and R 6 , have the same meanings as described and defined above for the compound of formula (I), including the same preferred meanings.

[0280] In this twenty-fifth embodiment, R 1 is -(C 1-4 alkylene)-S-heterocyclyl, preferably -(C 1-4 alkylene)-S-heteroaryl (such as, for example, -CH2-S-heteroaryl), wherein the -(C1-4 The heterocyclic moiety of the -(C 1-4 alkylene)-S-heterocyclic group or the -(C 1-6 alkylene)-S-heteroaryl group or the heteroaryl moiety of the -CH2-S-heteroaryl group is optionally substituted with one or more (e.g., one, two, or three) groups independently selected from C 2-6 alkyl, C 2-6 alkenyl, C 1-6 alkynyl, halogen, C 11 (R 11 )(R 11 ), -O(R 11 ), -S(R 1 ), -SO3H, a carbocyclic group, and a heterocyclic group. Specific examples of such R 1 groups include the corresponding R

[0281] In a twenty-sixth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0282]

[0283] wherein R 1 is as defined below, and wherein the additional groups and variables in formula (Ia), specifically including R 2 , R 3 , R 4 , R 5 , and R 6 , have the same meanings as described and defined above for the compound of formula (I), including the same preferred meanings.

[0284] In this twenty-sixth embodiment, R 1 is -(C 1-4 alkylene)-O-(C 0-4 alkylene)-carbocyclic group, preferably -(C 1-4 alkylene)-O-(C 0-4 alkylene)-phenyl (such as, for example, -CH2-O-phenyl or -CH2-O-CH2-phenyl), wherein the carbocyclic moiety of the -(C 1-4 alkylene)-O-(C 0-4 alkylene)-carbocyclic group or the phenyl moiety of the -(C 1-4 alkylene)-O-(C 0-4 alkylene)-phenyl (or the -CH2-O-phenyl or -CH2-O-CH2-phenyl) is optionally substituted with one or more groups independently selected from C 1-6 alkyl, C 2-6 alkenyl, C2-6 Alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ), -SO3H, a carbocyclic group, and a heterocyclic group, one or more (e.g., one, two, or three) groups of which are substituted. Specific examples of such R 1 groups include the corresponding groups R of the compounds described in the Examples section 1 .

[0285] In the twenty-seventh embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0286]

[0287] wherein R 1 is as defined below, and wherein the additional groups and variables in formula (Ia), specifically including R 2 , R 3 , R 4 , R 5 , and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0288] In this twenty-seventh embodiment, R 1 is -(C 1-4 alkylene)-heterocyclic group, preferably -CH2-heterocyclic group, wherein the heterocyclic group moiety of the -(C 1-4 alkylene)-heterocyclic group or the -CH2-heterocyclic group is optionally independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ), -SO3H, a carbocyclic group, and a heterocyclic group, one or more (e.g., one, two, or three) groups of which are substituted. The heterocyclic group moiety can be, for example, a heterocycloalkyl (such as, for example, pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl), a heterocycloalkenyl (such as, for example, tetrahydropyridinyl), or a heteroaryl. Specific examples of such R 1 groups include the corresponding groups R of the compounds described in the Examples section 1 .

[0289] In the twenty-eighth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0290]

[0291] wherein R 1 is -COOH, wherein R 3 is -SO2-NH2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NH2, and wherein the further groups and variables in formula (Ia), specifically including R 2 、R 4a and R 6 have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0292] In the twenty-ninth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0293]

[0294] wherein R 1 is -COOH, wherein R 3 is -SO2-NH2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ia), specifically including R 2 、R 4a and R 6 have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0295] In the thirtieth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0296]

[0297] wherein R 1 is -COOH, wherein R 3 is -SO2-NH2, wherein R 4 is the group R 4a wherein R 5 is the group R5a , wherein R 5a is -NO2, and wherein the further groups and variables in formula (Ia), specifically including R 2 , R 4a and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0298] In the thirty - first embodiment, the compound of formula (I) is a compound of the following formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0299]

[0300] wherein R 1 is -COOH, wherein R 3 is -SO2-N=CH-N(CH3)2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NH2, and wherein the further groups and variables in formula (Ia), specifically including R 2 , R 4a and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0301] In the thirty - second embodiment, the compound of formula (I) is a compound of the following formula (Ia) or a pharmaceutically acceptable salt or solvate thereof:

[0302]

[0303] wherein R 1 is -COOH, wherein R 3 is -SO2-N=CH-N(CH3)2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ia), specifically including R 2 , R 4a and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0304] In the thirty-third embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0305]

[0306] wherein R 1 is -COOH, wherein R 3 is -SO2-N=CH-N(CH3)2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NO2, and wherein the further groups and variables in formula (Ia), specifically including R 2 R 4a and R 6 have the same meanings as described and defined above for the compound of formula (I), including the same preferred meanings.

[0307] In the thirty-fourth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0308]

[0309] wherein R 1 is -COO-CH3, wherein R 3 is -SO2-NH2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NH2, and wherein the further groups and variables in formula (Ia), specifically including R 2 R 4a and R 6 have the same meanings as described and defined above for the compound of formula (I), including the same preferred meanings.

[0310] In the thirty-fifth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0311]

[0312] wherein R 1 is -COO-CH3, wherein R 3 is -SO2-NH2, wherein R 4 is the group R 4a wherein R 5 is the group R5a , wherein R 5a is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ia), specifically including R 2 , R 4a and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0313] In a thirty-sixth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0314]

[0315] wherein R 1 is -COO-CH3, wherein R 3 is -SO2-NH2, wherein R 4 is the group R 4a , wherein R 5 is the group R 5a , wherein R 5a is -NO2, and wherein the further groups and variables in formula (Ia), specifically including R 2 , R 4a and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0316] In a thirty-seventh embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0317]

[0318] wherein R 1 is -COO-CH3, wherein R 3 is -SO2-N=CH-N(CH3)2, wherein R 4 is the group R 4a , wherein R 5 is the group R 5a , wherein R 5a is -NH2, and wherein the further groups and variables in formula (Ia), specifically including R 2 , R 4a and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0319] In the thirty-eighth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0320]

[0321] wherein R 1 is -COO-CH3, wherein R 3 is -SO2-N=CH-N(CH3)2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ia), specifically including R 2 R 4a and R 6 have the same meanings as described and defined above for the compound of formula (I), including the same preferred meanings.

[0322] In the thirty-ninth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0323]

[0324] wherein R 1 is -COO-CH3, wherein R 3 is -SO2-N=CH-N(CH3)2, wherein R 4 is the group R 4a wherein R 5 is the group R 5a wherein R 5a is -NO2, and wherein the further groups and variables in formula (Ia), specifically including R 2 R 4a and R 6 have the same meanings as described and defined above for the compound of formula (I), including the same preferred meanings.

[0325] In the fortieth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0326]

[0327] wherein R 4 is the group R 4a wherein R 5 is the group R 5a, and wherein the further groups and variables in formula (Ib), specifically including R X and R 6 , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0328] In this fortieth embodiment, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 alkyl)-R 41 , halogen (e.g., -Cl), carbocyclic group and heterocyclic group, wherein each of the carbocyclic group and the heterocyclic group is optionally substituted by one or more (e.g., one, two or three) groups R 42 . Preferably, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 alkyl)-R 41 , halogen, carbocyclic group (e.g., aryl, cycloalkyl or cycloalkenyl) and heterocyclic group (e.g., heteroaryl, heterocycloalkyl or heterocycloalkenyl), wherein each of the carbocyclic group and the heterocyclic group is optionally substituted by one or more groups R 42 . More preferably, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-4 alkyl)-R 41 , halogen, aryl and heteroaryl, wherein each of the aryl and the heteroaryl is optionally substituted by one or more groups R 42 . Even more preferably, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-4 alkyl)-R 41 and halogen. Still more preferably, R 4a is -O-R 41 or halogen.

[0329] R 41 is selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the -(C 0-4The carbocyclic moiety of the (C-alkylene)-carbocyclic group and the (C 0-4 alkylene)-heterocyclic group of the heterocyclic moiety are each optionally substituted by one or more (e.g., one, two, or three) groups R 42 and wherein the C 1-6 alkyl group, the C 2-6 alkenyl group, the C 2-6 alkynyl group, the (C 0-4 alkylene)-carbocyclic group of the alkylene moiety and the (C 0-4 alkylene)-heterocyclic group of the alkylene moiety are each optionally substituted by one or more (e.g., one, two, or three) groups R 43 . Preferably, R 41 is selected from (C 0-4 alkylene)-carbocyclic group, (C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl group, C 2-6 alkenyl group, and C 2-6 alkynyl group, wherein the carbocyclic moiety of the (C 0-4 alkylene)-carbocyclic group is selected from cycloalkyl, cycloalkenyl, and aryl, wherein the heterocyclic moiety of the (C 0-4 alkylene)-heterocyclic group is selected from heterocycloalkyl, heterocycloalkenyl, and heteroaryl, wherein the carbocyclic moiety of the (C 0-4 alkylene)-carbocyclic group and the heterocyclic moiety of the (C 0-4 alkylene)-heterocyclic group are each optionally substituted by one or more (e.g., one, two, or three) groups R 42 and further, wherein the C 1-6 alkyl group, the C 2-6 alkenyl group, the C 2-6 alkynyl group, the (C 0-4 alkylene)-carbocyclic group of the alkylene moiety and the (C 0-4 alkylene)-heterocyclic group of the alkylene moiety are each optionally substituted by one or more (e.g., one, two, or three) groups R 43 . More preferably, R 41 is selected from (C 0-4 alkylene)-aryl and (C 0-4 alkylene)-heteroaryl, wherein the aryl moiety of the (C 0-4 alkylene)-aryl and the heteroaryl moiety of the (C 0-4 alkylene)-heteroaryl are each optionally substituted by one or more (e.g., one, two, or three) groups R 42 and further, wherein the alkylene moiety of the (C 0-4 alkylene)-aryl and the alkylene moiety of the (C 0-4The alkylene moieties of the (alkylene)-heteroaryl are each optionally substituted by one or more (e.g., one, two, or three) groups R 43 . Even more preferably, R 41 is selected from -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, wherein the aryl moiety of the -(C 0-4 alkylene)-aryl and the heteroaryl moiety of the -(C 0-4 alkylene)-heteroaryl are each optionally substituted by one or more (e.g., one, two, or three) groups R 42 . Preferred examples of the aryl moiety of the -(C 0-4 alkylene)-aryl are phenyl. Preferred examples of the heteroaryl moiety of the -(C 0-4 alkylene)-heteroaryl are 5- or 6-membered monocyclic heteroaryls having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (where the remaining ring atoms are carbon atoms), such as, for example, imidazolyl, phenylthio, or pyrimidinyl. Still more preferably, R 41 is selected from phenyl and heteroaryl, wherein the heteroaryl is a 5- or 6-membered monocyclic heteroaryl having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (the remaining ring atoms of the monocyclic heteroaryl are carbon atoms), and further, wherein the phenyl or the heteroaryl is optionally substituted by one or more (e.g., one, two, or three) groups R 42 .

[0330] Each R 42 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, each R 42 is independently selected from C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0331] Each R 43 is independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3, -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl) and -N(C 1-6 alkyl)-CO-(C 1-6 alkyl). Preferably, each R 43 is independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3, and -CN.

[0332] According to the above definition, particularly preferably, R 4a is -O-aryl or halogen, wherein the aryl moiety of the -O-aryl is optionally independently substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, and -CN. Even more preferably, R 4a is -O-phenyl or halogen (such as, specifically, -Cl), wherein the phenyl moiety of the -O-phenyl is optionally independently substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, and -CN.

[0333] In this fortieth embodiment, R 5a is selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -NO2, and hydrogen, wherein the alkyl moiety of the -NH(C 1-6 alkyl) and the -N(C 1-6 alkyl)(C 1-6One or both of the alkyl moieties of (alkyl) are each optionally independently substituted by one or more (e.g., one, two, or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), a carbocyclic group, and a heterocyclic group, wherein each of the carbocyclic group and the heterocyclic group is optionally substituted by one or more (e.g., one, two, or three) groups R 51 . Preferably, R 5a is selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -NO2, and hydrogen, wherein the alkyl moiety of -NH(C 1-6 alkyl) and one or both of the alkyl moieties of -N(C 1-6 alkyl)(C 1-6 alkyl) are each optionally independently substituted by one or more (e.g., one, two, or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH, and -S(C 1-6 alkyl). More preferably, R 5a is selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -NO2, and hydrogen. Particularly preferred examples of R 5a are -NH2, -NH-CH2CH2CH2CH3, -NO2, or hydrogen.

[0334] Each R 51 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, each R 51 is independently selected from C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0335] In the forty-first embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0336]

[0337] wherein the groups and variables in formula (Ib) have the following meanings:

[0338] In this forty-first embodiment, R x is selected from -COOH, -COO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-4(alkyl), -SO2-N(C 1-4 (alkyl)(C 1-4 (alkyl) and -SO2-N=(C 1-4 (alkylidene), wherein the -SO2-NH(C 1-4 (alkyl) alkyl moiety, the -SO2-N(C 1-4 (alkyl)(C 1-4 (alkyl) one or two alkyl moieties and the -SO2-N=(C 1-4 (alkylidene) alkylidene moiety is each optionally selected from -NH2, -NH(C 1-4 (alkyl) and -N(C 1-4 (alkyl)(C 1-4 (alkyl) substituted by a group. Preferably, R x is selected from -COOH, -COOCH3, -SO2-NH2 and -SO2-N=CH-N(CH3)2.

[0339] In this forty-first embodiment, R 4 is the group R 4a .

[0340] R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 (alkyl)-R 41 , halogen (e.g., -Cl), carbocyclic group and heterocyclic group, wherein the carbocyclic group and the heterocyclic group are each optionally substituted by one or more (e.g., one, two or three) groups R 42 . Preferably, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 (alkyl)-R 41 , halogen, carbocyclic group (e.g., aryl, cycloalkyl or cycloalkenyl) and heterocyclic group (e.g., heteroaryl, heterocycloalkyl or heterocycloalkenyl), wherein the carbocyclic group and the heterocyclic group are each optionally substituted by one or more groups R 42 . More preferably, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-4 (alkyl)-R 41 , halogen, aryl and heteroaryl, wherein the aryl and the heteroaryl are each optionally substituted by one or more groups R 42 . Even more preferably, R 4aSelected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-4 alkyl)-R 41 and halogen. Even more preferably, R 4a is -O-R 41 or halogen.

[0341] R 41 is selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the carbocyclic group portion of the -(C 0-4 alkylene)-carbocyclic group and the heterocyclic group portion of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted with one or more (e.g., one, two or three) groups R 42 , and wherein the C 1-6 alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl, the alkylene portion of the -(C 0-4 alkylene)-carbocyclic group and the alkylene portion of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted with one or more (e.g., one, two or three) groups R 43 . Preferably, R 41 is selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the carbocyclic group portion of the -(C 0-4 alkylene)-carbocyclic group is selected from cycloalkyl, cycloalkenyl and aryl, wherein the heterocyclic group portion of the -(C 0-4 alkylene)-heterocyclic group is selected from heterocycloalkyl, heterocycloalkenyl and heteroaryl, wherein the carbocyclic group portion of the -(C 0-4 alkylene)-carbocyclic group and the heterocyclic group portion of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted with one or more (e.g., one, two or three) groups R 42 , and further, wherein the C 1-6 alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl, the alkylene portion of the -(C 0-4 alkylene)-carbocyclic group and the -(C0-4 The alkylene moieties of the (alkylene)-heterocyclyl are each optionally substituted by one or more (e.g., one, two, or three) groups R 43 . More preferably, R 41 is selected from -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, wherein the aryl moiety of the -(C 0-4 alkylene)-aryl and the heteroaryl moiety of the -(C 0-4 alkylene)-heteroaryl are each optionally substituted by one or more (e.g., one, two, or three) groups R 42 , and further, wherein the alkylene moiety of the -(C 0-4 alkylene)-aryl and the alkylene moiety of the -(C 0-4 alkylene)-heteroaryl are each optionally substituted by one or more (e.g., one, two, or three) groups R 43 . Even more preferably, R 41 is selected from -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, wherein the aryl moiety of the -(C 0-4 alkylene)-aryl and the heteroaryl moiety of the -(C 0-4 alkylene)-heteroaryl are each optionally substituted by one or more (e.g., one, two, or three) groups R 42 . Preferred examples of the aryl moiety of the -(C 0-4 alkylene)-aryl are phenyl. Preferred examples of the heteroaryl moiety of the -(C 0-4 alkylene)-heteroaryl are 5- or 6-membered monocyclic heteroaryls having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (where the remaining ring atoms are carbon atoms), such as, for example, imidazolyl, phenylthio, or pyrimidinyl. Still more preferably, R 41 is selected from phenyl and heteroaryl, wherein the heteroaryl is a 5- or 6-membered monocyclic heteroaryl having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (the remaining ring atoms of the monocyclic heteroaryl are carbon atoms), and further, wherein the phenyl or the heteroaryl is optionally substituted by one or more (e.g., one, two, or three) groups R 42 .

[0342] Each R 42 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C1-6 alkyl), -SH, -S(C 1-6 Alkyl), -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), halogen, C 1-6 Haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 Alkyl), -CO-N(C 1-6 Alkyl)(C 1-6 Alkyl), -NH-CO-(C 1-6 Alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 Alkyl), -SO2-NH2, -SO2-NH(C 1-6 Alkyl), -SO2-N(C 1-6 Alkyl)(C 1-6 Alkyl), -NH-SO2-(C 1-6 Alkyl) and -N(C 1-6 Alkyl)-SO2-(C 1-6 Preferably, each R 42 Independently selected from C 1-6 Alkyl, -OH, -O(C 1-6 Alkyl), -O(C 1-6 Alkylene)-OH, -O(C 1-6 Alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 Alkyl), -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), halogen, C 1-6 Haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0343] Each R 43 are independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 Alkyl), -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6(alkyl), halogen, -CF3, -CN, -NO2, -CHO, -CO-(C 1-6 (alkyl), -COOH, -COO-(C 1-6 (alkyl), -O-CO-(C 1-6 (alkyl), -CO-NH2, -CO-NH(C 1-6 (alkyl), -CO-N(C 1-6 (alkyl)(C 1-6 (alkyl), -NH-CO-(C 1-6 (alkyl) and -N(C 1-6 (alkyl)-CO-(C 1-6 (alkyl). Preferably, each R 43 is independently selected from -OH, -O(C 1-6 (alkyl), -SH, -S(C 1-6 (alkyl), -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), halogen, -CF3 and -CN.

[0344] According to the above definition, particularly preferably, R 4a is -O-aryl or halogen, wherein the aryl moiety of the -O-aryl is optionally substituted by one or more groups independently selected from C 1-6 (alkyl), C 2-6 (alkenyl), C 2-6 (alkynyl), -OH, -O(C 1-6 (alkyl), -O(C 1-6 (alkylene)-OH, -O(C 1-6 (alkylene)-O(C 1-6 (alkyl), -SH, -S(C 1-6 (alkyl), -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), halogen, C 1-6 (haloalkyl) and -CN. Even more preferably, R 4a is -O-phenyl or halogen (for example, specifically -Cl), wherein the phenyl moiety of the -O-phenyl is optionally substituted by one or more groups independently selected from C 1-6 (alkyl), C 2-6 (alkenyl), C 2-6 (alkynyl), -OH, -O(C 1-6 (alkyl), -O(C 1-6 (alkylene)-OH, -O(C 1-6 (alkylene)-O(C 1-6 (alkyl), -SH, -S(C 1-6 (alkyl), -NH2, -NH(C1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 substituted by one or more groups of haloalkyl and -CN.

[0345] In this forty-first embodiment, R 5 is the group R 5a .

[0346] R 5a is selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -NO2 and hydrogen, wherein the alkyl moiety of the -NH(C 1-6 alkyl) and one or both of the alkyl moieties of the -N(C 1-6 alkyl)(C 1-6 alkyl) are each optionally independently substituted by one or more (e.g., one, two or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), carbocyclic group and heterocyclic group, wherein the carbocyclic group and the heterocyclic group are each optionally substituted by one or more (e.g., one, two or three) groups of R 51 . Preferably, R 5a is selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -NO2 and hydrogen, wherein the alkyl moiety of the -NH(C 1-6 alkyl) and one or both of the alkyl moieties of the -N(C 1-6 alkyl)(C 1-6 alkyl) are each optionally independently substituted by one or more (e.g., one, two or three) groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH and -S(C 1-6 alkyl). More preferably, R 5a is selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C1-6 alkyl), -NO2, and hydrogen. R 5a Particularly preferred examples of are -NH2, -NH-CH2CH2CH2CH3, -NO2, or hydrogen.

[0347] Each R 51 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, each R 51 is independently selected from C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0348] R 6 is selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, R 6 is selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN. More preferably, R 6 is hydrogen or C 1-4 alkyl. Even more preferably, R 6 is hydrogen.

[0349] In the forty-second embodiment, the compound of formula (I) is a compound of the following formula (Ib) or a pharmaceutically acceptable salt or solvate thereof:

[0350]

[0351] wherein R x is selected from -COOH, -COOCH3, -SO2-NH2 and -SO2-N=CH-N(CH3)2, and wherein the further groups and variables in formula (Ib), specifically including R 4 , R 5 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0352] In the forty-third embodiment, the compound of formula (I) is a compound of the following formula (Ib) or a pharmaceutically acceptable salt or solvate thereof:

[0353]

[0354] wherein R x is -COOH, and wherein the further groups and variables in formula (Ib), specifically including R 4 , R 5 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0355] In the forty-fourth embodiment, the compound of formula (I) is a compound of the following formula (Ib) or a pharmaceutically acceptable salt or solvate thereof:

[0356]

[0357] wherein R x is -COOCH3, and wherein the further groups and variables in formula (Ib), specifically including R 4 , R 5 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0358] In the forty-fifth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0359]

[0360] wherein R x is -SO2-NH2, and wherein the further groups and variables in formula (Ib), specifically including R 4 、R 5 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0361] In the forty-sixth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0362]

[0363]

[0364] wherein R x is -SO2-N=CH-N(CH3)2, and wherein the further groups and variables in formula (Ib), specifically including R 4 、R 5 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0365] In the forty-seventh embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0366]

[0367] wherein R 4 is -O-phenyl, wherein the phenyl moiety of the -O-phenyl is optionally independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6substituted with one or more groups of haloalkyl and -CN; and wherein the further groups and variables in formula (Ib), specifically including R x , R 5 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0368] In the forty-eighth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0369]

[0370] wherein R 4 is a halogen (for example, specifically -Cl), and wherein the further groups and variables in formula (Ib), specifically including R x , R 5 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0371] In the forty-ninth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0372]

[0373] wherein R x is -COOH, wherein R 5 is -NH2, and wherein the further groups and variables in formula (Ib), specifically including R 4 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0374] In the fiftieth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0375]

[0376] wherein R x is -COOCH3, wherein R 5 is -NH2, and wherein the further groups and variables in formula (Ib), specifically including R 4 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0377] In the fifty-first embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0378]

[0379] wherein R x is -SO2-NH2, wherein R 5 is -NH2, and wherein the other groups and variables in formula (Ib), specifically including R 4 and R 6 have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0380] In the fifty-second embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0381]

[0382] wherein R x is -SO2-N=CH-N(CH3)2, wherein R 5 is -NH2, and wherein the other groups and variables in formula (Ib), specifically including R 4 and R 6 have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0383] In the fifty-third embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0384]

[0385] wherein R x is -COOH, wherein R 5 is -NH-CH2CH2CH2CH3, and wherein the other groups and variables in formula (Ib), specifically including R 4 and R 6 have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0386] In the fifty-fourth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0387]

[0388] wherein R x is -COOCH3, wherein R5 is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ib), specifically including R 4 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0389] In the fifty-fifth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0390]

[0391] wherein R x is -SO2-NH2, wherein R 5 is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ib), specifically including R 4 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0392] In the fifty-sixth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0393]

[0394] wherein R x is -SO2-N=CH-N(CH3)2, wherein R 5 is -NH-CH2CH2CH2CH3, and wherein the further groups and variables in formula (Ib), specifically including R 4 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0395] In the fifty-seventh embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0396]

[0397] wherein R x is -COOH, wherein R 5 is -NO2, and wherein the further groups and variables in formula (Ib), specifically including R 4 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0398] In the fifty-eighth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0399]

[0400] wherein R x is -COOCH3, wherein R 5 is -NO2, and wherein the further groups and variables in formula (Ib), specifically including R 4 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0401] In the fifty-ninth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0402]

[0403] wherein R x is -SO2-NH2, wherein R 5 is -NO2, and wherein the further groups and variables in formula (Ib), specifically including R 4 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0404] In the sixtieth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0405]

[0406] wherein R x is -SO2-N=CH-N(CH3)2, wherein R 5 is -NO2, and wherein the further groups and variables in formula (Ib), specifically including R 4 and R 6 , have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0407] In the sixty-first embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0408]

[0409] wherein R x is -COOH, wherein R5 is hydrogen, and the further groups and variables in formula (Ib), specifically including R 4 and R 6 have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0410] In the sixty-second embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0411]

[0412] wherein R x is -COOCH3, wherein R 5 is hydrogen, and the further groups and variables in formula (Ib), specifically including R 4 and R 6 have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0413] In the sixty-third embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0414]

[0415] wherein R x is -SO2-NH2, wherein R 5 is hydrogen, and the further groups and variables in formula (Ib), specifically including R 4 and R 6 have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0416] In the sixty-fourth embodiment, the compound of formula (I) is a compound of formula (Ib) below or a pharmaceutically acceptable salt or solvate thereof:

[0417]

[0418] wherein R x is -SO2-N=CH-N(CH3)2, wherein R 5 is hydrogen, and the further groups and variables in formula (Ib), specifically including R 4 and R 6 have the same meanings as described and defined in the forty-first embodiment, including the same preferred meanings.

[0419] In the sixty-fifth embodiment, the compound of formula (I) is a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof:

[0420]

[0421] wherein R 1 and R 6 are linked to each other to form a group -R 16 -, wherein R 4 is the group R 4a and wherein R 4a is hydrogen, wherein R 5 is the group R 5a and wherein the additional groups and variables in formula (Ia), specifically including R 16 , R 2 , R 3 and R 5a , have the same meanings as described and defined above for the compounds of formula (I), including the same preferred meanings.

[0422] In each of the embodiments described above, the respective compound can be used as a medicine, in particular for the treatment or prevention of diseases or disorders involving NKCC (preferably NKCC1), including for the treatment or prevention of any of the corresponding specific diseases / disorders mentioned in this specification. Particularly preferably, the respective compound is used for the treatment or prevention of hyperhidrosis.

[0423] The present invention also relates to novel compounds. Specifically, the present invention relates to compounds of formula (I) as described and defined herein, including any of the examples and embodiments of the compounds of formula (I) described in this specification, or pharmaceutically acceptable salts or solvates thereof. The present invention further relates to any such compound for use as a medicine, and provides a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in combination with a pharmaceutically acceptable excipient.

[0424] Specifically, the present invention relates to a compound of formula (Ia) below or a pharmaceutically acceptable salt or solvate thereof (and furthermore, the present invention also relates to said compound for use as a medicine, and a pharmaceutical composition comprising said compound and a pharmaceutically acceptable excipient):

[0425]

[0426] In formula (Ia), R 1 is selected from -COOH, -COO-(C 1-15 alkyl), -COO-(C 0-15 alkylene)-carbocyclic group, -COO-(C 0-15Alkylene)-heterocyclic group, -O-CHO, -O-CO-(C 1-15 alkyl), -O-CO-(C 0-15 alkylene)-carbocyclic group, -O-CO-(C 0-15 alkylene)-heterocyclic group, -CHO, -CO-(C 1-15 alkyl), -CO-(C 0-15 alkylene)-carbocyclic group, -CO-(C 0-15 alkylene)-heterocyclic group, -CO-NH2, -CO-N(R 11 )(C 1-15 alkyl), -CO-N(R 11 )(C 0-15 alkylene)-carbocyclic group, -CO-N(R 11 )(C 0-15 alkylene)-heterocyclic group, -N(R 11 )(-CHO, -N(R 11 )(-CO-(C 1-15 alkyl), -N(R 11 )(-CO-(C 0-15 alkylene)-carbocyclic group, -N(R 11 )(-CO-(C 0-15 alkylene)-heterocyclic group, C 1-15 alkyl, -(C 0-15 alkylene)-carbocyclic group, -(C 0-15 alkylene)-heterocyclic group, C 2-15 alkenyl, -(C 2-15 alkenylene)-carbocyclic group, -(C 2-15 alkenylene)-heterocyclic group, C 2-15 alkynyl, -(C 2-15 alkynylene)-carbocyclic group and -(C 2-15 alkynylene)-heterocyclic group,

[0427] wherein the alkyl moiety of any one of the above groups, the alkylene moiety of any one of the above groups, the alkenylene moiety of any one of the above groups, the alkynylene moiety of any one of the above groups, the C 1-15 alkyl, the C 2-15 alkenyl and the C 2-15 alkynyl are each optionally independently substituted with one or more groups selected from halogen, -CF3, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ) and -SO3H,

[0428] Including in the alkyl moiety of any of the above groups, in the alkylene moiety of any of the above groups, in the alkenylene moiety of any of the above groups, in the alkynylene moiety of any of the above groups, the C 1-15 alkyl, the C 2-15 alkenyl or the C 2-15 alkynyl, one or more -CH2- units are each optionally independently replaced by a group selected from -O-, -CO-, -COO-, -O-CO-, -N(R 11 ), -N(R 11 )-CO-, -CO-N(R 11 ), -S-, -SO-, -SO2-, -SO2-N(R 11 ), and -N(R 11 )-SO2-.

[0429] And further, wherein the carbocyclic moiety of any of the above groups and the heterocyclic moiety of any of the above groups are each optionally independently substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ), -SO3H, carbocyclic and heterocyclic groups.

[0430] Each R 11 is independently hydrogen or C 1-6 alkyl. Preferably, each R 11 is independently hydrogen or C 1-4 alkyl (e.g., methyl or ethyl).

[0431] R 1 can be, for example, any of the specific groups R 1 included in any of the compounds described in the Examples section.

[0432] Specifically, R 1 can be, for example, -COO-(C 1-15 alkyl), wherein the alkyl moiety of the -COO-(C 1-15 alkyl) is optionally independently selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-4 alkyl), -N(C 1-4 alkyl)(C 1-4 alkyl), -OH, -O(C 1-4 alkyl), -SH, and -S(C1-4 is substituted by one or more (e.g., one, two or three) groups of (alkyl), and further, wherein one or two -CH2- units in the alkyl moiety of the -COO-(C 1-15 alkyl) are each optionally independently replaced by a group selected from -O-, -CO-, -COO-, -O-CO-, -NH-, -N(C 1-4 alkyl)-, -NH-CO-, -N(C 1-4 alkyl)-CO-, -CO-NH-, -CO-N(C 1-4 alkyl)-, -S-, -SO-, -SO2-, -SO2-NH-, -SO2-N(C 1-4 alkyl)-, -NH-SO2- and -N(C 1-4 alkyl)-SO2-. The alkyl moiety of the -COO-(C 1-15 alkyl) has 1 to 15 carbon atoms, particularly 1 to 10 carbon atoms. Preferred examples of such R 1 groups include the corresponding groups R of the compounds described in the Examples section 1 (including, for example, -COO-CH3 or -COO-CH2CH3; particularly -COO-CH3).

[0433] R 1 Another preferred example is -COOH.

[0434] R 1 Another preferred example is -(C 1-4 alkylene)-NH-(C 1-4 alkylene)-R 12 (such as, for example, -CH2-NH-CH2-R 12 ), -COO-(C 1-4 alkylene)-R 12 (for example, -COO-CH2-R 12 ), -O-CO-(C 1-4 alkylene)-R 12 , -CO-(C 1-4 alkylene)-R 12 , -CO-NH-(C 1-4 alkylene)-R 12 (for example, -CO-NH-CH2-R 12 ), -CO-N(C 1-4 alkyl)-(C 1-4 alkylene)-R 12 , -NH-CO-(C 1-4 alkylene)-R 12 or -N(C 1-4 alkyl)-CO-(C1-4 (alkylene)-R 12 , wherein R 12 is independently selected from -CF3, -CN, and halogen (e.g., -F, -Cl, -Br, or -I); preferably, R 12 is independently selected from -CF3 and -CN; more preferably, R 12 is -CF3. Specific examples of such R 1 groups include the corresponding R groups of the compounds described in the Examples section 1 . Particularly preferred examples of R 1 are -(C 1-4 alkylene)-NH-(C 1-4 alkylene)-CF3, and an even more preferred example is -CH2-NH-CH2-CF3.

[0435] R 1 Another example of R 1-4 is -(C 1-4 alkylene)-S-heterocyclic group, especially -(C 1-4 alkylene)-S-heteroaryl (such as, for example, -CH2-S-heteroaryl), wherein the heterocyclic group portion of the -(C 1-4 alkylene)-S-heterocyclic group or the heteroaryl portion of the -(C 1-6 alkylene)-S-heteroaryl or the -CH2-S-heteroaryl is optionally substituted by one or more (e.g., one, two, or three) groups independently selected from C 2-6 alkyl, C 2-6 alkenyl, C 1-6 alkynyl, halogen, C 11 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 1 groups include the corresponding R groups of the compounds described in the Examples section 1 .

[0436] R 1 Another example of R 1-4 is -(C 0-4 alkylene)-O-(C 1-4 alkylene)-carbocyclic group, especially -(C 0-4 alkylene)-O-(C 1-4 alkylene)-phenyl (such as, for example, -CH2-O-phenyl or -CH2-O-CH2-phenyl), wherein the carbocyclic group portion of the -(C 0-4 alkylene)-O-(C1-4 (alkylene)-O-(C 0-4 (alkylene)-phenyl (or the -CH2-O-phenyl or -CH2-O-CH2-phenyl) of the phenyl moiety is optionally independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 )), -O(R 11 )), -S(R 11 )), -SO3H, carbocyclic group and heterocyclic group by one or more (e.g., one, two or three) groups. Specific examples of such R 1 groups include the corresponding groups R of the compounds described in the Examples section 1 .

[0437] R 1 Another example of is -(C 1-4 (alkylene)-heterocyclic group, especially -CH2-heterocyclic group, wherein the -(C 1-4 (alkylene)-heterocyclic group or the -CH2-heterocyclic group of the heterocyclic moiety is optionally independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ), -SO3H, carbocyclic group and heterocyclic group by one or more (e.g., one, two or three) groups. The heterocyclic moiety can be, for example, heterocycloalkyl (such as, for example, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl), heterocycloalkenyl (such as, for example, tetrahydropyridyl) or heteroaryl. Specific examples of such R 1 groups include the corresponding groups R of the compounds described in the Examples section 1 .

[0438] R 2 is selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 (alkylene)-OH, -O(C 1-6 (alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, R 2 is selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN. More preferably, R 2 is hydrogen or C 1-4 alkyl. Even more preferably, R 2 is hydrogen.

[0439] R 3 is selected from -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -SO2-N=(C 1-6 alkylidene) and -SO2-halogen, wherein the -SO2-NH(C 1-6the alkyl moiety of (alkyl), the -SO2-N(C 1-6 alkyl)(C 1-6 one or two alkyl moieties of alkyl) and the -SO2-N=(C 1-6 the alkylidene moiety of alkylidene) is each optionally independently selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH and -S(C 1-6 alkyl) is substituted by one or more groups. Preferably, R 3 is selected from -SO2-NH2, -SO2-NH(C 1-4 alkyl), -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and -SO2-N=(C 1-4 alkylidene), wherein the alkyl moiety of the -SO2-NH(C 1-4 alkyl), one or two alkyl moieties of the -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and the alkylidene moiety of the -SO2-N=(C 1-4 alkylidene) is each optionally independently selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH and -S(C 1-6 alkyl) is substituted by one or more groups (especially one group). More preferably, R 3 is selected from -SO2-NH2, -SO2-NH(C 1-4 alkyl), -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and -SO2-N=(C 1-4 alkylidene), wherein the alkyl moiety of the -SO2-NH(C 1-4 alkyl), one or two alkyl moieties of the -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and the alkylidene moiety of the -SO2-N=(C 1-4 alkylidene) is each optionally selected from -NH2, -NH(C 1-4 alkyl) and -N(C 1-4 alkyl)(C 1-4is replaced by one group of (alkyl). Even more preferably, R 3 is selected from -SO2-NH2, -SO2-NH(C 1-4 alkyl), -SO2-N(C 1-4 alkyl)(C 1-4 alkyl), -SO2-NH-(C 1-4 alkylene)-NH2, -SO2-NH-(C 1-4 alkylene)-NH(C 1-4 alkyl), -SO2-NH-(C 1-4 alkylene)-N(C 1-4 alkyl)(C 1-4 alkyl), -SO2-N=(C 1-4 alkylidene)-NH2, -SO2-N=(C 1-4 alkylidene)-NH(C 1-4 alkyl) and -SO2-N=(C 1-4 alkylidene)-N(C 1-4 alkyl)(C 1-4 alkyl). Even more preferably, R 3 is selected from -SO2-NH2, -SO2-NH-CH3, -SO2-N(CH3)2, -SO2-NH-(C 1-4 alkylene)-NH2, -SO2-NH-(C 1-4 alkylene)-NH-CH3, -SO2-NH-(C 1-4 alkylene)-N(CH3)2 (for example, -SO2-NH-CH2CH2-N(CH3)2), -SO2-N=(C 1-4 alkylidene)-NH2, -SO2-N=(C 1-4 alkylidene)-NH-CH3 and -SO2-N=(C 1-4 alkylidene)-N(CH3)2 (for example, -SO2-N=CH-N(CH3)2). A particularly preferred example of R 3 is -SO2-NH2. A further particularly preferred example of R 3 is -SO2-N=CH-N(CH3)2.

[0440] R 4 and R 5 are connected to each other to form a group -R 5b -.

[0441] R 5b is selected from -R 5b1 -R 5b2 -R 5b1 -, -N=C(R 53 )-R 5b3 -R5b1 -, -R 5b1 -R 5b3 -C(R 53 )=N- and

[0442] -N=C(R 53 )-R 5b4 -C(R 53 )=N-. Each R 5b1 is independently selected from -N(R 52 )-, -O-, and -S-.

[0443] R 5b2 is selected from -C(R 53 )(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )(R 53 )-, -C(R 53 )=C(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-, and -C(R 53 )=C(R 53 )-C(R 53 )(R 53 ). R 5b3 is selected from a covalent bond, -C(R 53 )(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )(R 53 )-, and -C(R 53 )=C(R 53 ). R 5b4 is selected from a covalent bond and -C(R 53 )(R 53 ).

[0444] Each R 52 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -(C 0-4 )-aryl, and -(C 0-4 )-heteroaryl. Preferably, each R 52 is independently selected from hydrogen, C 1-4 alkyl (e.g., n-butyl), C 2-4 alkenyl, and C 2-4An alkynyl group (e.g., -CH2-C≡CH). Even more preferably, each R 52 is hydrogen.

[0445] Each R 53 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl), -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl), -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, and any two groups R 53 connected to the same carbon atom may also together form a group =O, and any two groups R 53 connected to adjacent carbon atoms joined by a double bond may also be joined to each other to form a group -C(R 54 )=C(R 54 )-C(R 54 )=C(R 54 )-. Preferably, each R 53 is independently selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6(alkyl), -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN, and any two groups R attached to the same carbon atom 53 may also together form the group =O, and any two groups R attached to adjacent carbon atoms joined by a double bond 53 may also be joined to each other to form the group -C(R 54 )=C(R 54 )-C(R 54 )=C(R 54 )-. More preferably, each R 53 is independently selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN, and any two groups R attached to the same carbon atom 53 may also together form the group =O. Even more preferably, each R 53 is independently selected from hydrogen, C 1-4 alkyl, -OH, -O(C 1-4 alkyl), -NH2, -NH(C 1-4 alkyl), -N(C 1-4 (alkyl)(C 1-4 (alkyl), halogen, C 1-4 haloalkyl, -O-(C 1-4 haloalkyl) and -CN, and any two groups R attached to the same carbon atom 53 may also together form the group =O.

[0446] Each R 54 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), halogen, C 1-6Halogenated alkyl, -O-(C 1-6 halogenated alkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, each R 54 is independently selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 halogenated alkyl, -O-(C 1-6 halogenated alkyl) and -CN. More preferably, each R 54 is hydrogen.

[0447] Particularly preferably, R 5b is selected from -N(R 52 )-C(R 53 )(R 53 )-N(R 52 )-, -N=C(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )=N-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-, -N=C(R 53 )-C(R 53 )(R53 )(R-N 52 -、-N(R 52 )(R-C 53 )(R=C 53 )(R-N 52 -、-N(R 52 )(R-C 53 )(R 53 )(R-C 53 -、-N=C(R 53 )(R-C 53 -、-N(R 52 )(R-C 53 )(R 53 )(R-C 53 )(R 53 )(R-C 53 )(R 53 )(R-N 52 -、-N=C(R 53 )(R-C 53 )(R 53 )(R-C 53 )(R 53 )(R-N 52 -、-N(R 52 )(R-C 53 )(R 53 )(R-C 53 )(R=C 53 )(R-N 52 -、-N(R 52 )(R-C 53 )(R=C 53 )(R-C 53 )(R 53 )(R-N 52 -、-N(R 52 )(R-C 53 )(R 53 )(R-C 53 )(R 53 )(R-C 53 -、-N=C(R 53 )(R-C 53 )(R 53 )(R-C 53 -、-N=C(R-O 53 )(R 53 )(R-N 52 -、-O-C(R 53 )(R 53 )(R-C 53 )(R 53 )(R-N52 )-, -O-C(R 53 )=C(R 53 )-N(R 52 )-, -O-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-, -O-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-N(R 52 )-, -O-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-N(R 52 )-, -N(R 52 )-C(R 53 )(R 53 )-O-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-O-, -N(R 52 )-C(R 53 )=C(R 53 )-O-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-O-, -N(R 52 )-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-O-, -N(R 52 )-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-O-, -S-C(R 53 )(R 53 )-N(R 52 )-, -S-C(R 53 )(R 53 )-C(R 53)(R 53 )-N(R 52 )-、-S-C(R 53 )=C(R 53 )-N(R 52 )-、-S-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-S-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-N(R 52 )-、-S-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-N(R 52 )-C(R 53 )(R 53 )-S-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-S-、-N(R 52 )-C(R 53 )=C(R 53 )-S-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-S-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-S-、-N(R 52 )-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-S-、-N(R 52 )-C(R 53 )(R 53 )-N(R 52 )-、-N(R52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-N(R 52 )-C(R 53 )=C(R 53 )-N(R 52 )-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-C(R 53 )(R 53 )-N(R 52 )-、-N(R 52 )-C(R 53 )(R 53 )-C(R 53 )=C(R 53 )-N(R 52 )- and -N(R 52 )-C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-N(R 52 )-.

[0448] Even more preferably, choose R 5b The compound of formula (Ia) has any of the following structures:

[0449]

[0450]

[0451] R 6 Selected from hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, -OH, -O(C 1-6 Alkyl), -O(C 1-6 Alkylene)-OH, -O(C 1-6 Alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 Alkyl), -NH2, -NH(C 1-6 Alkyl), -N(C 1-6 Alkyl)(C 1-6 alkyl), halogen, C 1-6 Haloalkyl, -O-(C 1-6(haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, R 6 is selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN. More preferably, R 6 is hydrogen or C 1-4 alkyl. Even more preferably, R 6 is hydrogen.

[0452] In addition, the present invention provides a compound of the following formula (Ib) or a pharmaceutically acceptable salt or solvate thereof (and it also relates to the use of said compound as a drug, and a pharmaceutical composition comprising said compound and a pharmaceutically acceptable excipient):

[0453]

[0454] In formula (Ib), R x is selected from -COOH, -COO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-4 alkyl), -SO2-N(C1-4 alkyl)(C 1-4 alkyl) and -SO2-N=(C 1-4 alkylidene), wherein the alkyl moiety of the -SO2-NH(C 1-4 alkyl), the -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and one or both of the alkyl moieties of the -SO2-N=(C 1-4 alkylidene) are each optionally substituted with a group selected from -NH2, -NH(C 1-4 alkyl) and -N(C 1-4 alkyl)(C 1-4 alkyl). Preferably, R x is selected from -COOH, -COOCH3, -SO2-NH2 and -SO2-N=CH-N(CH3)2.

[0455] R 4 is the group R 4a , and R 5 is the group R 5a .

[0456] R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 alkyl)-R 41 , halogen (e.g., -Cl), carbocyclic group and heterocyclic group, wherein the carbocyclic group and the heterocyclic group are each optionally substituted with one or more groups R 42 . Preferably, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 alkyl)-R 41 , halogen, carbocyclic group (e.g., aryl, cycloalkyl or cycloalkenyl) and heterocyclic group (e.g., heteroaryl, heterocycloalkyl or heterocycloalkenyl), wherein the carbocyclic group and the heterocyclic group are each optionally substituted with one or more groups R 42 . More preferably, R 4a is selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-4 alkyl)-R 41 , halogen, aryl and heteroaryl, wherein the aryl and the heteroaryl are each optionally substituted with one or more groups R 42 . Even more preferably, R 4a is selected from -O-R41 、 -S-R 41 、 -NH-R 41 、 -N(C 1-4 alkyl)-R 41 and halogen. Still more preferably, R 4a is -O-R 41 or halogen.

[0457] R 41 is selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the carbocyclic moiety of the -(C 0-4 alkylene)-carbocyclic group and the heterocyclic moiety of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted with one or more groups R 42 , and wherein the C 1-6 alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl, the alkylene moiety of the -(C 0-4 alkylene)-carbocyclic group and the alkylene moiety of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted with one or more groups R 43 . Preferably, R 41 is selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the carbocyclic moiety of the -(C 0-4 alkylene)-carbocyclic group is selected from cycloalkyl, cycloalkenyl and aryl, wherein the heterocyclic moiety of the -(C 0-4 alkylene)-heterocyclic group is selected from heterocycloalkyl, heterocycloalkenyl and heteroaryl, wherein the carbocyclic moiety of the -(C 0-4 alkylene)-carbocyclic group and the heterocyclic moiety of the -(C 0-4 alkylene)-heterocyclic group are each optionally substituted with one or more (e.g., one, two or three) groups R 42 , and further, wherein the C 1-6 alkyl, the C 2-6 alkenyl, the C 2-6 alkynyl, the alkylene moiety of the -(C 0-4 alkylene)-carbocyclic group and the alkylene moiety of the -(C 0-4The alkylene moieties of the (alkylene)-heterocyclyl are each optionally substituted with one or more (e.g., one, two, or three) groups R 43 . More preferably, R 41 is selected from -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, wherein the aryl moiety of the -(C 0-4 alkylene)-aryl and the heteroaryl moiety of the -(C 0-4 alkylene)-heteroaryl are each optionally substituted with one or more (e.g., one, two, or three) groups R 42 , and further, wherein the alkylene moiety of the -(C 0-4 alkylene)-aryl and the alkylene moiety of the -(C 0-4 alkylene)-heteroaryl are each optionally substituted with one or more (e.g., one, two, or three) groups R 43 . Even more preferably, R 41 is selected from -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, wherein the aryl moiety of the -(C 0-4 alkylene)-aryl and the heteroaryl moiety of the -(C 0-4 alkylene)-heteroaryl are each optionally substituted with one or more (e.g., one, two, or three) groups R 42 . Preferred examples of the aryl moiety of the -(C 0-4 alkylene)-aryl are phenyl. Preferred examples of the heteroaryl moiety of the -(C 0-4 alkylene)-heteroaryl are 5- or 6-membered monocyclic heteroaryls having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (where the remaining ring atoms are carbon atoms), such as, for example, imidazolyl, phenylthio, or pyrimidinyl. Still more preferably, R 41 is selected from phenyl and heteroaryl, wherein the heteroaryl is a 5- or 6-membered monocyclic heteroaryl having 1 or 2 ring heteroatoms independently selected from oxygen, nitrogen, and sulfur (the remaining ring atoms of the monocyclic heteroaryl are carbon atoms), and further, wherein the phenyl or the heteroaryl is optionally substituted with one or more (e.g., one, two, or three) groups R 42 .

[0458] Each R 42 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6(alkyl), -SH, -S(C 1-6 (alkyl), -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 (alkyl), -COOH, -COO-(C 1-6 (alkyl), -O-CO-(C 1-6 (alkyl), -CO-NH2, -CO-NH(C 1-6 (alkyl), -CO-N(C 1-6 (alkyl)(C 1-6 (alkyl), -NH-CO-(C 1-6 (alkyl), -N(C 1-6 (alkyl)-CO-(C 1-6 (alkyl), -SO2-NH2, -SO2-NH(C 1-6 (alkyl), -SO2-N(C 1-6 (alkyl)(C 1-6 (alkyl), -NH-SO2-(C 1-6 (alkyl) and -N(C 1-6 (alkyl)-SO2-(C 1-6 (alkyl). Preferably, each R 42 is independently selected from C 1-6 alkyl, -OH, -O(C 1-6 (alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 (alkyl), -SH, -S(C 1-6 (alkyl), -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0459] Each R 43 is independently selected from -OH, -O(C 1-6 (alkyl), -SH, -S(C 1-6 (alkyl), -NH2, -NH(C 1-6 (alkyl), -N(C 1-6 (alkyl)(C 1-6 (alkyl), halogen, -CF3, -CN, -NO2, -CHO, -CO-(C1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl) and -N(C 1-6 alkyl)-CO-(C 1-6 alkyl). Preferably, each R 43 is independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3 and -CN.

[0460] According to the above definition, particularly preferably, R 4a is -O-aryl or halogen, wherein the aryl moiety of the -O-aryl is optionally substituted by one or more groups independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl and -CN. Even more preferably, R 4a is -O-phenyl or halogen (for example, specifically -Cl), wherein the phenyl moiety of the -O-phenyl is optionally substituted by one or more groups independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6(alkyl)(C 1-6 (alkyl), halogen, C( 1-6 One or more groups of haloalkyl and -CN are substituted. ( (

[0461] R( 5a is selected from -NH2, -NH(C( 1-6 (alkyl) and -N(C( 1-6 (alkyl)(C( 1-6 (alkyl), wherein the alkyl moiety of the -NH(C( 1-6 (alkyl) and the -N(C( 1-6 (alkyl)(C( 1-6 (alkyl) of one or both alkyl moieties are each optionally independently selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C( 1-6 (alkyl), -N(C( 1-6 (alkyl)(C( 1-6 (alkyl), -OH, -O(C( 1-6 (alkyl), -SH, -S(C( 1-6 (alkyl), a carbocyclic group and a heterocyclic group are substituted by one or more groups R( 51 (substituted). Preferably, R( 5a is selected from -NH2, -NH(C( 1-6 (alkyl) and -N(C( 1-6 (alkyl)(C( 1-6 (alkyl), wherein the alkyl moiety of the -NH(C( 1-6 (alkyl) and the -N(C( 1-6 (alkyl)(C( 1-6 (alkyl) of one or both alkyl moieties are each optionally independently selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C( 1-6 (alkyl), -N(C( 1-6 (alkyl)(C( 1-6 (alkyl), -OH, -O(C( 1-6 (alkyl), -SH and -S(C( 1-6 (alkyl) are substituted by one or more (e.g., one, two or three) groups. More preferably, R( 5a is selected from -NH2, -NH(C( 1-6 (alkyl) and -N(C( 1-6 (alkyl)(C( 1-6 (alkyl). A particularly preferred example of R( 5a is -NH2 or -NH-CH2CH2CH2CH3. ( (

[0462] Each R( 51 is independently selected from C( 1-6 (alkyl), C( 2-6 (alkenyl), C2-6 Alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, each R 51 is independently selected from C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN.

[0463] R 6 is selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6Alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl). Preferably, R 6 is selected from hydrogen, C 1-6 alkyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl) and -CN. More preferably, R 6 is hydrogen or C 1-4 alkyl. Even more preferably, R 6 is hydrogen.

[0464] The present invention further relates to a compound of any one of the following formulas, or a pharmaceutically acceptable salt or solvate thereof (and it also relates to said compound for use as a medicament, and a pharmaceutical composition comprising said compound and a pharmaceutically acceptable excipient):

[0465]

[0466]

[0467]

[0468]

[0469]

[0470]

[0471]

[0472]

[0473] For those skilled in the art of synthetic chemistry, various ways of preparing the compound of formula (I) will be obvious. For example, the compound of formula (I) can be prepared according to or similar to the synthetic routes described in the Examples section.

[0474] Unless otherwise specifically indicated, the following definitions apply throughout the specification.

[0475] The term "hydrocarbyl" refers to a group consisting of carbon and hydrogen atoms.

[0476] The term "alicyclic" is used in conjunction with a cyclic group and means that the corresponding cyclic group is non-aromatic.

[0477] As used herein, the term "alkyl" refers to a monovalent saturated acyclic (i.e., non-cyclic) hydrocarbyl group, which can be straight-chain or branched-chain. Thus, an "alkyl" group does not include any carbon-carbon double bonds or any carbon-carbon triple bonds. "C 1-6 alkyl" represents an alkyl group having 1 to 6 carbon atoms. Preferred exemplary alkyl groups are methyl, ethyl, propyl (e.g., n-propyl or isopropyl), or butyl (e.g., n-butyl, isobutyl, sec-butyl, or tert-butyl). Unless otherwise defined, the term "alkyl" preferably refers to C 1-4 alkyl, more preferably methyl or ethyl, and even more preferably methyl.

[0478] As used herein, the term "alkenyl" refers to a monovalent unsaturated acyclic hydrocarbyl group, which can be straight-chain or branched-chain, and includes one or more (e.g., one or two) carbon-carbon double bonds, however it does not include any carbon-carbon triple bonds. The term "C2-6 "Alkenyl" means that the alkenyl has 2 to 6 carbon atoms. Preferred exemplary alkenyls are vinyl, propenyl (e.g., prop-1-en-1-yl, prop-1-en-2-yl or prop-2-en-1-yl), butenyl, butadienyl (e.g., buta-1,3-dien-1-yl or buta-1,3-dien-2-yl), pentenyl or pentadienyl (e.g., isoprenyl). Unless otherwise defined, the term "alkenyl" preferably refers to C 2-4 alkenyl.

[0479] As used herein, the term "alkynyl" refers to a monovalent unsaturated acyclic hydrocarbon group which may be straight-chain or branched-chain and which includes one or more (e.g., one or two) carbon-carbon triple bonds and optionally one or more carbon-carbon double bonds. The term "C 2-6 alkynyl" means an alkynyl having 2 to 6 carbon atoms. Preferred exemplary alkynyls are ethynyl, propynyl (e.g., propargyl) or butynyl. Unless otherwise defined, the term "alkynyl" preferably refers to C 2-4 alkynyl.

[0480] As used herein, the term "alkylene" refers to an alkanediyl, i.e., a divalent saturated acyclic hydrocarbon group which may be straight-chain or branched-chain. "C 1-15 alkylene" means an alkylene having 1 to 15 carbon atoms, and the term "C 0-15 alkylene" indicates the presence of a covalent bond (corresponding to the option "C0 alkylene") or C 1-15 alkylene. Preferred exemplary alkylenes are methylene (-CH2-), ethylene (e.g., -CH2-CH2- or -CH(-CH3)-), propylene (e.g., -CH2-CH2-CH2-, -CH(-CH2-CH3)-, -CH2-CH(-CH3)- or -CH(-CH3)-CH2-) or butylene (e.g., -CH2-CH2-CH2-CH2-). Unless otherwise defined, the term "alkylene" preferably refers to C 1-4 alkylene (specifically including straight-chain C 1-4 alkylene), more preferably methylene or ethylene, and even more preferably methylene.

[0481] As used herein, the term "alkenylene" refers to an alkenediyl, i.e., a divalent unsaturated acyclic hydrocarbon group which may be straight-chain or branched-chain and which includes one or more (e.g., one or two) carbon-carbon double bonds, however it does not include any carbon-carbon triple bonds. "C 2-15 alkenylene" means an alkenylene having 2 to 15 carbon atoms. Unless otherwise defined, the term "alkenylene" preferably refers to C 2-4 alkenylene (specifically including straight-chain C 2-4 alkenylene).

[0482] As used herein, the term "alkynylene" refers to alkynediyl, i.e., a divalent unsaturated acyclic hydrocarbon group which may be straight-chain or branched-chain and which includes one or more (e.g., one or two) carbon-carbon triple bonds and optionally one or more carbon-carbon double bonds. "C 2-15 alkynylene" means an alkynylene group having 2 to 15 carbon atoms. Unless otherwise defined, the term "alkynylene" preferably refers to C 2-4 alkynylene (specifically including straight-chain C 2-4 alkynylene).

[0483] As used herein, the term "alkylidene" refers to a divalent acyclic hydrocarbon group which may be straight-chain or branched-chain, which is attached to the remainder of the corresponding compound via a double bond, and which does not include any other double bonds (i.e., except for the double bond attaching the alkylidene to the remainder of the corresponding compound, it does not include any double bonds) or any triple bonds. The alkylidene may be attached, for example, to a carbon atom or a nitrogen atom of the remainder of the corresponding compound. "C 1-6 alkylidene" means an alkylidene group having 1 to 6 carbon atoms. Preferred exemplary alkylidenes are methylidene (=CH2), ethylidene (=CH-CH3), propylidene (e.g., =CH-CH2CH3 or =C(-CH3)-CH3) or butylidene (e.g., =CH-CH2CH2CH3, =C(-CH3)-CH2CH3 or =CH-CH(-CH3)-CH3). Unless otherwise defined, the term "alkylidene" preferably refers to C 1-4 alkylidene.

[0484] As used herein, the term "carbocyclic group" refers to a hydrocarbon ring group, including monocyclic as well as bridged, spiro and / or fused ring systems (which may consist, for example, of two or three rings), where the ring group may be saturated, partially unsaturated (i.e., unsaturated, but non-aromatic) or aromatic. Unless otherwise defined, "carbocyclic group" preferably refers to aryl, cycloalkyl or cycloalkenyl.

[0485] As used herein, the term "heterocyclic group" refers to a ring group, including monocyclic as well as bridged, spiro and / or fused ring systems (which can consist of, for example, two or three rings), wherein the ring group includes one or more (such as, for example, one, two, three or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) can be optionally oxidized, wherein one or more carbon ring atoms can be optionally oxidized (i.e., form an oxygen-containing group), and wherein the ring group can be saturated, partially unsaturated (i.e., unsaturated but non-aromatic) or aromatic. For example, each heteroatom-containing ring included in the ring group can contain one or two O atoms and / or one or two S atoms (which can be optionally oxidized) and / or one, two, three or four N atoms (which can be optionally oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1-4, and there is at least one carbon ring atom in the corresponding heteroatom-containing ring. Unless otherwise defined, "heterocyclic group" preferably refers to heteroaryl, heterocycloalkyl or heterocycloalkenyl.

[0486] As used herein, the term "aryl" refers to an aromatic hydrocarbon ring group, including monocyclic aromatic rings as well as bridged and / or fused ring systems containing at least one aromatic ring (e.g., a ring system consisting of two or three fused rings, wherein at least one of these fused rings is aromatic; or a bridged ring system consisting of two or three rings, wherein at least one of these bridged rings is aromatic). "Aryl" can refer to, for example, phenyl, naphthyl, dialinyl (i.e., 1,2-dihydronaphthyl), tetrahydronaphthyl (i.e., 1,2,3,4-tetrahydronaphthyl), indanyl, indenyl (e.g., 1H-indenyl), anthryl, phenanthryl, 9H-fluorenyl or azulyl. Unless otherwise defined, "aryl" preferably has 6 to 14 ring atoms, more preferably 6 to 10 ring atoms, even more preferably refers to phenyl or naphthyl, and most preferably refers to phenyl.

[0487] As used herein, the term "heteroaryl" refers to an aromatic ring group, including monocyclic aromatic rings and bridged and / or fused ring systems containing at least one aromatic ring (e.g., a ring system composed of two or three fused rings, where at least one of these fused rings is aromatic; or a bridged ring system composed of two or three rings, where at least one of these bridged rings is aromatic), where the aromatic ring group includes one or more (such as, for example, one, two, three, or four) ring heteroatoms independently selected from O, S, and N, and the remaining ring atoms are carbon atoms, where one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further, where one or more carbon ring atoms may optionally be oxidized (i.e., to form oxygen-containing groups). For example, each heteroatom-containing ring included in the aromatic ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three, or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4, and there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. "Heteroaryl" may refer, for example, to thienyl (i.e., phenylthio), benzo[b]thienyl, naphtho[2,3-b]thienyl, thianthrenyl, furyl (i.e., furanyl), benzofuranyl, isobenzofuranyl, chromanyl, pyranyl (e.g., 2H-1-benzopyranyl or 4H-1-benzopyranyl), isopyranyl (e.g., 1H-2-benzopyranyl), benzopyrone, xanthenyl, phenoxathiinyl, pyrrolyl (e.g., 1H-pyrrolyl), imidazolyl, pyrazolyl, pyridyl (i.e., pyridinyl; e.g., 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl), pyrazinyl, pyrimidinyl, pyridazinyl, indolyl (e.g., 3H-indolyl), isoindolyl, indazolyl, indazolizinyl, purinyl, quinolinyl, isoquinolinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, cinnolinyl, pteridinyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, selenidinyl, phenanthrolinyl (e.g., [1,10]phenanthrolinyl, [1,7]phenanthrolinyl, or [4,7]phenanthrolinyl), phenazinyl, thiazolyl, isothiazolyl, phenothiazinyl, oxathiinyl, pyrrolyl (e.g., 1H-pyrrolyl), imidazolyl, pyrazolyl, pyridyl (i.e., pyridinyl; e.g., 2-pyridinyl, 3-pyridinyl, or 4-pyridinyl), pyrazinyl, pyrimidinyl, pyridazinyl, indolyl (e.g., 3H-indolyl), isoindolyl, indazolyl, indazolizinyl, purinyl, quinolinyl, isoquinolinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, cinnolinyl, pteridinyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, selenidinyl, phenanthrolinyl (e.g., [1,10]phenanthrolinyl, [1,7]phenanthrolinyl, or [4,7]phenanthrolinyl), phenazinyl, thiazolyl, isothiazolyl, phenothiazinyl, oxazolyl, iso oxazolyl, diazolyl (e.g., 1,2,4- diazolyl, 1,2,5- diazolyl (i.e., furazanyl), or 1,3,4- diazolyl), thiazolyl (e.g., 1,2,4-thiazolyl, 1,2,5-thiazolyl, or 1,3,4-thiazolyl), phen oxazine, pyrazolo[1,5-a]pyrimidinyl (e.g., pyrazolo[1,5-a]pyrimidin-3-yl), 1,2-benzisoxazine, oxazol-3-yl, benzothiazolyl, benzothiadiazolyl, benzo Azolyl, benzyl oxazolyl, benzimidazolyl, benzo[b]phenylthio (i.e., benzothiophenyl), triazolyl (e.g., 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl, or 4H-1,2,4-triazolyl), benzotriazolyl, 1H-tetrazolyl, 2H-tetrazolyl, triazinyl (e.g., 1,2,3-triazinyl, 1,2,4-triazinyl, or 1,3,5-triazinyl), furano[2,3-c]pyridinyl, dihydro furanyl (e.g., 2,3-dihydrofuro[2,3-c]pyridinyl or 1,3-dihydrofuro[3,4-c]pyridinyl), imidazopyridinyl (e.g., imidazo[1,2-a]pyridinyl or imidazo[3,2-a]pyridinyl), quinazolinyl, thienopyridinyl, tetrahydrothienopyridinyl (e.g., 4,5,6,7-tetrahydrothieno[3,2-c]pyridinyl), dibenzofuranyl, 1,3-benzodioxolyl, benzodioxolyl Alkyl (e.g., 1,3-benzodiphenyl Alkyl or 1,4-benzodiphenyl alkyl) or coumarin. Unless otherwise defined, the term "heteroaryl" preferably refers to a 5- to 14-membered (more preferably 5- to 10-membered) monocyclic or fused ring system comprising one or more (e.g., one, two, three or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; even more preferably, "heteroaryl" refers to a 5- or 6-membered monocyclic ring comprising one or more (e.g., one, two or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized. Furthermore, unless otherwise defined, particularly preferred examples of “heteroaryl” include pyridyl (e.g., 2-pyridyl, 3-pyridyl or 4-pyridyl), imidazolyl, thiazolyl, 1H-tetrazolyl, 2H-tetrazolyl, thienyl (i.e., phenylthio) or pyrimidinyl.

[0488] As used herein, the term "cycloalkyl" refers to a saturated hydrocarbon ring group, including monocyclic as well as bridged, spiro and / or fused ring systems (which may consist of, for example, two or three rings; such as, for example, a fused ring system consisting of two or three fused rings). "Cycloalkyl" may refer, for example, to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, decalinyl (i.e., decahydronaphthyl) or adamantyl. Unless otherwise defined, "cycloalkyl" preferably refers to C 3-11 cycloalkyl, and more preferably refers to C 3-7 cycloalkyl. Particularly preferred "cycloalkyl" is a monocyclic saturated hydrocarbon ring having 3 to 7 ring members. In addition, unless otherwise defined, particularly preferred examples of "cycloalkyl" include cyclohexyl or cyclopropyl, especially cyclohexyl.

[0489] As used herein, the term "heterocycloalkyl" refers to a saturated ring group, including monocyclic as well as bridged, spiro and / or fused ring systems (which may consist of, for example, two or three rings; such as, for example, a fused ring system consisting of two or three fused rings), wherein said ring group contains one or more (such as, for example, one, two, three or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) may optionally be oxidized, and further, wherein one or more carbon ring atoms may optionally be oxidized (i.e., to form an oxygen-containing group). For example, each heteroatom-containing ring included in said saturated ring group may contain one or two O atoms and / or one or two S atoms (which may optionally be oxidized) and / or one, two, three or four N atoms (which may optionally be oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and there is at least one carbon ring atom (which may optionally be oxidized) in the corresponding heteroatom-containing ring. "Heterocycloalkyl" may refer, for example, to aziridinyl, azetidinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, azepanyl, diazepanyl (e.g., 1,4-diazepanyl), oxazolidinyl, iso oxazolidinyl, thiazolidinyl, isothiazolinyl, morpholinyl (e.g., morpholin-4-yl), thiomorpholinyl (e.g., thiomorpholin-4-yl), oxepanyl, oxiranyl, oxetanyl, tetrahydrofuryl, 1,3-dioxolanyl, tetrahydropyranyl, 1,4-di alkyl, oxepanyl, thiiranyl, thietanyl, thiolanyl (i.e., tetrahydrothiophenyl), 1,3-dithiolanyl, thianyl, thiepanyl, decahydroquinolinyl, decahydroisoquinolinyl or 2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl. Unless otherwise defined, "heterocycloalkyl" preferably refers to a 3- to 11-membered saturated ring group, which is a monocyclic or fused ring system (e.g., a fused ring system composed of two fused rings), wherein the ring group contains one or more (e.g., one, two, three or four) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized; more preferably, "heterocycloalkyl" refers to a 5- to 7-membered saturated monocyclic group containing one or more (e.g., one, two or three) ring heteroatoms independently selected from O, S and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, and wherein one or more carbon ring atoms are optionally oxidized. In addition, unless otherwise defined, particularly preferred examples of "heterocycloalkyl" include tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, pyrrolidinyl or tetrahydrofuryl.

[0490] As used herein, the term "cycloalkenyl" refers to an unsaturated alicyclic (non-aromatic) hydrocarbon ring group, including monocyclic as well as bridged, spiro and / or fused ring systems (which may be composed of, for example, two or three rings; such as, for example, a fused ring system composed of two or three fused rings), wherein the hydrocarbon ring group includes one or more (e.g., one or two) carbon-carbon double bonds and does not include any carbon-carbon triple bonds. "Cycloalkenyl" may refer, for example, to cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, cycloheptenyl or cycloheptadienyl. Unless otherwise defined, "cycloalkenyl" preferably refers to C 3-11 cycloalkenyl, and more preferably refers to C 3-7 cycloalkenyl. Particularly preferred "cycloalkenyl" is a monocyclic unsaturated alicyclic hydrocarbon ring having 3 to 7 ring members and containing one or more (e.g., one or two; preferably one) carbon-carbon double bonds.

[0491] As used herein, the term "heterocyclenyl" refers to an unsaturated alicyclic (non-aromatic) ring group, including monocyclic as well as bridged, spiro and / or fused ring systems (which can consist of, for example, two or three rings; such as, for example, a fused ring system consisting of two or three fused rings), wherein said ring group contains one or more (such as, for example, one, two, three or four) ring heteroatoms independently selected from O, S and N, and the remaining ring atoms are carbon atoms, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) can be optionally oxidized, wherein one or more carbon ring atoms can be optionally oxidized (i.e., to form oxygen-containing groups), and further, wherein said ring group includes at least one double bond between adjacent ring atoms and does not include any triple bonds between adjacent ring atoms. For example, each heteroatom-containing ring included in said unsaturated alicyclic ring group can contain one or two O atoms and / or one or two S atoms (which can be optionally oxidized) and / or one, two, three or four N atoms (which can be optionally oxidized), provided that the total number of heteroatoms in the corresponding heteroatom-containing ring is 1 to 4 and there is at least one carbon ring atom (which can be optionally oxidized) in the corresponding heteroatom-containing ring. "Heterocyclenyl" can refer to, for example, imidazolinyl (e.g., 2-imidazolinyl (i.e., 4,5-dihydro-1H-imidazolyl), 3-imidazolinyl or 4-imidazolinyl), tetrahydropyridyl (e.g., 1,2,3,6-tetrahydropyridyl), dihydropyridyl (e.g., 1,2-dihydropyridyl or 2,3-dihydropyridyl), pyranyl (e.g., 2H-pyranyl or 4H-pyranyl), thiopyranyl (e.g., 2H-thiopyranyl or 4H-thiopyranyl), dihydropyranyl, dihydrofuryl, dihydropyrazolyl, dihydropyrazinyl, dihydroisoindolyl, octahydroquinolinyl (e.g., 1,2,3,4,4a,5,6,7-octahydroquinolinyl) or octahydroisoquinolinyl (e.g., 1,2,3,4,5,6,7,8-octahydroisoquinolinyl).Unless otherwise defined, "heterocycloalkenyl" preferably refers to an unsaturated alicyclic ring group having 3 to 11 ring members, which is a monocyclic or fused ring system (e.g., a fused ring system consisting of two fused rings), wherein the ring group contains one or more (e.g., one, two, three, or four) ring heteroatoms independently selected from O, S, and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, wherein one or more carbon ring atoms are optionally oxidized, and wherein the ring group includes at least one double bond between adjacent ring atoms and does not include any triple bond between adjacent ring atoms; more preferably, "heterocycloalkenyl" refers to a 5- to 7-membered monocyclic unsaturated non-aromatic ring group containing one or more (e.g., one, two, or three) ring heteroatoms independently selected from O, S, and N, wherein one or more S ring atoms (if present) and / or one or more N ring atoms (if present) are optionally oxidized, wherein one or more carbon ring atoms are optionally oxidized, and wherein the ring group includes at least one double bond between adjacent ring atoms and does not include any triple bond between adjacent ring atoms.

[0492] As used herein, the term "halogen" refers to fluorine (-F), chlorine (-Cl), bromine (-Br), or iodine (-I).

[0493] As used herein, the term "haloalkyl" refers to an alkyl group substituted with one or more (preferably 1 to 6, more preferably 1 to 3) halogen atoms independently selected from fluorine, chlorine, bromine, and iodine, and preferably all are fluorine atoms. It should be understood that the maximum number of halogen atoms is limited by the number of available attachment sites and thus depends on the number of carbon atoms contained in the alkyl portion of the haloalkyl. "Haloalkyl" can refer to, for example, -CF3, -CHF2, -CH2F, -CF2-CH3, -CH2-CF3, -CH2-CHF2, -CH2-CF2-CH3, -CH2-CF2-CF3, or -CH(CF3)2. A particularly preferred "haloalkyl" group is -CF3.

[0494] As used herein, the terms "optional", "optionally", and "may" mean that the indicated feature may be present but may also be absent. Whenever the terms "optional", "optionally", and "may" are used, the present invention particularly relates to two possibilities, namely, the presence or absence of the corresponding feature. For example, the expression "X is optionally substituted by Y" (or "X may be substituted by Y") means that X is either substituted by Y or not substituted. Similarly, if a component of a composition is indicated as "optional", the present invention particularly relates to two possibilities, namely, the presence (being included in the composition) or absence of the corresponding component in the composition.

[0495] In this specification, various groups are referred to as "optionally substituted". Generally, these groups may bear one or more substituents, for example, one, two, three, or four substituents. It should be understood that the maximum number of substituents is limited by the number of available attachment sites on the substituted moiety. Unless otherwise defined, the "optionally substituted" groups mentioned in this specification preferably bear no more than two substituents, and particularly may bear only one substituent. In addition, unless otherwise defined, preferably no optional substituents are present, i.e., the corresponding group is unsubstituted.

[0496] Those skilled in the art will recognize that the substituent groups included in the compounds of the present invention may be attached to the remainder of the corresponding compound via multiple different positions of the corresponding specific substituents. Unless otherwise defined, the preferred attachment positions of various specific substituents are illustrated in the examples.

[0497] As used herein, unless explicitly stated or inconsistent with the context, the terms "a", "an", and "the" are used interchangeably with "one or more" and "at least one". Thus, for example, a composition comprising "a" compound of formula (I) can be interpreted to mean a composition comprising "one or more" compounds of formula (I).

[0498] As used herein, the term "about" preferably refers to the indicated value ±10%, more preferably to the indicated value ±5%, and in particular to the exact value indicated. If the term "about" is used in connection with the endpoints of a range, it preferably refers to a range from -10% of the lower endpoint of its indicated value to +10% of the upper endpoint of its indicated value, more preferably a range from -5% of the lower endpoint to +5% of the upper endpoint, and even more preferably a range defined by the exact values of the lower and upper endpoints. If the term "about" is used in connection with the endpoints of an open-ended range, it preferably refers to the corresponding range starting from -10% of the lower endpoint or from +10% of the upper endpoint, more preferably a range starting from -5% of the lower endpoint or from +5% of the upper endpoint, and even more preferably an open range defined by the exact values of the corresponding endpoints. If the term "about" is used in connection with a parameter that is quantized in whole numbers (such as the number of nucleotides in a given nucleic acid), the numbers corresponding to ±10% or ±5% of the indicated value shall be rounded to the nearest integer (using the tie-breaking rule "round half up").

[0499] As used herein, unless otherwise expressly stated or inconsistent with the context, the term "comprising" (or "comprise", "comprises", "contain", "contains" or "containing") has the meaning of "including other things", i.e., "including other optional elements". In addition to this, the term also includes the narrower meanings of "consisting essentially of" and "consisting of". For example, the term "A comprises B and C" has the meaning of "A contains B and C etc.", where A may contain other optional elements (e.g., it also encompasses "A contains B, C and D"), but the term also includes the meanings of "A consists essentially of B and C" and "A consists of B and C" (i.e., no other components are included in A except for B and C).

[0500] The scope of the present invention encompasses all pharmaceutically or physiologically acceptable salt forms of the compounds of formula (I), which can be formed, for example, by protonation of an atom carrying a lone pair of electrons susceptible to protonation such as an amino group with an inorganic or organic acid, or as a salt of an acid group (such as a carboxylic acid group) with a physiologically acceptable cation. Exemplary base addition salts include, for example: alkali metal salts such as sodium or potassium salts; alkaline earth metal salts such as calcium or magnesium salts; zinc salts; ammonium salts; aliphatic amine salts such as trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, procaine salt, meglumine salt, ethylenediamine salt or choline salt; aralkylamine salts such as N,N-dibenzylethylenediamine salt, benzathine salt, benethamine salt; heteroaromatic amine salts such as pyridine salt, methylpyridine salt, quinoline salt or isoquinoline salt; quaternary ammonium salts such as tetramethylammonium salt, tetraethylammonium salt, benzyltrimethylammonium salt, benzyltriethylammonium salt, benzyltributylammonium salt, methyltrioctylammonium salt or tetrabutylammonium salt; and basic amino acid salts such as arginine salt, lysine salt or histidine salt. Exemplary acid addition salts include, for example: inorganic acid salts such as hydrochloride, hydrobromide, hydroiodide, sulfate (such as sulfate or bisulfate), nitrate, phosphate (such as phosphate, hydrogenphosphate or dihydrogenphosphate), carbonate, bicarbonate, perchlorate, borate or thiocyanate; organic acid salts such as acetate, propionate, butyrate, valerate, hexanoate, heptanoate, octanoate, cyclopentanepropionate, decanoate, undecanoate, oleate, stearate, lactate, maleate, oxalate, fumarate, tartrate, malate, citrate, succinate, adipate, gluconate, glycolate, nicotinate, benzoate, salicylate, ascorbate, pamoate (embonate), camphorate, glucoheptonate or pivalate; sulfonate salts such as methanesulfonate (mesylate), ethanesulfonate (esylate), 2-hydroxyethanesulfonate (isethionate), benzenesulfonate (besylate), p-toluenesulfonate (tosylate), 2-naphthalenesulfonate (napsylate), 3-benzenesulfonate or camphorsulfonate; glycerophosphate; and acidic amino acid salts such as aspartate or glutamate. Preferred pharmaceutically / physiologically acceptable salts of the compounds of formula (I) include hydrochloride, hydrobromide, mesylate, sulfate, tartrate, fumarate, acetate, citrate and phosphate. A particularly preferred pharmaceutically / physiologically acceptable salt of the compounds of formula (I) is hydrochloride.

[0501] In addition, the scope of the present invention encompasses compounds of formula (I) in any solvated form, including, for example, solvates with water (i.e., as hydrates) or solvates with organic solvents such as, for example, methanol, ethanol or acetonitrile (i.e., as methanolates, ethanolates or acetonitriles), or in any crystalline form (i.e., as any polymorph), or in amorphous form. It should be understood that such solvates of the compounds of formula (I) also include solvates of pharmaceutically acceptable salts of the compounds of formula (I).

[0502] In addition, the compounds of formula (I) can exist in different isomeric forms, in particular stereoisomers (including, for example, geometric isomers (or cis / trans isomers), enantiomers and diastereomers) or tautomers. All such isomers of the compounds of formula (I) in mixture or in pure or substantially pure form are considered to be part of the present invention. For stereoisomers, the present invention encompasses the separated optical isomers of the compounds according to the present invention and any mixtures thereof (specifically including racemic mixtures / racemates). Racemates can be resolved by physical methods such as, for example, fractional crystallization, separation or crystallization of diastereomeric derivatives or by chiral column chromatography. The individual optically active isomers can also be obtained from the racemate by forming salts with optically active acids followed by crystallization. The present invention further includes any tautomers of the compounds provided herein.

[0503] The scope of the present invention also encompasses compounds of formula (I) in which one or more atoms are replaced by a specific isotope of the corresponding atom. For example, the present invention encompasses compounds of formula (I) in which one or more hydrogen atoms (or, for example, all hydrogen atoms) are replaced by deuterium atoms (i.e., 2 H; also referred to as "D"). Thus, the present invention also encompasses deuterium-enriched compounds of formula (I). Naturally occurring hydrogen consists of approximately 99.98 mol-% hydrogen-1 ( 1 H) and approximately 0.0156 mol-% deuterium ( 2An isotopic mixture of H or D). Deuteration techniques known in the art can be used to increase the content of deuterium in one or more hydrogen positions of the compounds of formula (I). For example, deuterium oxide (D2O) can be used, for example, to subject the compounds of formula (I), the reactants or precursors used in the synthesis of the compounds of formula (I) to an H / D exchange reaction. Other suitable deuteration techniques are described in Atzrodt J et al., Bioorg Med Chem, 20(18), 5658 - 5667, 2012; William JS et al., Journal of Labelled Compounds and Radiopharmaceuticals, 53(11 - 12), 635 - 644, 2010; Modvig A et al., J Org Chem, 79, 5861 - 5868, 2014. The content of deuterium can be determined using, for example, mass spectrometry or NMR spectroscopy. Unless otherwise specifically stated, it is preferred that the compounds of formula (I) are not enriched with deuterium. Thus, the presence of hydrogen atoms or 1 H hydrogen atoms is preferred.

[0504] The present invention also includes compounds of formula (I) in which one or more atoms are replaced by a positron-emitting isotope of the corresponding atom, such as, for example 18 F, 11 C, 13 N, 15 O, 76 Br, 77 Br, 120 I and / or 124 I. Such compounds can be used as tracers, tracking agents or imaging probes in positron emission computed tomography (PET). Thus, the present invention includes (i) compounds of formula (I) in which one or more fluorine atoms (or, for example, all fluorine atoms) are replaced by 18 F atoms, (ii) compounds of formula (I) in which one or more carbon atoms (or, for example, all carbon atoms) are replaced by 11 C atoms, (iii) compounds of formula (I) in which one or more nitrogen atoms (or, for example, all nitrogen atoms) are replaced by 13 N atoms, (iv) compounds of formula (I) in which one or more oxygen atoms (or, for example, all oxygen atoms) are replaced by 15 O atoms, (v) compounds of formula (I) in which one or more bromine atoms (or, for example, all bromine atoms) are replaced by 76 Br atoms, (vi) compounds of formula (I) in which one or more bromine atoms (or, for example, all bromine atoms) are replaced by 77Replacement of Br atoms, (vii) a compound of formula (I) in which one or more iodine atoms (or for example all iodine atoms) are 120 replaced by I atoms, and (viii) a compound of formula (I) in which one or more iodine atoms (or for example all iodine atoms) are 124 replaced by I atoms. Generally, preferably none of the atoms in the compound of formula (I) are replaced by a specific isotope.

[0505] The compounds provided herein can be administered as compounds per se or can be formulated into medicaments. The medicament / drug composition can optionally include one or more pharmaceutically acceptable excipients, such as carriers, diluents, fillers, disintegrants, lubricants, binders, colorants, pigments, stabilizers, preservatives, antioxidants and / or solubility enhancers.

[0506] The drug composition can include one or more solubility enhancers, such as for example poly(ethylene glycol), including poly(ethylene glycol) having a molecular weight in the range of about 200 to about 5,000 Da (for example, PEG 200, PEG 300, PEG 400 or PEG 600), ethylene glycol, propylene glycol, glycerol, nonionic surfactants, tyloxapol, polysorbate 80, polyethylene glycol-15-hydroxystearate (for example, HS15, CAS 70142-34-6), phospholipids, lecithin, dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, distearoyl phosphatidylcholine, cyclodextrins, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, hydroxyethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxyethyl-γ-cyclodextrin, hydroxypropyl-γ-cyclodextrin, dipropyl-β-cyclodextrin, sulfobutyl ether-β-cyclodextrin, sulfobutyl ether-γ-cyclodextrin, glucosyl-α-cyclodextrin, glucosyl-β-cyclodextrin, diglucosyl-β-cyclodextrin, maltosyl-α-cyclodextrin, maltosyl-β-cyclodextrin, maltosyl-γ-cyclodextrin, maltotriosyl-β-cyclodextrin, maltotriosyl-γ-cyclodextrin, dimaltosyl-β-cyclodextrin, methyl-β-cyclodextrin, carboxyalkyl thioethers, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, vinyl acetate copolymer, vinylpyrrolidone, sodium dodecyl sulfate, sodium dioctyl sulfosuccinate or any combination thereof.

[0507] The pharmaceutical compositions can be formulated by techniques known to those skilled in the art, such as those disclosed in “Remington: The Science and Practice of Pharmacy”, Pharmaceutical Press, 22nd Edition. The pharmaceutical compositions can be formulated into dosage forms for oral, parenteral such as intramuscular, intravenous, subcutaneous, intradermal, intraarterial, intracardiac, rectal, nasal, topical, aerosol or vaginal administration. Dosage forms for oral administration include coated and uncoated tablets, soft gelatin capsules, hard gelatin capsules, troches, lozenges, solutions, emulsions, suspensions, syrups, elixirs, powders and granules for reconstitution, dispersible powders and granules, medicinal gums, chewable tablets and effervescent tablets. Dosage forms for parenteral administration include solutions, emulsions, suspensions, dispersions and powders and granules for reconstitution. Emulsions are the preferred dosage form for parenteral administration. Dosage forms for rectal and vaginal administration include suppositories and ovula. Dosage forms for nasal administration can be administered via inhalation and insufflation, for example, by a metered inhaler. Dosage forms for topical administration include creams, gels, ointments, pastes, patches and transdermal delivery systems.

[0508] The compound of formula (I) or the above pharmaceutical composition comprising the compound of formula (I) can be administered to a subject by any convenient route of administration, whether systemic / peripheral or at the desired site of action, including but not limited to one or more of the following: oral (e.g., as tablets, capsules or absorbable solutions), topical (e.g., transdermal, intranasal, intraocular, buccal and sublingual), parenteral (e.g., using injection techniques or infusion techniques and including, for example, by injection, such as subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subepidermal, intraarticular, subarachnoid or intrasternal, e.g., by implanting a depot, e.g., subcutaneously or intramuscularly), pulmonary (e.g., by using an aerosol, e.g., inhalation or insufflation therapy via the mouth or nose), gastrointestinal, intrauterine, intraocular, subcutaneous, ophthalmic (including intravitreal or intracameral), rectal or vaginal administration.

[0509] If the compound or pharmaceutical composition is administered parenterally, examples of such administration include one or more of the following: intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracardiac, intracranial, intramuscular or subcutaneous administration of the compound or pharmaceutical composition, and / or by using infusion techniques. For parenteral administration, the compound is preferably used in the form of a sterile aqueous solution, which may contain other substances, for example, sufficient salts or glucose to render the solution isotonic with blood. If necessary, the aqueous solution should be appropriately buffered (preferably to a pH of 3 to 9). The preparation of suitable parenteral formulations under sterile conditions can be readily accomplished by standard pharmaceutical techniques well known to those skilled in the art.

[0510] The compound or pharmaceutical composition may also be administered orally in the form of tablets, capsules, ovules, elixirs, solutions or suspensions, which may contain flavoring or coloring agents for immediate, delayed, modified, sustained, pulsed or controlled release applications.

[0511] Tablets may contain excipients such as microcrystalline cellulose, lactose, sodium citrate, calcium carbonate, calcium hydrogen phosphate and glycine, disintegrants such as starch (preferably corn, potato or tapioca starch), sodium starch glycolate, croscarmellose sodium and certain complex silicates, and granulating binders such as polyvinylpyrrolidone, hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), sucrose, gelatin and acacia. Additionally, lubricants such as magnesium stearate, stearic acid, glyceryl behenate and talc may be included. Solid compositions of similar types may also be used as fillers in gelatin capsules. In this regard, preferred excipients include lactose, starch, cellulose or high molecular weight polyethylene glycol. For aqueous suspensions and / or elixirs, the agent may combine various sweetening or flavoring agents, coloring substances or dyes with emulsifying and / or suspending agents and with diluents such as water, ethanol, propylene glycol and glycerol and combinations thereof.

[0512] Optionally, the compound or pharmaceutical composition may be administered in the form of suppositories or vaginal suppositories, or may be administered topically in the form of gels, hydrogels, lotions, solutions, creams, ointments or dusting powders. The compounds of the present invention may also be administered transdermally or percutaneous, for example, by using skin patches.

[0513] The compound or pharmaceutical composition may also be administered by a sustained release system. Suitable examples of sustained release compositions include shaped articles such as semipermeable polymer matrices in the form of films or microcapsules. Sustained release matrices include, for example, poly(lactide) (see, e.g., US 3,773,919), copolymers of L-glutamic acid and γ-ethyl-L-glutamic acid (Sidman, U. et al., Biopolymers 22:547-556 (1983)), poly(2-hydroxyethyl methacrylate) (R. Langer et al., J. Biomed. Mater. Res. 15:167-277 (1981) and R. Langer, Chem. Tech. 12:98-105 (1982)), ethylene vinyl acetate (R. Langer et al., Id.) or poly-D-(-)-3-hydroxybutyric acid (EP 133988). Sustained release pharmaceutical compositions also include liposome-encapsulated compounds. Liposomes containing the compounds of the invention can be prepared by methods known in the art, for example, the methods described in any of the following documents: DE 3218121; Epstein et al., Proc. Natl. Acad. Sci. (USA) 82:3688-3692 (1985); Hwang et al., Proc. Natl. Acad. Sci. (USA) 77:4030-4034 (1980); EP 0052322; EP 0036676; EP 088046; EP 0143949; EP 0142641; JP 83-118008; US 4,485,045; US 4,544,545; and EP 0102324.

[0514] The compound or pharmaceutical composition may also be administered by the pulmonary, rectal or ocular routes. For ophthalmic use, they may be formulated as a micronized suspension in isotonic, pH-adjusted sterile saline, or preferably as a solution in isotonic, pH-adjusted sterile saline, optionally in combination with a preservative such as benzalkonium chloride. Optionally, they may be formulated as an ointment such as petrolatum.

[0515] It is also contemplated to prepare dry powder formulations of the compounds of formula (I) for pulmonary administration, in particular inhalation. Such dry powders can be prepared by spray drying under conditions that result in a substantially amorphous glassy state or a substantially crystalline bioactive powder. Thus, the dry powders of the compounds of the present invention can be prepared according to the emulsification / spray drying methods disclosed in WO 99 / 16419 or WO 01 / 85136. Spray drying of the solution formulations of the compounds of the present invention can be carried out as described, for example, in "Spray Drying Handbook", 5th Edition, K. Masters, John Wiley & Sons, Inc., NY (1991), WO 97 / 41833 or WO 03 / 053411.

[0516] For topical application on the skin, the compound or pharmaceutical composition can be formulated into a suitable ointment that contains the active compound suspended or dissolved in a mixture of, for example, one or more of the following: mineral oil, liquid petrolatum, white petrolatum, propylene glycol, emulsifying wax, and water. Optionally, they can be formulated into a suitable lotion or cream that is suspended or dissolved in a mixture of, for example, one or more of the following: mineral oil, sorbitan monostearate, polyethylene glycol, liquid paraffin, polysorbate 60, cetyl ester wax, 2-octyldodecanol, benzyl alcohol, and water.

[0517] Accordingly, the present invention relates to the compounds or pharmaceutical compositions provided herein, wherein the corresponding compound or pharmaceutical composition is administered by any one of the following routes: oral route; topical route, including transdermal, intranasal, intraocular, buccal, or sublingual routes; parenteral route using injection techniques or infusion techniques, including by subcutaneous, intradermal, intramuscular, intravenous, intraarterial, intracardiac, intrathecal, intraspinal, intracapsular, subcapsular, intraorbital, intraperitoneal, intratracheal, subepidermal, intraarticular, subarachnoid, intrasternal, intraventricular, intraurethral, or intracranial routes; pulmonary route, including by inhalation or insufflation therapy; gastrointestinal route; intrauterine route; intraocular route; subcutaneous route; ophthalmic route, including by intravitreal or intracameral routes; rectal route; or vaginal route. Particularly preferred routes of administration are topical administration, oral administration, or parenteral administration. For the treatment or prevention of hyperhidrosis, topical administration is even more preferred.

[0518] Generally, a physician will determine the actual dosage most suitable for an individual subject. The specific dosage level and dosing frequency for any particular individual subject can vary and will depend on a variety of factors, including the activity of the specific compound employed, the metabolic stability and duration of action of the compound, age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular disorder, and the individual subject being treated.

[0519] The proposed but non-limiting dose for oral administration of the compounds according to the invention to a human (body weight approximately 70 kg) can be from 0.05 to 2000 mg per unit dose, in particular from 0.1 mg to 1000 mg of active ingredient. The unit dose can be administered, for example, 1 to 3 times a day. The unit dose can also be administered 1 to 7 times a week, for example not more than once a day. It should be understood that it may be necessary to make routine changes to the dose depending on the age and weight of the patient / subject and the severity of the condition being treated. The exact dose and the route of administration will ultimately be determined by the attending physician or veterinarian.

[0520] The compounds of formula (I) or the pharmaceutical compositions comprising the compounds of formula (I) can be administered in monotherapy (e.g., without the need to administer simultaneously any other therapeutic agent, or without the need to administer simultaneously any other therapeutic agent for the same disease being treated or prevented with the compounds of formula (I)). However, the compounds of formula (I) or the pharmaceutical compositions comprising the compounds of formula (I) can also be administered in combination with one or more other therapeutic agents, such as, for example, one or more other therapeutic agents selected from phenobarbital, sodium phenytoin, valproate (or valproic acid), carbamazepine, lamotrigine, levetiracetam, ethosuximide and pharmaceutically acceptable salts of any of the above agents. If the compounds of formula (I) are used in combination with a second therapeutic agent that is active against the same disease or condition, the dose of each compound may be different from the dose when the respective compound is used alone, specifically, a lower dose of each compound can be used. The combination of the compounds of formula (I) with one or more other therapeutic agents (e.g., one or more of the above-mentioned respective exemplary therapeutic agents) can include the simultaneous / concomitant administration of the compounds of formula (I) and the other therapeutic agent(s) (one or more) (in a single pharmaceutical formulation or in separate pharmaceutical formulations), or the sequential / separate administration of the compounds of formula (I) and the other therapeutic agent(s) (one or more). If the administration is sequential, the compounds of formula (I) according to the invention or one or more other therapeutic agents can be administered first. If the administration is simultaneous, one or more other therapeutic agents can be included in the same pharmaceutical formulation with the compounds of formula (I), or they can be administered in one or more different (separate) pharmaceutical formulations.

[0521] The subject or patient to be treated according to the invention can be an animal (e.g., a non-human animal). Preferably, the subject / patient is a mammal. More preferably, the subject / patient is a human (e.g., male or female) or a non-human mammal (such as, for example, guinea pig, hamster, rat, mouse, rabbit, dog, cat, horse, monkey, ape, lesser ape, baboon, gorilla, chimpanzee, orangutan, gibbon, sheep, cow or pig). Most preferably, the subject / patient to be treated according to the invention is a human.

[0522] As used herein, the term "treatment" of a disorder or disease (e.g., "treatment" of hyperhidrosis) is well known in the art. "Treatment" of a disorder or disease means that a disorder or disease is suspected or has been diagnosed in a patient / subject. A patient / subject suspected of having a disorder or disease typically exhibits certain clinical and / or pathological symptoms that can be readily attributed by a person skilled in the art to a specific pathological condition (i.e., diagnosing the disorder or disease).

[0523] "Treatment" of a disorder or disease can, for example, result in a halt in the progression of the disorder or disease (e.g., the symptoms do not worsen) or a delay in the progression of the disease or disorder (in cases where the halt in progression is only temporary). "Treatment" of a disorder or disease can also result in a partial response (e.g., improvement of symptoms) or a complete response (e.g., disappearance of symptoms) in a subject / patient having the disorder or disease. Thus, "treatment" of a disorder or disease can also refer to an improvement in a condition or disease, which can, for example, result in a halt in the progression of the disorder or disease or a delay in the progression of the disorder or disease. Recurrence may occur after such partial or complete response. It should be understood that a subject / patient can experience a wide range of responses to treatment (such as the exemplary responses described above). Treatment of a disorder or disease can specifically include curative treatment (preferably resulting in complete remission of the condition or disease and ultimately a cure) and palliative treatment (including symptom relief).

[0524] As used herein, the term "prevention" of a disorder or disease (e.g., "prevention" of hyperhidrosis) is also well known in the art. For example, a patient / subject suspected of being prone to a disorder or disease may particularly benefit from prevention of the disorder or disease. A subject / patient may have a sensitivity or susceptibility to a disorder or disease, including but not limited to genetic susceptibility. Such susceptibility can be determined using, for example, genetic markers or phenotypic indicators by standard methods or assays. It should be understood that the disorder or disease to be prevented according to the present invention has not been diagnosed or cannot be diagnosed in a patient / subject (e.g., a patient / subject who does not exhibit any clinical or pathological symptoms). Thus, the term "prevention" includes the use of the compounds of the present invention before any clinical and / or pathological symptoms have been diagnosed or determined or can be diagnosed or determined by the attending physician.

[0525] It should be understood that the present invention particularly relates to all and each combination of the features described herein, including any combination of general and / or preferred features. Specifically, the present invention particularly relates to each combination of the meanings (including general and / or preferred meanings) of the various groups and variables included in formula (I).

[0526] In this specification, numerous documents including patent applications and scientific literature are cited. Although the disclosures of these documents are not considered relevant to the patentability of the present invention, their entire contents are incorporated herein by reference. More specifically, all reference documents are incorporated by reference as if each individual document was specifically and individually indicated to be incorporated by reference.

[0527] The citation in this specification of any prior publication (or information derived therefrom) is not, and should not be taken as, an admission or acceptance or any form of implication that the corresponding prior publication (or information derived therefrom) forms part of the common general knowledge in the technical field to which this specification pertains.

[0528] The present invention specifically relates to the following clauses:

[0529] 1. A compound of any one of the following formulas, or a pharmaceutically acceptable salt or solvate thereof:

[0530]

[0531]

[0532]

[0533]

[0534]

[0535]

[0536]

[0537]

[0538]

[0539] It is used for treating or preventing diseases or disorders involving NKCC.

[0540] 2. A pharmaceutical composition comprising a compound as defined in clause 1 and a pharmaceutically acceptable excipient, which is used for treating or preventing diseases or disorders involving NKCC.

[0541] 3. Use of a compound as defined in clause 1 in the manufacture of a medicament for treating or preventing diseases or disorders involving NKCC.

[0542] 4. A method for treating or preventing diseases or disorders involving NKCC, the method comprising administering a compound as defined in clause 1 or a pharmaceutical composition as defined in clause 2 to a subject in need thereof.

[0543] 5. The method according to clause 4, wherein the subject is a human.

[0544] 6. The compound used according to clause 1, or the pharmaceutical composition used according to clause 2, or the use according to clause 3, or the method according to clause 4 or 5, wherein the disease or disorder involving NKCC is hyperhidrosis.

[0545] 7. The non-therapeutic use of the compound as defined in clause 1 for inhibiting or reducing sweating in a subject.

[0546] 8. A non-therapeutic method for inhibiting or reducing sweating in a subject, wherein the method comprises administering the compound as defined in clause 1 to the subject.

[0547] 9. The non-therapeutic use according to clause 7 or the non-therapeutic method according to clause 8, wherein the compound is administered topically.

[0548] 10. The non-therapeutic use according to clause 7 or 9 or the non-therapeutic method according to clause 8 or 9, wherein the compound is provided in the form of an article comprising the compound, and the article is a wipe, insole or garment.

[0549] 11. An article comprising the compound as defined in clause 1, wherein the article is a wipe, insole or garment.

[0550] 12. The compound used according to clause 1, or the pharmaceutical composition used according to clause 2, or the use according to clause 3, or the method according to clause 4 or 5, wherein the disease or disorder involving NKCC is selected from anxiety disorders, autism spectrum disorders, autism, Asperger's syndrome, childhood disintegrative disorder, pervasive developmental disorder as part of the autism spectrum disorder, traumatic brain injury, spinal cord injury, peripheral nerve injury, stroke, Alzheimer's disease, schizophrenia, asthma, edema, Down syndrome, intellectual disability in Down syndrome patients, glaucoma, primary open-angle glaucoma, angle-closure glaucoma, and parasitic infections,

[0551] wherein the parasitic infections are preferably selected from worm infections, hookworm infections, roundworm infections, whipworm infections, tapeworm infections, guinea worm infections, pinworm infections, Toxocara infections, Strongyloides infections, Ascaris lumbricoides infections, parasitic fluke infections, schistosomiasis, gnathostomiasis, paragonimiasis, fascioliasis, schistosome dermatitis, protozoan infections, malaria, amoebiasis, giardiasis, African trypanosomiasis, toxoplasmosis, Acanthamoeba keratitis, leishmaniasis, babesiosis, granulomatous amoebic encephalitis, cryptosporidiosis, coccidiosis, primary amoebic meningitis, ectoparasite infections, scabies infections, head lice infections, pubic lice infections, human botfly maggot infections, tungiasis, and Ixodidae infections.

[0552] 13. Use of the compound according to clause 1 as an NKCC inhibitor in vitro.

[0553] 14. An in vitro method of inhibiting NKCC, the method comprising administering a compound as defined in clause 1.

[0554] 15. A compound of any of the following formulas or a pharmaceutically acceptable salt or solvate thereof:

[0555]

[0556]

[0557]

[0558]

[0559]

[0560]

[0561]

[0562]

[0563]

[0564] 16. The compound as defined in clause 15, for use as a medicament.

[0565] 17. A pharmaceutical composition comprising a compound as defined in clause 15 and a pharmaceutically acceptable excipient.

[0566] The present invention will now be described by reference to the following examples, which are merely exemplary and should not be construed as limiting the scope of the invention.

[0567] Examples

[0568] The compounds described in this section are defined by their chemical formulas and corresponding chemical names. In the event of any conflict between any chemical formula and the corresponding chemical name indicated herein, the present invention relates to both the compounds defined by the chemical formula and the compounds defined by the chemical name, and particularly to the compounds defined by the chemical formula.

[0569] Example 1: Synthesis of various compounds according to the present invention

[0570] General method

[0571] All chemicals and solvents were purchased in analytical grade from commercial suppliers (Sigma Aldrich, Merck, Apollo Scientific, and TCI Europe). Bumetanide was obtained from OChem Inc., Des Plaines, IL, US.

[0572] To monitor the reactions by thin layer chromatography, silica gel F 254 coated aluminum plates from Merck were used.

[0573] As stationary phase for column chromatography, silica gel 60 70 - 230 mesh ASTM from Merck was used.

[0574] Melting points were measured on a Thermo Galen Kofler hot stage microscope.

[0575] 1H- and 1 1H- and 13 13C-NMR spectra (200 and 50 MHz, respectively) were recorded on a Bruker Advance, and chemical shifts were reported in ppm relative to the solvent residual line or tetramethylsilane as internal standard.

[0576] Mass spectra were recorded on a Shimadzu (GC - 17A; MS - QP5050A) spectrometer. Peak intensities were specified as percentages relative to the largest signal in the spectrum.

[0577] Elemental analyses were performed by Mag. Johannes Theiner at the University of Vienna, and all reported values were within + / - 0.4% of the calculated values.

[0578] Ethyl 3-(butylamino)-4-phenoxy-5-sulfamoyl-benzoate (TEPS1)

[0579]

[0580] Under an argon atmosphere, 11 mmol (0.8 mL) of SOCl2 was added to a suspension of 5 mmol (1.82 g) of bumetanide in 3 mL of EtOH and stirred overnight. After complete conversion (monitored by TLC T / EtOAc 6 + 4), the mixture was extracted several times with 5% NaHCO3, saturated brine, and water. The organic layer was then dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The crude product was recrystallized from ethanol to yield 1.67 g (85%) of TEPS1. 11H NMR (200 MHz, chloroform-d) δ 8.05 - 7.92 (m, 1H), δ 7.66 - 7.54 (m, 1H), δ 7.45 - 7.25 (m, 2H), δ 7.21 - 7.05 (m, 1H), δ 7.00 - 6.89 (m, 2H), δ 4.96 (s, 2H), δ 4.40 (q, J = 7.1 Hz, 2H), δ 4.03 - 3.45 (br s, 1H), δ 3.21 - 3.01 (m, 2H), δ 1.41 (t, J = 7.1 Hz, 3H), δ 1.31 - 1.07 (m, 4H), δ 0.95 - 0.76 (m, 3H).

[0581] N-Benzyl-3-(butylamino)-4-phenoxy-5-sulfamoyl-benzamide (TEPS2)

[0582]

[0583] Dissolve 3 mmol (1.09 g) of bumetanide in 20 ml of dichloromethane and add 3.38 mmol (0.65 g) of EDC·HCl. After 5 minutes, add 3.37 mmol (0.52 g) of HOBt and stir the reaction mixture for another 5 minutes. Then add 3 mmol (328 μl) of benzylamine and stir the reaction mixture at room temperature overnight. Once the reaction is complete, extract it three times with ethyl acetate, wash the combined organic layers with brine and dry over Na2SO4. Then evaporate the solvent under reduced pressure and purify the crude product by column chromatography (toluene / ethyl acetate 6 + 4) and by recrystallization from 50% ethanol. 1 1H-NMR (200 MHz, chloroform-d): δ 7.55 - 7.45 (m, 2H), δ 7.40 - 7.20 (m, 7H), δ 7.14 - 7.02 (m, 1H), δ 6.96 - 6.80 (m, 3H), δ 5.09 (s, 2H), δ 4.59 (d, J = 5.8 Hz, 2H), δ 3.07 (t, J = 6.9 Hz, 2H), δ 1.49 - 1.30 (m, 2H), δ 1.23 - 1.01 (m, 2H), δ 0.79 (t, J = 7.2 Hz, 3H).

[0584] Methyl 3-(butylamino)-5-(dimethylsulfamoyl)-4-phenoxy-benzoate (TEPS 3)

[0585]

[0586] Dissolve 3 mmol (1.09 g) of bumetanide in 5 mL of DMF, and add 9.9 mmol (1.37 g) of K2CO3 and 10 mmol (0.62 mL) of methyl iodide. Stir the reaction mixture for 5 h and pour it into ice water. Filter out the resulting precipitate, and purify the crude product by column chromatography (toluene / ethyl acetate 8 + 2). 1H-NMR (200 MHz, chloroform-d): δ 7.95 (d, J = 1.9 Hz, 1H), δ 7.57 (d, J = 1.9 Hz, 1H), 7.34 - 7.22 (m, 2H), δ 7.06 (t, J = 7.3 Hz, 1H), δ 6.83 (d, J = 7.9 Hz, 2H), δ 3.94 (s, 3H), δ 3.69 (s, 1H), δ 3.10 (t, J = 6.9 Hz, 2H), δ 2.79 (s, 6H), 1.52 - 1.35 (m, 2H), δ 1.26 - 1.06 (m, 2H), δ 0.82 (t, J = 7.2 Hz, 3H).

[0587] 3-(Butylamino)-5-(dimethylaminosulfonyl)-4-phenoxy-benzoic acid (TEPS 4)

[0588]

[0589] Dissolve 3 mmol (1.09 g) of bumetanide in 20 ml of dichloromethane, and then add 3.38 mmol (0.65 g) of EDC.HCl. After 5 min, add 3.37 mmol (0.52 g) of HOBt, and stir the reaction mixture for 5 min. Then add 3.01 mmol (274 μl) of aniline, and stir the reaction overnight at room temperature. Then extract the mixture with ethyl acetate, wash it with saturated NaHCO3 solution, and dry it over Na2SO4. Evaporate the solvent under reduced pressure, and recrystallize the crude product from EtOH to obtain 3-(butylamino)-4-phenoxy-N-phenyl-5-sulfamoyl-benzamide. Dissolve 0.3 mmol (0.265 g) of 3-(butylamino)-4-phenoxy-N-phenyl-5-sulfamoyl-benzamide in 4 mL of methanol and 2 mL of THF. Then add 2 mL of 1M LiOH solution, and stir the mixture at room temperature until the reaction is complete. Acidify the reaction mixture with 2M HCl and extract it 3 times with ethyl acetate. Wash the combined organic layers with brine and dry them over Na2SO4. Then evaporate the solvent under reduced pressure. 1H-NMR (200 MHz, chloroform-d): δ 8.05 (d, J = 2.0 Hz, 1H), δ 7.63 (d, J = 2.0 Hz, 1H), δ 7.37 - 7.24 (m, 2H), δ 7.07 (t, J = 7.3 Hz, 1H), δ 6.91 - 6.79 (m, 2H), δ 3.13 (t, J = 6.9 Hz, 2H), δ 2.81 (s, 6H), δ 1.53 - 1.37 (m, 2H), δ 1.29 - 1.08 (m, 2H), δ 0.83 (t, J = 7.2 Hz, 3H).

[0590] 3-(Butylamino)-5-(chloromethyl)-2-phenoxy-benzenesulfonamide (TEPS 76)

[0591]

[0592] Dissolve 1 mmol (0.35 g) of 3-(butylamino)-5-(hydroxymethyl)-2-phenoxy-benzenesulfonamide (Toellner K et al., Annals of Neurology (2014), 75(4), 550 - 562) in 5 mL of thionyl chloride and heat to 80 °C for three hours. Evaporate the thionyl chloride under reduced pressure and dry the substance in vacuo for 1 hour. Purify the product by recrystallization from 70% MeOH to give 0.34 g of brown crystals (yield 92%). 1 H NMR (200 MHz, chloroform-d) δ 7.43 - 7 - 27 (m, 3H), δ 7.08 (t, J = 7.3 Hz, 1H), δ 7.02 - 6.79 (m, 3H), δ 4.88 (s, 2H) δ 4.57 (s, 2H), δ 3.07 (t, J = 6.9 Hz, 2H), δ 1.54 - 1.33 (m, 2H), δ 1.28 - 1.08 (m, 2H), δ 0.83, J = 7.1 Hz (t, 3H). MS m / z: 368 / 370 M +

[0593] 3-(Butylamino)-2-phenoxy-5-[(2,2,2-trifluoroethylamino)methyl]benzenesulfonamide (TEPS 5)

[0594]

[0595] General procedure A:

[0596] Dissolve 1 mmol (369 mg) of 3-(butylamino)-5-(chloromethyl)-2-phenoxy-benzenesulfonamide (TEPS 76) in 3 mL of dimethylformamide (DMF). Add 2 mmol (157 μl) of 2,2,2-trifluoroethylamine thereto and stir the mixture overnight at room temperature. After verifying the completion of the reaction by thin layer chromatography, evaporate the fluid under reduced pressure to obtain a white crude product. Purify the crude product by column chromatography (ethyl acetate / petroleum ether 6 + 4) and recrystallize from 70% MeOH to obtain 130 mg of white crystals (yield 30%). 1 H NMR (200 MHz, methanol-d4) δ 7.34 - 7.18 (m, 3H), δ 7.09 - 6.96 (m, 2H), δ 6.94 - 6.83 (m, 2H), δ 3.90 (s, 2H), δ 3.29 - 3.17 (m, 2H), δ 3.09 (t, J = 6.8 Hz, 2H), δ 1.49 - 1.32 (m, 2H), δ 1.26 - 1.06 (m, 2H), δ 0.81 (t, J = 7.2 Hz, 3H). MS m / z: 431 M +

[0597] 3-(Butylamino)-5-(morpholinomethyl)-2-phenoxy-benzenesulfonamide (TEPS 6)

[0598]

[0599] Prepare TEPS 6 according to General Procedure A, except that instead of 2,2,2-trifluoroethylamine, 2 mL of morpholine is added. Purify the crude product by column chromatography (ethyl acetate / petroleum ether 1 + 1) and recrystallize from EtOH to obtain 130 mg of beige crystals (yield 31%). 1 H NMR (200 MHz, chloroform-d) δ 7.38 - 7.23 (m, 3H), δ 7.20 - 6.80 (m, 4H), δ 5.10 (s, 2H), δ 3.98 - 3.66 (m, 5H), δ 3.54 (s, 2H), δ 3.16 - 2.98 (m, 2H), δ 2.77 - 2.36 (m, 4H), δ 1.52 - 1.30 (m, 2H), δ 1.27 - 1.08 (m, 2H), δ 0.82 (t, J = 7.1 Hz, 3H). MS m / z: 419 M +

[0600] 3-(Butylamino)-5-(1H-imidazol-2-ylsulfanylmethyl)-2-phenoxy-benzenesulfonamide (TEPS 7)

[0601]

[0602] TEPS 7 was prepared according to General Procedure A, except that 1 mmol (100 mg) of 2-mercaptoimidazole was added instead of 2,2,2-trifluoroethylamine, and the reaction was stirred for two days. The crude product was purified by column chromatography (ethyl acetate / petroleum ether / triethylamine 6 + 3 + 1) and recrystallized from 70% EtOH to give 0.22 g of white crystals (yield 51%). 1 H NMR (200 MHz, chloroform-d) δ 7.36 - 7.21 (m, 2H), δ 7.14 (s, 2H), δ 7.10 - 6.96 (m, 2H), δ 6.94 - 6.80 (m, 2H), δ 6.63 (d, J = 2.0 Hz, 1H), δ 4.17 (s, 2H), δ 2.95 (t, J = 6.8 Hz, 2H), δ 1.42 - 1.26 (m, 2H), δ 1.22 - 1.02 (m, 2H), δ 0.80 (t, J = 7.2 Hz, 3H). MS m / z: 432 M +

[0603] 3-(Butylamino)-2-phenoxy-5-(pyrimidin-2-ylsulfanylmethyl)benzenesulfonamide (TEPS 8)

[0604]

[0605] TEPS 8 was prepared according to General Procedure A, except that 1 mmol (112 mg) of 2-mercaptopyrimidine was added instead of 1,2,2,2-trifluoroethylamine. The crude product was purified by column chromatography (ethyl acetate / petroleum ether 7 + 3) and recrystallized from 70% MeOH to give 210 mg of white crystals (yield 47%). 1 H NMR (200 MHz, chloroform-d) δ 8.55 (d, J = 4.8 Hz, 2H), δ 7.38 (d, J = 1.8 Hz, 1H), δ 7.35 - 7.23 (m, 2H), δ 7.18 - 6.83 (m, 5H), δ 4.90 (s, 2H), δ 4.41 (s, 2H), δ 3.80 (t, J = 5.3 Hz, 1H), δ 3.17 - 2.91 (m, 2H), δ 1.49 - 1.31 (m, 2H), δ 1.26 - 1.05 (m, 2H), δ 0.81 (t, J = 7.1 Hz, 3H). MS m / z: 444 M +

[0606] 3-(Butylamino)-5-[(1-methylimidazol-2-yl)sulfanylmethyl]-2-phenoxy-benzenesulfonamide (TEPS9)

[0607]

[0608] TEPS 9 was prepared according to General Procedure A, except that 1 mmol (114 mg) of 2-mercapto-1-methylimidazole was added instead of 2,2,2-trifluoroethylamine. The crude product was purified by column chromatography (ethyl acetate / petroleum ether / triethylamine 6 + 3 + 1) and recrystallized from 70% MeOH to give 180 mg of white crystals (yield 40%). 1 H NMR (200 MHz, chloroform-d) δ 7.33 - 7.08 (m, 5H), δ 7.07 - 6.91 (m, 3H), δ 6.81 (d, J = 7.7 Hz, 2H), δ 6.65 (d, J = 1.7 Hz, 1H), δ 4.75, (t, J = 5.7 Hz, 1H), δ 4.17 (s, 2H), δ 3.43 (s, 3H), δ 2.98 - 2.81 (m, 2H), δ 2.98 - 2.81 (m, 2H), δ 1.17 - 0.99 (m, 2H), δ 0.77 (t, J = 7.1 Hz, 3H). MS m / z: 446 M +

[0609] 3-(Butylamino)-5-(1-hydroxy-1-methylethyl)-2-phenoxy-benzenesulfonamide (TEPS10)

[0610]

[0611] To a solution of 4 mmol of methyl 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoate (WO 2013 / 087090) in 10 mL of dry THF was added 15 ml of methylmagnesium bromide solution (1.4 M in THF), and the mixture was stirred at room temperature. An additional 3 mL of methylmagnesium bromide solution (1.4 M in THF) was added at 30-minute intervals for a total of 5 times. After stirring for a total of three hours, the mixture was quenched with aqueous 5% NH4Cl, which resulted in the precipitation of a white solid. The mixture was then extracted with ethyl acetate, washed twice with water, and once with brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The resulting crude product was purified by column chromatography (EtOAc / petroleum ether 1 + 1) and recrystallized from 70% EtOH to give 1.06 g of a brown solid (yield 70%). 11H NMR (200 MHz, chloroform-d) δ 7.40 - 7.21 (m, 3H), CH (aromatic), δ 7.17 - 6.99 (m, 2H), δ 6.99 - 6.83 (m, 2H), δ 5.07 (s, 2H), δ 3.78 (t, J = 5.1 Hz, 1H), δ 3.16 - 2.97 (m, 2H), δ 2.33 (s, 1H), δ 1.57 (s, 6H), δ 1.49 - 1.32 (m, 2H), δ 1.29 - 1.10 (m, 2H), δ 0.81 (t, J = 7.1 Hz, 3H). MS m / z: 378 M +

[0612] 3-(Butylamino)-5-isopropenyl-2-phenoxy-benzenesulfonamide (TEPS11)

[0613]

[0614] 0.5 mmol of TEPS10 was dissolved in 5 mL of thionyl chloride, and the mixture was stirred for one day. After the reaction was completed, the thionyl chloride was evaporated under reduced pressure. The resulting crude product was purified by column chromatography (ethyl acetate / petroleum ether 1 + 1) and recrystallized from 70% EtOH to give 120 mg of a beige solid (yield 67%). 1 1H NMR (200 MHz, chloroform-d) δ 7.44 - 7.27 (m, 3H), δ 7.12 - 6.90 (m, 4H), δ 5.39 (s, 1H), δ 5.23 - 5.10 (m, 1H), δ 4.89 (s, 2H), δ 3.78 (t, J = 5.3 Hz, 1H), δ 3.16 - 3.00 (m, 2H), δ 2.17 (s, 3H), δ 1.51 - 1.35 (m, 2H), δ 1.24 - 1.11 (m, 2H), δ 0.83 (t, J = 7.2 Hz, 3H). MS m / z: 360 M +

[0615] 3-(Butylamino)-5-[(4-hydroxy-4-phenyl-1-piperidinyl)methyl]-2-phenoxy-benzenesulfonamide (TEPS12)

[0616]

[0617] TEPS12 was prepared according to General Procedure A, except that instead of 2,2,2-trifluoroethylamine, 1.2 mmol (213 mg) of 4-hydroxy-4-phenylpiperidine was added and the mixture was stirred at room temperature for two days. The crude product was purified by column chromatography (EtOAc / petroleum ether 1 + 1) and recrystallized from 70% MeOH to give 210 mg of white crystals (yield 41%). 11H NMR (200 MHz, chloroform-d) δ 7.64 - 7.46 (m, 2H), δ 7.41 - 7.25 (m, 6H), δ 7.16 - 6.85 (m, 4H), δ 4.95 (s, 2H), δ 5.21 - 4.72 (m, 1H), δ 3.57 (s, 2H), δ = 3.20 - 2.99 (m, 2H), δ 2.97 - 2.72 (m, 2H), δ 2.53 (t, J = 10.8 Hz, 2H), δ 2.32 - 2.02 (m, 2H), δ 1.88 - 1.61 (m, 3H), δ 1.51 - 1.32 (m, 2H), δ 1.28 - 1.12 (m, 2H), δ 0.83 (t, J = 7.1 Hz, 3H). MS m / z: 510 M +

[0618] 3-(Butylamino)-5-[(cyanomethylamino)methyl]-2-phenoxy-benzenesulfonamide (TEPS13)

[0619]

[0620] TEPS13 was prepared according to General Procedure A, except that 1.2 mmol (167 μl) of triethylamine and 1.2 mmol (71 μl) of aminoacetonitrile were added instead of 2,2,2-trifluoroethylamine. The crude product was purified by column chromatography (EtOAc / petroleum ether 1 + 1) and recrystallized from 70% EtOH to give 180 mg of a beige powder (yield 46%). 1 1H NMR (200 MHz, chloroform-d) δ 7.40 - 7.22 (m, 3H), δ 7.16 - 6.85 (m, 4H), δ 5.02 (s, 2H), δ 3.91 (s, 2H), δ 3.88 - 3.78 (m, 1H), δ 3.60 (s, 2H), δ 3.20 - 3.00 (m, 2H), δ 2.99 - 2.83 (d, 1H), δ 1.49 - 1.34 (m, 2H), δ 1.26 - 1.12 (m, 2H), δ 0.90 - 0.74 (m, 3H). MS m / z: 388 M +

[0621] 3-(Butylamino)-2-phenoxy-5-[(4-phenyl-3,6-dihydro-2H-pyridin-1-yl)methyl]benzenesulfonamide (TEPS14)

[0622]

[0623] TEPS14 was prepared according to General Procedure A, except that 1.2 equivalents of 4-phenyl-1,2,3,6-tetrahydropyridine were added instead of 2,2,2-trifluoroethylamine. The resulting crude product was purified by column chromatography (ethyl acetate / petroleum ether 3+7) to afford 110 mg of TEPS14 (yield 29.3%). 1 H NMR (200 MHz, chloroform-d) δ 7.54 - 7.21 (m, 9H), δ 7.07 (t, J = 7.5 Hz, 1H), δ 7.00 - 6.83 (m, 2H), δ 6.07 (s, 1H), δ 5.06 (s, 2H), δ 4.00 - 3.72 (m, 3H), δ 3.50 - 3.28 (m, 2H), δ 3.17 - 3.03 (m, 2H), δ 3.00 - 2.80 (m, 2H), δ 2.80 - 2.56 (m, 2H), δ 1.54 - 1.32 (m, 2H), δ 1.28 - 1.06 (m, 2H), δ 0.81 (t, J = 7.1 Hz, 3H). MS m / z: 491 M +

[0624] N'-[3-(butylamino)-2-phenoxy-5-[(2-thiophenemethylamino)methyl]phenyl]sulfonyl-N,N-dimethyl-formamidine hydrochloride (TEPS15)

[0625]

[0626] 3-(Butylamino)-2-phenoxy-5-[(2-thiophenemethylamino)methyl]benzenesulfonamide was prepared according to General Procedure A, except that 1 mmol (104 μl) of 2-thiophenemethylamine was added instead of aniline. The crude product was purified by column chromatography (ethyl acetate / petroleum ether 1+1) and recrystallized from 70% EtOH to afford 0.23 g of beige crystals (yield 52%). 0.22 mmol (0.100 g) of 3-(butylamino)-2-phenoxy-5-[(2-thiophenemethylamino)methyl]benzenesulfonamide was dissolved in 5 ml of dry THF, and 0.48 mmol (0.068 mL) of DMF-DMA was added. The reaction was stirred overnight and purified by column chromatography (ethyl acetate). The resulting brown solid was then dissolved in dry THF, and 3 ml of 1 M diethyl ether HCl solution was added. The precipitated HCl salt was filtered off to afford beige crystals (yield 37.5%). 11H NMR (200 MHz, chloroform-d) δ 10.36 (s, 1H), δ 7.91 (s, 1H), δ 7.49 (d, J = 11.9 Hz, 3H), δ 7.37 - 7.20 (m, 3H), δ 7.11 - 6.70 (m, 4H), δ 4.30 (s, 2H), δ 4.10 (s, 2H), δ 3.74 (t, J = 6.6 Hz, 1H), δ 3.13 (s, 2H), δ 2.70 (d, J = 43.2 Hz, 6H), δ 2.00 - 1.70 (m, 1H), δ 1.47 - 1.25 (m, 2H), δ 1.23 - 1.00 (m, 2H), δ 0.76 (t, J = 6.9 Hz, 3H).

[0627] Methyl 3-(butylamino)-5-[2-(dimethylamino)ethylsulfamoyl]-4-phenoxy-benzoate (TEPS16)

[0628]

[0629] Dissolve 0.19 mmol (0.087 g) of methyl 3-(butylamino)-4-phenoxy-5-sulfamoyl-benzoate (WO2013 / 087090) in 5 ml of DMF, and add 1.3 mmol (0.188 g) of 2-dimethylaminoethyl chloride·HCl and 2.2 mmol (0.304 g) of K2CO3. Stir the reaction at 40 °C for two days, and purify the resulting crude product by column chromatography (ethyl acetate / petroleum ether / triethylamine 3 + 6.5 + 0.5) to obtain a white powder (yield 39.6%). 1 1H NMR (200 MHz, chloroform-d) δ 7.95 (d, J = 1.8 Hz, 1H), δ 7.67 - 7.53 (m, 1H), δ 7.29 (t, J = 7.7 Hz, 2H), δ 7.06 (t, J = 7.3 Hz, 1H), δ 6.88 (d, J = 7.8 Hz, 2H), δ 3.93 (s, 3H), δ 3.88 (s, 1H), δ 3.26 - 3.07 (m, 2H), δ 3.05 - 2.90 (m, 2H), δ 2.44 - 2.29 (m, 2H), δ 2.16 (s, 6H), δ 1.51 - 1.35 (m, 2H), δ 1.21 - 1.05 (m, 2H), δ 0.81 (t, J = 7.1 Hz, 3H). MS m / z: 449 M +

[0630] Methyl 3-(butylamino)-5-[2-(dimethylamino)ethylsulfamoyl]-4-phenoxy-benzoate (TEPS17)

[0631]

[0632] TEPS16 was dissolved in dry THF, and 3 ml of 1 M diethyl ether HCl solution was added. The precipitated HCl salt was filtered out to obtain a white powder (yield 92.5%). 1 H NMR (200 MHz, chloroform-d) δ 11.28 (s, 1H), δ 7.88 (s, 1H), δ 7.56 (s, 1H), δ 7.33 - 7.19 (m, 3H), δ 7.02 (t, J = 8.1 Hz, 2H), δ 3.93 (s, 3H), δ 3.31 (d, J = 22.4 Hz, 4H), δ 3.09 (t, J = 6.8 Hz, 2H), δ 2.83 (s, 6H), δ 1.52 - 1.32 (m, 2H), δ 1.28 - 1.07 (m, 2H), δ 0.81 (t, J = 7.1 Hz, 3H).

[0633] 5-(Anilinomethyl)-3-(butylamino)-N-[2-(dimethylamino)ethyl]-2-phenoxy-benzenesulfonamide (TEPS18)

[0634]

[0635] 0.5 mmol (0.213 g) of 5-(anilinomethyl)-3-(butylamino)-2-phenoxy-benzenesulfonamide (Lykke K et al., British Journal of Pharmacology (2015), 172(18), 4469 - 4480) was dissolved in 5 ml of DMF, and 2 mmol (0.288 g) of 2-dimethylaminoethyl chloride.HCl and 2 mmol (0.278 g) of K2CO3 were added. The reaction was stirred overnight at 40 °C, and the resulting crude product was purified by column chromatography (ethyl acetate / petroleum ether / triethylamine 3 + 6.5 + 0.5) to obtain a brown solid (yield 38.3%). 1 H NMR (200 MHz, chloroform-d) δ 7.42 - 7.09 (m, 6H), δ 7.08 - 6.84 (m, 4H), δ 6.83 - 6.58 (m, 3H), δ 5.33 (s, 1H), δ 4.33 (s, 2H), δ 3.83 (t, J = 5.3 Hz, 1H), δ 3.13 - 3.00 (m, 2H), δ 2.99 - 2.87 (m, 2H), δ 2.38 - 2.27 (m, 2H), δ 2.17 (s, 6H), δ 1.41 - 1.27 (m, 2H), δ 1.19 - 1.03 (m, 2H), δ 0.79 (t, J = 7,1 Hz, 3H). MS m / z: 496 M +

[0636] 3-(Butylamino)-5-(ethoxymethyl)-2-phenoxy-benzenesulfonamide (TEPS19)

[0637]

[0638] Dissolve 0.27 mmol (100 mg) of TEPS 76 in acetonitrile and add 0.44 mmol (34 μl) of sodium ethoxide. Stir the reaction mixture overnight at room temperature and then add an additional 0.15 mmol (12 μl) of sodium ethoxide. After the reaction is complete, add 5% aqueous NaHCO3 and extract the mixture with ethyl acetate. Wash the combined organic layers with brine, dry over Na2SO4 and concentrate under reduced pressure. Purify the resulting crude product by recrystallization from EtOH to give 38 mg of a brown solid (yield 22.7%). 1 1H NMR (200 MHz, chloroform-d) δ 7.39 - 7.23 (m, 3H), δ 7.20 - 6.80 (m, 4H), δ 4.92 (s, 2H), δ 4.49 (s, 2H), δ 3.59 (q, J = 7.0 Hz, 2H), δ 3.05 (t, J = 7.0 Hz, 2H), δ 1.52 - 1.33 (m, 2H), δ 1.27 (t, J = 7.0 Hz, 3H), δ 1.23 - 1.05 (m, 2H), δ 0.81 (t, J = 6.8 Hz, 3H). MS m / z: 378 M +

[0639] 3-(Butylamino)-2-phenoxy-5-(phenoxymethyl)benzenesulfonamide (TEPS20)

[0640]

[0641] Dissolve 0.64 mmol (60 mg) of phenol in 5 mL of DMF and add 0.54 mmol (200 mg) of TEPS 76 in three portions over 15 minutes. Stir the reaction overnight at room temperature. After the reaction is complete, add 5% aqueous NaHCO3 and extract the mixture three times with ethyl acetate. Wash the combined organic layers with brine, dry over Na2SO4 and concentrate under reduced pressure. Purify the resulting crude product by column chromatography (ethyl acetate / petroleum ether 3+7) to give 43 mg of TEPS20 (yield 15.6%). 11H NMR (200 MHz, chloroform-d) δ 7.62 - 7.20 (m, 6H), δ 7.19 - 6.83 (m, 6H), δ 5.04 (s, 2H), δ 4.94 (s, 2H), δ 3.04 (t, J = 6.8 Hz, 2H), δ 1.53 - 1.30 (m, 2H), δ 1.29 - 1.01 (m, 2H), δ 0.81 (t, J = 6.0 Hz, 3H). MS m / z: 426 M +

[0642] 3-(Butylamino)-2-phenoxy-5-(4-phenyl-3,6-dihydro-2H-pyridine-1-carbonyl)benzenesulfonamide (TEPS21)

[0643]

[0644] 1 mmol (364 mg) of bumetanide and 1.1 mmol (179 mg) of CDI were added to dry THF. Once a clear solution was formed, 1.3 mmol (200 mg) of 4-phenyl-1,2,3,6-tetrahydropyridine was added and the reaction was stirred overnight at room temperature. After the reaction was completed, 5% aqueous NaHCO3 was added and the mixture was extracted 3 times with ethyl acetate. The combined organic layers were washed with brine, dried over NaHCO3 and concentrated under reduced pressure. The resulting crude product was recrystallized from EtOH to give 294 mg of a white powder (yield 58%). 1 1H NMR (200 MHz, chloroform-d) δ 7.59 - 7.21 (m, 8H), δ 7.20 - 6.79 (m, 4H), δ 6.39 - 5.78 (m, 1H), δ 5.16 (s, 2H), δ 4.47 - 4.07 (m, 2H), δ 4.02 - 3.61 (m, 2H), δ 3.05 (t, J = 6.8 Hz, 2H), δ 2.63 (s-br, 2H), δ 1.52 - 1.29 (m, 2H), δ 1.29 - 1.03 (m, 2H), δ 0.80 (t, J = 7.1 Hz, 3H). MS m / z: 505 M +

[0645] 3-(Butylamino)-5-[2-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]ethoxymethyl]-2-phenoxy-benzenesulfonamide (TEPS22)

[0646]

[0647] Dissolve 0.27 mmol (100 mg) of TEPS 76 in 3 mL of dry THF, then add 22 mg of NaH and 63 μL of tetraethyleneglykole. After the reaction is complete, add an aqueous solution of 5% NaHCO3, and extract the mixture three times with ethyl acetate. Wash the combined organic layers with brine, dry over Na2SO4 and concentrate under reduced pressure. Purify the resulting crude product by column chromatography (ethyl acetate / petroleum ether 3 + 7) to obtain 40 mg of TEPS22 (yield 27%). 1 1H NMR (200 MHz, chloroform-d) δ 7.28 - 7.14 (m, 3H), δ 7.06 - 6.73 (m, 4H), δ 5.19 (s, 2H), δ 4.46 (s, 2H), δ 3.86 - 3.39 (m, 14H), δ 3.27 (m, 2H), δ 2.97 (t, J = 6.8 Hz, 2H), δ 1.54 - 0.97 (m, 7H), δ 0.74 (t, J = 7.2 Hz, 3H). MS m / z: 540 M +

[0648] 3-(Butylamino)-4-phenoxy-5-sulfamoyl-N-(2,2,2-trifluoroethyl)benzamide (TEPS23)

[0649]

[0650] To a solution of 1 mmol (364 mg) of bumetanide in 5 mL of dry THF, add 1.2 mmol (194 mg) of 1,1-carbonyldiimidazole (CDI), and stir the mixture for 2 hours. Once TLC shows that no bumetanide remains, add 2 mmol (157 μL) of trifluoroethylamine, and stir the mixture overnight at room temperature. Once the reaction is complete, pour it into 20 mL of 5% NaHCO3 and extract with ethyl acetate. Then dry the organic phase over Na2SO4 and remove the solvent under reduced pressure. Then purify the crude product by recrystallization from EtOH to obtain 159 mg of a white powder (yield 36%). 1 1H NMR (200 MHz, methanol-d4) δ 7.73 (d, J = 2.1 Hz, 1H), 7.44 (d, J = 2.1 Hz, 1H), 7.38 - 7.20 (m, 2H), 7.14 - 6.98 (m, 1H), 6.98 - 6.86 (m, 2H), 4.10 (q, J = 9.3 Hz, 2H), 3.13 (t, J = 6.8 Hz, 2H), 1.56 - 1.34 (m, 2H), 1.30 - 1.03 (m, 3H), 0.82 (t, J = 7.2 Hz, 3H). MS m / z: 445 M +

[0651] 4-Morpholino-3-nitro-5-sulfamoyl-benzoic acid (TEPS24)

[0652]

[0653] 1 mmol (280 mg) of 4-chloro-3-nitro-5-sulfamoylbenzoic acid was dissolved in 2 mL of morpholine and refluxed overnight with stirring. Once the reaction was complete, the crude product was purified by recrystallization from water to afford 222 mg of yellow crystals (yield 67%). 1 H NMR (200 MHz, DMSO-d6) δ 14.02 (s, 1H), δ 8.86 - 8.71 (m, 1H), δ 8.61 - 8.43 (m, 1H), δ 7.69 (s, 2H), δ 4.18 - 3.57 (m, 4H), δ 3.28 - 3.07 (m, 4H).

[0654] Methyl 3-[(E)-dimethylaminomethyleneamino]sulfonyl-5-nitro-4-(prop-2-ynylamino)benzoate (TEPS25)

[0655]

[0656] 1 mmol (350 mg) of TEPS28 was dissolved in 5 mL of acetonitrile, and 2 mmol (276 mg) of K2CO3 and 1.1 mmol (70 μl) of propargylamine were added. The mixture was stirred overnight, and after TLC showed no remaining TEPS28, it was extracted with ethyl acetate and washed with brine. The combined organic layers were evaporated under reduced pressure, and the resulting brown solid was recrystallized from 70% ethanol to afford 108 mg of brown crystals (yield 30%). 1 H NMR (200 MHz, DMSO-d6) δ 8.53 - 8.39 (m, 2H), δ 8.31 (s, 1H), δ 7.29 (t, J = 5.6 Hz, 1H), δ 4.31 - 4.07 (m, 2H), δ 3.85 (s, 3H), δ 3.32 (s, 1H), δ 3.26 (t, J = 2.3 Hz, 1H), δ 3.15 (s, 1H), δ 2.94 (s, 1H).

[0657] Methyl 3-(dibutylamino)-4-phenoxy-5-sulfamoyl-benzoate (TEPS26) (WO 2013 / 087090)

[0658]

[0659] 2 mmol (228 μl) of butyraldehyde was added to a solution of 1 mmol of methyl 3-(butylamino)-4-phenoxy-5-sulfamoylbenzoate (WO 2013 / 087090) in 10 mL of 1,2-dichloroethane. 1.5 mmol (87 μl) of acetic acid was added to this solution. The reaction mixture was cooled to 0 °C, and 3 mmol (0.64 g) of sodium triacetoxyborohydride (NaBH(OAc)3) was added over 2 hours, and the mixture was stirred overnight. After the reaction was complete, 10 mL of water was added and it was stirred for 1 hour. The reaction mixture was extracted with 20 mL of dichloromethane and washed with brine. The organic phase was then dried over Na2SO4 and evaporated under reduced pressure. The crude product was purified by column chromatography (ethyl acetate / petroleum ether 7+3) and recrystallized from EtOH to give 223 mg of white crystals (yield 51%). 1 H NMR (200 MHz, chloroform-d) δ 8.23 (d, J = 1.2 Hz, 1H), δ 7.87 (s, 1H), 7.37 - 7.15 (m, 2H), δ 7.14 - 6.97 (m, 1H), δ 6.93 - 6.73 (m, 2H), δ 4.99 (s, 2H), δ 4.12 - 3.79 (m, 3H), δ 3.02 (t, J = 7.2 Hz, 4H), δ 1.35 - 1.09 (m, 4H), δ 1.10 - 0.92 (m, 4H), δ 0.77 (t, J = 6.8 Hz, 6H). MS m / z: 434 M +

[0660] 3-(Dibutylamino)-5-(hydroxymethyl)-2-phenoxy-benzenesulfonamide (TEPS27) (WO 2013 / 087090)

[0661]

[0662] 1 mmol of TEPS26 was dissolved in 5 mL of anhydrous THF and stirred at room temperature under an argon atmosphere. Then 2 mL of a toluene solution of 1 M DIBAL-H was added. After 1, 2, 3, and 4 hours, an additional 1 mL of a toluene solution of 1 M DIBAL-H was added each time, and the reaction was stirred overnight. After TLC showed no remaining TEPS26, the mixture was cooled to 0 °C and quenched with 5% aqueous NH4Cl, resulting in the precipitation of a gelatinous material. The precipitate was then dissolved in 2N HCl and extracted 3 times with ethyl acetate. The combined organic layers were washed three times with water, once with brine, and dried over Na2SO4. The fluid was evaporated under reduced pressure and purified by recrystallization from ethanol to give 360 mg of a beige powder (yield 89%). 11H NMR (200 MHz, methanol-d4) δ 7.63 (brs, 1H), δ 7.40 (brs, 1H), 7.32 - 7.14 (m, 2H), δ 7.00 (t, J = 7.3 Hz, 1H), δ 6.82 (d, J = 7.5 Hz, 2H), δ δ 4.66 (s, 2H), 3.13 (t, J = 7.4 Hz, 4H), δ 1.43 - 0.92 (m, 8H), δ 0.78 (t, J = 7.0 Hz, 6H). MS m / z: 406 M +

[0663] 3-(Butylamino)-5-[(n-butylanilino)methyl]-2-phenoxy-benzenesulfonamide (TEPS28)

[0664]

[0665] 2 mmol (180 μl) of butyraldehyde was added to a solution of 1 mmol of 5-(anilinomethyl)-3-(butylamino)-2-phenoxy-benzenesulfonamide (Lykke K et al., British Journal of Pharmacology (2015), 172(18), 4469 - 4480) in 10 mL of 1,2-dichloroethane. 2 mmol (116 μl) of acetic acid and 3 mmol (0.64 g) of sodium triacetoxyborohydride (NaBH(OAc)3) were added to this solution, and the mixture was stirred overnight. The mixture was then diluted with 10 mL of water and 20 mL of dichloromethane. The organic phase was dried over Na2SO4 and then evaporated under reduced pressure. The crude product obtained was purified by column chromatography (ethyl acetate / petroleum ether 7 + 3) to give 312 mg of a white powder (yield 58%). 1 1H NMR (200 MHz, chloroform-d) δ 7.89 (s, 1H), 7.45 - 7.15 (m, 5H), δ 7.00 (t, J = 7.3 Hz, 1H), δ 6.89 - 6.59 (m, 6H), δ 4.52 (s, 2H), δ 3.41 (t, J = 7.6 Hz, 2H), δ 2.88 (t, J = 7.0 Hz, 2H), δ 2.75 (s, 3H), δ 2.58 (s, 3H), δ 1.64 (s, 1H), δ 1.49 - 1.17 (m, 6H), δ 1.18 - 0.87 (m, 4H), δ 0.73 (t, J = 7.2 Hz, 3H). MS m / z: 536 M +

[0666] 3-(Dibutylamino)-4-phenoxy-5-sulfamoyl-benzoic acid (TEPS29) (WO 2013 / 087090)

[0667]

[0668] Dissolve 1 mmol (434 mg) of TEPS26 in 3 mL of MeOH and add 2 mL of 2N NaOH. Stir the reaction at room temperature for 2 h. After TLC showed no remaining TEPS26, the solution was acidified with 2N HCl and the resulting precipitate was filtered out and dried under vacuum to give 380 mg of a white powder (90% yield). 1 H NMR (200 MHz, methanol-d4) δ 8.22 (d, J = 2.0 Hz, 1H), δ 7.91 (d, J = 2.1 Hz, 1H), δ 7.37 - 7.15 (m, 2H), δ 7.02 (t, J = 7.3 Hz, 1H), δ 6.83 (d, J = 7.5 Hz, 2H), δ 3.10 (t, J = 7.2 Hz, 4H), δ 1.38 - 1.15 (m, 4H), δ 1.13 - 0.93 (m, 4H), δ 0.78 (t, J = 7.1 Hz, 6H).

[0669] Methyl 7-[(E)-dimethylaminomethyleneamino]sulfonyl-2-methyl-1-prop-2-ynyl-1H-benzo[d]imidazole-5-carboxylate (TEPS 30)

[0670]

[0671] Add 1 mmol of TEPS25 (368 mg) to 15 mL of ethanol and 3 mL of di ane. Heat the mixture to 85 °C and stir until it is completely dissolved. Then add 10 mmol of ammonium chloride (535 mg) in 6 mL of water. Add 4 mmol of iron powder (223 mg) in three portions at 2 min intervals. Stir the reaction at 85 °C for an additional 2.5 h until TEPS25 could no longer be detected by TLC. Cool the mixture to 60 °C and then extract it three times with 25 mL of dichloromethane. Wash the combined organic layers with water and brine and dry over Na2SO4. Purify the crude product by flash chromatography (ethyl acetate) and recrystallize from methanol to give 90 mg of white crystals (25% yield). 1 H NMR (200 MHz, chloroform-d) δ 8.56 (s, 1H), δ 8.48 (s, 1H), δ 8.16 (s, 1H), δ 5.80 (d, J = 2.5 Hz, 2H), δ 3.95 (s, 3H), δ 3.15 (s, 3H), δ 3.12 (s, 3H), δ 2.85 (s, 3H), δ 2.38 (t, J = 5.0, 2.5 Hz, 2H). MS m / z: 362 M +

[0672] Methyl 4-(butylamino)-3-[(E)-dimethylaminomethyleneamino]sulfonyl-5-nitrobenzoate (TEPS31)

[0673]

[0674] To a suspension of 3 mmol (842 mg) of 4-chloro-3-nitro-5-sulfamoylbenzoic acid in 3 mL of H2O was carefully added 10.8 mmol (907 mg) of NaHCO3, followed by 6 mmol (595 μl) of butylamine. The resulting solution was stirred at 85 °C for 16 h. After completion of the reaction, 10 mL of H2O was added and then the mixture was acidified by adding 2N HCl. The mixture was then cooled and the precipitate was filtered off to afford 825 mg of white crystals (yield 86.6%). 1 H NMR (200 MHz, chloroform-d) δ 8.56 (d, J = 2.2 Hz, 1H), 8.43 (d, J = 2.2 Hz, 1H), 8.10 (s, 1H), 7.03 (s, 1H), 3.89 (s, 3H), 3.18 (s, 3H), 3.05 (s, 3H), 3.02 - 2.90 (m, 2H), 1.77 - 1.57 (m, 2H), 1.55 - 1.35 (m, 2H), 0.93 (t, J = 7.1 Hz, 3H). 13 C NMR (50 MHz, CDCl3) δ 164.7, 159.1, 143.7, 136.8, 133.1, 132.2, 129.5, 116.1, 52.3, 46.6, 41.8, 35.8, 32.1, 19.9, 13.7. MS m / z: 387 M +

[0675] Methyl 3-[(E)-dimethylaminomethyleneamino]sulfonyl-4-(1-methylimidazol-2-yl)thio-5-nitrobenzoate (TEPS 32)

[0676]

[0677] To 10 ml of acetonitrile were added 3 mmol (1.05 g) of methyl 4-chloro-3-[(E)-dimethylaminomethyleneamino]sulfonyl-5-nitro-benzoate (WO 2012 / 018635), 3.3 mmol (376 mg) of 2-mercapto-1-methylimidazole and 6.6 mmol (910 mg) of K2CO3. The solution was stirred overnight at room temperature. When TLC showed no remaining methyl 4-chloro-3-[(E)-dimethylaminomethyleneamino]sulfonyl-5-nitro-benzoate, the reaction mixture was diluted with 10 ml of water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4 and evaporated under reduced pressure. The crude product was then purified by recrystallization from ethanol to give 1.04 g of yellow crystals (yield 81%). 1 1H NMR (200 MHz, DMSO-d6) δ 8.66 (d, J = 1.9 Hz, 1H), δ 8.34 (d, J = 1.8 Hz, 2H), δ 7.28 (s, 1H), δ 6.87 (s, 1H), δ 3.91 (s, 3H), 3.51 (s, 3H), δ 3.10 (s, 3H), δ 2.92 (s, 3H). MS m / z: not found

[0678] Methyl 3-amino-5-[(E)-dimethylaminomethyleneamino]sulfonyl-4-(1-methylimidazol-2-yl)thio-benzoate (TEPS 33)

[0679]

[0680] 1 mmol of TEPS 32 (428 mg) was added to 15 mL of ethanol and 3 mL of di ane. The mixture was heated to 85 °C and stirred until it was completely dissolved. Then 10 mmol of ammonium chloride (535 mg) in 6 mL of water was added. In three portions, 4 mmol of iron powder (223 mg) was added at 2-minute intervals. The reaction was stirred at 85 °C for a further 2.5 h until TEPS 32 could no longer be detected by TLC. The mixture was cooled to 60 °C and then extracted three times with 25 mL of dichloromethane. The combined organic layers were washed with water and brine and dried over Na2SO4. The crude product was purified by flash chromatography (ethyl acetate) to give 290 mg of a yellow solid (yield 73%). 11H NMR (200 MHz, DMSO-d6) δ 8.25 (s, 1H), δ 7.79 (d, J = 1.9 Hz, 1H), δ 7.50 (d, J = 2.0 Hz, 1H), δ 7.27 (d, J = 1.3 Hz, 1H), δ 6.93 (d, J = 1.3 Hz, 1H), δ 6.07 (s, 2H), 3.85 (s, 3H), δ 3.54 (s, 3H), δ 3.10 (s, 3H), δ 2.85 (s, 3H). MS m / z: EI-MS not possible

[0681] Methyl 3-(butylamino)-5-[(E)-dimethylaminomethyleneamino]sulfonyl-4-(1-methylimidazol-2-yl)thio-benzoate (TEPS 34)

[0682]

[0683] 2 mmol (228 μl) of butyl iodide was added to a solution of 1 mmol of TEPS 33 in 10 mL of 1,2-dichloroethane. 1.5 mmol (87 μl) of acetic acid was added to this solution. Then 3 mmol (0.64 g) of sodium triacetoxyborohydride (NaBH(OAc)3) was added over 2 h, and the mixture was stirred overnight. After completion of the reaction, it was poured into 30 ml of water. The reaction mixture was extracted twice with 20 mL of dichloromethane, and the combined organic layers were washed with brine. The organic phase was then dried over Na2SO4 and evaporated under reduced pressure. The crude product was purified by column chromatography (ethyl acetate) to give 234 mg of a yellow powder (yield 52%). 1 1H NMR (200 MHz, chloroform-d) δ 8.16 (s, 1H), δ 8.09 (d, J = 1.8 Hz, 1H), δ 7.36 (d, J = 1.8 Hz, 1H), δ 7.10 (d, J = 1.4 Hz, 1H), δ 6.96 (d, J = 1.4 Hz, 1H), δ 5.79 (s, 1H), δ 3.91 (s, 3H), δ 3.59 (s, 3H), δ 3.10 (d, J = 17.3 Hz, 8H), δ 1.62 - 1.44 (m, 2H), δ 1.43 - 1.15 (m, 2H), δ 0.92 (t, J = 7.2 Hz, 3H). MS m / z: 453 M +

[0684] 3-(Butylamino)-4-(1-methylimidazol-2-yl)thio-5-sulfamoyl-benzoic acid (TEPS 35)

[0685]

[0686] Dissolve 1 mmol (454 mg) of TEPS 34 in 3 ml of MeOH, and add 2 ml of 2N NaOH. Stir the reaction at room temperature for 2 hours. After TLC shows no remaining TEPS 34, acidify the solution with 2N HCl, filter out the resulting precipitate, and recrystallize from EtOH to obtain 346 mg of yellow crystals (yield 90%). 1 H NMR (200 MHz, methanol-d4) δ 8.78 (s, 1H), δ 8.03 (dd, J = 4.7, 1.7 Hz, 1H), δ 7.56 (s, 1H), δ 7.37 (s, 1H), δ 7.18 (s, 1H), δ 3.69 (s, 3H), δ 3.28 - 3.10 (m, 2H), δ 1.68 - 1.43 (m, 2H), δ 1.41 - 1.18 (m, 2H), δ 0.92 (t, J = 6.9 Hz, 3H). MS: Not possible in EI

[0687] Methyl 4-(4,5-dihydrothiazol-2-ylthio)-3-[(E)-dimethylaminomethyleneamino]sulfonyl-5-nitro-benzoate (TEPS 36)

[0688]

[0689] In a three-necked flask, dissolve 1 mmol of methyl 4-chloro-3-[(E)-dimethylaminomethyleneamino]sulfonyl-5-nitro-benzoate (350 mg) in acetonitrile (10 mL). Then add 1.2 mmol of 2-mercapto-thiazoline (MW = 119.21 g / mol; 143 mg) and 2 mmol of K2CO3 (MW = 138 g / mol; 276 mg) to the flask. Stir the reaction mixture at room temperature overnight. Add water to the reaction, and extract 3 times with ethyl acetate, wash with brine. Dry the organic layer over Na2SO4 and remove the solvent under reduced pressure. Then purify the crude product by column chromatography (ethyl acetate / petroleum ether 7 + 3). Obtain 283 mg of yellow crystalline solid (yield 78.0%).

[0690] Methyl 3-[(E)-dimethylaminomethyleneamino]sulfonyl-5-nitro-4-(3-thienyl)benzoate (TEPS39)

[0691]

[0692] Dissolve 1 mmol of methyl 4-chloro-3-[(E)-dimethylaminomethyleneamino]sulfonyl-5-nitro-benzoate (320 mg) in 3 ml of di- In an alkane. Then 1.3 mmol (167 mg) of 3-thienyl-boronic acid, 3 mmol (414 mg) of potassium carbonate, and 100 mg of tetrakis(triphenylphosphine)palladium(0) were added. The reaction flask was filled with argon, heated to 90 °C and stirred overnight. Then the mixture was cooled to room temperature, diluted with ethyl acetate, and washed with water and brine. The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (ethyl acetate / petroleum ether 7 + 3) to give 278 mg of a brown solid (yield 70%). 1 1H NMR (200 MHz, chloroform-d) δ 9.13 (d, J = 1.8 Hz, 1H), δ 8.46 (d, J = 1.8 Hz, 1H), δ 7.60 - 7.29 (m, 2H), δ 7.22 - 7.07 (m, 2H), δ 4.01 (s, 3H), δ 2.90 (s, 3H), δ 2.84 (s, 3H). MS m / z: 398 M +

[0693] Methyl 3-amino-5-[(E)-dimethylaminomethyleneamino]sulfonyl-4-(3-thienyl)benzoate (TEPS40)

[0694]

[0695] 1 mmol of TEPS 39 (397 mg) was added to 15 ml of ethanol and 3 ml of di ane, and the mixture was heated to 85 °C and stirred until it was completely dissolved. Then 10 mmol of ammonium chloride (535 mg) in 6 mL of water was added. 4 mmol of iron powder (223 mg) was added in three portions at 2-minute intervals. The reaction was stirred at 85 °C for another 2.5 hours until TEPS 39 could no longer be detected by TLC. The mixture was cooled to 60 °C and then extracted three times with 25 mL of dichloromethane. The combined organic layers were washed with water and brine and dried over Na2SO4. The crude product was purified by flash chromatography (ethyl acetate / petroleum ether 7 + 3) to give 334 mg of a yellow solid (yield 90%). 1 1H NMR (200 MHz, chloroform-d) δ 8.43 (d, J = 1.6 Hz, 1H), δ 7.73 (d, J = 1.7 Hz, 1H), δ 7.47 - 7.35 (m, 2H), δ 7.18 - 7.02 (m, 2H), δ 3.93 (s, 3H), δ 2.88 (s, 3H), δ 2.84 (s, 3H). MS m / z: 367 M +

[0696] Methyl 3-(butylamino)-5-[(E)-dimethylaminomethyleneamino]sulfonyl-4-(3-thienyl)benzoate (TEPS 41)

[0697]

[0698] Dissolve 1 mmol (367 mg) of TEPS 40 in 5 mL of acetonitrile. Then add 3 mmol (408 mg) of K2CO3 and 3 mmol (3418 μl) of butyl iodide. Stir the reaction mixture at 90 °C for two days. After the reaction is complete, pour the reaction mixture into 20 mL of water and extract it three times with ethyl acetate. Wash the combined organic layers with brine and dry over Na2SO4. Then evaporate the solvent under reduced pressure and purify the resulting crude product by column chromatography (ethyl acetate / toluene 1+1) to obtain 90 mg of a white powder (yield 21.0%). 1 1H NMR (200 MHz, chloroform-d) δ 8.37 (d, J = 1.6 Hz, 1H), δ 7.66 (d, J = 1.7 Hz, 1H), δ 7.52 - 7.36 (m, 2H), δ 7.12 (s, 1H), δ 7.13 - 7.00 (m, 1H), δ 3.94 (s, 3H), δ 3.13 - 2.99 (m, 2H), δ 2.89 (s, 3H), δ 2.85 (s, 3H), δ 1.56 - 1.35 (m, 2H), δ 1.32 - 1.12 (m, 2H), δ 0.86 (t, J = 7.2 Hz, 3H). MS m / z: 424 M +

[0699] Methyl 3-(dibenzylamino)-5-[(E)-dimethylaminomethyleneamino]sulfonyl-4-(3-thienyl)benzoate (TEPS 42)

[0700]

[0701] Dissolve 1 mmol (367 mg) of TEPS 40 in 5 mL of acetonitrile. Then add 2 mmol (276 mg) of K2CO3 and 2 mmol (238 μl) of benzyl bromide. Stir the reaction mixture at 70 °C overnight. After the reaction is complete, pour the reaction mixture into 20 mL of water and extract it three times with ethyl acetate. Wash the combined organic layers with brine and dry over Na2SO4. Then evaporate the solvent under reduced pressure and purify the resulting crude product by column chromatography (ethyl acetate / toluene 1.5+8.5) to obtain 193 mg of a white powder (yield 35%). 11H NMR (200 MHz, chloroform-d) δ 8.70 (d, J = 1.7 Hz, 1H), δ 8.01 (d, J = 1.7 Hz, 1H), δ 7.43 - 7.28 (m, 1H), 7.30 - 7.15 (m, 8H), 7.07 (s, 1H), 7.03 - 6.88 (m, 5H), 4.04 - 3.80 (m, 7H), 2.87 (s, 3H), 2.79 (s, 3H). MS m / z: 547 M +

[0702] 5-(Benzyloxymethyl)-3-(butylamino)-2-phenoxy-benzenesulfonamide (TEPS 43)

[0703]

[0704] 1.5 mmol (37 mg) of NaH and 1.1 mmol (114 μl) of benzyl alcohol were added to 10 mL of dry THF. The solution was stirred for 10 minutes and then 1 mmol (369 mg) of TEPS 76 was added. The reaction was stirred overnight at room temperature. When TLC showed no remaining TEPS 76, the reaction mixture was dried under reduced pressure and purified by column chromatography (ethyl acetate / petroleum ether 3 + 7) to give 100 mg of a white powder (yield 22%). 1 1H NMR (200 MHz, chloroform-d) δ 7.51 - 7.20 (m, 8H), δ 7.06 (t, J = 7.4 Hz, 1H), δ 7.00 - 6.88 (m, 3H), δ 4.85 (s, 2H), 4.60 (s, 2H), δ 4.53 (s, 2H), δ 3.83 (s, 1H), δ 3.05 (t, J = 6.9 Hz, 2H), δ 1.57 - 1.29 (m, 2H), δ 1.29 - 1.05 (m, 2H), δ 0.81 (t, J = 7.2 Hz, 3H). MS m / z: 440 M +

[0705] Methyl 3-[(E)-dimethylaminomethyleneamino]sulfonyl-5-nitro-4-pyrimidin-2-ylthio-benzoate (TEPS 44)

[0706]

[0707] In a three-necked flask, 1 mmol of methyl 4-chloro-3-[(E)-dimethylaminomethyleneamino]sulfonyl-5-nitro-benzoate (350 mg) was dissolved in acetonitrile (10 mL). Then 1.2 mmol of 2-mercaptopyrimidine (MW = 112.15 g / mol; 135 mg) and 2 mmol of K2CO3 (MW = 138 g / mol; 276 mg) were added to the flask. The reaction mixture was stirred o...

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof for treating or preventing hyperhidrosis, wherein: Ring part Yes R x is R 1 or R 3 ; R 1 Selected from -COOH, -COO-(C 1-15 alkyl), -COO-(C 0-15 alkylene)-carbocyclic group, -COO-(C 0-15 alkylene)-heterocyclic group, -O-CHO, -O-CO-(C 1-15 alkyl), -O-CO-(C 0-15 alkylene)-carbocyclic group, -O-CO-(C 0-15 alkylene)-heterocyclic group, -CHO, -CO-(C 1-15 alkyl), -CO-(C 0-15 alkylene)-carbocyclic group, -CO-(C 0-15 alkylene)-heterocyclic group, -CO-NH2, -CO-N(R 11 )(C 1-15 alkyl), -CO-N(R 11 )(C 0-15 alkylene)-carbocyclic group, -CO-N(R 11 )(C 0-15 alkylene)-heterocyclic group, -N(R 11 )(-CHO), -N(R 11 )(-CO-(C 1-15 alkyl)), -N(R 11 )(-CO-(C 0-15 alkylene)-carbocyclic group), -N(R 11 )(-CO-(C 0-15 alkylene)-heterocyclic group), C 1-15 alkyl, -(C 0-15 alkylene)-carbocyclic group, -(C 0-15 alkylene)-heterocyclic group, C 2-15 alkenyl, -(C 2-15 alkenylene)-carbocyclic group, -(C 2-15 alkenylene)-heterocyclic group, C 2-15 alkynyl, -(C 2-15 alkynylene)-carbocyclic group and -(C 2-15 alkynylene)-heterocyclic group, wherein the alkyl moiety of any one of the above groups, the alkylene moiety of any one of the above groups, the alkenylene moiety of any one of the above groups, the alkynylene moiety of any one of the above groups, the C 1-15 alkyl, the C 2-15 alkenyl and the C 2-15 alkynyl are each optionally independently substituted with one or more groups selected from halogen, -CF3, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ) and -SO3H, Including in the alkyl moiety of any of the above groups, in the alkylene moiety of any of the above groups, in the alkenylene moiety of any of the above groups, in the alkynylene moiety of any of the above groups, the C 1-15 alkyl, the C 2-15 alkenyl or the C 2-15 alkynyl, one or more -CH2- units are each optionally and independently replaced by a group selected from -O-, -CO-, -COO-, -O-CO-, -N(R 11 ), -N(R 11 )-CO-, -CO-N(R 11 ), -S-, -SO-, -SO2-, -SO2-N(R 11 )- and -N(R 11 )-SO2-, And further, wherein the carbocyclic moiety of any one of the above groups and the heterocyclic moiety of any one of the above groups are each optionally independently substituted with one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -CN, -NO2, -N(R 11 )(R 11 ), -O(R 11 ), -S(R 11 ), -SO3H, a carbocyclic group and a heterocyclic group; Each R 11 is independently hydrogen or C 1-6 alkyl; R 2 selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl); R 3 selected from -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -SO2-N=(C 1-6 alkylidene) and -SO2-halogen, wherein the alkyl moiety of said -SO2-NH(C 1-6 alkyl), one or both of the alkyl moieties of said -SO2-N(C 1-6 alkyl)(C 1-6 alkyl) and the alkylidene moiety of said -SO2-N=(C 1-6 alkylidene) are each optionally independently substituted by one or more groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH and -S(C 1-6 alkyl); R 4 is the group R 4a , and R 5 is the group R 5a , or R 4 and R 5 are connected to each other to form the group -R 5b -; R 4a selected from -O-R 41 , -S-R 41 , -NH-R 41 , -N(C 1-6 alkyl)-R 41 、halogens, hydrogen, carbocyclic groups and heterocyclic groups, wherein each of the carbocyclic group and the heterocyclic group is optionally substituted by one or more groups R 42 ; R 41 selected from -(C 0-4 alkylene)-carbocyclic group, -(C 0-4 alkylene)-heterocyclic group, C 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl, wherein the carbocyclic group portion of said -(C 0-4 alkylene)-carbocyclic group and the heterocyclic group portion of said -(C 0-4 alkylene)-heterocyclic group are each optionally substituted by one or more groups R 42 ; and wherein said C 1-6 alkyl, said C 2-6 alkenyl, said C 2-6 alkynyl, the alkylene portion of said -(C 0-4 alkylene)-carbocyclic group and the alkylene portion of said -(C 0-4 alkylene)-heterocyclic group are each optionally substituted by one or more groups R 43 ; Each R 42 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl); Each R 43 is independently selected from -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, -CF3, -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl) and -N(C 1-6 alkyl)-CO-(C 1-6 alkyl); R 5a selected from -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -NO2 and hydrogen, wherein the alkyl moiety of said -NH(C 1-6 alkyl) and one or both of the alkyl moieties of said -N(C 1-6 alkyl)(C 1-6 alkyl) are each optionally independently substituted by one or more groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), a carbocyclic group and a heterocyclic group, wherein the carbocyclic group and the heterocyclic group are each optionally substituted by one or more groups R 51 substituted; Each R 51 is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl); R 5b Selected from -R 5b1 -R 5b2 -R 5b1 -, -N=C(R 53 )-R 5b3 -R 5b1 -, -R 5b1 -R 5b3 -C(R 53 )=N- and -N=C(R 53 )-R 5b4 -C(R 53 )=N-; Each R 5b1 is independently selected from -N(R 52 )-, -O-, and -S-; R 5b2 Selected from -C(R 53 )(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )(R 53 )-, -C(R 53 )=C(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )=C(R 53 )- and -C(R 53 )=C(R 53 )-C(R 53 )(R 53 )-; R 5b3 selected from a covalent bond, -C(R 53 )(R 53 )-, -C(R 53 )(R 53 )-C(R 53 )(R 53 )- and -C(R 53 )=C(R 53 ); R 5b4 Selected from a covalent bond and -C(R 53 )(R 53 )-; Each R 52 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl; Each R 53 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl), -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl), -(C 0-4 alkylene)-aryl and -(C 0-4 alkylene)-heteroaryl, and any two groups R that are attached to the same carbon atom 53 may also together form a group =O, and any two groups R that are attached to adjacent carbon atoms that are connected by a double bond 53 may also be joined to each other to form a group -C(R 54 )=C(R 54 )-C(R 54 )=C(R 54 )-; Each R 54 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl); and R 6 selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl, -O-(C 1-6 haloalkyl), -CN, -NO2, -CHO, -CO-(C 1-6 alkyl), -COOH, -COO-(C 1-6 alkyl), -O-CO-(C 1-6 alkyl), -CO-NH2, -CO-NH(C 1-6 alkyl), -CO-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-CO-(C 1-6 alkyl), -N(C 1-6 alkyl)-CO-(C 1-6 alkyl), -SO2-NH2, -SO2-NH(C 1-6 alkyl), -SO2-N(C 1-6 alkyl)(C 1-6 alkyl), -NH-SO2-(C 1-6 alkyl) and -N(C 1-6 alkyl)-SO2-(C 1-6 alkyl); or R 1 and R 6 are connected to each other to form the group -R 16 -, wherein: R 16 is the group -C(R 161 )(R 161 )-C(R 161 )(R 161 )-C(R 161 )(R 161 )-C(R 161 )(R 161 )-, wherein one or two -C(R 161 )(R 161 )- units in said group are each replaced by -R 163 -; Each R 161 is independently selected from hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, halogen, C 1-6 haloalkyl, -(C 0-6 alkylene)-CF3, -(C 0-6 alkylene)-CN, -(C 0-6 alkylene)-NO2, -(C 0-6 alkylene)-N(R 162 )(R 162 ), -(C 0-6 alkylene)-O(R 162 ), -(C 0-6 alkylene)-S(R 162 ), -(C 0-6 alkylene)-SO3H, -(C 0-6 alkylene)-carbocyclic group, and -(C 0-6 alkylene)-heterocyclic group; Each R 162 is independently hydrogen or C 1-6 alkyl; and Each R 163 is independently selected from -N(R 161 )-, -O-, and -S-; The condition is that if the ring moiety is R 2 is hydrogen, R 3 is -SO2-NH2, R 4 is -O-phenyl, R 5 is -NH-CH2CH2CH2CH3 and R 6 is hydrogen, then R 1 is different from -COOH.

2. The compound used according to claim 1, wherein the compound of formula (I) is a compound of formula (Ia) or a pharmaceutically acceptable salt or solvate thereof: wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in claim 1.

3. The compound used according to claim 2, wherein R 1 is -COO-(C 1-15 alkyl), wherein the alkyl moiety of the -COO-(C 1-15 alkyl) is optionally independently substituted by one or more groups selected from halogen, -CF3, -CN, -NO2, -NH2, -NH(C 1-4 alkyl), -N(C 1-4 alkyl)(C 1-4 alkyl), -OH, -O(C 1-4 alkyl), -SH and -S(C 1-4 alkyl), and further, wherein one or two -CH2- units in the alkyl moiety of the -COO-(C 1-15 alkyl) are each optionally independently replaced by a group selected from -O-, -CO-, -COO-, -O-CO-, -NH-, -N(C 1-4 alkyl)-, -NH-CO-, -N(C 1-4 alkyl)-CO-, -CO-NH-, -CO-N(C 1-4 alkyl)-, -S-, -SO-, -SO2-, -SO2-NH-, -SO2-N(C 1-4 alkyl)-, -NH-SO2- and -N(C 1-4 alkyl)-SO2-.

4. The compound used according to claim 2 or 3, wherein R 1 is -COO-CH3.

5. The compound used according to claim 2, wherein R 1 is -COOH.

6. The compound used according to claim 2, wherein R 1 is selected from -(C 1-4 alkylene)-NH-(C 1-4 alkylene)-R 12 , -COO-(C 1-4 alkylene)-R 12 , -O-CO-(C 1-4 alkylene)-R 12 , -CO-(C 1-4 alkylene)-R 12 , -CO-NH-(C 1-4 alkylene)-R 12 , -CO-N(C 1-4 alkyl)-(C 1-4 alkylene)-R 12 , -NH-CO-(C 1-4 alkylene)-R 12 and -N(C 1-4 alkyl)-CO-(C 1-4 alkylene)-R 12 , wherein R 12 is independently selected from -CF3, -CN and halogen.

7. The compound used according to claim 2 or 6, wherein R 1 is -(C 1-4 alkylene)-NH-(C 1-4 alkylene)-CF3.

8. A compound used according to any one of claims 2 to 7, wherein R 2 is hydrogen.

9. The compound used according to any one of claims 2 to 8, wherein R 3 is selected from -SO2-NH2, -SO2-NH(C 1-4 alkyl), -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and -SO2-N=(C 1-4 alkylidene), and further, wherein the alkyl moiety of the -SO2-NH(C 1-4 alkyl), one or both of the alkyl moieties of the -SO2-N(C 1-4 alkyl)(C 1-4 alkyl) and the alkylidene moiety of the -SO2-N=(C 1-4 alkylidene) are each optionally substituted by a group selected from -NH2, -NH(C 1-4 alkyl) and -N(C 1-4 alkyl)(C 1-4 alkyl).

10. The compound used according to any one of claims 2 to 9, wherein R 4 is a group R 1-4 selected from -O-aryl, -O-heteroaryl, -S-aryl, -S-heteroaryl, -NH-aryl, -NH-heteroaryl, -N(C 1-4 alkyl)-aryl, -N(C 4a alkyl)-heteroaryl, aryl and heteroaryl, and wherein the aryl moiety of any of the above groups, the heteroaryl moiety of any of the above groups, the said aryl and the said heteroaryl are each optionally independently substituted by one or more groups selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -OH, -O(C 1-6 alkyl), -O(C 1-6 alkylene)-OH, -O(C 1-6 alkylene)-O(C 1-6 alkyl), -SH, -S(C 1-6 alkyl), -NH2, -NH(C 1-6 alkyl), -N(C 1-6 alkyl)(C 1-6 alkyl), halogen, C 1-6 haloalkyl and -CN.

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